title: Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder.
abstract: BACKGROUND
  Previous studies suggest elevated inflammation in schizophrenia and bipolar disorder, with increased activity of the Interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF)-alpha, von Willebrand factor (vWf) and osteoprotegerin (OPG). It is unclear how immune activation is involved in the psychopathology. We investigated if elevated inflammation was associated with disease severity (trait) or current symptom level (state), comparing psychotic with general characteristics.
  
  
  METHODS
  Plasma levels of sTNF receptor 1 (sTNF-R1), IL-1 receptor antagonist (IL-1Ra), IL-6, vWf and OPG were measured with ELISA techniques in 322 patients with schizophrenia spectrum and bipolar disorder. Current symptom level (state) was measured with Global Assessment of Functioning (GAF) and Positive and Negative Syndrome Scale (PANSS). Disease severity (trait) was measured with premorbid adjustment scale (PAS), age at onset, number of psychotic episodes and number and length of hospitalizations.
  
  
  RESULTS
  After controlling for confounders, IL-1Ra and TNF-R1 were independently associated with GAF, and significantly correlated with PANSS negative and positive, respectively. In addition, Il-1Ra was associated with PAS, and sTNF-R1 with number of hospitalizations and psychotic episodes. VWf was significantly correlated with psychotic episodes, OPG with hospitalizations and IL-6 with history of psychosis. Linear regression analysis showed that GAF remained associated with sTNF-R1 and IL-1Ra with PANSS, after controlling for the other clinical measures.
  
  
  CONCLUSIONS
  This supports that inflammatory markers, particularly IL-1Ra and sTNF-R1 are associated with both general disease severity and psychotic features. This supports a role of immune activation in the core pathological mechanisms of severe mental disorders.
authors: KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. sigrun.hope@ous-hf.no
authors: Sigrun
authors: S
authors: Hope
authors: Thor
authors: T
authors: Ueland
authors: Nils Eiel
authors: NE
authors: Steen
authors: Ingrid
authors: I
authors: Dieset
authors: Steinar
authors: S
authors: Lorentzen
authors: Akiah O
authors: AO
authors: Berg
authors: Ingrid
authors: I
authors: Agartz
authors: Pål
authors: P
authors: Aukrust
authors: Ole A
authors: OA
authors: Andreassen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000209:etiology*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D012044:Regression Analysis; D012559:Schizophrenia / Q000150:complications* / Q000378:metabolism; D012720:Severity of Illness Index; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D053244:Osteoprotegerin; D018124:Receptors, Tumor Necrosis Factor; D014841:von Willebrand Factor