In this section we review the literature on electrophysiological biomarkers, with an emphasis on those that are candidate endophenotypes. We begin by addressing how well putative endophenotypes satisfy the threshold criteria in Table 1. Some have been the focus of years of research, whereas investigations into others have only recently been undertaken. However, with the exception of resting heart rate, none of the candidate endophenotypes meet the criteria in Section II of Table 1 for molecular genetic verification. Of note, they do not satisfy criterion #5, which requires demonstration of a verified association with a specific genetic variant. Given this failure, they of course cannot satisfy criterion #6, which requires the verified variant to also be associated with the clinical phenotype. As with our investigation of 17 endophenotypes described in our special issue of Psychophysiology, we do not feel that it is likely that the failure of endophenotypes in general to lead to verified molecular genetic discovery is due to poor measurement. For one thing, it is unlikely that the candidate endophenotypes listed in Table 5 are uniformly poorly measured.
