Projektbeschreibung
Neue Biomarker für den Energiestoffwechsel bei Depression
Neueste Forschungsergebnisse deuten darauf hin, dass schwere Depressionen mit verminderter Energieerzeugung in den Mitochondrien und eingeschränkter Sauerstoffhomöostase sowie erhöhter Entzündungsaktivität und verstärktem oxidativem Stress einhergehen. Das EU-finanzierte Projekt MitO2Health will darum die physiologischen Mechanismen der schweren Depression erforschen. Das Team wird den klinischen und biologischen Zustand von Erkrankten, die kognitive Verhaltenstherapie erhalten, mit unbehandelten Erkrankten sowie einer gesunden Kontrollgruppe vergleichen. Aus der Studie werden sich Biomarker für das individuelle Ansprechen auf die Therapie sowie das Rückfallverhalten ableiten lassen. So trägt sie zur Entwicklung neuer biologisch fundierter Diagnosekriterien für die schwere Depression bei und ebnet gleichzeitig den Weg für innovative Therapiekonzepte.
Ziel
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.
Wissenschaftliches Gebiet
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
89081 Ulm
Deutschland