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

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

Author information

1
Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy.
2
Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
3
Psychiatric Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
4
Psychiatric Hospital "Villa Santa Chiara", Verona, Italy.
5
Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Faculty of Psychology, eCampus University, Novedrate, Como, Italy.
6
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.

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.

PMID:
25658856
PMCID:
PMC4319917
DOI:
10.1371/journal.pone.0116686
[Indexed for MEDLINE]
Free PMC Article

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