title: Altered gene expression in schizophrenia: findings from transcriptional signatures in fibroblasts and blood.
abstract: BACKGROUND
  Whole-genome expression studies in the peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insight into the molecular basis of the disorder and innovative biomarkers that may be of great utility in clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful for investigating molecular alterations in psychiatric disorders.
  
  
  METHODS
  A microarray expression study was conducted comparing skin fibroblast transcriptomic profiles from 20 SCZ patients and 20 controls. All genes strongly differentially expressed were validated by real-time quantitative PCR (RT-qPCR) in fibroblasts and analyzed in a sample of peripheral blood cell (PBC) RNA from patients (n = 25) and controls (n = 22). To evaluate the specificity for SCZ, alterations in gene expression were tested in additional samples of fibroblasts and PBCs RNA from Major Depressive Disorder (MDD) (n = 16; n = 21, respectively) and Bipolar Disorder (BD) patients (n = 15; n = 20, respectively).
  
  
  RESULTS
  Six genes (JUN, HIST2H2BE, FOSB, FOS, EGR1, TCF4) were significantly upregulated in SCZ compared to control fibroblasts. In blood, an increase in expression levels was confirmed only for EGR1, whereas JUN was downregulated; no significant differences were observed for the other genes. EGR1 upregulation was specific for SCZ compared to MDD and BD.
  
  
  CONCLUSIONS
  Our study reports the upregulation of JUN, HIST2H2BE, FOSB, FOS, EGR1 and TCF4 in the fibroblasts of SCZ patients. A significant alteration in EGR1 expression is also present in SCZ PBCs compared to controls and to MDD and BD patients, suggesting that this gene could be a specific biomarker helpful in the differential diagnosis of major psychoses.
authors: Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy.
authors: Nadia
authors: N
authors: Cattane
authors: Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy.
authors: Alessandra
authors: A
authors: Minelli
authors: Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors: Elena
authors: E
authors: Milanesi
authors: Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors: Carlo
authors: C
authors: Maj
authors: Psychiatric Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors: Stefano
authors: S
authors: Bignotti
authors: Psychiatric Hospital "Villa Santa Chiara", Verona, Italy.
authors: Marco
authors: M
authors: Bortolomasi
authors: Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Faculty of Psychology, eCampus University, Novedrate, Como, Italy.
authors: Luisella
authors: L
authors: Bocchio Chiavetto
authors: Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy; Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors: Massimo
authors: M
authors: Gennarelli
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D003865:Major Depressive Disorder / Q000097:blood / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000097:blood* / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012559:Schizophrenia / Q000097:blood / Q000235:genetics*; D012867:Skin / Q000166:cytology
chemical_list: D015415:Biomarkers; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1