THE BAROREFLEX MECHANISM: TRANSLATION TO AUD TREATMENT AND PROGNOSTIC MODELS

描述（由申请人提供）：100多年来，人们已经知道大脑和心脏在思想、情感和行为中双向交流的重要性，但这一知识对酒精使用障碍（AUD）的治疗几乎没有影响。这项由一位职业生涯中期的转化临床科学家提出的K24修正应用，通过将一种新的神经心脏信号模型（称为barreflex [BAR]模型）转化为aud的行为干预，解决了这一空白。研究目标是基于她支持BAR作为一种积极的行为改变机制的基础研究来完善和测试干预措施。影响BAR机制的干预措施增加了大脑和心血管系统之间的反馈。本K24的首要假设是，增强BAR功能将增加对酒精的行为灵活性，这可以通过减少饮酒、预防复发、减少抑郁和其他积极的社会心理结果来证明。第一个具体目标是使用四个正在进行的临床试验的数据来评估两种已建立的（有氧运动，冥想）和一种新的（心率变异性生物反馈）干预措施的疗效，并确定BAR是否是每种干预措施的共同作用机制。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。是否遗传指标可以提高预测也将探讨职业发展目标是移动候选人的病人为导向的研究项目从早期到后期临床翻译。培训目标是获得随机临床试验的设计、实施和分析方面的专业知识，使用神经影像学和神经心脏工具来区分治疗反应者和无反应者，以及应用非线性敏感性和不确定性分析来建立多层次预后模型。拟议的研究和职业发展战略将为五名正在上升的初级教师和一名研究生提供独特的培训机会，他们在转化临床科学、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为团队带来了独特的背景和合作。研究和培训里程碑的实现将从年度会议报告、同行评审出版物和以患者为导向的研究资助提交中正式衡量。

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.