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Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain.
Sæther, Linn Sofie; Szabo, Attila; Akkouh, Ibrahim A; Haatveit, Beathe; Mohn, Christine; Vaskinn, Anja; Aukrust, Pål; Ormerod, Monica B E G; Eiel Steen, Nils; Melle, Ingrid; Djurovic, Srdjan; Andreassen, Ole A; Ueland, Torill; Ueland, Thor.
Afiliación
  • Sæther LS; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway. Electronic address: l.s.sather@psykologi.uio.no.
  • Szabo A; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
  • Akkouh IA; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital/University of Oslo, Oslo, Norway.
  • Haatveit B; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Mohn C; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; National Centre for Suicide Research and Prevention, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Vaskinn A; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Centre for Research and Education in Forensic Psychiatry, Oslo University Hospital, Oslo, Norway.
  • Aukrust P; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
  • Ormerod MBEG; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo Norway.
  • Eiel Steen N; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospita
  • Melle I; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Djurovic S; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital/University of Oslo, Oslo, N
  • Andreassen OA; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Ueland T; Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
  • Ueland T; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Centre, University of Tromsø, Tromsø, Norway.
Brain Behav Immun ; 118: 287-299, 2024 May.
Article en En | MEDLINE | ID: mdl-38461955
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Células Madre Pluripotentes Inducidas Límite: Humans Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Células Madre Pluripotentes Inducidas Límite: Humans Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos