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

• Published in: Translational psychiatry Vol. 1; no. 12; p. e59
• Main Authors: Perroud, N, Paoloni-Giacobino, A, Prada, P, Olié, E, Salzmann, A, Nicastro, R, Guillaume, S, Mouthon, D, Stouder, C, Dieben, K, Huguelet, P, Courtet, P, Malafosse, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2011; Nature Publishing Group
• Subjects: 631/208/176/1988; 631/477; 692/699/476; Adult; Behavioral Sciences; Biological Psychology; Child; Child Abuse, Sexual - psychology; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - epidemiology; Depressive Disorder, Major - genetics; DNA Methylation - genetics; Female; Humans; Hypothalamo-Hypophyseal System - physiopathology; Male; Medicine; Medicine & Public Health; Neurosciences; Original; original-article; Pharmacotherapy; Pituitary-Adrenal System - physiopathology; Psychiatry; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Severity of Illness Index; Stress Disorders, Post-Traumatic - diagnosis; Stress Disorders, Post-Traumatic - epidemiology; Stress Disorders, Post-Traumatic - genetics; childhood maltreatment; NR3C1; epigenetic; methylation; borderline personality disorder
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2011.60

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.