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

BACKGROUND: Essential 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.

METHODS: COMT 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-D(21)). In the analysis of association, response was defined as >or=50% decrease in HAM-D(21) score after treatment and then further clarified by intra-individual changes in HAM-D(21) score.

RESULTS: We 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-D(21) 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-D(21) scores in the eighth week.

LIMITATIONS: There was a lack of placebo control and the serum fluoxetine concentration was not taken into account.

CONCLUSIONS: This identified association between the COMT genetic variation and antidepressant response may be useful either as a clinical predictor in the future.