Abstract
To identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes . The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD, and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ.
Highlights
Schizophrenia (SZ) is a severe chronic mental disorder affecting about 1% of the population worldwide
differentially expressed (DE) mRNAs were identified through FC and P value filtering
With P values adjusted using Bonferroni correction (FC ≥ 2 and Padjusted < 0.05), 84 mRNAs were DE, of which, 82 were upregulated and 2 downregulated in SZ patients compared with healthy control subjects (Fig. 1, Supplementary Table S1)
Summary
Schizophrenia (SZ) is a severe chronic mental disorder affecting about 1% of the population worldwide. It is almost impractical to obtain biopsied brain tissue from SZ patients for the development of a molecular signature that may assist a diagnosis In this regard, peripheral blood mononuclear cells (PBMCs) can be collected from patients and followed longitudinally with gene expression analyses, which may provide a way of identifying the signatures of clinical subtypes, their prognosis and treatment response. Kumarasinghe et al.[11] detected 416 (67%) down-regulated and 208 up-regulated genes in blood of treatment-naive patients (age 36.1 ± 1 4.8) when compared to controls These studies showed that the patients had diverse disease durations and their age spanned a wide range (> 20 years), which will certainly affect the results. It remains controversial concerning the global direction of changes in genome expression for SZ
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