Peripheral Blood Cell–Stratified Subgroups of Inflamed Depression
Open accessAbstract
Background Depression has been associated with increased inflammatory proteins, but changes in circulating immune cells are less well defined.Methods We used multiparametric flow cytometry to count 14 subsets of peripheral blood cells in 206 depression cases and 77 age- and sex-matched controls (N = 283). We used univariate and multivariate analyses to investigate the immunophenotypes associated with depression and depression severity.Results Depression cases, compared with controls, had significantly increased immune cell counts, especially neutrophils, CD4+ T cells, and monocytes, and increased inflammatory proteins (C-reactive protein and interleukin-6). Within-group analysis of cases demonstrated significant associations between the severity of depressive symptoms and increased myeloid and CD4+ T-cell counts. Depression cases were partitioned into 2 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 C-reactive protein and interleukin-6; and more severe depression than the uninflamed majority of cases. Relaxing the presumption of a binary classification, data-driven analysis identified 4 subgroups of depression cases, 2 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.
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Immune dysfunction in the CNS has been implicated in the pathogenesis of major depression.
“Recently, immune dysfunction in the CNS has been implicated in the pathogenesis of major depression [8, 9].”
From Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain (2022) · cites this paper as [9]
The Introduction links inflammation with major depressive disorder, and “Immune cell systems and depression” notes that neutrophils can enter the brain and affect inflammation-related behavior in animal models. The paper’s human findings concern peripheral blood cells, however; they do not establish immune dysfunction within the CNS in people with major depression. (LLM, conf=0.84)
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Self-citation
- 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., & Bullmore, E.
- Affiliations
- University of Cambridge (GB)
- Queen Elizabeth University Hospital (GB)
- King's College London (GB)
- Janssen (United Kingdom) (GB)
- Janssen Research & Development (United States) (US)
- Warneford Hospital (GB)
- Cardiff University (GB)
- Corresponding author
- Lynall, Mary-Ellen
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 88
- Issue
- 2
- Pages
- 185-196
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2991010196
- Cited by
- 187
- References
- 44
- Citations by year
- 2026: 22 · 2025: 38 · 2024: 40 · 2023: 9 · 2022: 42 · 2021: 27 · 2020: 9
- FWCI
- 6.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Apollo
- Funders
- Addenbrooke's Charitable Trust, Cambridge University Hospitals
- Arthritis Research UK
- Medical Research Council
- National Institute for Health Research
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- depression, peripheral blood cells, immune cell subsets, inflammation, depression severity, neutrophils, CD4+ T cells, monocytes, C-reactive protein, interleukin-6, myeloid cells, lymphoid cells, immunophenotype
- MeSH terms
- Depression, Flow Cytometry, Monocytes, Immunophenotyping, Lymphocyte Count
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