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

• Applicant: Professorin Dr. Iris-Tatjana Kolassa
• Subject Area: Biological Psychology and Cognitive Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 522508425

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.

• DFG Programme: Research Grants