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

Loïc Angrand, Wahid Boukouaci, Mohamed Lajnef, Jean Romain Richard, Ana Andreazza, Chieng Lien Wu, Jihène Bouassida, Ismail Rafik, Marianne Foiselle, Esma Mezouad, Soumia Naamoune, Leila Chami, Ons Mihoub, Sofiane Salah, Arij Benchaaben, Philippe Le Corvoisier, Caroline Barau, Bruno Costes, Robert Yolken, Guillemette CrepeauxMarion Leboyer, Ryad Tamouza

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)349-356
Number of pages8
JournalBrain, Behavior, and Immunity
Volume98
DOIs
StatePublished - Nov 2021

Keywords

  • Bipolar disorders (BD), Mania, Mitochondria (mt)

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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