title: Inflammatory evidence for the psychosis continuum model.
abstract: BACKGROUND
  Inflammation and immune activation have been implicated in the pathophysiology of severe mental disorders. Previous studies of inflammatory markers, however, have been limited with somewhat inconsistent results.
  
  
  OBJECTIVE
  We aimed to determine the effect sizes of inflammatory marker alterations across diagnostic groups of the psychosis continuum and investigate association to antipsychotic medications.
  
  
  METHODS
  Plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), and von Willebrand factor (vWf) were measured in patients (n=992) with schizophrenia spectrum (SCZ, n=584), schizoaffective disorder (SA, n=93), affective spectrum disorders (AFF, n=315), and healthy controls (HC, n=638).
  
  
  RESULTS
  Levels of sTNF-R1 (p=1.8×10(-8), d=0.23) and IL-1Ra (p=0.002, d=0.16) were increased in patients compared to HC. The SCZ group had higher levels of sTNF-R1 (p=8.5×10(-8), d=0.27) and IL-1Ra (p=5.9×10(-5), d=0.25) compared to HC, and for sTNF-R1 this was also seen in the SA group (p=0.01, d=0.3) and in the AFF group (p=0.002, d=0.12). Further, IL-1Ra (p=0.004, d=0.25) and vWf (p=0.02, d=0.21) were increased in the SCZ compared to the AFF group. There was no significant association between inflammatory markers and use of antipsychotic medication.
  
  
  CONCLUSIONS
  We demonstrate a small increase in sTNF-R1 and IL-1Ra in patients with severe mental disorders supporting a role of inflammatory mechanisms in disease pathophysiology. The increase was more pronounced in SCZ compared to AFF supporting a continuum psychosis model related to immune factors.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway. Electronic address: ragnihm@medisin.uio.no.
authors.forename: Ragni H
authors.initials: RH
authors.lastname: Mørch
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, 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 and Oslo University Hospital, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Ann
authors.initials: A
authors.lastname: Færden
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, 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 and Oslo University Hospital, 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: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Nerhus
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Erlend S
authors.initials: ES
authors.lastname: Gardsjord
authors.affiliation: Centre for Clinical Research in Psychosis, Psychiatric Division, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Inge
authors.initials: I
authors.lastname: Joa
authors.affiliation: The Department of Psychiatry, St. Olav University Hospital of Trondheim, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Morken
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, 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; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, 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: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. 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 and Oslo University Hospital, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D008297:Male; D008960:Models, Psychological; D019964:Mood Disorders / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D053244:Osteoprotegerin / Q000097:blood*; D011618:Psychotic Disorders / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D011619:Psychotropic Drugs / Q000627:therapeutic use; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012559:Schizophrenia / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D053244:Osteoprotegerin; D011619:Psychotropic Drugs; D047888:Receptors, Tumor Necrosis Factor, Type I; D014841:von Willebrand Factor
keywords: Antipsychotics; Bipolar disorder; Inflammation; Psychosis continuum model; Schizophrenia