Altered Gene Expression in Schizophrenia: Findings from Transcriptional Signatures in Fibroblasts and Blood

Abstract

BackgroundWhole-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.MethodsA 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).ResultsSix 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.ConclusionsOur 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.

Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression and proliferation of progenitor cells from the developing human neocortex

“…Immature neurons derived from induced pluripotent stem cells from individuals with schizophrenia have been found to exhibit increased TCF4 RNA expression compared with those derived from healthy controls, 29 suggesting that early developmental disturbances in TCF4 expression are relevant to the disorder. Increased TCF4 RNA expression in fibroblasts and blood from adults with schizophrenia 30 and psychosis 31 has also been reported.…”

Are There Schizophrenia Genetic Markers and Mutations? A Systematic Review and Meta-Analyses

“…(2015) [74] A microarray expression study was conducted comparing skin fibroblast transcriptomic profiles from 20 SCZ patients and 20…”

Human dermal fibroblasts in psychiatry research

“…In a recent analysis, Cattane et al (2015) performed transcriptome profiling of HDFs from SZ patients and controls using DNA microarrays and RT-qPCR. The study identified 6 differentially expressed genes ( Egr1, Fos, Fosb, Hist2h2be, Jun and Tcf4 ), 5 of which have been previously implicated in the pathophysiology of schizophrenia in postmortem brain, peripheral blood and genetic studies (Forrest et al, 2014; Kurian et al, 2011; Kyosseva, 2004).…”

“…Prolonged neuroinflammation with glial involvement is a key step in the progression of multiple psychiatric diseases (Leonard, 2007; Müller et al, 2012). Consequently, altered expression of immune and cell-cell communication molecular pathways in HDFs from subjects with MD and SZ (Cattane et al, 2015; Garbett et al, 2015b), as well as BD specific changes in the basal and cytokine-induced tryptophan-kynurenine metabolism (Brown et al, 2014; Johansson et al, 2013a) may reflect disrupted glial inflammatory functions in the brains of diseased individuals.…”