Neurodevelopmental Maturation and Alcohol Use in Adolescents

描述（由申请人提供）：本R21申请是对RFA-AA-07-006的回应，拟启动一个项目，以确定青春期酒精暴露对发育中大脑的影响。该研究检查了在青春期积极发展的大脑区域，涉及心理调节，对奖励的反应，被认为容易受到酒精暴露的发育不良的影响，并使用当代神经成像技术进行评估。将采用加速纵向设计。将确定、招募和筛选一个具有代表性的社区样本，并将选择160名12至15岁青少年的分层样本。将根据年龄、性别和人种对受试者进行分层。在开始使用酒精之前，将招募相当大比例的样本，我们之前使用类似方法进行的纵向研究表明，样本将显示出足够的酒精使用轨迹变异性，以实现研究目标。神经发育评估将侧重于有助于心理调节和奖励反应的结构和回路，包括前额叶皮层、杏仁核、海马体和腹侧纹状体，以及相关的白色脑。该项目将专门研究的白色物质的组织服务于额叶皮层的扩散张量成像（DTI），前额叶和杏仁核激活功能磁共振成像（fMRI）在任务涉及情感负载的面孔，区域激活的任务，需要抑制在一个反眼跳任务中的优势眼反应，并响应系统变化的奖励意外事件的情绪反应。测量的心理失调结构将包括行为控制不足，消极情绪和执行认知功能。我们假设，神经发育成熟指标将系统和显着相关的心理失调和父母酒精使用障碍的行为指标。预计利用这些数据在一个更大的研究，我们预测，这些神经结构和电路的成熟将受到不良影响，青少年酒精暴露。这项研究还将考虑环境和遗传因素。除了人口统计学特征外，环境影响还包括父母参与、创伤经历和邻里环境。该项目将收集DNA用于研究与神经生物学内表型和酒精参与轨迹相关的遗传多态性。R21数据收集将提供足够的数据来确定青春期早期神经发育成熟、心理失调和AUD风险之间的关系。除了为关于酒精暴露对青少年大脑发育影响的确定性研究提供初始队列外，R21项目还将促进招募程序的完善，并将收集统计功效计算和样本量估计所需的数据。 R21项目将启动一项研究，以确定酒精暴露对青少年大脑发育的影响。该研究将涉及160名青少年的代表性样本，采用加速纵向设计，检查12至18岁的青少年。已知参与心理调节和奖励反应的神经回路被假设为特别容易受到酒精的影响，并将用创新的神经成像方法进行评估。

DESCRIPTION (provided by applicant): This R21 application, in response to RFA-AA-07-006, proposes to initiate a project to determine the effects of alcohol exposure on the developing brain during adolescence. The study examines brain areas that are actively developing during adolescence, involved in psychological regulation, response to rewards, thought to be vulnerable to dysmaturation by alcohol exposure, and evaluate with contemporary neuroimaging techniques. An accelerated longitudinal design will be utilized. A representative community sample will be identified, recruited and screened, and a stratified sample of 160 adolescents ages 12 through 15 years old will be selected. Subject stratification will be based on age, gender and race. A substantial proportion of the sample will be recruited prior to the initiation of alcohol use, and our prior longitudinal study using similar methods indicates that the sample will show sufficient variability in alcohol use trajectories for the study aims to be fulfilled. The neurodevelopmental evaluation will focus on structures and circuits subserving psychological regulation and responses to rewards, including the prefrontal cortex, amygdala, hippocampus and ventral striatum, as well as associated white mater. The project will specifically examine the organization of white matter areas serving the frontal cortex by diffusion tensor imaging (DTI), prefrontal and amygdalar activation by functional magnetic resonance imaging (fMRI) during tasks involving emotional responses to affectively-laden faces, regional activation to a task requiring inhibition of pre-potent oculomotor responses in an anti-saccade task, and responses to systematically varied reward contingencies. Psychological dysregulation constructs measured will include behavioral undercontrol, negative emotionality, and executive cognitive functioning. We hypothesize that neurodevelopmental maturation indicators will be systematically and significantly correlated to behavioral indicators of psychological dysregulation and parental alcohol use disorders. Anticipating the utilization of these data in a larger study, we predict that the maturation of these neural structures and circuits will be adversely affected by adolescent alcohol exposure. The study will also consider environmental and genetic factors. In addition to demographic characteristics, environmental influences considered will include parent involvement, traumatic experiences, and neighborhood context. The project will collect DNA for studies of genetic polymorphisms associated with neurobiological endophenotypes and alcohol involvement trajectories. The R21 data collection will provide sufficient data to determine relationships among neurodevelopmental maturation in early adolescence, psychological dysregulaiton and AUD risk. In addition to providing the initial cohorts for a definitive study on the effects of alcohol exposure on adolescent brain development, the R21 project will facilitate the refinement of recruitment procedures and will collect data needed for statistical power calculations and sample size estimates. Project Narrative: This R21 project will initiate a study to determine the effects of alcohol exposure on adolescent brain development. The study will involve a representative sample of 160 adolescents in an accelerated longitudinal design examining ages 12 through 18 years. Neural circuits known to be involved in psychological regulation and reward responses are hypothesized to be particularly vulnerable to alcohol effects and will be assessed with innovative neuroimaging methods.