A more radical way of dealing with the shortcomings of the nosological system is to look deeper into the possibilities of using (ADHD) endophenotypes for GWAS. Endophenotypes, or intermediate phenotypes, represent heritable phenotypic constructs that are, presumably, more directly affected by genes than clinical symptoms or disease categories (Gottesman and Gould 2003; Szatmari et al. 2007a; Walters and Owen 2007). This should result in a stronger association between causal genes and the endophenotype than the clinical disease phenotype. The success of an endophenotype strategy requires either a higher heritability of the endophenotype compared to the disease phenotype (which is generally not generally observed, Szatmari et al. 2007a) or a reduced complexity of the genetic architecture of the endophenotype due to the involvement of less genes (see Fig. 1). Endophenotypes for ADHD have been proposed at different levels, e.g. those based on neuropsychological performance (Doyle et al. 2005; Rommelse 2008) and those based on neuroimaging (Castellanos and Tannock 2002), i.e. brain activity and structure. Recent genome-wide linkage studies of neuropsychological endophenotypes for ADHD indeed suggest that these measure offer increased power
