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dc.contributor.authorLochner, Christineen
dc.contributor.authorChamberlain, Samuelen
dc.contributor.authorKidd, Martinen
dc.contributor.authorFineberg, Naomi Aen
dc.contributor.authorStein, Dan Jen
dc.date.accessioned2015-12-17T17:10:35Z
dc.date.available2015-12-17T17:10:35Z
dc.date.issued2015-12-09en
dc.identifier.citationPsychopharmacology (2016) 233: 883-891en
dc.identifier.issn0033-3158
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253021
dc.description.abstractRATIONALE: 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.
dc.description.sponsorshipThis 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).
dc.languageEnglishen
dc.language.isoenen
dc.publisherSpringer
dc.subjectObsessive-compulsive disorderen
dc.subjectEndophenotypesen
dc.subjectDecision-makingen
dc.subjectRisk adjustmenten
dc.subjectGamblingen
dc.titleAltered cognitive response to serotonin challenge as a candidate endophenotype for obsessive-compulsive disorderen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4172-yen
prism.endingPage891
prism.publicationDate2015en
prism.publicationNamePsychopharmacologyen
prism.startingPage883
prism.volume233en
dcterms.dateAccepted2015-11-21en
rioxxterms.versionofrecord10.1007/s00213-015-4172-yen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-12-09en
dc.contributor.orcidChamberlain, Samuel [0000-0001-7014-8121]
dc.identifier.eissn1432-2072
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2016-12-09


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