Microarray Studies in Mood Disorders: Distinct Patterns Seen Between Major Depression and Bipolar Disorder in Two Frontal Cortical Regions
Huda Akil; Simon Evans; Prabhakara Choudary; Marquis P. Vawter; Hiroaki Tomita; Jun Li; Jim Meador-Woodruff; Juan Lopez ; Fan Meng; Richard Myers; William E. Bunney; Edward G. Jones; Stanley J. Watson
41st Annual Meeting of the American College of Neuropsychopharmacology. 2002.
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 suffering from severe mood disorders. Two separate cohorts of subjects, each including 10 mood disorder and 10 matched control subjects were studied. The total of 20 mood disorder brains (across the two cohorts) included 9 bipolar and 11 MDD patients. Each pair (case and its control) was individually matched on the basis of gender, age and postmortem interval. Three brain regions, the Dorsolateral Prefrontal Cortex (DLPFC), the Anterior Cingulate Cortex (AnCg) and the Cerebellum were extracted for RNA and subjected to analysis with Affymetrix Oligonucleotide Chips (probing 12, 600 transcripts). Each RNA sample was subjected to independent analysis across two separate sites (eg. University of Michigan and University of California Davis), to allow for assessment of technical reliability. Numerous issues regarding quality controls and extraneous variables were systematically investigated. The results revealed some unexpected findings: a) Even though the two cortical regions, DLPF and AnCg had nearly identical gene expression profiles in normal controls, they were significantly different in their response to mood disorders. b) The two types of disorders, MDD and Bipolar, showed distinctly different profiles of gene expression, with few genes shared in common between them. c) Thus, there was a disease by region interaction, whereby the Bipolar subjects showed profound changes in the AnCg but not in the DLPFC whereas the MDD subjects showed less profound changes in general in these cortical regions, but greater effects in the DLPFC than in the AnCg. The alterations in Cerebellum were of lesser magnitude and comparable across the two disorders. The presentation will discuss these findings and will focus on the results associated with MDD, as the Bipolar results will be described in detail by Vawter et al in the sa me symposium. It will also point to a number of important caveats that need to be considered in using microarray technology in the context of postmortem human brains, and will discuss the necessary future steps to validate these findings. This work was funded by the Pritzker Neuropsychiatric Disorders Research Consortium, Pritzker Family Philanthropic Fund, NIH Conte Center grant #L99MH60398, and NIMH Program Project Grant 5 P01 MH42251.