National Consortium on Alcohol and NeuroDevelopment in Adolescence: San Diego

描述(由申请人提供)：为响应RFA-AA-12-006，本申请提出国家青少年酒精与神经发育联盟(N-Canda)的加州大学圣迭戈分校研究部分，以确定酒精使用对青少年大脑发育的影响。招募年龄在12岁至21岁之间的高风险增强型社区样本170名圣地亚哥受试者(来自所有4个地点的N=680人)将完成基线评估，并以加速纵向设计接受三次年度跟踪评估。在每次就诊时，将测量多模式磁共振成像(MRI)方案、全面的神经心理学组合、酒精和其他物质使用及相关问题的评估、精神健康症状学以及物质使用障碍的风险因素。脑成像包括最先进的高分辨率结构磁共振成像(SMRI)、扩散张量成像(DTI)和静息状态磁共振成像(RsMRI)。对酒精后果的研究将集中在大脑区域的结构和功能成熟上，这些区域在青春期活跃发展，参与心理调节，对奖励做出反应，并似乎容易受到酒精的神经毒性影响。此外，我们的研究部分还将合作进行另外两项研究。首先，我们将与杜克大学网站合作，研究这些异常的恢复。具体地说，我们将检查在4周的监测戒酒中，与大量饮酒相关的神经认知和大脑完整性缺陷的缓解程度。第二，我们将与SRI国际网站合作研究默认模式网络。特别是，我们将使用Stroop匹配期间的功能连通性分析来采样任务，并结合任务前后获得的休息状态fMRI数据，来检查青少年大量饮酒对默认模式网络完整性的影响，以及这在多大程度上调节认知表现。在风险和基线大脑特征的背景下进行研究，我们将确定酒精暴露对青少年大脑发育轨迹的影响，并确定可能使青少年患酒精使用障碍风险增加的先前存在的心理生物脆弱性。

DESCRIPTION (provided by applicant): In response to RFA-AA-12-006, this application proposes the UCSD Research Component of the National Consortium on Alcohol and Neurodevelopment in Adolescence (N-CANDA) to determine the effects of alcohol use on the developing adolescent brain. Recruited at ages 12 through 21, a high risk enhanced community sample of 170 San Diego subjects (N=680 from all 4 sites) will complete a baseline assessment and undergo three annual follow-up assessments in an accelerated longitudinal design. At each visit, a multimodal magnetic resonance imaging (MRI) protocol, comprehensive neuropsychological battery, and assessments of alcohol and other substance use and related problems, mental health symptomatology, and substance use disorder risk factors will be measured. Brain imaging includes state-of-the-art high-resolution structural MRI (sMRI), diffusion tensor imaging (DTI), and resting state MRI (rsMRI). The examination of alcohol consequences will focus on structural and functional maturation of brain areas that actively develop during adolescence, are involved in psychological regulation, respond to rewards, and appear vulnerable to neurotoxic effects of alcohol. In addition, our Research Component will collaborate on two additional studies. First, we will collaborate with the Duke University site to study recovery of these abnormalities. Specifically, we will examine the degree to which targeted heavy drinking related neurocognitive and brain integrity deficits remit over 4 weeks of monitored abstinence. Second, we will collaborate with the SRI International site to study the default mode network. In particular, we will examine the influence of adolescent heavy drinking on default mode network integrity, and the extent to which this mediates cognitive performance, using functional connectivity analyses during a Stroop Match to Sample task in conjunction with resting state fMRI data acquired both before and after the task. Studied in the context of risks and baseline brain characteristics, we will determine both the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities that may put an adolescent at elevated risk for an alcohol use disorder.