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Animal models of neuropsychiatric disorders
Open accessAbstract
Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression and bipolar disorder. We argue for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders, and for explicit guidelines when animal models are reported.
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“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 [132]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“These include chronic unpredictable stress, restraint stress or foot-shock stress, followed by behavioral measures of anhedonia (e.g., sucrose preference) or behavioral despair (e.g., forced swim test and tail suspension test), which are often responsive to acute antidepressant treatment and do not address the multiple validities necessary for an effective animal model of depression4.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [4]
Experimental — accuracy not yet measuredIn the citing paper
“However, for complex psychiatric disorders with largely unknown genetic etiologies, environmental insults, specific pathologies, or biomarkers, the building of animal models with high construct validity has not yet been possible [94].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [94]
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“Mice subjected to chronic social defeat stress (CSDS) develop depression-like symptoms [134,135]”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [134]
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“The stress-induced behavioral phenotypes are reversed by chronic, but not acute antidepressant treatment, and are thus posited to have both face and predictive validity [8].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [8]
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“Stressed animals also tend to spend less time struggling against inescapable stressors such as forced swimming or tail suspension.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [8]
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“In contrast, the mouse and, more recently, the rat allow facile creation of genetic models of disease risk [Nestler & Hyman, 2010].”
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Metadata
- Authors
- Nestler, E. J., & Hyman, S. E.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Harvard University (US)
- Corresponding author
- Nestler, Eric J
- Venue
- Nature Neuroscience
- Published
- 2010-09-27
- Volume
- 13
- Issue
- 10
- Pages
- 1161-1169
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3750731
- OpenAlex
- W2007816528
- Cited by
- 2,023
- References
- 72
- Citations by year
- 2026: 81 · 2025: 109 · 2024: 101 · 2023: 103 · 2022: 114 · 2021: 144 · 2020: 146 · 2019: 160 · 2018: 135 · 2017: 151 · 2016: 131 · 2015: 168 · 2014: 140 · 2013: 109 · 2012: 109
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P50MH090963, R01MH051399, P50MH066172)
- National Institute on Drug Abuse (R01DA014133)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Keywords
- animal models of psychiatric disorders, schizophrenia, bipolar disorder, depression, neuropsychiatric disorders, model validation, reporting guidelines, biomarkers, treatment development, pathophysiology
- MeSH terms
- Animals, Mental Disorders, Disease Models, Animal, Humans, Nerve Tissue Proteins, Reproducibility of Results, Neurotransmitter Agents
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