Importance Nucleic acid damage from oxidative stress (NA-OXS) may be a molecular mechanism driving the severely increased morbidity and mortality from somatic causes in adults with psychiatric disorders. Objective To systematically retrieve and analyze data on NA-OXS across the psychiatric disorder diagnostic spectrum. Data Sources The PubMed, Embase, and PsycINFO databases were searched from inception to November 16, 2021. A hand search of reference lists of relevant articles was also performed. Study Selection Key study inclusion criteria in this meta-analysis were as follows: adult human study population, measurement of any marker of DNA or RNA damage from oxidative stress, and either a (1) cross-sectional design comparing patients with psychiatric disorders (any diagnosis) with a control group or (2) prospective intervention. Two authors screened the studies, and 2 senior authors read the relevant articles in full and assessed them for eligibility. Data Extraction and Synthesis The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two authors performed data extraction independently, and a senior coauthor was consulted in cases of disagreement. Data were synthesized with random-effects and multilevel meta-analyses. Main Outcomes and Measures The predefined hypothesis was that individuals with psychiatric disorders have increased NA-OXS levels. The main outcome was the standardized mean differences (SMDs) among patients and controls in nucleic acid oxidation markers compared across diagnostic groups. Analyses were divided into combinations of biological matrices and nucleic acids. Results Eighty-two studies fulfilled the inclusion criteria, comprising 205 patient vs control group comparisons and a total of 10 151 patient and 10 532 control observations. Overall, the data showed that patients with psychiatric disorders had higher NA-OXS levels vs controls across matrices and molecules. Pooled effect sizes ranged from moderate for urinary DNA markers (SMD = 0.44 [95% CI, 0.20-0.68]; P < .001) to very large for blood cell DNA markers (SMD = 1.12 [95% CI, 0.69-1.55; P < .001). Higher NA-OXS levels were observed among patients with dementias followed by psychotic and bipolar disorders. Sensitivity analyses excluding low-quality studies did not materially alter the results. Intervention studies were few and too heterogenous for meaningful meta-analysis. Conclusions and Relevance The results of this meta-analysis suggest that there is an association with increased NA-OXS levels in individuals across the psychiatric disorder diagnostic spectrum. NA-OXS may play a role in the somatic morbidity and mortality observed among individuals with psychiatric disorders.

中文翻译：

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氧化应激诱导的核酸损伤与成人精神疾病的关联：系统评价和荟萃分析。

氧化应激引起的核酸损伤 (NA-OXS) 可能是导致成人精神疾病患者因躯体原因导致发病率和死亡率严重增加的一种分子机制。目的 系统地检索和分析精神疾病诊断范围内的 NA-OXS 数据。数据来源 PubMed、Embase 和 PsycINFO 数据库的检索时间从建库到 2021 年 11 月 16 日。还对相关文章的参考文献列表进行了手工检索。研究选择 本荟萃分析中的关键研究纳入标准如下：成人研究人群、氧化应激引起的 DNA 或 RNA 损伤的任何标记物的测量，以及比较精神疾病患者（任何诊断）与对照组或（2）前瞻性干预。两位作者对研究进行了筛选，两位资深作者完整阅读了相关文章并评估了它们的资格。数据提取和合成遵循系统评价和荟萃分析（PRISMA）指南的首选报告项目。两位作者独立进行数据提取，如有分歧，会咨询资深合著者。通过随机效应和多级荟萃分析来合成数据。主要结果和措施 预先设定的假设是患有精神疾病的个体 NA-OXS 水平升高。主要结果是跨诊断组比较患者和对照组核酸氧化标记物的标准化平均差异（SMD）。分析分为生物基质和核酸的组合。结果 82 项研究满足纳入标准，包括 205 项患者与对照组的比较以及总共 10 151 名患者和 10 532 名对照观察结果。总体而言，数据显示，在基质和分子方面，精神疾病患者的 NA-OXS 水平高于对照组。尿液 DNA 标记物的汇总效应大小范围为中等（SMD = 0.44 [95% CI, 0.20-0.68]；P < .001）到血细胞 DNA 标记物的非常大（SMD = 1.12 [95% CI, 0.69-1.55；P < .001]）。 P < .001)。在痴呆症患者中观察到较高的 NA-OXS 水平，其次是精神病和双相情感障碍患者。排除低质量研究的敏感性分析并未对结果产生实质性改变。干预研究很少，而且异质性太强，无法进行有意义的荟萃分析。结论和相关性 这项荟萃分析的结果表明，在整个精神疾病诊断范围内，NA-OXS 水平升高与个体存在关联。NA-OXS 可能在精神疾病个体的躯体发病率和死亡率中发挥作用。