Publication Details

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

Authors:Ogden CA, Rich ME, Schork NJ, Paulus MP, Geyer MA, Lohr JB, Kuczenski R, Niculescu AB
Title:Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach.
Journal:Molecular psychiatry Nov 2004 , Vol 9 , pp. 1007-29
Abstract: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
Ontological Annotations:
  • D014635: Valproic Acid (PubMed MeSH Annotations)
  • D006801: Humans (Publication, NCBO Annotator)
  • D057181: Pleasure (Publication, NCBO Annotator)
  • D009186: Myelin Sheath (Publication, NCBO Annotator)
  • D000697: Central Nervous System Stimulants (PubMed MeSH Annotations)
  • D001921: Brain (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D011498: Protein Precursors (PubMed MeSH Annotations)
  • D015320: Tachykinins (PubMed MeSH Annotations)
  • D008810: Mice, Inbred C57BL (PubMed MeSH Annotations)
  • D018692: Antimanic Agents (PubMed MeSH Annotations)
  • D010988: Play and Playthings (Publication, NCBO Annotator)
  • D020869: Gene Expression Profiling (PubMed MeSH Annotations)
  • D000339: Affect (Publication, NCBO Annotator)
  • D010750: Phosphoproteins (PubMed MeSH Annotations)
  • D012380: Role (Publication, NCBO Annotator)
  • D008694: Methamphetamine (PubMed MeSH Annotations)
  • D004745: Enkephalins (PubMed MeSH Annotations)
  • D020022: Genetic Predisposition to Disease (PubMed MeSH Annotations)
  • MA:0000168: brain (Publication, NCBO Annotator)
  • D015398: Signal Transduction (Publication, NCBO Annotator)
  • GO:0009293: transduction (Publication, NCBO Annotator)
  • D051937: Dopamine and cAMP-Regulated Phosphoprotein 32 (PubMed MeSH Annotations)
  • D018377: Neurotransmitter Agents (Publication, NCBO Annotator)
  • D010597: Pharmacogenetics (PubMed MeSH Annotations)
  • D013373: Substance P (PubMed MeSH Annotations)
  • D046228: Microarray Analysis (PubMed MeSH Annotations)
  • GO:0007165: signal transduction (Publication, NCBO Annotator)
  • D005820: Genetic Testing (PubMed MeSH Annotations)
  • D005823: Genetics (Publication, NCBO Annotator)
  • D010146: Pain (Publication, NCBO Annotator)
  • D009419: Nerve Tissue Proteins (PubMed MeSH Annotations)
  • D019964: Mood Disorders (Publication, NCBO Annotator)
  • D051379: Mice (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D023281: Genomics (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D013812: Therapeutics (Publication, NCBO Annotator)
  • GO:0010467: gene expression (Publication, NCBO Annotator)

1 GeneSets from this Publication:


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Expand Tier III Mouse 77 Genes GS3649: Candidate genes for bipolar (manic-depressive) and related disorders-Differentially expressed in mouse brain in response to Methamphetamine or Valproate