Obsessive Compulsive Disorder Biology and Management

Prof. Hani Hamed Dessoki, M.D.PsychiatryProf. Hani Hamed Dessoki, M.D.PsychiatryProf. PsychiatryProf. Psychiatry

Chairman of Psychiatry DepartmentChairman of Psychiatry Department

Beni Suef UniversityBeni Suef University

Supervisor of Psychiatry DepartmentSupervisor of Psychiatry Department

El-Fayoum UniversityEl-Fayoum University

APA memberAPA member

History

• Since the fourth century BC, obsessional behaviour was explained as “melancholia”, a distinct disease with particular mental and physical symptoms.

• Melancholia (Greek for black bile) was supposedly caused by an imbalance the four bodily fluids or humours.

• Hippocrates, in his Aphorisms, characterized “all fears and despondencies, if they last a long time" as being symptomatic of melancholia.

History

• In 17th century England, the concept of "religious melancholy" became established as the cause of a many mental disorders including those with OCD-like symptoms.

Facts and Figures

• Prevalence– Originally believed to be rare

• >0.1%

– Recent evidence suggests 1-3% Onset / Characteristics:

– Males:, high prevalence of checking– Females:, high prevalence of washing

OCD in DSM 5

APA 2013

CHANGERemoves obsessive-compulsive disorder from category of Anxiety Disorders and places it in new category of Obsessive-Compulsive and Related Disorders

Obsessive-Compulsive DisorderBody dysmorphic disorderHoarding disorderHair-pulling disorder (trichotillomania)Excoriation (Skin-Picking) disorderSubstance/Medication –induced OCDOthers

Obsessive-Compulsive and related Disorders

OCD

undesired, Irrational, Intrusive, Repetitive compulsions or obsessions, (Ego- Dystonic,

alien), unwanted thought, urges or actions,

unsuccessful ability to resist, unacceptable (Patient realizes its absurdity) + anxiety and impaired functioning

What is an Obsession?

• Involuntary intrusive cognition

• Types

• Doubts (74%)

• Thinking (34%)

• Fears (26%)

• Impulses (17%)

• Images (7%)

• Other (2%)

Themes in Obsessions

• Obsessions often have common themes– Contamination, dirt, disease, illness (46%)– Violence and aggression (29%)– Moral and religious topics (11%)– Symmetry and sequence (27%)– Sex (10%)– Other (22%)

• The themes often reflect contemporary concerns (the devil, germs, AIDS)

Linking Obsessions and Compulsions

OCD and “Normal” Experience

• Obsessional thoughts found in 90% of people– It is well replicated that 80%+ of normal people

have intrusive thoughts– There thoughts are similar in content and form

to OCD patients

• Compulsions– Many people have compulsions such as

stereotyped or superstitious behaviors– 66% of normal people report some form of

checking behavior

• Is OCD qualitatively distinct?

NEUROBIOLOGY OF OCD

A. Genetics1. Twin Studies - high concordance in

monozygotic twins.2. Family Studies - frequency of OCD

higher among 1st degree relatives.3. Link between TS and OCD

a. 50% of TS have OCBb. Sex-specific phenotype (females

who inherit TS gene may only have OCB)

NEUROBIOLOGY OF OCD

B. Neuroanatomy1. Basal ganglia dysfunction

a. OCB is observed in movement disorders (PD, HD, TS) b. High conc. 5-HT in BG

2. “Frontal Lobe” Dysfunction a. Abnormalities on imaging b. Hypermetabolism on PET c. Similar patterns of cognitive test

performance

(5HT) exaggerated sensitivity of post-synaptic 5HT1A & 2A , as well as abnormal reg. of pre-synaptic 5HT1A

Stimulation of 5HT1B, 1C, 1D exacerbate OCD Stimulation of 5HT3 exacerbate anxiety, OCD?

The role of serotonin

Pytliak M et al. Physiol. Res. 2011, 60:15-25Camarena B et al., International Journal of Neuropsychopharmacology (2004), 7, 49–53.

Family of 5HT receptors

Mood

Exacerbate OCD

Anxiety, agitation, appetite

Exacerbate OCD

Sleep-sex-anxiety

Anxiety, GIT

Anxiety, appetite, ↓ learning

Sleep

Anxiety, cognition

Anxiety, memory

Pytliak M et al. Physiol. Res. 2011, 60:15-25Camarena B et al., International Journal of Neuropsychopharmacology (2004), 7, 49–53.

Treatment of moderate to severe depression - SSRIs

5HT in Vesicles5HT in VesiclesPre synapsePre synapse

5HT 1a

Anti. DEP.

5HT 1a

Anti. DEP.

5HT2

Sleep

Sex

5HT2

Sleep

Sex

5HT 3

G.I.T.

Disturbances

5HT 3

G.I.T.

Disturbances

Post Synaptic

Rs

Post Synaptic

Rs

Reuptake.Reuptake.

Proves of 5HT Dysfunction in OCD

1. Efficacy of SSRIs and clomipramine

2. Serotonin receptor dysfunction

3. Hypersensitivity of postsynaptic 5-HT receptors

4. Treatment response correlated with decreased CSF serotonin

metabolite 5-HIAA in OCD patients

5. Administration of m-chlorophenylpiperazine (mCPP), which

decreases seroternergic activity, increases obsessional symptoms

6. Correlations of platelet 5-HT transporter dysfunction, 5-HT

concentrations and monoamine oxidase activity with symptom

severity and response to SSRIs

7. Challenge tests suggest 5-HT1 receptors altered in OCD

8. Polymorphisms of 5-HT transporter linked to OCD

OCD responds to dopamine antagonists

Exacerbation with stimulants (increases DA activity) i.e.

Dextroamphetamine, methylphenidiate

The dopamine metabolite HVA is low in CSF

Related to early onset OCD

Related to hoarding disorder

Dopamine in PFC may have its role in control of

emotions?

Neurochemical Aspect The role of dopamine

» 5HT1A is dopamine accelerator. However, 5HT2A is dopamine brake (opposite effect is on glutamate).

Neurochemical Changes

Neural correlates of OCD Symptom factors

Aggression / Harm

Contamination

Symmetry / Order

Saving / Collection

Increased activity of striatum

Increased activity of Orbito frontal cortex & Anterior Cingulate Gyrus.

Decreased activity of striatum

Decreased activity of Cingulate gyrus.

Ranch et al 1998; Saxena et al 2003.

Associated Symptoms

• Amygdla different structures in the brain stem.

• Hypothalamus – Cortisol.

• Locus Ceruleus – Tachycardia.

• Parabrachial Nuclei – Tachypnea.

• Periaqueductal gray – Fight, Flight or Flee.

Neuroimmunological Aspect

Paediatric Autoimmune Neuropsychiatric Disease Associated with Streptococcal Infection – PANDAS

Neurocognitive Model

Executive dysfunction in organizational strategies

Set shifting problems

Perseveration of responses

Deficits in planning, problem solving

Problems in decision making tasks

Failure to predict and suppress the sensory consequences of their actions

Flexibility problem

SiteFunction

DLPFCObsession

OFPFCCompulsion

VMPFCAffective

OCD

Neurologic

Tourettes

Sydenhams ch.

Torticolis

Autism

Preoccupation with bodily sensation or appearance

Impulsive disorders

Sexual Compulsions

Trichotillomania

Pathological gambling

Kleptomania

Self injurious behaviors

BDD

Depersonalization

Anorexia Nervosa

Hypochondriasis

OCD Spectrum disorders

OCD Spectrum

OCD BDD A.N. DEP HYPO. T.S.

Trich

Binge Eating

Comp. Buy

Klep

PG

Sexual Comp.

BPD.

Anti Social PD

Compulsive Impulsive

Risk Aversive Risk Seeking

Psychiatric co-morbidities

Personality disorders

MDD

Simple phobia

Social phobia

Eating disorders

Bipolar disorder

Alcohol abuse

Comorbidities Estimated prevalence

63 %

28 to 31%

7 to 48%

11 to 16%

15%

8 to 13%

8% Panic disorder 6 to 12 %

Differential Diagnosis

Anxiety disorder Due to a

General Medical

Conditions Substance induced

Anxiety Disorder Body Dysmorphic

Disorder Obsessive compulsive

personality Pathological gambling Paraphillias

Major Depressive

Episode Generalized Anxiety Dis. Hypochondriasis Specific Phobia Delusional Disorder Psychotic Disorder Not

Otherwise Specified Schizophrenia Tic/stereotypic behavior

Math SB and Janardhan RYC, Int J Clin Pract, July 2007, 61, 7, 1188-1197

ConclusionConclusion

• OCD is a disabling disorder which needs integrative evidence-based approach