MAJOR DEPRESSIVE DISORDER, ENVIRONMENTAL FACTORS AND EPIGENETICS

Abstract

New insights in the epigenetics have declared depression as genetic malady. For psychiatric disorders evaluation of epigenetic basis influenced by environment insults showed deeper understanding of complex multifactorial psychiatric disorder like Major depressive disorder (MDD). The World Health Organization (2008 report) has ranked MDD globally as the third cause of burden of diseases and predicted it to be the number one by 2030. Eight hallmarks of insults that lead to MDD are contaminated air, soil, food/water, ecological stressors, chemicals in households, occupational hazards as well as food/diet linked to absence of essential nutrients. Epigenetics, according to National Human Genome Research Institute, refers to changes in gene function causing their activation or deactivation without any alteration in DNA sequence.  Epigenetics include histone modifications, DNA methylations, miRNAs and lncRNAs. Hypermethylation of serotonin transporter gene has been consistently found in loci encoding brain derived neurotrophic factors BDNF and SLC6A4. During pregnancy fetal epigenetic reprogramming may occur due to maternal stress and nutritional restriction.  Increased cortisol or malnutrition in mothers, down-regulate cortisol enzyme, decreasing its expression in  fetal cortex, making these children 4 times more at risk to stress later in life. Histones modifications including methylation and acetylation at lysine moiety during posttranslational modifications, affect neurons of CNS significantly leading to pathophysiology of MDD. Dysregulation of miRNAs  and lncRNAs cause negative neural plasticity, stress responses, neurotrophic factors expression, neuroinflammation, neurotransmission, HPA axis, neurogenesis and gliogenesis and neural stem cell maintenance. Among epigenetic multifactorial disorders, psychiatric ailments have received prominence in etiology than other diseases.