5-HTTLPR modulates antidepressant efficacy in depressed women

As compared with the long variant (L), the short variant (S) of the functional polymorphic region of the serotonin transporter gene (5-HTTLPR) has been associated with a lower antidepressant efficacy in major depression, but some replication studies have evidenced contradictory results. Sex differences may explain these contradictory results.

One hundred and three inpatients (74 women and 29 men) with a major depressive episode were assessed prospectively for antidepressant efficacy after 4 weeks of treatment with selective serotonin reuptake inhibitors (SSRI) and non-SSRI drugs.

As compared with LL/LS, the SS genotype of the 5-HTTLPR was associated with a lower antidepressant efficacy in depressed women (79 vs. 50% responders, P = 0.035). This result was shown with both SSRI and non-SSRI antidepressants. The logistic regression performed in women showed that response to treatment was related to genotype (odds ratio=0.15; 95% confidence interval=0.03-0.85; P = 0.03) and not to other variables. No effect of 5-HTTLPR was found in depressed men.

Despite a low power, this study suggests a significant effect of 5-HTTLPR genotype on antidepressant efficacy in depressed women but not in men, with both SSRI and non-SSRI drugs. Further research is needed to confirm this result and investigate its underlying mechanisms.