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.