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Greater methylation of the IL-6 promoter region is associated with decreased integrity of the corpus callosum in schizophrenia
Journal of Psychiatric Research ( IF 4.8 ) Pub Date : 2024-05-04 , DOI: 10.1016/j.jpsychires.2024.05.013
Anna Michalczyk , Ernest Tyburski , Piotr Podwalski , Katarzyna Waszczuk , Krzysztof Rudkowski , Jolanta Kucharska-Mazur , Monika Mak , Katarzyna Rek-Owodziń , Piotr Plichta , Maksymilian Bielecki , Wojciech Andrusewicz , Elżbieta Cecerska-Heryć , Agnieszka Samochowiec , Błażej Misiak , Leszek Sagan , Jerzy Samochowiec

Schizophrenia is associated with chronic subclinical inflammation and decreased integrity of the corpus callosum (CC). Our previous study showed associations between peripheral IL-6 levels and the integrity of the CC. Epigenetic studies show associations between methylation of the genes related to immunological processes and integrity of the CC. To investigate correlations between methylation status of IL-6 promotor and peripheral IL-6 levels and the integrity of the CC in schizophrenia. The participants were 29 chronic schizophrenia patients (SCH) and 29 controls. Decreased integrity of the CC was understood as increased mean diffusivity (MD) and/or decreased fractional anisotropy (FA) in diffusion tensor imaging. Peripheral IL-6 concentrations were measured in serum samples and IL-6 promoter methylation status of 6 CpG sites was analyzed in peripheral leukocytes by pyrosequencing. Moderate positive correlations were found between CpG1 methylation and the MD of proximal regions of the CC (CCR1–CCR3) and between CpG and MD of CCR1 in SCH. Weaker positive correlations were found for CpG with CCR2 and CCR3 and negative correlations were found for CpG1 and FA of CCR3 in SCH. Multivariate regression showed that methylation of CpG1, type of antipsychotic treatment, and their interaction were significant independent predictors of MD of CCR1 in SCH. Methylation of CpG2 was negatively correlated with serum IL-6 in SCH. The methylation level of the IL-6 promotor region in peripheral leukocytes is associated with the integrity of the CC in schizophrenia and this association may depend on the type of antipsychotic treatment. Further studies are necessary to explain the mechanisms of the observed associations.

中文翻译:

IL-6启动子区甲基化程度较高与精神分裂症患者胼胝体完整性降低相关

精神分裂症与慢性亚临床炎症和胼胝体 (CC) 完整性降低有关。我们之前的研究表明外周 IL-6 水平与 CC 完整性之间存在关联。表观遗传学研究表明,与免疫过程相关的基因甲基化与 CC 完整性之间存在关联。旨在研究精神分裂症中 IL-6 启动子的甲基化状态和外周 IL-6 水平与 CC 完整性之间的相关性。参与者包括 29 名慢性精神分裂症患者 (SCH) 和 29 名对照者。 CC 完整性的降低被理解为扩散张量成像中平均扩散率 (MD) 的增加和/或分数各向异性 (FA) 的减少。测量血清样品中的外周IL-6浓度,并通过焦磷酸测序分析外周白细胞中6个CpG位点的IL-6启动子甲基化状态。发现 CpG1 甲基化与 CC 近端区域 (CCR1-CCR3) 的 MD 之间以及 SCH 中 CCR1 的 CpG 与 MD 之间呈中度正相关。在 SCH 中,CpG 与 CCR2 和 CCR3 呈较弱的正相关,而 CpG1 和 CCR3 的 FA 呈负相关。多变量回归显示,CpG1 甲基化、抗精神病药物治疗类型及其相互作用是 SCH 中 CCR1 MD 的显着独立预测因子。 SCH 中 CpG2 甲基化与血清 IL-6 呈负相关。外周白细胞中 IL-6 启动子区的甲基化水平与精神分裂症中 CC 的完整性相关,并且这种关联可能取决于抗精神病药物治疗的类型。需要进一步的研究来解释所观察到的关联的机制。
更新日期:2024-05-04
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