Brain-Behavior Reactivity to Threat and Alcohol Abuse Risk in Young Adults

年轻人对威胁和酒精滥用风险的大脑行为反应

• 批准号: 9314793
• 负责人: Stephanie Gorka
• 金额: $ 19.24万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9314793
• 关键词: Acute; Address; Adult; Affect; Affective; Age; Alcohol abuse; Alcohol consumption; Alcoholic Intoxication; Alcoholism; Anxiety; Area; Award; Behavior; Behavioral; Behavioral Mechanisms; Biometry; Blinking; Brain; Clinical; Cognitive; Cohort Studies; Communities; Coupled; Data; Detection; Development; Early Diagnosis; Enrollment; Exhibits; Family history of; First Degree Relative; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Human; Individual; Individual Differences; Intervention; Knowledge; Laboratories; Laboratory Study; Link; Longitudinal Studies; Measures; Mediating; Mentors; Modality; Modeling; Monitor; Neurobiology; Neurosciences; Outcome; Participant; Phenotype; Prevention; Prevention strategy; Preventive Intervention; Preventive treatment; Process; Recruitment Activity; Research; Research Design; Rewards; Risk; Risk Factors; Role; Sampling; Scientist; Source; Specificity; Stress; Testing; Training; Work; Youth; alcohol risk; alcohol use disorder; base; biobehavior; brain behavior; brain dysfunction; career; design; drinking; drinking behavior; emerging adult; emerging adulthood; follow-up; high risk; improved; indexing; innovation; network dysfunction; novel; prospective; relating to nervous system; response; skills; translational neuroscience; treatment strategy; young adult

Problematic alcohol use emerges early and poses tremendous burden. There is an urgent need to understand who is vulnerable, and why, to facilitate accurate detection, prevention, and treatment. To address this critical issue, a more precise mechanistic understanding of behavioral-brain risk is needed. Data from my graduate research suggests that one source of risk for problematic alcohol use may be heightened reactivity to uncertain threat (U-threat), meaning threat that is ambiguous, temporally unpredictable or uncertain in its intensity. To date, however, no study has directly tested whether reactivity to U-threat functions as a risk factor. The neural processes that mediate this potential source of risk are also unknown; although, there is evidence to suggest that a coordinated frontolimbic circuit, referred to as the Anticipatory Anxiety Network (AAN), modulates U-threat responding. Given that establishing a validated biobehavioral risk model, and elucidating mechanisms underlying excessive alcohol use, has the potential to significantly improve clinical efforts, the proposed study combines behavioral and neural measures, with a prospective design, to test whether reactivity to U-threat is a phenotypic risk factor for problematic alcohol use. This study will enroll 150 healthy, emerging adults, ages 17-19, prior to the onset of alcohol use problems and assess their behavioral (i.e., startle eyeblink) and neural (i.e., functional magnetic resonance imaging [fMRI]) reactivity to U-threat as indices of potential risk. All individuals will subsequently be tracked every 3 mos. for 1-2 years to ascertain onset of problematic alcohol use and escalation in drinking behaviors. Data from this project will allow for an innovative and well-controlled test of whether behavioral reactivity to U-threat is associated with AAN dysfunction (Aim 1), and whether it is a risk factor for problematic alcohol use that is mediated by AAN functioning (Aim 2). In addition, the current study will test the discriminative validity of reactivity to U-threat as a risk factor by also examining whether behavioral and neural reactivity to uncertain rewards (U-reward), which similarly elicit anticipation, is also a risk phenotype for problematic alcohol use (Aim 3). This study concurrently provides an excellent opportunity to receive mentor-directed, hands-on training in several key areas necessary to refine my knowledge and skill-sets. Specifically, I propose a training plan that will focus on three new domains: 1) advanced cognitive behavioral neuroscience and task development; 2) behavioral and subjective laboratory assessments in the context of a longitudinal study design with young adults; and 3) biostatistics. This study coupled with completion of the training goals will effectively propel me towards my long-term goal of an independent career in the translational neuroscience of alcoholism, and will lay the foundation for several future, high- impact R01 studies focused on the prevention and intervention of alcohol use disorder.

有问题的饮酒较早出现，并造成了巨大的负担。迫切需要 了解谁脆弱，为什么要促进准确的检测，预防和治疗。到 解决这个关键问题，需要对行为 - 脑风险的更精确的机械理解。 我的研究生研究的数据表明，饮酒有问题的风险来源可能是 对不确定威胁的反应性提高（U威胁），这意味着威胁模棱两可，在时间上 其强度不可预测或不确定。然而，迄今为止，尚未直接测试反应性是否 为了成为危险因素。调解这种潜在风险来源的神经过程也是 未知;虽然，有证据表明，协调的额叶额回路被称为 预期性焦虑网络（AAN）调节U威胁的反应。鉴于建立经过验证的 生物行为风险模型和阐明过度酒精使用的机制具有潜力 为了显着改善临床努力，拟议的研究将行为和神经措施与 一种前瞻性设计，以测试对U-Theat的反应性是否是有问题酒精的表型风险因素 使用。这项研究将在17-19岁的17-19岁的健康成年人中注册150名健康的成年人 问题并评估其行为（即惊吓eyeblink）和神经（即功能性磁共振） 成像[fMRI]）对U-Traineat的反应性，作为潜在风险的指数。随后将跟踪所有个人 每3个月。 1 - 2年以确定有问题的酒精使用和饮酒升级的发作 行为。该项目的数据将允许对行为的创新且控制良好的测试 对U-Theat的反应性与AAN功能障碍有关（AIM 1），以及它是否是危险因素 有问题的饮酒是由AAN功能介导的（AIM 2）。此外，当前的研究将测试 反应性对U-Theat的反应性作为危险因素的歧视有效性还通过研究行为和是否是否 对不确定奖励的神经反应性（u-reward）类似地引起了人们的预期，也是一种风险表型 对于饮酒有问题（AIM 3）。这项研究同时提供了一个绝佳的机会 指导指导的，在几个关键领域进行的动手培训，以完善我的知识和技能。 具体来说，我提出了一个培训计划，该计划将重点关注三个新领域：1）高级认知 行为神经科学和任务发展； 2）行为和主观实验室评估 与年轻人的纵向研究设计的背景； 3）生物统计学。这项研究与 完成培训目标将有效地推动我实现独立的长期目标 酗酒的转化神经科学的职业，将为几个未来的高级，高级 影响R01研究的重点是预防酒精使用障碍。