Serotonin Transporter Gene: A New Polymorphism May Affect Response to Antidepressant Treatments in Major Depressive Disorder

Several gene variants have been related to major depressive disorder (MDD) treatment outcomes; however, few studies have investigated a possible different effect on pharmacotherapy and brief psychotherapy response. A total of 137 MDD patients were randomized to either interpersonal counseling (IPC; n = 40) or antidepressant pharmacological treatment (n = 97). Outcomes were remission, response, and symptom improvement at week 8. Five genetic variants were investigated (5HTR2A rs6314, BDNF rs6265, SLC6A4 rs8076005, CREB1 rs2253206, and TPH2 rs11179023) as possible modulators of outcomes. The LC6A4 rs8076005 AA genotype and A allele were associated with response rate in the antidepressant group (p = 0.015 and 0.005, respectively) and in the whole sample (p = 0.03 and 0.02, respectively). In the IPC group a non-significant trend in the same direction was observed. The TPH2 rs11179023 A allele showed a marginal association with symptom improvement in the IPC group only. Other gene variants did not impact on outcomes in any treatment group. Our study suggests that rs8076005 in the SLC6A4 gene may be a modulator of antidepressant response, especially when pharmacological treatment is used.