THE BAROREFLEX MECHANISM: TRANSLATION TO AUD TREATMENT AND PROGNOSTIC MODELS

压力反射机制：AUD 治疗和预后模型的转化

• 批准号: 8723704
• 负责人: MARSHA E. BATES
• 金额: $ 16.19万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723704
• 关键词: Accounting; Address; Aerobic Exercise; Affect; Alcohols; Applications Grants; Area; Arousal; Award; Baroreflex; Basic Science; Behavior; Behavior Therapy; Behavioral; Biofeedback; Brain; Breathing; Cardiovascular system; Clinical; Clinical Sciences; Clinical Trials; Cognitive; Collaborations; Communication; Data; Disease remission; Drug Use Disorder; Emotional; Emotions; Ensure; Exercise; Faculty; Feedback; Foundations; Genes; Genetic; Genetic Polymorphism; Genomic DNA; Goals; Heart; Individual Differences; Inpatients; Interpersonal Violence; Intervention; Knowledge; Measures; Meditation; Mental Depression; Mentors; Modeling; Moods; National Institute of Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Outcome; Outpatients; Participant; Patients; Peer Review; Persons; Productivity; Psychopathology; Psychophysiology; Publications; Randomized Clinical Trials; Recovery; Regulation; Relapse; Research; Research Personnel; Research Project Grants; Research Support; Research Training; Resources; Rest; Sampling; Science; Scientist; Signal Transduction; Staging; Stress; Students; Symptoms; System; Testing; Training; Translating; Translational Research; Translations; Treatment outcome; Uncertainty; United States National Institutes of Health; Woman; Work; alcohol use disorder; base; binge drinker; biological adaptation to stress; career; career development; craving; design; disorder later incidence prevention; drinking; drinking behavior; emotion regulation; flexibility; graduate student; heart rate variability; improved; insight; interest; male; men; neural circuit; neural patterning; neuroimaging; novel; patient oriented; patient oriented research; post intervention; prognostic; programs; psychosocial; public health relevance; relating to nervous system; research and development; resilience; response; skills; success; symposium; tool; treatment as usual; treatment response; university student

DESCRIPTION (provided by applicant): The critical importance of two-way communication between the brain and the heart during thought, emotion, and behavior has been known for over 100 years, but this knowledge had little impact on alcohol use disorder (AUD) treatment .This revised K24 application by a mid-career translational clinical scientist addresses this gap by translating a new model of neurocardiac signaling (called the baroreflex [BAR] model) into behavioral interventions for AUDs. The research goal is to refine and test interventions based on her basic research supporting the BAR as an active behavioral change mechanism. Interventions that affect the BAR mechanism increase feedback between the brain and cardiovascular system. The overarching hypothesis of this K24 is that enhancing BAR functioning will increase behavioral flexibility towards alcohol as evidenced by reduced drinking, relapse prevention, decreased depression, and other positive psychosocial outcomes. The first specific aim is to use data from four ongoing clinical trials to evaluate the efficacy of two established (aerobic exercise, meditation) and one new (heart rate variability biofeedback) intervention and determine whether the BAR is a common mechanism of action in each intervention. The second aim is to examine whether treatment responders show different patterns of neural connectivity compared to those who do not respond. The third exploratory aim is to build prognostic models using clinical, cardiovascular, and neural indicators to predict which persons are most likely to benefit from interventions that target the BAR mechanism. Whether genetic indicators can improve prediction will also be explored the career development goal is to move the Candidate's patient oriented research program from early to late stage clinical translation. Training aims are to gain expertise in the design, conduct, and analysis of randomized clinical trials, the use of neuroimaging and neurocardiac tools to differentiate treatment responders versus non-responders, and the application of nonlinear sensitivity and uncertainty analysis to build a multi-level prognostic model. The proposed research and career development strategy will provide a unique training opportunity for five rising junior faculty and one graduate student with shared interests in translational clinical science, emotion regulation, and alcohol use disorders. The mentees bring to the team unique backgrounds and collaborations in the clinical psychopathology of emotional dysregulation and interpersonal violence, psychophysiology and exercise science, neuroimaging, and genetics. Attainment of research and training milestones will be gauged formally from yearly conference presentations, peer-reviewed publications, and patient-oriented research grant submissions.

描述（由申请人提供）：100 多年来，人们就知道大脑和心脏之间在思想、情感和行为过程中双向沟通的重要性，但这一知识对酒精使用障碍 (AUD) 的治疗影响甚微一位职业中期转化临床科学家修订后的 K24 应用程序通过将神经心脏信号传导的新模型（称为压力感受反射 [BAR] 模型）转化为 AUD 的行为干预来解决这一差距。研究目标是根据她支持 BAR 作为主动行为改变机制的基础研究来完善和测试干预措施。影响 BAR 机制的干预措施会增加大脑和心血管系统之间的反馈。 K24 的总体假设是，增强 BAR 功能将增加对酒精的行为灵活性，减少饮酒、预防复发、减少抑郁和其他积极的心理社会结果就证明了这一点。第一个具体目标是使用四项正在进行的临床试验的数据来评估两种已建立的干预措施（有氧运动、冥想）和一种新的干预措施（心率变异性生物反馈）的效果，并确定 BAR 是否是每种干预措施中的常见作用机制。第二个目的是检查治疗反应者与无反应者相比是否表现出不同的神经连接模式。第三个探索性目标是利用临床、心血管和神经指标建立预后模型，以预测哪些人最有可能从针对 BAR 机制的干预措施中受益。还将探讨遗传指标是否可以改善预测。职业发展目标是将候选人以患者为导向的研究项目从早期临床转化到后期临床转化。培训目的是获得随机临床试验的设计、实施和分析方面的专业知识，使用神经影像和神经心脏工具来区分治疗反应者与无反应者，以及应用非线性敏感性和不确定性分析来建立多层次的模型预后模型。拟议的研究和职业发展战略将为五名正在崛起的初级教师和一名在转化临床科学、情绪调节和酒精使用障碍方面有共同兴趣的研究生提供独特的培训机会。学员为团队带来了情绪失调和人际暴力的临床精神病理学、心理生理学和运动科学、神经影像学和遗传学方面的独特背景和合作。研究和培训里程碑的实现将通过年度会议演讲、同行评审出版物和以患者为导向的研究拨款提交来正式衡量。