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

说明（由申请人提供）：本申请是申请“指导研究科学家发展奖”（K01）。候选人Robert Leeman博士对高风险酒精使用和自我控制困难有着程序性的兴趣，特别是对年轻人的兴趣。作为耶鲁大学的一名初级教员，Leeman博士的目标是获得在酒精研究领域成为一名独立科学家的技能。培训和研究计划包括Stephanie O'Malley博士，精神病学教授，耶鲁大学酒精中毒转化神经科学中心（CTNA）药物滥用研究部门主任和临床核心主任，以及Marc Potenza医学博士，精神病学和儿童研究中心副教授，耶鲁大学冲动和冲动控制障碍研究项目主任。这些导师和顾问都在各自的领域享有国际声誉，他们将协助Leeman博士完成他的培训目标，完成研究计划中详细的项目，并帮助他成为一名独立的研究人员。Leeman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，以模拟潜在变量并分析前瞻性数据。第二个训练目标是更多地了解与特征和酒精诱导的去抑制有关的神经回路，以及典型酒精中毒的神经回路的长期改变。研究计划包括三个相互关联的研究，这与Leeman博士对酒精使用和自我控制的兴趣有关，并将使他能够应用从奖项中提出的培训中获得的知识：1)测试结构方程模型，以评估特征解除抑制、酒精解除抑制效果的预期和对酒精使用的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断面预测因子；2)在一项纳曲酮和BASICS咨询减少年轻人大量饮酒的临床试验中，二级数据分析以检验对酒精使用的去抑制预期和控制受损作为结果的中介；3)开发和验证人类酒精自我给药范式，旨在模拟对酒精使用的控制受损。拟议的酒精自我管理范式需要对无视受控饮酒指南的非适度饮酒提供抑制措施。这项提议的研究有可能让我们了解各种自我控制困难导致高风险饮酒的方式。拟议研究的结果将为Leeman博士在奖励期间完成的R01申请提供初步数据。完成拟议的培训和研究将使他能够过渡到独立的研究者，完成该奖项，并为他的长期职业目标奠定基础。

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.