fMRI and Cognition in Youth at Risk for Alcoholism

描述(由申请人提供)：相关性：酒精和其他药物的使用在美国青少年中很常见。我们先前的研究发现，患有酒精使用障碍(AUD)的青少年在脑功能指标上表现出异常，包括神经心理测试、海马体体积和对认知任务的功能磁共振成像(FMRI)反应。我们还发现，这些指标中的一些指标与青少年酗酒的风险因素有关。因此，目前尚不清楚在患有AUD的青少年中观察到的异常是由酒精暴露引起的，还是在开始大量饮酒之前。描述：该更新项目将遵循R01 AA13419第一个资助期中最初描述的青年。在基线上，这些年轻人是12-14岁的年轻人，平均只有一次酒精使用经历，没有任何精神障碍，其中一半根据酒精依赖家族史有患AUD的风险。基线评估包括神经心理测试、高分辨率磁共振成像，以及在空间工作记忆和抑制任务中的功能磁共振成像获得。在这次竞争性的更新中，我们将把基线样本从128名青少年扩大到285名青少年，并每季度跟踪这些青少年进行关于药物使用和一般功能的访谈。每个开始大量饮酒的受试者(定义为在一个月内饮酒5次)，以及年龄、性别和家族史状况相匹配的非饮酒者，将被邀请在为期5年的项目期间每年重复该方案。根据我们招募的学区(A/=5420)的调查，我们预计20%(n&gt；50)的人会开始大量饮酒，50%(n&gt；125)的人将在4年内(即到16-18岁)保持不饮酒。目的：本研究的目的是确定在大量饮酒开始后，大脑功能指标(即神经心理测试；海马体、前额叶皮质和小脑体积；以及对空间工作记忆和前额顶区抑制任务的功能磁共振反应)是否发生了与正常青少年神经发育不同的程度的变化。我们假设，在青春期开始大量饮酒将与大脑结构和功能的变化有关，并且AUD和性别的家族史将调节这种关系。其他物质的使用(大麻和尼古丁)和其他导致SUD的风险因素(外化行为、对酒精的反应水平和酒精预期)将被评估为大脑功能变化的潜在贡献者。基于我们之前的研究，我们进一步假设，基线大脑反应模式将显著预测下一年的物质参与。

DESCRIPTION (provided by applicant): Relevance: Alcohol and other drug use are common among U.S. adolescents. Our prior studies found that adolescents with alcohol use disorders (AUD) show abnormalities on indices .of brain functioning, including neuropsychological testing, hippocampal volume, and functional magnetic resonance imaging (FMRI) response to cognitive tasks. We also found abnormalities on some of these measures related to risk factors for adolescent alcohol involvement. Thus, it is unclear if abnormalities observed in adolescents with AUD are caused by alcohol exposure, or predated the onset of heavy drinking. Description: This renewal project will follow youth initially characterized in the first funding period of R01 AA13419. At baseline, these youth are 12-14 year-olds free from any psychiatric disorder with, on average, one alcohol use experience, and half are at risk for AUD based on a family history of alcohol dependence. Baseline assessment includes neuropsychological testing, high resolution MRI, and FMRI acquisition during spatial working memory and inhibition tasks. In this competing renewal, we will expand the baseline sample from 128 to 285 youth, and follow these adolescents quarterly with interviews on substance use and general functioning. Each subject who initiates heavy drinking (defined as consuming >5 drinks on an occasion >5 times in a month), as well as a non-user matched for age, gender, and family history status, will be invited back to repeat the protocol on an annual basis for the duration of the 5-year project. Based on surveys in the school districts we recruit from (A/=5420), we anticipate that >20% (n>50) will initiate heavy drinking and 50% (n>125) will remain non-users as of the 4-year follow-up (i.e., by age 16-18). Aims: The goal of this study is to ascertain if indices of brain functioning (i.e., neuropsychological testing; hippocampal, prefrontal cortex, and cerebellar volumes; and FMRI response to spatial working memory and inhibition tasks in prefrontal and parietal regions) change after the onset of heavy drinking to a different degree than would be accounted for by normal adolescent neurodevelopment. We hypothesize that initiation of heavy drinking during adolescence will be associated with changes in brain structure and function, and that family history of AUD and gender will moderate this relationship. Other substance use (marijuana and nicotine) and other risk factors for SUD (externalizing behaviors, level of response to alcohol, and alcohol expectancies) will be evaluated as potential contributors to change in brain functioning. Based on our previous studies, we further hypothesize that baseline brain response patterns will significantly predict substance involvement in the following year.