L Stertz1,2,3, G R Fries1,2, A R Rosa2,4, M Kauer-Sant'anna1,2, P Ferrari2, A V C Paz2, C Green5, Â B M Cunha4,6, F Dal-Pizzol7, C Gottfried1, F Kapczinski2,3. 1. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, BRA. 2. Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 3. Department of Psychiatry and Behavioral Sciences, Center for Molecular Psychiatry, University of Texas Health Science Center, Houston, TX, USA. 4. Department of Pharmacology, Basic Science Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 5. Department of Pediatrics, Center for Clinical Research and Evidence-Based Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA. 6. Department of Neuropsychiatry, Centro de Ciências da Saude, Universidade Federal de Santa Maria, Santa Maria, Brazil. 7. Laboratorio de FisiopatologiaExperimental, Unidade Academica de Ciencias da Saude, Universidade do Extremo Sul Catarinense, Criciuma, SC, USA.
Abstract
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.
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.