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

项目摘要 本项目将绘制ADHD的多个临床和神经认知功能领域的共同发展 从童年到青春期后期。它提出了一种新的地理空间编码和其他暴露风险的组合 沿着多基因评分，以确定病程和结局相关的病因机制， 多动症。要检查的功能和特质领域包括注意力不集中，多动-冲动（两个 ADHD领域），易怒，执行功能，警惕性和奖励延迟折扣（一个方面， 冲动）。他们将在第一个数据集（称为俄勒冈-ADHD- 1000，约1450青年）和9-17岁的第二个数据集（纵向国家青少年大脑， 认知和发展或ABCD研究约11，800名儿童）。行为轨迹将是 与基准PRS和暴露度量（包括通过地理空间地址编码提供的度量）有关， 以及随时间变化的变化和累积暴露度量。暴露或环境影响 在邻里层面（邻里劣势，污染暴露风险）也被概念化 作为家庭内一级（社会经济指标、父母或养育子女的特点）。发育 轨迹及其遗传和环境影响也将与情绪的关键结果有关， 行为障碍，自杀，吸毒和酗酒，所有这些都与ADHD症状有关。 这项研究是重要的，它的潜力，介绍了最新的组合的焦虑-PRS模型的多动症 在基因型和环境（GxE或G+E）背景下，在使用 方法或后续密度提出了这里。它还具有澄清问题的潜力， 为什么多动症经常导致有害的结果和潜在的可预防的调节影响。是 创新性地将PRS分数和地理空间编码措施相结合，并在密度和长度方面 时间的发展将能够使用这些措施进行审查。目标直接针对NIMH 战略优先事项的设计将包括对可推广性的评价，并增加关于以下方面的知识： 发展，病因和机制。如果成功，该项目将有助于分离可采取行动的因果关系， 结果调节因子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.