Endophenotypes for Molecular Genetic Studies of ADHD

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The genetic influences that contribute to psychiatric disorders are most often complex, and are the result of interactions between several genes of small effect. Thus, it is necessary to develop phenotypic data that is as closely related to the action of the gene as is possible in order to detect their effect. Biological markers hypothesized to represent genetic liability to a given disorder, termed "endophenotypes", may provide phenotypic data useful in identifying such genes. Performance on sustained attention and executive functions measures, thought to depend heavily on neural circuits involving the prefrontal cortex, might represent an endophenotype for ADHD given that children diagnosed with this disorder often show deficits on such measures. The purpose of the current proposal is to begin developing a research program for evaluating sustained attention and executive functions measures as endophenotypes for ADHD. This research program will focus on evaluating the psychometric properties of these measures (reliability, internal validity, and external validity), the extent to which performance on these measures is heritable using univariate and multivariate behavior genetic analyses, and the ability of these measures to replicate previously observed evidence of association and linkage between ADHD and selected candidate genes.