MOLECULAR
ANALYSIS OF SCHIZOPHRENIA AND BIPOLAR DISORDER BY cDNA EXPRESSION
ARRAY
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