Reverse translational strategies for developing animal models of bipolar disorder
Open accessAbstract
Bipolar disorder (BD) affects a significant portion of the population of the world, yet there has been limited success in developing novel treatments for the disorder. One of the major reasons for this dearth is the absence of suitable animal models for BD. Traditionally, animal models of human phenomena have been evaluated based on similarity to the human syndrome, response to appropriately corresponding medications, and the degree to which a model supports a common mechanistic theory between the human disorder and the model itself. The following review emphasizes the use of ‘reverse translation’, drawing on patient-based findings to develop suitable animal models for BD. We highlight some examples of this strategy, emphasizing their construct validity as a starting point. These studies have produced informative models that have altered the expression of genes/pathways implicated in BD, including the point mutation D181A of mouse mitochondrial DNA polymerase (POLG), glutamate receptor 6 (GluR6), Clock, extracellular regulated kinase 1 (ERK1), glycogen synthase kinase-3β (GSK-3β), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated athanogene (BAG-1). These studies demonstrate that this method is useful, viable and deserves attention in new efforts to generate animal models of BD.
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There is a paucity of animal studies of bipolar disorder mainly because there are no animal models that satisfy the validity criteria for modeling this complex multifactorial disorder.
“There is a paucity of animal studies of BD mainly because there are no animal models that satisfy the validity criteria for modeling this complex multifactorial disorder130–133.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [131]
The Introduction says that no proposed bipolar-disorder animal model completely satisfies all three validity criteria and that limitations of existing models have constrained research. It does not say animal studies are scarce or that a scarcity of studies is mainly caused by those limitations; it instead describes many attempts to develop models. (LLM, conf=0.87)
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Flagged first, then by citations
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- Authors
- Malkesman, O., Austin, D. R., Chen, G., & Manji, H. K.
- Affiliations
- National Institutes of Health (US)
- Venue
- Disease Models & Mechanisms
- Publisher
- The Company of Biologists
- Published
- 2009-04-30
- Volume
- 2
- Issue
- 5-6
- Pages
- 238-245
- ISSN
- 1754-8403 (ISSN-L)
- 1754-8411
- PMC
- PMC2675806
- OpenAlex
- W2020415498
- Cited by
- 70
- References
- 108
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 3 · 2015: 9 · 2014: 13 · 2013: 3 · 2012: 5
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Disease Models & Mechanisms (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Keywords
- bipolar disorder, animal models, reverse translation, construct validity, GluR6, clock genes, ERK1, glycogen synthase kinase-3β, Bcl-2, BAG-1, gene expression
- MeSH terms
- Animals, Bipolar Disorder, Depression, Disease Models, Animal, Disease Susceptibility, Humans, Mutation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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