Systemic neuro-dysregulation in depression: Evidence from genome-wide association

Depression is the world's leading cause of disability. Greater understanding of the neurobiological basis of depression is necessary for developing novel treatments with improved efficacy and acceptance. Recently, major advances have been made in the search for genetic variants associated with depression which may help to elucidate etiological mechanisms. The present review has two major objectives. First, we offer a brief review of two major biological systems with strong evidence for involvement in depression pathology: neurotransmitter systems and the stress response. Secondly, we provide a synthesis of the functions of the 269 genes implicated by the most recent genome-wide meta-analysis, supporting the importance of these systems in depression and providing insights into other possible mechanisms involving neurodevelopment, neurogenesis, and neurodegeneration. Our goal is to undertake a broad, preliminary stock-taking of the most recent hypothesis-free findings and examine the weight of the evidence supporting these existing theories and highlighting novel directions. This qualitative review and accompanying gene function table provides a valuable resource and guide for basic and translational researchers, with suggestions for future mechanistic research, leveraging genetics to prioritize studies on the neurobiological processes involved in depression etiology and treatment.