Project description
Novel biomarkers of energy metabolism in depression
Emerging evidence indicates that Major depressive disorder (MDD) is associated with reduced mitochondrial energy production and impaired oxygen homeostasis along with elevated levels of inflammatory activity and oxidative stress. The key objective of the EU-funded MitO2Health project is to investigate the physiological mechanisms underlying MDD. Scientists will assess the clinical and biological status of patients receiving cognitive behavioural therapy (CBT) in comparison with untreated individuals as well as healthy controls. The study will help to identify biomarkers related to individual therapy response and relapse and, thereby, it will contribute to develop novel biologically founded diagnostic criteria for MDD along with paving the way for innovative treatment concepts.
Objective
MitO2Health aims to develop and empirically prove a radically new pathophysiological model of Major Depressive Disorder (MDD) as a systemic energy deficiency disease. Traditionally, MDD is conceptualized as a neurotransmitter deficiency in the brain. However, with pioneering methods my group has provided evi-dence for reduced mitochondrial energy production in MDD, characterizing it as a cellular-metabolic disorder with a lowered production of adenosine triphosphate (ATP). Reduced mitochondrial bioenergy production and impairments in oxygen (O2) homeostasis (reduced levels of erythrocytes, less hemoglobin and its lower O2-binding affinity due to oxidative stress), as well as oxidative stress and inflammation (the “MitO2Health parameters”) were consistently associated with an increased risk for MDD, but have been neglected so far in MDD research and therapy. In MitO2Health we will more comprehensively than ever before investigate the physiological mechanisms underlying MDD and will provide first longitudinal evidence on the mutual in-terplay between the MitO2Health parameters and MDD. Moreover, we will apply cognitive-behavioral therapy (CBT) as randomized treatment condition to test whether CBT-related MDD symptom reduction is coupled to a normalization of the MitO2Health parameters. We will treat 100 MDD patients with 6 months of CBT and compare them to 100 MDD patients of a waiting-list group and 100 healthy controls. Clinical and biological status will be assessed at four points over 18 months. We will thus characterize the biomarker pro-files of MDD treatment response and resistance as well as MDD symptom recurrence during a follow-up pe-riod. MitO2Health will not only establish a modern etiological model of MDD, but also identify biomarkers of individual therapy response and relapse. This will lead to new diagnostic standards and inspire personalized MDD treatment concepts that will fundamentally improve clinical outcomes in psychotherapy and psychiatry.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
89081 Ulm
Germany