Neural Dimensions of Threat Reactivity and Regulation for Understanding Anxiety

威胁反应的神经维度和理解焦虑的调节

• 批准号: 8705033
• 负责人: Leanne Williams
• 金额: $ 53.38万
• 依托单位: PALO ALTO VETERANS INSTIT FOR RESEARCH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705033
• 关键词: Address; Affect; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Arousal; Behavior; Behavioral; Blood specimen; Brain imaging; Breathing; Caring; Clinic; Cognitive; Communities; Community Psychology; Conflict (Psychology); Depressed mood; Diagnostic; Dimensions; Disease; Disease remission; Emotional; Emotions; Facial Expression; Fright; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Genes; Genetic; Genetic Risk; Glucocorticoid Receptor; Goals; Heart; Hormones; Image; Impairment; Individual; Lead; Masks; Measures; Medicine; Mental Health; Moods; Outcome; Participant; Patient Self-Report; Patients; Performance; Process; Productivity; Quality of life; Race; Reaction Time; Recruitment Activity; Regulation; Relative (related person); Research Domain Criteria; Severities; Social Functioning; Structure; Symptoms; System; Time; Validation; Walking; Work; behavior measurement; behavioral impairment; burden of illness; clinically significant; cognitive control; cost; design; emotion regulation; expectation; experience; innovation; insight; neuromechanism; processing speed; psychologic; public health relevance; relating to nervous system; response; risk variant; serotonin transporter

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.

描述（由申请人提供）：该项目的直接目标是在研究领域标准（RDoC）的负价系统中，使用功能成像来定义反应性和潜在威胁调节的维度结构。通过使用这些结构，我们将对焦虑的理解建立在神经机制的基础上，而不是使用预先设定的诊断界限，后者对焦虑症状的结构有固有的假设。在我们的社区中，焦虑的经历很普遍，每年花费470亿美元用于护理和浪费时间。许多焦虑症都有焦虑唤起的共同症状，并在功能成像研究中表现出杏仁核的过度反应，我们称之为过度的“威胁反应”。其中一些障碍还包括更广泛的适应能力丧失，并伴有更多的认知焦虑体验，如忧虑性期望。他们表现出腹-吻侧前扣带的低激活，我们称之为糟糕的“威胁调节”。鉴于焦虑现象和影像学发现的共性，我们的目标是确定影像学定义的威胁反应性和调节维度是否为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现实世界中社交和工作能力的影响提供了一个主要的组织原则。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，他们会处理各种各样的焦虑和情绪相关症状。这些参与者将不服用药物，并使用功能成像、行为、自我报告和基因探针的协调电池进行研究，并具有良好的威胁反应和调节范例。直接目的是确定杏仁核威胁反应性和前扣带威胁调节的成像定义维度是否与焦虑症状的严重程度有关，特别是焦虑唤醒和忧虑预期。第二个目标是确定这些维度如何以一种连贯的方式与情感和认知领域的行为表现联系起来，因为例如，威胁处理的中断会暂时损害认知控制。该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现实世界功能，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，这种方法将导致最可能导致症状缓解的特定治疗。结果将产生概念上有效的构念，以理解产生特定焦虑体验的神经机制。