Role of serotonin transporter-linked polymorphic region in suicide: Beyond association, meta-analysis, and future prospects

Serotonin transporter-linked polymorphic regions (5-HTTLPR) have been investigated intensively in suicide with inconsistent findings. However, a recent meta-analysis has observed an association of S allele with violent attempted suicide. The S allele causes a lower expression of 5-HTTLPR and is correlated with higher amygdala response to unpleasant stimuli. However, studies show that effect 5-HTTLPR genotype on mRNA expression is additive and linear. It suggests that apart from genotype, the expression of 5-HTTLPR is also controlled by epigenetic factors. Therefore, the purpose of this narrative review is to re-evaluate the findings of retrospective studies 5-HTTLPR in suicide with their limitations and highlight a new approach to understand the role of 5-HTTLPR in suicide. Reviews, meta-analysis, research articles, brief reports, and scientific correspondence were searched through PubMed, library web portal of Sikkim University, Bio-Med, and Science Direct using the terms such as “serotonin or serotonin system and suicide,” “5-HTTLPR and suicide,” “5-HTTLPR and attempted suicide,” “5-HTTLPR and completed suicide,” “5-HTTLPR meta-analysis and suicide,” and “5-HTTLPR and epigenetics.” The articles written in English were initially screened by title and later selected by abstract for possible inclusion. After the literature review, it was observed that previous studies were limited by variability of sample size, heterogeneous populations, varied social stressors, and variations in the assay and statistical methods. Hence, the cumulative study of environmental factors, 5-HTTLPR gene polymorphism, and epigenetic factors is hereby proposed in the well-defined ethnic population to understand the role of 5-HTTLPR in suicide.