A Population-Based Study of the Genomics and Long-Term Outcomes of AD/HD

AD/HD 的基因组学和长期结果的人群研究

• 批准号: 7149021
• 负责人: WILLIAM J. BARBARESI
• 金额: $ 49.75万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-11 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7149021
• 关键词: academic achievement; attention deficit disorder; behavioral /social science research tag; clinical research; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; longitudinal human study; mental disorder chemotherapy; mental health epidemiology; outcomes research; psychometrics; psychopharmacology; quality of life; questionnaires; social adjustment; social psychology; young adult human (21-34)

DESCRIPTION (provided by Applicant): This application describes a population-based study of the genomics and long-term outcomes of Attention- Deficit/Hyperactivity Disorder (AD/HD), in response to an NIH Program Announcement (PAS-03-092). Significant gaps exist in knowledge of long-term outcomes and the genomics of AD/HD, the most common, complex, neurobehavioral disorder in childhood. In our published study, all incidence cases of childhood AD/HD (n=379), and subjects with sub threshold childhood AD/HD (n=271), were identified in the 1976-1982, Rochester, Minnesota birth cohort (n=5,718). Subsequently, a pilot study has been completed, involving assessment of the current status of a sample of these subjects, now young adults with a history of childhood AD/HD, young adults with a history of sub-threshold childhood AD/HD, and matched controls from the birth cohort. The pilot study included a direct, standardized, structured, diagnostic neuropsychiatric interview, assessment of reading/math achievement, questionnaires to assess psychosocial outcomes, and blood samples for genomic studies. An adult AD/HD-specific health-related quality of life questionnaire (HRQOL) has also been piloted with these subjects. In the current application, these well developed research procedures will be applied to the entire cohort of young adult subjects with childhood AD/HD, sub threshold childhood AD/HD and matched controls from the 1976-1982 birth cohort to determine their clinical phenotype and to estimate the extent to which AD/HD persists into young adulthood. A nested, case-control design will be employed to compare the frequency of polymorphic alleles in potentially important components of the dopaminergic system; a primary focus will be the comparison between young adults with childhood AD/HD and non-AD/HD controls. During the subjects' assessments, long-term psychosocial and academic outcomes will be determined for AD/HD cases and controls and the association between medication treatment during childhood and psychosocial/academic outcomes in young adulthood will be determined. The psychometric properties of the adult AD/HD-specific HRQOL questionnaire will also be determined. Through this study, involving a multidisciplinary research team, a unique population-based birth cohort and exceptional research facilities, knowledge of the persistence of AD/HD into adulthood, genomics of the dopaminergic system in AD/HD, long-term psychosocial and academic outcomes associated with this disorder, and the association between medication treatment during childhood and outcomes in young adulthood will be substantially advanced.

描述（由申请人提供）：本申请描述了一项针对注意力缺陷/多动障碍 (AD/HD) 的基因组学和长期结果的人群研究，以响应 NIH 计划公告 (PAS-03-092) 。 AD/HD（儿童期最常见、最复杂的神经行为障碍）的长期结果和基因组学知识存在显着差距。在我们发表的研究中，所有儿童 AD/HD 的发病病例 (n=379) 以及儿童 AD/HD 低于阈值的受试者 (n=271) 均在 1976-1982 年明尼苏达州罗彻斯特出生队列中确定 (n= 5,718）。随后，一项试点研究已经完成，涉及评估这些受试者样本的当前状态，其中包括有儿童 AD/HD 病史的年轻人、有亚阈值儿童 AD/HD 病史的年轻人，以及匹配的受试者。来自出生队列的对照。试点研究包括直接、标准化、结构化的诊断性神经精神病学访谈、阅读/数学成绩评估、评估心理社会结果的问卷以及用于基因组研究的血液样本。针对成人 AD/HD 的健康相关生活质量问卷 (HRQOL) 也已在这些受试者中进行了试点。在当前的应用中，这些完善的研究程序将应用于整个年轻成年受试者队列，其中包括儿童 AD/HD、亚阈值儿童 AD/HD 以及来自 1976-1982 年出生队列的匹配对照，以确定他们的临床表型并估计 AD/HD 持续到成年早期的程度。将采用嵌套病例对照设计来比较多巴胺能系统潜在重要组成部分中多态性等位基因的频率；主要关注点是患有儿童 AD/HD 的年轻人与非 AD/HD 对照组之间的比较。在受试者评估过程中，将确定 AD/HD 病例和对照的长期心理社会和学业结果，并将确定儿童期药物治疗与青年期心理社会/学业结果之间的关联。成人 AD/HD 特定 HRQOL 问卷的心理测量特性也将被确定。通过这项研究，涉及多学科研究团队、独特的基于人群的出生队列和卓越的研究设施、AD/HD 成年期持续存在的知识、AD/HD 中多巴胺能系统的基因组学、长期心理社会和学术成果与这种疾病相关的疾病，以及儿童时期的药物治疗与成年早期的结果之间的关联将大大提高。