| Revisiting DARPP-32 in postmortem human brain: changes in schizophrenia and bipolar disorder and genetic associations with t-DARPP-32 expression. | |
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MedLine Citation:
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PMID: 23295814 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-08 |
Journal Detail:
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Title: Molecular psychiatry Volume: - ISSN: 1476-5578 ISO Abbreviation: Mol. Psychiatry Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9607835 Medline TA: Mol Psychiatry Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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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