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Revisiting DARPP-32 in postmortem human brain: changes in schizophrenia and bipolar disorder and genetic associations with t-DARPP-32 expression.
MedLine Citation:
PMID:  23295814     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32 or PPP1R1B) has been of interest in schizophrenia owing to its critical function in integrating dopaminergic and glutaminergic signaling. In a previous study, we identified single-nucleotide polymorphisms (SNPs) and a frequent haplotype associated with cognitive and imaging phenotypes that have been linked with schizophrenia, as well as with expression of prefrontal cortical DARPP-32 messenger RNA (mRNA) in a relatively small sample of postmortem brains. In this study, we examined the association of expression of two major DARPP-32 transcripts, full-length (FL-DARPP-32) and truncated (t-DARPP-32), with genetic variants of DARPP-32 in three brain regions receiving dopaminergic input and implicated in schizophrenia (the dorsolateral prefrontal cortex (DLPFC), hippocampus and caudate) in a much larger set of postmortem samples from patients with schizophrenia, bipolar disorder, major depression and normal controls (>700 subjects). We found that the expression of t-DARPP-32 was increased in the DLPFC of patients with schizophrenia and bipolar disorder, and was strongly associated with genotypes at SNPs (rs879606, rs90974 and rs3764352), as well as the previously identified 7-SNP haplotype related to cognitive functioning. The genetic variants that predicted worse cognitive performance were associated with higher t-DARPP-32 expression. Our results suggest that variation in PPP1R1B affects the abundance of the splice variant t-DARPP-32 mRNA and may reflect potential molecular mechanisms implicated in schizophrenia and affective disorders.Molecular Psychiatry advance online publication, 8 January 2013; doi:10.1038/mp.2012.174.
Authors:
Y Kunii; T M Hyde; T Ye; C Li; B Kolachana; D Dickinson; D R Weinberger; J E Kleinman; B K Lipska
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-08
Journal Detail:
Title:  Molecular psychiatry     Volume:  -     ISSN:  1476-5578     ISO Abbreviation:  Mol. Psychiatry     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607835     Medline TA:  Mol Psychiatry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Section on Neuropathology, Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA [2] Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan.
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