Identifying a series of candidate genes for mania and psychosis: a convergent functional genomics approach

We have used methamphetamine treatment of rats as an animal model for psych otic mania. Specific brain regions were analyzed comprehensively for change s in gene expression using oligonucleotide GeneChip microarrays. The data w as cross-matched against human genomic loci associated with either bipolar disorder or schizophrenia. Using this convergent approach, we have identifi ed several novel candidate genes (e.g., signal transduction molecules, tran scription factors, metabolic enzymes) that may be involved in the pathogene sis of mood disorders and psychosis. Furthermore, for one of these genes, G protein-coupled receptor kinase 3 (GRK3), we found by Western blot analysi s evidence for decreased protein levels in a subset of patient lymphoblasto id cell lines that correlated with disease severity. Finally, the classific ation of these candidate genes into two prototypical categories, psychogene s and psychosis-suppressor genes, is described.