CD4⁺ T-cell subsets are associated with chronic stress effects in newly diagnosed anxiety disorders

Prior research has indicated a connection between CD4⁺ T cells and the development of anxiety, but the specific CD4⁺ T cell subsets linked to anxiety disorders remain uncertain. Our study seeks to investigate the relationship between distinct CD4⁺ T cell subsets and anxiety, as well as to explore whether CD4⁺ T cell subsets mediate the effect of chronic psychological stress on anxiety.

56 eligible matched participants were recruited in Peking Union Medical College Hospital. The diagnosis was made based on DSM-5 diagnostic criteria. The severity of anxiety and depression symptoms was assessed using the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale, respectively. The Life Events Scale (LES) evaluated the chronic stress level. CD4⁺ T cell subsets were characterized using multiparametric flow cytometry. To assess the impact of CD4⁺ T cells on the effect of chronic psychological stress on anxiety, Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis was employed.

We discovered fifteen notably distinct CD4⁺ T-cell subsets in anxiety disorder patients compared to healthy controls. Multiple linear regression analysis unveiled an association between anxiety severity and CD27⁺CD45RA^- Th cells, CD27⁺CD28⁺ Tregs, and the total Life Events Scale (LES) score. The PLS-SEM analysis demonstrated that CD4⁺ T cell subsets and LES could explain 80.2% of the variance in anxiety. Furthermore, it was observed that CD27⁺CD28⁺ Th/Treg cells acted as inverse mediators of the effects of LES on anxiety (P = 0.031).

Drug naïve anxiety disorder patients exhibited significant alterations in numerous CD4⁺ T-cell subsets. Specifically, the memory subset of CD27⁺CD45RA^- Th cells and the naïve subset of CD27⁺CD28⁺ Treg cells were found to be independent factors associated with the severity of anxiety. Additionally, the CD27⁺CD28⁺ Th and Treg cell subsets played a significant mediating role in the influence of long-term psychological stress on anxiety.