Children and adolescents exposed to maltreatment already exhibit epigenetic patterns suggestive of heightened low-grade inflammation

Abstract

Introduction

Childhood maltreatment (CM) is one of the best described environmental risk factors for developing any psychiatric disorder, while it also confers increased odds for obesity, cardiometabolic disorders and all-cause mortality. Inflammation has been suggested to mediate the widespread clinical effects of CM. Previously, Ligthart et al. (2016) identified a polyepigenetic signature of circulating CRP levels, a measure of chronic low-grade inflammation, that has been reliably associated with a wide array of complex disorders. The study of this biomarker could dilucidate the mechanistic relationship between CM and psychiatric outcomes.

Objectives

Thus, CRP-associated epigenetic modifications were explored regarding proximal exposure to CM.

Methods

Genomic DNA was extracted from peripheral blood mononuclear cells of 157 children and adolescents (7 to 17 years old). Exposure to CM was assessed following the TASSCV criteria. Genome-wide DNA methylation was assessed by means of the EPIC array. Fifty-two out of the 58 original CRP-associated CpG sites surpassed quality control and were included in the analysis. Age, sex, psychopathological status and cell type proportions were included as covariates.

Results

DNA methylation at 12 out of 52 CpG sites (23%) was significantly associated with exposure to CM (p < .05); 8 of these associations survived correction for multiple testing (q < .05).

Conclusions

This is the first study to date to explore the relationship between childhood maltreatment and an epigenetic signature of chronic low-grade inflammation. Our findings underscore the presence of immune dysregulation early after exposure to CM; further studies are needed to assess the long-term clinical implications of this signature in psychiatric patients.

Disclosure

No significant relationships.