Cerebrospinal fluid synaptic biomarker changes in bipolar disorder – A longitudinal case-control study
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Cerebrospinal fluid synaptic biomarker changes in bipolar disorder – A longitudinal case-control study. / Knorr, Ulla; Simonsen, Anja Hviid; Nilsson, Johanna; Brinkmalm, Ann; Zetterberg, Henrik; Blennow, Kaj; Knudsen, Mark Bech; Forman, Julie; Hasselbalch, Steen Gregers; Kessing, Lars Vedel.
In: Journal of Affective Disorders, Vol. 358, 2024, p. 250-259.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cerebrospinal fluid synaptic biomarker changes in bipolar disorder – A longitudinal case-control study
AU - Knorr, Ulla
AU - Simonsen, Anja Hviid
AU - Nilsson, Johanna
AU - Brinkmalm, Ann
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Knudsen, Mark Bech
AU - Forman, Julie
AU - Hasselbalch, Steen Gregers
AU - Kessing, Lars Vedel
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Bipolar disorder
KW - Case-control
KW - Cerebrospinal fluid
KW - Longitudinal
KW - Synaptic dysfunction
U2 - 10.1016/j.jad.2024.05.034
DO - 10.1016/j.jad.2024.05.034
M3 - Journal article
C2 - 38723679
AN - SCOPUS:85192453215
VL - 358
SP - 250
EP - 259
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
ER -
ID: 391680465