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dc.contributor.authorSæther, Linn Sofie
dc.contributor.authorSzabo, Attila
dc.contributor.authorAkkouh, Ibrahim Ahmed
dc.contributor.authorHaatveit, Beathe
dc.contributor.authorMohn, Christine
dc.contributor.authorVaskinn, Anja
dc.contributor.authorAukrust, Pål
dc.contributor.authorOrmerod, Monica Bettina E. Greenwood
dc.contributor.authorSteen, Nils Eiel
dc.contributor.authorMelle, Ingrid
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorAndreassen, Ole A.
dc.contributor.authorUeland, Torill
dc.contributor.authorUeland, Thor
dc.date.accessioned2024-10-14T10:58:08Z
dc.date.available2024-10-14T10:58:08Z
dc.date.issued2024-03-08
dc.description.abstractRecent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers (n = 25) associated with cognitive domains (n = 9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n = 10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n = 776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n = 474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high neuroinflammatory subgroup in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness.en_US
dc.identifier.citationSæther, Szabo, Akkouh, Haatveit, Mohn, Vaskinn, Aukrust, Ormerod MBEG, Steen, Melle, Djurovic, Andreassen, Ueland, Ueland. Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain. Brain, Behavior, and Immunity. 2024;118:287-299en_US
dc.identifier.cristinIDFRIDAID 2262280
dc.identifier.doi10.1016/j.bbi.2024.03.014
dc.identifier.issn0889-1591
dc.identifier.issn1090-2139
dc.identifier.urihttps://hdl.handle.net/10037/35217
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalBrain, Behavior, and Immunity
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2024 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleCognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brainen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)