DORSAL LATERAL PREFRONTAL CORTEX AND MEDIODORSAL THALAMUS IN SCHIZOPHRENIC BRAINS SHOW CONCORDANT AND DISCORDANT ALTERATIONS IN GENE EXPRESSION.
P.V. Choudary; S.J. Evans; M.P. Vawter; J. Li; J.F. Lopez; R.M. Myers; W.E. Bunney; S.J. Watson; H. Akil; E.G. Jones
Society for Neuroscience 33rd Annual Meeting. 2003.
A million Americans suffer from schizophrenia, a debilitating mental illness, characterized by various combinations of delusions, hallucinations, catatonic behavior, social dysfunction, apathy and poor motivation. To identify candidate genes conferring vulnerability to schizophrenia, as a first step, we profiled gene expression changes in different functional areas of postmortem brains of schizophrenic patients using Affymetrix HG_U133A,B GeneChips. The signal intensity values of the perfect match (PM) probe sets of each gene were corrected for background and normalized, and expression measures were derived using the PM-only model of the log scale robust multi-array analysis (RMA) package. The top (up-regulated) 500 and bottom (down-regulated) 500 candidate genes that showed differential expression between two connected regions, i.e., dorsal lateral prefrontal cortex (DLPFC) and medio-dorsal thalamus (MThal) were analyzed for biological relevance in the context of schizophrenia using Gene Ontology (GO) tools. Classification by molecular and cellular functions categorized candidate genes into many subgroups. Some biological processes seemed to be involved in both regions while others were affected in a single region. The affected processes ranged widely from organogenesis to signal transduction, and cell death. Possible relations between the dysregulated biological functions and the brain areas will be discussed. Support Contributed By: The Pritzker Neuropsychiatric Disorders Research Consortium Fund, WM Keck Foundation, and NIH Conte grant #MH60398-03. We acknowledge participation of all Consortium members in this work.