The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-Analysis Revisited: Evidence of Genetic Moderation

Context-The initial report of an interaction between a serotonin transporter promoter polymorphism (5-HTTLPR) and stress in the development of depression is perhaps the bestknown and most cited finding in psychiatric genetics.Two recent meta-analyses explored the studies seeking to replicate this initial report and concluded that the evidence did not support the presence of the interaction.However, even the larger of the meta-analyses included only 14 of the 56 studies that have explored the relationship between 5-HTTLPR, stress and depression.Objective-We sought to perform a meta-analysis including all relevant studies assessing whether 5-HTTLPR moderates the relationship between stress and depression.Data Sources-We identified relevant articles from previous meta-analyses and reviews and a PubMed database search.Study Selection-We excluded two studies presenting data that were included in other, larger, studies already included in our meta-analysis to avoid duplicate counting of subjects.Data Extraction-In order to perform a more inclusive meta-analysis, we used the Liptak-Stouffer Z-score method to combine findings of primary studies at the significance test level rather than raw data level.