Peripheral CD4⁺ T helper lymphocytes alterations in major depressive disorder: A systematic review and meta-analysis

Previous research has shown that patients with major depressive disorder (MDD) develop immune dysfunction. However, the exact alterations of cluster of differentiation (CD)4⁺ T helper (Th) lymphocytes in MDD remains unclear. This meta-analysis aimed to examine the specific changes in CD4⁺ Th cells. A comprehensive search of PubMed, EMBASE, Web of Science, and PsycINFO databases was conducted to identify studies investigating CD4⁺ Th, Th1, Th2, Th17, and T regulatory (Treg) cell counts in the peripheral blood of MDD patients and healthy controls (HCs), covering the period up to June 22, 2024. Our findings revealed that patients with MDD might exhibit higher CD4⁺ Th cells (SMD=0.26, 95 %CI, 0.02 to 0.50), CD4⁺/CD8⁺ cell ratios (SMD=0.51, 95 %CI, 0.14 to 0.89), Th1/Th2 cell ratios (SMD=0.15, 95 %CI, 0.01 to 0.30) and lower Th1 (SMD=-0.17, 95 %CI, -0.30 to -0.03), Th2 (SMD=-0.25, 95 %CI, -0.40 to -0.11), and Treg cells (SMD=-0.69, 95 %CI, -1.27 to -0.11). However, no significant difference was observed in terms of Th17 cells and Th17/Treg cell ratios between MDD patients and the HCs. Heterogeneity was large (I²:18.1-95.2 %), and possible sources of heterogeneity were explored (e.g., age, depression scale, country, and antidepressant use). Our findings indicate that peripheral CD4⁺ T cells in depressed patients exhibit features of adaptive immune dysfunction, as evidenced by increased CD4⁺ Th cells and CD4⁺/CD8⁺ and decreased Treg cells. These findings offer insights into the underlying mechanism of MDD.