This Project represents an innovative integration of two theoretical approaches that have great potential for improving prediction of schizophrenia and for helping to clarify the neural mechanisms involved in the onset of psychosis. Although late adolescence/eariy adulthood is the period when onset typically occurs, few prospective prodromal studies have focused on the changes in brain function that occur during this period. Information about the neural processes leading to illness during this eariy phase of development could both improve accurate prediction and potentially lead to novel interventions targeting the specific abnormalities identified. The proposed Project combines the expertise of two established investigators (Cornblatt and Javitt) who currently collaborate on studies of D-serine effects on symptoms in the SZ prodrome, and will provide the funding and resources to introduce Dr. Javitt's biological approach into Dr. Cornblatt's prospective, longitudinal prodromal study. Dr. Cornblatt has conducted research concerned with identifying neurocognitive, behavioral and clinical risk factors of schizophrenia for over 20 years. Since 1998, she has been the director of the Recognition and Prevention (RAP) program, a prospective study of adolescents between the ages of 12-22 who are at clinical risk (i.e., prodromal) for schizophrenia at Zucker Hillside Hospital (ZHH). She will serve as PI for this project. The project will incorporate event-related potential (ERP) and behavioral measures of sensory processing dysfunction to enhance existing neurocognitive batteries.
Specific aims of the project are 1. to introduce a sensory processing battery (behavioral measures/ERP procedures) to the existing RAP baseline procedures and assess the extent to which sensory deficits are present in the prodromal stage of illness;2. to evaluate short-term changes in sensory processing and ERPs at six months in subjects who are medication free as compared to those stabilized on medication, and 3. to assess long-term change in processing associated with a two-year retest. We have elected to follow all participants for two years, since previous findings indicate that conversions peak during this time period, and can be expected to be about 35%. Primary ERP support for this Project will be provided by Core B. ERP measures will be compared across Project 1, 5 and 6 to assess deficits in chronic, prodromal and first episode cohorts, respectively. This project integrates as well with database component of Project 6, and will receive database and statistical support from Core C.

Public Health Relevance

Schizophrenia is a major mental disorder. Neurocognitive dysfunction is a core component of schizophrenia and a major determinant of poor long-term outcome. This project is part of a Center application to determine brain mechanisms underiying neurocognitive dysfunction in schizophrenia with particular emphasis on sensory processing dysfunction. This project will evaluate deficits in sensory processing in patients showing prodi^omal symptoms of schizophrenia , in collaboration with other projects and core programs, as a way to improve eariy detection and intervention.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZMH1-ERB-F)
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Columbia University (N.Y.)
New York
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