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: 10576356
• 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/10576356
• 关键词: Address; Adjuvant; Adjuvant Therapy; 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; Diagnostic; Disease; Disease remission; Dorsal; Dropout; Educational workshop; Ensure; Fostering; Fright; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Human; Impairment; Individual; Institution; International; Intervention; Knowledge; Laboratories; Major Depressive Disorder; Maps; Mediating; Medical; Mental Depression; Mental Health Services; 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; Productivity; Psychiatry; Publications; Reflex action; Research; Research Domain Criteria; Research Methodology; Research Personnel; Rewards; Science; South Carolina; Stimulus; Symptoms; Techniques; Testing; Training; Translational Research; Treatment outcome; Universities; Ventral Striatum; Work; Writing; anxiety spectrum disorders; anxious; approach avoidance behavior; avoidance behavior; 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; translational applications

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指导了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中的回避机制；而且，它提供了博士。 克里斯托弗·塞格（Christopher Sege）具有成为领先的临床研究人员所必需的技能。 Sege博士的主要临床 研究职业目标是使用尖端的翻译科学来通过靶向来改善心理保健 精确的疾病机制。对这项研究的需求非常重要，并且与NIMH的优先级一致， RDOC框架。避免是动画和相关障碍治疗的核心目标，但回避行为 症状减轻后通常会持续存在，并完全防止许多人从事治疗。新方法 需要在治疗早期的早期避免的目标驱动因素以改善保留率和结果 尤其是对于20％的人中没有受益的人，而没有完成治疗的40％。基本的 科学为可能是间接或 当前的治疗技术无法充分解决。这里提出的工作的关键目标是确定 这些机制如何推动临床行为并支持后来发展直接干预的工作 工具。拟议的项目使用直接的神经刺激（重复的经颅磁刺激； RTMS） 使用精确的实验方法进行音乐会，以测试特定反应性（逃脱）和主动（避免） 可以调节应对神经环节以改变下游的恐惧和避免进近的决策。 随后的R级应用程序以这项工作为基础，以确定治疗完成者的应对配置文件 未完成的人，并测试如何更精确地针对改善预后。一个团队 专家导师（George，Liu，McTeague，MOBBS，UHDE）将在基于研究的基于研究中的广泛知识 以及临床神经刺激，高级功能磁共振成像分析和研究方法以及转化的创建 科学知识的治疗调节器，以支持Sege博士的发展。指导，动手研究 K23提供的教程，课程，课程/讲习班和国际会议出席 确保Sege博士实现自己的职业目标：1）在尖端神经刺激方面发展专业知识 研究和临床用途，2）在fMRI分析和研究工具方面开发专业知识，以便与 RTMS更精确地针对与生态相关的避免行为，并且； 3）发展创建专业知识 通过应用转化科学改善认知行为疗法结果的佐剂。这 拟议的K23还将促进出版，赠款写作和部门间的发展 合作，所有机构 - 南卡罗来纳州医科大学 - 有很强的往绩 并致力于早期调查人员。拟议的K23活动将使Sege博士做好准备成为一个 尖端的临床研究人员和精神病学精确医学发展的领导者。