OCD & Tourettes

Obsessive Compulsiv Disorder

• until 2013, considered a type of anxiety disorder

• introduced now as a new, separate section

• characterized by the presence of obsessions and/or compulsive behaviors

obsessions

intrusive thoughts, associated with anxiety, distress, or disgust

compulsions

repetitive behaviors that are meant to ease the distress of obsessions

OCD — DSM-5 criteria

a. presence of obsessions, compulsions, or both

b. obsessions/compulsions are time consuming or cause clinically significant distress

c. symptoms are not attributable to the physiological effects of a substance of another medical condition

d. disturbance is not better explained by the symptoms of another mental disorder

subtypes of OCD

• contamination obsessions w/ cleaning compulsions

• hoarding

• symmetry obsessions w/ ordering compulsions

• obsessions w/o visible compulsions

• harm obsessions w/ checking compulsions

epidemiology of OCD

• prevalence of 1-3%

• slightly more common i males during childhood, more common in females during adolescence and adulthood

• childhood onset OCD ore severe, stronger genetic influence, higher comorbidity with tic-related disorders

outcomes and treatments of OCD

• can be severely impairing

• majority of individuals have a comorbid disorder (eating and addiction disorders)

• higher risk of suicide attempts

• treatments include psychotherapy and pharmacological options

• cognitive behavior therapy is most effective

non-genetic risk factors of OCD

• perinatal complications, childhood trauma, other stressul life events

• some evidence that infections may be linked, esp in sudden early-onset cases (PANDAS)

basal ganglia

group of structures that includes striatum (caudate nucleus, putamen, nucleus accumbens), globus pallidus, etc; involved in motor control, executive function, reward processing

genetic epidemiology

• strong evidence of familial clustering

• twin studies estimate h² 45-61%, little evidence of shared environment factors

GWAS of OCD

• SNP-h² = 6.7%

• 30 significant loci

• largest GWAS N_cases = 53,660

OCD Genetic Correlation w/ other Disorders

anxiety disorders — 0.7

depression — 0.6

anorexia nervosa — 0.52

tourette syndrome — 0.47

Genetic Architecture of OCD

• both common and rare variants play a role

• studies of rare CNVs and mutations still in early days, but there is evidence that both are important in OCD risk

• CNVs and de novo mutations enriched in genes that have been implicated in other neurodevelopmental disorders, such as ADHD and tic disorders

Tourette Syndrome

• childhood onset disorder characterized by multiple motor tics and at least one vocal tic

• tics are sudden, involuntary, rapid, recurrent motor movements or vocalizations

  • can be simple or more complex

  • common tics include

DSM5 diagnosis of Tourette syndrome

• included in a section of the DSM5 referred to as TIC Disorders

  • onset must be before 18 years of age

  • cannot be attributable to physiological of a substance or another medical condition

  • the tics may wax and wane in frequency but have persisted for more than 1 year since first tic onset

  • multiple motor and one or more vocal tics must be present at some time during the illness, although not necessarily concurrently

Chronic tic disorder

presence of vocal or motor tics

Transient tic disorder

symptoms last <1 year

Epidemiology

• Prevalence of 0.3-1% in children; 10-fold higher rate of TS in children compared to adults

• Gender imbalance; skewed toward males, estimates from 2:1 to 4:1

• Average age of onset = 4-6 years; Most severe around 10-12 years

• Usually decreases in severity in adolescence or young adulthood – in adulthood, ~20% show total remission and ~60% have mild form of disorder

• Most (85%) individuals with Tourette syndrome have a comorbid psychiatric disorder

• OCD most common (50%), followed by ADHD (54%)

Risk factors for TS

Obstetrical complications, older paternal age, lower birth weight, and maternal smoking during pregnancy

Genetic risk factors of TS

• Highly heritable (60-70%)

• First-degree relatives of affected individuals have ~20-fold increased risk of TS/CTD compared with the overall population

• Rare variant and copy number variant analyses have identified potential risk genes (e.g.,NRXN1, WWC1)

Genetic Studies of TS

1. TS PRS distributions highest for TS cases, but also higher for other tic disorder cases compared to population controls

2. Higher TS PRS significantly associated with greater worst-ever tic severity score

3. TS PRS burden higher in multiplex families (multiple relatives affected) compared to simplex families (only one affected case)

Suggests that TS and other tic disorders represent a spectrum, and increased polygenic burden is correlated w/ increased severity

Associations with brain circuitry for TS

• Cortico–striato–thalamo–cortical (CSTC) circuit implicated in neuroimaging and postmortem

• Tourette syndrome patients show lower volumes of basal ganglia

• Common genetic variants influencing TS/CTD risk are enriched in basal ganglia tissues

• Suggests that Tourette syndrome is a developmental circuit disorder, might explain symptoms associated with motor, cognitive, and behavioral control (tics, ADHD, and OCD symptoms)