The C(–1019)G polymorphism of the 5-HT1A gene promoter and antidepressant response in mood disorders: preliminary findings

Several studies have demonstrated the involvement of 5-HT1A receptors in the pathogenesis of depression and in the antidepressant response to SSRIs. A functional new variant in the promoter region of the 5-HT1A gene was recently reported (-1019 C>G). The aim of this study is to investigate a possible association between this 5-HT1A receptor variant and antidepressant response to fluvoxamine in a sample of 262 mood-disorder subjects (151 major depressed and 111 bipolars) treated with fluvoxamine for 6 wk. The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression (HAMD). 5-HT1A variants did not influence antidepressant response in the whole sample and in unipolar subjects. In bipolars, 5-HT1A*C/C genotype carriers showed a better response to fluvoxamine (p=0.036), independently from clinical variables. The 5-HT1A polymorphism effect on antidepressant response was independent from the previously reported effect of the 5-HTTLPR polymorphism. In conclusion, 5-HT1A variants could influence the antidepressant efficacy in bipolar subjects, even if results must be verified on larger samples.