Electrophysiological Phenotypes

The rationale for the use of an endophenotype in genetic studies of psychiatric disorders is that these disorders are likely to be multi-determined, with multiple environmental and genetic origins, so that a discrete biological phenotype is more likely to reflect a single major gene effect. This strategy has been used successfully in the linkage and segregation analysis of several illnesses, including hemochromatosis, for which elevated serum iron was used as the relevant endophenotype, and colon cancer, for which elevated numbers of polyps were used as the phenotype. For psychiatric illnesses, various phenotypic approaches have been suggested. These include the use of variants within the illness, such as differences in age of onset, which may reflect differences in disease (see Chapter 6 ) and the use of personality characteristics as indicators of underlying biological differences. Physiological mechanisms, the focus of this chapter, are favored because of their presumed relationship to synaptic neurotransmission, a basic unit of function in the central nervous system. This chapter describes three examples of physiological endophenotypes that have been used successfully in linkage analysis, and discusses general issues in their use and the interpretation of results.