Cited by 361Tryptophan and brain disordersStress Responses and CortisolAdipokines, Inflammation, and Metabolic Diseases

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The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression

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Mac Giollabhui, Naoise, Ng, Tommy H., Ellman, Lauren M., Alloy, Lauren B.·2021·Molecular Psychiatry

DOI 10.1038/s41380-020-00867-4PMC PMC7887136

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Abstract

The innate immune system is dysregulated in depression; however, less is known about the longitudinal associations of depression and inflammatory biomarkers. We investigated the prospective associations of depression and inflammatory biomarkers [interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α), and C-reactive protein (CRP)] in community samples, both unadjusted and adjusted for covariates. The review, registered with PROSPERO, searched for published and unpublished studies via MEDLINE/PsycINFO/PsycARTICLES/EMBASE/Proquest Dissertation. Standardized Fisher transformations of the correlation/beta coefficients, both unadjusted and adjusted for covariates, were extracted from studies examining the prospective associations of depression and inflammatory biomarkers. Systematic review conducted in January, 2019 included 38 studies representing 58,256 participants, with up to 27 studies included in random-effects meta-analysis. Higher CRP/IL-6 were associated with future depressive symptoms, and higher depressive symptoms were associated with higher future CRP/IL-6 in both unadjusted and adjusted analyses - this is the first meta-analysis reporting an adjusted association of IL-6 with future depression. The adjusted prospective associations of depression with CRP/CRP with depression were substantially attenuated and small in magnitude. No significant associations were observed for TNF-α. No conclusive results were observed in studies of clinical depression. Meta-regression indicated that the association of CRP and future depression was larger in older samples and in studies not controlling for possible infection. Small, prospective associations of depression and inflammatory biomarkers are observed in both directions, particularly for IL-6; however, the strength and importance of this relationship is likely obscured by the heterogeneity in depression and profound study/methodological differences. Implications for future studies are discussed.

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Authors: Mac Giollabhui, N., Ng, T. H., Ellman, L. M., & Alloy, L. B.
Affiliations: Temple University (US)
Corresponding author: Alloy, Lauren B.
ORCID: Mac Giollabhui, Naoise
Ng, Tommy H.
Ellman, Lauren M.
Alloy, Lauren B.
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2020-08-17
Volume: 26
Issue: 7
Pages: 3302-3314
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/s41380-020-00867-4
PMC: PMC7887136
OpenAlex: W3049499252
Cited by: 361
References: 80
Citations by year: 2026: 60 · 2025: 88 · 2024: 67 · 2023: 61 · 2022: 50 · 2021: 33 · 2020: 2
FWCI: 2.35
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH101168, MH079369, F31MH118808, MH118545, MH096478)
American Psychological Foundation
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: depression, inflammatory markers, interleukin-6, TNF-α, C-reactive protein, innate immune system, prospective associations, depressive symptoms, infection, community sample
MeSH terms: Aged, C-Reactive Protein, Depression, Humans, Inflammation, Tumor Necrosis Factor-alpha, Biomarkers, Interleukin-6

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The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression

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