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 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.
Niculescu
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AB
Department of Psychiatry, School of Medicine, University of California, San Diego, USA. aniculescu@ucsd.edu
Segal
D S
DS
Kuczenski
R
R
Barrett
T
T
Hauger
R L
RL
Kelsoe
J R
JR
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015239:Arylsulfotransferase; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics; D054770:G-Protein-Coupled Receptor Kinase 3; D023281:Genomics / Q000379:methods*; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011618:Psychotic Disorders / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D015238:Sulfotransferases / Q000235:genetics; D033921:Vesicular Transport Proteins
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C099173:LIN-7 protein, C elegans; C119588:LIN-7 protein, mammalian; C486532:LIN7A protein, human; C486531:LIN7C protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins; D007334:Insulin-Like Growth Factor I; D010088:Oxidoreductases; D013186:Farnesyl-Diphosphate Farnesyltransferase; D017346:Protein Serine-Threonine Kinases; D054770:G-Protein-Coupled Receptor Kinase 3; C517848:GRK3 protein, human; C517851:Grk3 protein, rat; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human