Epigenetic alterations associated with childhood trauma and adult mental health outcomes: A systematic review.

Objectives: Multiple, chronic and repeated trauma exposure in childhood is associated with adverse mental health outcomes in adulthood. In this paper we synthesise the literature on epigenetic modifications in childhood trauma (CT) and the mediating effects of differential epigenetic mechanisms on the association between CT and the later onset of psychiatric disorders.Methods: We reviewed the literature up to March 2018 in four databases: PubMed, Web of Science, EBSCOhost and SCOPUS. Non-human studies were excluded. All studies investigating CT exposure both in healthy adults (18 years and older) and adults with psychiatric disorders were included.Results: Thirty-six publications were included. For mood disorders, methylation of the glucocorticoid receptor NR3C1 gene, specifically at the NGFI-A binding site in exon 1F, and correlation with CT was a robust finding. Several studies documented differential methylation of SLC6A4, BDNF, OXTR and FKBP5 in association with CT. Common pathways identified include neuronal functioning and maintenance, immune and inflammatory processes, chromatin and histone modification, and transcription factor binding.Conclusions: A variety of epigenetic mediators that lie on a common pathway between CT and psychiatric disorders have been identified, although longitudinal studies and consistency in methodological approach are needed to disentangle cause and effect associations.