Modeling and Modulating Mechanisms of Escape, Avoidance, and Approach in the Anxiety Disorder Spectrum

焦虑症谱系中逃避、回避和接近的建模和调节机制

• 批准号: 10215704
• 负责人: Christopher Sege
• 金额: $ 20.9万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-02 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10215704
• 关键词: Address; Adjuvant; Ambulatory Care; Amygdaloid structure; Anhedonia; Animals; Anxiety; Area; Aversive Stimulus; Basic Science; Behavior; Clinical; Clinical Research; Cognitive Therapy; Collaborations; Computer Models; Conflict (Psychology); Coping Behavior; Corpus striatum structure; Data; Decision Making; Development; Development Plans; Disease; Disease remission; Dorsal; Dropout; Educational workshop; Ensure; Fostering; Fright; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Healthcare; Human; Impairment; Individual; Institution; International; Intervention; Knowledge; Laboratories; Major Depressive Disorder; Maps; Mediating; Medical; Mental Depression; Mental Health; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Modeling; Motivation; National Institute of Mental Health; Neurosciences; Outcome; Participant; Patients; Pattern; Physiology; Prefrontal Cortex; Preparation; Psychiatry; Publications; Reflex action; Research; Research Domain Criteria; Research Methodology; Research Personnel; Research Training; Rewards; Science; South Carolina; Stimulus; Symptoms; Techniques; Testing; Training; Translational Research; Treatment outcome; Universities; Ventral Striatum; Work; Writing; anxiety spectrum disorders; anxiety-related disorders; anxious; approach avoidance behavior; avoidance behavior; base; career; career development; clinical practice; coping; cost; effective therapy; evidence base; hands on research; improved; improved outcome; multimodality; neural circuit; neuroregulation; noninvasive brain stimulation; novel; pre-clinical; precision medicine; prevent; reduce symptoms; repetitive transcranial magnetic stimulation; response; skills; substance misuse; symposium; therapy outcome; tool

PROJECT ABSTRACT The proposed K23 Mentored Patient-Oriented Research Career Development Award launches a line of work aiming to comprehensively target mechanisms of avoidance in anxiety and other disorders; and, it provides Dr. Christopher Sege with skills necessary to becoming a leading clinical researcher. Dr. Sege’s primary clinical research career goal is to use cutting-edge translational science to improve mental health care by targeting precise disorder mechanisms. Need for this research is significant and consistent with NIMH priorities and the RDoC framework. Avoidance is a core target of anxiety and related disorder treatment, but avoidant behaviors often persist after symptom reduction and keep many from engaging in treatment at all. Novel methods to target multiple motive drivers of avoidance early in treatment are needed to improve retention and outcome especially for the 20% of individuals who do not benefit from and 40% who do not complete treatment. Basic science provides critical clues as to the multiple mechanisms of real-world avoidance that may be indirectly or inadequately addressed by current treatment techniques. Crucial goals of work proposed here is to determine how these mechanisms drive clinical behavior and support subsequent work that develops direct intervention tools. The proposed project uses direct neurostimulation (repetitive transcranial magnetic stimulation; rTMS) in concert with precise experimental methods to test how specific reactive (escape) and proactive (avoidance) coping neurocircuits can be modulated to alter downstream fear and approach-avoid decision-making. Subsequent R-level applications build on this work to determine coping profiles of treatment completers versus non-completers, and to test how profiles can be more precisely targeted to improve outcomes. A team of expert mentors (George, Liu, McTeague, Mobbs, Uhde) will use their extensive knowledge in research-based and clinical neurostimulation, advanced fMRI analysis and research methods, and creation of translational science-informed treatment adjuvants to support Dr. Sege in his development. Mentorship, hands-on research tutorials, coursework, seminars/ workshops, and international conference attendance afforded by the K23 will ensure that Dr. Sege achieves his career goals to: 1) develop expertise in cutting-edge neurostimulation for research and clinical use, 2) develop expertise in fMRI analysis and research tools for use in concert with rTMS to more precisely target ecologically-relevant avoidance behavior, and; 3) develop expertise in creating adjuvants that improve cognitive behavior therapy outcomes through application of translational science. The proposed K23 will also foster development in areas of publication, grant writing, and inter-departmental collaboration, all at an institution – the Medical University of South Carolina – which has a strong track record and commitment to early stage investigators. Proposed K23 activities will prepare Dr. Sege to become a cutting-edge clinical researcher and a leader in the development of a precision medicine of psychiatry.

项目摘要 拟议的 K23 以患者为导向的研究职业发展奖启动了一系列工作 旨在全面针对焦虑和其他疾病的回避机制；并且，它提供了博士。 Christopher Sege 拥有成为领先临床研究员所需的技能。 Sege 博士的主要临床 研究职业目标是利用尖端的转化科学来改善心理健康护理 精确的紊乱机制。这项研究的需求非常大，并且与 NIMH 的优先事项和 RDoC 框架。回避是焦虑和相关疾病治疗的核心目标，但回避行为 通常在症状减轻后仍然存在，并使许多人根本无法接受治疗。新方法 需要在治疗早期针对回避的多种动机驱动因素，以提高保留率和结果 尤其是对于 20% 未从治疗中受益和 40% 未完成治疗的个体而言。基本的 科学提供了关于现实世界回避的多种机制的关键线索，这些机制可能是间接或间接的 目前的治疗技术不足以解决这一问题。这里提出的工作的关键目标是确定 这些机制如何驱动临床行为并支持后续开展直接干预的工作 工具。拟议的项目使用直接神经刺激（重复经颅磁刺激；rTMS） 结合精确的实验方法来测试具体的反应（逃避）和主动（回避） 可以调节应对神经回路来改变下游的恐惧和回避决策。 随后的 R 级应用程序建立在这项工作的基础上，以确定治疗完成者与 未完成者，并测试如何更精确地定位个人资料以改善结果。一个团队 专家导师（George、Liu、McTeague、Mobbs、Uhde）将利用他们丰富的知识进行基于研究的研究 和临床神经刺激、先进的功能磁共振成像分析和研究方法以及转化模型的创建 科学指导的治疗佐剂支持 Sege 博士的发展。指导、实践研究 K23 提供的教程、课程作业、研讨会/讲习班以及参加国际会议将 确保 Sege 博士实现他的职业目标：1) 发展尖端神经刺激方面的专业知识 研究和临床使用，2）开发功能磁共振成像分析和研究工具方面的专业知识，以便与 rTMS 更精确地针对生态相关的回避行为； 3）培养创造方面的专业知识 通过应用转化科学来改善认知行为治疗结果的佐剂。这 拟议的 K23 还将促进出版、资助写作和跨部门领域的发展 合作全部在一个机构——南卡罗来纳医科大学——拥有良好的记录 以及对早期研究人员的承诺。拟议的 K23 活动将使 Sege 博士成为一名 尖端临床研究员和精神病学精准医学开发的领导者。