Wan Lin, Wei Jing
Department of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Aug 3;17:2511-2525. doi: 10.2147/NDT.S320680. eCollection 2021.
Patients with early-onset schizophrenia usually exhibit more severe symptoms, revealing a potentially distinctive disease phenotype. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate conversion and methylation modification associated with the disease. We aimed to investigate the potential effects of polymorphisms and related methylation patterns in patients with early-onset schizophrenia, which implies special phenotypes of schizophrenia.
In 177 patients with schizophrenia, polymorphism at three sites (C677T, A1298C, and G1793A) and the Positive and Negative Syndrome Scale (PANSS) were tested. Differential methylation positions (DMPs) and enrichment of genes and related pathways were analyzed by testing the genomic methylation level. Catechol-O-methyltransferase (), solute carrier family 6 member 4 (), neuregulin1 (), and brain-derived neurotrophic factor () were selected to evaluate the methylation levels of specific CpG regions by pyrosequencing.
Higher levels of symptom severity and polymorphisms and lower levels of global DNA methylation in patients with early-onset schizophrenia were observed in this study. was hypermethylated, and was hypomethylated in specific regions of patients with early-onset schizophrenia.
Aggravating symptoms, increased polymorphisms, and reduced genomic methylation levels may be characteristics and underlying mechanisms of early-onset schizophrenia, which implies a special disease phenotype. Beyond that, specific genes and biological pathways may imply the potential phenotype of schizophrenia.
早发性精神分裂症患者通常表现出更严重的症状，揭示出一种潜在独特的疾病表型。亚甲基四氢叶酸还原酶（MTHFR）是与该疾病相关的叶酸转化和甲基化修饰中的关键酶。我们旨在研究早发性精神分裂症患者中多态性和相关甲基化模式的潜在影响，这暗示了精神分裂症的特殊表型。
对177例精神分裂症患者进行三个位点（C677T、A1298C和G1793A）的多态性及阳性和阴性症状量表（PANSS）检测。通过检测基因组甲基化水平分析差异甲基化位点（DMPs）以及基因和相关通路的富集情况。选择儿茶酚-O-甲基转移酶（）、溶质载体家族6成员4（）、神经调节蛋白1（）和脑源性神经营养因子（），通过焦磷酸测序评估特定CpG区域的甲基化水平。
本研究观察到早发性精神分裂症患者症状严重程度和多态性水平较高，而全基因组DNA甲基化水平较低。在早发性精神分裂症患者的特定区域，呈高甲基化，而呈低甲基化。
症状加重、多态性增加和基因组甲基化水平降低可能是早发性精神分裂症的特征和潜在机制，这暗示了一种特殊的疾病表型。除此之外，特定基因和生物学通路可能暗示精神分裂症的潜在表型。
