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dc.contributor.authorHjell, Gabriela
dc.contributor.authorSzabo, Attila
dc.contributor.authorMørch-Johnsen, Lynn Egeland
dc.contributor.authorHolst, Rene
dc.contributor.authorTesli, Natalia
dc.contributor.authorBell, Christina
dc.contributor.authorFischer-Vieler, Thomas
dc.contributor.authorWerner, Maren Caroline Frogner
dc.contributor.authorLunding, Synve Hoffart
dc.contributor.authorOrmerod, Monica Bettina E. Greenwood
dc.contributor.authorJohansen, Ingrid Torp
dc.contributor.authorDieset, Ingrid
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorMelle, Ingrid
dc.contributor.authorUeland, Thor
dc.contributor.authorAndreassen, Ole
dc.contributor.authorSteen, Nils Eiel
dc.contributor.authorHaukvik, Unn Kristin Hansen
dc.description.abstractObjective Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated with agitation in severe mental disorders. Methods Individuals with a psychotic or affective disorder (N = 660) underwent blood sampling and clinical characterization. Plasma levels of interleukin (IL)‐18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), and IL-1 receptor antagonist (IL-1RA) were measured. Agitation levels were estimated with the Positive and Negative Syndrome Scale Excited Component. Multiple linear- and logistic regression were used to investigate the associations between agitation and the immune markers, while controlling for confounders. The influence of psychotic and affective symptoms was assessed in follow-up analyses. Results Agitation was positively associated with IL-18BP (β = 0.13, t = 3.41, p = 0.0007) after controlling for multiple confounders, including BMI, smoking, medication, and substance use. Adjustment for psychotic, manic, and depressive symptoms did not affect the results. There were no significant associations between agitation and the other investigated immune markers (IL-1RA (β = 0.06, t = 1.27, p = 0.20), IL-18 (β = 0.05, t = 1.25, p = 0.21), IL-18R1 (β = 0.04, t = 1.01, p = 0.31), IL-18RAP (odds ratio = 0.96, p = 0.30)). In a subsample (N = 463), we also adjusted for cortisol levels, which yielded unaltered results. Conclusion Our findings add to the accumulating evidence of immune system disturbances in severe mental disorders and suggest the IL-18 system as a part of the biological correlate of agitation independent of affective and psychotic symptoms.en_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleInterleukin-18 signaling system links to agitation in severe mental disordersen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.identifier.citationPsychoneuroendocrinology. 2022, 140, 105721.en_US

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