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SFB 1193:  Neurobiology of Resilience to stress-related mental dysfunction: from understanding mechanisms to promoting prevention

Subject Area Medicine
Term from 2016 to 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 264810226
 
Stress-related mental disorders such as anxiety, depression, chronic pain, and addiction cause enormous personal suffering and large economic and societal costs. Progress in our understanding of disease mechanisms and, in particular, in the development of new therapies in the last decades has been limited, despite intense research. The incidence of stress-related mental disorders remains high. In CRC 1193, we therefore complement pathophysiological research with an alternative strategy, which is to investigate protective mechanisms that support the maintenance of mental health during and after adversity (e.g., potentially traumatizing events, challenging life circumstances or transitions, physical illness). Focusing on resilience rather than on pathophysiology represents a paradigm shift in mental health research and has great potential for the development of new prevention strategies. In CRC 1193, we aim at advancing this paradigm shift by (i) developing a coherent theoretical framework for the neurobiological study of resilience to stress-related mental dysfunction (Goal 1), (ii) identifying and understanding neurobiological resilience mechanisms (Goal 2), and (iii) exploiting the obtained insights for the development of new or improved prevention strategies (Goal 3). Goal 1 (theory development) starts with the assumption that flexible short- and long-term regulation of stress responses is key in minimizing resource depletion and allostatic costs caused by stress. On this basis, researchers in the CRC initiative pursue two theoretical approaches, the first one of which is centered on the regulation of neural excitability and neural-network activity during and after stress, and the second one on the neurobiological underpinnings of stress-regulatory appraisal (emotional evaluation) processes. Over the course of the CRC, both frameworks will be evaluated and refined with the ultimate goal to consolidate the results into a unified theory of neurobiological resilience mechanisms. Goal 1 and Goal 2 (empirical investigation of neurobiological resilience mechanisms) require an interdisciplinary and integrative research strategy combining molecular-cellular and neural network-based with behavioral and cognitive analyses. To this end, all subprojects are designed to include at least two of these levels of analysis. The projects are focused on fine-grained mechanistic studies in animal and human models, and the results obtained will be incorporated into theory development. Wherever possible, the projects perform causal manipulations of the neural mechanisms that they investigate, in order to gain new ideas for the development of preventive interventions.
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