ABCD-USA Consortium: 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。加州大学圣地亚哥分校和桂冠脑研究所的这项研究项目现场申请是为了响应作为ABCD-USA联盟(5/13)的一部分的RFA-DA-15-015，以前瞻性地确定物质使用对儿童和青少年的神经发育和行为预测因素和后果。将招募1086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，并将从ABCD-USA联盟的11个中心收集11,111个样本。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的数据将阐明：1)物质使用模式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概况和物质使用结果的影响；以及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、使用流行率高的特殊人群以及大麻以外的药物的使用。(1)我们将确定杏仁核、脑岛和前扣带回反奖赏(即负强化机制)神经加工的个体差异是否与负性情绪和疼痛的增加有关，预测开始使用和问题使用，并反过来进一步受到物质使用的失调。(2)我们将确定少数民族青年中的保护性环境因素和种族认同是否与更健康的反奖励处理和更好的药物使用结果有关。(3)我们将确定抗奖赏神经加工是否预测了除MJ以外的非法药物使用的增加，包括滥用处方药，如果这种使用预测了随后夸大的反奖赏加工，以及物质之间是否存在门户相互作用。最后，我们将使用机器学习方法来开发一种特定于年轻人的风险计算器，它将使我们能够识别基于个人的可修改的风险因素，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 f 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.