Immune cell composition in unipolar depression: a comprehensive systematic review and meta-analysis

Depression has been associated with inflammatory pathophysiological mechanisms, including alterations in amount of circulating immune cells. However, no meta-analysis within the past 20 years have reevaluated the circulating immune cells in blood and cerebrospinal fluid (CSF) from patients with depression compared to healthy controls. The aim of this study was to systematically evaluate the circulating immune cells in blood and CSF from patients with unipolar depression compared to healthy controls. Databases were searched up until February 12, 2021. Data-extraction was performed by two independent reviewers. 104 studies were included in the meta-analysis using fixed and random-effects models. Patients with depression had a significantly higher overall leukocyte count (35 studies; SMD, 0.46; 95% CI: 0.31-0.60, I 2  = 68%), higher neutrophil count (24 studies; SMD, 0.52; 95% CI: 0.33-0.71, I 2  = 77%) and higher monocyte count (27 studies; SMD, 0.32; 95% CI: 0.11-0.53, I 2  = 77%) compared to healthy controls. Leukocyte counts were higher in inpatients, indicating a relation to depression severity. Furthermore, there were significant alterations in several lymphocyte subsets, including higher natural killer cells and T cell subsets. Higher neutrophil/lymphocyte ratio (11 studies; SMD = 0.24; 95% CI: 0.06-0.42, I 2  = 73%), CD4/CD8 cell-ratio (26 studies; SMD = 0.14; 95% CI: 0.01-0.28, I 2  = 42%) and T helper 17/T regulatory ratio (2 studies; SMD = 1.05; 95% CI: 0.15-1.95, I 2  = 86%) were found in patients compared to healthy controls. CSF white cell count was higher in patients compared to controls (3 studies; SMD = 0.20; 95% CI: 0.01-0.38, I 2  = 0%). There were no data for CSF cell subsets. This study suggests that there are several blood immune cell alterations in patients with unipolar depression compared to healthy controls, both in major leukocyte subsets and more specialized immune cell subsets.