Abstract

Gene Expression Discovery in Post-Mortem Human Brain: Bipolar and Major Depressive Disorders

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

Abstract

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.