Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects

Abstract Background Neuroinflammation has been suggested as a contributor to the pathophysiology of depression; however, large case–control studies investigating cytokine levels in the cerebrospinal fluid (CSF) from patients with recent-onset depression by multiplex analyses are missing. Methods An...

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Main Authors: Nina Vindegaard Sørensen, Nis Borbye-Lorenzen, Rune Haubo Bojesen Christensen, Sonja Orlovska-Waast, Rose Jeppesen, Kristin Skogstrand, Michael Eriksen Benros
Format: Article
Language:English
Published: BMC 2023-04-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:https://doi.org/10.1186/s12974-023-02757-2
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author Nina Vindegaard Sørensen
Nis Borbye-Lorenzen
Rune Haubo Bojesen Christensen
Sonja Orlovska-Waast
Rose Jeppesen
Kristin Skogstrand
Michael Eriksen Benros
author_facet Nina Vindegaard Sørensen
Nis Borbye-Lorenzen
Rune Haubo Bojesen Christensen
Sonja Orlovska-Waast
Rose Jeppesen
Kristin Skogstrand
Michael Eriksen Benros
author_sort Nina Vindegaard Sørensen
collection DOAJ
description Abstract Background Neuroinflammation has been suggested as a contributor to the pathophysiology of depression; however, large case–control studies investigating cytokine levels in the cerebrospinal fluid (CSF) from patients with recent-onset depression by multiplex analyses are missing. Methods An individually matched (sex and age) prospective case–control study comparing patients with recent-onset depression to healthy controls. CSF was analyzed with the Mesoscale V-PLEX Neuroinflammation Panel 1. Outcomes: comparisons of analyte levels in the CSF between groups with interleukin (IL)-6 and IL-8 as primary outcomes and 23 other cytokines as secondary outcomes. Results We included 106 patients (84.0% outpatients) with recent-onset depression and 106 healthy controls. There were no significant differences in the primary outcomes IL-6 (relative mean difference (MD): 1.10; 95% confidence interval (CI) 0.93–1.30; p = 0.276) or IL-8 levels (MD: 1.05; 95% CI 0.96–1.16; p = 0.249) relative to healthy controls. IL-4 was 40% higher (MD: 1.40; 95% CI 1.14–1.72; p = 0.001), monocyte chemoattractant protein (MCP)-1 was 25% higher (MD: 1.25; 95% CI 1.06–1.47; p = 0.009) and macrophage inflammatory protein (MIP)-1β was 16% higher (MD: 1.16; 95% CI 1.02–1.33; p = 0.025) in patients with depression relative to healthy controls. However, only IL-4 was significantly elevated after correction for multiple testing of secondary outcomes (p = 0.025). Conclusion We found no significant differences in CSF levels of the co-primary outcomes IL-6 and IL-8, however, the higher CSF levels of IL-4, MCP-1 and MIP-1β among patients with recent-onset depression compared to healthy controls indicate a potential role of these cytokines in the neuroinflammatory response to depression.
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spelling doaj.art-d6807a5b76534dc4a6f30ecb7bac5d872023-04-09T11:22:57ZengBMCJournal of Neuroinflammation1742-20942023-04-0120111110.1186/s12974-023-02757-2Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjectsNina Vindegaard Sørensen0Nis Borbye-Lorenzen1Rune Haubo Bojesen Christensen2Sonja Orlovska-Waast3Rose Jeppesen4Kristin Skogstrand5Michael Eriksen Benros6Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University HospitalCenter for Neonatal Screening, Department of Congenital Disorders, Statens Serum InstitutCopenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University HospitalCopenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University HospitalCopenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University HospitalCenter for Neonatal Screening, Department of Congenital Disorders, Statens Serum InstitutCopenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University HospitalAbstract Background Neuroinflammation has been suggested as a contributor to the pathophysiology of depression; however, large case–control studies investigating cytokine levels in the cerebrospinal fluid (CSF) from patients with recent-onset depression by multiplex analyses are missing. Methods An individually matched (sex and age) prospective case–control study comparing patients with recent-onset depression to healthy controls. CSF was analyzed with the Mesoscale V-PLEX Neuroinflammation Panel 1. Outcomes: comparisons of analyte levels in the CSF between groups with interleukin (IL)-6 and IL-8 as primary outcomes and 23 other cytokines as secondary outcomes. Results We included 106 patients (84.0% outpatients) with recent-onset depression and 106 healthy controls. There were no significant differences in the primary outcomes IL-6 (relative mean difference (MD): 1.10; 95% confidence interval (CI) 0.93–1.30; p = 0.276) or IL-8 levels (MD: 1.05; 95% CI 0.96–1.16; p = 0.249) relative to healthy controls. IL-4 was 40% higher (MD: 1.40; 95% CI 1.14–1.72; p = 0.001), monocyte chemoattractant protein (MCP)-1 was 25% higher (MD: 1.25; 95% CI 1.06–1.47; p = 0.009) and macrophage inflammatory protein (MIP)-1β was 16% higher (MD: 1.16; 95% CI 1.02–1.33; p = 0.025) in patients with depression relative to healthy controls. However, only IL-4 was significantly elevated after correction for multiple testing of secondary outcomes (p = 0.025). Conclusion We found no significant differences in CSF levels of the co-primary outcomes IL-6 and IL-8, however, the higher CSF levels of IL-4, MCP-1 and MIP-1β among patients with recent-onset depression compared to healthy controls indicate a potential role of these cytokines in the neuroinflammatory response to depression.https://doi.org/10.1186/s12974-023-02757-2DepressionImmunologyCerebrospinal fluidBiomarkersCytokinesChemokines
spellingShingle Nina Vindegaard Sørensen
Nis Borbye-Lorenzen
Rune Haubo Bojesen Christensen
Sonja Orlovska-Waast
Rose Jeppesen
Kristin Skogstrand
Michael Eriksen Benros
Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects
Journal of Neuroinflammation
Depression
Immunology
Cerebrospinal fluid
Biomarkers
Cytokines
Chemokines
title Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects
title_full Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects
title_fullStr Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects
title_full_unstemmed Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects
title_short Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects
title_sort comparisons of 25 cerebrospinal fluid cytokines in a case control study of 106 patients with recent onset depression and 106 individually matched healthy subjects
topic Depression
Immunology
Cerebrospinal fluid
Biomarkers
Cytokines
Chemokines
url https://doi.org/10.1186/s12974-023-02757-2
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