PROJECT: JTC2023 - Resilience: PROGRESS

The concept of tipping points is receiving particular attention in the context of climate change: here, abrupt and persistent changes are often the result of a series of slower processes that undermine resilience and push systems to crossing a critical threshold. Surprisingly, the concept of tipping points has been largely neglected in stress research, and the precise determinants that decide about positive or negative consequences of stress remain unclear. PROGRESS will for the first time leverage complementary expertise and cutting-edge methods to close these gaps by pursuing the following three objectives: 1) To establish the time course and temporal dynamics of events associated with the tipping point, including refined behavioral and molecular changes, 2) To identify and validate predictive signatures for stress resilience and susceptibility in mouse models and humans and 3) To test the hypothesis that actively promoting resilience can shift the tipping point. To achieve our goals, we will leverage the power of dedicated, deeply phenotyped human cohorts, empower translationally valid animal models with emerging methods for longitudinal assessment of phenotypes across scales and advanced computational tools to finally enable direct translation to humans. Successful completion will enable early prediction of the tipping point and personalized risk stratification. Ultimately, we expect our research to help transform modern psychiatry into a science of prevention.