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

多基因和环境对儿童期至青春期 ADHD 轨迹和结果的贡献

• 批准号: 10564573
• 负责人: Michael A Mooney
• 金额: $ 78.97万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10564573
• 关键词: Address; Adolescence; Adolescent; Age; Alcohol consumption; Anxiety Disorders; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Brain; Characteristics; Child; Child Rearing; Childhood; Clinical; Code; Cognition; Conduct Disorder; Conflict (Psychology); Data Set; Development; Diagnosis; Dimensions; Disadvantaged; Disease; Drug usage; Education; Emotional; Environment; Environmental Exposure; Environmental Risk Factor; Etiology; Evaluation; Evolution; Exposure to; Family; Family Characteristics; Future; Genetic; Genetic Risk; Genotype; Heritability; Heterogeneity; Hyperactivity; Impulsivity; Intervention; Knowledge; Length; Maps; Measures; Mediating; Mediation; Mental Depression; Mental disorders; Methods; Modeling; Mood Disorders; National Institute of Mental Health; Neighborhoods; Neurocognitive; Neuropsychology; Oregon; Outcome; Parents; Phenotype; Pollution; Population; Prevention; Psychopathology; Rewards; Risk; Severities; Shapes; Structure; Symptoms; Testing; Time; Variant; Waxes; Work; Youth; case control; cohort; conduct problem; density; design; discounting; economic indicator; emerging adult; emotion regulation; executive function; family burden; follow-up; frontier; inattention; innovation; lead exposure; neighborhood disadvantage; neurodevelopment; novel; polygenic risk score; social disparities; socioeconomics; substance use; suicidal; suicidal risk; theories; traffic-related air pollution; trait; vigilance

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.

项目概要 该项目将描绘 ADHD 多个临床和神经认知功能领域的共同开发 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颖组合 以及多个多基因评分，以确定与相关的病程和结果的病因机制 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（这两个 ADHD 领域）、烦躁、执行功能、警惕性和奖励延迟折扣（奖励延迟折扣的一个方面） 冲动）。他们将在第一个数据集中对 7 至 19 岁的年龄跨度进行检查（称为俄勒冈州 ADHD- 第二个数据集中的 1000 名青少年（约 1450 名青少年）和 9-17 岁（纵向国家青少年大脑， 对约 11,800 名儿童进行的认知与发展或 ABCD 研究）。行为轨迹将是 与基线 PRS 和暴露指标（包括通过地理空间地址编码获得的指标）相关， 以及随时间变化的变化和累积暴露指标。暴露或环境影响 也在邻里层面上进行概念化（邻里劣势、污染暴露风险） 作为家庭内部层面（社会经济指标、父母或养育特征）。发展性的 轨迹及其遗传和环境影响也将与情绪和情绪的关键结果有关。 行为障碍、自杀、吸毒和酗酒，所有这些都与多动症症状相关。 该研究具有重要意义，因为它有可能引入最新的 ADHD 组合暴露-PRS 模型 在使用之前尚未在基因型和环境（GxE 或 G+E）背景下完成的开发 此处提出的方法或后续密度。它对于澄清问题也具有重要意义 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。这是 创新之处在于将 PRS 分数和地理空间编码措施相结合，以及密度和长度 可以使用这些措施来检查时间的发展。目标直接针对 NIMH 战略优先事项的设计将包括评估普遍性并增加有关知识 发展、病因和机制。如果成功，该项目将有助于隔离可操作的因果关系和 结果调节因素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。