Mitochondria (Mt) are intra-cellular components essential for cellular energy processes whose dysfunction may induce premature cellular senescence and/or inflammation, both observed in bipolar disorders (BD). We investigated mitochondrial DNA copy number (mtDNAcn) levels in patients with BD being in manic, depressive or euthymic phase and in healthy controls (HC) both characterized for the levels of blood-based inflammatory markers and stigma of pathogens.

312 patients with BD were compared to 180 HC. mtDNAcn were measured using a digital droplet PCR. Serum levels of 14 inflammatory molecules and 3 anti-infectious IgG stigma were respectively evaluated by electro-chemiluminescence, ELISA and dedicated immunoassays. The statistical analyses were performed using Spearman’s correlation, Wilcoxon signed-rank and Kruskal-Wallis rank sum tests. P-values were adjusted for multiple testing with Benjamini-Hochberg method.

We found low levels of mtDNAcn in BD patients as compared to HC (P = 0.008) especially during manic episodes (P = 0.0002). We also observed that low levels of mtDNAcn are negatively correlated with mood and psychotic scales (PANSS, YMRS and CGI) (adjusted P (Adj P) = 0.02, 0.003 and 0.05 respectively) and positively with the GAF severity scale (Adj P = 0.002). They were also correlated with high levels of both intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 (Adj P = 0.003 and 0.001) along with a trend toward increased IL-2, IL-10 and B2M circulating levels (Adj P = 0.05).

Here, we report correlations between marker of mitochondria functioning and both clinical scales and inflammatory markers in BD patients experiencing manic episodes. If replicated, these finding might allow to predict transition between disease phases and to design accurate therapeutic options.

线粒体 (Mt) 是细胞能量过程必不可少的细胞内成分，其功能障碍可能会导致细胞过早衰老和/或炎症，这两者都在双相情感障碍 (BD) 中观察到。我们调查了处于躁狂期、抑郁期或心境正常期的 BD 患者和健康对照 (HC) 的线粒体 DNA 拷贝数 (mtDNAcn) 水平，两者均以基于血液的炎症标志物和病原体的污名为特征。

312 名 BD 患者与 180 名 HC 进行了比较。使用数字液滴 PCR 测量 mtDNAcn。分别通过电化学发光、ELISA 和专用免疫测定法评估 14 种炎症分子和 3 种抗感染 IgG 柱头的血清水平。使用 Spearman 相关性、Wilcoxon 符号秩和 Kruskal-Wallis 秩和检验进行统计分析。使用 Benjamini-Hochberg 方法针对多重测试调整 P 值。

我们发现与 HC 相比，BD 患者的 mtDNAcn 水平较低（P =  0.008），尤其是在躁狂发作期间（P =  0.0002）。我们还观察到低水平的 mtDNAcn 与情绪和精神病量表（PANSS、YMRS 和 CGI​​）呈负相关（调整后的 P ( Adj P ) = 0.02、0.003 和 0.05），与 GAF 严重程度量表呈正相关（Adj P  = 0.002 ）。它们还与高水平的细胞间粘附分子 (ICAM)-1 和血管细胞粘附分子 (VCAM)-1（Adj P  = 0.003 和 0.001）以及 IL-2、IL-10 和 B2M 增加的趋势相关循环水平（Adj P  = 0.05）。

在这里，我们报告了线粒体功能标志物与经历躁狂发作的 BD 患者的临床量表和炎症标志物之间的相关性。如果被复制，这些发现可能允许预测疾病阶段之间的转变并设计准确的治疗方案。