Translational research in bipolar disorder: emerging insights from genetically based models
Open accessAbstract
Bipolar disorder (BPD) is characterized by vulnerability to episodic depression and mania and spontaneous cycling. Because of marked advances in candidate-gene and genome-wide association studies, the list of risk genes for BPD is growing rapidly, creating an unprecedented opportunity to understand the pathophysiology of BPD and to develop novel therapeutics for its treatment. However, genetic findings are associated with major unresolved issues, including whether and how risk variance leads to behavioral abnormalities. Although animal studies are key to resolving these issues, consensus is needed regarding how to define and monitor phenotypes related to mania, depression and mood swing vulnerability in genetically manipulated rodents. In this study we discuss multiple facets of this challenging area, including theoretical considerations, available tests, limitations associated with rodent behavioral modeling and promising molecular-behavioral findings. These include CLOCK, glycogen synthase kinase 3beta (GSK-3beta), glutamate receptor 6 (GluR6), extracellular signal-regulated kinase-1 (ERK1), p11 (or S100A10), vesicular monoamine transporter 2 (VMAT2 or SLC18A2), glucocorticoid receptors (GRs), Bcl-2-associated athanogene-1 (BAG1) and mitochondrial DNA polymerase-gamma (POLG). Some mutant rodent strains show behavioral clusters or activity patterns that cross-species phenocopy objective/observable facets of mood syndromes, and changes in these clustered behaviors can be used as outcome measures in genetic-behavioral research in BPD.
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Stress is a critical factor in promoting susceptibility to depression.
“Stress is a critical factor in promoting susceptibility to depression (2, 38)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [38]
The “Vulnerability to BPD” section says physical and social–psychological stressors can trigger relapse in people with bipolar disorder who have remitted from a manic or depressive episode. That supports a role for stress in mood-episode vulnerability, but it does not establish stress as a critical factor in susceptibility to depression generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe expression of HPA axis-related genes is associated with different clinical features of bipolar disorder.
“the expression of HPA axis-related genes is associated with different clinical features of BD (Colasanti et al. 2013;Spijker et al. 2011;Chen et al. 2010)”
From The HPA axis in bipolar disorder: Systematic review and meta-analysis (2016) · cites this paper as Chen et al. 2010
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References 78 · Cited by 95
Research works printed but not linked: 1
- [2]Goodwin FK Jamison KR Manic-Depressive Illness: Bipolar and Recurrent Unipolar Disorders 2007 2nd edn. New York Oxford University Press
- Authors
- Chen, G., Henter, I. D., & Manji, H. K.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Chen, G
- ORCID
- Henter, I D
- Venue
- Molecular Psychiatry
- Published
- 2010-02-09
- Volume
- 15
- Issue
- 9
- Pages
- 883-895
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC2999816
- OpenAlex
- W1988422061
- Cited by
- 95
- References
- 78
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 5 · 2021: 25 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 6 · 2016: 1 · 2015: 7 · 2014: 11 · 2013: 3 · 2012: 14
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 MH999999)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar disorder, candidate genes, risk genes, mania, depression, behavioral phenotyping, clock genes, glycogen synthase kinase-3β, GluR6, ERK1, p11, vesicular monoamine transporter 2, glucocorticoid receptor, BAG-1, DNA polymerase gamma, phenocopy, translational research
- MeSH terms
- Animals, Bipolar Disorder, Disease Models, Animal, Humans, Models, Genetic, Biomedical Research
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