DNA Methylation Signature of Childhood Chronic Physical Aggression in T Cells of Both Men and Women

Abstract

BackgroundHigh frequency of physical aggression is the central feature of severe conduct disorder and is associated with a wide range of social, mental and physical health problems. We have previously tested the hypothesis that differential DNA methylation signatures in peripheral T cells are associated with a chronic aggression trajectory in males. Despite the fact that sex differences appear to play a pivotal role in determining the development, magnitude and frequency of aggression, most of previous studies focused on males, so little is known about female chronic physical aggression. We therefore tested here whether or not there is a signature of physical aggression in female DNA methylation and, if there is, how it relates to the signature observed in males.Methodology/Principal FindingsMethylation profiles were created using the method of methylated DNA immunoprecipitation (MeDIP) followed by microarray hybridization and statistical and bioinformatic analyses on T cell DNA obtained from adult women who were found to be on a chronic physical aggression trajectory (CPA) between 6 and 12 years of age compared to women who followed a normal physical aggression trajectory. We confirmed the existence of a well-defined, genome-wide signature of DNA methylation associated with chronic physical aggression in the peripheral T cells of adult females that includes many of the genes similarly associated with physical aggression in the same cell types of adult males.ConclusionsThis study in a small number of women presents preliminary evidence for a genome-wide variation in promoter DNA methylation that associates with CPA in women that warrant larger studies for further verification. A significant proportion of these associations were previously observed in men with CPA supporting the hypothesis that the epigenetic signature of early life aggression in females is composed of a component specific to females and another common to both males and females.

Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review

“…Three studies reported on the methylation status of exon 1 H , with one study reporting no change (21), one reporting increased methylation (40) and one reporting decreased methylation (29). Additionally, one study reported decreased GR gene methylation, but did not specify the region investigated (43). …”

Sex differences in the development of physical aggression: An intergenerational perspective and implications for preventive interventions

“…A total of 448 distinct gene promoters were found to be differentially methylated in the two groups of boys (Provençal et al., ). An identical study with girls showed similar differences between the aggressive and nonaggressive girls, but often on different genes (Guillemin et al., ).…”

Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology

“…() found that youth with a lifetime diagnosis of an externalising disorder showed lower levels of NR3C1 methylation at exon 1F (whole blood), compared with both youth with a depressive disorder and healthy controls. Based on data extracted from white blood cells, one research group also found that, compared with controls, adult males with a history of chronic childhood aggression differed in (a) SLC6A4 promoter methylation and in vivo levels of brain serotonin synthesis (Wang et al., ); (b) DNAm levels in a set of genes involved in cytokine function and inflammation (Provençal, Suderman, Vitaro, Szyf, & Tremblay, ); and (c) DNAm patterns across a large number of gene promoter regions in an epigenome‐wide scan (Provençal et al., ) – a finding that was later extended to a small sample of adult females as well (Guillemin et al., ). In the ALSPAC sample, we found that methylomic variation at seven loci across the genome at birth (cord blood) differentiated children who go on to develop early‐onset ( n = 174) versus low ( n = 86) conduct problems, including sites in the vicinity of MGLL – a gene involved in endocannabinoid signalling and pain perception (Cecil, et al., ).…”