Huang Yiran, Chen Zhenni, Xu Yang, Ren Biqiong
Clinical Medical College, Hunan University of Traditional Chinese Medicine, Changsha, China.
Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Psychiatry. 2025 Jul 18;16:1550958. doi: 10.3389/fpsyt.2025.1550958. eCollection 2025.
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.
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, %) 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.
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 ( < 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 ( < 0.05), with no significant changes in CD4+ T subsets. Correspondingly, MMP significantly decreased in CD4+ Tn, CD8+ Tn, CD8+ Tcm, and CD8+ Tem cells ( < 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.
Our results suggest that mitochondrial alterations in CD8+ T-cell subsets may represent immunometabolic adaptations accompanying clinical improvement in depression. MM and MMP in CD8+ T lymphocytes may serve as preliminary biomarkers for assessing therapeutic response in depression.
抑郁症在其病理生理学中涉及免疫炎症反应和线粒体功能障碍。然而，T淋巴细胞中线粒体改变与抑郁症临床治疗反应之间的关联仍不清楚。
40例诊断为抑郁症的住院患者参与了本研究，在入院和出院时采集外周血样本。采用流式细胞术监测抑郁症患者T淋巴细胞亚群的频率，使用淋巴细胞线粒体功能分析软件（专利技术）结合各亚群的中位荧光强度计算线粒体质量（MM）和低线粒体膜电位（MMP，%）。患者进一步分为常规住院时间（≤21天）和长期住院时间（>21天）组，以探讨住院时间与线粒体变化之间的潜在关联。
治疗前后CD4+和CD8+T细胞亚群的比例保持稳定，而CD4+中枢记忆T细胞（Tcm）、CD4+效应记忆T细胞（Tem）和CD8+Tem的绝对计数显著下降（<0.05）。在线粒体功能方面，治疗后CD4+Tcm、CD8+初始T细胞（Tn）、CD8+Tcm、CD8+效应T细胞（Tef）和CD8+Tem亚群中的MM显著增加（<0.05），CD4+T亚群无显著变化。相应地，CD4+Tn、CD8+Tn、CD8+Tcm和CD8+Tem细胞中的MMP显著降低（<0.05），表明线粒体极化得到改善。基于住院时间的探索性亚组分析显示，这些线粒体改善主要在常规住院时间组中观察到，而长期住院时间组未检测到显著变化。
我们的结果表明，CD8+T细胞亚群中的线粒体改变可能代表抑郁症临床改善伴随的免疫代谢适应。CD8+T淋巴细胞中的MM和MMP可能作为评估抑郁症治疗反应的初步生物标志物。
