Fear Profiles: Identification and characterization of individual trajectories in fear and anxiety

在实验恐惧和焦虑研究领域进行范式转变的时机已经成熟。在过去的几十年里，临床和实验工作通过基于人群的推断为一般原理提供了宝贵的见解，而个体差异在很大程度上被忽视为“剩余方差”或孤立研究。在这里，我主张这种差异提供了一个独特的机会和有希望的起点，为一种新颖的、开创性的方法提供了一个机会，利用人口异质性作为一个机会，推进对恐惧和焦虑相关过程的机制洞察，超越传统的先验理论的确认性或拒绝性调查。这是通过一系列系统的、多方法的和多元的研究来实现的，这些研究将成熟的实验范例与尖端的技术工具和方法的进步相结合。重要的是，实验设计、参与者选择和数据分析工具都是为检测个体差异而量身定制的。该计划将允许识别基于经验的亚组，这些亚组在涉及恐惧和焦虑的关键过程中，在可观察到的行为、神经生物学或生理反应方面存在差异（恐惧档案）。这些群体随后将根据神经功能、神经结构、生物学、经验和心理因素（深度和数字表型）进行特征描述，这些因素将被纳入（部分纵向）预测框架。我希望这些结果能够对完善恐惧和焦虑的多原因病因学框架做出独特的贡献，并为研究个体差异提供方法上的进步。最后，我设想对亚组特定机制缺陷的见解，为未来基于机制的干预和预防计划的发展奠定基础，以减轻社会和个体患者日益增长的焦虑症负担。

The time is ripe for a paradigm shift in the field of experimental fear and anxiety research. In the past decades, clinical and experimental work has provided invaluable insights into generic principles via population-based inferences, whereas individual differences have been largely neglected as ‘residual variance’ or studied in isolation. Here, I advocate that this variance provides a unique opportunity and promising starting point for a novel, pioneering approach in utilizing population heterogeneity as an opportunity to advance mechanistic insights into fear and anxiety-related processes beyond traditional confirmatory or refusive investigations on a-priori theories. This is implemented in a series of systematic, multi-methodological and -variate studies that combine well-established experimental paradigms with cutting-edge technical tools and methodological advances. Importantly, experimental design, participant selection and data analysis tools are tailored towards the detection of individual differences. The program will allow for the identification of empirically-based subgroups differing in observable behavioral, neurobiological or physiological responding in key processes implicated in fear and anxiety (FEAR PROFILES). These groups will subsequently be characterized with respect to the neurofunctional, neurostructural, biological, experiential and psychological factors (deep and digital phenotyping) which will be incorporated into a (partly longitudinal) predictive framework. I expect the results to make a unique contribution to a refined framework on the multicausal etiopathology of fear and anxiety and provide methodological advances for research into individual differences. Ultimately, I envision insights into subgroup specific mechanistic deficits to break the grounds for the future development of mechanistically-based intervention and prevention programs to reduce the ever-growing burden of anxiety disorders on society and the individual patient.