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dc.contributor.authorSzabo, Attila
dc.contributor.authorO'Connell, Kevin Sean
dc.contributor.authorUeland, Thor
dc.contributor.authorSheikh, Mashhood Ahmed
dc.contributor.authorAgartz, Ingrid
dc.contributor.authorAndreou, Dimitrios
dc.contributor.authorAukrust, Pål
dc.contributor.authorBoye, Birgitte
dc.contributor.authorBøen, Erlend
dc.contributor.authorDrange, Ole Kristian
dc.contributor.authorElvsåshagen, Torbjørn
dc.contributor.authorEngh, John
dc.contributor.authorHope, Sigrun
dc.contributor.authorHøegh, Margrethe Collier
dc.contributor.authorJoa, Inge
dc.contributor.authorJohnsen, Erik
dc.contributor.authorKroken, Rune Andreas
dc.contributor.authorLagerberg, Trine Vik
dc.contributor.authorLekva, Tove
dc.contributor.authorMalt, Ulrik Fredrik
dc.contributor.authorMelle, Ingrid
dc.contributor.authorMorken, Gunnar
dc.contributor.authorNærland, Terje
dc.contributor.authorSteen, Vidar Martin
dc.contributor.authorSørensen, Kjetil
dc.contributor.authorWedervang-Resell, Kirsten
dc.contributor.authorWeibell, Melissa Anne Elin Authen
dc.contributor.authorWestlye, Lars Tjelta
dc.contributor.authorSteen, Nils Eiel
dc.contributor.authorAndreassen, Ole
dc.contributor.authorDjurovic, Srdjan
dc.description.abstractBackground Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients. Methods We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (n = 1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; n = 1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers. Results We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA, IL-18R1), and increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol types and the expression of inflammasome system elements in SMI. Conclusions Based on these results, we suggest a role for inflammasome activation/dysregulation in SMI. Our findings further the understanding of possible underlying inflammatory mechanisms and may expose important therapeutic targets in SMI.en_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleIncreased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activationen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.source.journalBrain, Behavior, and Immunityen_US
dc.identifier.citationBrain, Behavior, and Immunity. 2022, 99, 299-306.en_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal