Attention-deficit/hyperactivity disorder endophenotypes

Biol Psychiatry. 2005 Jun 1;57(11):1324-35. doi: 10.1016/j.biopsych.2005.03.015.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adoption
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Brain / pathology
  • Brain / physiopathology
  • Diagnostic Imaging
  • Evoked Potentials
  • Family
  • Genetic Predisposition to Disease*
  • Humans
  • Molecular Biology
  • Neuropsychological Tests
  • Problem Solving
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D5
  • Receptors, Glutamate / genetics
  • Twin Studies as Topic*


  • DRD5 protein, human
  • Receptors, Dopamine D1
  • Receptors, Glutamate
  • Receptors, Dopamine D5