Genetic Risk Factors in MDD: The Role of Serotonin Transporter Genes and Polygenic Risk Architecture

Abstract

This narrative review examines the role of genetic risk factors in the development of Major Depressive Disorder, majorly talking about the contribution of serotonin transporter gene variation (5-HTTLPR) and polygenic risk architecture. Using existing literature, the review explores how inherited susceptibility contributes to individual vulnerability while interacting with other psychological factors. Evidence suggests that genetic factors account for a considerable portion of risk for MDD, influencing neurobiological functions such as emotional regulation and stress reactivity. Although these factors are not fully deterministic and require environmental contributors, which are consistent with the diathesis–stress model. This research also talks about additional genetic influences, including brain-derived neurotrophic factor (BDNF) and stress-regulation pathways, as well as the role of epigenetic mechanisms in modifying gene expression, further supporting that MDD is a multifactorial disorder arising from complex gene–environment interactions. While advances in genomic research have revamped the understanding of vulnerability to the condition, the limitations remain in predictive accuracy and clinical approach.