Catechol-O-methyltranferase gene expression is associated with response to citalopram in obsessive-compulsive disorder

Objective. To determine whether polymorphisms of the dopamine D-2 receptor (DRD2) and catechol-O-methyl-transferase (COMT) receptor genes affect the efficacy of quetiapine addition to citalopram in patients with OCD. Methods. Sixty-four drug-free or drug-naive patients meeting DSM-IV criteria for OCD were randomized to 10 weeks double-blind treatment with citalopram (60 mg/day) with quetiapine (300-450 mg/day) or with placebo. The change from baseline to endpoint on the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the response to treatment were the primary outcome measures. Response was defined as a 25% decrease in Y-BOCS score. Responders and nonresponders were stratified according to DRD2 TaqI A and COMT Val(158)Met genotypes. Results. No significant differences in genotype distribution or allele frequencies of the COMT or DRD2 receptor were found between responders and nonresponders to citalopram with quetiapine. However, nearly half of responders to citalopram with placebo carried the Met/Met (48%) genotype of the COMT polymorphism compared to none of the nonresponders (chi(2) = 10.06, df = 2, P = 0.007). Conclusions. The Met allele load of the COMT receptor gene was associated with response to 10 weeks of treatment with citalopram in drug-free or drug-naive OCD patients