Peripheral blood cellular immunophenotype in depression: a systematic review and meta-analysis

Foley, É. M., Parkinson, J. T. , Mitchell, R. E., Turner, L. and Khandaker, G. M. (2023) Peripheral blood cellular immunophenotype in depression: a systematic review and meta-analysis. Molecular Psychiatry, 28(3), pp. 1004-1019. (doi: 10.1038/s41380-022-01919-7) (PMID:36577838) (PMCID:PMC10005954)

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Introduction: Meta-analyses implicate immune dysfunction in depression confirming increased levels of circulating immune proteins (e.g., cytokines) in depression cases compared to controls. White blood cells (WBC) both produce and are influenced by cytokines, and play key roles in orchestrating innate and adaptive immune responses, but their role in depression remains unclear. Therefore, a systematic review of studies of various WBC subsets in depression is required for a greater understanding of the nature of immune dysfunction in this illness. Methods: We searched PubMed and PsycINFO databases (inception to 5th April 2022) and conducted a systematic review and meta-analysis of identified studies comparing absolute count and/or relative percentage of flow cytometry-derived WBC subsets between depression cases and controls. Selected studies were quality assessed. Random-effect meta-analysis was performed. Results: Thirty-three studies were included and 27 studies (n = 2277) were meta-analysed. We report an increase in mean absolute counts of WBC (seven studies; standardised mean difference [SMD] = 1.07; 95% CI, 0.61–1.53; P < 0.01; I2 = 64%), granulocytes (two studies; SMD = 2.07; 95% CI, 1.45–2.68; P < 0.01; I2 = 0%), neutrophils (four studies; SMD = 0.91; 95% CI, 0.23–1.58; P < 0.01; I2 = 82%), monocytes (seven studies; SMD = 0.60; 95% CI, 0.19–1.01; P < 0.01; I2 = 66%), CD4+ helper T cells (11 studies; SMD = 0.30; 95% CI, 0.15–0.45; P < 0.01; I2 = 0%), natural killer cells (11 studies; SMD = 1.23; 95% CI, 0.38–2.08; P < 0.01; I2 = 95%), B cells (10 studies; SMD = 0.30; 95% CI, 0.03–0.57; P = 0.03; I2 = 56%), and activated T cells (eight studies; SMD = 0.45; 95% CI, 0.24–0.66; P < 0.01; I2 = 0%) in depression, compared to controls. Fewer studies reported relative percentage, indicating increased neutrophils and decreased total lymphocytes, Th1, and Th2 cells in depression. Conclusions: Depression is characterised by widespread alterations in circulating myeloid and lymphoid cells, consistent with dysfunction in both innate and adaptive immunity. Immune cells could be useful biomarkers for illness subtyping and patient stratification in future immunotherapy trials of depression, along with cytokines, other biomarkers, and clinical measures.

Item Type:Articles
Additional Information:This research was funded in whole, or in part, by the Wellcome Trust (Grant number 201486/B/16/Z). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. EMF is supported by a Medical Research Council Integrative Epidemiology Unit PhD Studentship (MC_UU_00011/1). JTP acknowledges funding from the Versus Arthritis Award (Grant No. 22453). REM is supported by the Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/1). LT acknowledges funding support from NIHR Cambridge BioResource. GMK is supported by the Wellcome Trust (Grant No. 201486/Z/16/Z), the Medical Research Council (Grant No. MC_PC_17213, Grant No. MR/S037675/1, and Grant No. MR/W014416/1), The MQ: Transforming Mental Health (Grant No. MQDS17/40), and the BMA Foundation (J. Moulton Grant 2019).
Glasgow Author(s) Enlighten ID:Parkinson, Dr Joel
Authors: Foley, É. M., Parkinson, J. T., Mitchell, R. E., Turner, L., and Khandaker, G. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Molecular Psychiatry
Publisher:Springer Nature
ISSN (Online):1476-5578
Published Online:28 December 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Molecular Psychiatry 28(3): 1004-1019
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306717Probing the Rheumatoid Arthritis Brain to Expose Central Pain PathwaysNeil BasuVersus Arthritis (ARTRESUK)22453III - Immunology