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Schizophrenia gene expression profile reverted to normal levels by antipsychotics

Abstract: BACKGROUND: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. METHODS: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. RESULTS: We found that 17 genes, among the 21 495 genes analyzed, have significantly-altered expression after medication (p-value adjusted [Padj] <0.05). Six genes (ADAMTS2, CD177, CNTNAP3, ENTPD2, RFX2, and UNC45B) out of the 17 are among the 200 genes that we characterized with differential expression in a previous study between antipsychotic-naïve schizophrenia patients and controls (Sainz et al., 2013). This number of schizophrenia-altered expression genes is significantly higher than expected by chance (Chi-test, Padj 1.19E-50), suggesting that at least part of the antipsychotic beneficial effects is exerted by modulating the expression of these genes. Interestingly, all six of these genes were overexpressed in patients and reverted to control levels of expression after treatment. We also found a significant enrichment of genes related to obesity and diabetes, known adverse affects of antipsychotics. CONCLUSIONS: These results may facilitate understanding of unknown molecular mechanisms behind schizophrenia symptoms and the molecular mechanisms of antipsychotic drugs.

 Fuente: Int J Neuropsychopharmacol. 2014 Oct 31;18(4). pii: pyu066

Editorial: Cambridge University Press

 Año de publicación: 2015

Nº de páginas: 7

Tipo de publicación: Artículo de Revista

 DOI: 10.1093/ijnp/pyu066

ISSN: 1461-1457,1469-5111

Proyecto español: Proyects SAF2010-20840-C02-01 and SAF2010- 20840-C02-02), Fundación Leonardo Torres Quevedo-Universidad de Cantabria (Exp.: FLTQ-2010), Foundation Ramón Areces; and Instituto de Investigación Marqués de Valdecilla (Exp.: AIP2011-02)