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 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.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Chen G,Henter ID,Manji HKdoi
10.1038/mp.2010.3subject
Has Abstractpub_date
2010-09-01 00:00:00pages
883-95issue
9eissn
1359-4184issn
1476-5578pii
mp20103journal_volume
15pub_type
杂志文章,评审abstract::Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysi...
journal_title:Molecular psychiatry
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pub_type: 杂志文章,meta分析
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pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Molecular psychiatry
pub_type: 杂志文章
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更新日期:2009-06-01 00:00:00