BMC Psychiatry. 2025 Oct 1;25(1):911. doi: 10.1186/s12888-025-07344-8.

ABSTRACT

BACKGROUND: Immune system dysfunction has been associated with depressive disorders; however, the specific alterations in CD4 + T lymphocytes and cytokines among individuals with varying severities of depression remain unclear. This study aimed to investigate the immunological changes in patients with mild, moderate, and severe depression, to identify potential biomarkers for clinical diagnosis and disease severity assessment, and to uncover the immunological mechanisms involved in depression.

METHODS: Twenty-eight mild depression patients, thirty-one moderate depression patients, twenty-two severe depression patients and eighty-three healthy subjects were included in the mild, moderate, severe and control group. The relative proportions and absolute quantities of Th1, Th2, Th17 and Treg cells in peripheral blood were determined by flow cytometry. In addition, the levels of cytokines in serum were detected by cytometric bead array (CBA), including IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α.

RESULTS: The levels of Th1%, Th17, Th1/Th2, and Th17/Treg ratios were significantly higher in the mild depression group compared to the control group (p < 0.05), with a concurrent decrease in Treg% (p < 0.05). In the moderate depression group, elevated levels of Th1%, Th17%, Th1, Th17, Th1/Th2, and Th17/Treg were observed (p < 0.05), alongside reduced Treg% and Treg counts (p < 0.05). The severe depression group exhibited further increases in Th1%, Th17%, Th1, Th17, Th1/Th2, and Th17/Treg (p < 0.05). IL-4 levels progressively decreased, while IL-6 levels increased across the mild, moderate, and severe depression groups (p < 0.05). A negative correlation was found between depression severity and IL-4 (r = -0.544, p < 0.001), and a positive correlation with IL-6 (r = 0.553, p < 0.001). IL-4 and IL-6 were identified as independent factors influencing depression severity (p < 0.01).

CONCLUSIONS: The study’s findings suggest that abnormalities in CD4 + T lymphocytes and cytokines are characteristic of depression across its severity spectrum, with an increase in Th1 and Th17 cells and a decrease in Treg cells. IL-4 and IL-6 may serve as indicators of depression severity and are significant biomarkers for assessing disease progression. These insights enhance our understanding of the immunological basis of depression and provide novel strategies for its management and treatment.

PMID:41034792 | DOI:10.1186/s12888-025-07344-8