Gene expression profile in anterior cingulate of bipolar disorder

Marquis P. Vawter; Hiroaki Tomita; Simon Evans; Prabhakara Choudary Jim Meador-Woodruff; Jun Li; Richard Myers; Edward G. Jones; Stan Watson; Huda Akil; William E. Bunney
Society of Biological Psychiatry 57th Annual Convention. 2002.


Bipolar disorder is believed to have a high genetic inheritance component from family studies. Genome-wide scans to date have shown that genes of major effect are not common causes of bipolar disorder, but independent linkage studies looking for bipolar disorder susceptibility genes are converging on a several chromosomal locations, although replication remains an issue. Until recently most postmortem brain studies only examined a few or several genes in one experiment. Microarray analysis allows simultaneous measurements of >10,000 transcripts and can screen for differences in the concentration of mRNA transcripts between groups of samples. In order to profile gene expression differences between bipolar I disorder patients (n = 9) and matched controls (n = 9) we have extensively documented each group for family psychiatric history, drug abuse, and medication history, using psychiatric records and family interviews. We have minimized variables that might influence gene expression such as gender, age, pH, autolysis time, and have used replication as a further stringent criteria for selection of genes. We present results from our functional genomic screening of three brain regions using Affymetrix oligonucleotide chips (12,600 transcripts) in three brain regions, dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum. We show that gene expression is altered in the anterior cingulate cortex, which has been previously suggested to be involved in mood behavior. In comparison, a smaller number of genes were differentially expressed in the cerebellum and DLPFC in bipolar disorder. The present results suggest that few genes are globally dysregulated in 2-3 brain regions in bipolar disorder. Knowledge based annotation of the results suggest novel candidate genes and some overlap with hot spots from genome wide linkage studies. Our work will be compared to other recent investigations of alterations in gene expression in bipolar disorder. The microarray analysis al lows for identification of candidate genes that show regional interaction in the brain thus providing additional information for further neurobiological research into mental disorders and refinement by genetic linkage and association studies.