Background and Hypothesis The complex immune-brain interactions and the regulatory role of mitochondria in the immune response suggest that mitochondrial damage reported in schizophrenia (SZ) may be related to abnormalities observed in immune and brain functions. Study Design Mitochondrial DNA copy number (mtDNA CN), a biomarker of mitochondrial function, was assessed in peripheral blood leukocytes (PBLs) of 121 healthy individuals and 118 SZ patients before and after 8 weeks of antipsychotic treatment, and a meta-analysis related to blood mtDNA CN was conducted. Plasma C-reactive protein (CRP) levels in SZ patients were obtained from the medical record system. Spearman correlation analysis and hierarchical linear regression were used to analyze the relationships among mtDNA CN, CRP levels, and cognitive function. A mediation model was constructed using the PROCESS program. Study Results Our results revealed the decreased mtDNA CN in PBLs from SZ patients (P = .05). The meta-analysis supported the decreased blood mtDNA CN in SZ patients (P < .01). The mtDNA CN in PBL was positively correlated with working memory (P = .02) and negatively correlated with plasma CRP levels (P = .039). Furthermore, a lower mtDNA CN in PBL in SZ patients was a significant predictor of worse working memory (P = .006). CRP acted as a mediator with an 8.0% effect. Conclusions This study revealed an association between peripheral mitochondrial dysfunction and cognitive impairment in SZ, with inflammation acting as a mediating effect. Therefore, mitochondrial dysfunction might provide novel targets for new treatments for cognitive impairment in SZ.

中文翻译：

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精神分裂症中的线粒体功能障碍和认知障碍：炎症的作用


背景和假设复杂的免疫-大脑相互作用和线粒体在免疫反应中的调节作用表明，精神分裂症 （SZ） 中报告的线粒体损伤可能与观察到的免疫和大脑功能异常有关。研究设计 线粒体 DNA 拷贝数 （mtDNA CN） 是线粒体功能的生物标志物，在抗精神病药物治疗 8 周前后，在 121 名健康个体和 118 名 SZ 患者的外周血白细胞 （PBL） 中进行评估，并进行了与血液 mtDNA CN 相关的荟萃分析。SZ 患者的血浆 C 反应蛋白 （CRP） 水平是从病历系统获得的。采用 Spearman 相关分析和分层线性回归分析 mtDNA CN、CRP 水平与认知功能之间的关系。使用 PROCESS 程序构建中介模型。研究结果我们的结果显示 SZ 患者 PBL 中的 mtDNA CN 降低 （P = .05）。荟萃分析支持 SZ 患者血液 mtDNA CN 降低 （P < .01）。PBL 中的 mtDNA CN 与工作记忆呈正相关 （P = .02），与血浆 CRP 水平呈负相关 （P = .039）。此外，SZ 患者 PBL 中较低的 mtDNA CN 是工作记忆较差的重要预测因子 （P = .006）。CRP 充当中介，具有 8.0% 的效果。结论 本研究揭示了 SZ 患者外周线粒体功能障碍与认知功能障碍之间的关联，炎症起中介作用。因此，线粒体功能障碍可能为 SZ 认知障碍的新疗法提供新的靶点。