EFFECTS OF BIPOLAR DISORDER, MAJOR DEPRESSION AND SUICIDE ON GENE EXPRESSION PROFILES IN POSTMORTEM BRAINS
H Tomita; MP Vawter; S Evans; P Choudary; J Li; B Bolstad; T Speed; RM Myers; EG Jones; S Watson; H Akil; WE Bunney
American Society of Human Genetics 53nd annual meeting . 2003.
To examine gene expression changes in mood disorders, gene transcript abundance was measured by microarray analysis in patients with bipolar disorder type I (BPD, n = 9), major depressive disorder (MD, n=11), and compared to a control group (n=20) matched for age, gender, and post mortem interval (PMI). Also, a subgroup of 4 BPD and 6 MD patients who committed suicide was compared to the remaining mood disorder patients, and controls who died rapidly by accident or acute diseases. Total RNA was extracted from three brain regions, anterior cingulate, dorsolateral prefrontal and cerebellar cortices, and each sample was run in duplicate on Affymetrix U95Av2 chips at 3 laboratories. Signal intensity of each gene was extracted using three independent methods, microarray suite version 5.0, robust multi-array analysis (RMA) and probe level model analysis (PLM). Microarray findings were validated by quantitative RT-PCR. Effects of agonal state, brain pH, age, gender, and PMI on gene expression profile were evaluated along with the disorders. These differences in gene expression profile involving multiple signaling pathways such as MAPK pathway will be discussed in the context of pathogeneses of severe mood disorders involving suicidal behavior. This work was supported by NIH Conte grant MH60398-03 and the Pritzker Neuropsychiatric Disorder Research Consortium Fund. We acknowledge participation of all Consortium members in this work.