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.

项目摘要 该项目将绘制多动症的多个临床和神经认知功能域的共同开发 从童年到青春期。它提出了地理空间编码和其他暴露风险的新型组合 以及多个多基因分数，以确定病因学机制，以及与 多动症。要检查的功能和性状结构域包括注意力不集中，多动冲动（这两个 多动症域），易怒，执行功能，警惕和奖励延迟打折（一个方面 冲动）。在第一个数据集中，将在7-19岁的年龄范围内对它们进行检查（称为俄勒冈-Adhd-- 在第二个数据集中，有1000个，大约1450名青年和9-17岁（纵向国家青少年大脑， 认知，大约11,800名儿童的发展或ABCD研究）。行为轨迹将是 与基线PR和暴露指标有关（包括通过地理空间地址编码可用的指标）， 以及时间变化的变化和累积暴露指标。暴露或环境影响 在社区层面上都被概念化（邻里劣势，污染风险） 作为家庭内部（社会经济指标，父母或育儿特征）。发展 轨迹及其遗传和环境影响也将与情绪的关键结果和 进行障碍，自杀，毒品和饮酒，所有这些都与多动症症状有关。 该研究在引入最新的多动症的最新曝光PRS模型中很重要 在使用基因型和环境（GXE或G+E）中未完成的开发之前 在此提出的方法或后续密度。它的潜力也很重要 为什么ADHD经常导致有害结果和潜在的可预防主持人影响。这是 创新的PRS分数和地理空间编码措施以及密度和长度的创新性 时间开发将可以使用这些措施进行检查。目的直接针对NIMH 具有设计的战略优先事项将包括评估通用性并增加有关的知识 发展，病因和机制。如果成功，该项目将有助于隔离可行的因果关系，并且 结果主持人作为青少年风险的干预目标，包括自杀风险的重要优先级。