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

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.