Resilience and vulnerability: from neural circuits to networks

• Applicant: Professor Dr. Igor Nenadic
• Subject Area: Biological Psychiatry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544085564

Environmental stressors, spanning early-life adversities to critical life events in adulthood, have the potential to significantly shape mental health trajectories. Yet whether an individual can adapt and rebound from these stressors ultimately influences whether poor mental health will manifest. Currently our understanding of why some individuals adapt better to adversity, and are thus more resilient than others, is limited. To understand resilience comprehensively, we need to understand both what the mechanisms are that allow a person to compensate for adversity, as well as the risk and protective factors that contribute to mental health outcomes by interactively influencing these mechanisms. The brain represents a promising candidate to study in this regard, given that several aspects of its structural and functional architecture have been linked to individual differences in cognition, behaviour and mental health. However, there has been limited research explicitly aimed at identifying neural markers of resilience or vulnerability to date. That which does exist focuses on single diagnostic categories in small samples and is thus limited in its generalizability to the broader spectrum of environmental stressors and mental health outcomes. The ResilNet project overcomes this, taking a novel approach to understanding resilience by considering at its core, neural circuits and systems in the context of broader genetic and environmental influences that may confer risk and protection. Specifically, the project brings together a critical mass of multidisciplinary expertise to address important questions about the nature of resilience using large existing datasets for complex analysis, at the same time as collecting new data to both replicate and extend findings. In this work cutting-edge analytic methods (machine learning, network analysis, twin and GxE modelling) will be applied to multiple analysis units (genetics, neural systems, cognition, and behaviour) across multiple resilience proxies (outcome-based, psychological, genetic) using both hypothesis-driven and data-driven approaches in transdiagnostic and dimensional cohorts with subthreshold and threshold affective, schizophrenia spectrum, and autism spectrum disorders. We will also test the extent to which the hypothesised mechanisms and moderators of resilience apply to otherwise healthy individuals who are at increased risk of adverse mental health outcomes by virtue of exposure to recent traumatic events. The project will provide a major advance in our understanding of vulnerability and resilience to adverse mental health outcomes by uncovering moderators and mechanisms of resilience. Expected outcomes include an increased capacity for mental health risk stratification, and the potential development of new and scalable resilience-focused intervention strategies with significant clinical benefit and implications for public health, the economy and society at large.

• DFG Programme: Research Grants
• International Connection: Australia, Israel, Italy, Spain, Turkey
• Cooperation Partners: Professor Dr. Ahmad Abu-Akel, Ph.D.; Professor Dr. Paolo Brambilla; Professorin Tamsyn Van Rheenen, Ph.D.; Privatdozent Dr. Rafael Romero-Garcia; Professorin Timothea Toulopoulou, Ph.D.