Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder

• Published in: Journal of psychiatric research Vol. 57; pp. 34 - 40
• Main Authors: Martín-Blanco, Ana, Ferrer, Marc, Soler, Joaquim, Salazar, Juliana, Vega, Daniel, Andión, Oscar, Sanchez-Mora, Cristina, Arranz, Maria Jesús, Ribases, Marta, Feliu-Soler, Albert, Pérez, Víctor, Pascual, Juan Carlos
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2014; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Borderline personality disorder; Borderline Personality Disorder - genetics; Borderline Personality Disorder - psychology; Child; Child Abuse - psychology; Childhood trauma; DNA Methylation - genetics; Epigenetics; Female; Gene-Environment Interaction; Genetics; Glucocorticoid receptor gene; Hospitalization; Humans; Male; Medical sciences; Methylation; Personality disorders; Promoter Regions, Genetic - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptors, Glucocorticoid - genetics; Self-Injurious Behavior - genetics; Severity of Illness Index; Victimology; Young Adult; Glucocorticoid receptor gene; Epigenetics; Genetics; Methylation; Childhood trauma; Borderline personality disorder; Borderline; Victimology; Genetic determinism; Personality disorder; Child abuse; Gene; Glucocorticoid receptor; Early traumatism; Epigenesis; Severity score
• ISSN: 0022-3956; 1879-1379; 1879-1379
• DOI: 10.1016/j.jpsychires.2014.06.011

The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available. The aim of this study was to evaluate the association between NR3C1 methylation status, the history of childhood trauma, and current clinical severity in subjects with BPD. A sample of 281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic interviews) was recruited. Clinical variables included previous hospitalizations, self-injurious behavior, and self-reported history of childhood trauma. DNA was extracted from peripheral blood. The results indicated a significant positive correlation between NR3C1 methylation status and childhood maltreatment (specifically physical abuse). In addition, a positive correlation between methylation status and clinical severity (DIB-R total score and hospitalizations) was observed. These findings suggest that NR3C1 methylation in subjects with BPD may be associated not only with childhood trauma but also with clinical severity, adding new evidence to the involvement of gene-environment interactions in this disorder. •Epigenetic mechanisms seem to have a role in pathogenesis of BPD.•Childhood trauma and BPD severity are associated with higher NR3C1 methylation.•According to previous data, childhood trauma may lead to higher NR3C1 methylation.•If BPD severity is cause or consequence of increased methylation should be clarified.