Abstract：
BACKGROUND: Disrupted cellular communication, inflammatory responses and mitochondrial dysfunction are consistently observed in late-life depression (LLD). Exosomes (EXs) mediate cellular communication by transporting molecules, including mitochondrial DNA (EX-mtDNA), playing critical role in immunoregulation alongside tumor necrosis factor (TNF). Changes in EX-mtDNA are indicators of impaired mitochondrial function and might increase vulnerability to adverse health outcomes. Our study examined EX-mtDNA levels and integrity, exploring their associations with levels of TNF receptors I and II (TNFRI and TNFRII), and clinical outcomes in LLD.
METHODS: Ninety older adults (50 LLD and 40 controls (HC)) participated in the study. Blood was collected and exosomes were isolated using size-exclusion chromatography. DNA was extracted and EX-mtDNA levels and deletion were assessed using qPCR. Plasma TNFRI and TNFRII levels were quantified by multiplex immunoassay. Correlation analysis explored relationships between EX-mtDNA, clinical outcomes, and inflammatory markers.
RESULTS: Although no differences were observed in EX-mtDNA levels between groups, elevated levels correlated with poorer cognitive performance (r = -0.328, p = 0.002) and increased TNFRII levels (r = 0.367, p = 0.004). LLD exhibited higher deletion rates (F(83,1) = 4.402, p = 0.039), with a trend remaining after adjusting for covariates (p = 0.084). Deletion correlated with poorer cognitive performance (r = -0.335, p = 0.002). No other associations were found.
CONCLUSIONS: Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center.
CONCLUSIONS: Our findings suggest that EX-mtDNA holds promise as an indicator of cognitive outcomes in LLD. Additional research is needed to further comprehend the role of EX-mtDNA levels/integrity in LLD, paving the way for its clinical application in the future.
METHODS: Ninety older adults (50 LLD and 40 controls (HC)) participated in the study. Blood was collected and exosomes were isolated using size-exclusion chromatography. DNA was extracted and EX-mtDNA levels and deletion were assessed using qPCR. Plasma TNFRI and TNFRII levels were quantified by multiplex immunoassay. Correlation analysis explored relationships between EX-mtDNA, clinical outcomes, and inflammatory markers.
RESULTS: Although no differences were observed in EX-mtDNA levels between groups, elevated levels correlated with poorer cognitive performance (r = -0.328, p = 0.002) and increased TNFRII levels (r = 0.367, p = 0.004). LLD exhibited higher deletion rates (F(83,1) = 4.402, p = 0.039), with a trend remaining after adjusting for covariates (p = 0.084). Deletion correlated with poorer cognitive performance (r = -0.335, p = 0.002). No other associations were found.
CONCLUSIONS: Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center.
CONCLUSIONS: Our findings suggest that EX-mtDNA holds promise as an indicator of cognitive outcomes in LLD. Additional research is needed to further comprehend the role of EX-mtDNA levels/integrity in LLD, paving the way for its clinical application in the future.
摘要：
背景：蜂窝通信中断，在晚年抑郁症(LLD)患者中,炎症反应和线粒体功能障碍均得到持续观察.外泌体（EXs）通过转运分子介导细胞通讯，包括线粒体DNA（EX-mtDNA），与肿瘤坏死因子（TNF）一起在免疫调节中起关键作用。EX-mtDNA的变化是线粒体功能受损的指标，可能会增加对不良健康结果的脆弱性。我们的研究检查了EX-mtDNA水平和完整性，探索它们与TNF受体I和II（TNFRI和TNFRII）水平的关联，和LLD的临床结果。
方法：90名老年人（50名LLD和40名对照（HC））参与了这项研究。收集血液并使用尺寸排阻色谱法分离外泌体。提取DNA并使用qPCR评估EX-mtDNA水平和缺失。通过多重免疫测定定量血浆TNFRI和TNFRII水平。相关分析探讨了EX-mtDNA，临床结果，和炎症标志物。
结果：尽管没有观察到组间EX-mtDNA水平的差异，水平升高与认知能力较差(r=-0.328,p=0.002)和TNFRII水平升高(r=0.367,p=0.004)相关.LLD表现出更高的缺失率（F（83,1）=4.402，p=0.039），在调整协变量后保持趋势(p=0.084)。缺失与较差的认知表现相关(r=-0.335,p=0.002)。没有发现其他关联。
结论：对来自专门老年精神病学治疗中心的少数参与者进行的横断面研究。
结论：我们的研究结果表明，EX-mtDNA有望作为LLD认知结果的指标。需要更多的研究来进一步理解EX-mtDNA水平/完整性在LLD中的作用，为其未来的临床应用铺平了道路。
方法：90名老年人（50名LLD和40名对照（HC））参与了这项研究。收集血液并使用尺寸排阻色谱法分离外泌体。提取DNA并使用qPCR评估EX-mtDNA水平和缺失。通过多重免疫测定定量血浆TNFRI和TNFRII水平。相关分析探讨了EX-mtDNA，临床结果，和炎症标志物。
结果：尽管没有观察到组间EX-mtDNA水平的差异，水平升高与认知能力较差(r=-0.328,p=0.002)和TNFRII水平升高(r=0.367,p=0.004)相关.LLD表现出更高的缺失率（F（83,1）=4.402，p=0.039），在调整协变量后保持趋势(p=0.084)。缺失与较差的认知表现相关(r=-0.335,p=0.002)。没有发现其他关联。
结论：对来自专门老年精神病学治疗中心的少数参与者进行的横断面研究。
结论：我们的研究结果表明，EX-mtDNA有望作为LLD认知结果的指标。需要更多的研究来进一步理解EX-mtDNA水平/完整性在LLD中的作用，为其未来的临床应用铺平了道路。
