Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder affecting some 5 percent of children and adolescents and 3 percent or more of adults. ADHD is characterized by behavioral symptoms of inattention, hyperactivity, and impulsively with neurocognitive deficits in response inhibition, aspects of attention and memory, thought, in part, to underlie the behavioral symptoms. The cause of ADHD is as yet unknown although family, twin, adoption, and molecular studies strongly suggest that about 60-80 percent of the underlying risk or liability to develop ADHD is likely to be genetic in origin with environmental risk factors making up about 20-40 percent of the liability. The long-term goal of our research is to identify susceptibility genes, environmental risk factors and their interactions in ADHD, it's component symptoms, and putative core neurocognitive processes. We have available a unique population of 9,432 adolescents (ages 15-16) living in Northern Finland who have been followed longitudinally since 12- weeks gestation as part of the Northern Finland Birth Cohort Studies (NFBC) to conduct this work. The frequency of ADHD in this cohort is approximately 5-6 percent. The sample and their parents were assessed at ages 0-1 and ages 7-8 years for a variety of significant environmental risk variables that may contribute to ADHD. As part of the NFBC studies, the birth cohort is going to be assessed in 2001-2003, at which time additional clinical assessments and DNA can be collected on a subset of adolescents (400 ADHD cases and 200 non-ADHD controls) to conduct linkage and association studies.
The specific aims of the project are to i) conduct a genome scan looking for shared DHA segments in ADHD members of the NFBC who are related through common ancestors; ii) identify novel 'risk' genes in ADHD through an investigation of approximately 500 brain-expressed, non-synonymous (likely functional), single nucleotide polymorphisms (cSNPs); iii) replicate findings generated in this study in the Finnish cohort; and iv) compare ADHD and control cases on identified genes and environmental variables to determine their effects and interactions on the development of ADHD. Discovery of the genes and environmental determinants of ADHD, it's behavioral symptoms, and certain core neurocognitive processes will lay the foundation for the development of specific molecular based diagnostic tests, new preventive interventions, and better - gene specific - treatment interventions in this condition. The advantages of conducting this work in the NFBC stem from the wealth of prospective and longitudinally collected environmental risk measures already available on the sample, the likely reduced heterogeneity afforded by a Finnish genetic isolate, and the feasibility of mounting such a large-scale project efficiently due to the availability of the planned 14-15 years follow-up of this cohort.
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