Damage-associated molecular patterns and immune activation in bipolar disorder

• Published in: Acta psychiatrica Scandinavica Vol. 132; no. 3; pp. 211 - 217
• Main Authors: Stertz, L., Fries, G. R., Rosa, A. R., Kauer-Sant'anna, M., Ferrari, P., Paz, A. V. C., Green, C., Cunha, Â. B. M., Dal-Pizzol, F., Gottfried, C., Kapczinski, F.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2015
• Subjects: acute mood episode; Adult; Aged; Biomarkers - blood; bipolar disorder; Bipolar Disorder - blood; Bipolar Disorder - genetics; Bipolar Disorder - immunology; Case-Control Studies; cell death; Chaperonin 60 - blood; circulating cell-free DNA; damage-associated molecular patterns; DNA - blood; DNA - genetics; Female; heat-shock proteins; HSP70 Heat-Shock Proteins - blood; HSP90 Heat-Shock Proteins - blood; Humans; Male; Middle Aged; Multivariate Analysis; Precision Medicine; acute mood episode; bipolar disorder; cell death; damage-associated molecular patterns; heat-shock proteins; circulating cell-free DNA
• ISSN: 0001-690X; 1600-0447; 1600-0447
• DOI: 10.1111/acps.12417

Objective Immune activation in bipolar disorder (BD) has been frequently reported. Damage‐associated molecular patterns (DAMPs) are key players in the immune activation reaction. The aim of this study was to assess DAMP levels in drug‐free patients with BD during acute episodes. Method Serum levels of a predetermined set of DAMPs were assessed in drug‐free patients with BD (n = 20) during an acute mood episode. We also included two control groups: healthy subjects, used as a negative control (n = 20); and patients with sepsis, used as a positive control for severe immune activation (n = 20). Results Multivariate analysis using generalized linear mixed model indicated that all DAMPs differed as a function of group membership after controlling for age and addressing multiplicity (P < 0.0006 for all comparisons). Follow‐up analyses showed higher levels in BD subjects of circulating cell‐free (ccf) nuclear (n)DNA (P = 0.02), HSP70 (P = 0.03) and HSP90α (P = 0.02) as compared to healthy subjects. Also, patients with BD showed lower levels of ccf nDNA (P = 0.04), HSP60 (P = 0.03), HSP70 (P = 0.01), and HSP90α (P = 0.002) as compared to patients with sepsis and higher levels of ccf mitochondrial DNA (P < 0.0001). Conclusion The present findings may be linked to the inflammatory activity previously described among patients with BD and may help in the development of more targeted and personalized treatments for patients under acute episodes of BD.