Angelin Mary, Gopinath Padmavathi, Raghavan Vijaya, Thara Rangaswamy, Ahmad Faraz, Munirajan Arasamabattu Kannan, Sudesh Ravi
Department of Genetics, University of Madras, Dr ALM PG Institute of Basic Medical Sciences, Taramani Campus, Chennai, Tamil Nadu, 600 113, India.
Schizophrenia Research Foundation, Chennai, Tamil Nadu, 600 101, India.
Neuropsychiatr Dis Treat. 2024 Jul 19;20:1435-1444. doi: 10.2147/NDT.S466502. eCollection 2024.
Schizophrenia is a heterogeneous chronic psychiatric disorder influenced by genetic and environmental factors. Environmental factors can alter epigenetic marks, which regulate gene expression and cause an array of systemic changes. Several studies have demonstrated the association of epigenetic modulations in schizophrenia, which can influence clinical course, symptoms, and even treatment. Based on this, we have examined the global DNA methylation patterns, namely the 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC); and the global RNA modification N6-methyladenosine (m6A) RNA methylation status in peripheral blood cells. First-Episode Psychosis (FEP) patients who were diagnosed with Schizophrenia (SCZ) and undergoing treatment were stratified as Treatment-Responsive (TR) and Treatment-Non-Responsive (TNR). Age- and sex-matched healthy subjects served as controls.
The methylation pattern of 5mC and 5hmC showed significant increases in patients in comparison to controls. Further, when patients were classified based on their response to treatment, there was a statistically significant increase in methylation patterns in the treatment non-responder group. 5fC and m6A levels did not show any statistical significance across the groups. Further, gender-based stratification did not yield any significant difference for the markers.
The study highlights the increased global methylation pattern in SCZ patients and a significant difference between the TR versus TNR groups. Global 5mC and 5hmC epigenetic marks suggest their potential roles in schizophrenia pathology, and also in the treatment response to antipsychotics. Since not many studies were available on the treatment response, further validation and the use of more sensitive techniques to study methylation status could unravel the potential of these epigenetic modifications as biomarkers for SCZ as well as distinguishing the antipsychotic treatment response in patients.
精神分裂症是一种受遗传和环境因素影响的异质性慢性精神疾病。环境因素可改变表观遗传标记，这些标记调节基因表达并导致一系列系统性变化。多项研究已证实精神分裂症中表观遗传调控的关联，其可影响临床病程、症状甚至治疗。基于此，我们检测了外周血细胞中的整体DNA甲基化模式，即5-甲基胞嘧啶（5mC）、5-羟甲基胞嘧啶（5hmC）、5-甲酰基胞嘧啶（5fC）；以及整体RNA修饰N6-甲基腺苷（m6A）的RNA甲基化状态。被诊断为精神分裂症（SCZ）并正在接受治疗的首发精神病（FEP）患者被分层为治疗反应良好（TR）组和治疗无反应（TNR）组。年龄和性别匹配的健康受试者作为对照。
与对照组相比，患者的5mC和5hmC甲基化模式显著增加。此外，当根据患者对治疗的反应进行分类时，治疗无反应组的甲基化模式有统计学显著增加。5fC和m6A水平在各组之间未显示任何统计学意义。此外，基于性别的分层对这些标记物未产生任何显著差异。
该研究突出了SCZ患者整体甲基化模式增加以及TR组与TNR组之间的显著差异。整体5mC和5hmC表观遗传标记表明它们在精神分裂症病理学以及对抗精神病药物的治疗反应中的潜在作用。由于关于治疗反应的研究不多，进一步验证以及使用更敏感的技术来研究甲基化状态可能会揭示这些表观遗传修饰作为SCZ生物标志物以及区分患者抗精神病治疗反应的潜力。
