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Inflammatory markers are altered in severe mental disorders independent of comorbid cardiometabolic disease risk factors

Published online by Cambridge University Press:  28 January 2019

Ragni H. Mørch Open the ORCID record for Ragni H. Mørch [Opens in a new window] ,
Ingrid Dieset ,
Ann Færden ,
Elina J. Reponen ,
Sigrun Hope ,
Eva Z. Hoseth ,
Erlend S. Gardsjord ,
Monica Aas ,
Trude Iversen  and
Inge Joa
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Ragni H. Mørch*
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway
Ingrid Dieset
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway Department of Acute Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital Ullevål, Oslo, Norway
Ann Færden
Affiliation:
Department of Acute Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital Ullevål, Oslo, Norway
Elina J. Reponen
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway
Sigrun Hope
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway Department of Neuro Habilitation, Oslo University Hospital Ullevål, Oslo, Norway
Eva Z. Hoseth
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway Division of Mental Health and Addiction, Møre and Romsdal Health Trust, Kristiansund, Norway
Erlend S. Gardsjord
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway
Monica Aas
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway
Trude Iversen
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway
Inge Joa
Affiliation:
Centre for Clinical Research in Psychosis, Psychiatric Division, Stavanger University Hospital, Stavanger, Norway Network for Medical Sciences, Faculty of Social Sciences, University of Stavanger, Stavanger, Norway
Gunnar Morken
Affiliation:
Department of Psychiatry, St. Olav University Hospital, Trondheim, Norway Department of Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology – NTNU, Trondheim, Norway
Ingrid Agartz
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
Ingrid Melle
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway
Pål Aukrust
Affiliation:
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Norway K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
Srdjan Djurovic
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
Thor Ueland
Affiliation:
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Norway K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
Ole A. Andreassen
Affiliation:
NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo and Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Norway
*
Author for correspondence: Ragni H. Mørch, E-mail: [email protected]
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Abstract

Background

Inflammation and immune activation have been implicated in the pathogenesis of severe mental disorders and cardiovascular disease (CVD). Despite high level of comorbidity, many studies of the immune system in severe mental disorders have not systematically taken cardiometabolic risk factors into account.

Methods

We investigated if inflammatory markers were increased in schizophrenia (SCZ) and affective (AFF) disorders independently of comorbid CVD risk factors. Cardiometabolic risk factors (blood lipids, body mass index and glucose) and CVD-related inflammatory markers CXCL16, soluble interleukin-2 receptor (sIL-2R), soluble CD14 (sCD14), macrophage inhibitory factor and activated leukocyte cell adhesion molecule (ALCAM) were measured in n = 992 patients (SCZ, AFF), and n = 647 healthy controls. We analyzed the inflammatory markers before and after controlling for comorbid cardiometabolic risk factors, and tested for association with psychotropic medication and symptom levels.

Results

CXCL16 (p = 0.03) and sIL-2R (p = 7.8 × 10−5) were higher, while sCD14 (p = 0.05) were lower in patients compared to controls after controlling for confounders, with significant differences in SCZ for CXCL16 (p = 0.04) and sIL-2R (p = 1.1 × 10−5). After adjustment for cardiometabolic risk factors higher levels of sIL-2R (p = 0.001) and lower sCD14 (p = 0.002) remained, also in SCZ (sIL-2R, p = 3.0 × 10−4 and sCD14, p = 0.01). The adjustment revealed lower ALCAM levels (p = 0.03) in patients. We found no significant associations with psychotropic medication or symptom levels.

Conclusion

The results indicate that inflammation, in particular enhanced T cell activation and impaired monocyte activation, are associated with severe mental disorders independent of comorbid cardiometabolic risk factors. This suggests a role of novel pathophysiological mechanisms in severe mental disorders, particularly SCZ.

Keywords

Bipolar disordercomorbid cardiometabolic risk factorsimmune activationinflammationschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 10 , July 2019 , pp. 1749 - 1757
Copyright
Copyright © Cambridge University Press 2019 

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