Low peripheral mitochondrial DNA copy number during manic episodes of bipolar disorders is associated with disease severity and inflammation
Low peripheral mitochondrial DNA copy number during manic episodes of bipolar disorders is associated with disease severity and inflammation
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DOI：
10.1016/j.bbi.2021.09.003
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发表时间：
2021-09-08
影响因子：
15.1
通讯作者：
Tamouza, Ryad
中科院分区：
文献类型：
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作者：
Angrand, Loic;Boukouaci, Wahid;Tamouza, Ryad
线粒体（Mt）是细胞能量过程所必需的细胞内组分，其功能障碍可诱导细胞过早衰老和/或炎症，这两者都在双相情感障碍（BD）中观察到。我们研究了处于躁狂、抑郁或正常情绪期的BD患者和健康对照（HC）的线粒体DNA拷贝数（mtDNA Acn）水平，两者均以血液炎症标志物和病原体污名水平为特征。312例BD患者与180例HC患者进行了比较。使用数字液滴PCR测量mtDNA Acn。分别采用电化学发光法、ELISA法和专用免疫分析法检测血清中14种炎性分子和3种抗感染IgG抗体水平。使用斯皮尔曼相关性、Wilcoxon符号秩和Kruskal-Wallis秩和检验进行统计分析。使用Benjamini-Hochberg方法调整P值以进行多重检验。我们发现BD患者的mtDNAn水平较HC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mtDNAc n与情绪和精神病量表（PANSS，YMRS和CGI）呈负相关（校正P（Adj P）分别= 0.02，0.003和0.05），与GAF严重程度量表呈正相关（Adj P = 0.002）。它们还与细胞间粘附分子（ICAM）-1和血管细胞粘附分子（VCAM）-1的高水平相关（Adj P = 0.003和0.001），沿着IL-2、IL-10和B2 M循环水平升高的趋势（Adj P = 0.05）。在这里，我们报告的线粒体功能的标志物和临床规模和炎症标志物在BD患者经历躁狂发作之间的相关性。如果重复，这些发现可能允许预测疾病阶段之间的过渡，并设计准确的治疗方案。
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 electrochemiluminescence, 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.