Gene Expression Gene Expression Discovery in Post

Gene Expression Gene Expression Discovery in Post-Mortem Human Brain: Bipolar

and Major Depressive Disorders



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



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



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 (

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.