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.
Key Words
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Article info
Publication history
Accepted:
March 9,
2005
Received in revised form:
March 9,
2005
Received:
July 27,
2004
Footnotes
This work was supported in part by Grant Nos. K08-MH-66072 to AED and R21-MH066191 (Networking Grant) to SVF. We thank Joel Nigg, Ph.D., Bruce Pennington, Ph.D., and Irwin Waldman, Ph.D., for their comments on a related draft.
AED is a member of the McNeil Speakers Bureau and has served on the Eli Lilly Cognition Advisory Board. JB receives research support from the following pharmaceutical companies: Shire, Eli Lilly, Pfizer, McNeil, Abbott, Bristol-Myers-Squibb, New River Pharmaceuticals, Cephalon, Janssen, Neurosearch. He is a speaker for the following speaker’s bureaus: Shire, Lilly, McNeil, and Cephalon; he is on the advisory board for the following companies: Eli Lilly, Shire, McNeil, Janssen, Novartis, and Cephalon.
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© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
