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

C. A. Ogden, M. E. Rich, N. J. Schork, M. P. Paulus, M. A. Geyer, J. B. Lohr, R. Kuczenski, Alexander Niculescu

Research output: Contribution to journalArticle

182 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1007-1029
Number of pages23
JournalMolecular Psychiatry
Volume9
Issue number11
DOIs
StatePublished - Nov 2004

Fingerprint

Depressive Disorder
Genomics
Dopamine and cAMP-Regulated Phosphoprotein 32
Postmortem Changes
Genes
Tachykinins
Pleasure
Methamphetamine
Information Storage and Retrieval
Pharmacogenetics
Neurogenesis
Medical Genetics
Brain
Valproic Acid
Substance P
Myelin Sheath
Mood Disorders
Bipolar Disorder
Neurotransmitter Agents
Signal Transduction

Keywords

  • Bipolar
  • Convergent functional genomics
  • Methamphetamine
  • Microarray
  • Pain
  • Valproate

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders : An expanded convergent functional genomics approach. / Ogden, C. A.; Rich, M. E.; Schork, N. J.; Paulus, M. P.; Geyer, M. A.; Lohr, J. B.; Kuczenski, R.; Niculescu, Alexander.

In: Molecular Psychiatry, Vol. 9, No. 11, 11.2004, p. 1007-1029.

Research output: Contribution to journalArticle

Ogden, C. A. ; Rich, M. E. ; Schork, N. J. ; Paulus, M. P. ; Geyer, M. A. ; Lohr, J. B. ; Kuczenski, R. ; Niculescu, Alexander. / Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders : An expanded convergent functional genomics approach. In: Molecular Psychiatry. 2004 ; Vol. 9, No. 11. pp. 1007-1029.
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