title: Altered cognitive response to serotonin challenge as a candidate endophenotype for obsessive-compulsive disorder.
abstract: BACKGROUND
  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.
authors.affiliation: US/UCT MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry, University of Stellenbosch, PO Box 241, Cape Town, 8000, South Africa. cl2@sun.ac.za.
authors.forename: Christine
authors.initials: C
authors.lastname: Lochner
authors.affiliation: Department of Psychiatry, University of Cambridge School of Clinical Medicine and Cambridge and Peterborough NHS Foundation Trust (CPFT), Cambridge, UK.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Chamberlain
authors.affiliation: Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: Martin
authors.initials: M
authors.lastname: Kidd
authors.affiliation: Department of Psychiatry, University of Cambridge School of Clinical Medicine and Cambridge and Peterborough NHS Foundation Trust (CPFT), Cambridge, UK.|Hertfordshire Partnership University NHS Foundation Trust and University Of Hertfordshire, Hatfield, UK.
authors.forename: Naomi A
authors.initials: NA
authors.lastname: Fineberg
authors.affiliation: US/UCT MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D015283:Citalopram / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003657:Decision Making / Q000187:drug effects; D004311:Double-Blind Method; D058068:Endophenotypes; D005260:Female; D005715:Gambling / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000523:psychology*; D011597:Psychomotor Performance / Q000187:drug effects; D020379:Risk Adjustment; D012701:Serotonin / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D055815:Young Adult
chemical_list: D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Decision-making; Endophenotypes; Gambling; Obsessive-compulsive disorder; Risk adjustment