Seminar Series

Just can't stop: endophentypes of obsessive-compulsive spectrum disorders

Neuropsychological and neuroimaging parameters may help bridge the gap between genotype and phenotype for heritable mental disorders such as obsessive-compulsive disorder (OCD). Such markers, if present in people 'at risk' e.g. unaffected family members of individuals with OCD, constitute candidate endophenotypes whose identification may help narrow the search for the genetic basis of the disorder. Recent work combined genetic measures, neurocognitive assessment and structural neuroimaging in OCD patients and their unaffected relatives. Compared to healthy controls, OCD patients showed impairment on laboratory-based tasks of executive function measuring motor inhibition (stop-signal reaction time; SSRT) and cognitive flexibility (intradimensional-extradimensional set shift) (Chamberlain et al 2006a). These deficits were present despite SSRI treatment, implying trait rather than state-marker status. Compared to healthy controls without a family history of OCD, unaffected first-degree relatives of OCD patients also showed impaired motor inhibition (p<0.01) and cognitive inflexibility (p<0.01) similar to deficits in patients (Chamberlain et al, 2007). That these changes occurred in the absence of the confounding effect of medication further supports their candidacy as neurocognitive OCD endophenotypes. Patients and unaffected relatives were subjected to structural MRI. Variation in motor inhibition (SSRT) was chosen as a candidate endophenotype. SSRT scores were found to correlate with structural variation within fronto-striatal neurocircuitry, implying a novel cognitive-neuroimaging endophenotype of the disorder (Menzies et al., 2007). Cortical structures not previously associated with OCD were also identified. Further exploration within OCD families of relationships between these cognitive-neural abnormalities, genetics, clinical features and environmental factors may clarify aetiological contributions to OCD and related spectrum disorders.