Abstract

Schizophrenia: Patterns of Differential Gene Expression in Cortical Regions

M.P. Vawter; S. Evans; P.Choudary; M. Atz; H. Tomita; B. Bolstad; J. Lopez; J. Li; T. Speed; R.M. Myers; S.J. Watson; H. Akil; E.G. Jones; W.E. Bunney
Stanley Foundation Meeting. 2003.

This project involves a multi-site collaborative effort to investigate gene expression in neuropsychiatric disorders in multiple brain regions. This abstract focuses on the investigation of schizophrenia by microarray analysis using Affymetrix U133A chips. Three cortical regions comprising neocortex (dorsolateral prefrontal cortex, anterior cingulate, and superior temporal gyrus), archicortex (hippocampus) and paleocortex (entorhinal cortex) were compared in schizophrenia and controls. The differentially expressed genes were selected from a robust probe level linear model analysis(http://stat.www.berkeley.edu/users/bolstad/AffyExtensions/ AffyExtensions.html) for each brain region. The differentially expressed genes were further classified using Gene Ontology and KEGG classifications. There was over-representation of ribosomal genes, heat shock related genes, glutamine catabolism, and immune genes in cortical regions. Synaptic transmission is over-represented significantly when gene dysregulation is considered across these 5 brain regions. The pattern of synaptic transmission gene dysregulation shows approximately equal numbers of over- and under- expressed genes. These results and other findings suggests that alterations in synaptic transmission occurs in several cortical regions implicated in schizophrenia. These results require independent confirmation by other techniques and are subject to limitations involved in postmortem human studies. This work was funded by NIH CONTE Center Grant #L99MH60398, Pritzker Neuropsychiatric Disorders Research Consortium, and the William Lion Penzner Foundation. The academic and philanthropic entities involved in this Consortium are jointly filing patent applications related to the present findings.