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

与压力相关的精神障碍，如焦虑、抑郁、慢性疼痛和成瘾，会造成巨大的个人痛苦和巨大的经济和社会成本。尽管进行了大量的研究，但在过去几十年里，我们对疾病机制的理解，特别是新疗法的开发方面取得的进展有限。与压力有关的精神障碍的发病率仍然很高。因此，在CRC 1193中，我们用另一种策略来补充病理生理学研究，即调查在逆境期间和逆境之后支持维持心理健康的保护机制（例如，潜在的创伤事件，具有挑战性的生活环境或转变，身体疾病）。将重点放在复原力而不是病理生理学上，代表了心理健康研究的一种范式转变，在制定新的预防战略方面具有巨大潜力。在CRC 1193中，我们的目标是通过(i)为压力相关精神功能障碍的恢复力的神经生物学研究开发一个连贯的理论框架（目标1），（ii）识别和理解神经生物学恢复力机制（目标2），以及（iii）利用获得的见解开发新的或改进的预防策略（目标3）来推进这种范式转变。目标1（理论发展）首先假设，灵活的短期和长期调节应激反应是最大限度地减少资源消耗和应激引起的适应成本的关键。在此基础上，CRC倡议的研究人员追求两种理论途径，一种是集中在应激期间和应激后神经兴奋性和神经网络活动的调节，另一种是集中在应激调节评价（情绪评价）过程的神经生物学基础上。在CRC的过程中，这两个框架将被评估和完善，最终目标是将结果整合到神经生物学弹性机制的统一理论中。目标1和目标2（神经生物学弹性机制的实证研究）需要一种跨学科的综合研究策略，将基于分子细胞和神经网络的研究与行为和认知分析相结合。为此目的，所有子项目都被设计为至少包括这些分析层次中的两个。这些项目的重点是动物和人类模型的细粒度机制研究，所获得的结果将纳入理论发展。只要有可能，这些项目就会对他们所研究的神经机制进行因果操作，以便为预防性干预的发展获得新的想法。

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.