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Immune cell composition in unipolar depression: a comprehensive systematic review and meta-analysis

Molecular Psychiatry volume 28, pages 391–401 (2023)Cite this article

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Abstract

Depression has been associated with inflammatory pathophysiological mechanisms, including alterations in amount of circulating immune cells. However, no meta-analysis within the past 20 years have reevaluated the circulating immune cells in blood and cerebrospinal fluid (CSF) from patients with depression compared to healthy controls. The aim of this study was to systematically evaluate the circulating immune cells in blood and CSF from patients with unipolar depression compared to healthy controls. Databases were searched up until February 12, 2021. Data-extraction was performed by two independent reviewers. 104 studies were included in the meta-analysis using fixed and random-effects models. Patients with depression had a significantly higher overall leukocyte count (35 studies; SMD, 0.46; 95% CI: 0.31–0.60, I2 = 68%), higher neutrophil count (24 studies; SMD, 0.52; 95% CI: 0.33–0.71, I2 = 77%) and higher monocyte count (27 studies; SMD, 0.32; 95% CI: 0.11–0.53, I2 = 77%) compared to healthy controls. Leukocyte counts were higher in inpatients, indicating a relation to depression severity. Furthermore, there were significant alterations in several lymphocyte subsets, including higher natural killer cells and T cell subsets. Higher neutrophil/lymphocyte ratio (11 studies; SMD = 0.24; 95% CI: 0.06–0.42, I2 = 73%), CD4/CD8 cell-ratio (26 studies; SMD = 0.14; 95% CI: 0.01–0.28, I2 = 42%) and T helper 17/T regulatory ratio (2 studies; SMD = 1.05; 95% CI: 0.15–1.95, I2 = 86%) were found in patients compared to healthy controls. CSF white cell count was higher in patients compared to controls (3 studies; SMD = 0.20; 95% CI: 0.01–0.38, I2 = 0%). There were no data for CSF cell subsets. This study suggests that there are several blood immune cell alterations in patients with unipolar depression compared to healthy controls, both in major leukocyte subsets and more specialized immune cell subsets.

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Fig. 1: Graphical abstract of main findings.
Fig. 2: Blood leukocyte counts in patients with unipolar depression compared to healthy controls.
Fig. 3: Blood granulocyte counts in patients with unipolar depression compared to healthy controls.
Fig. 4: Blood monocyte counts in patients with unipolar depression compared to healthy controls.
Fig. 5: Blood natural killer cell counts and T cell subset counts in patients with unipolar depression compared to healthy controls.
Fig. 6: Blood immune cell ratios in patients with unipolar depression compared to healthy controls.

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Funding

This study was funded by grants from The Lundbeck Foundation (grant number R268–2016–3925 and R277–2018–1411). The funding agencies had no impact on the study design, data collection, data analysis, data interpretation, or writing of the report.

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  1. These authors contributed equally: Nina Vindegaard Sørensen, Beate Holmelund Frandsen.

Authors and Affiliations

  1. Biological and Precision Psychiatry, Copenhagen Research Centre for Mental Health, Copenhagen University Hospital, Hellerup, Denmark

    Nina Vindegaard Sørensen, Beate Holmelund Frandsen, Sonja Orlovska-Waast, Rune Haubo Christensen & Michael Eriksen Benros

  2. Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Nina Vindegaard Sørensen, Sonja Orlovska-Waast, Terkild Brink Buus, Niels Ødum & Michael Eriksen Benros

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Contributions

MEB, SOW and BHF designed the study and systematic literature search. BHF conducted the screening of titles and abstracts. BHF and SOW did full text screening independently. BHF extracted all data. Data was validated by either NVS or SOW. TBB and NØ helped categorize immune cells. RHC made the statistical analysis plan and conducted the statistical analyses. All authors contributed to data interpretation. RHC, NVS and BHF conducted figures and tables. NVS drafted the manuscript including preparation of the supplementary. All authors contributed to the editing of the manuscript and all authors have read and accepted the final version of the manuscript.

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Correspondence to Michael Eriksen Benros.

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Sørensen, N.V., Frandsen, B.H., Orlovska-Waast, S. et al. Immune cell composition in unipolar depression: a comprehensive systematic review and meta-analysis. Mol Psychiatry 28, 391–401 (2023). https://doi.org/10.1038/s41380-022-01905-z

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