Document Detail


Common effect of antipsychotics on the biosynthesis and regulation of fatty acids and cholesterol supports a key role of lipid homeostasis in schizophrenia.
MedLine Citation:
PMID:  19150222     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
For decades, the dopamine hypothesis has gained the most attention in an attempt to explain the origin and the symptoms of schizophrenia. While this hypothesis offers an explanation for the relationship between psychotic symptoms and dopamine kinetics, it does not provide a direct explanation of the etiology of schizophrenia which remains poorly understood. Consequently, current antipsychotics that target neurotransmitter receptors, have limited and inconsistent efficacy. To gain insights into the mechanism of action of these drugs, we studied the expression profile of 12,490 human genes in a cell line treated with 18 antipsychotics, and compared it to that of a library of 448 other compounds used in a variety of disorders. Analysis reveals a common effect of antipsychotics on the biosynthesis and regulation of fatty acids and cholesterol, which is discussed in the context of a lipid hypothesis where alterations in lipid homeostasis might underlie the pathogenesis of schizophrenia. This finding may help research aimed at the development of novel treatments for this devastating disease.
Authors:
Mihael H Polymeropoulos; Louis Licamele; Simona Volpi; Kendra Mack; Shruti N Mitkus; Eugene D Carstea; Lise Getoor; Andrew Thompson; Christian Lavedan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-15
Journal Detail:
Title:  Schizophrenia research     Volume:  108     ISSN:  0920-9964     ISO Abbreviation:  Schizophr. Res.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-23     Completed Date:  2009-06-16     Revised Date:  2010-09-02    
Medline Journal Info:
Nlm Unique ID:  8804207     Medline TA:  Schizophr Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  134-42     Citation Subset:  IM    
Affiliation:
Vanda Pharmaceuticals Inc., 9605 Medical Center Drive, Rockville, Maryland 20850, USA.
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MeSH Terms
Descriptor/Qualifier:
Antipsychotic Agents / pharmacology*
Cell Line, Transformed
Cholesterol / metabolism*
Epithelial Cells / drug effects*
Fatty Acids / metabolism*
Gene Expression Profiling / methods
Gene Expression Regulation / drug effects*,  physiology
Humans
Microarray Analysis / methods
Receptors, Estrogen / genetics,  metabolism
Retina / cytology
Statistics, Nonparametric
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 0/Fatty Acids; 0/Receptors, Estrogen; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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