One proposed approach to addressing the phenotype definition issues is to employ alternative measurements of ADHD symptoms instead of traditional behavioral rating scale data. This approach has been subject of much recent research and debate. Endophenotypes have been defined as stable, heritable measurements that are more proximal to the biological etiology of a disorder than the clinical diagnosis itself32 and thus partly a better measurement of the underlying genetic liability for a disorder. In ADHD research, this approach is seen as especially valuable because it eliminates rater effects. Further, whereas ADHD is a complex phenotype encompassing many different behaviors, endophenotypes measure simpler traits that may be influenced by a smaller number of genetic loci. In consequence, each genetic variant may account for a larger proportion of the variance and may be detected with smaller samples. There is controversy over what constitutes a measurement that is biologically closer to the underlying susceptibility, and some researchers differentiate “intermediate” and “objective” phenotypes from endophenotypes. In this article we consider ADHD endophenotypes to be those measurements that are designed to assess a heritable, genetically simpler construct, which covaries with ADHD outcomes.
