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Attention-deficit/hyperactivity disorder endophenotypes.

Doyle AE, Willcutt EG, Seidman LJ, Biederman J, Chouinard VA, Silva J, Faraone SV

Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. doylea@helix.mgh.harvard.edu

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder with a multifactorial pattern of inheritance. For complex conditions such as this, biologically based phenotypes that lie in the pathway from genes to behavior may provide a more powerful target for molecular genetic studies than the disorder as a whole. Although their use in ADHD is relatively new, such "endophenotypes" have aided the clarification of the etiology and pathophysiology of several other conditions in medicine and psychiatry. In this article, we review existing data on potential endophenotypes for ADHD, emphasizing neuropsychological deficits because assessment tools are cost effective and relatively easy to implement. Neuropsychological impairments, as well as measures from neuroimaging and electrophysiological paradigms, show correlations with ADHD and evidence of heritability, but the familial or genetic overlap between these constructs and ADHD remains unclear. We conclude that these endophenotypes will not be a quick fix for the field but offer potential if careful consideration is given to issues of heterogeneity, measurement and statistical power.

Published 13 June 2005 in Biol Psychiatry, 57(11): 1324-35.
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