Hammann Nicole, Kaess Michael, Rujescu Dan, Brunner Romuald, Hartmann Annette M, Reichl Corinna
Department of Child and Adolescent Psychiatry, University Hospital Heidelberg, Heidelberg, Germany.
Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Psychopathology. 2024;57(2):81-90. doi: 10.1159/000531253. Epub 2023 Aug 2.
Non-suicidal self-injury (NSSI) is a large phenomenon among adolescents, and adverse childhood experiences (ACEs) are a major risk factor in its development. Malfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis has been repeatedly reported for ACE as well as for NSSI. The glucocorticoid receptor (GR) is essential for the correct functioning of the HPA axis, thus alterations in the expression of the GR through altered methylation of the GR gene (NR3C1) (and more specifically exon 1F) might contribute to the development of NSSI in individuals with a history of ACEs, as has been reported for different other mental disorders.
In this case-control study, we compared the methylation levels of exon 1F of the GR gene (NR3C1-1F) in adolescents with engagement in NSSI (n = 67) and a healthy control group (HC; n = 47). We preserved buccal swabs and used a mass spectrometry-based method called EpiTYPER for analyzing mean methylation of NR3C1-1F.
Adolescents in the NSSI group reported significantly more ACEs. The mean methylation level was about 3% in both groups with no significant group differences. Furthermore, no significant relation was found between ACE and methylation of NR3C1-1F, neither in the overall sample nor in the NSSI or HC group.
Our results are contradictory to previous research showing an increased methylation in individuals with ACE. Regarding relations between methylation of NR3C1-1F and mental disorders, previous studies reported inconsistent findings. Our study points to NSSI being either unrelated to methylation of NR3C1-1F or to yet not identified moderators on relations between methylation of NR3C1-1F and engagement in NSSI during adolescence.
非自杀性自伤行为（NSSI）在青少年中是一种普遍现象，童年不良经历（ACEs）是其发展的主要风险因素。下丘脑-垂体-肾上腺（HPA）轴功能失调在ACEs以及NSSI中均有反复报道。糖皮质激素受体（GR）对于HPA轴的正常功能至关重要，因此，如针对其他不同精神障碍所报道的那样，GR基因（NR3C1）（更具体地说是外显子1F）甲基化改变导致的GR表达改变可能促成有ACEs病史个体的NSSI发展。
在这项病例对照研究中，我们比较了参与NSSI的青少年（n = 67）和健康对照组（HC；n = 47）中GR基因外显子1F（NR3C1-1F）的甲基化水平。我们保存了口腔拭子，并使用一种基于质谱的方法EpiTYPER来分析NR3C1-1F的平均甲基化水平。
NSSI组的青少年报告的ACEs明显更多。两组的平均甲基化水平均约为3%，无显著组间差异。此外，在总体样本中以及在NSSI组或HC组中，均未发现ACE与NR3C1-1F甲基化之间存在显著关联。
我们的结果与先前研究显示ACE个体甲基化增加的结果相矛盾。关于NR3C1-1F甲基化与精神障碍之间的关系，先前的研究报告结果不一致。我们的研究表明，NSSI要么与NR3C1-1F甲基化无关，要么与尚未确定的调节因子有关，这些调节因子影响青春期NR3C1-1F甲基化与参与NSSI之间的关系。
