title: 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.
authors: Department of Psychiatry, University of Geneva, Chêne-Bourg, Switzerland. nader.perroud@hcuge.ch
authors: N
authors: N
authors: Perroud
authors: A
authors: A
authors: Paoloni-Giacobino
authors: P
authors: P
authors: Prada
authors: E
authors: E
authors: Olié
authors: A
authors: A
authors: Salzmann
authors: R
authors: R
authors: Nicastro
authors: S
authors: S
authors: Guillaume
authors: D
authors: D
authors: Mouthon
authors: C
authors: C
authors: Stouder
authors: K
authors: K
authors: Dieben
authors: P
authors: P
authors: Huguelet
authors: P
authors: P
authors: Courtet
authors: A
authors: A
authors: Malafosse
mesh_terms: D000328:Adult; D002648:Child; D002650:Child Abuse, Sexual / Q000523:psychology*; D019175:DNA Methylation / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid