The recent development of DNA microarray technology has created the possibility of simultaneously studying the expression levels of thousands of different genes during a single experiment. DNA microarrays are therefore likely to be powerful tools for the study of complex diseases, which may involve abnormalities in the expression levels of many genes, and which may be secondary to upstream genetic or environmental effects. Schizophrenia is a complex disease of unknown cause and there are currently no genetic or biochemical tests that can diagnose or predict its onset. This pilot project will test the hypothesis that schizophrenia sufferers have conserved patterns of leukocyte gene expression levels, which are altered compared to normal control subjects. Blood samples were selected for this pilot gene expression study because they are readily obtainable from patients in our facilities, and because results obtained in previous studies showing altered concentrations of immune response system (IRS) mediators in schizophrenia provide some evidence to suggest there may be altered leukocyte gene expression levels in the disorder. In this study, blood samples will be obtained from ten male Caucasian schizophrenic patients and ten male Caucasian control subjects of similar age. This sex and ethnic restriction will minimize sample heterogeneity and maximize the usefulness of the pilot sample size Cy3 or Cy5 fluorescently labeled cDNA will be made from the blood leukocytes of each subject and two of the cDNA samples (one Cy3- and one Cy5-labeled) will be hybridized to each of ten cDNA microarrays containing approximately 9,000 known human cDNAs and ESTs. The microarrays will be scanned and the fluorescence intensities of each spot will be measured. The resulting gene expression level patterns will be analyzed and compared by 2-way clustering analyses. Also as part of the expression level data analysis, the expression levels of the IRS markers represented on the microarrays will be analyzed. If the project data indicate different gene expression levels between schizophrenic subjects and control subjects, and/or expression level clustering characteristic for schizophrenia, further studies to confirm the finding in larger numbers of subjects will be performed and will include other ethnic groups and women. This study has the potential of providing information that will allow us to develop microarray-based tests which may help in the diagnosis of schizophrenia, and may also help in the identification of individuals at risk. Such tests would have major public health benefits.
