title: Inflammatory markers are associated with general cognitive abilities in schizophrenia and bipolar disorder patients and healthy controls.
abstract: BACKGROUND
  The mechanisms underlying cognitive impairment in schizophrenia and bipolar disorders are largely unknown. Immune abnormalities have been found in both disorders, and inflammatory mediators may play roles in cognitive function. We investigated if inflammatory markers are associated with general cognitive abilities.
  
  
  METHODS
  Participants with schizophrenia spectrum (N=121) and bipolar spectrum (N=111) disorders and healthy controls (N=241) were included. General intellectual abilities were assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serum concentrations of the following immune markers were measured: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin, von Willebrand factor, C-reactive protein, interleukin-6 and CD40 ligand.
  
  
  RESULTS
  After adjusting for age, sex and diagnostic group, significant negative associations with general cognitive function were found for sTNF-R1 (p=2×10(-5)), IL-1Ra (p=0.002) and sCD40 ligand (p=0.003). Among patients, the associations remained significant (p=0.006, p=0.005 and p=0.02) after adjusting for possible confounders including education, smoking, psychotic and affective symptoms, body mass index, cortisol, medication and time of blood sampling. Subgroup analysis, showed that general cognitive abilities were significantly associated with IL-1Ra and sTNF-R1 in schizophrenia patients, with sCD40L and IL-1Ra in bipolar disorder patients and with sTNF-R1 in healthy controls.
  
  
  CONCLUSIONS
  The study shows significant negative associations between inflammatory markers and general cognitive abilities after adjusting for possible confounders. The findings strongly support a role for inflammation in the neurophysiology of cognitive impairment.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Neuro Habilitation, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Hope
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Eva
authors.initials: E
authors.lastname: Hoseth
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dieset
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Ragni H
authors.initials: RH
authors.lastname: Mørch
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Aas
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Torill
authors.initials: T
authors.lastname: Ueland
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Lars T
authors.initials: LT
authors.lastname: Westlye
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D001714:Bipolar Disorder / Q000150:complications*; D003072:Cognition Disorders / Q000097:blood* / Q000209:etiology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Cognitive; IL-1Ra; IL-6; Inflammation; Osteoprotegerin; Severe mental disorders; Von Willebrand factor; Wechsler Abbreviated Scale of Intelligence (WASI); hsCRP; sTNF-R1