Serotonin receptor 1A-1019C/G variant: impact on antidepressant pharmacoresponse in melancholic depression?

Previous studies on the effects of serotonin receptor 1A (5-HT1A) gene variation on treatment response in depression revealed inconsistent results with studies pointing towards a detrimental influence of the 5-HT1A-1019G allele on antidepressant treatment response, while others did not discern any involvement of 5-HT1A variants. In order to further delineate the impact of 5-HT1A gene variation on pharmacoresponse in depression over 6 weeks of antidepressant treatment, the influence of the 5-HT1A-1019C/G (rs6295) polymorphism was investigated in 340 Caucasian patients with a Major Depressive Episode (DSM-IV) with particular attention to the subtype of depression (major depression and melancholic depression). Antidepressant treatment response across 5-HT1A-1019C/G genotype groups showed no differences in either Major Depressive Episode or major depression between genotype groups, whereas stratification for the melancholic subtype of depression revealed a significantly worse treatment response as conferred by the -1019CC genotype (p=0.02). The poorer treatment response in melancholic depression could first be detected in week 2 (p=0.03), continuing until week 6 and showing a maximum effect in week 3 (p=0.01). The present study adds to the clarification of the role of 5-HT1A variation in treatment response in major depression by providing preliminary support for poor treatment response mediated by the 5-HT1A-1019C allele repressing 5-HT1A activity specifically in the melancholic subtype of depression.