Elsevier

Neuroscience Letters

Volume 436, Issue 2, 9 May 2008, Pages 111-115
Neuroscience Letters

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

https://doi.org/10.1016/j.neulet.2008.03.001Get rights and content

Abstract

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.

Section snippets

Acknowledgement

We gratefully acknowledge the skillful technical support of Ms. Kathrin Schwarte.

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      Our meta-analysis, that included 1599 subjects more than the previous one focused on HTR1A gene (Zhao et al., 2012a), confirmed no association between rs6295 and AD response or remission. Several studies reported that the G/G genotype or G allele were associated with worse AD efficacy (Arias et al., 2005; Hong et al., 2006; Lemonde et al., 2004; Parsey et al., 2006; Serretti et al., 2004a; Villafuerte et al., 2009; Yu et al., 2006), whereas others reported an opposite association (Baune et al., 2008b; Kato et al., 2009), or no association (Brent et al., 2010; Bukh et al., 2009; Illi et al., 2009; Lin et al., 2009; Noro et al., 2010; Peters et al., 2004; Zhao et al., 2012b). These inconsistent results and the negative findings confirmed by the present review, suggest that rs6295 probably does not play a major role in AD response.

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