As nearly 1% of the U.S. population is affected by schizophrenia and the country's annual expense related to the mental disorder is over 70 billion dollars, the disorder remains a pressing concern. Although genetic linkage studies initially appeared promising, they have yielded inconsistent results in the search for the location of major genes predisposing for schizophrenia. It is believed that this is due to in large part to the partial penetrance of the affected genes and a clinical diagnosis of the disorder that only identifies a fraction of the relevant population (i.e. only those who display full symptom expression). To increase the strength of genetic linkage studies, investigators have begun to study individuals with genetic liability for schizophrenia rather than those who manifest full symptom expression. The present fellowship applicant is principally interested in examining markers (e.g. eye movement dysfunction) that show promise for identifying genetic risk. Also, it is important to identify and study the affected biological relatives of schizophrenia patients who share the genetic diathesis. By examining relatives for vulnerability markers, it may be possible to identify relatives with genetic liability for the disorder and families that may be most informative for genetic linkage studies. Some such vulnerability markers suggest deficits related to reduced integrity of prefrontal cortical brain areas in relatives of schizophrenia patients. Further investigation of these genetic liability indicators may yield insights into the neuropathology of the schizophrenia diathesis.
