Neural Dimensions of Threat Reactivity and Regulation for Understanding Anxiety

描述（由申请人提供）：本项目的直接目标是在研究领域标准（RDoC）的负价系统内，使用功能成像来定义潜在威胁的反应性和调节的维度结构。通过使用这些结构，我们将焦虑的理解建立在神经机制上，而不是使用预先设定的诊断边界，这些边界对焦虑症状的结构有固有的假设。 在我们的社区，焦虑的经历是普遍的，每年花费470亿美元的护理和损失的时间。广泛的焦虑症有着共同的焦虑唤醒症状，并且在功能成像研究中表现出杏仁核的高反应性，我们称之为过度的“威胁反应性”。其中一些疾病还涉及更广泛的适应性丧失，伴随着更多的焦虑认知体验，如忧虑性期望。它们显示腹侧-喙侧前扣带回的低激活，我们称之为不良的“威胁调节”。考虑到焦虑现象和成像结果的共性，我们的目标是确定是否成像定义的威胁反应和调节维度提供了一个主要的组织原则，以区分焦虑和情绪症状的具体特征，它们产生的行为，以及它们对真实的世界的影响，以发挥社会和工作的功能。为了做到这一点，我们将招募所有通过大型社区心理诊所的人，该诊所关注广泛的焦虑和情绪相关症状。这些参与者将不接受药物治疗，并使用功能成像，行为，自我报告和遗传探针的协调电池进行研究，并建立了威胁反应和调节的范例。直接的目的是确定是否成像定义的杏仁核威胁反应和前扣带回威胁调节的尺寸与焦虑症状的严重程度，特别是焦虑唤醒和忧虑的期望。第二个目标是确定这些维度如何以内聚的方式与情感和认知领域的行为表现相关，因为例如，威胁处理的中断可能会暂时损害认知控制。本研究的第三个目的是评估成像定义的维度如何影响与疾病负担相关的真实的世界功能，特别是社会功能、生活质量和工作效率。这将为焦虑症的治疗创造一种个性化的医学方法，这将导致最有可能缓解症状的特定治疗。结果将导致概念上有效的结构，以了解什么神经机制产生特定的焦虑体验。

DESCRIPTION (provided by applicant): The immediate goal of this project is to use functional imaging to define dimensional constructs for reactivity and regulation of potential threat, within the Negative Valence system of the Research Domain Criteria (RDoC). By using these constructs we ground the understanding of anxiety in neural mechanisms, rather than using pre-set diagnostic boundaries, which have inherent assumptions about the structure of anxiety symptoms. In our community, the experience of anxiety is prevalent, and costs $47 billion per year in care and lost time. A wide range of anxiety disorders share common symptoms of anxious arousal, and show hyper- reactivity of the amygdala in functional imaging studies, which we call excessive "Threat reactivity". Some of these disorders also involve a more generalized loss of adaption accompanied by more cognitive experiences of anxiety, such as apprehensive expectations. They show hypo-activation of the ventral-rostral anterior cingulate, which we call poor "Threat regulation". Given the commonalities in anxiety phenomena and imaging findings, our goal is to determine whether imaging-defined dimensions of Threat reactivity and regulation provide a primary organizing principle for distinguishing specific features of anxiety and mood symptoms, the behaviors they generate, and their impact on the real world capacity to function socially and at work. To do this we will recruit all people who come through a large community psychology clinic which attends to a broad spectrum of anxiety and mood-related symptoms. These participants will be unmedicated and studied using a coordinated battery of functional imaging, behavioral, self-report and genetic probes, with well established paradigms for threat reactivity and regulation. The immediate aim is to determine if imaging-defined dimensions of amygdala threat reactivity and anterior cingulate threat regulation relate to severity of anxiety symptoms, specifically anxious arousal and apprehensive expectations. A second aim is to determine how these dimensions also relate in a cohesive way to behavioral performance in emotional and cognitive domains since, for instance, disruptions to threat processing can temporarily impair cognitive control. The third aim of the study is to assess how the imaging-defined dimensions affect real world functions related to burden of illness, specifically social functioning, quality of life and work productivity. This will create a personalized medicine approach for the treatment of anxiety disorders that will lead to specific treatments most likely t result in remission of symptoms. Outcomes will result in conceptually valid constructs for understanding what neural mechanisms generate specific experiences of anxiety.