title: Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder.
abstract: Antidepressant drugs are the preferred choice for the treatment of generalized anxiety disorder (GAD). However, the choice of pharmacotherapy is determined on a trial-and-error basis, as the underlying mechanisms of treatment response are unknown. We examined whether the COMT gene, which has been known to play a role in antidepressant treatment response in major depressive disorder (MDD), has a pharmacogenetic effect in antidepressant treatment response in GAD. In our study, 156 patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study. Genotypes were obtained for the COMT functional variant rs4680 (Val158Met) for all patients; however, pharmacogenetic analysis was only conducted for the European American population (n=112). We found no significant association between our primary Hamilton Anxiety Scale outcome measure and rs4680. However, we did find a nominally significant allelic association between this variant and a secondary treatment outcome measure (CGI-I) in our European American population (n=112). Furthermore, we show a slight dominant effect of the A-allele with the CGI-I measure in the European American population indicating a possible pharmacogenetic role of rs4680 in antidepressant treatment outcome in GAD. Further studies in a larger population are needed to confirm this effect.
authors.affiliation: Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Narasimhan
authors.forename: Tiffany D
authors.initials: TD
authors.lastname: Aquino
authors.forename: Pushpinder K
authors.initials: PK
authors.lastname: Multani
authors.forename: Karl
authors.initials: K
authors.lastname: Rickels
authors.forename: Falk W
authors.initials: FW
authors.lastname: Lohoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003511:Cyclohexanols / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010597:Pharmacogenetics; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride; D002394:Catechol O-Methyltransferase