Clinicalfeatures and cognitive impairments in methamphetamine use disorder Clinical features and...
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Transcript of Clinicalfeatures and cognitive impairments in methamphetamine use disorder Clinical features and...
ClinicalClinical features and cognitive features and cognitive impairments in methamphetamine impairments in methamphetamine use disorderuse disorderMin Zhao, M.D & Ph.D., Prof. of Psychiatry
Shanghai Mental Health CenterShanghai Mental Health Center
Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong University School of Medicine
April 22-24, 2015, Hangzhou, ChinaApril 22-24, 2015, Hangzhou, China
MA recreational use have increased dramatically in recent yearsThe second most widely abused drugs 38% are ATS users in 2013 in China 90% new drug usersAnnual prevalence of drug use at the global level, by illicit drug category, 2009-2010
18%
6.6%
42.1%
20.6%Nu
mb
er o
f re
sist
ed d
rug
u
sers
in C
hin
a (m
illio
n)
Background
NNCC, 2013 UNODC, 2013
Consequences of chronic MA useprolonged psychiatric symptoms (Scott, 2007)
Depression, anxiety and so on
Conginitive impairments
Poor quality of life, stress
HIV/AIDS risk, and other psychosocial consequences
Background
MA abuse associates with substantial neurotoxicityImpact multiple neurotransmitter systems,
e.g. Dopamine (DA), serotonin, glutamate (Volz, 2007)
Background
MA use relates with brain structural and functional abnormotiesStructural
frontal-striatum, limbic system, hippocampus, anterior cingulate cortex, amygdaloid (Sekine, 2001, 2006)
corpus callosum (Nakama, 2011)Functional
Frontal lobar, ventral inferior frontal gyrus (tobias 2010)
Background
MA addicts showes broad cognitive impairmentsE.g. verbal memory, visual spatial memory, prospective memory, working
memory, cognitive inhibition, attention networks, decision-making (Scott, 2007)Could these impairments improve after MA abstinence? (Iudicello 2010 )
Broad cognitive impairments
remain after 3-month abstinence improve partially
after 1-year abstinence
Background
MA executive function impairment and the Stroop Task
MA addicts suffer from executive function impairment, which might relate with relapse
The stroop task: test the congnitive controlCould predict drop-out treatment risk
(Lubman,2004)fMRI: prefrontal lobar hypoactivition (Chang
L,2007)
Background
Clinical features and psychosocial wellbeing of MA dependent individuals
Cogitive impairments and its changes after MA abstinence
Brain activity of abstinent MA users in word-color interference Stroop task
Hippocampal volume in recent abstinent MA users
Outline of the presentation
Part 1: The clinical features and psychosocial wellbeing of MA dependent individuals
Aims: Describe and understand the clinical features
and psychosocial wellbeing of chronic MA users
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
Methods
Cross-section survey, MA users were recruited from compulsory rehabilitation center in 2013
Interviewed by SCID-I for diagonsis (substance use disorder module), and diagnosed as ATS dependenc or abuse by DSM-IV were recruited
ASI, BIS, GAD, PSS and social support rating scale(SSRS), psychiatric symptom checklist were adminitrated to the participants
Approved by the Institutional Review
Total (n=216)gender male, n(%) 76.2% female, n(%) 23.8%age, mean(SD) 37.05 (9.84)nation han, n(%) 97.1% minority, n(%) 2.9%education 1-9 years, n(%) 64.5%
>10 years, n(%) 35.5%marriage married , n(%) 63.0% unmarried, n(%) 37.0%employment unemployed, n(%) 50.6% employed, n(%) 49.4%
Demographic characteristics of the participants
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
The age of onset of MA, 32.14 ±10.10 years old
The average years of MA use, 4.49 ±3.93 years
The frequencies of MA use in last month, 9.1±20.5 days
The average dose, 0.39±0.35gram
61(28.2%) diagnosed as MA induced psychosis
167(77.3%) diagnosed as MA dependence, 49(22.7%) diagnosed as ATS abuse
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
Drug use and clinical diagonosis for the participants
49 (90.7%) 47 (87.1%)
30 (55.6%)25 (46.3%)
13 (24.1%)
5 (9.3%)
0%
25%
50%
75%
100%
Halluc
inatio
ns
Delusio
ns
Lack
of t
hough
t
Hypob
ulia
Suicida
l ideat
ion
Suicida
l beha
vior
Pro
port
ions
of
MA
use
rsw
ith p
sych
iatr
ic s
ympt
om;
n, %
Distributions of psychiatric Symptoms among participants who reported psychaitric symtoms
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
Psychological wellbings(M±q , n ( %)项 目 Total(n=216) Male(n=159) Femal(n=57 ) Z 值 / 2值 p
Depression 6.802 0.009
BDI 分 <20 119 ( 55%) 96 ( 60.4%) 23(40.4%)
BDI分≥ 20 97 ( 45%) 63(39.6%) 34(59.6%)
Anxity 4.362 0.037
GAD 分 <5 107 ( 49.5%) 87(54.7%) 22(38.6%)
GAD分≥ 5 109 ( 50.5%) 72(45.3%) 35(61.4%)
PSS* 16.7±8 16±8 19±8 -2.692 0.007
SSRS* 26.95±8.06 26.5±11.2 27±9 -0.363 0.717
注: * 数据非正态分布,采用秩和检验;其余采用卡方检验
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
ASI scores among MA induced psychoses ( M±q)
项 目 MA induces psychoses(n=61)
Without MA induced psychoses
( n=155 )Z p
ASI total scores 2.01±0.88 1.61±1.03 -3.709 <0.001
Physical health 0±0.24 0±0.23 -0.57 0.568
Employment 0.67±0.52 0.67±0.41 -1.055 0.291
Alcohol ues 0.085±0.24 0.059±0.3 -0.37 0.711
Drug use 0.16±0.152 0.13±0.153 -2.297 0.022
Legal problems 0.2±0.37 0.2±0.35 -0.346 0.729
Family and social support
0.27±0.49 0.2±0.27 -2.642 0.008
Mental health 0.4±0.41 0.14±0.34 -5.427 <0.001
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
Pschological wellbings among ATS induced psychoses ( M±q , n( % ) )
项 目ATS induces
psychoses( n=61)
Without ATS induces psychoses
( n=155 )Z 值 /2值 p
Depression 12.44 <0.001
BDI评分 <20 22(36.1%) 97(62.6%)
BDI ≥评分 20 39(63.9%) 58(37.4%)
Anxity 10.625 0.001
GAD评分 <5 20(32.8%) 89(57.4%)
GAD ≥评分 5 41(67.2%) 66(42.6%)
SSRS* 25±9.5 27±10 -0.898 0.369
PSS* 20±7.5 16±8 -4.373 <0.001
注: * 数据非正态分布,采用秩和检验;其余采用卡方检验
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
ASI between ATS dependence and abuse ( M±q)
Dependence(n=167)
Abuse ( n=49 ) Z p
ASI total scores 1.88±0.94 1.31±0.6 -4.501 <0.001
Physical health 0±0.27 0±0.11 -1.433 0.152
Employment 0.67±0.52 0.67±0.32 -0.071 0.944
Alcohol ues 0.089±0.3 0.028±0.24 -1.786 0.074
Drug use 0.15±0.16 0.082±0.115 -4.999 <0.001
Legal problems 0.2±0.4 0.05±0.225 -2.492 0.013
Family and social support 0.22±0.35 0.19±0.13 -2.181 0.029
Mental health 0.27±0.41 0.09±0.21 -4.702 <0.001
Part 1. The clinical features and psychosocial wellbeing of MA dependent individuals
Pschological wellbings betweem ATS dependence and abuse ( M±q , n( % ) )
dependence ( n=167)
Abuse(n=49 ) Z/ 2 p
Depression 2.672 0.102
BDI评分 <20 87(52.1%) 32(65.3%)
BDI ≥评分 20 80(47.9%) 17(34.7%)
Anxity 9.08 0.003
GAD评分 <5 75(44.9%) 34(69.4%)
GAD ≥评分 5 92(55.1%) 15(30.6%)
SSRS* 27±10 27±12 -0.242 0.808
PSS* 17±7 14±10.5 -2.803 0.005
注: * 数据非正态分布,采用秩和检验;其余采用卡方检验
Part 2. Cognitive functions among ATS dependent patients
Aim: to understand the cognitive function and its
changes after MA abstinence for 6 months
Case control and longitudinal study Subjects: MA=54, HC=58 Inclusion criteria:
(1) more than 9 years of education; (2) aged between 18 and 45 years old; (3) Han nationality and proficient at Chinese (4) normal or corrected-to-normal vision and hearing.
Exclusive criteria: (1) physical or neurological illnesses affecting cognitive
function (e.g., stroke, seizure, or a severe head injury);(2) other Axis I disorder of DSM-IV criteria; (3) use of cognitive enhancing drugs within 6 months of
study enrollment; and (4) substance dependence other than nicotine, within the
past 5 years.
Part 2. Cognitive functions among ATS dependent patients
Measurements:The cognitive assessments: the CogState
batteryWHO-quality of life instrument (WHOQOL-BREF) Social Adaptation Self-evaluation Scale (SASS) Beck depression scale-II CogState Battery: 8 dimensions, baseline, 3, 6
months afterInternational shopping list task (ISL, verbal memory)Detection Task (DET, processing speed) Identification Task (IDN, tapping attention/vigilance)One Card Learning Task (OCL, visual memory)Two Back Task (TWOB, working memory)Social Emotional Cognition Task (SEC, social cognition)Continuous Paired Association Learning Task (CPAL,
spatial working) The Groton Maze Learning Task (GML, memoryproblem
solving and error monitoring)
Part 2. Cognitive functions among ATS dependent patients
Demographics data and drug use history
MA group (n=54)HC group (n=58)
χ2 or t P
Male$, n (%) 40 (74.1%) 37 (63.8%) 1.37 0.503Age#(years), mean (SD) 33.89 (7.47) 30.52 (6.55) 2,54 0.12
Years of Education#, mean (SD) 9.80 (1.83)*** 14.26 (3.70) 8.18 <0.001
Married$, n (%) 16(29.63%) *** 36 (62.07%) 11.83 <0.001
Smoking$, n (%) 5 (90.74%) *** 36 (62.07%) 12.56 <0.001
Employed within the last year, n (%) 24 (44.4%)
MA onset age (years), mean (SD) 28.78 (8.59)Years of MA use, mean (SD) 4.14 (3.42)Days of abstinence, mean (SD) 44.85 (20.65)Heroin users 5 years ago before study entry, n (%)
22 (40.7%)
Part 2. Cognitive functions among ATS dependent patients
The psychological wellbeing of MA addicts
MA group (n =54) HC group (n=58) t value P
SASS 31.98 (6.95) 35.97(6.51) 3.13 0.002
WHO-QOL
Physical health 24.46 (3.54) 26.40 (3.21) 3.03 0.003
Psychological health 18.48 (4.18) 21.67 (3.40) 4.44 <0.001
Social relationships 10.50 (2.16) 11.60 (2.66) 2.04 0.018
Environment 25.41 (5.50) 28.52 (9.04) 2.18 0.031
Total score 78.81 (12.30) 86.77 (10.30) 3.7 <0.001
Part 2. Cognitive functions among ATS dependent patients
Cognitive function of MA addicts
MA group HC group
Baseline 3m later 6m later Baseline 3m later 6m later
DET 2.54 (0.15) 2.58 (0.10) 2.61 (0.09) 2.59 (0.11) 2.60 (0.09) 2.55 (0.09)
IDN 2.71 (0.08) 2.73 (0.08) 2.75 (0.08) 2.73 (0.06) 2.73 (0.09) 2.73 (0.07)
OCL 1.01 (0.10) 1.01 (0.11) 1.05 (0.12) 1.01 (0.12) 1.11 (0.37) 1.05 (0.10)
TWOB 1.17 (0.18) 1.21 (0.22) 1.25 (0.17) 1.27 (0.16) 1.27 (0.17) 1.29 (0.17)
GML 72.3 (25.9)62.39 (23.5)
51.41 (25.5) 55.16 (27.6)43.12 (13.5)
46.16 (19.6)
ISL 19.62 (4.3)22.52 (4.26)
23.44 (3.93) 24.36 (4.0)24.84 (4.70)
26.00 (4.14)
SEC 1.06 (0.16) 1.14 (0.11) 1.16 (0.14) 1.22 (0.12) 1.16 (0.10) 1.15 (0.08)
CPAL 114.62 (54.26)
77.36 (43.06)
70.09 (47.24)
48.00 (29.45)
24.16 (12.79)
30.72 (16.81)
Part 2. Cognitive functions among ATS dependent patients
-0.10 OCL
IDN0.19
DET0.22
-0.40 TWOB* -0.57
GML**
-1.28 ISL***
-0.62 SEC**
-0.96 CPAL***
-0.44 COMP***
-1.50
-1.20
-0.90
-0.60
-0.30
0.00
0.30
Healthy control means
Z-s
core
s
Figure 3. Magnitude of impairment of relative to healthy controls in the CogState Battery. Abbreviation: ISLT International Shopping List Task, DET Detection Task, IDN Identification Task, OCL One Card Learning Task, ONB One Back Task, CPAL Continuous Paired Association Task, GML Groton Maze Learning Task, SEC social emotional cognition, COMP composite score. Numbers of the figure are Z score. *P<0.05, **P<0.01, ***P<0.001
Part 2. Cognitive functions among ATS dependent patients
Figure 4. Follow-up assessment of cognitive function in the MA and HC groups *P<0.05. Abbreviation: GML Groton Maze Learning Task. ISL International Shopping, SEC social emotional cognition, List Task
** * *
*
Hoffman (2006) √ Morgan (2012) √ Hoffman (2006) ×
Verbal memory Visual memory
Salo (2009a) √ van der Plas (2009) √
Salo (2009b) ×
Working memory
Error monitoring
Attention
Processing speed
Social cognition Kim (2011) √ Payer (2008) √
•MA addicts endure broad cognitive impairments
Verbal memory
• longitudinal : Indicelllo (2010)
• Cross sectional: no improvement in 3 month abstinence
Error monitoring
• longitudinal : Indicelllo (2010)
• Cross sectional : Van der Plas (2010), IGT 、 WCST 、 Stroop
Social cognition • Henry (2009),6-month
abstinence , MA<HC
•MA addcits cognitive impariments could partially improve
MethodsSubjects: MA group (n=28):
over 1 year MA useTotal lifetime MA consumption > 50 g
Health control (n=26): age, sex matched
Inform consent
• fMRI scan• stroop task simultaneously
•Demorgraphic data•Abuse history•Clinical data
•Stroop task training•8min
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
The words-color interference Stroop taskE-prime 2.0 Block design, psudo-random
congruency incongruency rest
red red/red/red +
•Stimulus presented 2 s •Rest 2-12 s
•Mean 5875ms• reaction time, total errors
•( RTincon—RTcon ) / RTcon
Methods
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
fMRI: Simens 3.0T, event related fMRI
EPIT1
AC-PC lineLocalizing
Scans
TR=2530msTE=2.34ms1*1*1plane resolution192 layer
TR=2000msTE=30ms90°flip angle31 layer , 4.5mm thickness64*64 matrix3*3*4.5 plane resolution
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
Mean (SD)MA group ( n=28)
HC group (n=26)
Age 32.81 ( 6.62) 32.80 ( 7.15)Male % 18 ( 66.7%) 16 ( 61.5%)Years of education* 9.65 ( 1.83) 11.52 ( 2.40)Marriage % 5 ( 18.5%)
MA onset age 26.05 ( 7.23)
Lifetime MA use 6.76 ( 3.82)
Days of MA abstinent 168.48 ( 46.08)
•Demographic and clinical data
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
•Stroop effects
•No main effects in group or interaction无
•( RTincon—RTcon ) / RTcon ( t=1.43,P=0.16 )
MA group HC group
congruent In-- congruent In--
RT a 932.17 (158.68)
1088.93 (150.30)
908.28 (138.86)
1038.56 (192.12)
error 29.98 (3.17) 29.63 (2.57) 30.69 (1.69) 29.96 (2.32)
•The performance of the Stroop task
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
whole brain one-sample t-test for brain activity in both groups
• robust activations in whole brain, mainly in anterior cingulated cortex (ACC), parietal lobe, insula, precuneus, prefrontal, temporal, occipital lobes , cerebellum
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
The comparison of brain activity in MA addicts and health controls
BrodmannX
(mm)Y
(mm)Z
(mm)Z P
Incongruent and congruent condition ( MA<HC)
precuneus 7 -21 -42 48 3.35 0.000
Cingulated gyrus 32 -21 9 36 2.89 0.001
Postcentral gyrus 2 -36 -30 30 3.14 0.001
Left anterior lobe -- -12 -45 -27 3.14 0.001
Right anterior lobe -- 24 -30 -27 2.97 0.001
Congruent condition ( MA>HC)
Right insula 13 42 15 -9 3.66 0.000
Left insula 13 -45 -9 0 3.50 0.000
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
precuneus
Postcentral gyrus
Cingulated gyrus
anterior lobe
Right insula Left insula
Precuneus sensormotor anterior region
Relates with memory, executive function, attention
ACC (BA24、 32、 33): solving conflicts e.g. Kerns 2009; Salo 2009
PCC(BA23): AD
anterior lobe
Relates with attention, language
MA addicts showed hypofunction in areas related with cognitive function
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
•within lateral sulcus
•elated with interoceptive awareness, emotion, motor, social cognition
•craving
• Some studies revealed that insular may have relationship with cocaine, alcohol, heroin and nicotine addictio
MA addcits showed heperfunction in areas related with craving
Part 3. Brain activity of abstinent MA users in word-color interference Stroop task
a cross-sectional study to examine hippocampal volume, and its relationship with cognitive function
29 healthy controls and 32 patients
Part 4. Hippocampal volume in recent abstinent MA users
CharacteristicsControls (N=29) Patients(N=30)
t / F P(Mean±SD) (Mean±SD)
Gender (Male/Female) Fisher’s exact
test 0.779
Male Female Male Female F Age (years) 33.42±6.45 32.00±8.23 34.00±4.87 30.30±8.71 0.772 0.515
Education (years) 10.95±2.39 13.00±2.58 9.48±1.87 10.40±2.22 5.684 0.002
Total Male Female t
Duration of abstinence (months) N/A 5.52±1.59 6.41±1.03 3.75±0.82 7.084 <0.001
Age of onseta N/A 26.10±7.15 27.40±6.60 23.50±7.85 1.434 0.163
Duration of drug use (months) N/A 75.93±43.28 74.75±31.04 78.30±63.19 -0.208 0.836
Duration of continuous drug useb (months)
N/A 7.98±13.69 7.53±14.18 8.89±13.32 -0.254 0.802
Average number of grams of MA used per occasionc (gram)
N/A 0.66±0.48 0.55±0.35 0.87±0.64 -1.467 0.169
Part 4.Hippocampal volume in recent abstinent MA users
• No group or gender main effect, group*gender interaction for the
right (p=0.020) but not left (p=0.249) relative hippocampal
volume
• female patients and female controls (t(18) =-1.984, p=0.063), male
patients and male controls (t(37) = 0.802, p=0.427)
Part 4.Hippocampal volume in recent abstinent MA users
• male controls and female controls (t(27) = -4.443, p<0.001) , male patients and female patients (t(28) = -1.303, p=0.203)
• a smaller volume of right hippocampus in female but not in male abstinent MA users compared to healthy controls.
Part 4.Hippocampal volume in recent abstinent MA users
Summery and conclusions
ATS dependent individuals experience high rates of psychaitric symtoms and had poor psychosocial wellbeing (such as depression, anxity, stress, quality of life, social adaption)
ATS dependent individuals show broad cognitive impairments (e.g. memory, working memory, executive function, social cognition) , some cognitive domain(executive function, verbal memory, social cognition) improve after abstinence
ATS dependent individuals appear to have hypo-activity in some brain regions related to cognitive function, and hyper-activity in region related with craving
Hippocampal volume reduction in female but not male recent abstinent MA users
Thanks for your attention
Min ZhaoMin Zhao
[email protected]@gmail.com
Look forward to collaborating with you in futureLook forward to collaborating with you in future