Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.