Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach
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.
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The valproate-induced changes in CK1ε and Cry2 expression were prevented by co-treatment with methamphetamine.
“These changes were prevented by co-treatment with methamphetamine, which was given to induce manic-like symptoms”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Ogden et al., 2004
Valproate decreased the expression of CK1ε and Cry2 in the amygdala.
“a microarray study by Ogden et al., found that the mood stabilizer, valproate, decreased the expression of CK1ε and Cry2 in the amygdala”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Ogden et al., 2004
The valproate-induced changes in CK1ε and Cry2 expression may be involved in the treatment of mania.
“suggesting that they may be involved in the treatment of mania (Ogden et al., 2004).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Ogden et al., 2004
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- Authors
- Ogden, C. A., Rich, M. E., Schork, N. J., Paulus, M. P., Geyer, M. A., Lohr, J. B., Kuczenski, R., & Niculescu, A. B.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Niculescu, A B
- Venue
- Molecular Psychiatry
- Published
- 2004-08-17
- Volume
- 9
- Issue
- 11
- Pages
- 1007-1029
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2114272370
- Cited by
- 221
- References
- 154
- Citations by year
- 2024: 4 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 12 · 2015: 13 · 2014: 5 · 2013: 10 · 2012: 19
- FWCI
- 11.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of California, San Diego
- Veterans Affairs San Diego Healthcare System
- National Institute of Mental Health (T32MH018399)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- bipolar disorder, candidate genes, methamphetamine, valproic acid, DARPP-32, proenkephalin, TAC1, substance P, dopamine, mood regulation, neurogenesis, neurotrophic factors, neurotransmitters, signal transduction, circadian rhythm, synaptic function, myelin
- MeSH terms
- Central Nervous System Stimulants, Animals, Bayes Theorem, Bipolar Disorder, Brain, Disease Models, Animal, Enkephalins, Genetic Testing, Humans, Genetic Linkage, Male, Methamphetamine, Mice, Inbred C57BL, Nerve Tissue Proteins, Pharmacogenetics, Phosphoproteins, Protein Precursors, Substance P, Valproic Acid, Tachykinins, Antimanic Agents, Genetic Predisposition to Disease, Gene Expression Profiling, Genomics, Microarray Analysis, Mice, Dopamine and cAMP-Regulated Phosphoprotein 32
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