ANALYSIS OF GENE EXPRESSION IN BIPOLAR DISORDER REVEALS DYSREGULATED SIGNALING PATHWAYS
H. Tomita; M.P. Vawter; S. Evans; P. Choudary; J.H. Meador-Woodruff; J. Li; R.M. Myers; E.G. Jones; S. Watson; H. Akil; W. Bunney Jr
Society for Neuroscience 32nd annual meeting. 2002.
Prior reports of signaling pathway abnormalities in bipolar disorder have broadly implicated signal transduction molecules in the cyclic adenosine monophosphate and phosphatidylinositol cascades. To examine gene expression in multiple pathways, we measured gene transcript abundance by microarray analysis in bipolar disorder type I patients (n = 9) and compared to a control group matched for age, gender, and post mortem interval. We used tissue from three brain regions, anterior cingulate and dorsolateral prefrontal cortices, and cerebellar cortex. Each sample was run in duplicate on Affymetrix U95Av2 chips at 3 laboratories. Gene expression in each patient was compared to that in the individual matched control using MAS5 software to generate Signal Intensity Log2 Ratios. Bipolar patients showed increased expression of 210 and decreased expression of 360 genes in anterior cingulate cortex. By filtering the anterior cingulate gene list with Increased/Decreased calls we obtained a significant gene expression profile (56 genes). Expression differences occurred in genes associated with signaling pathways, and energy metabolism pathways in the anterior cingulate. In the cerebellum and DLPFC bipolar patients also showed alterations in gene expression compared to controls. Dysregulation of gene expression in signaling and metabolic pathways suggests compromised anterior cingulate circuitry occurring as a consequence of abnormalities of cell signaling pathways.