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: 8581593
• 负责人: MARSHA E. BATES
• 金额: $ 16.69万
• 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/8581593
• 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; DNA; Data; Disease remission; Drug Use Disorder; Emotional; Emotions; Ensure; Exercise; Faculty; Feedback; Foundations; Genes; Genetic; Genetic Polymorphism; Genomics; 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(申请人提供)：大脑和心脏之间的双向沟通在思想、情绪和行为中的关键重要性已经被知道了100多年，但这一知识对酒精使用障碍(AUD)的治疗几乎没有影响。这项由职业生涯中期的翻译临床科学家修订的K24应用程序通过将一种新的神经心脏信号模型(称为压力感受器反射[BAR]模型)转化为对AUD的行为干预来解决这一缺口。研究目标是在她的基础研究的基础上提炼和测试干预措施，支持BAR作为一种积极的行为改变机制。影响BAR机制的干预措施增加了大脑和心血管系统之间的反馈。K24的主要假设是，增强酒吧功能将增加对酒精的行为灵活性，这体现在减少饮酒、预防复发、减少抑郁和其他积极的心理社会结果。第一个具体目标是使用来自四个正在进行的临床试验的数据来评估两个已建立的(有氧运动、冥想)和一个新的(心率变异性生物反馈)干预的有效性，并确定BAR是否是每个干预的共同作用机制。第二个目标是检查治疗应答者与无反应者是否表现出不同的神经连接模式。第三个探索性目标是使用临床、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机制的干预中受益。是否遗传指标可以提高预测也将被探索，职业发展目标是将候选人的以患者为中心的研究计划从早期临床翻译转移到晚期临床翻译。培训的目的是获得以下方面的专业知识：设计、实施和分析随机临床试验，使用神经成像和神经心脏工具区分治疗有效和无效，以及应用非线性敏感性和不确定性分析建立多水平预后模型。拟议的研究和职业发展战略将为五名正在崛起的初级教员和一名研究生提供一个独特的培训机会，他们在翻译临床科学、情绪调节和酒精使用障碍方面有共同的兴趣。学员们为团队带来了独特的背景和在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、神经成像和遗传学方面的合作。研究和培训里程碑的实现将通过每年的会议报告、同行评审的出版物和以患者为导向的研究拨款申请来正式衡量。