Schizophrenia (SZ) is a severe chronic mental disorder with a high heritability. Current microarray analyses typically focus on identifying differentially expressed genes or enriched pathways relevant to phenotypes. Whether there is a variability change of the genomic transcription in diseases has rarely been explored. In this study, we compared coefficient of variation (CV, the ratio of the standard deviation to the mean) of genome transcription of early-onset SZ (EOS) patients with controls in a blood mRNA microarray dataset and a blood microRNA (miRNA) microarray dataset. Furthermore, we compared CV of the expression levels of 17 genes in blood of the 30 patients before and after the 12-week treatment using real-time quantitative PCR (RT-qPCR) analysis. Our results indicated a significant increase of CV of genome transcription in patients compared with controls in both the mRNA and the miRNA datasets. The 30 after-treatment patients showed a significant decrease of CV of gene expression compared with the before-treatment patients. Our study may implicate the blood gene expression variability in SZ, providing further evidence supporting the abnormality of peripheral blood transcriptome in SZ. Given that peripheral blood can be easily collected from patients and followed longitudinally, our results may indicate a new way to facilitate the identification of the signatures of clinical subtypes, their prognosis and treatment response.