Peripheral blood cell-stratified subgroups of inflamed depression

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