Peripheral blood cell-stratified subgroups of inflamed depression

Lynall, M.-E. et al. (2020) Peripheral blood cell-stratified subgroups of inflamed depression. Biological Psychiatry, 88(2), pp. 185-196. (doi: 10.1016/j.biopsych.2019.11.017) (PMID:32000983)

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Abstract

Background: Depression has been associated with increased inflammatory proteins but changes in circulating immune cells are less well defined. Methods: We used multi-parametric flow cytometry to count 14 subsets of peripheral blood cells in 206 cases of depression and 77 age- and sex-matched controls (total N = 283). We used univariate and multivariate analyses to investigate the immunophenotypes associated with depression and depression severity. Results: Depressed cases, compared to controls, had significantly increased immune cell counts, especially neutrophils, CD4+ T cells and monocytes, and increased inflammatory proteins (C-reactive protein, CRP, and interleukin-6, IL-6). Within-group analysis of cases demonstrated significant associations between the severity of depressive symptoms and increased myeloid and CD4+ T cell counts. Depressed cases were partitioned into two subgroups by forced binary clustering of cell counts: the inflamed depression subgroup (N=81 out of 206; 39%) had increased monocyte, CD4+ and neutrophil counts, increased CRP and IL-6, and was more depressed than the uninflamed majority of cases. Relaxing the presumption of a binary classification, data-driven analysis identified four subgroups of depressed cases: two of which (N=38 and N=100; 67% collectively) were associated with increased inflammatory proteins and more severe depression, but differed in terms of myeloid and lymphoid cell counts. Results were robust to potentially confounding effects of age, sex, body mass index, recent infection, and tobacco use. Conclusions: Peripheral immune cell counts were used to distinguish inflamed and uninflamed subgroups of depression and to indicate that there may be mechanistically distinct subgroups of inflamed depression.

Item Type:Articles
Additional Information:This work was supported by the Wellcome Trust [104025]. M Lynall was supported by a fellowship and grant from Addenbrooke’s Charitable Trust, Cambridge and a fellowship from the Medical Research Council (MR/S006257/1). M. R. Clatworthy is supported by the NIHR Cambridge Biomedical Research Centre (Transplant and Regenerative Medicine), NIHR Blood and Transplant Research Unit, MRC New Investigator Research Grant, MR/N024907/1; Arthritis Research UK Cure Challenge Research Grant, 21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). E. T. Bullmore and C. M. Pariante are each supported by a NIHR Senior Investigator award. This work was also supported by the NIHR Cambridge Biomedical Research Centre (Mental Health) and the Cambridge NIHR BRC Cell Phenotyping Hub, as well as the NIHR BRC at the South London and Maudsley NHS Foundation Trust and King's College London, London.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cavanagh, Professor Jonathan
Authors: Lynall, M.-E., Turner, L., Bhatti, J., Cavanagh, J., de Boer, P., Mondelli, V., Jones, D., Drevets, W. C., Cowen, P., Harrison, N. A., Pariante, C. M., Pointon, L., Clatworthy, M. R., and Bullmore, E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Biological Psychiatry
Publisher:Elsevier
ISSN:0006-3223
ISSN (Online):0006-3223
Published Online:02 December 2019
Copyright Holders:Copyright © 2019 Published by Elsevier Inc on behalf of Society of Biological Psychiatry
First Published:First published in Biological Psychiatry 88(2): 185-196
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
308675Consortium of Neuroimmunology of Mood Disorders and Alzheimer's DiseaseJonathan CavanaghWellcome Trust (WELLCOTR)104025HW - Mental Health and Wellbeing