Both severe mental illness and atypical antipsychotics have been independently associated with insulin resistance and weight gain. Altered regulation of skeletal muscle DNA methylation may play a role. We aimed to evaluate DNA methylation modifications in human skeletal muscle samples to further understand its potential role in the metabolic burden observed in psychiatric patients and psychopharmacologic treatment. Subjects were included in our study if they had a bipolar diagnosis and were currently treated with a mood stabilizer or atypical antipsychotic. A healthy control group free of psychiatric or physical disease was also included for comparisons. Anthropometric, BMI and hemoglobin A1C (HbA1C%) were measured. Fasting skeletal muscle biopsies were obtained and methylation levels of 5-methycytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 5-formylcytosine (5-fC) were measured. Skeletal muscle global methylation of 5-mC and 5-fC were significantly higher in bipolar subjects compared to healthy controls. 5-mC was significantly higher in the AAP group compared to the mood stabilizer group. Significant correlations were observed between 5-fC methylation and HbA1C%. Our findings suggest that psychiatric disease and treatment may influence some methylation measures in the skeletal muscle of patients with bipolar disorder, which may be further influenced by medication treatment.

中文翻译：

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双相情感障碍的骨骼肌 DNA 甲基化修饰和精神药理学治疗

严重的精神疾病和非典型抗精神病药都与胰岛素抵抗和体重增加独立相关。骨骼肌 DNA 甲基化的调节改变可能起作用。我们旨在评估人类骨骼肌样本中的 DNA 甲基化修饰，以进一步了解其在精神病患者和精神药理学治疗中观察到的代谢负担中的潜在作用。如果受试者患有双相情感障碍并且目前正在接受情绪稳定剂或非典型抗精神病药治疗，则他们被纳入我们的研究。还包括一个没有精神或身体疾病的健康对照组进行比较。测量了人体测量学、BMI 和血红蛋白 A1C（HbA1C%）。获得空腹骨骼肌活检和 5-甲基胞嘧啶 (5-mC) 的甲基化水平，测量了 5-羟甲基胞嘧啶 (5-hmC) 和 5-甲酰基胞嘧啶 (5-fC)。与健康对照相比，双相受试者的骨骼肌 5-mC 和 5-fC 整体甲基化显着更高。与情绪稳定剂组相比，AAP 组的 5-mC 显着更高。在 5-fC 甲基化和 HbA1C% 之间观察到显着相关性。我们的研究结果表明，精神疾病和治疗可能会影响双相情感障碍患者骨骼肌中的一些甲基化指标，而这可能会受到药物治疗的进一步影响。在 5-fC 甲基化和 HbA1C% 之间观察到显着相关性。我们的研究结果表明，精神疾病和治疗可能会影响双相情感障碍患者骨骼肌中的一些甲基化指标，而这可能会受到药物治疗的进一步影响。在 5-fC 甲基化和 HbA1C% 之间观察到显着相关性。我们的研究结果表明，精神疾病和治疗可能会影响双相情感障碍患者骨骼肌中的一些甲基化指标，而这可能会受到药物治疗的进一步影响。