5‐HT2A Receptor ‐1438 G/A Polymorphism and Serotonergic Antidepressant‐Induced Sexual Dysfunction in Male Patients with Major Depressive Disorder: A Prospective Exploratory Study

Abstract

To date, few studies have specifically investigated the genetic determinants of antidepressant-induced sexual dysfunction (SD). The aim of this prospective study was to examine whether the 5-HT2A receptor -1438 G/A polymorphism has functional consequences on sexual well-being in young adult men presenting with their first episode of major depressive disorder (MDD) after serotonergic antidepressant treatment. Between May 2010 and June 2011, a total of 56 drug-naïve patients presenting with their first episode of MDD were recruited from a psychiatric hospital and received either a selective serotonin reuptake inhibitor or venlafaxine monotherapy; the patients were then genotyped. Over the course of antidepressant treatment, the population was divided into a SD group (N=16) and a non-SD group (N=29) based on the Arizona Sexual Experience Scale (ASEX). Participants who did not achieve a significant improvement, as assessed by the Hamilton Depression Rating Scale (HAMD-17), were excluded from the final data analysis. The primary outcome measures were the differences in the genotype distribution and allele frequencies between groups. In the SD group, the AA genotype was significantly overrepresented (P=0.004), and the mean baseline HAMD-17 score, the mean baseline ASEX score, and the mean end-point ASEX score were significantly higher than those in the non-SD group (P=0.026, P=0.004, and P<0.001, respectively). The mean end-point HAMD-17 score (P=0.115) did not differ significantly between the two groups. These results suggest that the AA genotype may be a genetic trait offering an opportunity to strengthen early detection of serotonergic antidepressant-induced SD in young adult male patients with MDD, whereas the G allele is protective against SD in this population.