4.7 Article

Low peripheral mitochondrial DNA copy number during manic episodes of bipolar disorders is associated with disease severity and inflammation

期刊

BRAIN BEHAVIOR AND IMMUNITY
卷 98, 期 -, 页码 349-356

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2021.09.003

关键词

Bipolar disorders (BD); Mania; Mitochondria (mt)

资金

  1. Agence Nationale de la Recherche [ANR-13-SAMA-0004-01, ANR-18-0008-01]
  2. INSERM (Institut National de la Sante et de la Recherche Medicale)
  3. Fondation FondaMental
  4. E3M association (Entraide aux malades de myofasciite a macrophages)
  5. Agence Nationale de la Recherche (ANR) [ANR-13-SAMA-0004] Funding Source: Agence Nationale de la Recherche (ANR)

向作者/读者索取更多资源

The study found that patients with bipolar disorder have lower levels of mitochondrial DNA copy number, particularly during manic episodes. These low levels were negatively correlated with mood and psychotic symptom scales, but positively correlated with severity scales. Additionally, they were correlated with high levels of certain inflammatory markers.
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.

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