Genetic and Epigenetic Consequence of Early-Life Social Stress on Depression: Role of Serotonin-Associated Genes

Abstract

Early-life adversity caused by poor social bonding and deprived maternal care is known to affect mental wellbeing and physical health. It is a form of chronic social stress that persists because of a negative environment, and the consequences are long-lasting on mental health. The presence of social stress during early life can have an epigenetic effect on the body, possibly resulting in many complex mental disorders, including depression in later life. Here, we review the evidence for early-life social stress-induced epigenetic changes that modulate juvenile and adult social behavior (depression and anxiety). This review has a particular emphasis on the interaction between early-life social stress and genetic variation of serotonin associate genes including the serotonin transporter gene (5-HTT; also known as SLC6A4), which are key molecules involved in depression.

Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection

“…High methylation by DNMT3 in CpG islands from promoter regions entails the downregulation of serotonin and its transporter (i.e., SERT) together with the upregulation of monoamine oxidase A (MAO-A) and tryptophan hydroxylase 2 (TPH2). All these genes are part of the process of brain development, stress response, and emotional control ( 53 ). Moreover, maltreated children have shown hypermethylation in the promoter region of GR gene NR3C1 compared with non-maltreated children, entailing transcriptional silencing.…”

Multi-Omics Characterization of Early- and Adult-Onset Major Depressive Disorder

“…Epigenetics may be particularly valuable in future studies for explaining the differential gene-metabolite associations in early versus adult-onset depression. Early life adversity can confer epigenetic modifications linked to development of depression in youth and adults [ 102 ]. Epigenomic alterations may drive neuropsychiatric disease through changes in gene expression and neural function, and individuals with adult versus later onset depression have been successfully discriminated by genome-wide DNA methylation markers [ 103 , 104 ].…”

Genetic and epigenetic factors associated with depression: An updated overview

“…Epigenetic regulation is fundamental to many cellular mechanisms, involving Gene Expr., DNA-protein interactions, transposable element repression, cellular differentiation, embryogenesis, X chromosome inhibition, etc. ( Soga et al, 2021 ).…”