Schizophrenia is a genetic disorder, but being psychiatrically normal is consistent with being a gene carrier for this illness. This suggests that the clinical diagnosis of affection alone may be an inefficient means of defining the phenotype for subtle genetic analyses. The main purpose of this project is to evaluate the efficacy of variables other than interview and questionnaire which might more adequately identify """"""""clinically nonpenetrant"""""""" gene carriers. Perhaps the three most promising measures for such an enterprise are ocular motor functioning, deficient sensory gating of the first positive-going wave in an auditory evoked potential paradigm (P50), and challenging tasks of sustained attention (CPT d'). These measures will be obtained from probands with schizophrenia and their first-degree biological relatives. It will first be determined whether these variables are related to syndromal and subsyndromal manifestations of schizophrenia among the relatives (specifically, if they are related to social-interpersonal schizophrenia-related characteristics). Second, we will determine what mode of genetic transmission is most likely for these variables within the families of schizophrenic probands. Third, we will determine whether these variables seem to be segregating in different families or whether they seem to be pleiotropic manifestations of the same predisposing factor. If these variables demonstrate interesting patterns of results in such analyses, then they may be more useful for linkage and segregation analyses than the clinical diagnosis of schizophrenia (and spectrum disorders). Research projects such as this may be necessary if the genetic factors predisposing to this clinical phenotype are to be understood.
