Polygenic and environmental contributions to ADHD trajectory and outcome from childhood through adolescence

项目摘要 该项目将绘制ADHD的多个临床和神经认知功能领域的共同发展图 从童年到青春期后期。它提出了地理空间编码和其他暴露风险的新组合 以及多个多基因评分，以确定与病程和结局相关的病因机制 多动症。要检查的功能和特征领域包括注意力不集中、多动-冲动(两者 ADHD领域)、易怒、执行功能、警觉性和奖励延迟折扣(这是 冲动)。他们将在第一个数据集中接受7-19岁的检查(称为俄勒冈州-ADHD- 约1450名青年中的1000人)和年龄9-17岁的第二数据集(纵向全国青少年大脑， 约11,800名儿童的认知、发展或ABCD研究)。行为轨迹将是 与基线PR和曝光度量(包括通过地理空间地址编码可获得的那些)相关， 以及随时间变化的变化和累积曝光指标。暴露或环境影响 也是在社区层面(社区劣势、污染暴露风险)进行概念化 作为家庭内部的一级(社会经济指标、父母或育儿特点)。发展中的 轨迹及其遗传和环境影响也将与情绪和环境的关键结果有关 品行障碍、自杀、吸毒和酗酒，所有这些都与ADHD症状有关。 这项研究具有重要意义，因为它有可能引入最新的ADHD联合暴露-PRS模型 在使用之前尚未在基因型和环境(GxE或G+E)上下文中完成的开发 方法或本文提出的随诊密度。它还具有使问题变得清晰的潜力，这一点也很重要 为什么ADHD经常导致有害的结果和潜在的可预防的调节影响。它是 在将PRS分数和地理空间编码措施以及密度和长度相结合方面具有创新 将能够使用这些措施来检查时间发展的情况。目标直接针对NIMH 战略优先事项，其设计将包括对可推广性的评估，并添加关于以下方面的知识 发展、病因和机制。如果成功，该项目将有助于隔离可起诉的因果关系和 结果调节剂作为青少年风险的干预目标，包括自杀风险的重要优先事项。

Project Summary This project will map the co-development of multiple clinical and neurocognitive functional domains of ADHD from childhood to late adolescence. It proposes a novel mix of geospatial coded and other exposure risks along with multiple polygenic scores to identify etiological mechanisms of course and outcome related to ADHD. The functional and trait domains to be examined include inattention, hyperactivity-impulsivity (the two ADHD domains), irritability, executive functioning, vigilance, and reward delay discounting (an aspect of impulsivity). They will be examined over an age span of 7-19 in the first data set (called the Oregon-ADHD- 1000, of some 1450 youth) and ages 9-17 in the second data set (the longitudinal national Adolescent Brain, Cognition, and Development or ABCD study of some 11,800 children). The behavioral trajectories will be related to both baseline PRS and exposure metrics (including those available via geo-spatial address coding), as well as to time-varying changes and cumulative exposure metrics. Exposures or environmental influences are conceptualized both at a neighborhood level (neighborhood disadvantage, pollution exposure risk) as well as a within-family level (socio-economic indicators, parent or parenting characteristics). The developmental trajectories and their genetic and environmental influences will also be related to critical outcomes of mood and conduct disorder, suicidality, drug and alcohol use, all of which are elevated in relation to ADHD symptoms. The study is significant in its potential to introduce up-to-date combined exposure-PRS models of ADHD development that have not been done in a genotype and environment (GxE or G+E) context before using the methods or follow up density proposed here. It is also significant in its potential to bring clarity to the question of why ADHD so often leads to deleterious outcomes and to potential preventable moderator influences. It is innovative in its combining of PRS scores and geospatial coding measures as well as in the density and length of time development will be able to be examined using these measures. The aims directly target NIMH Strategic Priorities with a design that will include evaluation of generalizability and add knowledge about development, etiology, and mechanism. If successful the project will help to isolate actionable causal and outcome moderators as intervention targets for adolescent risk, including the important priority of suicide risk.