Elementary phenotypes in the neurobiological and genetic study of schizophrenia

This review describes the strategy of using elementary phenotypes for neuro biological and genetic linkage studies of schizophrenia. The review concent rates oil practical aspects of selecting the phenotype and then understandi ng the confounds in its measurement and interpretation, Examples from the a uthors' studies of deficits in P50 inhibition and smooth pursuit eye moveme nt dysfunction are presented. These two phenotypes share considerable simil arity in their neurobiology, including a similar response to nicotine. They also appear to co-segregate with the genetic risk for schizophrenia as aut osomal co-dominant phenotypes. Although most schizophrenic patients inherit these abnormalities unilinealy, ie., from one parent, apparent bilineal in heritance produces a more severe illness, observed clinically as childhood- onset schizophrenia. The initial study showing linkage of the P50 deficit t o the chromosome 15q14 locus of the alpha 7-nicotinic acetylcholine recepto r is an example of the potential usefulness of these phenotypes for combine d generic and neurobiological study of schizophrenia. (C) 1999 Society of B iological Psychiatry.