Cerebrospinal fluid synaptic biomarker changes in bipolar disorder - A longitudinal case-control study

Ulla Knorr; Anja Hviid Simonsen; Johanna Nilsson; Ann Brinkmalm; Henrik Zetterberg; Kaj Blennow; Mark Bech Knudsen; Julie Forman; Steen Gregers Hasselbalch; Lars Vedel Kessing

doi:10.1016/j.jad.2024.05.034

Cerebrospinal fluid synaptic biomarker changes in bipolar disorder - A longitudinal case-control study

J Affect Disord. 2024 May 7:358:250-259. doi: 10.1016/j.jad.2024.05.034. Online ahead of print.

Authors

Affiliations

¹ Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Department Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: ulla.knorr@regionh.dk.
² Danish Dementia Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, University College London, Queen Square, London, United Kingdom; UK Dementia Research Institute University College London, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁶ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, PR China.
⁷ Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark.
⁸ Danish Dementia Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.
⁹ Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Department Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.

PMID: 38723679
DOI: 10.1016/j.jad.2024.05.034

Abstract

Background: This exploratory study investigated cerebrospinal fluid (CSF) synaptic protein biomarkers in bipolar disorder (BD), aiming to highlight the neurobiological basis of the disorder. With shared cognitive impairment features between BD and Alzheimer's disease, and considering increased dementia risk in BD patients, the study explores potential connections.

Methods: Fifty-nine well-characterized patients with BD and thirty-seven healthy control individuals were examined and followed for one year. Synaptic proteins encompassing neuronal pentraxins (NPTX)1, NPTX2, and NPTX-receptor, 14-3-3 protein family epsilon, and zeta/delta, activating protein-2 complex subunit beta, synucleins beta-synuclein and gamma-synuclein, complexin-2, phosphatidylethanolamine-binding protein 1, rab GDP dissociation inhibitor alpha, and syntaxins 1B and 7 were measured in CSF using a microflow liquid chromatography-mass spectrometric multiple reaction monitoring set-up. Biomarker levels were compared between BD and HC and in BD before, during, and after mood episodes.

Results: The synaptic proteins revealed no statistically significant differences between BD and HC, neither at baseline, one-year follow-up, or in terms of changes from baseline to follow-up. Moreover, the CSF synaptic protein levels in patients with BD were unaltered compared to baseline when they stabilized in euthymia following an affective episode and at one-year follow-up.

Limitation: It is uncertain what the CSF biomarker concentrations reflect since we yet do not know the mechanisms of release of these proteins, and we are uncertain of what increased or decreased levels reflect.

Conclusion: This first-ever investigation of a panel of CSF protein biomarkers of synaptic dysfunction in patients with BD and HC individuals found no statistically significant differences cross-sectionally or longitudinally.

Keywords: Biomarkers; Bipolar disorder; Case-control; Cerebrospinal fluid; Longitudinal; Synaptic dysfunction.