Hyperactivity Disorder (ADHD) is a genetically influenced brain disorder has been undertaken using a two armed approach: 1) Isolated population analysis from a large, extended pedigree study done in Colombia, South America in a population isolate called the Paisa have been studied for the last 7 years; and a recently added second isolated in USA from Amish population at Lancaster, Co Pennsylvania; with different background and environmental influences, and 2) a U.S. based study of nuclear families with at least one affected child and at least one sibling (either affected or unaffected), and their parents. Following careful phenotyping, DNA from blood samples from these two genetically different groups will be analyzed through a genomewide scan for linkage and positional candidate approach to search for genes associated with ADHD. In addition comparison of genetic-environment interactions will be done on these two different populations. Genetic influence are to modulate biological aspects in cognition and behavioral manifestations. The prefrontal cortex and its connections is known to play a very important role in the processing of emotions and impulsivity. It is considered the primary biological component of a brain circuit that would explain the main clinical characteristics present in ADHD phenotype. Measurement of brain metabolites in this region may be very useful in phenotyping ADHD. Thus, after identification of specific genotype implicated in ADHD risk in the Colombian population, in a subset of already recruited individuals, phenotyping will include proton magnetic resonance spectroscopy (H MRS) to detect biochemical phenotypes which may be correlated with genetic markers for ADHD. Additional analysis for potential genetic-environment interactions will be done to compare isolated populations in different environments. Identification of a biological marker to be used to support and confirm clinical diagnosis is highly desirable.