PROJECT: JTC2023 - Resilience: MASE

Major depressive disorder (MDD) is considered the worldwide leading disability-source, affecting about 29 million Europeans to date. Still, expedient behavioral treatment targets and their underlying neurobiology imperative for precision medicine approaches remain immature. From a clinical perspective, both psychomotor retardation and diminished mood constitute central MDD diagnostic criteria. MDD-patients but also remitted individuals vs. controls show reduced motor activity, and treatment response relates to increased activity. Intriguingly, a prominent recent study identified momentary interactions between motor activity and subjective energy in everyday life as a previously uncharted intervention target, and we were able to unravel neurobiological underpinnings of this dynamic real-life mechanism. The findings argue for targeted behavioral activation interventions, but which neurobiological phenotypes benefit the most in which intervention-environment (type, time, place) remains elusive. Therefore, in MASE, we aim to implement brain network analysis to unravel neurobiological activity–energy phenotypes, employ artificial intelligence to predict phenotype-tailored real-life intervention-environments, set up a daily life experimental study to validate results towards causality, and maximize adherence through smartphone APP designs. This will set the basis towards evidence-based, tailored and expedient mental health interventions fostering primary and secondary prevention.