Animal models of bipolar mania: The past, present and future
Open accessAbstract
Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly six million (∼2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying 'mood' cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD.
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Most animal models of bipolar disorder are endophenotype-based and probe various states of bipolar disorder from depression to mania-like behaviors, yet none have adequately captured the hallmark of bipolar disorder: state switching.
“Most animal models of BD are endophenotype-based and probe the various states of BD from depression (see above) to mania-like behaviors (for a detailed review see Logan and McClung133, yet none have adequately captured the hallmark of BD: state switching.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [133]
The section on evaluating animal models says the vast majority reproduce specific aspects of mania and identifies mood switching as a hallmark of BD. The genetic-models section says spontaneous cycling has been difficult to model, but also reports models that induce switching between mania- and depression-related behaviors. Thus the categorical claim that none adequately captures state switching goes beyond what the review says. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThere 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 [133]
The section on evaluating animal models of BD describes substantial challenges to face, predictive, and construct validity, and says no model can fully reproduce this complex disease. It does not establish that no models satisfy validity criteria or that a lack of such models is the main reason for a paucity of animal studies; the review discusses several existing models. (LLM, conf=0.84)
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References 315 · Cited by 136
Research works printed but not linked: 1
- Morissette J Villeneuve A Bordeleau L Rochette D Laberge C Gagne B Laprise C Bouchard G Plante M Gobeil L Shink E Weissenbach J Barden N 1999 Genome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in quebec points to a locus of major effect on chromosome 12q23-q24 Am J Med Genet 88 567 587 10490718
- Authors
- Logan, R. W., & McClung, C. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- McClung, C.A.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 321
- Pages
- 163-188
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC4766066
- OpenAlex
- W1155976162
- Cited by
- 136
- References
- 315
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 19 · 2019: 14 · 2018: 12 · 2017: 14 · 2016: 8 · 2014: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- IMHRO
- NARSAD (MH082876, DA023988, NS058339)
- The McKnight Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- bipolar disorder, mania, animal models, genetically modified mice, switching behavior, model validity, lithium, valproic acid, pathophysiology, mood stabilizers, translational research
- MeSH terms
- Animals, Antidepressive Agents, Bipolar Disorder, Disease Models, Animal, Humans, Mice, Transgenic, Antimanic Agents, Mice
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