Sexually dimorphic effect of catechol-O-methyltransferase val158met polymorphism on clinical response to fluoxetine in major depressive patients

BackgroundEssential in dopamine degradation, it was suggested that catechol-O-methyltransferase (COMT) might be involved in the action of antidepressants and may therefore be a promising candidate for antidepressant pharmacogenetic studies.MethodsCOMT Val158met polymorphism was genotyped in 334 Chinese major depressive disorder (MDD) patients who were treated with fluoxetine for at least 4 weeks. Clinical response was evaluated using the 21-item Hamilton Rating Scale for Depression (HAM-D21). In the analysis of association, response was defined as ≥ 50% decrease in HAM-D21 score after treatment and then further clarified by intra-individual changes in HAM-D21 score.ResultsWe found that the COMT val158met polymorphism was not associated with 4-week fluoxetine therapeutic response; however, association analysis showed that patients with the COMT Val/Val genotype had poorer responses in the eighth week (CLUMP T1 P = 0.020) and consistently showed significantly smaller reductions in HAM-D21 scores in the eighth week (P = 0.027). Further stratification based on gender revealed an isolated effect of the COMT genotype in males (P = 0.035) but not in females (P = 0.650) in percent reduction in HAM-D21 scores in the eighth week.LimitationsThere was a lack of placebo control and the serum fluoxetine concentration was not taken into account.ConclusionsThis identified association between the COMT genetic variation and antidepressant response may be useful either as a clinical predictor in the future.