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Serotonin Related Genes Affect Antidepressant Treatment in Obsessive–Compulsive Disorder

Published online by Cambridge University Press:  12 December 2007

F. Van Nieuwerburgh ,
D. Deforce  and
D.A.J.P. Denys
F. Van Nieuwerburgh
Affiliation:
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium; Email: Filip.VanNieuwerburgh@UGent.be
D. Deforce
Affiliation:
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium; Email: Dieter.Deforce@Ugent.be
D.A.J.P. Denys
Affiliation:
AMC, University of Amsterdam, Amsterdam, The Netherlands; Email: D.Denys@amc.nl
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Extract

ABSTRACT

Up to 60% of OCD patients do not respond to a regular serotonin reuptake inhibitor (SRI) treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT1Dβ, and 5-HT2A receptor genes affect the efficacy of SRI treatment in OCD. Ninety-one outpatients with primary OCD according to DSM-IV criteria consented to the study were randomly assigned a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine, or 60 mg/day of paroxetine. Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive–compulsive scale (Y-BOCS), and response was defined as a ≥25% reduction on the Y-BOCS. All of the paroxetine treated patients, with the G/G genotype of the 5-HT2A polymorphism were responders (χ2 = 8.66, df = 2, p = 0.013). In the venlafaxine treated patients, the majority of responders carried the S/L genotype of the 5-HTTLPR polymorphism (χ2 = 9.71, df = 2, p = 0.008). The small group of patients who both carried the S/L genotype of the 5-HTTLPR polymorphism and the G/G genotype of the 5-HT2A polymorphism responded all to treatment.

The results of this study suggest that the response in paroxetine and in venlafaxine treated OCD patients is associated with the G/G genotype of the 5-HT2A polymorphism and with the S/L genotype of the 5-HTTLPR polymorphism, respectively.

Keywords

5-HT1Dβ5-HT2A5-HTT5-HTTLPRassociation studyobsessive–compulsive disorderpharmacogeneticsserotoninserotonin reuptake inhibitorSSRI
Type
Research Article
Information
Progress in Neurotherapeutics and Neuropsychopharmacology , Volume 3 , Issue 1 , January 2008 , pp. 227 - 240
Copyright
© 2008 Cambridge University Press

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