Translational research in bipolar disorder: emerging insights from genetically based models
Open Access
- 9 February 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 15 (9), 883-895
- https://doi.org/10.1038/mp.2010.3
Abstract
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 3β (GSK-3β), 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-γ (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.Keywords
This publication has 75 references indexed in Scilit:
- Role of mitochondrial DNA in calcium signaling abnormality in bipolar disorderCell Calcium, 2008
- The When and Where of BDNF and the Antidepressant ResponseBiological Psychiatry, 2008
- Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim testNeuropharmacology, 2008
- Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in AdultsJAMA, 2008
- Whole-genome association study of bipolar disorderMolecular Psychiatry, 2008
- Behavioral Phenotyping Strategies for Mutant MiceNeuron, 2008
- Genetics of Bipolar Disorder: Focus on BDNF Val66Met PolymorphismPublished by Wiley ,2008
- The FKBP5-Gene in Depression and Treatment Response—an Association Study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) CohortBiological Psychiatry, 2008
- Cellular Mechanisms Underlying the Antidepressant Effects of Ketamine: Role of α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid ReceptorsBiological Psychiatry, 2007
- A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorderMolecular Psychiatry, 2007