GeneSet Information

Tier III GS3649 • Candidate genes for bipolar and related disorders-Differentially expressed in mouse brain in response to Methamphetamine or Valproate


Genes reproducibly changed by Methamphetamine and/or Valproate treatment in mouse brain including PreFrontal Cortex, Amygdala, CaudatePutamen, Nucleus Accumbens and Ventral Tegmentum. (Tables 1-3 of paper)


Bipolar Disorder









Ogden CA, Rich ME, Schork NJ, Paulus MP, Geyer MA, Lohr JB, Kuczenski R, Niculescu AB


Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach.


Molecular psychiatry Nov 2004, Vol 9, pp. 1007-29


Identifying genes for bipolar mood disorders through classic genetics has proven difficult. Here, we present a comprehensive convergent approach that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a stimulant--methamphetamine, and a mood stabilizer--valproate), with human data (linkage loci from human genetic studies, changes in postmortem brains from patients), as a bayesian strategy of crossvalidating findings. Topping the list of candidate genes, we have DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) located at 17q12, PENK (preproenkephalin) located at 8q12.1, and TAC1 (tachykinin 1, substance P) located at 7q21.3. These data suggest that more primitive molecular mechanisms involved in pleasure and pain may have been recruited by evolution to play a role in higher mental functions such as mood. The analysis also revealed other high-probability candidates genes (neurogenesis, neurotrophic, neurotransmitter, signal transduction, circadian, synaptic, and myelin related), pathways and mechanisms of likely importance in pathophysiology. PUBMED: 15314610
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Annotation Information

Play and Playthings (D010988)
Genetics (D005823)
Genetic Testing (D005820)
Valproic Acid (D014635)
Myelin Sheath (D009186)
Tachykinins (D015320)
Mood Disorders (D019964)
Gene Expression Profiling (D020869)
Methamphetamine (D008694)
Central Nervous System Stimulants (D000697)
Microarray Analysis (D046228)
Genetic Predisposition to Disease (D020022)
Therapeutics (D013812)
Substance P (D013373)
Amygdala (D000679)
Enkephalins (D004745)
Prefrontal Cortex (D017397)
Nucleus Accumbens (D009714)
Dopamine and cAMP-Regulated Phosphoprotein 32 (D051937)
Pleasure (D057181)
Mice, Inbred C57BL (D008810)
Nerve Tissue Proteins (D009419)
Protein Precursors (D011498)
Neurotransmitter Agents (D018377)
Pharmacogenetics (D010597)
Genomics (D023281)
Signal Transduction (D015398)
Antimanic Agents (D018692)
Phosphoproteins (D010750)
transduction (GO:0009293)
signal transduction (GO:0007165)
gene expression (GO:0010467)

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