Altered gene expression in schizophrenia: findings from transcriptional signatures in fibroblasts and blood

PLoS One. 2015 Feb 6;10(2):e0116686. doi: 10.1371/journal.pone.0116686. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Bipolar Disorder / blood
  • Bipolar Disorder / genetics
  • Case-Control Studies
  • Cells, Cultured
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / genetics
  • Early Growth Response Protein 1 / blood*
  • Early Growth Response Protein 1 / genetics*
  • Female
  • Fibroblasts / metabolism*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Genes, jun / genetics
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Schizophrenia / blood
  • Schizophrenia / genetics*
  • Skin / cytology


  • Biomarkers
  • EGR1 protein, human
  • Early Growth Response Protein 1

Associated data

  • GEO/GSE62333

Grants and funding

This research was supported by grants from the Italian Ministry of Health (RC and RF2007 Conv. 42) and Regione Lombardia (ID: 17387 SAL-13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.