Neurodevelopmental Maturation and Alcohol Use in Adolescents

描述(申请人提供)：本R21申请，回应RFA-AA-07-006，建议启动一个项目，以确定酒精暴露对青春期发育中的大脑的影响。这项研究检查了青春期活跃发育的大脑区域，这些区域涉及心理调节、对奖励的反应，被认为容易因酒精暴露而发育不成熟，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、招募和筛选具有代表性的社区样本，并分层选择160名12至15岁的青少年。科目分层将以年龄、性别和种族为基础。很大一部分样本将在开始饮酒之前被招募，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心理调节和对奖励反应的结构和回路，包括前额叶皮质、杏仁核、海马体和腹侧纹状体，以及相关的白质。该项目将具体研究通过扩散张量成像(DTI)服务于额叶皮质的白质区域的组织，通过功能磁共振成像(FMRI)在任务中激活前额叶和杏仁核，涉及到对充满情感的面孔的情绪反应，在反眼跳任务中对需要抑制潜在眼球运动反应的任务的区域激活，以及对系统性不同的奖赏偶发事件的反应。测量的心理失调概念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与心理调节障碍和父母酒精使用障碍的行为指标系统地和显著相关。预计这些数据将在一项更大的研究中使用，我们预测这些神经结构和神经回路的成熟将受到青少年酒精暴露的不利影响。这项研究还将考虑环境和遗传因素。除了人口统计特征外，考虑的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。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、心理障碍和AUD风险之间的关系。除了为酒精暴露对青少年大脑发育的影响进行最终研究提供初始队列外，R21项目还将促进招募程序的完善，并将收集统计能力计算和样本量估计所需的数据。 项目简介：这个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。这项研究将对160名具有代表性的青少年进行加速纵向设计，调查年龄在12岁到18岁之间。已知的参与心理调节和奖赏反应的神经回路被假设为特别容易受到酒精影响，并将通过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.