Melamud Mark M, Buneva Valentina N, Ermakov Evgeny A
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
Int J Mol Sci. 2023 Feb 8;24(4):3402. doi: 10.3390/ijms24043402.
The cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. This meta-analysis aimed to analyze the concentrations of different cfDNA types in schizophrenia, BD, and DDs compared with healthy donors. The mitochondrial (cf-mtDNA), genomic (cf-gDNA), and total cfDNA concentrations were analyzed separately. The effect size was estimated using the standardized mean difference (SMD). Eight reports for schizophrenia, four for BD, and five for DDs were included in the meta-analysis. However, there were only enough data to analyze the total cfDNA and cf-gDNA in schizophrenia and cf-mtDNA in BD and DDs. It has been shown that the levels of total cfDNA and cf-gDNA in patients with schizophrenia are significantly higher than in healthy donors (SMD values of 0.61 and 0.6, respectively; < 0.00001). Conversely, the levels of cf-mtDNA in BD and DDs do not differ compared with healthy individuals. Nevertheless, further research is needed in the case of BD and DDs due to the small sample sizes in the BD studies and the significant data heterogeneity in the DD studies. Additionally, further studies are needed on cf-mtDNA in schizophrenia or cf-gDNA and total cfDNA in BD and DDs due to insufficient data. In conclusion, this meta-analysis provides the first evidence of increases in total cfDNA and cf-gDNA in schizophrenia but shows no changes in cf-mtDNA in BD and DDs. Increased circulating cfDNA in schizophrenia may be associated with chronic systemic inflammation, as cfDNA has been found to trigger inflammatory responses.
已知在各种病理状态下，生物体液中的游离DNA（cfDNA）水平会升高。然而，关于严重精神疾病（包括精神分裂症、双相情感障碍（BD）和抑郁症（DDs））中循环cfDNA的数据存在矛盾。本荟萃分析旨在分析精神分裂症、BD和DDs患者与健康供者相比不同类型cfDNA的浓度。分别分析了线粒体（cf-mtDNA）、基因组（cf-gDNA）和总cfDNA浓度。效应大小使用标准化平均差（SMD）进行估计。荟萃分析纳入了8篇关于精神分裂症的报告、4篇关于BD的报告和5篇关于DDs的报告。然而，仅有足够的数据来分析精神分裂症患者的总cfDNA和cf-gDNA，以及BD和DDs患者的cf-mtDNA。结果显示，精神分裂症患者的总cfDNA和cf-gDNA水平显著高于健康供者（SMD值分别为0.61和0.6；<0.00001）。相反，BD和DDs患者的cf-mtDNA水平与健康个体相比无差异。尽管如此，由于BD研究中的样本量较小以及DD研究中的数据异质性显著，BD和DDs仍需要进一步研究。此外，由于数据不足，精神分裂症中的cf-mtDNA或BD和DDs中的cf-gDNA及总cfDNA也需要进一步研究。总之，本荟萃分析首次证明了精神分裂症患者总cfDNA和cf-gDNA升高，但BD和DDs患者的cf-mtDNA无变化。精神分裂症患者循环cfDNA升高可能与慢性全身炎症有关，因为已发现cfDNA可引发炎症反应。
