title: Damage-associated molecular patterns and immune activation in bipolar disorder.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, BRA.|Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Department of Psychiatry and Behavioral Sciences, Center for Molecular Psychiatry, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Stertz
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, BRA.|Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: G R
authors.initials: GR
authors.lastname: Fries
authors.affiliation: Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Department of Pharmacology, Basic Science Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Rosa
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, BRA.|Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Kauer-Sant'anna
authors.affiliation: Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Ferrari
authors.affiliation: Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: A V C
authors.initials: AV
authors.lastname: Paz
authors.affiliation: Department of Pediatrics, Center for Clinical Research and Evidence-Based Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Green
authors.affiliation: Department of Pharmacology, Basic Science Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Department of Neuropsychiatry, Centro de Ciências da Saude, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Â B M
authors.initials: ÂB
authors.lastname: Cunha
authors.affiliation: Laboratorio de FisiopatologiaExperimental, Unidade Academica de Ciencias da Saude, Universidade do Extremo Sul Catarinense, Criciuma, SC, USA.
authors.forename: F
authors.initials: F
authors.lastname: Dal-Pizzol
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, BRA.
authors.forename: C
authors.initials: C
authors.lastname: Gottfried
authors.affiliation: Bipolar Disorder Program & INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Department of Psychiatry and Behavioral Sciences, Center for Molecular Psychiatry, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: F
authors.initials: F
authors.lastname: Kapczinski
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D018834:Chaperonin 60 / Q000097:blood; D004247:DNA / Q000097:blood* / Q000235:genetics; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D018841:HSP90 Heat-Shock Proteins / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D057285:Precision Medicine
chemical_list: D015415:Biomarkers; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D004247:DNA
keywords: acute mood episode; bipolar disorder; cell death; circulating cell-free DNA; damage-associated molecular patterns; heat-shock proteins