ABCD-USA: NYC Research Project

 描述（由申请人提供）：青春期是一个关键的神经发育时期，与物质使用率的急剧增加有关。确定物质使用的途径及其对儿童和青少年发展的影响至关重要，因为在持续成熟过程中物质使用的影响可能对大脑功能和行为，健康和心理结果产生长期影响。威尔康奈尔医学院和西奈山的这项研究项目研究中心申请是对RFA-DA-15-015的回应，作为ABCD-USA联盟（7/13）的一部分，旨在前瞻性地确定儿童和青少年的神经发育和行为预测因子以及物质使用的后果。将招募1100名9- 10奥尔兹的代表性社区样本，这些儿童富含高风险特征，有助于从ABCD-USA联盟的1个中心收集11，111名样本。所有参与者将接受全面的基线评估，包括最先进的脑成像，全面的神经心理学测试，生物测定，移动的监测和仔细评估物质使用，环境，精神病理学症状和社会功能，每2年一次。中期年度访谈和季度基于网络的评估将以最小的参与者负担提供行为，发展和生活事件的精确时间分辨率。这些在本项目过程中获得的全联盟范围的数据将阐明：1）物质使用模式的影响 青春期的大脑2）物质使用对行为和健康结果的影响; 3）精神病理学和物质使用模式之间的双向关系; 4）个体遗传、行为、神经生物学和环境差异对风险状况和物质使用结果的影响; 5）不同物质使用之间的“网关相互作用”。这个纽约网站研究项目的重点是风险和青少年大脑和行为发展的物质使用的结果。我们的理论和经验为基础的目标建立在威尔康奈尔大学的集体专业知识，山。西奈半岛，哥伦比亚大学和康奈尔理工学院在青少年大脑发育，成瘾大脑电路，和移动的技术评估物质使用和健康。这三个目标是：1）基于青少年的不平衡模型来研究前额叶和皮层下区域的发展的不匹配如何与物质使用的开始和频率相关; 2）基于成瘾的受损反应抑制和显著归因（iRISA）模型来研究物质滥用如何影响前额叶和皮层下区域的发展，这些发展涉及抑制控制和动机过程;以及3）基于显示从基因到电路到行为的垂直整合的敲入小鼠模型，研究内源性大麻素信号传导中的遗传变异如何影响人类物质使用的起始和频率以及潜在的电路发育，填补了从小鼠到人的翻译空白，其对于预防和治疗物质使用障碍具有潜在的治疗相关性。

 DESCRIPTION (provided by applicant): Adolescence is a critical neurodevelopmental period associated with dramatic increases in rates of substance use. Identifying the pathways to substance use and its effects on child and adolescent development is critically important, as the effects of substance use during ongoing maturation likely have long-lasting effects on brain functioning and behavioral, health, and psychological outcomes. This Research Project Site application from the Weill Cornell Medical College and Mount Sinai is in response to RFA-DA-15-015 as part of the ABCD-USA Consortium (7/13), to prospectively determine the neurodevelopmental and behavioral predictors and consequences of substance use on children and adolescents. A representative community sample of 1100 9- 10 year olds enriched for high-risk characteristics will be recruited, contributing to the sample of 11,111 to be collected from 1 hubs across the ABCD-USA Consortium. All participants will undergo a comprehensive baseline assessment, including state-of-the-art brain imaging, comprehensive neuropsychological testing, bioassays, mobile monitoring and careful assessment of substance use, environment, psychopathological symptoms, and social functioning every 2 years. Interim annual interviews and quarterly web-based assessments will provide refined temporal resolution of behaviors, development, and life events with minimal participant burden. These Consortium-wide data obtained during the course of this project will elucidate: 1) the effects of substance use patterns on the adolescent brain; 2) the effects of substance use on behavioral and health outcomes; 3) the bidirectional relationship between psychopathology and substance use patterns; 4) the effects of individual genetic, behavioral, neurobiological, and environmental differences on risk profiles and substance use outcomes; and 5) the "gateway interactions" between use of different substances. This NYC site Research Project focuses on risk for and outcomes of substance use on adolescent brain and behavioral development. Our theoretically and empirically grounded aims build on the collective expertise at Weill Cornell, Mt. Sinai, Columbia University and Cornell Tech in adolescent brain development, addiction brain circuitry, and mobile technology for assessing substance use and health. The three aims are: 1) to examine how mismatches in development of prefrontal and subcortical regions relate to initiation and frequency of substance use based on the Imbalance Model of Adolescence; 2) to examine how substance abuse impacts prefrontal and subcortical development implicated in inhibitory control and motivational processes based on the Impaired Response Inhibition and Salience Attribution (iRISA) Model of Addiction; and 3) to examine how genetic variation in endocannabinoid signaling impacts initiation and frequency of substance use and underlying circuit development in humans, based on a knock-in mouse model that shows vertical integration from gene to circuit to behavior, filling a translational gap from mouse to human of potential therapeutic relevance for prevention and treatment of substance use disorders.