Mediating effects of DNA methylation levels (cg04622888 and cg05037505) on the association between childhood maltreatment and non-suicidal self-injury in adolescents

Abstract

Aims It is unclear whether DNA methylation underlies the associations of childhood maltreatment (CM) with non-suicidal self-injury (NSSI) in adolescents. We aim to explore the mediating effect of specific DNA methylation sites’ levels on the associations of CM and its subtypes with NSSI, following investigation on the association between the specific DNA methylation sites’ levels and NSSI. Methods A nested case-control study was conducted to examine 155 adolescents aged 12–14 years who had NSSI and 201 controls. CM and its subtypes were evaluated using the Childhood Trauma Questionnaire. The 850k chip was used to discover the differences in the whole genome methylation levels in the peripheral blood of 10 NSSI cases and 10 controls. Pyrosequencing was employed to detect the levels of differential methylation sites among the study population, which were selected based on bioinformatics analysis. Results After controlling for potential confounders, CM and its subtypes, and the methylation levels of cg04622888 and cg05037505 were all significantly associated with NSSI. The methylation level of cg05037505 significantly mediated the association of emotional abuse (proportion mediated estimates: 0.09; 95% CI: 0.06–0.14), emotional neglect (0.08; 95%CI: 0.05–0.13), or physical neglect (0.18; 95%CI: 0.08–0.31) with NSSI. The methylation level of cg04622888 significantly mediated the association of physical neglect (0.14; 95%CI: 0.06–0.25) with NSSI. Conclusions The methylation levels of cg04622888 and cg05037505 were independently associated with NSSI among early adolescents, and they partially mediated the associations of emotional abuse, emotional neglect, and physical abuse with NSSI. Targeted interventions for NSSI should focus on individuals who have experienced of CM and exhibit high methylation levels of cg04622888 and cg05037505.