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: 10362709
• 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/10362709
• 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; 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; 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; 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 拟设立的K23导师患者导向研究职业发展奖推出一系列工作 旨在全面针对焦虑症和其他障碍的避免机制； 克里斯托弗·塞格拥有成为一名领先的临床研究人员所需的技能。塞格医生的初级临床 研究的职业目标是使用尖端的翻译科学通过有针对性地改善精神卫生保健 精确的无序机制。对这项研究的需求是重要的，并与NIMH的优先事项和 RDoC框架。回避是焦虑和相关障碍治疗的核心目标，但回避行为 通常在症状减轻后仍会持续，并使许多人根本不参与治疗。采用新方法 需要在治疗早期针对多种动机的回避，以改善保留率和结果 尤其是没有受益的20%的人和没有完成治疗的40%的人。基本信息 科学提供了关于现实世界逃避的多种机制的关键线索，这些机制可能是间接的或 目前的治疗技术没有充分解决这一问题。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开发直接干预的后续工作 工具。建议的项目使用直接神经刺激(重复经颅磁刺激；rTMS)在 配合精确的实验方法，测试特定的反应(逃避)和主动(回避) 应对神经回路可以被调节，以改变下游的恐惧和接近-避免决策。 随后的R-Level应用程序建立在这项工作的基础上，以确定完成治疗的患者与 非完成者，并测试如何更准确地针对个人资料来改善结果。一支由 专家导师(乔治、刘、麦克蒂格、莫布斯、乌德)将在基于研究的基础上使用他们丰富的知识 和临床神经刺激，先进的fMRI分析和研究方法，以及创建翻译 科学知情的治疗辅助剂，以支持Sege博士的发展。指导，实践研究 由K23提供的教程、课程作业、研讨会/研讨会和国际会议将 确保Sege博士实现他的职业目标：1)开发尖端神经刺激方面的专业知识 研究和临床应用，2)开发fMRI分析和研究工具方面的专业知识，以便与 RTMS，以更精确地针对与生态相关的回避行为；以及3)发展专门知识，创造 通过应用翻译科学改善认知行为治疗结果的佐剂。这个 拟议的K23还将促进出版、拨款撰写和跨部门领域的发展 合作，都是在一所机构-南卡罗来纳医科大学-有良好的记录 以及对早期调查的承诺。拟议的K23活动将使Sege博士准备成为 尖端临床研究人员和精神病学精准医学发展的领先者。