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Altered cognitive response to serotonin challenge as a candidate endophenotype for obsessive-compulsive disorder.

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Lochner, Christine 
Chamberlain, Samuel R 
Kidd, Martin 
Fineberg, Naomi A 
Stein, Dan J 


RATIONALE: Obsessive-compulsive disorder (OCD) implicates dysfunction of orbitofrontal and insula-related circuitry and of the serotonin system. There is an on-going search in psychiatry for intermediate biological markers, termed 'endophenotypes', that exist not only in patients with a given disorder but also in their clinically unaffected first-degree relatives. OBJECTIVE: Pharmacological challenge is recognized as a means of eliciting an endophenotype, but this strategy has yet to be used in OCD. METHODS: Twenty-three OCD patients without comorbidities (12 [52.2 %] female), 13 clinically asymptomatic first-degree relatives of OCD patients (11 [84.6 %] female) and 27 healthy controls (16 [59.3 %] female) received single-dose escitalopram (20 mg) and placebo in a randomized double-blind crossover design. Effects of treatment on decision-making were quantified using the Cambridge Gamble Task (CGT) in conjunction with a mixed model analysis of covariance (ANCOVA). RESULTS: There was a significant interaction between serotonergic challenge and group for risk adjustment on the CGT (F = 4.1406; p = 0.02). Only controls showed a significant placebo-drug change in risk adjustment (p = 0.02; versus p > 0.10). Numerically, escitalopram was associated with increase in risk adjustment in controls and reductions in the other groups. Change in risk adjustment was similar in OCD patients and relatives (p = 0.806) and differed significantly from controls (p = 0.007; p = 0.041, respectively). CONCLUSIONS: Individuals with OCD, and first-degree relatives, showed an altered cognitive response to serotonin challenge. This is the first demonstration of a candidate pharmacological challenge endophenotype for the disorder. Future work should confirm these findings in a larger sample size and ideally extend them to other cognitive paradigms, utilizing functional neuroimaging.



Decision-making, Endophenotypes, Gambling, Obsessive-compulsive disorder, Risk adjustment, Adolescent, Adult, Citalopram, Cognition, Cross-Over Studies, Decision Making, Double-Blind Method, Endophenotypes, Female, Gambling, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder, Psychomotor Performance, Risk Adjustment, Serotonin, Selective Serotonin Reuptake Inhibitors, Young Adult

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Psychopharmacology (Berl)

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Springer Science and Business Media LLC
This work was supported by the Medical Research Council of South Africa, the Obsessive-Compulsive Foundation (Prof Stein), the National Research Foundation of South Africa (Prof Lochner), an unrestricted grant from Lundbeck H/S and by a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences UK (Dr Chamberlain).