Mapping the Cerebrospinal Fluid Proteome in Bipolar Disorder

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: andreas.goteson@gu.se.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
³ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Sweden.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, Dementia Research Centre, University College London Institute of Neurology, 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-Madison, Madison, Wisconsin.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, 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 of Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of University of Science and Technology, Hefei, China.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

PMID: 39827936
DOI: 10.1016/j.biopsych.2025.01.007

Free article

Mapping the Cerebrospinal Fluid Proteome in Bipolar Disorder

Andreas Göteson et al. Biol Psychiatry. 2025.

Free article

. 2025 Jan 17:S0006-3223(25)00029-0.

doi: 10.1016/j.biopsych.2025.01.007. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: andreas.goteson@gu.se.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
³ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Sweden.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, Dementia Research Centre, University College London Institute of Neurology, 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-Madison, Madison, Wisconsin.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, 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 of Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of University of Science and Technology, Hefei, China.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

PMID: 39827936
DOI: 10.1016/j.biopsych.2025.01.007

Abstract

Background: Bipolar disorder (BD) is a severe psychiatric condition with unclear etiology and no established biomarkers. Here, we aimed to characterize the cerebrospinal fluid (CSF) proteome in euthymic individuals with BD to identify potential protein biomarkers.

Methods: We used nano-flow liquid chromatography coupled to high-resolution mass spectrometry to quantify over 2000 CSF proteins in 374 individuals from two independent clinical cohorts (n = 164 cases + 89 controls and 66 cases + 55 controls, respectively). A subset of the cases was followed longitudinally and reexamined after a median of 6.5 years.

Results: Differential abundance analysis revealed 41 proteins with robust case-control association in both cohorts. These included lower levels of synaptic proteins (e.g., APP, CLSTN1, NPTX2, NRXN1) and axon guidance and cell adhesion molecules (e.g., NEO1, NCAM1, SEMA7A) and higher levels of blood-brain barrier integrity proteins (e.g., VTN, SERPIN3) and complement components (e.g., C1RL, C3, C5). The findings were consistently driven by the BD type 1 subtype. Comparing BD type 1 participants with control participants increased discoverability, revealing 86 replicated associations despite a loss of statistical power. Moreover, longitudinal analyses of coexpression modules revealed dynamic changes in the CSF proteome composition that correlated with clinical outcomes, including disease severity, future manic episodes, and symptom improvement. Finally, we conducted association analyses of CSF proteins with genetic risk loci for BD and schizophrenia.

Conclusions: This study represents the first large-scale untargeted profiling of the CSF proteome in BD, unveiling potential biomarkers and providing in vivo support for altered synaptic and brain connectivity processes, impaired neurovascular integrity, and complement activation in the pathology of BD.

Keywords: Biomarker; Bipolar disorder; Cerebrospinal fluid; Mass spectrometry; Proteogenomics; Proteomics.

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Mapping the Cerebrospinal Fluid Proteome in Bipolar Disorder

Affiliations

Mapping the Cerebrospinal Fluid Proteome in Bipolar Disorder

Authors

Affiliations

Abstract

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous