Increased methylation of glucocorticoid receptor gene ( NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

Abstract

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene ( NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1 _F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation ( P=6.16 × 10 ⁻⁸, 5.18 × 10 ⁻⁷ and 1.25 × 10 ⁻⁹, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology.