2014 Lancet Autism Seminar & Appendix
Transcript of 2014 Lancet Autism Seminar & Appendix
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httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 143
Seminar
Autism
Meng-Chuan Lai Michael V Lombardo Simon Baron-Cohen
Autism is a set of heterogeneous neurodevelopmental conditions characterised by early-onset diffi culties in socialcommunication and unusually restricted repetitive behaviour and interests The worldwide population prevalence isabout 1 Autism aff ects more male than female individuals and comorbidity is common (gt70 have concurrent
conditions) Individuals with autism have atypical cognitive profiles such as impaired social cognition and socialperception executive dysfunction and atypical perceptual and information processing These profiles are underpinnedby atypical neural development at the systems level Genetics has a key role in the aetiology of autism in conjunctionwith developmentally early environmental factors Large-eff ect rare mutations and small-eff ect common variantscontribute to risk Assessment needs to be multidisciplinary and developmental and early detection is essential forearly intervention Early comprehensive and targeted behavioural interventions can improve social communication andreduce anxiety and aggression Drugs can reduce comorbid symptoms but do not directly improve social communicationCreation of a supportive environment that accepts and respects that the individual is diff erent is crucial
DefinitionIn 1943 child psychiatrist Leo Kanner described eight boysand three girls1 including 5-year-old Donald who wasldquohappiest when left alone almost never cried to go with hismother did not seem to notice his fatherrsquos home-comingsand was indiff erent to visiting relativeswandered aboutsmiling making stereotyped movements with his fingershellipspun with great pleasure anything he could seize upon tospinhellipWords to him had a specifically literal inflexiblemeaninghellipWhen taken into a room he completely
di d d th l d i t tl t f bj t rdquo I
evolved substantially in the past 70 years with anexponential growth in research since the mid-1990s(figure) Autism is now thought of as a set of neuro-developmental conditions some of which can beattributed to distinct aetiological factors such asMendelian single-gene mutations However most areprobably the result of complex interactions betweengenetic and non-genetic risk factors The many types arecollectively defined by specific behaviours centring onatypical development in social communication and un-
ll t i t d titi b h i d i t t
Lancet 2014 383 896ndash910
Published Online
September 26 2013
httpdxdoiorg101016S0140-6736(13)61539-1
Autism Research Centre
Department of Psychiatry
University of Cambridge
Cambridge UK (M-C Lai PhD
M V Lombardo PhD
Prof S Baron-Cohen PhD)
Department of Psychiatry
College of Medicine National
Taiwan University Taipei
Taiwan (M-C Lai) Department
of Psychology University ofCyprus Nicosia Cyprus
(M V Lombardo) and
Cambridgeshire and
Peterborough NHS Foundation
Trust Cambridge UK
(Prof S Baron-Cohen)
Correspondence to
Dr Meng-Chuan Lai Autism
Research Centre Department of
Psychiatry University of
Cambridge Douglas House
18B T i R d
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disregarded the people and instantly went for objectsrdquo In usually restricted or repetitive behaviour and interests18B T i t R d
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How prevalence estimates will be aff ected by the newcriteria and how autism spectrum disorder will relate tothe newly created social (pragmatic) communicationdisorder (defined by substantial diffi culties with socialuses of both verbal and non-verbal communication butotherwise not meeting criteria for autism spectrumdisorder) remain to be assessed
Autism could potentially be subgrouped at clinical (egby developmental pattern or trajectory and comorbidity)cognitive and aetiological levels (eg by genetic andenvironmental correlates)6 Although the term autismspectrum disorder is frequently used the term autismspectrum condition also signals a biomedical diagnosisfor which individuals need support and recognises areasin which aff ected individuals are diff erent from thosewithout autism but without the negative overtones of the
disorder label
EpidemiologyPrevalenceThe prevalence of autism has been steadily increasingsince the first epidemiological study7 which showed that4middot1 of every 10 000 individuals in the UK had autism Theincrease is probably partly a result of changes in diag-nostic concepts and criteria8 However the prevalencehas continued to rise in the past two decades particularly
in individuals without intellectual disability despite
Figure The growth of autism research
Almost three times as many reports about autism were published between2000 and 2012 (n=16 741) as between 1940 and 1999 (n=6054) These
calculations are based on a keyword search of PubMed with the term ldquolsquoautismrsquo
OR lsquoautism spectrum disorderrsquo OR lsquopervasive developmental disorderrsquo OR
lsquoAsperger syndromersquordquo
1940 1950 1960 1970 1980 1990 2000 2010 20200
500
1000
1500
2000
2500
3000
N u m b e r o f r e p o r t s
p u b l i s h e d p e r y e a r
Year
Features
Core features in DSM-5 criteria
Persistent deficits in social
communication and social
interaction across multiple
Deficits in socialndashemotional reciprocity
Deficits in non-verbal communicative behaviours used for social
interaction
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Proportion of individuals
with autism aff ected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is aff ected by the diagnostic boundary and the definition of intelligence (eg whether verbal ability is used
as a criterion)
In individuals discrepant performance between subtests is common
Lan guage disord ers Variable In D SM-IV l angua ge de lay was a d efining fea tu re of autism ( autistic d isorder) b ut is no longe r incl ude d in D SM-5
An autism-specific language profile (separate from language disorders) exists but with substantial inter-individual variability
Attention-deficit hyperactivity
disorder
2 8ndash44 In DSM-IV no t diagnosed wh en occu rr ing in indiv iduals with au tism but no lo nger so in DSM- 5
Clinical guidance available
Tic disorders 14ndash38 ~6middot5 have Tourettersquos syndrome
Motor abnormality le79 See table 1
General medical
Epilepsy 8ndash30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence
Increases risk of poor outcome
Clinical guidance available
Gastroint estinal pro blems 9 ndash70 Common sympto ms inclu de chronic co nstipation abdominal pain chronic diarrho ea and gast ro -o esophageal reflu x
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease inflammatory bowel disease coeliacdisease Crohnrsquos disease and colitis
Clinical guidance available
Immune dysregulation le38 Altered immune function which interacts with neurodevelopment could be a crucial biological pathway underpinning autism
Associated with allergic and autoimmune disorders
Genetic syndromes ~5 Collectively called syndromic autism
Examples include fragile X syndrome (21ndash50 of individuals aff ected have autism) Rett syndrome (most have autistic features
but with profiles diff erent from idiopathic autism) tuberous sclerosis complex (24ndash60) Downrsquos syndrome (5ndash39)
phenylketonuria (5ndash20) CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation of growth
and development or both genital and urinary abnormalities or both and ear abnormalities and deafness 15ndash50) Angelman
syndrome (50ndash81) Timothy syndrome (60ndash70) and Joubert syndrome (~40)
Sleep disorders 50ndash80 Insomnia is the most common
Cli i l id il bl
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Risk and protective factorsEpidemiological studies have identified various riskfactors32 but none has proven to be necessary or suffi cientalone for autism to develop Understanding of genendashenvironment interplay in autism is still at an early stage33 Advanced paternal or maternal reproductive age or bothis a consistent risk34ndash36 the underlying biology is unclearbut could be related to germline mutation particularly
hen paternal in origin 37ndash41 Alternati el indi iduals ho
the greater the individualrsquos disability58 The high frequencyof comorbidity could be a result of shared pathophysiologysecondary eff ects of growing up with autism sharedsymptom domains and associated mechanisms or over-lapping diagnostic criteria
Prognosis and outcomeA meta-analysis63 showed that individuals with autism
ha e a mortalit risk that is 2 8 times higher (95 CI
Proportion of individuals
with autism aff ected
Comments
(Continued from previous page)
Behavioural
Aggressive behaviours le68 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy diffi culties anxiety sensory overload disruption of routines and diffi culties with communication
Self-injurious behaviours le50 Associated with impulsivity and hyperactivity negative aff ect and lower levels of ability and speech
Could signal frustration in individuals with reduced communication as well as anxiety sensory overload or disruption of routines
Could also become a repetitive habit
Could cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed edible or sensory exploration or both
Suicidal ideation o r att empt 11ndash14 Risks increase wit h concu rrent depress io n and behaviou ral pro blems and af ter being t eased o r bul lied
For version with full references see appendix DSM-IV=Diagnostic and Statistical Manual of Mental Disorders 4th edition DSM-5=Diagnostic and Statistical Manual of Mental Disorders 5th edition Particularly
in high-functioning adults
Table 983090 Common co-occurring conditions
See Online for appendix
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full-time education is 4676 Furthermore little is knownabout how ageing aff ects people with autism7677
Early signs and screeningEarly identification allows early intervention Previouslychildren with autism were often identified when olderthan 3ndash4 years but toddlers are now frequently diag-
nosed because atypical development is recognised earlyEarly indicators are deficits or delays in the emergence ofjoint attention (ie shared focus on an object) and pretendplay atypical implicit perspective taking deficits inreciprocal aff ective behaviour decreased response to ownname decreased imitation delayed verbal and non-verbal communication motor delay unusually repetitivebehaviours atypical visuomotor exploration inflexibilityin disengaging visual attention and extreme variation intemperament7879 These indicators contribute to screen-ing and diagnostic instruments for toddlers79 How-ever identification of high-functioning individuals is stilloften later than it should be80 particularly for females2324
Variability in age cognitive ability and sex leads todiff erential presentation and the need for appropriatescreening instruments (table 3) Care should be takenduring selection of screening instruments (and the cutoff for further action) because the target sample and purposeof screening vary81 Routine early screening at ages 18 and
24 th h b d d 82 Th d t d
Clinical assessmentDiagnostic assessment should be multidisciplinary anduse a developmental framework of an interview with theparent or caregiver interaction with the individualcollection of information about behaviour in communitysettings (eg school reports and job performance)cognitive assessments and a medical examination92 Co-
occurring conditions should be carefully screenedThe interview of the parent or caregiver should cover
the gestational birth developmental and health historyand family medical and psychiatric history It shouldhave specific foci the development of social emotionallanguage and communication cognitive motor and self-help skills the sensory profile and unusual behavioursand interests Behavioural presentation across diff erentcontexts should be investigated Ideally a standardisedstructured interview should be incorporated into theassessment process (table 3) Adaptive skills should bechecked with standardised instruments (eg Vinelandadaptive behaviour scales) In children parentndashchildinteraction and parent coping strategies should bespecifically investigated because they are relevant for theplanning of interventions
Interviews with the individual should be interactiveand engaging to enable assessment of social-communi-cation characteristics in both structured and unstructured
t t A i i f ti h ld id ll b th d
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Age Description
Screening young children
Checklist for autism in toddlers (CHAT) 18 months 14-item questionnaire nine completed by parent or caregiver and five by
primary health-care provider takes 5ndash10 min
Ea rly scree ning of autistic traits (E SAT ) 14 mon ths 14-item questionnaire completed by health practitioners at well-baby visit
after interviewing parent or caregiver takes 5ndash10 min
Modified checklist for autism in toddlers (M-CHAT) 16ndash30 months 23-item questionnaire completed by parent or caregiver takes 5ndash10 min
Infant toddler checklist (ITC) 6ndash24 months 24-item questionnaire completed by parent or caregiver takes 5ndash10 min
Quantitative checklist for autism in toddlers
(Q-CHAT)
18ndash24 months 25-item questionnaire completed by parent or caregiver takes 5ndash10 min
ten-item short version available
Screening tool for autism in children aged 2 years
(STAT)
24ndash36 months 12 items and activities assessed by clinician or researcher after interacting
with the child takes 20 min intensive training nece ssary level-two
screening measure
Screening older children and adolescents
Social communication questionnaire (SCQ) gt4 years (and mental age
gt2 years)
40-item questionnaire completed by parent or caregiver takes 10ndash15 min
Social responsiveness scale first or second edition
(SRS SRS-2)
gt 2middot5 y ears 6 5-item quest io nnaire complet ed by parent caregiver t each er relat iv e or
friends (self-report form available for adult in SRS-2) takes 15ndash20 minChil dhood autism sc reening test (CA ST ) 4ndash11 years 37-ite m ques tionn aire completed by p arent or car egive r takes 10 ndash15 min
Autism spectrum screening questionnaire (ASSQ) 7ndash16 years 27-item questionnaire completed by parent caregiver or teacher takes
10 min
Autism spectrum quotient (AQ) child and
adolescent versions
Child 4ndash11 years
adolescent 10ndash16 years
50-item questionnaire completed by parent or caregiver takes 10ndash15 min
ten-item short versions available
Screening adults
Autism spectrum quotient (AQ) adult version gt16 years (with average or
above-average intelligence)
50-item questionnaire self-report takes 10ndash15 min ten-item short
version available
The Ritvo autism Asperger diagnostic scale-revised
(RAADS R)
gt18 years (with average or
above average intelligence)
80-item questionnaire self-report done with a clinicia n takes 60 min
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Although many (high-functioning) individuals withautism achieve some degree of explicit or controlledmentalising101 the implicit automatic and intuitivecomponents are still impaired even in adulthood102 Early-onset mentalising diffi culties seem to be specific toautism but late-onset deficits are reported in disorderssuch as schizophrenia103 Mentalising is closely entwined
with executive control and language104 so that thedichotomous view of social versus non-social cognition ispotentially misleading in autism
Historically the domain of mentalising has beenlargely centred on others but self-referential cognitionand its neural substrates are also atypical in autism105106 Therefore deficits in the social domain are not onlyabout diffi culties in the processing of information aboutother people but also about processing of self-referentialinformation the relationship that self has in a socialcontext and the potential for using self as a proxy tounderstand the social world
A consistent network of brain regionsmdashincluding themedial prefrontal cortex superior temporal sulcustemporoparietal junction amygdala and fusiform gyrusmdashare hypoactive in autism across tasks in which socialperception and cognition are used100107108 Dysfunction inthe so-called mirror system (ie brain regions that are activeboth when an individual performs an action and observes
th f i th ti ) h b
that frontal parietal and striatal circuitry are themain systems implicated in executive dysfunction inautism107108 Executive dysfunction is not specific toautism it is commonly reported in other neuropsychiatricconditions (although with diff erent patterns) One viewis that strong executive function early in life could protectat-risk individuals from autism or other neurodevelop-
mental conditions by compensating for deficits in otherbrain systems112
Individuals with autism often have a preference for andsuperiority in processing of local rather than globalsensory-perceptual features (table 4) Individuals withoutautism often show the opposite profile This diff erencecould explain the excellent attention to detail enhancedsensory-perceptual processing and discrimination andidiosyncratic sensory responsivity (ie hyper-reactivity orhyporeactivity to sensory input or unusual interest insensory features of the environment) in autism It couldalso contribute to the exceptional abilities disproportion-ately recorded in individuals with autism113114 Addition-ally top-down information processing in individuals withautism is often characterised by reduced recognition ofthe global context115 and a strong preference to deriverule-based systems113 The neural bases are spatiallydistributed and task dependent but converge onenhanced recruitment of primary sensory cortices
d d it t f i ti d f t l ti
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volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
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mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
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Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
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recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
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36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
7232019 2014 Lancet Autism Seminar amp Appendix
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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disregarded the people and instantly went for objectsrdquo In usually restricted or repetitive behaviour and interests18B T i t R d
Seminar
How prevalence estimates will be aff ected by the newcriteria and how autism spectrum disorder will relate tothe newly created social (pragmatic) communicationdisorder (defined by substantial diffi culties with socialuses of both verbal and non-verbal communication butotherwise not meeting criteria for autism spectrumdisorder) remain to be assessed
Autism could potentially be subgrouped at clinical (egby developmental pattern or trajectory and comorbidity)cognitive and aetiological levels (eg by genetic andenvironmental correlates)6 Although the term autismspectrum disorder is frequently used the term autismspectrum condition also signals a biomedical diagnosisfor which individuals need support and recognises areasin which aff ected individuals are diff erent from thosewithout autism but without the negative overtones of the
disorder label
EpidemiologyPrevalenceThe prevalence of autism has been steadily increasingsince the first epidemiological study7 which showed that4middot1 of every 10 000 individuals in the UK had autism Theincrease is probably partly a result of changes in diag-nostic concepts and criteria8 However the prevalencehas continued to rise in the past two decades particularly
in individuals without intellectual disability despite
Figure The growth of autism research
Almost three times as many reports about autism were published between2000 and 2012 (n=16 741) as between 1940 and 1999 (n=6054) These
calculations are based on a keyword search of PubMed with the term ldquolsquoautismrsquo
OR lsquoautism spectrum disorderrsquo OR lsquopervasive developmental disorderrsquo OR
lsquoAsperger syndromersquordquo
1940 1950 1960 1970 1980 1990 2000 2010 20200
500
1000
1500
2000
2500
3000
N u m b e r o f r e p o r t s
p u b l i s h e d p e r y e a r
Year
Features
Core features in DSM-5 criteria
Persistent deficits in social
communication and social
interaction across multiple
Deficits in socialndashemotional reciprocity
Deficits in non-verbal communicative behaviours used for social
interaction
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Seminar
Proportion of individuals
with autism aff ected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is aff ected by the diagnostic boundary and the definition of intelligence (eg whether verbal ability is used
as a criterion)
In individuals discrepant performance between subtests is common
Lan guage disord ers Variable In D SM-IV l angua ge de lay was a d efining fea tu re of autism ( autistic d isorder) b ut is no longe r incl ude d in D SM-5
An autism-specific language profile (separate from language disorders) exists but with substantial inter-individual variability
Attention-deficit hyperactivity
disorder
2 8ndash44 In DSM-IV no t diagnosed wh en occu rr ing in indiv iduals with au tism but no lo nger so in DSM- 5
Clinical guidance available
Tic disorders 14ndash38 ~6middot5 have Tourettersquos syndrome
Motor abnormality le79 See table 1
General medical
Epilepsy 8ndash30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence
Increases risk of poor outcome
Clinical guidance available
Gastroint estinal pro blems 9 ndash70 Common sympto ms inclu de chronic co nstipation abdominal pain chronic diarrho ea and gast ro -o esophageal reflu x
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease inflammatory bowel disease coeliacdisease Crohnrsquos disease and colitis
Clinical guidance available
Immune dysregulation le38 Altered immune function which interacts with neurodevelopment could be a crucial biological pathway underpinning autism
Associated with allergic and autoimmune disorders
Genetic syndromes ~5 Collectively called syndromic autism
Examples include fragile X syndrome (21ndash50 of individuals aff ected have autism) Rett syndrome (most have autistic features
but with profiles diff erent from idiopathic autism) tuberous sclerosis complex (24ndash60) Downrsquos syndrome (5ndash39)
phenylketonuria (5ndash20) CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation of growth
and development or both genital and urinary abnormalities or both and ear abnormalities and deafness 15ndash50) Angelman
syndrome (50ndash81) Timothy syndrome (60ndash70) and Joubert syndrome (~40)
Sleep disorders 50ndash80 Insomnia is the most common
Cli i l id il bl
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Seminar
Risk and protective factorsEpidemiological studies have identified various riskfactors32 but none has proven to be necessary or suffi cientalone for autism to develop Understanding of genendashenvironment interplay in autism is still at an early stage33 Advanced paternal or maternal reproductive age or bothis a consistent risk34ndash36 the underlying biology is unclearbut could be related to germline mutation particularly
hen paternal in origin 37ndash41 Alternati el indi iduals ho
the greater the individualrsquos disability58 The high frequencyof comorbidity could be a result of shared pathophysiologysecondary eff ects of growing up with autism sharedsymptom domains and associated mechanisms or over-lapping diagnostic criteria
Prognosis and outcomeA meta-analysis63 showed that individuals with autism
ha e a mortalit risk that is 2 8 times higher (95 CI
Proportion of individuals
with autism aff ected
Comments
(Continued from previous page)
Behavioural
Aggressive behaviours le68 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy diffi culties anxiety sensory overload disruption of routines and diffi culties with communication
Self-injurious behaviours le50 Associated with impulsivity and hyperactivity negative aff ect and lower levels of ability and speech
Could signal frustration in individuals with reduced communication as well as anxiety sensory overload or disruption of routines
Could also become a repetitive habit
Could cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed edible or sensory exploration or both
Suicidal ideation o r att empt 11ndash14 Risks increase wit h concu rrent depress io n and behaviou ral pro blems and af ter being t eased o r bul lied
For version with full references see appendix DSM-IV=Diagnostic and Statistical Manual of Mental Disorders 4th edition DSM-5=Diagnostic and Statistical Manual of Mental Disorders 5th edition Particularly
in high-functioning adults
Table 983090 Common co-occurring conditions
See Online for appendix
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Seminar
full-time education is 4676 Furthermore little is knownabout how ageing aff ects people with autism7677
Early signs and screeningEarly identification allows early intervention Previouslychildren with autism were often identified when olderthan 3ndash4 years but toddlers are now frequently diag-
nosed because atypical development is recognised earlyEarly indicators are deficits or delays in the emergence ofjoint attention (ie shared focus on an object) and pretendplay atypical implicit perspective taking deficits inreciprocal aff ective behaviour decreased response to ownname decreased imitation delayed verbal and non-verbal communication motor delay unusually repetitivebehaviours atypical visuomotor exploration inflexibilityin disengaging visual attention and extreme variation intemperament7879 These indicators contribute to screen-ing and diagnostic instruments for toddlers79 How-ever identification of high-functioning individuals is stilloften later than it should be80 particularly for females2324
Variability in age cognitive ability and sex leads todiff erential presentation and the need for appropriatescreening instruments (table 3) Care should be takenduring selection of screening instruments (and the cutoff for further action) because the target sample and purposeof screening vary81 Routine early screening at ages 18 and
24 th h b d d 82 Th d t d
Clinical assessmentDiagnostic assessment should be multidisciplinary anduse a developmental framework of an interview with theparent or caregiver interaction with the individualcollection of information about behaviour in communitysettings (eg school reports and job performance)cognitive assessments and a medical examination92 Co-
occurring conditions should be carefully screenedThe interview of the parent or caregiver should cover
the gestational birth developmental and health historyand family medical and psychiatric history It shouldhave specific foci the development of social emotionallanguage and communication cognitive motor and self-help skills the sensory profile and unusual behavioursand interests Behavioural presentation across diff erentcontexts should be investigated Ideally a standardisedstructured interview should be incorporated into theassessment process (table 3) Adaptive skills should bechecked with standardised instruments (eg Vinelandadaptive behaviour scales) In children parentndashchildinteraction and parent coping strategies should bespecifically investigated because they are relevant for theplanning of interventions
Interviews with the individual should be interactiveand engaging to enable assessment of social-communi-cation characteristics in both structured and unstructured
t t A i i f ti h ld id ll b th d
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Seminar
Age Description
Screening young children
Checklist for autism in toddlers (CHAT) 18 months 14-item questionnaire nine completed by parent or caregiver and five by
primary health-care provider takes 5ndash10 min
Ea rly scree ning of autistic traits (E SAT ) 14 mon ths 14-item questionnaire completed by health practitioners at well-baby visit
after interviewing parent or caregiver takes 5ndash10 min
Modified checklist for autism in toddlers (M-CHAT) 16ndash30 months 23-item questionnaire completed by parent or caregiver takes 5ndash10 min
Infant toddler checklist (ITC) 6ndash24 months 24-item questionnaire completed by parent or caregiver takes 5ndash10 min
Quantitative checklist for autism in toddlers
(Q-CHAT)
18ndash24 months 25-item questionnaire completed by parent or caregiver takes 5ndash10 min
ten-item short version available
Screening tool for autism in children aged 2 years
(STAT)
24ndash36 months 12 items and activities assessed by clinician or researcher after interacting
with the child takes 20 min intensive training nece ssary level-two
screening measure
Screening older children and adolescents
Social communication questionnaire (SCQ) gt4 years (and mental age
gt2 years)
40-item questionnaire completed by parent or caregiver takes 10ndash15 min
Social responsiveness scale first or second edition
(SRS SRS-2)
gt 2middot5 y ears 6 5-item quest io nnaire complet ed by parent caregiver t each er relat iv e or
friends (self-report form available for adult in SRS-2) takes 15ndash20 minChil dhood autism sc reening test (CA ST ) 4ndash11 years 37-ite m ques tionn aire completed by p arent or car egive r takes 10 ndash15 min
Autism spectrum screening questionnaire (ASSQ) 7ndash16 years 27-item questionnaire completed by parent caregiver or teacher takes
10 min
Autism spectrum quotient (AQ) child and
adolescent versions
Child 4ndash11 years
adolescent 10ndash16 years
50-item questionnaire completed by parent or caregiver takes 10ndash15 min
ten-item short versions available
Screening adults
Autism spectrum quotient (AQ) adult version gt16 years (with average or
above-average intelligence)
50-item questionnaire self-report takes 10ndash15 min ten-item short
version available
The Ritvo autism Asperger diagnostic scale-revised
(RAADS R)
gt18 years (with average or
above average intelligence)
80-item questionnaire self-report done with a clinicia n takes 60 min
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
Although many (high-functioning) individuals withautism achieve some degree of explicit or controlledmentalising101 the implicit automatic and intuitivecomponents are still impaired even in adulthood102 Early-onset mentalising diffi culties seem to be specific toautism but late-onset deficits are reported in disorderssuch as schizophrenia103 Mentalising is closely entwined
with executive control and language104 so that thedichotomous view of social versus non-social cognition ispotentially misleading in autism
Historically the domain of mentalising has beenlargely centred on others but self-referential cognitionand its neural substrates are also atypical in autism105106 Therefore deficits in the social domain are not onlyabout diffi culties in the processing of information aboutother people but also about processing of self-referentialinformation the relationship that self has in a socialcontext and the potential for using self as a proxy tounderstand the social world
A consistent network of brain regionsmdashincluding themedial prefrontal cortex superior temporal sulcustemporoparietal junction amygdala and fusiform gyrusmdashare hypoactive in autism across tasks in which socialperception and cognition are used100107108 Dysfunction inthe so-called mirror system (ie brain regions that are activeboth when an individual performs an action and observes
th f i th ti ) h b
that frontal parietal and striatal circuitry are themain systems implicated in executive dysfunction inautism107108 Executive dysfunction is not specific toautism it is commonly reported in other neuropsychiatricconditions (although with diff erent patterns) One viewis that strong executive function early in life could protectat-risk individuals from autism or other neurodevelop-
mental conditions by compensating for deficits in otherbrain systems112
Individuals with autism often have a preference for andsuperiority in processing of local rather than globalsensory-perceptual features (table 4) Individuals withoutautism often show the opposite profile This diff erencecould explain the excellent attention to detail enhancedsensory-perceptual processing and discrimination andidiosyncratic sensory responsivity (ie hyper-reactivity orhyporeactivity to sensory input or unusual interest insensory features of the environment) in autism It couldalso contribute to the exceptional abilities disproportion-ately recorded in individuals with autism113114 Addition-ally top-down information processing in individuals withautism is often characterised by reduced recognition ofthe global context115 and a strong preference to deriverule-based systems113 The neural bases are spatiallydistributed and task dependent but converge onenhanced recruitment of primary sensory cortices
d d it t f i ti d f t l ti
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Seminar
volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
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Seminar
mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
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Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1443
Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
7232019 2014 Lancet Autism Seminar amp Appendix
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
7232019 2014 Lancet Autism Seminar amp Appendix
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 343
Seminar
Proportion of individuals
with autism aff ected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is aff ected by the diagnostic boundary and the definition of intelligence (eg whether verbal ability is used
as a criterion)
In individuals discrepant performance between subtests is common
Lan guage disord ers Variable In D SM-IV l angua ge de lay was a d efining fea tu re of autism ( autistic d isorder) b ut is no longe r incl ude d in D SM-5
An autism-specific language profile (separate from language disorders) exists but with substantial inter-individual variability
Attention-deficit hyperactivity
disorder
2 8ndash44 In DSM-IV no t diagnosed wh en occu rr ing in indiv iduals with au tism but no lo nger so in DSM- 5
Clinical guidance available
Tic disorders 14ndash38 ~6middot5 have Tourettersquos syndrome
Motor abnormality le79 See table 1
General medical
Epilepsy 8ndash30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence
Increases risk of poor outcome
Clinical guidance available
Gastroint estinal pro blems 9 ndash70 Common sympto ms inclu de chronic co nstipation abdominal pain chronic diarrho ea and gast ro -o esophageal reflu x
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease inflammatory bowel disease coeliacdisease Crohnrsquos disease and colitis
Clinical guidance available
Immune dysregulation le38 Altered immune function which interacts with neurodevelopment could be a crucial biological pathway underpinning autism
Associated with allergic and autoimmune disorders
Genetic syndromes ~5 Collectively called syndromic autism
Examples include fragile X syndrome (21ndash50 of individuals aff ected have autism) Rett syndrome (most have autistic features
but with profiles diff erent from idiopathic autism) tuberous sclerosis complex (24ndash60) Downrsquos syndrome (5ndash39)
phenylketonuria (5ndash20) CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation of growth
and development or both genital and urinary abnormalities or both and ear abnormalities and deafness 15ndash50) Angelman
syndrome (50ndash81) Timothy syndrome (60ndash70) and Joubert syndrome (~40)
Sleep disorders 50ndash80 Insomnia is the most common
Cli i l id il bl
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Risk and protective factorsEpidemiological studies have identified various riskfactors32 but none has proven to be necessary or suffi cientalone for autism to develop Understanding of genendashenvironment interplay in autism is still at an early stage33 Advanced paternal or maternal reproductive age or bothis a consistent risk34ndash36 the underlying biology is unclearbut could be related to germline mutation particularly
hen paternal in origin 37ndash41 Alternati el indi iduals ho
the greater the individualrsquos disability58 The high frequencyof comorbidity could be a result of shared pathophysiologysecondary eff ects of growing up with autism sharedsymptom domains and associated mechanisms or over-lapping diagnostic criteria
Prognosis and outcomeA meta-analysis63 showed that individuals with autism
ha e a mortalit risk that is 2 8 times higher (95 CI
Proportion of individuals
with autism aff ected
Comments
(Continued from previous page)
Behavioural
Aggressive behaviours le68 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy diffi culties anxiety sensory overload disruption of routines and diffi culties with communication
Self-injurious behaviours le50 Associated with impulsivity and hyperactivity negative aff ect and lower levels of ability and speech
Could signal frustration in individuals with reduced communication as well as anxiety sensory overload or disruption of routines
Could also become a repetitive habit
Could cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed edible or sensory exploration or both
Suicidal ideation o r att empt 11ndash14 Risks increase wit h concu rrent depress io n and behaviou ral pro blems and af ter being t eased o r bul lied
For version with full references see appendix DSM-IV=Diagnostic and Statistical Manual of Mental Disorders 4th edition DSM-5=Diagnostic and Statistical Manual of Mental Disorders 5th edition Particularly
in high-functioning adults
Table 983090 Common co-occurring conditions
See Online for appendix
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full-time education is 4676 Furthermore little is knownabout how ageing aff ects people with autism7677
Early signs and screeningEarly identification allows early intervention Previouslychildren with autism were often identified when olderthan 3ndash4 years but toddlers are now frequently diag-
nosed because atypical development is recognised earlyEarly indicators are deficits or delays in the emergence ofjoint attention (ie shared focus on an object) and pretendplay atypical implicit perspective taking deficits inreciprocal aff ective behaviour decreased response to ownname decreased imitation delayed verbal and non-verbal communication motor delay unusually repetitivebehaviours atypical visuomotor exploration inflexibilityin disengaging visual attention and extreme variation intemperament7879 These indicators contribute to screen-ing and diagnostic instruments for toddlers79 How-ever identification of high-functioning individuals is stilloften later than it should be80 particularly for females2324
Variability in age cognitive ability and sex leads todiff erential presentation and the need for appropriatescreening instruments (table 3) Care should be takenduring selection of screening instruments (and the cutoff for further action) because the target sample and purposeof screening vary81 Routine early screening at ages 18 and
24 th h b d d 82 Th d t d
Clinical assessmentDiagnostic assessment should be multidisciplinary anduse a developmental framework of an interview with theparent or caregiver interaction with the individualcollection of information about behaviour in communitysettings (eg school reports and job performance)cognitive assessments and a medical examination92 Co-
occurring conditions should be carefully screenedThe interview of the parent or caregiver should cover
the gestational birth developmental and health historyand family medical and psychiatric history It shouldhave specific foci the development of social emotionallanguage and communication cognitive motor and self-help skills the sensory profile and unusual behavioursand interests Behavioural presentation across diff erentcontexts should be investigated Ideally a standardisedstructured interview should be incorporated into theassessment process (table 3) Adaptive skills should bechecked with standardised instruments (eg Vinelandadaptive behaviour scales) In children parentndashchildinteraction and parent coping strategies should bespecifically investigated because they are relevant for theplanning of interventions
Interviews with the individual should be interactiveand engaging to enable assessment of social-communi-cation characteristics in both structured and unstructured
t t A i i f ti h ld id ll b th d
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Seminar
Age Description
Screening young children
Checklist for autism in toddlers (CHAT) 18 months 14-item questionnaire nine completed by parent or caregiver and five by
primary health-care provider takes 5ndash10 min
Ea rly scree ning of autistic traits (E SAT ) 14 mon ths 14-item questionnaire completed by health practitioners at well-baby visit
after interviewing parent or caregiver takes 5ndash10 min
Modified checklist for autism in toddlers (M-CHAT) 16ndash30 months 23-item questionnaire completed by parent or caregiver takes 5ndash10 min
Infant toddler checklist (ITC) 6ndash24 months 24-item questionnaire completed by parent or caregiver takes 5ndash10 min
Quantitative checklist for autism in toddlers
(Q-CHAT)
18ndash24 months 25-item questionnaire completed by parent or caregiver takes 5ndash10 min
ten-item short version available
Screening tool for autism in children aged 2 years
(STAT)
24ndash36 months 12 items and activities assessed by clinician or researcher after interacting
with the child takes 20 min intensive training nece ssary level-two
screening measure
Screening older children and adolescents
Social communication questionnaire (SCQ) gt4 years (and mental age
gt2 years)
40-item questionnaire completed by parent or caregiver takes 10ndash15 min
Social responsiveness scale first or second edition
(SRS SRS-2)
gt 2middot5 y ears 6 5-item quest io nnaire complet ed by parent caregiver t each er relat iv e or
friends (self-report form available for adult in SRS-2) takes 15ndash20 minChil dhood autism sc reening test (CA ST ) 4ndash11 years 37-ite m ques tionn aire completed by p arent or car egive r takes 10 ndash15 min
Autism spectrum screening questionnaire (ASSQ) 7ndash16 years 27-item questionnaire completed by parent caregiver or teacher takes
10 min
Autism spectrum quotient (AQ) child and
adolescent versions
Child 4ndash11 years
adolescent 10ndash16 years
50-item questionnaire completed by parent or caregiver takes 10ndash15 min
ten-item short versions available
Screening adults
Autism spectrum quotient (AQ) adult version gt16 years (with average or
above-average intelligence)
50-item questionnaire self-report takes 10ndash15 min ten-item short
version available
The Ritvo autism Asperger diagnostic scale-revised
(RAADS R)
gt18 years (with average or
above average intelligence)
80-item questionnaire self-report done with a clinicia n takes 60 min
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Although many (high-functioning) individuals withautism achieve some degree of explicit or controlledmentalising101 the implicit automatic and intuitivecomponents are still impaired even in adulthood102 Early-onset mentalising diffi culties seem to be specific toautism but late-onset deficits are reported in disorderssuch as schizophrenia103 Mentalising is closely entwined
with executive control and language104 so that thedichotomous view of social versus non-social cognition ispotentially misleading in autism
Historically the domain of mentalising has beenlargely centred on others but self-referential cognitionand its neural substrates are also atypical in autism105106 Therefore deficits in the social domain are not onlyabout diffi culties in the processing of information aboutother people but also about processing of self-referentialinformation the relationship that self has in a socialcontext and the potential for using self as a proxy tounderstand the social world
A consistent network of brain regionsmdashincluding themedial prefrontal cortex superior temporal sulcustemporoparietal junction amygdala and fusiform gyrusmdashare hypoactive in autism across tasks in which socialperception and cognition are used100107108 Dysfunction inthe so-called mirror system (ie brain regions that are activeboth when an individual performs an action and observes
th f i th ti ) h b
that frontal parietal and striatal circuitry are themain systems implicated in executive dysfunction inautism107108 Executive dysfunction is not specific toautism it is commonly reported in other neuropsychiatricconditions (although with diff erent patterns) One viewis that strong executive function early in life could protectat-risk individuals from autism or other neurodevelop-
mental conditions by compensating for deficits in otherbrain systems112
Individuals with autism often have a preference for andsuperiority in processing of local rather than globalsensory-perceptual features (table 4) Individuals withoutautism often show the opposite profile This diff erencecould explain the excellent attention to detail enhancedsensory-perceptual processing and discrimination andidiosyncratic sensory responsivity (ie hyper-reactivity orhyporeactivity to sensory input or unusual interest insensory features of the environment) in autism It couldalso contribute to the exceptional abilities disproportion-ately recorded in individuals with autism113114 Addition-ally top-down information processing in individuals withautism is often characterised by reduced recognition ofthe global context115 and a strong preference to deriverule-based systems113 The neural bases are spatiallydistributed and task dependent but converge onenhanced recruitment of primary sensory cortices
d d it t f i ti d f t l ti
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volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
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mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
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Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
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recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
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Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3143
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
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J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 443
Seminar
Risk and protective factorsEpidemiological studies have identified various riskfactors32 but none has proven to be necessary or suffi cientalone for autism to develop Understanding of genendashenvironment interplay in autism is still at an early stage33 Advanced paternal or maternal reproductive age or bothis a consistent risk34ndash36 the underlying biology is unclearbut could be related to germline mutation particularly
hen paternal in origin 37ndash41 Alternati el indi iduals ho
the greater the individualrsquos disability58 The high frequencyof comorbidity could be a result of shared pathophysiologysecondary eff ects of growing up with autism sharedsymptom domains and associated mechanisms or over-lapping diagnostic criteria
Prognosis and outcomeA meta-analysis63 showed that individuals with autism
ha e a mortalit risk that is 2 8 times higher (95 CI
Proportion of individuals
with autism aff ected
Comments
(Continued from previous page)
Behavioural
Aggressive behaviours le68 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy diffi culties anxiety sensory overload disruption of routines and diffi culties with communication
Self-injurious behaviours le50 Associated with impulsivity and hyperactivity negative aff ect and lower levels of ability and speech
Could signal frustration in individuals with reduced communication as well as anxiety sensory overload or disruption of routines
Could also become a repetitive habit
Could cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed edible or sensory exploration or both
Suicidal ideation o r att empt 11ndash14 Risks increase wit h concu rrent depress io n and behaviou ral pro blems and af ter being t eased o r bul lied
For version with full references see appendix DSM-IV=Diagnostic and Statistical Manual of Mental Disorders 4th edition DSM-5=Diagnostic and Statistical Manual of Mental Disorders 5th edition Particularly
in high-functioning adults
Table 983090 Common co-occurring conditions
See Online for appendix
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Seminar
full-time education is 4676 Furthermore little is knownabout how ageing aff ects people with autism7677
Early signs and screeningEarly identification allows early intervention Previouslychildren with autism were often identified when olderthan 3ndash4 years but toddlers are now frequently diag-
nosed because atypical development is recognised earlyEarly indicators are deficits or delays in the emergence ofjoint attention (ie shared focus on an object) and pretendplay atypical implicit perspective taking deficits inreciprocal aff ective behaviour decreased response to ownname decreased imitation delayed verbal and non-verbal communication motor delay unusually repetitivebehaviours atypical visuomotor exploration inflexibilityin disengaging visual attention and extreme variation intemperament7879 These indicators contribute to screen-ing and diagnostic instruments for toddlers79 How-ever identification of high-functioning individuals is stilloften later than it should be80 particularly for females2324
Variability in age cognitive ability and sex leads todiff erential presentation and the need for appropriatescreening instruments (table 3) Care should be takenduring selection of screening instruments (and the cutoff for further action) because the target sample and purposeof screening vary81 Routine early screening at ages 18 and
24 th h b d d 82 Th d t d
Clinical assessmentDiagnostic assessment should be multidisciplinary anduse a developmental framework of an interview with theparent or caregiver interaction with the individualcollection of information about behaviour in communitysettings (eg school reports and job performance)cognitive assessments and a medical examination92 Co-
occurring conditions should be carefully screenedThe interview of the parent or caregiver should cover
the gestational birth developmental and health historyand family medical and psychiatric history It shouldhave specific foci the development of social emotionallanguage and communication cognitive motor and self-help skills the sensory profile and unusual behavioursand interests Behavioural presentation across diff erentcontexts should be investigated Ideally a standardisedstructured interview should be incorporated into theassessment process (table 3) Adaptive skills should bechecked with standardised instruments (eg Vinelandadaptive behaviour scales) In children parentndashchildinteraction and parent coping strategies should bespecifically investigated because they are relevant for theplanning of interventions
Interviews with the individual should be interactiveand engaging to enable assessment of social-communi-cation characteristics in both structured and unstructured
t t A i i f ti h ld id ll b th d
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Seminar
Age Description
Screening young children
Checklist for autism in toddlers (CHAT) 18 months 14-item questionnaire nine completed by parent or caregiver and five by
primary health-care provider takes 5ndash10 min
Ea rly scree ning of autistic traits (E SAT ) 14 mon ths 14-item questionnaire completed by health practitioners at well-baby visit
after interviewing parent or caregiver takes 5ndash10 min
Modified checklist for autism in toddlers (M-CHAT) 16ndash30 months 23-item questionnaire completed by parent or caregiver takes 5ndash10 min
Infant toddler checklist (ITC) 6ndash24 months 24-item questionnaire completed by parent or caregiver takes 5ndash10 min
Quantitative checklist for autism in toddlers
(Q-CHAT)
18ndash24 months 25-item questionnaire completed by parent or caregiver takes 5ndash10 min
ten-item short version available
Screening tool for autism in children aged 2 years
(STAT)
24ndash36 months 12 items and activities assessed by clinician or researcher after interacting
with the child takes 20 min intensive training nece ssary level-two
screening measure
Screening older children and adolescents
Social communication questionnaire (SCQ) gt4 years (and mental age
gt2 years)
40-item questionnaire completed by parent or caregiver takes 10ndash15 min
Social responsiveness scale first or second edition
(SRS SRS-2)
gt 2middot5 y ears 6 5-item quest io nnaire complet ed by parent caregiver t each er relat iv e or
friends (self-report form available for adult in SRS-2) takes 15ndash20 minChil dhood autism sc reening test (CA ST ) 4ndash11 years 37-ite m ques tionn aire completed by p arent or car egive r takes 10 ndash15 min
Autism spectrum screening questionnaire (ASSQ) 7ndash16 years 27-item questionnaire completed by parent caregiver or teacher takes
10 min
Autism spectrum quotient (AQ) child and
adolescent versions
Child 4ndash11 years
adolescent 10ndash16 years
50-item questionnaire completed by parent or caregiver takes 10ndash15 min
ten-item short versions available
Screening adults
Autism spectrum quotient (AQ) adult version gt16 years (with average or
above-average intelligence)
50-item questionnaire self-report takes 10ndash15 min ten-item short
version available
The Ritvo autism Asperger diagnostic scale-revised
(RAADS R)
gt18 years (with average or
above average intelligence)
80-item questionnaire self-report done with a clinicia n takes 60 min
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Although many (high-functioning) individuals withautism achieve some degree of explicit or controlledmentalising101 the implicit automatic and intuitivecomponents are still impaired even in adulthood102 Early-onset mentalising diffi culties seem to be specific toautism but late-onset deficits are reported in disorderssuch as schizophrenia103 Mentalising is closely entwined
with executive control and language104 so that thedichotomous view of social versus non-social cognition ispotentially misleading in autism
Historically the domain of mentalising has beenlargely centred on others but self-referential cognitionand its neural substrates are also atypical in autism105106 Therefore deficits in the social domain are not onlyabout diffi culties in the processing of information aboutother people but also about processing of self-referentialinformation the relationship that self has in a socialcontext and the potential for using self as a proxy tounderstand the social world
A consistent network of brain regionsmdashincluding themedial prefrontal cortex superior temporal sulcustemporoparietal junction amygdala and fusiform gyrusmdashare hypoactive in autism across tasks in which socialperception and cognition are used100107108 Dysfunction inthe so-called mirror system (ie brain regions that are activeboth when an individual performs an action and observes
th f i th ti ) h b
that frontal parietal and striatal circuitry are themain systems implicated in executive dysfunction inautism107108 Executive dysfunction is not specific toautism it is commonly reported in other neuropsychiatricconditions (although with diff erent patterns) One viewis that strong executive function early in life could protectat-risk individuals from autism or other neurodevelop-
mental conditions by compensating for deficits in otherbrain systems112
Individuals with autism often have a preference for andsuperiority in processing of local rather than globalsensory-perceptual features (table 4) Individuals withoutautism often show the opposite profile This diff erencecould explain the excellent attention to detail enhancedsensory-perceptual processing and discrimination andidiosyncratic sensory responsivity (ie hyper-reactivity orhyporeactivity to sensory input or unusual interest insensory features of the environment) in autism It couldalso contribute to the exceptional abilities disproportion-ately recorded in individuals with autism113114 Addition-ally top-down information processing in individuals withautism is often characterised by reduced recognition ofthe global context115 and a strong preference to deriverule-based systems113 The neural bases are spatiallydistributed and task dependent but converge onenhanced recruitment of primary sensory cortices
d d it t f i ti d f t l ti
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volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
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mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
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Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
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recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3043
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3143
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
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ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
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Seminar
full-time education is 4676 Furthermore little is knownabout how ageing aff ects people with autism7677
Early signs and screeningEarly identification allows early intervention Previouslychildren with autism were often identified when olderthan 3ndash4 years but toddlers are now frequently diag-
nosed because atypical development is recognised earlyEarly indicators are deficits or delays in the emergence ofjoint attention (ie shared focus on an object) and pretendplay atypical implicit perspective taking deficits inreciprocal aff ective behaviour decreased response to ownname decreased imitation delayed verbal and non-verbal communication motor delay unusually repetitivebehaviours atypical visuomotor exploration inflexibilityin disengaging visual attention and extreme variation intemperament7879 These indicators contribute to screen-ing and diagnostic instruments for toddlers79 How-ever identification of high-functioning individuals is stilloften later than it should be80 particularly for females2324
Variability in age cognitive ability and sex leads todiff erential presentation and the need for appropriatescreening instruments (table 3) Care should be takenduring selection of screening instruments (and the cutoff for further action) because the target sample and purposeof screening vary81 Routine early screening at ages 18 and
24 th h b d d 82 Th d t d
Clinical assessmentDiagnostic assessment should be multidisciplinary anduse a developmental framework of an interview with theparent or caregiver interaction with the individualcollection of information about behaviour in communitysettings (eg school reports and job performance)cognitive assessments and a medical examination92 Co-
occurring conditions should be carefully screenedThe interview of the parent or caregiver should cover
the gestational birth developmental and health historyand family medical and psychiatric history It shouldhave specific foci the development of social emotionallanguage and communication cognitive motor and self-help skills the sensory profile and unusual behavioursand interests Behavioural presentation across diff erentcontexts should be investigated Ideally a standardisedstructured interview should be incorporated into theassessment process (table 3) Adaptive skills should bechecked with standardised instruments (eg Vinelandadaptive behaviour scales) In children parentndashchildinteraction and parent coping strategies should bespecifically investigated because they are relevant for theplanning of interventions
Interviews with the individual should be interactiveand engaging to enable assessment of social-communi-cation characteristics in both structured and unstructured
t t A i i f ti h ld id ll b th d
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Age Description
Screening young children
Checklist for autism in toddlers (CHAT) 18 months 14-item questionnaire nine completed by parent or caregiver and five by
primary health-care provider takes 5ndash10 min
Ea rly scree ning of autistic traits (E SAT ) 14 mon ths 14-item questionnaire completed by health practitioners at well-baby visit
after interviewing parent or caregiver takes 5ndash10 min
Modified checklist for autism in toddlers (M-CHAT) 16ndash30 months 23-item questionnaire completed by parent or caregiver takes 5ndash10 min
Infant toddler checklist (ITC) 6ndash24 months 24-item questionnaire completed by parent or caregiver takes 5ndash10 min
Quantitative checklist for autism in toddlers
(Q-CHAT)
18ndash24 months 25-item questionnaire completed by parent or caregiver takes 5ndash10 min
ten-item short version available
Screening tool for autism in children aged 2 years
(STAT)
24ndash36 months 12 items and activities assessed by clinician or researcher after interacting
with the child takes 20 min intensive training nece ssary level-two
screening measure
Screening older children and adolescents
Social communication questionnaire (SCQ) gt4 years (and mental age
gt2 years)
40-item questionnaire completed by parent or caregiver takes 10ndash15 min
Social responsiveness scale first or second edition
(SRS SRS-2)
gt 2middot5 y ears 6 5-item quest io nnaire complet ed by parent caregiver t each er relat iv e or
friends (self-report form available for adult in SRS-2) takes 15ndash20 minChil dhood autism sc reening test (CA ST ) 4ndash11 years 37-ite m ques tionn aire completed by p arent or car egive r takes 10 ndash15 min
Autism spectrum screening questionnaire (ASSQ) 7ndash16 years 27-item questionnaire completed by parent caregiver or teacher takes
10 min
Autism spectrum quotient (AQ) child and
adolescent versions
Child 4ndash11 years
adolescent 10ndash16 years
50-item questionnaire completed by parent or caregiver takes 10ndash15 min
ten-item short versions available
Screening adults
Autism spectrum quotient (AQ) adult version gt16 years (with average or
above-average intelligence)
50-item questionnaire self-report takes 10ndash15 min ten-item short
version available
The Ritvo autism Asperger diagnostic scale-revised
(RAADS R)
gt18 years (with average or
above average intelligence)
80-item questionnaire self-report done with a clinicia n takes 60 min
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Although many (high-functioning) individuals withautism achieve some degree of explicit or controlledmentalising101 the implicit automatic and intuitivecomponents are still impaired even in adulthood102 Early-onset mentalising diffi culties seem to be specific toautism but late-onset deficits are reported in disorderssuch as schizophrenia103 Mentalising is closely entwined
with executive control and language104 so that thedichotomous view of social versus non-social cognition ispotentially misleading in autism
Historically the domain of mentalising has beenlargely centred on others but self-referential cognitionand its neural substrates are also atypical in autism105106 Therefore deficits in the social domain are not onlyabout diffi culties in the processing of information aboutother people but also about processing of self-referentialinformation the relationship that self has in a socialcontext and the potential for using self as a proxy tounderstand the social world
A consistent network of brain regionsmdashincluding themedial prefrontal cortex superior temporal sulcustemporoparietal junction amygdala and fusiform gyrusmdashare hypoactive in autism across tasks in which socialperception and cognition are used100107108 Dysfunction inthe so-called mirror system (ie brain regions that are activeboth when an individual performs an action and observes
th f i th ti ) h b
that frontal parietal and striatal circuitry are themain systems implicated in executive dysfunction inautism107108 Executive dysfunction is not specific toautism it is commonly reported in other neuropsychiatricconditions (although with diff erent patterns) One viewis that strong executive function early in life could protectat-risk individuals from autism or other neurodevelop-
mental conditions by compensating for deficits in otherbrain systems112
Individuals with autism often have a preference for andsuperiority in processing of local rather than globalsensory-perceptual features (table 4) Individuals withoutautism often show the opposite profile This diff erencecould explain the excellent attention to detail enhancedsensory-perceptual processing and discrimination andidiosyncratic sensory responsivity (ie hyper-reactivity orhyporeactivity to sensory input or unusual interest insensory features of the environment) in autism It couldalso contribute to the exceptional abilities disproportion-ately recorded in individuals with autism113114 Addition-ally top-down information processing in individuals withautism is often characterised by reduced recognition ofthe global context115 and a strong preference to deriverule-based systems113 The neural bases are spatiallydistributed and task dependent but converge onenhanced recruitment of primary sensory cortices
d d it t f i ti d f t l ti
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volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
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mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1143
Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1243
Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1443
Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
7232019 2014 Lancet Autism Seminar amp Appendix
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
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httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
Age Description
Screening young children
Checklist for autism in toddlers (CHAT) 18 months 14-item questionnaire nine completed by parent or caregiver and five by
primary health-care provider takes 5ndash10 min
Ea rly scree ning of autistic traits (E SAT ) 14 mon ths 14-item questionnaire completed by health practitioners at well-baby visit
after interviewing parent or caregiver takes 5ndash10 min
Modified checklist for autism in toddlers (M-CHAT) 16ndash30 months 23-item questionnaire completed by parent or caregiver takes 5ndash10 min
Infant toddler checklist (ITC) 6ndash24 months 24-item questionnaire completed by parent or caregiver takes 5ndash10 min
Quantitative checklist for autism in toddlers
(Q-CHAT)
18ndash24 months 25-item questionnaire completed by parent or caregiver takes 5ndash10 min
ten-item short version available
Screening tool for autism in children aged 2 years
(STAT)
24ndash36 months 12 items and activities assessed by clinician or researcher after interacting
with the child takes 20 min intensive training nece ssary level-two
screening measure
Screening older children and adolescents
Social communication questionnaire (SCQ) gt4 years (and mental age
gt2 years)
40-item questionnaire completed by parent or caregiver takes 10ndash15 min
Social responsiveness scale first or second edition
(SRS SRS-2)
gt 2middot5 y ears 6 5-item quest io nnaire complet ed by parent caregiver t each er relat iv e or
friends (self-report form available for adult in SRS-2) takes 15ndash20 minChil dhood autism sc reening test (CA ST ) 4ndash11 years 37-ite m ques tionn aire completed by p arent or car egive r takes 10 ndash15 min
Autism spectrum screening questionnaire (ASSQ) 7ndash16 years 27-item questionnaire completed by parent caregiver or teacher takes
10 min
Autism spectrum quotient (AQ) child and
adolescent versions
Child 4ndash11 years
adolescent 10ndash16 years
50-item questionnaire completed by parent or caregiver takes 10ndash15 min
ten-item short versions available
Screening adults
Autism spectrum quotient (AQ) adult version gt16 years (with average or
above-average intelligence)
50-item questionnaire self-report takes 10ndash15 min ten-item short
version available
The Ritvo autism Asperger diagnostic scale-revised
(RAADS R)
gt18 years (with average or
above average intelligence)
80-item questionnaire self-report done with a clinicia n takes 60 min
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
Although many (high-functioning) individuals withautism achieve some degree of explicit or controlledmentalising101 the implicit automatic and intuitivecomponents are still impaired even in adulthood102 Early-onset mentalising diffi culties seem to be specific toautism but late-onset deficits are reported in disorderssuch as schizophrenia103 Mentalising is closely entwined
with executive control and language104 so that thedichotomous view of social versus non-social cognition ispotentially misleading in autism
Historically the domain of mentalising has beenlargely centred on others but self-referential cognitionand its neural substrates are also atypical in autism105106 Therefore deficits in the social domain are not onlyabout diffi culties in the processing of information aboutother people but also about processing of self-referentialinformation the relationship that self has in a socialcontext and the potential for using self as a proxy tounderstand the social world
A consistent network of brain regionsmdashincluding themedial prefrontal cortex superior temporal sulcustemporoparietal junction amygdala and fusiform gyrusmdashare hypoactive in autism across tasks in which socialperception and cognition are used100107108 Dysfunction inthe so-called mirror system (ie brain regions that are activeboth when an individual performs an action and observes
th f i th ti ) h b
that frontal parietal and striatal circuitry are themain systems implicated in executive dysfunction inautism107108 Executive dysfunction is not specific toautism it is commonly reported in other neuropsychiatricconditions (although with diff erent patterns) One viewis that strong executive function early in life could protectat-risk individuals from autism or other neurodevelop-
mental conditions by compensating for deficits in otherbrain systems112
Individuals with autism often have a preference for andsuperiority in processing of local rather than globalsensory-perceptual features (table 4) Individuals withoutautism often show the opposite profile This diff erencecould explain the excellent attention to detail enhancedsensory-perceptual processing and discrimination andidiosyncratic sensory responsivity (ie hyper-reactivity orhyporeactivity to sensory input or unusual interest insensory features of the environment) in autism It couldalso contribute to the exceptional abilities disproportion-ately recorded in individuals with autism113114 Addition-ally top-down information processing in individuals withautism is often characterised by reduced recognition ofthe global context115 and a strong preference to deriverule-based systems113 The neural bases are spatiallydistributed and task dependent but converge onenhanced recruitment of primary sensory cortices
d d it t f i ti d f t l ti
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
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Seminar
mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
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Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1443
Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
7232019 2014 Lancet Autism Seminar amp Appendix
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
Although many (high-functioning) individuals withautism achieve some degree of explicit or controlledmentalising101 the implicit automatic and intuitivecomponents are still impaired even in adulthood102 Early-onset mentalising diffi culties seem to be specific toautism but late-onset deficits are reported in disorderssuch as schizophrenia103 Mentalising is closely entwined
with executive control and language104 so that thedichotomous view of social versus non-social cognition ispotentially misleading in autism
Historically the domain of mentalising has beenlargely centred on others but self-referential cognitionand its neural substrates are also atypical in autism105106 Therefore deficits in the social domain are not onlyabout diffi culties in the processing of information aboutother people but also about processing of self-referentialinformation the relationship that self has in a socialcontext and the potential for using self as a proxy tounderstand the social world
A consistent network of brain regionsmdashincluding themedial prefrontal cortex superior temporal sulcustemporoparietal junction amygdala and fusiform gyrusmdashare hypoactive in autism across tasks in which socialperception and cognition are used100107108 Dysfunction inthe so-called mirror system (ie brain regions that are activeboth when an individual performs an action and observes
th f i th ti ) h b
that frontal parietal and striatal circuitry are themain systems implicated in executive dysfunction inautism107108 Executive dysfunction is not specific toautism it is commonly reported in other neuropsychiatricconditions (although with diff erent patterns) One viewis that strong executive function early in life could protectat-risk individuals from autism or other neurodevelop-
mental conditions by compensating for deficits in otherbrain systems112
Individuals with autism often have a preference for andsuperiority in processing of local rather than globalsensory-perceptual features (table 4) Individuals withoutautism often show the opposite profile This diff erencecould explain the excellent attention to detail enhancedsensory-perceptual processing and discrimination andidiosyncratic sensory responsivity (ie hyper-reactivity orhyporeactivity to sensory input or unusual interest insensory features of the environment) in autism It couldalso contribute to the exceptional abilities disproportion-ately recorded in individuals with autism113114 Addition-ally top-down information processing in individuals withautism is often characterised by reduced recognition ofthe global context115 and a strong preference to deriverule-based systems113 The neural bases are spatiallydistributed and task dependent but converge onenhanced recruitment of primary sensory cortices
d d it t f i ti d f t l ti
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volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
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Seminar
mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
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Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
7232019 2014 Lancet Autism Seminar amp Appendix
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
volume and microstructural properties)121ndash123 moleculargenetics (cell adhesion molecules and synaptic proteinsand excitatoryndashinhibitory imbalance)124 and informationprocessing have given rise to the idea that autism ischaracterised by atypical neural connectivity rather thanby a discrete set of atypical brain regions Ideas about theprecise way in which connectivity is atypical vary from
decreased fronto-posterior and enhanced parietal-occipitalconnectivity117125 reduced long-range and increased short-range connectivity126 to temporal binding deficits127 Al-though none fully explains all the data (findings dependon the definition of connectivity the developmental stageof the individual the spatial and temporal scales task vs no-task conditions how motion artifacts are handled andspecific neural systems of concern) they support theheuristic value of the tenet that neural networks in autismare atypical in various ways
One frequently reported neuroanatomical feature ofautism is a trajectory of generalised early brain over-growth when aged 6ndash24 months128 Other than increasesin total brain volume the amygdala is enlarged in youngchildren with autism129 although this enlargement is nolonger present by adolescence130 Early brain overgrowthtends to be reported more in boys who have develop-mental regression than in other subgroups131 and mightbe a result of generalised physical overgrowth132 or biased
f h d i f i t t di 133 Add
dogma of the so-called immune privilege of the CNS 141 Frequency of immunological anomalies is increased inindividuals with autism and their families142 In autismaltered immune processes aff ect a wide array of neuro-developmental processes (eg neurogenesis proliferationapoptosis synaptogenesis and synaptic pruning) withpersistent active neuroinflammation increased concen-
trations of pro-inflammatory cytokines in serum and cere-brospinal fluid and altered cellular immune functions143 Maternal IgG antibodies that target the fetal brain or othergestational immune dysregulation could be pathogenic insome cases144 Neuroimmune mechanisms could have keyroles in some aspects of the pathophysiology of autismbut the exact biology awaits clarification
In autism alterations in both serotonin andγ-aminobutyric-acid (GABA) systems have been reportedquite consistently145 such as hyperserotonaemia and analtered developmental trajectory of brain serotoninsynthesis capacity and reduction in the expression ofGABA synthetic enzymes and receptors Because of theirrelation with affi liative and social behaviours theoxytocin and vasopressin systemsrsquo roles in social impair-ments in autism are an active focus of investigationincluding treatment trials146 The role of androgens (andoestrogens) in modulation of risks and protectionsparticularly prenatally in the emergence of autism is also
b i t t d22 147 i i f th l ti id f
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
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Seminar
to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
7232019 2014 Lancet Autism Seminar amp Appendix
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1943
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
7232019 2014 Lancet Autism Seminar amp Appendix
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 943
Seminar
mutations with large eff ect sizes and common variationswith smaller eff ect sizes have a role124151
Rare mutations (ie minor allele frequency lt5 in thegeneral population) are frequently identified in autism andcan occur in the form of Mendelian genetic syndromes (so-called syndromic autism occurring in about 5 of allindividuals with autism) chromosomal abnormalities
(about 5) rare copy number variations (5ndash10)151ndash153 andde novo and transmitted point mutations (single nucleotidevariants) identified by exome sequencing150153 De novomutations (copy number variations in the form of micro-deletion or microduplication and single nucleotide vari-ants in the form of nonsense splice-site and frameshiftmutations) that occurred in the germline (especiallypaternal) have a large eff ect size and could be causal37ndash41 particularly in simplex cases (ie when only one individualin the family has autism) Equally copy number variationswith moderate eff ect sizes and variable expressivity andpenetrance could have some role124 However each identi-fied copy number variation only occurs in at most about1 of individuals with autism again suggesting sub-stantial genetic heterogeneity152 Some of these raremutations are clinically identifiable therefore screening isrecommended as part of routine clinical examination9495
In terms of common variants (eg single nucleotidepolymorphisms with allele frequency gt5 in the general
l ti ) id i ti t di h
communication reductions in disability and comorbiditypromotion of independence and provision of support tofamilies Additionally individuals should be helped tofulfil their potential in areas of strength Although autismis rooted in biology most eff ective interventions so farare behavioural and educational drugs have had only aminor role so far
Behavioural approachesVarious behavioural approaches exist156ndash158 and are classi-fied here into five complementary categories (table 5)Comprehensive approaches target a broad range of skills(cognitive language sensorimotor and adaptive behav-iours) via long-term intensive programmes and aregrouped into applied behaviour analysis and structuredteaching (table 5)159 The models based on applied behav-iour analysis originate from the Lovaas method160 and arecollectively referred to as early intensive behaviouralintervention The Early Start Denver Model is a furtherdevelopment in which a developmental framework andrelationship aspects are emphasised (table 5) Earlyintensive behavioural intervention seems to enable thedevelopment of intelligence communication and adap-tive function and to a lesser extent language daily livingskills and socialisation161 A shift from atypical to typi-cal neurophysiology has been reported after 2 years of
i t ti ith th E l St t D M d l 162 H
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1143
Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1443
Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
7232019 2014 Lancet Autism Seminar amp Appendix
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
7232019 2014 Lancet Autism Seminar amp Appendix
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
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=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
to enable transfer of skills to real-life settings andincreasing parentsrsquo and caregiversrsquo self-confidence(table 5)156 Programmes can be comprehensive(eg parent delivery of the Early Start Denver Model) ortargeted (eg at joint attention or communicationtable 5) The benefit of parent-mediated interventionalone is unclear and results are inconsistent (table 5)
Nevertheless parental and family involvement isimportant in therapist-mediated programmes79158
Sensory integration therapymdashfrequently used inoccupational therapymdashis sometimes off ered as one
component of a comprehensive programme to addresssensory-based problems However its eff ectiveness isinconclusive167 and it should not be considered as aroutine intervention for autism168
The US Health Resources and Services Administration158 and the UK National Institute for Health and CareExcellence74 have provided clinical guidelines for behav-
ioural interventions They stress that comprehensiveintervention should immediately follow diagnosis andshould be individualised (on the basis of developmen-tal level needs and assets) and engage the family
Target group Evidence for
eff ectiveness
Intervention framework and goals
Behavioural approaches
Comprehensive ABA-based
Early intensive behavioural intervention Young children (usually
aged lt5 years)
Low or moderate Based on ABA principles usually home-based or school-based application of discrete
trial training (ie teaching in simplified and structured steps) 11 adult-to-child ratiointensive teaching for 20ndash40 hweek for 1ndash4 years
Early intensive behavioural intervention
integrated with developmental and
relationship-based approaches (eg ESDM
and floortime [developmental individual-
diff erence relationship-based model])
Young children (usually
aged lt5 years)
Moderate or insuffi cient for
ESDM not established for
floortime
ESDM aims to accelerate childrenrsquos development in all domains intervention targets
derived from assessment of developmental skills stresses social-communicative
development interpersonal engagement imitation-based interpersonal
development and social attention and motivation integration of ABA principles and
pivotal response training (ie a naturalistic approach targeting so-called pivotal areas
of a childrsquos development including motivation response to multiple cues
self-management and initiation of social interactions)
Floortime emphasises functional emotional development individual diff erences in
sensory modulation processing and motor planning relationships and interactions
Comprehensive structured teaching
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1143
Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1443
Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
7232019 2014 Lancet Autism Seminar amp Appendix
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
7232019 2014 Lancet Autism Seminar amp Appendix
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1143
Seminar
Additionally they emphasise that social-communicationtraining (with a focus on social skills) should be off ered
d b l i di id l h ld h t iti t
disorder requires more study170 but is promising and hasbeen recommended (table 5)171 Initial evidence suggests
th t t ti l d i t f
Target group Evidence for
eff ectiveness
Intervention framework and goals
(Continued from previous page)
Drugs
Antipsychotic drugs
Risperidone aripiprazole Children adolescents
and adults
Children moderate
(risperidone) or high
(aripiprazole) for eff ect andhigh for adverse eff ect
adolescents and adults
insuffi cient but might have
eff ects as in children
To reduce challenging behaviours and repetitive behaviours potential adverse eff ects
include weight gain sedation extrapyramidal symptoms and hyperprolactinaemia
(risperidone)
Selective serotonin reuptake inhibitors
Citalopram escitalopram fluoxetine and
others
Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect
To reduce repetitive behaviours potential adverse eff ects include activation symptoms
(agitation) and gastrointestinal discomfort
Stimulant
Methylphenidate Children adolescents
and adults
Insuffi cient for eff ect and
adverse eff ect might be
helpful clinical guidelineestablished
To reduce attention-deficit hyperactivity disorder symptoms potential adverse eff ects
include insomnia decreased appetite weight loss headache and irritability
For version with full references see appendix ABA=applied behaviour analysis ESDM=Early Start Denver Model Suggested by available systematic reviews and meta-analyses with criteria directly following or
similar to the Grading of Recommendations Assessment Development and Evaluation Working Group recommendation diff erent ratings for the same model or agent are from diff erent reports
Table983093 Interventions by major model or agent
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3143
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
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ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
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I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
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ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
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ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
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ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
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ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
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QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1243
Seminar
recognition and interventions rely Third eff ective indiv-idualised educational and biomedical interventions for thewhole lifespan need to be established Fourth key environ-mental factors that interact with the complex geneticarchitecture of autism need to be identified Fifth howautism aff ects individuals in diff erent cultural contextsneeds to be understood Finally environments should be
made more autism friendlyContributors
M-CL did the initial literature search summarised findings andprepared the first draft of the report MVL prepared figures All authorscontributed to the writing of the report
Conflicts of interest
We declare that we have no conflicts of interest
Acknowledgments
All authors are supported by the European Autism InterventionsmdashA Multicentre Study for Developing New Medications (which receivessupport from the Innovative Medicines Initiative Joint Undertaking[grant agreement 115300] resources of which are composed of financialcontribution from the European Unionrsquos Seventh FrameworkProgramme [FP72007-2013] European Federation of PharmaceuticalIndustries and Associations companies and Autism Speaks) M-CL issupported by Wolfson College (University of Cambridge UK) MVL issupported by the British Academy and Jesus College (University ofCambridge UK) SB-C is supported by the Wellcome Trust the UKMedical Research Council the National Institute for Health ResearchCollaboration for Leadership in Applied Health Research and Care forCambridgeshire and Peterborough NHS Foundation Trust the AutismResearch Trust the European Union ASC-Inclusion Project and Target
A ti G W th k W i T S d Di b T t f
14 Baron-Cohen S Scott FJ Allison C et al Prevalence ofautism-spectrum conditions UK school-based population studyBr J Psychiatry 2009 194 500ndash09
15 Hsu S-W Chiang P-H Lin L-P Lin J-D Disparity in autismspectrum disorder prevalence among Taiwan National HealthInsurance enrollees age gender and urbanization eff ectsRes Autism Spectr Disord 2012 6 836ndash41
16 Idring S Rai D Dal H et al Autism spectrum disorders in thestockholm youth cohort design prevalence and validity PLoS One
2012 7 e41280 17 Blumberg SJ Bramlett MD Kogan MD Schieve LA Jones JR
Lu MC Changes in prevalence of parent-reported autism spectrumdisorder in school-aged US children 2007 to 2011ndash2012 HyattsvilleMD National Center for Health Statistics 2013
18 Russell G Rodgers LR Ukoumunne OC Ford T Prevalence ofparent-reported ASD and ADHD in the UK findings from theMillennium Cohort Study J Autism Dev Disord 2013 publishedonline May 30 DOI101007s10803-013-1849-0
19 Saemundsen E Magnusson P Georgsdottir I Egilsson ERafnsson V Prevalence of autism spectrum disorders in anIcelandic birth cohort BMJ Open 2013 3 e002748
20 Brugha TS McManus S Bankart J et al Epidemiology of autismspectrum disorders in adults in the community in EnglandArch Gen Psychiatry 2011 68 459ndash65
21 Barger BD Campbell JM McDonough JD Prevalence and onset ofregression within autism spectrum disorders a meta-analyticreview J Autism Dev Disord 2013 43 817ndash28
22 Baron-Cohen S Lombardo MV Auyeung B Ashwin EChakrabarti B Knickmeyer R Why are autism spectrum conditionsmore prevalent in males PLoS Biol 2011 9 e1001081
23 Begeer S Mandell D Wijnker-Holmes B et al Sex diff erences in thetiming of identification among children and adults with autismspectrum disorders J Autism Dev Disord 2013 43 1151ndash56
24 Giarelli E Wiggins LD Rice CE et al Sex diff erences in the
l ti d di i f ti t di d
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
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NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
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7232019 2014 Lancet Autism Seminar amp Appendix
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A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
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NU NB)41 ltltR 9gt G=HGF1
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VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
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VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
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QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
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ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
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)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
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amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
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GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1343
Seminar
36 Lampi KM Hinkka-Yli-Salomaki S Lehti V et al Parental age andrisk of autism spectrum disorders in a Finnish national birthcohort J Autism Dev Disord 2013 published online March 12DOI101007s10803-013-1801-3
37 Michaelson JJ Shi Y Gujral M et al Whole-genome sequencing inautism identifies hot spots for de novo germline mutation Cell 2012 151 1431ndash42
38 Kong A Frigge ML Masson G et al Rate of de novo mutations andthe importance of fatherrsquos age to disease risk Nature 2012 488 471ndash75
39 Neale BM Kou Y Liu L et al Patterns and rates of exonic de novomutations in autism spectrum disorders Nature 2012 485 242ndash45
40 OrsquoRoak BJ Vives L Girirajan S et al Sporadic autism exomesreveal a highly interconnected protein network of de novomutations Nature 2012 485 246ndash50
41 Sanders SJ Murtha MT Gupta AR et al De novo mutationsrevealed by whole-exome sequencing are strongly associated withautism Nature 2012 485 237ndash41
42 Sucksmith E Roth I Hoekstra RA Autistic traits below the clinicalthreshold re-examining the broader autism phenotype in the 21stcentury Neuropsychol Rev 2011 21 360ndash89
43 Roelfsema MT Hoekstra RA Allison C et al Are autism spectrum
conditions more prevalent in an information-technology regionA school-based study of three regions in the Netherlands J Autism Dev Disord 2012 42 734ndash39
44 Brown AS Sourander A Hinkka-Yli-Salomaki S McKeague IWSundvall J Surcel HM Elevated maternal C-reactive protein andautism in a national birth cohort Mol Psychiatry 2013 publishedonline Jan 22 DOI101038mp2012197
45 Gardener H Spiegelman D Buka SL Prenatal risk factors forautism comprehensive meta-analysis Br J Psychiatry 2009 195 7ndash14
46 Volk HE Lurmann F Penfold B Hertz-Picciotto I McConnell RTraffi c-related air pollution particulate matter and autism JAMA Psychiatry 2013 70 71ndash77
47 Roberts EM English PB Grether JK Windham GC Somberg L
W lff C M t l id i lt l ti id li ti
59 Lugnegard T Hallerback MU Gillberg C Personality disorders andautism spectrum disorders what are the connectionsCompr Psychiatry 2012 53 333ndash40
60 Joshi G Wozniak J Petty C et al Psychiatric comorbidity andfunctioning in a clinically referred population of adults with autismspectrum disorders a comparative study J Autism Dev Disord 201343 1314ndash25
61 Kohane IS McMurry A Weber G et al The co-morbidity burden ofchildren and young adults with autism spectrum disorders
PLoS One 2012 7 e33224 62 Simonoff E Jones CR Baird G Pickles A Happe F Charman T
The persistence and stability of psychiatric problems in adolescentswith autism spectrum disorders J Child Psychol Psychiatry 201354 186ndash94
63 Woolfenden S Sarkozy V Ridley G Coory M Williams K Asystematic review of two outcomes in autism spectrum disordermdashepilepsy and mortality Dev Med Child Neurol 2012 54 306ndash12
64 Bilder D Botts EL Smith KR et al Excess mortality and causes ofdeath in autism spectrum disorders a follow up of the 1980s UtahUCLA autism epidemiologic study J Autism Dev Disord 201343 1196ndash204
65 Howlin P Goode S Hutton J Rutter M Adult outcome for childrenwith autism J Child Psychol Psychiatry 2004 45 212ndash29
66 Billstedt E Gillberg C Gillberg C Autism after adolescencepopulation-based 13- to 22-year follow-up study of 120 individualswith autism diagnosed in childhood J Autism Dev Disord 200535 351ndash60
67 Howlin P Moss P Savage S Rutter M Social outcomes in mid- tolater adulthood among individuals diagnosed with autism andaverage nonverbal IQ as children J Am Acad Child Adolesc Psychiatry 2013 52 572ndash81
68 Farley MA McMahon WM Fombonne E et al Twenty-yearoutcome for individuals with autism and average or near-averagecognitive abilities Autism Res 2009 2 109ndash18
69 F t i C Wi t AS B PS Si d l t l
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1443
Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1743
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
7232019 2014 Lancet Autism Seminar amp Appendix
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
7232019 2014 Lancet Autism Seminar amp Appendix
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
7232019 2014 Lancet Autism Seminar amp Appendix
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
7232019 2014 Lancet Autism Seminar amp Appendix
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
7232019 2014 Lancet Autism Seminar amp Appendix
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2343
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
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=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1443
Seminar
83 Al-Qabandi M Gorter JW Rosenbaum P Early autism detectionare we ready for routine screening Pediatrics 2011 128 e211ndash17
84 Ozonoff S Iosif AM Baguio F et al A prospective study of theemergence of early behavioral signs of autism J Am Acad Child Adolesc Psychiatry 2010 49 256ndash66
85 Chawarska K Macari S Shic F Decreased spontaneous attention tosocial scenes in 6-month-old infants later diagnosed with autismspectrum disorders Biol Psychiatry 2013 74 195ndash203
86 Wan MW Green J Elsabbagh M Johnson M Charman T
Plummer F Quality of interaction between at-risk infants andcaregiver at 12ndash15 months is associated with 3-year autism outcome J Child Psychol Psychiatry 2013 54 763ndash71
87 Elison JT Paterson SJ Wolff JJ et al White matter microstructureand atypical visual orienting in 7-month-olds at risk for autismAm J Psychiatry 2013 published online March 20 DOI101176appiajp201212091150
88 Elsabbagh M Fernandes J Jane Webb S Dawson G Charman TJohnson MH Disengagement of visual attention in infancy isassociated with emerging autism in toddlerhood Biol Psychiatry 2013 74 189ndash94
89 Elsabbagh M Mercure E Hudry K et al Infant neural sensitivity todynamic eye gaze is associated with later emerging autismCurr Biol 2012 22 338ndash42
90 Wolff JJ Gu H Gerig G et al Diff erences in white matter fibertract development present from 6 to 24 months in infants withautism Am J Psychiatry 2012 169 589ndash600
91 Messinger D Young GS Ozonoff S et al Beyond autism a babysiblings research consortium study of high-risk children at threeyears of age J Am Acad Child Adolesc Psychiatry 2013 52 300ndash08
92 Ozonoff S Goodlin-Jones BL Solomon M Evidence-basedassessment of autism spectrum disorders in children andadolescents J Clin Child Adolesc Psychol 2005 34 523ndash40
93 Coleman M Gillberg C The autisms 4th edn New York NYOxford University Press 2012
94 H il KM S h f CP Th ti f ti t
108 Philip RC Dauvermann MR Whalley HC Baynham K Lawrie SMStanfield AC A systematic review and meta-analysis of the fMRIinvestigation of autism spectrum disorders Neurosci Biobehav Rev 2012 36 901ndash42
109 Hamilton AF Reflecting on the mirror neuron system in autisma systematic review of current theories Dev Cogn Neurosci 20133 91ndash105
110 Geurts HM Corbett B Solomon M The paradox of cognitiveflexibility in autism Trends Cogn Sci 2009 13 74ndash82
111 White SJ The triple I hypothesis taking another(lsquos) perspectiveon executive dysfunction in autism J Autism Dev Disord 201343 114ndash21
112 Johnson MH Executive function and developmental disordersthe flip side of the coin Trends Cogn Sci 2012 16 454ndash57
113 Baron-Cohen S Ashwin E Ashwin C Tavassoli T Chakrabarti BTalent in autism hyper-systemizing hyper-attention to detail andsensory hypersensitivity Philos Trans R Soc Lond B Biol Sci 2009364 1377ndash83
114 Mottron L Bouvet L Bonnel A et al Veridical mapping in thedevelopment of exceptional autistic abilities Neurosci Biobehav Rev 2013 37 209ndash28
115 Happe F Frith U The weak coherence account detail-focusedcognitive style in autism spectrum disorders J Autism Dev Disord 2006 36 5ndash25
116 Samson F Mottron L Soulieres I Zeffi ro TA Enhanced visualfunctioning in autism an ALE meta-analysis Hum Brain Mapp 2012 33 1553ndash81
117 Minshew NJ Keller TA The nature of brain dysfunction in autismfunctional brain imaging studies Curr Opin Neurol 201023 124ndash30
118 Ohnishi T Matsuda H Hashimoto T et al Abnormal regionalcerebral blood flow in childhood autism Brain 2000 123 1838ndash44
119 Baruth JM Wall CA Patterson MC Port JD Proton magneticresonance spectroscopy as a probe into the pathophysiology of
ti t di d (ASD) i A ti R 2013
7232019 2014 Lancet Autism Seminar amp Appendix
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Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1643
Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3143
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1543
Seminar
133 Raznahan A Wallace GL Antezana L et al Compared to whatEarly brain overgrowth in autism and the perils of populationnorms Biol Psychiatry 2013 published online May 23DOI101016jbiopsych201303022
134 Via E Radua J Cardoner N Happe F Mataix-Cols D Meta-analysisof gray matter abnormalities in autism spectrum disorder shouldAsperger disorder be subsumed under a broader umbrella ofautistic spectrum disorder Arch Gen Psychiatry 2011 68 409ndash18
135 Duerden EG Mak-Fan KM Taylor MJ Roberts SW Regional
diff erences in grey and white matter in children and adults withautism spectrum disorders an activation likelihood estimate (ALE)meta-analysis Autism Res 2012 5 49ndash66
136 Schumann CM Noctor SC Amaral DG Neuropathology of autismspectrum disorders postmortem studies In Amaral DGDawson G Geschwind DH eds Autism spectrum disordersNew York NY Oxford University Press 2011 539ndash65
137 Courchesne E Mouton PR Calhoun ME et al Neuron number andsize in prefrontal cortex of children with autism JAMA 2011306 2001ndash10
138 Voineagu I Wang X Johnston P et al Transcriptomic analysis ofautistic brain reveals convergent molecular pathology Nature 2011474 380ndash84
139 Casanova MF Neuropathological and genetic findings in autismthe significance of a putative minicolumnopathy Neuroscientist 2006 12 435ndash41
140 Rubenstein JL Three hypotheses for developmental defects thatmay underlie some forms of autism spectrum disorderCurr Opin Neurol 2010 23 118ndash23
141 McAllister AK van de Water J Breaking boundaries inneural-immune interactions Neuron 2009 64 9ndash12
142 Goines P Zimmerman A Ashwood P Van de Water J Theimmune system autoimmunity allergy and autism spectrumdisorders In Amaral DG Dawson G Geschwind DH eds Autismspectrum disorders New York NY Oxford University Press
2011 395 419
156 Dawson G Burner K Behavioral interventions in children andadolescents with autism spectrum disorder a review of recentfindings Curr Opin Pediatr 2011 23 616ndash20
157 Vismara LA Rogers SJ Behavioral treatments in autismspectrum disorder what do we know Annu Rev Clin Psychol 2010 6 447ndash68
158 Maglione MA Gans D Das L Timbie J Kasari C Nonmedicalinterventions for children with ASD recommended guidelines andfurther research needs Pediatrics 2012 130 (suppl 2) S169ndash78
159 Callahan K Shukla-Mehta S Magee S Wie M ABA versusTEACCH the case for defining and validating comprehensivetreatment models in autism J Autism Dev Disord 2010 40 74ndash88
160 Smith T Eikeseth S O Ivar Lovaas pioneer of applied behavioranalysis and intervention for children with autism J Autism Dev Disord 2011 41 375ndash8
161 Reichow B Barton EE Boyd BA Hume K Early intensive behavioralintervention (EIBI) for young children with autism spectrumdisorders (ASD) Cochrane Database Syst Rev 2012 10 CD009260
162 Dawson G Jones EJ Merkle K et al Early behavioral interventionis associated with normalized brain activity in young children withautism J Am Acad Child Adolesc Psychiatry 2012 51 1150ndash59
163 Kasari C Patterson S Interventions addressing social impairmentin autism Curr Psychiatry Rep 2012 14 713ndash25
164 Kaale A Smith L Sponheim E A randomized controlled trial ofpreschool-based joint attention intervention for children withautism J Child Psychol Psychiatry 2012 53 97ndash105
165 Kasari C Paparella T Freeman S Jahromi LB Language outcomein autism randomized comparison of joint attention and playinterventions J Consult Clin Psychol 2008 76 125ndash37
166 Landa RJ Holman KC OrsquoNeill AH Stuart EA Interventiontargeting development of socially synchronous engagement intoddlers with autism spectrum disorder a randomized controlledtrial J Child Psychol Psychiatry 2011 52 13ndash21
167 Zimmer M Desch L Sensory integration therapies for children
ith d l t l d b h i l di d P di t i 2012
7232019 2014 Lancet Autism Seminar amp Appendix
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Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
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lt
$amp )+- amp01 23 424$5-6
Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2643
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
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ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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=
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ltlt=KR 6B(BB2 =KK1
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7232019 2014 Lancet Autism Seminar amp Appendix
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5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
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(AB3 NU NB2561 ltR 9Ggt Ilt1
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7232019 2014 Lancet Autism Seminar amp Appendix
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9Kgt ltHFKH=1
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Supplementary appendix
This appendix formed part of the original submission and has been peer reviewedWe post it as supplied by the authors
Supplement to Lai M-C Lombardo MV Baron-Cohen S Autism Lancet2013 published
online Sept 26 httpdxdoiorg101016S0140-6736(13)61539-1
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Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
7232019 2014 Lancet Autism Seminar amp Appendix
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
7232019 2014 Lancet Autism Seminar amp Appendix
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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Appendix Table 1 Behavioural characteristics of autism
Core features in DSM-5 criteria
Persistent deficits in social communication
and social interaction across multiple
contexts
Deficits in social-emotional reciprocity
Deficits in non-verbal communicative behaviours used for social interaction
Deficits in developing maintaining and understanding relationships
Restricted repetitive patterns of behaviour
interests or activities
Stereotyped or repetitive motor movements use of objects or speech
Insistence on sameness inflexible adherence to routines or ritualised patterns of verbal or
non-verbal behaviour
Highly restricted fixated interests that are abnormal in intensity or focus
Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment
Associated features not in DSM-5 criteria
Atypical language development and
abilities2
Preschool age (lt 6 years) frequently deviant and delayed in comprehension two-thirds have
difficulty with expressive phonology and grammar
School age (≧6 years) deviant pragmatics semantics and morphology with relatively intact
articulation and syntax (ie early difficulties are resolved)
Motor abnormalities Motor delay hypotonia catatonia deficits in coordination movement preparation and planning
praxis gait and balance
Excellent attention to detail
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
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J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 1843
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Appendix Table 2 Common co-occurring conditions
Condition Proportion of
individualswith autism
affected
Comments
Developmental
Intellectual disability ~45 Prevalence estimate is affected by the diagnostic boundary and the definition of intelligence
(eg whether verbal ability is used as a criterion)
In individuals discrepant performance between subtests is common
Language disorders Variable In DSM-IV language delay was a defining feature of autism (autistic disorder) but is nolonger included in DSM-5
An autism-specific language profile (separate from language disorders) exists but with
substantial inter-individual variability2
Attention-deficit hyperactivitydisorder
28-44 - In DSM-IV not diagnosed when occurring in individuals with autism but no longer so inDSM-5
Clinical guidance available11
Tic disorders 14-38 ~6middot5 have Tourettersquos syndrome
Motor abnormality ≦7913 14 See Appendix Table 1
General medical
Epilepsy 8-30 Increased frequency in individuals with intellectual disability or genetic syndromes
Two peaks of onset early childhood and adolescence Increases risk of poor outcome
Clinical guidance available4 16
Gastrointestinal problems 9-70 Common symptoms include chronic constipation abdominal pain chronic diarrhoea and
gastro-oesophageal reflux18
Associated disorders include gastritis oesophagitis gastro-oesophageal reflux disease
inflammatory bowel disease coeliac disease Crohnrsquos disease and colitis19
Clinical guidance available17 18
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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7232019 2014 Lancet Autism Seminar amp Appendix
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=
Immune dysregulation ≦3820 Altered immune function which interacts with neurodevelopment could be a crucial
biological pathway underpinning autism21 Associated with allergic and autoimmune disorders20 22
Genetic syndromes ~5 Collectively called lsquosyndromic autismrsquo
Examples include fragile X syndrome (21-50 of individuals affected have autism) Rett
syndrome (most have autistic features but with profiles different from idiopathic autism)
tuberous sclerosis complex (24-60) Downrsquos syndrome (5-39) phenylketonuria (5-20)
CHARGE syndrome (coloboma of the eye heart defects atresia of the choanae retardation
of growth and development or both genital and urinary abnormalities or both and ear
abnormalities and deafness 15-50) Angelman syndrome (50-81) Timothy syndrome
(60-70) and Joubert syndrome (~40)
Sleep disorders 50-80 Insomnia is the most common
Clinical guidance available4 26 27
Psychiatric
Anxiety 42-56-
Common across all age groupsMost common are social anxiety disorder (13-29 of individuals with autism clinical
guidance available28) and generalised anxiety disorder (13-22)7-9
High-functioning individuals are more susceptible (or symptoms are more detectable)29
Depression 12-70 - Common in adults less common in children
High-functioning adults who are socially less impaired are more susceptible (or symptoms
are more detectable)30
Obsessive-compulsive disorder 7-24 - Shares the repetitive behaviour domain with autism that may cut across nosological
categories
Important to distinguish between repetitive behaviours that do not involve intrusive
anxiety-causing thoughts or obsessions (part of autism) and those that do (and are part of
obsessive-compulsive disorder)Psychotic disorders 12-17 Mainly in adults
Most commonly recurrent hallucinosis9
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
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)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
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JR amp9ltIgt lt=J=K1
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7232019 2014 Lancet Autism Seminar amp Appendix
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32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
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7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
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7232019 2014 Lancet Autism Seminar amp Appendix
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G
High frequency of autism-like features (even a diagnosis of autism spectrum disorder or
pervasive developmental disorder) preceding adult-onset (52)31 and childhood-onsetschizophrenia (30-50)32
Substance use disorders ≦16 Potentially because individual is using substances as self-medication to relieve anxiety
Oppositional defiant disorder 16-28 Oppositional behaviours could be a manifestation of anxiety resistance to change stubborn
belief in the correctness of own point of view difficulty seeing anotherrsquos point of view lack
of awareness of the effect of own behaviour on others or lack of interest in social
compliance10
Eating disorders 4-5 Could be a misdiagnosis of autism particularly in female individuals because both involverigid behaviour inflexible cognition self-focus and focus on details33
Personality disorders Particularly in high-functioning adults
Paranoid personality disorder 0-19 Could be secondary to difficulty understanding othersrsquo intentions and negative interpersonal
experiences34
Schizoid personality disorder 21-26 Partially overlapping diagnostic criteria with autism
Similar to Wingrsquos lsquolonersrsquo subgroup35
Schizotypal personality
disorder
2-13 Some overlapping criteria with autism especially those shared with schizoid personality
disorder
Borderline personality disorder 0-9 Could have similarity in behaviours (eg difficulties in interpersonal relationships
misattributing hostile intentions problems with affect regulation) which requires careful
differential diagnosis
Could be a misdiagnosis of autism particularly in female individuals
Obsessive-compulsive
personality disorder
19-32 Partially overlapping diagnostic criteria with autism
Avoidant personality disorder 13-25 Could be secondary to repeated failure in social experiences
Behavioural
Aggressive behaviours ≦6836 Often directed towards caregivers rather than non-caregivers
Could be a result of empathy difficulties anxiety sensory overload disruption of routines
and difficulties with communication
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltF
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NB)41 ltltR 9Igt ltJltH1
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BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
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QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
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F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
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=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
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G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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I
Self-injurious behaviours ≦5037 Associated with impulsivity and hyperactivity negative affect and lower levels of ability and
speech37 Could signal frustration in individuals with reduced communication as well as anxiety
sensory overload or disruption of routines
Could also become a repetitive habitCould cause tissue damage and need for restraint
Pica ~36 More likely in individuals with intellectual disability
Could be a result of a lack of social conformity to cultural categories of what is deemed
edible or sensory exploration or both
Suicidal ideation or attempt 11-14 Risks increase with concurrent depression and behavioural problems and after being teased
or bullied39
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
7232019 2014 Lancet Autism Seminar amp Appendix
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
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NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
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G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
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ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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F
Appendix Table 3 Screening and diagnostic instruments
Instrument Age Description Source
Screening young children
Checklist for Autism in Toddlers
(CHAT)41
at 18 months 14-item questionnaire nine completed by
parentcaregiver and five by primary
health-care provider takes 5-10 min
Public domain
httpwwwautismorgukworking-withh
ealthscreening-and-diagnosischecklist-fo
r-autism-in-toddlers-chataspx
Early Screening of Autistic Traits(ESAT)42
at 14 months 14-item questionnaire completed by health practitioners at well-baby visit after
interviewing parentcaregiver takes 5-10
min
Provided in the initial paper
Modified Checklist for Autism in
Toddlers (M-CHAT)44
16-30 months 23-item questionnaire completed by
parentcaregiver takes 5-10 min
Public domain
httpwwwmchatscreencom
Infant Toddler Checklist (ITC) 6-24 months 24-item questionnaire completed by parentcaregiver takes 5-10 min
Public domainhttpfirstwordsfsuedupdfchecklistpdf
Quantitative Checklist for Autism
in Toddlers (Q-CHAT)46
18-24 months 25-item questionnaire completed by
parentcaregiver takes 5-10 min 10-item
short version available47
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening Tool for Autism in
Children aged Two Years
(STAT)48
24-36 months 12 items and activities assessed by clinician
or researcher after interacting with the child
takes 20 min intensive training necessary
level-two screening measure
httpstatvueinnovationscom
Screening older children and
adolescents
Social CommunicationQuestionnaire (SCQ)49
gt4 years (andmental age gt2
years)
40-item questionnaire completed by parentcaregiver takes 10-15 min
Western Psychological Services(httpwwwwpspublishcom)
7232019 2014 Lancet Autism Seminar amp Appendix
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 2343
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H
Social Responsiveness Scale First
or Second Edition (SRS SRS-2)50
gt2middot5 years 65-item questionnaire completed by
parentcaregiver teacher relative or friends(self-report form available for adult in
SRS-2) takes 15-20 min
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Screening Test(CAST)51
4-11 years 37-item questionnaire completed by parentcaregiver takes 10-15 min
Public domainhttpwwwautismresearchcentrecomarc
_tests
Autism Spectrum Screening
Questionnaire (ASSQ)52
7-16 years 27-item questionnaire completed by
parentcaregiver or teacher takes 10 min
particularly sensitive for high-functioning
individuals
Provided in the initial paper
Autism Spectrum Quotient (AQ)
child53 and adolescent54 versions
Child 4-11
years
Adolescent
10-16 years
50-item questionnaire completed by
parentcaregiver takes 10-15 min 10-item
short versions available47 particularly
sensitive for high-functioning individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
Screening adults
Autism Spectrum Quotient (AQ)
adult version55
gt16 years (with
average or
above-average
intelligence)
50-item questionnaire self-report takes
10-15 min 10-item short version available47
particularly sensitive for high-functioning
individuals
Public domain
httpwwwautismresearchcentrecomarc
_tests
The Ritvo Autism Asperger
Diagnostic Scale-Revised
(RAADS-R )56
gt18 years (with
average or
above-average
intelligence)
80-item questionnaire self-report done with
a clinician takes 60 min
Provided in the initial paper
Diagnosis structured interview
The Autism DiagnosticInterview-Revised (ADI-R )57
Mental age gt2years
93-item interview of parentcaregiver takes1middot5-3 h intensive training necessary
Western Psychological Services(httpwwwwpspublishcom)
The Diagnostic Interview for All 362-item interview of parentcaregiver takes httpwwwautismorgukour-servicesdi
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
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BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
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K
Social and Communication
Disorders (DISCO)58
chronological
and mental ages
2-4 h intensive training necessary agnosing-complex-needsthe-diagnostic-i
nterview-for-social-and-communication-disorders-discoaspx
The Developmental Dimensional
and Diagnostic Interview (3Di)59
gt2 years 266-item computer-assisted interview of
parentcaregiver takes 2 h 53-itemshort-form available which takes 45 min60
intensive training necessary
httpwwwixdxorg3di-indexhtml
Diagnosis observational
measure
The Autism Diagnostic
Observation Schedule First or
Second Edition (ADOS
ADOS-2)61
gt12 months Clinical observation via interaction select
one from five available modules according to
expressive language level and chronological
age takes 40-60 min intensive training
necessary
Western Psychological Services
(httpwwwwpspublishcom)
Childhood Autism Rating ScaleFirst or Second Edition (CARS
CARS-2)62
gt2 years 15-item rating scale completed by clinicianor researcher takes 20-30 min accompanied
by a questionnaire done by parentcaregiver
moderate training necessary
Western Psychological Services(httpwwwwpspublishcom)
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
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ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
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J
Appendix Table 4 Cognitive domains in autism research
Domain Main behavioural features Main cognitive (psychological) constructs
Social cognition and
social perception
Atypical social interaction and social
communication
Gaze and eye contact emotion perception face processing biological
motion perception66 social attention and orienting67 social motivation68 social reward processing69 non-verbal communication70 imitation71
affective empathy and sympathy72 joint attention73 pretend play74 theory ofmind or mental perspective taking75-77 self-referential cognition78
alexithymia (difficulty understanding and describing own emotions)79 80
metacognitive awareness81
Executive function Repetitive and stereotyped behaviour
atypical social interaction and social
communication
Cognitive flexibility planning inhibitory control attention shifting
monitoring generativity working memory82
lsquoBottom-uprsquo and
lsquotop-downrsquo (local vs global) information
processing
Idiosyncratic sensory-perceptual
processing excellent attention todetail restricted interests and repetitive
behaviour atypical social interaction
and social communication
Global vs local perceptual functioning (superior low-level sensory-perceptual
processing)
83-85
lsquocentral coherencersquo (global vs local preference)
84
lsquosystemisingrsquo (drive to construct rule-based systems ability to understand
rule-based systems knowledge of factual systems)86
Local processing involves sensory and perceptual inputs global processing involves higher-level cortical control
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
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724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
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ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
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F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
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=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
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G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
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lt
Appendix Table 5 Interventions for autism
Category Major modelagent Target
group
Evidence foreffectiveness
Intervention framework and goals
Behaviouralapproaches
1
Comprehensive
ABA-based
EIBI Young
children
(usually aged
lt5 years)
Low or
moderate89
Based on ABA principles usually home-based or
school-based application of lsquodiscrete trial trainingrsquo (ie
a method of teaching in simplified and structured steps
instead of teaching an entire skill in one go the skill is
broken down and built-up using discrete trials that
teach each step one at a time) 11 adult-to-child ratio
intensive teaching for 20-40 hweek for 1-4 years87 90
EIBI integrated with
developmental and
relationship-basedapproaches (eg ESDM and
Floor-time)
Young
children
(usually agedlt5 years)
Moderate or
insufficient88 for
ESDM notestablished for
Floor-time
ESDM aims to accelerate childrenrsquos development in all
domains intervention targets derived from assessment
of developmental skills stresses social-communicativedevelopment interpersonal engagement
imitation-based interpersonal development and social
attention and motivation integration of ABA principles
and lsquopivotal response trainingrsquo (ie a naturalistic
approach targeting pivotal areas of a childs
development including motivation response to
multiple cues self-management and initiation of social
interactions)91
Floor-time (Developmental Individual-Difference
Relationship-Based model) emphasises functional
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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ltlt
emotional development individual differences in
sensory modulation processing and motor planning
relationships and interactions92
2 Comprehensive
structuredteaching
TEACCH Children
adolescentsand adults
Low Provides structures of the environment and activities
that can be understood by the individual usesindividualsrsquo relative strengths in visual skills and
interests to supplement weaker skills uses individualsrsquo
special interests to engage for learning supports
self-initiated use of meaningful communication93
3
Targeted
skill-based
intervention
PECS Non-verbal
individuals
Moderate Teaches spontaneous social-communication skills
through use of symbols or pictures94
Training in joint attention
pretend play socially
synchronous behaviourimitation emotion
recognition theory of
mind and functional
communication
Children Not established
but potentially
effective95
Fairly short-term (weeks to months) training sessions
targeting establishment of particular social cognitive
abilities fundamental to typical social-communicationdevelopment95-98
Teaching social skills (eg
emotion recognition
turn-taking) with areas of
interests (eg in machines
and systems)
Children
adolescents
and adults
Not established
but potentially
effective99-101
Short-term (weeks to months) interventions with DVDs
(eg Mindreading100 or The Transporters
99) or Lego
therapy101
Social skill training School-age
(≧6 years)
Low or
moderate89
Fairly short-term (weeks to months) training sessions to
build social skills usually through a group format95 102
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
children
adolescents
and adults
Training in living skills and
autonomy
Children
adolescentsand adults
Not established Targets establishment of living skills and
self-management to build autonomy positive behaviour support103 104
Vocational intervention Adolescentsand adults
Insufficient Eg interview training and on-the-job support
4 Targeted
behavioural
intervention for
anxiety and
aggression
CBT ABA Children
adolescents
and adults
Not established CBT to reducing anxiety modifies dysfunctional
thoughts compared with ordinary CBT CBT modified
for autism relies less on introspection and more on
teaching of practical adaptive skills with concrete
instructions often combined with social skill training
systematic desensitisation is useful particularly for
individuals with intellectual disability106
ABA to reduce aggression applies functional
behaviour assessment and teaches alternative
behaviours skills include antecedent manipulations
changes in instructional context reinforcement-basedstrategies and behaviour reduction strategies107
5 Parent-mediated
early
intervention
Training for joint
attention108 parent-child
interaction and
communication109 or
models like pivotal
response training
Young
children
Insufficient or
low112
Teaches parent or caregiver intervention strategies that
can be applied in home and community settings
potentially increasing parental efficacy and enabling
childrsquos generalisation of skills to real-life settings88 112
7232019 2014 Lancet Autism Seminar amp Appendix
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
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ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
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ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
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F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
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=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
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G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
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I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
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F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt=
P-ESDM and More
Than Words111
Drugs
1 Antipsychotic
drugs
Risperidone aripiprazole Children
adolescentsand adults
Children
moderate(risperidone) or
high(aripiprazole) for
effect and high
for adverse
effect113
adolescents and
adults
insufficient but
might have effects
as in children114
To reduce challenging behaviours and repetitive
behaviours potential adverse effects include weightgain sedation extrapyramidal symptoms and
hyperprolactinaemia (risperidone)
2
SSRI Citalopram escitalopram
fluoxetine and others
Children
adolescents
and adults
Insufficient for
effect and adverse
effect113-115
To reduce repetitive behaviours potential adverse
effects include lsquoactivation symptomsrsquo (agitation) and
gastro-intestinal discomfort
3 Stimulant Methylphenidate Children
adolescents
and adults
Insufficient for
effect and adverse
effect113 might be
helpful clinical
guideline
established11
To reduce attention-deficit hyperactivity disorder
symptoms potential adverse effects include insomnia
decreased appetite weight loss headache and
irritability
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
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H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltG
Evidence level Suggested by available systematic reviews and meta-analyses with criteria directly following or similar to the Grading of
Recommendations Assessment Development and Evaluation (GRADE) Working Group recommendation116 different ratings for the same model
or agent are from different reports lsquo Not establishedrsquo indicates no available systematic review or meta-analysis to date
Abbreviations ABA applied behaviour analysis CBT cognitive behavioural therapy EIBI early intensive behavioural intervention ESDM
Early Start Denver Model PECS Picture Exchange Communication System P-ESDM parent delivery of the ESDM SSRI selective serotonin
reuptake inhibitor TEACCH Treatment and Education of Autistic and related Communication-handicapped Children
7232019 2014 Lancet Autism Seminar amp Appendix
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ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
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NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
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$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
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GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltI
724$5- 284 $amp )+-
lt1 35) LBM)A5 BB2)A21 N)$2BA )6 7A)ABA) )() 2O A) NB2565B- IA 6A2 9N7Igt1 P)B$A2- Namp 35)
LBM)A5 L(4B$- Q1R lt=1
1 82(5 S1 TB)5 5UV BA5(A(5) )$()$ )(ABA BCA5(3 6B2565 )5)A5BAB )6 )(BB1 S amp6 LBM2 LBM)A5M1 ltR
9=gt ltJ==1
=1 W2(55 X- Y)BB ampS- Z)[ 7X- +26) Z- amp)(5)($ SY1 2A25 2256)A2 )(AB3 BCA5(3 6B2565B ) BMABB )6 3A)))MBB1 S
(AB3 NU NB2561 ltR $9ltgt ltHG1
G1 )B[ XL- SBA 77- 7C 7S1 amp2332 (522$) 232546AB )(AB3 BCA5(3 6B2565B1 amp(55 C L6)A51 ltltR 9Fgt FJltI1
I1 8)52amp2 7- BV ]- BV amp- ^)U)BB2 - amp)[5)4)5A 81 ^)A )(AB3 MC5BMBA3_$- MC5)AAA2 A2 6A) )6 BB25M
MC5BBAUAM1 L2B ^5)B T 72 +26 8 82 71 JR amp9ltIgt lt=HHK=1
F1 W2342 ]- (5[ 7- Y)$ 1 ]C6322$M 2O C5U)BU 6U2C3A) 6B2565B1 Q 3)5) Na- N)VB2 a- aBV6 NY- 6A25B1
(AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 Jltltlt1
H1 7322OO ]- L[B - amp)53) - amp)65 7- +2()B ^- 8)56 a1 LBM)A5 6B2565B 65 VA )(AB3 BCA5(3 6B2565B
C5U)- 232546AM- )6 )BB2)A6 O)A25B ) C2C()A265U6 B)3C1 S 3 )6 amp6 62B LBM)A5M1 KR 9Kgt JltJ1
K1 Y2OU)65 8- N253 T- amp)BA L- ZM6 - PA_ ]- 7A)45$ - A )1 LBM)A5 )6 CBM2B2) C5243B )6(AB VA
253)A$ )(AB3 BCA5(3 6B2565B1 8amp LBM)A5M1 JR ( =I1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltF
J1 +($$)56 ^- Y)54)[ c- a45$ amp1 LBM)A5 232546AM M2($ )6(AB VA ) ) 6)$2BB 2O BC5$5 BM65231 TB NU
NB)41 ltltR 9Igt ltJltH1
lt1 )AA) +- Y(5A$ ^- Y))CB)32 Y- S(BB) X- X((B[[2a)(OO 7- X - A )1 amp232546 CBM)A5 6B2565B )BB2)A6 VA BC5$5
BM6523D$O(A2$ )(AB3 ) 233(AM )6 4)B6 BA(6M1 S (AB3 NU NB2561 ltR $9Jgt ltKJ=1
ltlt1 ))d) T- 85) L- L)_5 T- PA)[5 - T245AB P- Y)6 8- A )1 amp) C5)A C)AV)MB O25 U)()A2 )6 36)A2 2
O25 )AAA26OADMC5)AUAM 6B2565 BM3CA23B )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltI=K1
lt1 8)52amp2 7- 7) 0+- Q_)$(55 S- Y25BM Y- T245AB2 1 ^ C5U) 2O aB 6 ) ^2(5AA BM6523 65 )6
)62BAB VA )(AB3 ) )5$ B) BA(6M1 LBM2 61 ltJJJR (9Igt ltltIltJ1
lt=1 a5 N- amp)53) ^- L[B - amp)65 7- +2()B ^- 7322OO ]- A )1 Q3C)53A 32U3A B[B 2O 65 VA )(ABA BCA5(3
6B2565B1 NU 6 amp6 Z(521 JR )9Ggt =ltltF1
ltG1 $ e- 853)234 - P)$5 aamp1 L5U) 2O 32A25 3C)53A )(AB3 BCA5(3 6B2565B1 85) NU1 HR (9Jgt IFIH1
ltI1 ^(3) T- amp()52 1 ]CCBM )6 )(AB3 (526U2C3A) C5BCAU1 amp(55 Z(52 Z(52B TC1 ltltR ))9Ggt GK=G1
ltF1 ^(3) T- BB)65 - amp()52 1 (AB3 BCA5(3 6B2565B )6 CCBM 32U$ A2V)56B ) 23C5BU )CC52) A2 A5)A3A1
85) NU1 ltR 9Jgt HltJ=1
ltH1 8( ^- amp)3C4 N8- W(B aS- =56- W(5(A) a^- +UM S- 0)6V)A5 S- A )1 ]U)()A2- 6)$2BB- )6 A5)A3A 2O $)BA52ABA)
6B2565B 6U6()B VA 7NB ) 2BB(B 5C25A1 L6)A5B1 ltR ) +-- ) 7ltltK1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltH
ltK1 8( ^- W(B aS- =56- W(5(A) a^- X2252B X- +UM S- +VB SN- A )1 T2336)A2B O25 U)()A2 )6 A5)A3A 2O 2332
$)BA52ABA) C5243B 65 VA 7NB1 L6)A5B1 ltR ) +-- ) 7ltJJ1
ltJ1 8)(3) +1 6) 232546AB )(AB3 )$B A2 6)$2BB )6 A5)A3A1 Z(52A5)C(AB1 ltR 9=gt =H1
1 amp Y- 7( ^L- amp b7- YB( SP- Y()$ X+- amp)$ PY- A )1 amp232546AM 2O )5$ )6 )(A233( 6B)BB C)AAB VA )(AB3
BCA5(3 6B2565 )A2V6 C2C()A24)B6 BA(6M1 TB)5 (AB3 7CA5(3 NB2565B1 lt=R 9gt Ilt1
lt1 25 amp- amp)5)$) - BV226 L1 ^ 52 2O 33( 6MBO(A2 A C)A2CMB22$M 2O )(AB31 85) 8)U Q33(1 ltR amp9=gt
=K=J1
1 a2B L- f3353) - BV226 L- 0) 6 P)A5 S1 ^ 33( BMBA3- )(A233(AM- )5$M- )6 )(AB3 BCA5(3 6B2565B1 Q
3)5) Na- N)VB2 a- aBV6 NY- 6A25B1 (AB3 7CA5(3 NB2565B1 ZV b25[- Zb EO256 cU5BAM L5BBR ltlt1 C1 =JIGltJ1
=1 7A S+- L)5[B)[ ZZ- aBV6 NY1 T)5 5A6 U)5)A2 )(AB3 4$$ A2 B A O25BA )6 ) OV A5B1 Z(521 lt=R 9gt
Jltlt1
G1 2BB S- Y2V L1 (AB3 BCA5(3 6B2565B $A BM6523B 3C)A2B O25 6)$2BB- A5UA2 )6 (65BA)6$ A V65
)(AB3 BCA5(3 6B2565 C2C()A21 S QAA NB)4 TB1 JR 9ltgt KIH=1
I1 8U(A2 - 2)U52 T- BB)65 T- )_ 8- amp(5)A22 L1 7M6523 )(AB3 )(BB )6 C)A2$A C)AV)MB1 P256 S L6)A51
JR 9=gt ltFJHF1
F1 X2A)$) 7- 85223) ]1 7C 65 VA )(AB3 BCA5(3 6B25651 L6)A5 Z(521 ltR 9Ggt GIlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
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=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
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K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
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lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3443
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ltK
H1 )2V 8- 8M)5B X- S2B2 X- PBB 7- 85) L- a263) 7]- A )1 C5)A C)AV)M O25 A 6AO)A2- U)()A2- )6
3))$3A 2O B23) 65 )6 )62BAB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$ +-- 7ltFG1
K1 ^MB2 X]- amp5(BB Na1 NOO5A)A$ $O(A2$ )(AB3 )6 B2) C24)1 S (AB3 NU NB2561 ltR 9Hgt ltGHHJ1
J1 PB452A N- a)62V XN- N0A ampS- L2352M S1 ^ C5BA)A2 2O )EAM 65 VA C5U)BU 6U2C3A) 6B2565B1 S
amp6 62B LBM2C)53)21 IR )9=gt GHHJF1
=1 7A5$ +- N)VB2 a- ]BAB - a5B2 S1 amp)5)A5BAB )BB2)A6 VA C5B 2O 6C5BBU BM3CA23B )6(AB VA )(AB3
BCA5(3 6B25651 S (AB3 NU NB2561 KR 9Fgt ltltltK1
=lt1 c$ Y)54)[ - +($$)56 ^- a45$ amp1 QB )(AB3 BCA5(3 6B2565 2332 B_2C5)g LBM)A5M TB1 ltR )(9ltgt ltH1
=1 T)C2C25A S- amp)U_ - a5BA N- 66$A2 - a2$A)M Z1 (AB3 BCA5(3 6B2565B )6 62262BA B_2C5) ) )6
422$) 2A54(A2B A2 ) 5)A2 5UBA61 S 3 )6 amp6 62B LBM)A5M1 JR 9ltgt ltK1
==1 65B)V - ^5)B(5 S- Y)34522[ N- ^)A(5) X- 736A c1 QB )25E) 5U2B) ) U5B2 2O )(AB3 BCA5(3 6B2565Bg ](5 ])A
NB256 TU1 ltltR )(9Fgt GFHG1
=G1 +($$)56 ^- Y)54)[ c- a45$ amp1 L5B2)AM 6B2565B )6 )(AB3 BCA5(3 6B2565B V)A )5 A 2A2Bg amp23C5
LBM)A5M1 ltR 9Ggt ===G1
=I1 P$ +1 )(ABA BCA5(31 +)A1 ltJJHR $9JJ=gt ltHFltF1
=F1 X) 7- )_(5[ 1 $$5BB2 65 )6 )62BAB VA 7N C5U) )6 5B[ O)A25B1 S (AB3 NU NB2561 ltltR )9Hgt
JF=H1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
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=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
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lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3543
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
ltJ
=H1 T)56B amp- U5 amp- ZB2 +- 2BB S1 7Od(52(B 4)U2(5 6U6()B VA )(AB3 BCA5(3 6B2565 )6 AA() 6B)4AM1 S
QAA NB)4 TB1 ltR amp9Igt GHFKJ1
=K1 +20(2 70- )AB2 S+1 amp232546 CBM2C)A22$M )6(AB VA (AB3 7CA5(3 NB2565B )6 AA() 6B)4AB1 TB NU NB)41
JR $9Fgt ltKKJF1
=J1 )MB 7N- a253) - YV$a)5) S- 7M6 ]1 7(6 6)A2 )6 )AA3CAB 65 VA )(AB31 TB)5 (AB3 7CA5(3
NB2565B1 lt=R 9ltgt ltJltJ1
G1 7A25 ]- 7([2VB[ +- Z)6)( S- +V 8- 526 ]8- (A LS- A )1 ^ C2322$M )6 ) 255)AB 2O B(6) A2($AB
)6 4)U25B M2(A VA )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 lt=1
Glt1 8)52amp2 7- amp2E - 8)56 a- 7VAA)3 S- Z$A$) Z- 25$) X- A )1 LBM22$) 3)5[5B A 6AA2 2O )(AB3 O)M
) )5$ C2C()A21 85 S LBM)A5M1 ltJJFR )amp9gt ltIKF=1
G1 NA_ amp- 7V[B 7- U) N)) ]- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 6B2565 65 )$6 ltGltI 32AB1 QQC2C()A2 B5$ VA A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 NB$ )6 $5) O6$B1 S (AB3 NU NB2561 FR
amp9Fgt Hlt=1
G=1 7V[B 7Y- NA_ amp- U) N)) ]- X5[2O QY- U) ]$)6 Y- 8(A))5 SX1 75$ O25 )(ABA BCA5(3 65 )$6 ltG A2 ltI
32AB1 Q A 6U2C3A 2O A ])5M 75$ 2O (ABA ^5)AB `(BA2)5 9]7^gt1 S (AB3 NU NB2561 FR amp9Fgt H==1
GG1 X3) S- T24B N+- 0A2) L]- L)6M S- 8225BA Yamp- ]BB5 ]+- A )1 ^ 326O6 [BA O25 )(AB3 A2665B ) O22V(C
BA(6M UBA$)A$ A )5M 6AA2 2O )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 KR 9Igt KH=J1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3643
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
GI1 PA54M - 852B))662E 7- L) 0- ZVA2 +1 0)6)A2 2O A QO)A^2665 amp[BA )B ) 452)64)6 B55 O25 )(AB3
BCA5(3 6B2565B O523 J A2 G 32AB 2O )$1 (AB31 KR )9Igt GKHIltlt1
GF1 B2 amp- 8)52amp2 7- PV5$A 7- amp)53) ^- T5 S- L)B2 a- A )1 ^ `ampY^ 9 ()AA)AU ampY[BA O25 (AB3 ^2665Bgt
) 253)M 6BA54(A6 h()AA)AU 3)B(5 2O )(ABA A5)AB )A ltKG 32AB 2O )$ C53)5M 5C25A1 S (AB3 NU NB2561 KR 9KgtltGltGI1
GH1 B2 amp- (M($ 8- 8)52amp2 71 ^2V)56 45O iT6 W)$Bi O25 )(AB3 B5$ ^ 725A (AB3 7CA5(3 (2AA )6 A 725A
`()AA)AU amp[BA O25 (AB3 A2665B lt- )BB )6 =- 2A52B j255A6k1 S 3 )6 amp6 62B LBM)A5M1 ltR )9gt
lt H1
GK1 7A2 P+- amp22526 ]]- ^(55 +- L2_62 7+1 LBM23A5 C52C5AB 2O A 7^^ O25 )5M )(AB3 B5$1 S (AB3 NU NB2561 GR
9Fgt FJltHlt1
GJ1 amp25B2 amp- Y(B 0- L[B - TB 7- amp22[ ]Y- S51- +UA) 8+- A )1 8AV ) Tamp )6 ) )56 C) 6B2 3)[$ )6 3)[$ 6B2B
)42(A (B$ A 7amp`1 S amp6 LBM2 LBM)A5M1 HR 9Jgt J=G1
I1 amp2BA)A2 SZ- +)UBB5 LN- f)$ b- 44) - a5)M ^- ^266 TN1 T)C6 h()AA)AU )BBBB3A 2O )(ABA B2) 3C)53A 4M
)BB5223 A)5B1 S 3 )6 amp6 62B LBM)A5M1 HR amp9ltgt ltFFKHF1
Ilt1 P)3B S- 72AA W- 7A2AA amp- B2 amp- 82A2 L- 8)52amp2 7- A )1 ^ amp7 9amp6226 BC5$5 7M6523 BAgt ABA )(5)M1 (AB31
IR (9ltgt GIFK1
I1 ]5B 7- a45$ amp- P$ +1 B5$ h(BA2)5 O25 BC5$5 BM6523 )6 2A5 $O(A2$ )(AB3 BCA5(3 6B2565B
B22 )$ 651 S (AB3 NU NB2561 ltJJJR (9gt ltJGlt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3743
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
lt
I=1 (M($ 8- 8)52amp2 7- PV5$A 7- B2 amp1 ^ (AB3 7CA5(3 `(2AA amp65lB 05B2 9`amp6gt1 S (AB3 NU NB2561
KR 9Hgt lt=G1
IG1 8)52amp2 7- Y2[BA5) T- X[3M5 T- PV5$A 71 ^ (AB37CA5(3 `(2AA 9`gt)62BA U5B21 S (AB3 NU NB2561
FR amp9=gt =G=I1
II1 8)52amp2 7- PV5$A 7- 7[5 T- )5A S- amp(4M ]1 ^ )(AB3BCA5(3 h(2AA 9`gt U6 O523 BC5$5
BM6523D$O(A2$ )(AB3- 3)B )6 O3)B- BABAB )6 3)A3)A)B1 S (AB3 NU NB2561 ltR )9ltgt IltH1
IF1 TAU2 T- TAU2 ]T- a(A5 N- TAU2 S- Y(O)$ NY- )2 P- A )1 ^ TAU2 (AB3 BC5$5 N)$2BA 7)TUB6 9TN7Tgt )
B) A2 )BBBA A 6)$2BB 2O (AB3 7CA5(3 NB2565 )6(AB ) A5)A2) U)6)A2 BA(6M1 S (AB3 NU NB2561 ltltR )9Kgt ltHFKJ1
IH1 +256 amp- T(AA5 - + amp2(A(5 1 (AB3 N)$2BA QA5UVTUB6 ) 5UB6 U5B2 2O ) 6)$2BA A5UV O25 )5$U5B 2O
6U6()B VA C2BB4 C5U)BU 6U2C3A) 6B2565B1 S (AB3 NU NB2561 ltJJGR 9Igt FIJKI1
IK1 P$ +- +[)3 7T- +44M 7S- a2(6 S- +)5234 1 ^ N)$2BA QA5UV O25 72) )6 amp233()A2 NB2565B 4)[$52(6-A55)A5 5)4AM )6 ) (B1 S amp6 LBM2 LBM)A5M1 R 9=gt =HI1
IJ1 7[(B N- P)55$A2 T- 8B2C N- amp2V6(5M c- +)( S- )6M P- A )1 6U2C3A)- 63B2) )6 6)$2BA A5UV 9=6gt )
2U 23C(A5_6 )BBBB3A O25 )(AB3 BCA5(3 6B2565B1 S 3 )6 amp6 62B LBM)A5M1 GR 9Igt IGKIK1
F1 7)A2B LS- )6M PL- L((5) X- X))5A - P)55$A2 T- 7[(B NY1 ^ 2BA5(A2 )6 U)6)A2 2O ) B25A O253 2O A
6U2C3A)- 6)$2BA )6 63B2) A5UV1 ](5 amp6 62B LBM)A5M1 JR )9Kgt IltG1
Flt1 +256 amp- TB 7- +)345A +- amp22[ ]Y- S51- +UA) 8+- N+)U25 Lamp- A )1 ^ )(AB3 6)$2BA 24B5U)A2 B6($5 ) BA)6)56
3)B(5 2O B2) )6 233()A2 6OAB )BB2)A6 VA A BCA5(3 2O )(AB31 S (AB3 NU NB2561 R $9=gt I=1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
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I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3843
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F1 )$M)5 ampQ- L)62O 01 W)A25 BA5(A(5 U)()A2 2O A 6226 )(AB3 5)A$ B)1 S (AB3 NU NB2561 HR 9Jgt ltHKHJG1
F=1 7d( - S2B2 Y1 AMC) M 2A)A )(AB3 326B- 3)B3B )6 6U2C3A1 Z(52B 824)U TU1 JR 9Kgt
ltGltG1
FG1 Y)53B 8- )5A - P)) a+1 W)) 32A2 52$A2 )(AB3 BCA5(3 6B2565B ) 5UV 2O 4)U25) )6 (523)$$
BA(6B1 Z(52CBM2 TU1 ltR $9=gt J=1
FI1 P$A 7- X26VM X- X)VB5 Z1 W) 6AAM 52$A2 )(AB3 BCA5(3 6B2565B 5UV 2O 4)U25) BA(6B1 Z(52B
824)U TU1 ltR amp9=gt ltFKG1
FF1 X)B5 N- LC5M X1 NB5(CA6 )A2 C5CA2 )(AB3 4)U25) U6- (5262C2AMCB- )6 6)$2BA (AAM1 NU
amp2$ Z(52B1 ltR 9ltgt I=I1
FH1 N)VB2 a- ^2A X- 442AA T- BA5$ S- (B2 S- ]BAB - A )1 ])5M B2) )AAA2 3C)53AB )(AB3 B2) 25A$- d2A
)AAA2- )6 )AAA2 A2 6BA5BB1 NU LBM21 GR $9gt HltK=1
FK1 ampU)5 amp- X2B a- ^52) 0- 8526[ ]7- 7(A_ T^1 ^ B2) 32AU)A2 A25M 2O )(AB31 ^56B amp2$ 71 ltR)amp9Ggt =ltJ1
FJ1 NA5 a71 W(A2) 3)$A 5B2) 3)$$ 2O )(AB3 BCA5(3 6B2565B1 N)2$(B amp Z(52B1 ltR )9=gt =ltJIlt1
H1 ^)A)3 N1 amp) A V256 )OO256 )(ABA BCA5(3 6B2565g +262- cX SBB) X$BM L(4B5BR J1
Hlt1 7UU5 - aB S1 E)3)A2 2O A BA)A 2O 3A)A2 5B)5 65 VA )(AB3 QBB(B 2O 6OA2 )6 3A2622$M1 TB
NU NB)41 ltR )9Igt JHFKG1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
H
ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 3943
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
=
H1 8)52amp2 7- PV5$A 71 ^ 3C)AM h(2AA ) UBA$)A2 2O )6(AB VA BC5$5 BM6523 25 $ O(A2$ )(AB3- )6
253) BE 6OO5B1 S (AB3 NU NB2561 GR 9gt ltF=HI1
H=1 (6M L- 7(U) +- )BA5$25$ 1 C)5) )6 6BA54(A6C52BB$ 326 2O d2A )AAA2- B2) 2$A2 )6 )(AB31 (AB3
TB1 JR 9ltgt lt1
HG1 S)5526 amp1 5UV 2O 5B)5 A2 C5A6 C)M )(AB31 (AB31 =R 9Ggt =HJJ1
HI1 82(5 S1 L(AA$ A25M 2O 36 AB C) CBM22$) EC))A2B 2O A B2232A2)233()AU 3C)53AB )(ABA
BCA5(3 6B25651 (AB31 ltR )amp9=gt FGF1
HF1 7d( 1 7C2A)2(B A25M 2O 36 )6 AB )4B )(AB3 BCA5(3 6B2565B1 Z(52BABA1 ltltR )9gt ltKlt=1
HH1 8)52amp2 71 646BB BB)M 2 )(AB3 )6 A25M 2O 361 82BA2 Q^ L5BBD85)6O256 822[BR ltJJI1
HK1 +234)562 0- 8)52amp2 71 ^ 52 2O A BO 3646BB )(AB31 amp2B2(B amp2$1 ltltR $9ltgt lt=G1
HJ1 W5A c1 PM V 6 2$AU EC))A2B 2O )(AB31 ` S ]EC LBM2 9Y2Ugt1 ltR amp9ltltgt H=J1
K1 856 a- amp22[ T1 E6 32A2B A 2A54(A2 2O )EAM3) A2 A 32A2) BM3CA23B 2O )(AB31 ^5)B)A2) CBM)A5M1 lt=R
KI1
Klt1 amp)55(A5B L1 Y2V V [2V 2(5 2V 36B A 5)A2BC 4AV 365)6$ )6 3A)2$A21 8)U 85) 71 JR 9gt
ltlt=KR 6B(BB2 =KK1
K1 Y ]+1 ]U)()A$ A A25M 2O E(AU 6MBO(A2 )(AB31 NU2C3A) TUV1 GR 9gt ltKJ==1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4043
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
G
K=1 2AA52 +- N)VB2 - 72(5B Q- Y(45A 8- 8(5)[ S1 ])6 C5CA() O(A2$ )(AB3 ) (C6)A- )6 $A C5CB 2O
)(ABA C5CA21 S (AB3 NU NB2561 FR amp9ltgt HG=1
KG1 Y)CC W- W5A c1 V)[ 25 )2(A 6A)O2(B6 2$AU BAM )(AB3 BCA5(3 6B2565B1 S (AB3 NU NB2561 FR
amp9ltgt II1
KI1 L)BA6 a5)A X- N)UB a1 L5CA2 )6 )CC5CA2 )(AB3 5dA$ A U5B )BB(3CA21 L2B ^5)B T 72 +26 8 82 71
JR amp9ltIgt lt=J=K1
KF1 8)52amp2 71 (AB3- MC5BMBA3_$- )6 A5(A1 S ]EC LBM2 9amp2BA5gt1 KR amp)9ltgt FGHI1
KH1 T2V 8- 8)5A2 ]]- 82M6 8- Y(3 X1 ])5M ABU 4)U25) A5UA2 9]Q8Qgt O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B
97Ngt1 amp25) N)A)4)B 7MBA TU1 ltR )$ ampNJF1
KK1 P)55 f- LA5B +- 7)A Z- W2BBW$ SY- a)BB5 - 0BA5)0)65V S1 BMBA3)A 5UV 2O )5M ABU A5UA2
O25 )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt==ltlt1
KJ1 )$2 - a)B N- N)B +- ^34 S- X)B)5 amp1 Z236) A5UA2B O25 65 VA 7N 523366 $(6B )6 O(5A5
5B)5 6B1 L6)A5B1 ltR )$ +-- 7ltFJHK1
J1 T2V 81 U5UV 2O 3A)))MBB 2 )5M ABU 4)U25) A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B1 S
(AB3 NU NB2561 ltR 9Ggt Ilt1
Jlt1 T2$5B 7S- N)VB2 a1 ])5M 7A)5A NU5 26 O25 b2($ amp65 VA (AB3 L5232A$ +)$()$- +)5$- )6 ]$)$3A1 ZV
b25[- Zb ^ a(O256 L5BBR lt1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
I
J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
F
lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4143
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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J1 a5BC) 7Q- P65 7- 732B T1 ^ amp6 VA 7C) Z6B ]2(5)$$ QAA() )6 ]32A2) a52VA1 T)6$- L5B(B
822[BR ltJJK1
J=1 B42U a8- 7) 01 ^ ^]ampampY C52$5)3 A 5) 2O U64)B6 C5)A1 S (AB3 NU NB2561 ltR $9Igt IHJ1
JG1 826M - W52BA +1 ^ LA(5 ]E)$ amp233()A2 7MBA31 8)U 26O1 ltR 9Igt HIGG1
JI1 X)B)5 amp- L)AA5B2 71 QA5UA2B )665BB$ B2) 3C)53A )(AB31 amp(55 LBM)A5M TC1 ltR )9Fgt Hlt=I1
JF1 8$5 7- aU5B amp- ampOO256 L- 052U - X)A X- Y2664) ]- A )1 ^25M 2O 6 A5)$ 65 VA )(AB3 ) 5)623_6
2A526 A5)1 S (AB3 NU NB2561 ltltR )9Kgt JJHltF1
JH1 Q$5B2 81 85O 5C25A OOA 2O ) O2(B6 3A)A2 A5UA2 2 B2) O(A2$ 65 VA )(AB31 S (AB3 NU NB2561 ltR
9Kgt ltHFKH=1
JK1 ) Ta1 W(A2) 233()A2 A5)$ 5UV 2O A A5)A(5 5)A6 A2 65 VA )(AB31 ]6()A2 )6 ^5)$ NU2C3A) NB)4AB1 FR )9=gt lt=1
JJ1 a2) - BV ]- a5))65 b- ampA2[ 7- N)M X- +$$AA 0- A )1 ])$ 32A2 52$A2 65 VA )(AB3 BCA5(3
26A2B ) A5UA2 (B$ )3)A6 UB VA 5) 32A2) O)B1 S (AB3 NU NB2561 ltR $9=gt FJHJ1
lt1 a2) - 8)52amp2 71 7MBA3_$ 3C)AM A)$ )6(AB VA BC5$5 BM6523 25 $O(A2$ )(AB3 A2 52$_ 23CE
32A2B (B$ A5)AU 3(A36)1 NU LBM2C)A21 FR )9gt IJltFltH1
ltlt1 VB a- a5))65 b- Y(3C5M - 8)52amp2 71 +]a A5)CM )6 A B2) (B 2O )$()$ C52$5)33 ) U)()A2 2O AV2 B2)
B[B A5UA2B O25 65 VA $ O(A2$ )(AB3 )6 BC5$5 7M65231 S (AB3 NU NB2561 KR 9ltgt ltJGGIH1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
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lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
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ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4243
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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lt1 T2V 8- 7A5 - 02[3)5 W1 72) B[B $52(CB O25 C2C )$6 F A2 lt VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25) N)A)4)B
7MBA TU1 ltR ampNKIltlt1
lt=1 7543) +- X2$ T+1 W2BA5$ BO3))$3A L)5A6U56 CU2A) 5BC2B A5)$ O25 65 VA )(ABA 6B25651 Q N1
Y]- SB L7- 6A25B1 LBM2B2) A5)A3A O25 6 )6 )62BA 6B2565B ]3C5)M 4)B6 BA5)A$B O25 ) C5)A1 P)B$A2-Namp 35) LBM22$) BB2)A2R ltJJF1 C1 III1
ltG1 +(MBM S- Y255 TY- N()C a- 4 TP- 8 XT1 L2BAU 4)U25 B(CC25A VA O)3B1 Q +(MBM S- N()C a- 4 TP-
6A25B1 W)3B )6 C2BAU 4)U25 B(CC25A 665BB$ C5243 4)U25B O)3M 2AEAB1 8)A325- N L)( 8522[BR 1 C1 =G=1
ltI1 ^)M25 S+- LA5B +- 7)A Z- N2U N- 0BA5)0)65V S- P)55 f1 BMBA3)A 5UV 2O U2)A2) A5UA2B O25
M2($ )6(AB VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltR )$9=gt I=ltK1
ltF1 +)$ T- T$BA5 - +)(656) 7- B4)($ X- Y)5$ 1 ^5)A3A 2O )EAM )(AB3 BCA5(3 6B2565B (B$ 2$AU 4)U2(5
A5)CM BMBA3)A 5UV1 NU Z(525)41 ltR )9ltgt I=F=1
ltH1 852B) S- Y)M 1 5UV 2O 4)U25) A5UA2B O25 A A5)A3A 2O )$$5BB2 6U6()B VA 6U2C3A) 6B)4AB1 TB
NU NB)41 ltltR 9gt G=HGF1
ltK1 X)B)5 amp- a(B5(6 amp- P2$ amp- XV2 7- +2[ S1 T)623_6 2A526 )5$U5 36)A6 d2A $)$3A A5UA2 O25 A2665B
VA )(AB31 S (AB3 NU NB2561 ltR $9Jgt ltGIIF1
ltJ1 a5 S- amp)53) ^- amp2) Y- 656 amp- 723B 0- Y2V L- A )1 L)5A36)A6 233()A2O2(B6 A5)A3A 65
VA )(AB3 9Lamp^gt ) 5)623B6 2A526 A5)1 +)A1 ltR 9JH=gt ltIF1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1
7232019 2014 Lancet Autism Seminar amp Appendix
httpslidepdfcomreaderfull2014-lancet-autism-seminar-appendix 4343
$amp() +)- ) 01 +234)562- 732 8)52amp21 9lt=gt1 73)5 (AB31 amp() 1 AACDD6E162125$Dlt1ltltFD7ltGFH=F9lt=gtFltI=Jlt
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ltlt1 T2$5B 7S- ]BAB - +256 amp- 0B3)5) +- PA5 S- WA_C)A5[ - A )1 ]OOAB 2O ) 85O ])5M 7A)5A NU5 26 9]7Ngt8)B6 L)5A
QA5UA2 2 ^2665B )A TB[ O25 (AB3 7CA5(3 NB2565B T)623_6 amp2A526 ^5)1 S 3 )6 amp6 62B LBM)A5M1 ltR
)9ltgt ltIFI1
ltltlt1 amp)5A5 7- BB$5 N7- 7A2 P+- amp3 7- Z)3)B 7- b265 L1 5)623_6 2A526 A5) 2O Y)lB l25 ^) P256Bl A2665B VA )5M )(AB3 BM3CA23B1 S amp6 LBM2 LBM)A5M1 ltltR 9Hgt HGltI1
ltlt1 22 QL- Y2M ]S- amp2) Y1 L)5A36)A6 )5M A5UA2 O25 M2($ 65 VA )(AB3 BCA5(3 6B2565B 97Ngt1 amp25)
N)A)4)B 7MBA TU1 lt=R ampNJHHG1
ltlt=1 LA5B +- P)55 f- 7)A Z- 85(_[ S+- X5B)BV)3 7- S523 TZ- A )1 BMBA3)A 5UV 2O 36) A5)A3AB O25 65
VA )(AB3 BCA5(3 6B2565B1 L6)A5B1 ltltR )9Igt lt=ltlt1
ltltG1 N2U N- P)55 f- LA5B +- ^)M25 S+- 7)A Z- 0BA5)0)65P S1 6)A2B O25 )62BAB )6 M2($ )6(AB VA
)(AB3 BCA5(3 6B2565B ) BMBA3)A 5UV1 L6)A5B1 ltR )$9Ggt HltHF1
ltltI1 P)3B X- 85$ - T)6) - 72U Z- Y)_ L1 7AU B52A2 5(CA)[ 4A25B 977TQBgt O25 )(AB3 BCA5(3 6B2565B 97Ngt1
amp25) N)A)4)B 7MBA TU1 lt=R ampNGFHH1
ltltF1 A[B N- 8BA N- 85BB L- ]B - W)[bAA5 b- W2AA25C 7- A )1 a5)6$ h()AM 2O U6 )6 BA5$A 2O 52336)A2B1 8S1
GR 9HGIGgt ltGJ1