The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression
The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression
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DOI：
10.1016/j.jad.2017.06.001
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发表时间：
2018-06-01
影响因子：
6.6
通讯作者：
Kato, Tadafumi
中科院分区：
文献类型：
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作者：
Kageyama, Yuki;Kasahara, Takaoki;Kato, Tadafumi
背景：虽然炎症因子是情绪障碍的生物标志物，但其分子机制尚不清楚。我们假设循环线粒体DNA （mtDNA）有助于炎症，可以用作生物标志物。我们研究了循环mtDNA水平是否与炎症细胞因子相关，并可作为情绪障碍的生物标志物。方法：对109例重度抑郁症（MDD）患者采用实时荧光定量PCR检测血浆mtDNA浓度，多重免疫分析法检测血浆中4种细胞因子（GM-CSF、IL-2、IL-4、IL-6）水平。用酶联免疫吸附试验（ELISA）验证了最显著相关的细胞因子。比较了28例双相情感障碍（BD）患者、17例精神分裂症（SZ）患者和29例健康对照者的数据。结果：MDD患者MtDNA水平与GM-CSF、IL-2和IL-4呈名义正相关。ELISA检测与IL-4相关性最显著（rho = 0.38, P < 0.00005） （rho = 0.19, P = 0.049）。出乎意料的是，MDD和BD患者的血浆mtDNA水平明显低于对照组。抑郁症患者的MtDNA水平在抑郁状态时低于正常心境时。抑郁症、双相情感障碍和精神分裂症患者的这四种细胞因子水平并没有明显高于对照组。局限性：本研究中的患者可能与先前报道细胞因子水平升高的研究不同。血浆细胞因子水平升高的患者应测量MtDNA水平。需要更大的样本来推广结果。结论：目前的发现与我们的假设一致，即循环mtDNA有助于MDD的炎症。血浆mtDNA是否是情绪障碍的生物标志物还需要进一步的研究。
Background: Although inflammatory cytokines are established biomarkers of mood disorders, their molecular mechanism is not known. We hypothesized that circulating mitochondrial DNA (mtDNA) contributes to inflammation and could be used as biomarkers. We investigated if circulating mtDNA level is associated with inflammatory cytokines and can be used as a biomarker of mood disorders.Methods: Plasma mtDNA concentration was measured with real-time quantitative PCR targeting two regions of the mtDNA and plasma levels of four cytokines (GM-CSF, IL-2, IL-4, and IL-6) were measured with a multiplex immunoassay method in 109 patients with major depressive disorder (MDD). The most significantly correlated cytokine was verified with an enzyme-linked immunosorbent assay (ELISA). The data from 28 patients with bipolar disorder (BD), 17 patients with schizophrenia (SZ), and 29 healthy controls were compared.Results: MtDNA levels showed a nominal positive correlation with GM-CSF, IL-2 and IL-4 in patients with MDD. The most significant correlation with IL-4 (rho = 0.38, P < 0.00005) was verified with an ELISA (rho = 0.19, P = 0.049). Unexpectedly, patients with MDD and BD showed significantly lower plasma mtDNA levels than controls. MtDNA levels were lower in the depressive state than in the euthymic state in patients with MDD. Patients with depression, bipolar disorder, and schizophrenia did not show significantly higher levels of these four cytokines than controls.Limitations: There is a possibility that the patients in this study are different from previous studies in which increased cytokine levels were reported. MtDNA levels should be measured in patients showing elevated plasma cytokine levels. A larger sample is required to generalize the results.Conclusions: The present findings coincide with our hypothesis that circulating mtDNA contributes to the inflammation in MDD. Further studies are needed to conclude whether plasma mtDNA would be a biomarker of mood disorders.