Abstract
BACKGROUND: Depression involves immune-inflammatory responses and mitochondrial dysfunction in its pathophysiology. However, the association between mitochondrial alterations in T lymphocytes and clinical treatment responses in depression remains unclear. METHODS: Forty hospitalized patients diagnosed with depression participated in this study, and peripheral blood samples were collected upon admission and discharge. Flow cytometry was used to monitor the frequency of T-lymphocyte subpopulations in depressed patients, mitochondrial mass (MM) and low mitochondrial membrane potential (MMP(Low), %) was calculated by using the lymphocyte mitochondrial function analysis software (patented technology) in conjunction with the median fluorescence intensity of each subpopulation. Patients were further stratified into routine-term hospitalization (≤21 days) and long-term hospitalization (>21 days) groups to explore potential associations between hospitalization duration and mitochondrial changes. RESULTS: The proportions of CD4+ and CD8+ T-cell subsets remained stable before and after treatment, while absolute counts of CD4+ central memory T (Tcm), CD4+ effector memory T (Tem) and CD8+ Tem significantly declined (P < 0.05). In terms of mitochondrial function, MM was significantly increased in CD4+ Tcm, CD8+ naïve T (Tn), CD8+ Tcm, CD8+ effector T (Tef), and CD8+ Tem subsets after treatment (P < 0.05), with no significant changes in CD4+ T subsets. Correspondingly, MMP(Low) significantly decreased in CD4+ Tn, CD8+ Tn, CD8+ Tcm, and CD8+ Tem cells (P < 0.05), suggesting improved mitochondrial polarization. Exploratory subgroup analysis based on hospitalization duration revealed that these mitochondrial improvements were predominantly observed in the routine-term hospitalization group, whereas no significant changes were detected in the long-term hospitalization group. CONCLUSION: Our results suggest that mitochondrial alterations in CD8+ T-cell subsets may represent immunometabolic adaptations accompanying clinical improvement in depression. MM and MMP(Low) in CD8+ T lymphocytes may serve as preliminary biomarkers for assessing therapeutic response in depression.