Glycocalyx shedding patterns identifies antipsychotic-naïve patients with first-episode psychosis.

Journal: Psychiatry research
Published Date: Jun 21, 2024

Abstract

Psychotic disorders have been linked to immune-system abnormalities, increased inflammatory markers, and subtle neuroinflammation. Studies further suggest a dysfunctional blood brain barrier (BBB). The endothelial Glycocalyx (GLX) functions as a protective layer in the BBB, and GLX shedding leads to BBB dysfunction. This study aimed to investigate whether a panel of 11 GLX molecules derived from peripheral blood could differentiate antipsychotic-naïve first-episode psychosis patients (n47) from healthy controls (HC, n49) and whether GLX shedding correlated with symptom severity. Blood samples were collected at baseline and serum was isolated for GLX marker detection. Machine learning models were applied to test whether patterns in GLX markers could classify patient groups. Associations between GLX markers and symptom severity were explored. Patients showed significantly increased levels of three GLX markers compared to HC. Based on the panel of 11 GLX markers, machine learning models achieved a significant mean classification accuracy of 81%. Post hoc analysis revealed associations between increased GLX markers and symptom severity. This study demonstrates the potential of GLX molecules as immuno-neuropsychiatric biomarkers for early diagnosis of psychosis, as well as indicate a compromised BBB. Further research is warranted to explore the role of GLX in the early detection of psychotic disorders.

Authors

  • Helle G Andersen
    Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark; Copenhagen Research Centre for Mental Health and VIRTU Research Group, Mental Health Centre Copenhagen, Denmark. Electronic address: Helle.Gade.Andersen.02@regionh.dk.
  • Brian DellaValle
    Department of Endocrinology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark; Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Denmark; GLX Analytix ApS, Copenhagen, Denmark.
  • Hjalte Bøgehave
    Department of Endocrinology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark; Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Denmark; GLX Analytix ApS, Copenhagen, Denmark.
  • Phillip Bredahl Mogensen
    Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Denmark; GLX Analytix ApS, Copenhagen, Denmark.
  • Margaret K Hahn
    Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, Canada; Banting and Best Diabetes Centre, University of Toronto, Canada; Department of Pharmacology, University of Toronto, Canada.
  • Christoffer K Goth
    Department of Endocrinology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark; Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Denmark; GLX Analytix ApS, Copenhagen, Denmark.
  • Mikkel E Sørensen
    Center for Neuropsychiatric Schizophrenia Research (CNSR) & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
  • Anne K Sigvard
    Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
  • Karen Tangmose
    Center for Neuropsychiatric Schizophrenia Research (CNSR) & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
  • Kirsten B Bojesen
    Center for Neuropsychiatric Schizophrenia Research (CNSR) & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
  • Mette Ø Nielsen
    Center for Neuropsychiatric Schizophrenia Research (CNSR) & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
  • Simone Tonetto
    Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Denmark; Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Mathias L Jørgensen
    Department of Endocrinology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark; Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Denmark; GLX Analytix ApS, Copenhagen, Denmark.
  • Casper Hempel
    Section for Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark. cash@dtu.dk.
  • Jørgen Rungby
    Department of Endocrinology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark; Copenhagen Center for Translational Research, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Denmark.
  • Birte Y Glenthøj
    Center for Neuropsychiatric Schizophrenia Research (CNSR) & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
  • Karen S Ambrosen
    Center for Neuropsychiatric Schizophrenia Research (CNSR) & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
  • Bjørn H Ebdrup
    Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia.

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