Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan; Department of Neuropsychiatry, Osaka City University, Graduate School of Medicine, Osaka, Japan.
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.
J Affect Disord. 2018 Jun;233:15-20. doi: 10.1016/j.jad.2017.06.001. Epub 2017 Jun 6.
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.
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.
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 (ρ = 0.38, P < 0.00005) was verified with an ELISA (ρ = 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.
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.
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.
虽然炎性细胞因子是心境障碍的既定生物标志物，但它们的分子机制尚不清楚。我们假设循环线粒体 DNA（mtDNA）有助于炎症，并可作为生物标志物。我们研究了循环 mtDNA 水平是否与炎性细胞因子相关，以及是否可以作为心境障碍的生物标志物。
采用实时定量 PCR 靶向 mtDNA 的两个区域测量血浆 mtDNA 浓度，采用多重免疫分析方法测量 109 例重性抑郁障碍（MDD）患者的四种细胞因子（GM-CSF、IL-2、IL-4 和 IL-6）的血浆水平。用酶联免疫吸附试验（ELISA）验证与最显著相关的细胞因子。比较了 28 例双相障碍（BD）患者、17 例精神分裂症（SZ）患者和 29 例健康对照者的数据。
MDD 患者的 mtDNA 水平与 GM-CSF、IL-2 和 IL-4 呈正相关。与 IL-4 的相关性最显著（ρ=0.38，P＜0.00005），用 ELISA 验证（ρ=0.19，P=0.049）。出乎意料的是，与对照组相比，MDD 和 BD 患者的血浆 mtDNA 水平显著降低。MDD 患者的 mtDNA 水平在抑郁状态下低于在心境正常状态下。与对照组相比，抑郁、双相障碍和精神分裂症患者的这四种细胞因子水平均无显著升高。
本研究中的患者与先前报道细胞因子水平升高的研究可能有所不同。应该在显示血浆细胞因子水平升高的患者中测量 mtDNA 水平。需要更大的样本量来推广结果。
目前的研究结果与我们的假设一致，即循环 mtDNA 有助于 MDD 的炎症。需要进一步的研究来确定血浆 mtDNA 是否为心境障碍的生物标志物。
