Sigrun Hope1, Eva Hoseth2, Ingrid Dieset2, Ragni H Mørch2, Monica Aas2, Pål Aukrust3, Srdjan Djurovic4, Ingrid Melle2, Torill Ueland5, Ingrid Agartz6, Thor Ueland7, Lars T Westlye8, Ole A Andreassen9. 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.
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.
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 tumornecrosis 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 schizophreniapatients, with sCD40L and IL-1Ra in bipolar disorderpatients 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.
Authors: Eva Zsuzsanna Hoseth; Thor Ueland; Ingrid Dieset; Rebecca Birnbaum; Joo Heon Shin; Joel Edward Kleinman; Thomas Michael Hyde; Ragni Helene Mørch; Sigrun Hope; Tove Lekva; Aurelija Judita Abraityte; Annika E Michelsen; Ingrid Melle; Lars Tjelta Westlye; Torill Ueland; Srdjan Djurovic; Pål Aukrust; Daniel R Weinberger; Ole Andreas Andreassen Journal: Schizophr Bull Date: 2017-07-01 Impact factor: 9.306
Authors: G Fond; F Berna; M Andrianarisoa; O Godin; M Leboyer; L Brunel; B Aouizerate; D Capdevielle; I Chereau; T D'Amato; H Denizot; C Dubertret; J Dubreucq; C Faget; F Gabayet; P M Llorca; J Mallet; D Misdrahi; C Passerieux; R Richieri; R Rey; A Schandrin; M Urbach; P Vidailhet; L Boyer; F Schürhoff Journal: Eur Arch Psychiatry Clin Neurosci Date: 2017-02-25 Impact factor: 5.270
Authors: C E Millett; J Harder; J J Locascio; M Shanahan; G Santone; R N Fichorova; A Corrigan; C Baecher-Allan; K E Burdick Journal: Brain Behav Immun Date: 2020-04-06 Impact factor: 7.217