Depression linked to the immune response in some people

Summary: Changes in different components of the immune system, both adaptive and innate immune responses, may play a role in the development of depression in some people.

Source: University of Bristol

A link between depression and changes in the number of several types of immune cells in the blood has been revealed by researchers from the MRC Integrative Epidemiology Unit at the University of Bristol.

These findings, published in Molecular psychiatrysuggest that changes in different components of our immune system – both the innate and adaptive immune response – may play a role in causing depression.

Although many isolated studies have already been conducted in this area of ​​research, this is the first large-scale investigation to examine and statistically combine data from all studies that have reported immune cell counts, such as as measured by flow cytometry (a state-of-the-art method for counting immune cells), in adults with and without a diagnosis of depression.

By combining these studies and increasing the total number of people involved, more definitive conclusions can be drawn.

The researchers systematically searched two databases and pooled data from 27 published scientific papers comparing the numbers of 19 different immune cell types in adults with and without a diagnosis of depression. Each study was quality controlled and only high quality studies were included.

Their analyzes of 2,277 individuals found that the numbers of eight different types of immune cells, for example B cells and T cells, were increased in depression compared to the numbers seen in the healthy comparison group without depression.

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These findings, published in Molecular Psychiatry, suggest that changes in different components of our immune system – both the innate and adaptive immune response – may play a role in depression. Image is in public domain

Éimear Foley, a Ph.D. student and lead author of the study at the MRC Integrative Epidemiology Unit in Bristol, said: “The question now is whether these changes in immune cells are a cause or a consequence of depression and we hope to examine this in future studies.

“It is also important to note that we are not suggesting that everyone with an increase in these types of immune cells will develop a depressive disorder. Rather, we highlight the differences that may exist between patients with depression and healthy individuals, who were included in our sample, in their numbers of particular immune cell types.

“Current treatments for depression do not work for all patients and immunotherapy may be useful for a subset of patients. Our goal is to use these results to better guide our selection of patients for future trials of immunotherapy for depression in hopes of working towards more effective and personalized mental health care.

About this depression research

Author: Press office
Source: University of Bristol
Contact: Press Office – University of Bristol
Picture: Image is in public domain

Original research: Free access.
“Peripheral blood cell immunophenotype in depression: a systematic review and meta-analysis” by Éimear M. Foley et al. Molecular psychiatry

See also

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


Meta-analyses implicate immune dysfunction in depression, confirming increased levels of circulating immune proteins (eg, cytokines) in depression cases compared to controls. White blood cells (WBCs) 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 white blood cell subsets in depression is needed for a better understanding of the nature of immune dysfunction in this disease.


We searched the PubMed and PsycINFO databases (from start to 5e April 2022) and conducted a systematic review and meta-analysis of identified studies comparing the absolute count and/or relative percentage of flow cytometry-derived white blood cell subsets between depression cases and controls. The quality of the selected studies was assessed. A random-effect meta-analysis was performed.


Thirty-three studies were included and 27 studies (not= 2277) were meta-analyzed. We report an increase in the mean absolute white blood cell count (seven studies; standardized 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 to 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 a relative percentage, indicating an increase in neutrophils and a decrease in total lymphocytes, Th1 and Th2 cells in depression.


Depression is characterized by generalized alterations in circulating myeloid and lymphoid cells, consistent with dysfunction of innate and adaptive immunity. Immune cells could be useful biomarkers for disease subtyping and patient stratification in future depression immunotherapy trials, along with cytokines, other biomarkers, and clinical measures.

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