Epigenome Mediation After Adverse Childhood Experiences: A Systematic Review and Meta-Analysis

Abstract

Epigenetic mechanisms may be potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to its environment, leading to changes in the regulation of multiple organ systems. This study aims to review the epigenetic mechanisms of childhood abuse as well as the long-term determinants that these epigenetic changes may have on future illnesses. We retrospectively analyzed the effect of exposure to Adverse Childhood Experiences (specifically those relating to childhood maltreatment) between the ages of 0-16 years on the human epigenome as well as possible clinical associations. After meeting inclusion and exclusion criteria, 36 articles were included in this systematic review. Eight of these studies did not find a relationship between childhood maltreatment and DNA methylation. Of the remaining 26 studies, eight were genome-wide association studies, whereas the rest were candidate- gene studies, mainly studying effects on neuroendocrine, serotoninergic and immunoregulatory systems. Meta-analysis of correlation coefficients from candidate gene studies estimated an association of childhood adversity and DNA methylation variation at r = 0.291 (p <0.0001), and meta-analysis of two EWAS identified 44 differentially methylated CpG sites. In conclusion, childhood maltreatment may mediate epigenetic mechanisms through DNA methylation, thereby affecting physiological responses and predisposing to an increased risk for psychopathology and forensic repercussions. Similar evidence for somatic illnesses is not yet available.