Schizophrenia is a heterogeneous mental disorder caused by genetic and environmental factors, and epigenetic mechanisms play a vital role in its pathogenesis. Evidence suggests that some psychiatric disorders are linked to methylation of the glucocorticoid receptor gene NR3C1, a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis. However, the contribution of NR3C1 methylation to schizophrenia has not yet been investigated. By applying a case-control approach (N = 128 controls, N = 80 patients), we for the first time examined the methylation state of the NR3C1 gene promoter region and its role in schizophrenia. Using peripheral blood samples, NR3C1 methylation in exons 1_D, 1_B, 1_F, and 1_H was assessed via sodium bisulfite treatment combined with the MethylTarget method. NR3C1 methylation at exon 1_B was positively associated with schizophrenia in females but not in males. Nonetheless, specific CpG sites in exon 1_D, 1_B, 1_H, and 1_F regions were found to be associated with schizophrenia, usually with sex specificity. These results suggest that epigenetic aberrations of NR3C1 are associated with the pathophysiology of schizophrenia, and epigenetic processes possibly mediate psychopathology through effects on HPA axis activity. Correlation analysis between NR3C1 gene methylation and schizophrenia may be helpful for the assessment of forensic psychiatry.

中文翻译：

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精神分裂症患者NR3C1基因的DNA甲基化分析。

精神分裂症是一种由遗传和环境因素引起的异质性精神障碍，表观遗传机制在其发病机理中起着至关重要的作用。有证据表明，某些精神疾病与糖皮质激素受体基因NR3C1（下丘脑-垂体-肾上腺（HPA）轴的关键调节剂）的甲基化有关。但是，尚未研究NR3C1甲基化对精神分裂症的贡献。通过采用病例对照方法（N  = 128名对照，N  = 80名患者），我们首次检查了NR3C1基因启动子区域的甲基化状态及其在精神分裂症中的作用。使用外周血样本，外显子1中的NR3C1甲基化_D，1 _B，1 _F和1 _H通过亚硫酸氢钠处理结合MethylTarget方法进行评估。外显子1 _B的NR3C1甲基化与女性精神分裂症呈正相关，而男性则与精神分裂症呈正相关。但是，发现外显子1 _D，1 _B，1 _H和1 _F区域中的特定CpG位点与精神分裂症有关，通常与性别特异性有关。这些结果表明NR3C1的表观遗传畸变与精神分裂症的病理生理相关，表观遗传过程可能通过对HPA轴活动的影响来介导心理病理学。NR3C1基因甲基化与精神分裂症之间的相关性分析可能有助于法医精神病学评估。