Peripheral blood cellular immunophenotype in depression: A systematic review

Background: Depression is a common mental disorder affecting about 10-20% of the population in a lifetime and has a complex aetiology [1]. Emerging evidence implicates systemic inflammation in the pathogenesis of depression. Studies of inflammation could provide novel mechanistic insights and identify biomarkers for the prediction and prognosis of depression. Extensive evidence suggests that elevated concentrations of circulating inflammatory markers, such as C-reactive protein and interleukin-6, are evident in patients with depression, as compared to controls [2–4]. However, studies of peripheral blood cellular immunophenotype in depressed individuals are relatively scarce. Further understanding of this research would be beneficial for (1) providing further evidence for immune dysregulation in depression, (2) helping to elucidate potential cellular source of cytokine alterations, (3) aiding the identification of subgroups of patients with inflammation-related depression amenable to immunotherapy, and (4) identifying novel treatment targets focused primarily on inflammatory mechanisms. Therefore, the aim of the current research was to perform a systematic review of published studies of peripheral blood cellular immunophenotype in depression.

Methods: A systematic literature search was conducted in PubMed and PsychInfo databases. Included studies measured peripheral blood cellular immunophenotype in depressed patients and non-depressed controls using flow or mass cytometry. Other inclusion criteria included: original article; written in English; human subjects; cohort or case-control studies; immune phenotype compared between cases with current depression and healthy controls; depression defined using an established method; controls defined as individuals with no current psychiatric history. Studies focused on immunophenotyping of one cell type only and those that did not primarily examine or report cellular phenotype were excluded. Included studies were quality assessed.

Results: Electronic search identified 852 articles, of which 35 studies (comprising in total 2,308 depressed patients and 2,540 healthy controls) met inclusion criteria and were included in the review. Flow cytometry panels differed between studies. Overall, the studies suggest that depressed patients have increased leukocyte, monocyte, and neutrophil absolute cell counts, increased percentage of neutrophils, and decreased percentage of Th17 cells. There was some evidence of increased CD4+, monocyte, intermediate monocyte, non-classical monocyte, and eosinophil absolute cell counts, increased percentage of non-classical monocytes, and decreased percentage of Th1 and Th2 cells in depressed patients. No differences in lymphocyte, CD3+, CD8+, T regulatory, T helper, CD19+, granulocyte, basophil, natural killer cell, platelet, or red blood cell absolute counts or percentages were identified between cases and controls.

Conclusion: Our systematic review of peripheral blood cellular immunophenotype in depression suggests a relatively clear signal for increased leukocytes, monocytes, and neutrophils and decreased Th17 cells in depressed patients as compared to controls. However, the data is mixed for much of the other cell types. This heterogeneity could be due to immunophenotyping method used and sample characteristics. There is a need for standardising methods for peripheral blood phenotyping in studies of depression.