An update on the interaction between the serotonin transporter promoter variant (5-HTTLPR), stress and depression, plus an exploration of non-confirming findings

•A meta analysis was conducted on 81 studies of the 5-HTTLPR, stress and depression.•The overall association was confirmed.•26% of studies failed to show significant associations.•Nearly 10% of studies showed opposite results.•Methodologies were not different across these findings. In the three years since the most recent meta-analysis of the association between the serotonin transported promoter polymorphism (5-HTTLPR), stress and the development of depression, another 27 studies have been published on this issue, which is an increase of 50% more studies than were previously reviewed. In addition, previous findings of inconsistency of results across studies argued for further exploration of this relationship. From the 81 studies identified to June 2013, the significant relationship between the short form of the 5-HTTLPR was confirmed (p=.0000009), which is stronger than the relationship reported in the most recent meta-analysis in 2011. However, nearly 26% of the 81 studies reviewed failed to show any significant association between the 5-HTTLPR, stress and depression, and four studies found opposite results to those expected. Examination of the methodologies of all studies failed to indicate any flaws in the opposite or unequivocal studies, and the latter had larger sample sizes than those studies which supported the expected association, arguing that the null results were not an outcome of insufficient statistical power. The need to consider aspects of samples and measures of depression, particularly the presence of subtypes of depression in future research is discussed.