dc.contributor.author | Sæther, Linn Sofie | |
dc.contributor.author | Szabo, Attila | |
dc.contributor.author | Akkouh, Ibrahim Ahmed | |
dc.contributor.author | Haatveit, Beathe | |
dc.contributor.author | Mohn, Christine | |
dc.contributor.author | Vaskinn, Anja | |
dc.contributor.author | Aukrust, Pål | |
dc.contributor.author | Ormerod, Monica Bettina E. Greenwood | |
dc.contributor.author | Steen, Nils Eiel | |
dc.contributor.author | Melle, Ingrid | |
dc.contributor.author | Djurovic, Srdjan | |
dc.contributor.author | Andreassen, Ole A. | |
dc.contributor.author | Ueland, Torill | |
dc.contributor.author | Ueland, Thor | |
dc.date.accessioned | 2024-10-14T10:58:08Z | |
dc.date.available | 2024-10-14T10:58:08Z | |
dc.date.issued | 2024-03-08 | |
dc.description.abstract | Recent 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.citation | Sæther, 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;118:287-299 | en_US |
dc.identifier.cristinID | FRIDAID 2262280 | |
dc.identifier.doi | 10.1016/j.bbi.2024.03.014 | |
dc.identifier.issn | 0889-1591 | |
dc.identifier.issn | 1090-2139 | |
dc.identifier.uri | https://hdl.handle.net/10037/35217 | |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.journal | Brain, Behavior, and Immunity | |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2024 The Author(s) | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | en_US |
dc.rights | Attribution 4.0 International (CC BY 4.0) | en_US |
dc.title | Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |