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.
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