Difficulties with Self-Control and High-Risk Alcohol Use in Young Adults

简介(申请人提供)：本申请表为“导师研究科学家发展奖”(K01)。候选人罗伯特·利曼(Robert Leeman)博士对高风险饮酒和自我控制困难有规划上的兴趣，对年轻成年人尤其感兴趣。作为耶鲁大学的初级教员，利曼博士的目标是掌握技能，发展成为酒精研究领域的独立科学家。该培训和研究计划得到了精神病学教授、耶鲁大学酒精中毒转化神经科学中心(CTNA)药物滥用研究部主任和临床核心斯蒂芬妮·奥马利博士和精神病学和儿童研究中心副教授、耶鲁大学冲动和脉冲控制障碍研究项目主任马克·庞滕扎博士的指导和合作。这些导师和顾问都在各自领域享有国际声誉，他们将协助利曼博士完成他的培训目标，完成研究计划中详细列出的项目，并帮助他成为一名独立研究人员。利曼博士对K01的主要培训目标是1)提高他进行酒精管理研究的技能，2)发展数据分析技术的专业技能，为潜在变量建模和分析预期数据。第二个训练目标是更多地了解与特质和酒精诱导的去抑制有关的神经回路，以及酒精中毒的典型神经回路的长期变化。研究计划包括三项与利曼博士在饮酒和自我控制方面的兴趣有关的相关研究，并将使他能够应用从该奖项建议的培训中获得的知识：1)测试结构方程模型，以评估特质去抑制、酒精去抑制效果的预期和酒精使用控制受损之间的关联，并评估这些结构作为高风险饮酒的横截面预测因素；2)二次数据分析，在纳曲酮和基础咨询减少年轻人大量饮酒的临床试验中，测试去抑制期望值和酒精使用控制受损作为结果的中介；3)开发和验证人类酒精自我管理范式，旨在模拟酒精使用控制受损。拟议的酒精自我管理范例需要为无视受控饮酒指南的非中度酒精使用提供抑制。这项拟议的研究有可能让我们了解自控方面的各种困难是如何导致高风险饮酒的。拟议研究的结果将为Leeman博士在获奖期间完成的R01申请提供初步数据。完成拟议的培训和研究将使他能够在完成这一奖项后过渡到作为一名调查员的独立，并为他的长期职业目标奠定基础。 公共卫生相关性：年轻人大量饮酒是一个重大的公共卫生问题。该奖项的候选人要求接受培训，并提出一项研究计划，以期作为一名研究人员走向独立，重点关注年轻人酗酒和酒精相关问题的风险因素和潜在机制。对风险因素和潜在机制的了解可以为减少这一人群中大量饮酒和与酒精相关的问题的干预方法提供依据。

DESCRIPTION (provided by applicant): This application is for a "Mentored Research Scientist Development Award" (K01). The candidate, Robert Leeman, Ph.D., has a programmatic interest in high-risk alcohol use and difficulties with self-control, with a particular interest in the young adult population. Dr. Leeman aims, as a junior faculty member at Yale, to acquire skills to develop into an independent scientist in the field of alcohol research. The training and research plan enlists the mentorship and collaboration of Stephanie O'Malley, Ph.D., Professor of Psychiatry, the Director of the Division of Substance Abuse Research and the Clinical Core of the Yale Center for the Translational Neuroscience of Alcoholism (CTNA) and Marc Potenza, M.D., Ph.D., Associate Professor of Psychiatry and the Child Study Center and Director of the Yale Program for Research on Impulsivity and Impulse Control Disorders. The mentors-along with consultants, all of whom have international reputations in their fields-will assist Dr. Leeman in accomplishing his training goals, in completing the projects detailed in the research plan and in his progression toward becoming an independent researcher. Dr. Leeman's primary training goals for the K01 are 1) to enhance his skills in conducting alcohol administration research and 2) to develop specialized skills in data analytic techniques to model latent variables and to analyze prospective data. A secondary training goal is to learn more about the neurocircuitry implicated in trait and alcohol-induced disinhibition as well as the long-term alterations of neurocircuitry that typify alcoholism. The Research Plan consists of three interrelated studies that relate to Dr. Leeman's interests in alcohol use and self-control and will allow him to apply knowledge gained from the training proposed in the award: 1) testing structural equation models to assess associations among trait disinhibition, expectancies of alcohol's disinhibiting effects and impaired control over alcohol use and to assess these constructs as cross-sectional predictors of high-risk drinking; 2) a secondary data analysis to test disinhibition expectancies and impaired control over alcohol use as mediators of outcome in a clinical trial of naltrexone and BASICS counseling for heavy drinking reduction in young adults and 3) development and validation of a human alcohol self-administration paradigm designed to model impaired control over alcohol use. The proposed alcohol self-administration paradigm entails provision of disincentives for non-moderate alcohol use that disregards a controlled drinking guideline. The proposed research has the potential to inform our understanding of the ways in which various difficulties with self-control contribute to high-risk drinking. Results from the proposed research will provide preliminary data for an R01 application to be completed by Dr. Leeman during the award period. Completion of the proposed training and research would allow him to transition to independence as an investigator by the completion of this award and lay the groundwork for his long-term career goals. PUBLIC HEALTH RELEVANCE: Young adult heavy drinking is a significant public health concern. The candidate for this award requests training and proposes a research plan to progress toward independence as an investigator with focus on risk factors for and mechanisms underlying heavy drinking and alcohol-related problems in young adults. Knowledge about risk factors and underlying mechanisms can inform intervention approaches to reduce heavy drinking and alcohol-related problems in this population.