Associations of the serotonin transporter promoter polymorphism (5-HTTLPR) with bipolar disorder and treatment response: A systematic review and meta-analysis

Background: Associations of the serotonin transporter promoter polymorphism (5-HTTLPR) with bipolar disorder (BPD) and treatment response in bipolar patients were not conclusive. This study not only assessed the association between the 5-HTTLPR and BPD with accumulating relevant studies, but also in the first time evaluated the effect of the 5-HTTLPR on both anti-depressive and anti-manic treatment responses in bipolar patients.

Methods: PubMed, Embase, PsycINFO, Cochrane Library and Cochrane Control Trials databases were systematically searched before February 2017. This meta-analysis followed the PRISMA guidelines.

Results: A total of 32 population-based studies (5567 cases and 6993 controls) and 9 family-based studies (837 trios) were finally screened out and statistically joined into a single meta-analysis that revealed an association between S allele and an increased risk of BPD (OR = 1.06, p = .038). Pooled analysis of the 32 population-based studies indicated an association of S-carrier genotypes with an increased risk of BPD (OR = 1.10, p = .029). Meanwhile, the association remained significant in Caucasians (OR = 1.15, p = .004), which could provide an enough power (88%) to detect a significant association. Regarding the treatment response studies, 6 studies reporting the relationship of the 5-HTTLPR in anti-depressive remission rate (1034 patients) and 7 studies reporting in response rate (1098 patients) were included for pooled analyses. We observed a significant association of S-carrier genotypes with a reduced anti-depressive remission rate (OR = 0.64, p = .006) but not with anti-depressive response rate. The association between the 5-HTTLPR with anti-manic response rate was not observed in the included 6 studies (676 patients).

Conclusions: The present study supported the presence of a marginal but detectable effect of the 5-HTTLPR on susceptibility to BPD. Moreover, the detected association in Caucasian was statistically reliable. Besides, the 5-HTTLPR was identified as a useful predictor for anti-depressive remission but not for anti-depressive or anti-manic response.