title: 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.
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Medicine & Psychiatry. School of Medicine University of Cantabria-IDIVAL, Santander, Spain (Dr Crespo-Facorro); CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain (Dr Crespo-Facorro); Spanish National Research Council (CSIC), Institute of Biomedicine and Biotechnology of Cantabria, Santander, Spain (Drs Prieto and Sainz).
authors.forename: Benedicto
authors.initials: B
authors.lastname: Crespo-Facorro
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Medicine & Psychiatry. School of Medicine University of Cantabria-IDIVAL, Santander, Spain (Dr Crespo-Facorro); CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain (Dr Crespo-Facorro); Spanish National Research Council (CSIC), Institute of Biomedicine and Biotechnology of Cantabria, Santander, Spain (Drs Prieto and Sainz).
authors.forename: Carlos
authors.initials: C
authors.lastname: Prieto
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Medicine & Psychiatry. School of Medicine University of Cantabria-IDIVAL, Santander, Spain (Dr Crespo-Facorro); CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain (Dr Crespo-Facorro); Spanish National Research Council (CSIC), Institute of Biomedicine and Biotechnology of Cantabria, Santander, Spain (Drs Prieto and Sainz). sainzjv@unican.es.
authors.forename: Jesus
authors.initials: J
authors.lastname: Sainz
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate / Q000627:therapeutic use; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D013844:Thiazoles / Q000627:therapeutic use; D059467:Transcriptome / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D000068180:Aripiprazole; D018967:Risperidone; D000077152:Olanzapine
keywords: RNA profile; antipsychotics; gene differential expression; next generation sequencing; schizophrenia