Schizophrenia: Patterns of Differential Gene Expression in Cortical Regions



Vawter1, S. Evans2, P.Choudary3, M. Atz1,

H. Tomita1, B. Bolstad5, J. Lopez2, J. Li4,

T. Speed5, R.M. Myers4, S.J. Watson2, H. Akil2,

E.G. Jones3, W.E. Bunney1



Department of Psychiatry University of California, Irvine CA


MHRI, University of Michigan, Ann Arbor, MI


Center for Neuroscience, University of California, Davis CA


Stanford Human Genome Center, Stanford University, Palo Alto CA


Department of Statistics, University of California, Berkeley CA




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( 

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.