ABCD-USA Consortium: 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，与药物使用率的急剧增加有关。确定药物使用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药物使用的影响可能对大脑功能以及行为、健康和心理结果产生长期影响。本研究项目网站申请来自加州大学圣地亚哥分校和劳瑞德脑研究所，是响应RFA-DA-15-015作为ABCD-USA联盟的一部分（5/13），旨在前瞻性地确定儿童和青少年药物使用的神经发育和行为预测因素及其后果。将招募1086名具有高风险特征的9-10岁儿童的代表性社区样本，为从ABCD- USA联盟的11个中心收集的11,111名样本做出贡献。所有参与者将接受全面的基线评估，包括最先进的脑成像、综合神经心理测试、生物测定、移动监测和每2年对物质使用、环境、精神病理症状和社会功能的仔细评估。中期年度访谈和季度网络评估将在参与者负担最小的情况下，为行为、发展和生活事件提供精确的时间解决方案。在该项目过程中获得的这些全联盟范围的数据将阐明：1)物质使用模式对青少年大脑的影响；2)药物使用对行为和健康结果的影响；3)精神病理与物质使用方式的双向关系；4)个体遗传、行为、神经生物学和环境差异对风险概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”。该中心的研究项目侧重于物质使用障碍的机制，高使用率的特殊人群，以及大麻以外药物的使用。(1)我们将确定杏仁核、脑岛和前扣带的反奖励神经加工（即负强化机制）的个体差异是否与负面情绪和疼痛的增加有关，预测药物使用的开始和问题使用，并反过来进一步被药物使用失调。(2)我们将确定保护环境因素和少数民族青少年的民族认同是否与更健康的反奖励加工和更好的物质使用结果有关。(3)我们将确定反奖励神经加工是否预测MJ以外的非法药物的使用增加，包括滥用处方药，这种使用是否预测随后的夸大的反奖励加工，以及物质之间是否存在网关相互作用。最后，我们将使用机器学习方法来开发一个针对年轻人的风险计算器，这将使我们能够识别基于个体的可修改风险因素，为未来新的预防和干预方法提供基于大脑的目标。

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 University of California, San Diego and Laureate Institute for Brain Research is in response to RFA-DA-15-015 as part of the ABCD-USA Consortium (5/13), to prospectively determine the neurodevelopmental and behavioral predictors and consequences of substance use on children and adolescents. A representative community sample of 1086 9-10 year olds enriched for high- risk characteristics will be recruited, contributing to the sample of 11,111 to be collected from 11 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 hub's Research Project focuses on mechanisms of substance use disorder, special populations with high use prevalence, and the use of drugs other than marijuana. (1) We will determine whether individual differences in neural processing of antireward (i.e., negative reinforcement mechanisms) in amygdala, insula, and anterior cingulate are associated with increased negative emotionality and pain, predict initiation of use and problem use, and are in turn further dysregulated by substance use. (2) We will determine whether protective environment factors and ethnic identification in minority youth are linked to healthier antireward processing and better substance use outcomes. (3) We will determine whether antireward neural processing predicts increased use of illicit drugs other than MJ including misuse of prescription drugs, if such use predicts subsequent exaggerated antireward processing, and if gateway interactions exist between substances. Finally, we will use machine learning approaches to develop a youth-specific risk calculator that will enable us to identify individually- based modifiable risk factor, providing brain-based targets of future novel prevention and intervention approaches.