Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder
Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder
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DOI：
10.1016/j.jpsychires.2014.06.011
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发表时间：
2014-10-01
影响因子：
4.8
通讯作者：
Carlos Pascual, Juan
中科院分区：
文献类型：
--
作者：
Martin-Blanco, Ana;Ferrer, Marc;Carlos Pascual, Juan
下丘脑-垂体-肾上腺轴（HPA）在应激反应的调节中是必不可少的。糖皮质激素受体基因（NR 3C 1）的启动子区域甲基化的增加在有儿童创伤史的受试者和边缘型人格障碍（BPD）患者中都有描述。然而，没有关于该基因的较高甲基化与临床严重程度之间可能相关的数据。本研究的目的是评估NR 3C 1甲基化状态、儿童期创伤史和BPD受试者当前临床严重程度之间的相关性。招募了281名BPD受试者（通过SCID-II和DIB-R半结构化诊断访谈诊断）。临床变量包括既往住院史、自伤行为和自我报告的儿童创伤史。从外周血中提取DNA。结果表明，NR 3C 1甲基化状态与儿童期虐待（特别是身体虐待）之间存在显著正相关。此外，观察到甲基化状态与临床严重程度（DIB-R总评分和住院）之间呈正相关。这些发现表明，BPD受试者的NR 3C 1甲基化可能不仅与儿童期创伤有关，而且与临床严重程度有关，为这种疾病中基因-环境相互作用的参与提供了新的证据。(C)2014爱思唯尔有限公司版权所有。
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. (C) 2014 Elsevier Ltd. All rights reserved.