Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain.
Journal: Brain, behavior, and immunity
Volume: 118
Issue:
Year of Publication:
Affiliated Institutions:
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.
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.
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.
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.
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.
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.
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.
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.
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 Hospital, Oslo, Norway.
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, Norway.
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.
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.
Abstract summary
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.
Authors & Co-authors:
Sæther
Szabo
Akkouh
Haatveit
Mohn
Vaskinn
Aukrust
Ormerod
Eiel Steen
Melle
Djurovic
Andreassen
Ueland
Ueland
Study Outcome
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