ABCD-USA: NYC Research Project

 描述(由申请人提供)：青春期是神经发育的关键时期，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，因为正在进行的成熟期物质使用的影响可能会对大脑功能和行为、健康和心理结果产生长期影响。来自威尔康奈尔医学院和西奈山的这项研究项目现场申请是为了响应ABCD-USA财团(7/13)的RFA-DA-15-015，以前瞻性地确定儿童和青少年使用药物的神经发育和行为预测因素和后果。将招募1,100名9-10岁儿童的具有代表性的社区样本，以丰富其高危特征，为从ABCD-USA联盟的1个中心收集的11,111名样本做出贡献。所有参与者将每两年接受一次全面的基线评估，包括最先进的脑成像、全面的神经心理测试、生物测试、移动监测和对物质使用、环境、精神病理症状和社会功能的仔细评估。临时年度访谈和基于网络的季度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细化时间解决方案。在本项目过程中获得的这些联盟范围内的数据将阐明：1)物质使用模式的影响 这些研究包括：1)对青少年大脑的影响；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“门户相互作用”。这项纽约站点研究项目关注的是青少年大脑和行为发育中物质使用的风险和结果。我们的理论和经验基础上的目标建立在威尔康奈尔山集体专业知识的基础上。西奈大学、哥伦比亚大学和康奈尔理工大学在青少年大脑发育、成瘾大脑电路和移动技术方面的研究，以评估物质使用和健康。这三个目标是：1)根据青春期的不平衡模型，研究前额叶和皮质下区域的发育不匹配如何与药物使用的开始和频率有关；2)根据成瘾的反应抑制和显著归因(IRSA)模型，研究物质滥用如何影响抑制控制和动机过程中涉及的前额叶和皮质下的发展；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，填补从小鼠到人类的翻译空白，对于预防和治疗物质使用障碍具有潜在的治疗意义。

 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.