| Evidence for disease and antipsychotic medication effects in post-mortem brain from schizophrenia patients. | |
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MedLine Citation:
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PMID: 20921955 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Extensive research has been conducted on post-mortem brain tissue in schizophrenia (SCZ), particularly the dorsolateral prefrontal cortex (DLPFC). However, to what extent the reported changes are due to the disorder itself, and which are the cumulative effects of lifetime medication remains to be determined. In this study, we employed label-free liquid chromatography-mass spectrometry-based proteomic and proton nuclear magnetic resonance-based metabonomic profiling approaches to investigate DLPFC tissue from two cohorts of SCZ patients grouped according to their lifetime antipsychotic dose, together with tissue from bipolar disorder (BPD) subjects, and normal controls (n=10 per group). Both techniques showed profound changes in tissue from low-cumulative-medication SCZ subjects, but few changes in tissue from medium-cumulative-medication subjects. Protein expression changes were validated by Western blot and investigated further in a third group of subjects who were subjected to high-cumulative-medication over the course of their lifetime. Furthermore, key protein expression and metabolite level changes correlated significantly with lifetime antipsychotic dose. This suggests that the detected changes are present before antipsychotic therapy and, moreover, may be normalized with treatment. Overall, our analyses revealed novel protein and metabolite changes in low-cumulative-medication subjects associated with synaptogenesis, neuritic dynamics, presynaptic vesicle cycling, amino acid and glutamine metabolism, and energy buffering systems. Most of these markers were altered specifically in SCZ as determined by analysis of the same brain region from BPD patients. |
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Authors:
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M K Chan; T M Tsang; L W Harris; P C Guest; E Holmes; S Bahn |
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Publication Detail:
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Type: Journal Article Date: 2010-10-05 |
Journal Detail:
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Title: Molecular psychiatry Volume: 16 ISSN: 1476-5578 ISO Abbreviation: Mol. Psychiatry Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9607835 Medline TA: Mol Psychiatry Country: England |
Other Details:
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Languages: eng Pagination: 1189-202 Citation Subset: IM |
Affiliation:
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Department of Chemical Engineering and Biotechnology, Institute of Biotechnology, University of Cambridge, Cambridge, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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