Molecular Analysis of Schizophrenia and Bipolar Disorder by cDNA Expression Assay




K. Hyder, R.

Yolken, a. Chenchik*, N. Johnston, K. Faridi, F. Yee, E.F. Torrey

and the Stanley Neuropathology Consortium. Clonetech Laboratories

Inc., Palo Alto, CA.

Schizophrenia and bipolar

disorder are important human psychiatric diseases affecting more

than 2,000,000 individuals in the United States. Recent

epidemiological studies have indicated that disease risk in some

individuals may be associated with environmental factors such as

infections and other modulators of inflammation within the

central nervous system. These factors may result in modulation of

gene transcription within the central nervous system with the

resulting manifestation of the disease phenotype. The study of

RNA expression in brain tissue obtained post-mortem from

individuals with these diseases might provide a practical method

for the analysis of gene-environmental interactions associated

with human neuropsychiatric diseases. We employed the Atlas cDNA

array for expression profiling of disease and normal brain tissue

obtained by the Stanley Neuropathology Consortium. The methods

used for brain collection and clinical evaluation have been

previously described (Johnston et al, J Neuroscience Methods

77:83-92, 1997). These samples were obtained from individuals

with documented schizophrenia and bipolar disorder and were

matched from age, sex, and pre- and post-mortem variables. We

extracted total RNA from each brain sample using the Atlas Pure

RNA kit and subsequently enriched for poly A+ mRNA. 32P-labeled

probes were synthesized from both total RNA and mRNA, then

hybridized to the Atlas Human I cDNA Expression Array, a layout

of 588 genes. On comparison of each disease and normal sample by

image analysis, we identified several differentially expressed

mRNAs which were successfully confirmed by RT-PCR