Consequences of Adolescent Alcohol Use on Brain Development

描述(由申请人提供)：本修订的R01 A1提案(AA022493)“青少年饮酒对大脑发育的影响”，回应了了解开始饮酒对青少年大脑成熟的影响的需要。我们与青少年物质滥用研究中心(Ceasar)和波士顿儿童医院合作实施了一项创新战略，该战略结合了多种神经成像和神经心理学方法，以确定与青春期早期和不断增加的酒精使用有关的神经发育脆弱性。青少年将从普通儿科医生办公室和青少年医学诊所招募，这些诊所包括新英格兰药物滥用研究伙伴关系(NEPSAR)，这是初级保健办公室的一个以实践为基础的研究网络。青少年将在开始使用酒精或其他药物之前参加这项研究，并在基线(13-14岁)和两次年度随访时进行纵向检查。为了提供全面的脑功能纵向图像，结构磁共振成像(MRI)、扩散张量成像(DTI)以及任务和静息状态下的血氧水平依赖(BOLD)功能磁共振成像(FMRI)将与磁共振波谱(MRS)配合使用，以测量前扣带回皮质(ACC)和内侧颞叶(MTL，包含海马)的GABA和谷氨酸水平。此外，动脉自旋标记(ASL)将被用来测量定量灌注，这将被用来校准在反应抑制和空间记忆fMRI任务中BOLD fMRI信号变化的幅度。磁共振测量将与临床评估和广泛的神经心理单元的测量相结合，旨在检测和进一步表征发育变化和青少年饮酒的影响。脑功能和神经可塑性的多模式互补测量的结合可以为大脑成熟的动态过程提供有价值的见解，并有助于识别与酒精使用的开始和升级相关的神经特征，这将为旨在减少青少年酒精消费的预防和干预工作提供信息基础。

DESCRIPTION (provided by applicant): This revised R01 A1 proposal (AA022493), "Consequences of Adolescent Alcohol Use on Brain Development", responds to the need to understand the impact of initiating alcohol consumption on adolescent brain maturation. We have teamed with the Center for Adolescent Substance Abuse Research (CeASAR) and Boston Children's Hospital to implement an innovative strategy that combines multiple neuroimaging and neuropsychological approaches to identify neurodevelopmental vulnerabilities associated with early and escalating alcohol use during adolescence. Adolescents will be recruited from general pediatrician offices and adolescent medicine clinics comprising the New England Partnership for Substance Abuse Research (NEPSAR), a practice-based research network of primary care offices. Adolescents will be enrolled into the study prior to the initiation of alcoho use or other drug use, and examined longitudinally, at baseline (13-14 yrs old) and again at two annual follow-up visits. To provide a comprehensive longitudinal profile of brain function, structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and task and resting state blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) will be paired with magnetic resonance spectroscopy (MRS) to measure GABA and glutamate levels in the anterior cingulate cortex (ACC) and medial temporal lobe (MTL, containing hippocampus). In addition, arterial spin labeling (ASL) will be used to measure quantitative perfusion, which will be used to calibrate the magnitude of BOLD fMRI signal changes during response inhibition and spatial memory fMRI tasks. Magnetic resonance measures will be integrated with measures from clinical assessments and an extensive neuropsychological battery, designed to detect and further characterize developmental changes and the influence of adolescent alcohol use. The incorporation of complementary multi-modal measures of brain function and neuroplasticity could offer valuable insight into the dynamic processes of brain maturation and help identify neural signatures associated with the onset and escalation of alcohol use, which will provide a foundation for informing prevention and intervention efforts aimed at reducing adolescent alcohol consumption.