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

Abstract

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.

Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

“…8 The À1019G allele or the homozygous À1019GG genotype has been associated with depression, suicide, bipolar disorder, panic disorder with agoraphobia, neuroticism and decreased antidepressant response. [8][9][10][11][12][13][14][15] We tested the hypothesis that the HTR1A À1019G allele increases depression risk in a Utah population. Observed frequencies of À1019G allele (350/688) and À1019GG genotype (89/344) were 1.10-and 1.34-fold higher among unrelated individuals affected with MDD compared to unaffected individuals (312/672 and 65/336; one-tailed Fisher's exact test P = 0.05 and 0.02, respectively).…”

Higher 5-HT1A Receptor Binding Potential During a Major Depressive Episode Predicts Poor Treatment Response: Preliminary Data from a Naturalistic Study

“…Further, GG depressed subjects are more likely to have higher 5-HT 1A BP (Parsey et al, in press). A poorer response to antidepressant treatment appears to be associated with the higher expressing GG genotype (Albert, 2004;Lemonde et al, 2004;Serretti et al, 2004).…”

Biological Alterations in Depression

“…In Asians, the G allele is associated with improved treatment outcomes (Hong et al, 2006;Kato et al, 2009). However, this finding was not observed in Caucasians (Lemonde et al, 2004;Serretti et al, 2004), suggesting a confounding effect of race. The relationship between HTR2A and antidepressant response is unclear due to conflicting results (reviewed in Kato 2010).…”