Immunometabolic alterations in depression: The relation of aerobic to anaerobic cellular energy production and its regulation

抑郁症的免疫代谢改变：有氧与无氧细胞能量产生及其调节的关系

• 批准号: 522508425
• 负责人: Professorin Dr. Iris-Tatjana Kolassa
• 金额: --
• 依托单位: Abteilung Klinische und Biologische Psychologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/522508425?language=en
• 关键词: Immunometabolic; alterations; depression; relation; aerobic

Major depressive disorder is a leading and increasing cause of disability world-wide that causes enormous individual suffering and socioeconomic costs. Mixed therapy success rates and insufficient protection against relapses indicate the need for better treatment concepts and novel research approaches. Besides elevated inflammation and oxidative stress, transdisciplinary research has already confirmed various far-reaching physiological aberrations in depression, including reduced mitochondrial energy production in immune cells, blood platelets, and muscle cells. Accordingly, a systemic energy deficiency may cause the characteristic depressive symptoms, namely, lack of energy, fatigue, difficulties in concentration, memory consolidation, and emotion regulation problems as well as dysregulated inflammatory processes. In the proposed study, we aim to investigate the role of mitochondrial upstream mechanism (e.g. glycolysis, pyruvate oxidation, citric acid cycle) and their regulating pathway in the immunometabolism of individuals with depression. In addition, therapy effects will be monitored to identify predictors of treatment outcome. For this purpose, immune cells from 258 participants that are equally divided in a treatment group for depression, a wait-list-control group and a healthy control group will be analyzed. Samples from a biobank will be used for the analyses. The necessity of alternative and better treatment strategies for individuals with depression is obvious. This study has great potential for mutually enhancing our understanding of maladapted mechanisms in depression and the influencing factors, as well as identifying potential therapeutic targets.

重度抑郁症是世界范围内导致残疾的主要和日益增加的原因，导致巨大的个人痛苦和社会经济成本。混合治疗成功率和对复发的保护不足表明需要更好的治疗概念和新的研究方法。除了炎症和氧化应激的升高，跨学科研究已经证实了抑郁症中各种影响深远的生理畸变，包括免疫细胞、血小板和肌肉细胞中线粒体能量产生的减少。因此，全身性能量缺乏可能导致特征性抑郁症状，即缺乏能量、疲劳、难以集中注意力、记忆巩固和情绪调节问题以及失调的炎症过程。本研究旨在探讨线粒体上游机制（如糖酵解、丙酮酸氧化、柠檬酸循环）及其调控途径在抑郁症患者免疫代谢中的作用。此外，将监测治疗效果，以确定治疗结局的预测因素。为此，将分析来自258名参与者的免疫细胞，这些参与者被平均分为抑郁症治疗组、等待列表对照组和健康对照组。将使用生物样本库中的样本进行分析。对于抑郁症患者来说，替代和更好的治疗策略的必要性是显而易见的。这项研究具有很大的潜力，相互增强我们对抑郁症的适应不良机制及其影响因素的理解，并确定潜在的治疗靶点。