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  • Systematic Review
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The association between inflammatory markers in blood and cerebrospinal fluid: a systematic review and meta-analysis

Molecular Psychiatry volume 28, pages 1502–1515 (2023)Cite this article

Subjects

Abstract

Background

Neuroinflammatory processes have been hypothesized to play a role in the pathogenesis of psychiatric and neurological diseases. Studies on this topic often rely on analysis of inflammatory biomarkers in peripheral blood. Unfortunately, the extent to which these peripheral markers reflect inflammatory processes in the central nervous system (CNS) is unclear.

Methods

We performed a systematic review and found 29 studies examining the association between inflammatory marker levels in blood and cerebrospinal (CSF) samples. We performed a random effects meta-analysis of 21 studies (pooled n = 1679 paired samples) that reported the correlation of inflammatory markers in paired blood-CSF samples.

Results

A qualitative review revealed moderate to high quality of included studies with the majority of studies reporting no significant correlation of inflammatory markers between paired blood-CSF. Meta-analyses revealed a significant low pooled correlation between peripheral and CSF biomarkers (r = 0.21). Meta-analyses of individual cytokines revealed a significant pooled correlation for IL-6 (r = 0.26) and TNFα (r = 0.3) after excluding outlier studies, but not for other cytokines. Sensitivity analyses showed that correlations were highest among participants with a median age above 50 (r = 0.46) and among autoimmune disorder patients (r = 0.35).

Conclusion

This systematic review and meta-analysis revealed poor correlation between peripheral and central inflammatory markers in paired blood-CSF samples, with increased correlations in certain study populations. Based on the current findings, peripheral inflammatory markers are a poor reflection of the neuroinflammatory profile.

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Fig. 1: Mechanisms of interaction between peripheral and central inflammatory markers.
Fig. 2: Flowchart of study selection.
Fig. 3: Pooled cytokine correlations.
Fig. 4: Cytokine correlations of individual cytokines in paired blood and CSF after excluding outlier studies.
Fig. 5: Sensitivity analyses.

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Acknowledgements

This study was funded through two R01 grants from the NIMH (1R01MH127315-01A1; 1R01MH124776-01A1) and the Friedman Brain Institute (FBI) Research Scholars Award (Dyal Award) at the Icahn School of Medicine at Mount Sinai. We would like to thank the Dyal family for their generous contribution.

Funding

MMP-R has received research grant funding from Neurocrine Biosciences, Inc, Millennium Pharmaceuticals, Takeda, and AI Cure. She is a consultant for Neurocrine Biosciences, Inc. and Alkermes. She has served on an advisory board for Neurocrine Biosciences Inc. LdW has received research grant funding from Alector Inc. FAJG, ES, BC, GS, DK, VB have nothing to disclose.

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Author notes

  1. These authors contributed equally: Frederieke A. J. Gigase, Emma Smith, M. Mercedes Perez-Rodriquez, Lotje D. De Witte.

Authors and Affiliations

  1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, NY, USA

    Frederieke A. J. Gigase, Emma Smith, Brett Collins, Kendall Moore, Veerle Bergink, M. Mercedes Perez-Rodriquez & Lotje D. De Witte

  2. Department of Clinical and Medical Psychology, Tilburg University, Tilburg, The Netherlands

    Frederieke A. J. Gigase

  3. Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands

    Frederieke A. J. Gigase & Gijsje J. L. J. Snijders

  4. Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA

    Daniel Katz

  5. Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands

    Veerle Bergink

  6. Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York City, NY, USA

    Veerle Bergink

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Contributions

FG, ES, MPR, and LW conceptualized the study. FG, ES, BC, and KM performed the systematic literature search and data extraction. FG and ES wrote the initial draft. FG, ES, BC, KM, GS, DK, VB, MPR, and LW critically revised the manuscript. LW and MPR supervised the project. All authors approved the final submission.

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Correspondence to Frederieke A. J. Gigase or Lotje D. De Witte.

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Gigase, F.A.J., Smith, E., Collins, B. et al. The association between inflammatory markers in blood and cerebrospinal fluid: a systematic review and meta-analysis. Mol Psychiatry 28, 1502–1515 (2023). https://doi.org/10.1038/s41380-023-01976-6

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  • DOI: https://doi.org/10.1038/s41380-023-01976-6

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