Epigenetics in Major Depressive Disorder

Major depressive disorder (MDD) is one of the most prevalent mental illnesses worldwide. Heritability studies implicate a strong environmental component to disease etiology, with most depressive episodes occurring after major stressful life events. In addition to genetic factors, a vulnerability to stress-induced depression may be conferred by many developmental risk factors, including maternal diet, anxiety and depression, early-life adversity, hormonal fluctuations, and inflammation. The deleterious effects of these environmental risk factors interact with the genome through epigenetic mechanisms, leaving lasting DNA methylation and histone modification marks that may lead to neuroconnectivity changes associated with disrupted emotional regulation and blunted reward circuitry. The parental transmission of epigenetic effects may lead to incidences of soft inheritance and require a careful reflection on the degree of genetic evidence for MDD. The efficacy of cross-tissue epigenetic findings in light of systemic hormonal etiological factors is discussed. The epigenetic effects of various environmental insults are beginning to be cataloged in a systemic manner with the help of genome-wide epigenetic profiling technologies; however, subcellular heterogeneity within sampled tissues may cause the identification of spurious disease associated findings. Application and refinement of novel techniques generated to control for such heterogeneity will be necessary to identify the full range of etiologically relevant environmentally induced epigenetic variation in future studies.