GLOBAL GENE EXPRESSION PROFILING OF POSTMORTEM BRAINS FROM PSYCHIATRIC PATIENTS REVEALS DIFFERENCES IN SEVERAL PHYSIOLOGICAL PATHWAYS BETWEEN DIFFERENT MOOD DISORDERS
Prabhakara Choudary; Simon Evans; Marquis Vawter; Hiroaki Tomita; Jun Li; James Meador-Woodruff; Juan Lopez; Richard Myers; William Bunney; Stanley Watson; Huda Akil; Edward Jones
XIX International Congress of Genetics. 2003.
We are interested in gaining a better understanding of the biological basis of psychiatric diseases. As one approach towards this goal, we profiled global gene expression levels in subjects with mood disorders, i.e., bipolar disorder (BPD), and major depressive disorder (MDD), relative to healthy control subjects using microarrays. We isolated total RNA from the anterior cingulate cortex (AnCg), dorsolateral prefrontal cortex (DLPFC) and cerebellum (CB) of postmortem brains from psychiatric patients (BPD, n=9; and MDD, n=11; and individually-matched controls, n=12). The RNA was labelled and interrogated with Affymetrix human GeneChips (HG_U95Av2; HG_U133). RNA preparations, each split into 2 identical samples were processed independently as technical replicates, with sample labelling, hybridization and scanning performed at two different laboratories. Probe sets that showed statistically significant (p<0.05) changes (increase/decrease) in each region were identified and clustered using Microarray Suite 5, dCHIP, and RMA. Candidate genes identified by microarray analysis were validated by quantitative polymerase chain reaction and in situ hybridization. Interesting differences marked the two mood disorders as well as different brains region examined. The physiological pathways that showed differential gene expression patterns between the two disorders include signaling and metabolic pathways (BPD-AnCg), and growth factor pathway (MDD-DLPFC). We will discuss the biological/neurophysiological significance of the functional correlates of each pathway affected in each case, i.e., between bipolar disorder and major depressive disorder, and across cortex and cerebellum. This research was supported by The Pritzker Neuropsychiatric Disorders Research Consortium, Pritzker Family Philanthropic Fund, NIH CONTE Center grant #L99MH60398, and WM Keck Foundation.