Nader Perroud, MD, Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, and Department of Psychiatry, University of Geneva; Alexandre Dayer, MD, Department of Mental Health and Psychiatry, Service of Psychiatric Specialties, University Hospitals of Geneva, and Departments of Basic Neuroscience and of Psychiatry, University of Geneva; Camille Piguet, MD, Department of Neuroscience, Faculty of Medicine, University of Geneva; Audrey Nallet, MSc, Sophie Favre, PhD, Department of Psychiatry, University of Geneva; Alain Malafosse, MD, PhD, Department of Psychiatry, University of Geneva, and Department of Genetic Medicine and Laboratories, Psychiatric Genetic Unit, University Hospitals of Geneva; Jean-Michel Aubry, MD, Department of Mental Health and Psychiatry, Bipolar Programme, Service of Psychiatric Specialties, University Hospitals of Geneva, Switzerland.
Br J Psychiatry. 2014 Jan;204(1):30-5. doi: 10.1192/bjp.bp.112.120055. Epub 2013 Jun 6.
Early-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. This may be the consequence of a sustained alteration of the hypothalamic-pituitary-adrenal (HPA) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (NR3C1).
To investigate whether severity of childhood maltreatment is associated with increased methylation of the exon 1F NR3C1 promoter in bipolar disorder.
A sample of people with bipolar disorder (n = 99) were assessed for childhood traumatic experiences. The percentage of NR3C1 methylation was measured for each participant.
The higher the number of trauma events, the higher was the percentage of NR3C1 methylation (β = 0.52, 95% CI 0.46-0.59, P<<0.0001). The severity of each type of maltreatment (sexual, physical and emotional) was also associated with NR3C1 methylation status.
Early-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood. This enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder.
早期生活逆境是双相情感障碍发展的危险因素，与疾病的严重程度更高有关。这可能是由于糖皮质激素受体（NR3C1）基因编码的基因发生表观遗传修饰，导致下丘脑-垂体-肾上腺（HPA）轴持续改变的结果。
研究童年期虐待的严重程度是否与双相情感障碍中 NR3C1 启动子外显子 1F 的甲基化增加有关。
对 99 名双相情感障碍患者进行了童年期创伤经历的评估。测量了每个参与者的 NR3C1 甲基化百分比。
创伤事件的数量越多，NR3C1 甲基化的百分比越高（β=0.52，95%CI 0.46-0.59，P<<0.0001）。每种虐待（性虐待、身体虐待和情感虐待）的严重程度也与 NR3C1 甲基化状态有关。
早期生活逆境通过表观遗传过程对 HPA 轴产生持续影响，这种影响可以在外周血中测量到。早期创伤的这种持久的生物学影响可能会改变大脑的发育，导致成年期精神病理障碍。
