Abstract

Bipolar and Major Depression Disorder Gene Expression Profiling in Three Brain Regions

MP Vawter; H Tomita; S Evans;, P Choudary; J Li; B. Bolstad; JH Meador-Woodruff; Juan Lopez; T. Speed; RM Myers; S Watson; H Akil; EG Jones; WE Bunney
11th World Congress for Psychiatric Genetics (ISPG). 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. Variables that might influence gene expression such as gender, age, pH, autolysis time, and agonal factors were investigated. We investigated probe level fit methods (http://www.stat.berkeley.edu/users/bolstad/AffyExtensions/AffyExtensions.html) for calculation of the group expression summaries that provides an expression coefficient for each group and a standard error for each group. Genes were selected for downstream analysis based upon technical replication as one criterion, as well as agreement between subgroup analyses, to establish high confidence gene lists for qRT-PCR verification. 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. The gene profile in bipolar disorder compared to controls was examined in 3 brain regions. The genes in the bipolar disorder profile show few overlaps with genes in the profile of major depression across 3 brain regions. The profiles of gene expression for bipolar and major depression within an individual brain region share genes within each of the three region profiles. The majority of genes appear to be non-shared between the mood disorders and between the regional profiles. The shared and non-shared genes between the disorders suggest that 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.