Schizophrenia: Patterns of Differential Gene Expression in Cortical Regions
M.P.
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
1
Department of Psychiatry University of California, Irvine CA
2
MHRI, University of Michigan, Ann Arbor, MI
3
Center for Neuroscience, University of California, Davis CA
4
Stanford Human Genome Center, Stanford University, Palo Alto CA
5
Department of Statistics, University of California, Berkeley CA
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.