Descrizione del progetto
Nuovi biomarcatori del metabolismo energetico per la depressione
Nuovi dati indicano che il disturbo depressivo maggiore (DDM) è associato a una ridotta produzione di energia mitocondriale e a una compromissione dell’omeostasi dell’ossigeno, unitamente a livelli elevati di attività infiammatoria e stress ossidativo. L’obiettivo chiave del progetto MitO2Health, finanziato dall’UE, è quello di studiare i meccanismi fisiologici alla base del DDM. Gli scienziati valuteranno lo stato clinico e biologico dei pazienti che ricevono la terapia cognitivo-comportamentale rispetto alle persone non trattate e ai controlli sani. Lo studio aiuterà a individuare i biomarcatori correlati alla risposta individuale alla terapia e alle ricadute e contribuirà così allo sviluppo di nuovi criteri diagnostici biologicamente fondati per il DDM, oltre a gettare le basi per concezioni di trattamento innovative.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
89081 Ulm
Germania