5-HTTLPR modulates antidepressant efficacy in depressed... : Psychiatric Genetics (original) (raw)

ORIGINAL ARTICLES

Gressier, Florencea; Bouaziz, Elodieb; Verstuyft, Célineb; Hardy, Patricka; Becquemont, Laurentb; Corruble, Emmanuellea

Departments of aPsychiatry

bPharmacology, Paris Sud University, Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, France

Correspondence to Florence Gressier, MD, Department of Psychiatry, Bicêtre University Hospital, 78 rue du Général Leclerc, Le Kremlin Bicêtre 94275, France

Tel: +33 145212524; fax: +33 145212864; e-mail: [email protected]

Received 2 December 2008 Revised 2 April 2009 Accepted 14 April 2009

Abstract

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.