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Physiol. Genomics 4: 83-91, 2000;
1094-8341/00 $5.00
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Received 31 July 2000; accepted in final form 15 September 2000.
Physiological Genomics 4:83-91 (2000)
1094-8341/00 $5.00 © 2000 American Physiological Society

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

ALEXANDER B. NICULESCU, III1,2, DAVID S. SEGAL1, RONALD KUCZENSKI1, THOMAS BARRETT1,2, RICHARD L. HAUGER1,2 and JOHN R. KELSOE1,2

1 Department of Psychiatry, School of Medicine, University of California, San Diego
2 Department of Psychiatry, San Diego Veterans Affairs Healthcare System, La Jolla, California 92093

We have used methamphetamine treatment of rats as an animal model for psychotic mania. Specific brain regions were analyzed comprehensively for changes in gene expression using oligonucleotide GeneChip microarrays. The data was cross-matched against human genomic loci associated with either bipolar disorder or schizophrenia. Using this convergent approach, we have identified several novel candidate genes (e.g., signal transduction molecules, transcription factors, metabolic enzymes) that may be involved in the pathogenesis of mood disorders and psychosis. Furthermore, for one of these genes, G protein-coupled receptor kinase 3 (GRK3), we found by Western blot analysis evidence for decreased protein levels in a subset of patient lymphoblastoid cell lines that correlated with disease severity. Finally, the classification of these candidate genes into two prototypical categories, psychogenes and psychosis-suppressor genes, is described.

brain; amphetamine; microarrays; GRK3




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