The purpose of this project is to find genetic loci linked to the impairment in cortical function found in schizophrenia. The method to be used is the affected sibling pair paradigm. Abnormalities of cortical function appear to be core features of chronic schizophrenia. Cortical function of patients and their siblings will be quantified using functional MRI, MR Spectroscopy and neuropsychological testing. These methods will be entered into the linkage analysis. Carefully diagnosed probands will recruited from our existing in patient population of persons with chronic schizophrenia. Other probands are recruited through the media and the National Alliance for the Mentally Ill. Diagnosis of probands is established from previous psychiatric records and a structured diagnostic interview. Siblings likewise are evaluated with a structured interview. All subjects give a blood sample for genetic analysis. Evaluation of cortical function is done using functional MRI and neuropsychological testing. These procedures have been chosen because it is already known that persons with schizophrenia demonstrate some abnormality compared to normal controls. It is hypothesized that some of the siblings will show one or more abnormal traits on these tests, thus suggesting that they may be phenotypically similar to their ill sibling even though they do not evidence (at the time of testing) the full blown syndrome. This study and the method of genetic analysis is unique in that it does not use diagnosis as the identifying variable. This is important because we already know that the genetic contribution to vulnerability to schizophrenia is not large. The best current estimates put it at around 20 to 40%.
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