GENE EXPRESSION PROFILES IN POSTMORTEM BRAINS OF MOOD DISORDER PATIENTS
H.Tomita; M.P.Vawter; S.Evans; P.V.Choudary; J.Li; B.M.Bolstad; T.P.Speed; R.M.Myers; E.G.Jones; S.J.Watson; H. Akil; E. Bunney
Society for Neuroscience 33rd 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 depression (MD, n=11), and control group (n=20) matched for age, gender, and post mortem interval (PMI). 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. A unique set of genes were found to be dysregulated in BPD and a second unique set in MD. A third set of genes was shared in common in BPD and MD. 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. These differences in gene expression profile will be discussed in the context of pathogeneses of the mood disorders and 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.