Inflammatory markers are associated with general cognitive abilities in schizophrenia and bipolar disorder patients and healthy controls

Sigrun Hope; Eva Hoseth; Ingrid Dieset; Ragni H Mørch; Monica Aas; Pål Aukrust; Srdjan Djurovic; Ingrid Melle; Torill Ueland; Ingrid Agartz; Thor Ueland; Lars T Westlye; Ole A Andreassen

doi:10.1016/j.schres.2015.04.004

Inflammatory markers are associated with general cognitive abilities in schizophrenia and bipolar disorder patients and healthy controls

Schizophr Res. 2015 Jul;165(2-3):188-94. doi: 10.1016/j.schres.2015.04.004. Epub 2015 May 5.

Authors

Affiliations

¹ NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Neuro Habilitation, Oslo University Hospital, Ullevål, Oslo, Norway.
² NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Oslo, Norway.
³ 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.
⁴ NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway.
⁵ NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
⁶ NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
⁷ 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.
⁸ 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.
⁹ 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.

PMID: 25956633
DOI: 10.1016/j.schres.2015.04.004

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.

Conclusion: 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.

Keywords: Cognitive; IL-1Ra; IL-6; Inflammation; Osteoprotegerin; Severe mental disorders; Von Willebrand factor; Wechsler Abbreviated Scale of Intelligence (WASI); hsCRP; sTNF-R1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Analysis of Variance
Biomarkers / blood*
Bipolar Disorder / complications*
Cognition Disorders / blood*
Cognition Disorders / etiology*
Cytokines / blood*
Female
Humans
Male
Middle Aged
Neuropsychological Tests
Psychiatric Status Rating Scales
Schizophrenia / complications*
Young Adult

Substances

Biomarkers
Cytokines