Early life adversity, genomic plasticity, and psychopathology

Abstract

Child maltreatment is associated with an increased risk of psychiatric disorders, and a range of health problems later in life. Research suggests that adverse events early in life can lead to changes in gene expression through epigenetic mechanisms that alter stress reactivity, brain function, and behaviour. Although epigenetic changes are often long lasting, they can be reversed with pharmacological and environmental manipulations. The complexity of the epigenome is not fully understood. The aim of this Review is to assess emerging data for the role of epigenetic mechanisms in stress-related psychiatric disorders with a focus on future research. We describe the epigenetic processes, key findings in this specialty, clinical implications of research, and methodological issues. Studies are needed to investigate new epigenetic processes other than methylation and assess the efficacy of interventions to reverse epigenetic processes associated with the effects of early life adversity.

Figure 1

DNA methylation and demethylation. Cytosine (C); 5-methylcytosine (5-mC); 5-hydroxymethylcytosine (5-hmC); 5-formylcytosine (5-fC); 5-carboxylcytosine (5-caC); DNA methyltransferase (DNMT); ten-eleven translocation enzyme (TET); active modification-passive dilution (AM-PD); thymine DNA glycosylase (TDG).

Figure 2

(a) Euchromatin is associated with active transcription, whereas (b) heterochromatin with transcriptional repression. (c) Each histone has N-termini tails that can be modified, activating or inhibiting transcription.