Ragni H Mørch1, Ingrid Dieset1, Ann Færden2, Elina J Reponen1, Sigrun Hope1, Eva Z Hoseth1, Erlend S Gardsjord1, Monica Aas1, Trude Iversen1, Inge Joa3, Gunnar Morken4, Ingrid Agartz1, Ingrid Melle1, Pål Aukrust5, Srdjan Djurovic6, Thor Ueland5, Ole A Andreassen1. 1. NORMENT-KG Jebsen Centre for Psychosis Research,University of Oslo and Oslo University Hospital,Oslo,Norway. 2. Department of Acute Psychiatry, Division of Mental Health and Addiction,Oslo University Hospital Ullevål,Oslo,Norway. 3. Centre for Clinical Research in Psychosis, Psychiatric Division,Stavanger University Hospital,Stavanger,Norway. 4. Department of Psychiatry,St. Olav University Hospital,Trondheim,Norway. 5. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet,Oslo,Norway. 6. Department of Medical Genetics,Oslo University Hospital,Oslo,Norway.
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.
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.
Authors: John Abel Engh; Thor Ueland; Ingrid Agartz; Dimitrios Andreou; Pål Aukrust; Birgitte Boye; Erlend Bøen; Ole Kristian Drange; Torbjørn Elvsåshagen; Sigrun Hope; Margrethe Collier Høegh; Inge Joa; Erik Johnsen; Rune Andreas Kroken; Trine Vik Lagerberg; Tove Lekva; Ulrik Fredrik Malt; Ingrid Melle; Gunnar Morken; Terje Nærland; Vidar Martin Steen; Kirsten Wedervang-Resell; Melissa Auten Weibell; Lars Tjelta Westlye; Srdjan Djurovic; Nils Eiel Steen; Ole Andreas Andreassen Journal: Schizophr Bull Date: 2022-01-21 Impact factor: 7.348
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Authors: Attila Szabo; Ibrahim A Akkouh; Thor Ueland; Trine Vik Lagerberg; Ingrid Dieset; Thomas Bjella; Pål Aukrust; Stephanie Le Hellard; Anne-Kristin Stavrum; Ingrid Melle; Ole A Andreassen; Srdjan Djurovic Journal: Front Psychiatry Date: 2020-07-02 Impact factor: 4.157
Authors: Attila Szabo; Ibrahim A Akkouh; Matthieu Vandenberghe; Jordi Requena Osete; Timothy Hughes; Vivi Heine; Olav B Smeland; Joel C Glover; Ole A Andreassen; Srdjan Djurovic Journal: Transl Psychiatry Date: 2021-10-29 Impact factor: 6.222
Authors: Kirsten Wedervang-Resell; Thor Ueland; Pål Aukrust; Svein Friis; Kirsten B Holven; Cecilie H Johannessen; Tove Lekva; Vera Lonning; Runar E Smelror; Attila Szabo; Ole A Andreassen; Anne M Myhre; Ingrid Agartz Journal: NPJ Schizophr Date: 2020-08-18
Authors: Ole A Andreassen; Srdjan Djurovic; Jordi Requena Osete; Ibrahim A Akkouh; Denis Reis de Assis; Attila Szabo; Evgeniia Frei; Timothy Hughes; Olav B Smeland; Nils Eiel Steen Journal: Mol Psychiatry Date: 2021-06-01 Impact factor: 15.992