Gene Expression Gene Expression Discovery in Post-Mortem Human Brain: Bipolar
and Major Depressive Disorders
M.P.
Vawter1, H. Tomita1, S. Evans2, P. Choudary3,
J. Li4, B. Bolstad5, J. Lopez2, 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
The body of research is conducted by a team of
investigators working closely across four universities, and is aimed at
characterizing gene expression patterns in the postmortem brains of individuals
with severe mood disorders. The profile of gene expression in bipolar I disorder
patients (n = 9) and major depressive disorder (n = 8) was compared to controls
(n = 12). All cases were extensively documented for family psychiatric history,
drug abuse, and medication history. Microarray screening of three brain
regions, dorsolateral prefrontal cortex, anterior cingulate cortex, and
cerebellum was performed with Affymetrix oligonucleotide chips. Each sample was
run in duplicate on Affymetrix U95A chips at 2 of 3 laboratories. A robust
probe level linear model (http://www.stat.berkeley.edu/users/bolstad/AffyExtensions/AffyExtensions.html)
for calculation of the group expression summaries was used. The gene profile
in bipolar disorder compared to controls was examined in 3 brain regions. Some
genes in the bipolar disorder profile show overlap with genes in the profile of
major depression across 3 brain regions. The majority of genes appear to be
non-shared between the mood disorders. The shared genes might represent common
vulnerability genes to mood disorders. The distinct nonshared gene expression
profiles between the two mood disorders suggests different underlying functional
pathways that could be connected to the different symptoms within each mood
disorder. Downstream validation of the gene expression results are underway
and the results will be compared to other recent investigations of alterations
in gene expression in mood disorders.
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.