Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain
Permanent lenke
https://hdl.handle.net/10037/35217Dato
2024-03-08Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Sæther, Linn Sofie; Szabo, Attila; Akkouh, Ibrahim Ahmed; Haatveit, Beathe; Mohn, Christine; Vaskinn, Anja; Aukrust, Pål; Ormerod, Monica Bettina E. Greenwood; Steen, Nils Eiel; Melle, Ingrid; Djurovic, Srdjan; Andreassen, Ole A.; Ueland, Torill; Ueland, ThorSammendrag
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.
Forlag
ElsevierSitering
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;118:287-299Metadata
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