Division of Social Neuropsychiatry and Evolutionary Medicine, LWL University Hospital Department of Psychiatry, Psychotherapy and Preventive Medicine, Ruhr-University Bochum, Bochum, Germany.
PLoS One. 2021 Mar 11;16(3):e0248514. doi: 10.1371/journal.pone.0248514. eCollection 2021.
Previous research suggests that childhood maltreatment is associated with epigenetic modification of genes involved in hypothalamic-pituitary-adrenal (HPA) functioning, which could cause dysregulation of the stress response system. If pervasive, this may be associated with the development of stress-related disorder in adults, including affective disorders, anxiety disorders, post-traumatic stress disorder (PTSD) or borderline-personality disorder (BPD). The majority of studies have focused on DNA methylation of the glucocorticoid receptor gene (NR3C1) and the FKBP5 encoding gene, which regulates the sensitivity of the glucocorticoid receptor (GR). How methylation of NR3C1 and FKBP5 interferes with childhood adversity and psychopathology as well as empathy is an under-researched issue. Here, we sought to investigate the association of childhood maltreatment in a sample of 89 individuals (44 healthy participants and 45 patients diagnosed with BPD) with the methylation of the 1F promoter region of NR3C1 and the intron 7 of FKBP5 as well as with different measures of psychopathology and empathy. Methylation of FKBP5 (bin 2) correlated with anxiety (SCL-90-R) and the global psychopathological symptom load index (GSI), as well as with lower empathic perspective-taking abilities. Psychopathology and empathy impairments correlated with the level of childhood maltreatment. No difference in FKBP5 methylation was observed between the clinical and the non-clinical group. Methylation of NR3C1 was lower in BPD patients compared to controls, yet with small differences. The results are discussed regarding their biological relevance, including possible evolutionary explanations. In short, the regulation of the GR sensitivity by methylation of FKBP5 correlated with psychopathology and empathy scores, while no correlation emerged with the severity of childhood adversity.
先前的研究表明，童年期虐待与涉及下丘脑-垂体-肾上腺 (HPA) 功能的基因的表观遗传修饰有关，这可能导致应激反应系统的失调。如果普遍存在，这可能与成年人应激相关障碍的发展有关，包括情感障碍、焦虑障碍、创伤后应激障碍 (PTSD) 或边缘型人格障碍 (BPD)。大多数研究都集中在糖皮质激素受体基因 (NR3C1) 和编码 FKBP5 的基因的 DNA 甲基化上，FKBP5 调节糖皮质激素受体 (GR) 的敏感性。NR3C1 和 FKBP5 的甲基化如何干扰童年逆境和精神病理学以及同理心是一个研究不足的问题。在这里，我们试图在 89 名个体样本中研究童年期虐待与 NR3C1 的 1F 启动子区域和 FKBP5 的内含子 7 的甲基化以及不同的精神病理学和同理心测量之间的关联。FKBP5 (bin 2) 的甲基化与焦虑 (SCL-90-R) 和全球精神病理学症状负荷指数 (GSI) 相关，与同理心的换位思考能力降低相关。精神病理学和同理心障碍与童年期虐待的程度相关。临床组和非临床组之间 FKBP5 甲基化没有差异。与对照组相比，BPD 患者的 NR3C1 甲基化水平较低，但差异较小。结果从生物学相关性方面进行了讨论，包括可能的进化解释。简而言之，FKBP5 甲基化对 GR 敏感性的调节与精神病理学和同理心评分相关，而与童年逆境的严重程度无关。
