Abstract
Background: Schizophrenia is a serious mental disorder with complicated biological mechanisms. Few studies explore the transcriptional features that are shared in brain tissue and peripheral blood. In the present study, we aimed to explore the biological pathways with similar expression patterns in both peripheral blood mononuclear cells (PBMCs) and brain tissues.Methods: The present study used transcriptomics technology to detect mRNA expression of PBMCs of 10 drug-naïve patients with schizophrenia and 20 healthy controls. Transcriptome data sets of brain tissue of patients with schizophrenia downloaded from public databases were also analyzed in our study. The biological pathways with similar expression patterns in the PBMCs and brain tissues were uncovered by differential expression analysis, weighted gene co-expression network analysis (WGCNA), and pathway analysis. Finally, the expression levels of differential expressed genes (DEGs) were validated by real-time fluorescence quantitative polymerase chain reaction (qPCR) in another 12 drug-naïve patients with schizophrenia and 12 healthy controls.Results: We identified 542 DEGs, 51 DEGs, 732 DEGs, and 104 DEGs in PBMCs, dorsolateral prefrontal cortex, anterior cingulate gyrus, and nucleus accumbent, respectively. Five DEG clusters were recognized as having similar gene expression patterns in PBMCs and brain tissues by WGCNA. The pathway analysis illustrates that these DEG clusters are mainly enriched in several biological pathways that are related to phospholipid metabolism, ribosome signal transduction, and mitochondrial oxidative phosphorylation. The differential significance of PLAAT3, PLAAT4, PLD2, RPS29, RPL30, COX7C, COX7A2, NDUFAF2, and ATP5ME were confirmed by qPCR.Conclusions: This study finds that the pathways associated with phospholipid metabolism, ribosome signal transduction, and energy metabolism have similar expression patterns in PBMCs and brain tissues of patients with schizophrenia. Our results supply a novel insight for revealing the pathogenesis of schizophrenia and might offer a new approach to explore potential biological markers of peripheral blood in schizophrenia.
Highlights
Schizophrenia is a serious mental disorder characterized by hallucinations and delusions [1] with a lifetime risk of 0.72% [2], which brings a huge burden to more than 20 million patients and their families worldwide [3]
Some studies demonstrate impaired glycolytic response [9] and altered neural signaling and immune pathways [14] in peripheral blood mononuclear cells (PBMCs) of patients with schizophrenia. It is still unclear which gene expression patterns and biological pathways in the brain are reflected by PBMCs in schizophrenia
We present a hypothesis that PBMCs could reflect the molecular alterations in brain tissues of patients with schizophrenia to a certain extent and be a valid surrogate to explore molecular alterations in schizophrenia
Summary
Schizophrenia is a serious mental disorder characterized by hallucinations and delusions [1] with a lifetime risk of 0.72% [2], which brings a huge burden to more than 20 million patients and their families worldwide [3]. Peripheral blood mononuclear cells (PBMCs) become an important investigation carrier of schizophrenia because they can be acquired from patients and partly reflect the molecular alterations in the CNS [8, 9]. Some studies demonstrate impaired glycolytic response [9] and altered neural signaling and immune pathways [14] in PBMCs of patients with schizophrenia. It is still unclear which gene expression patterns and biological pathways in the brain are reflected by PBMCs in schizophrenia. We aimed to explore the biological pathways with similar expression patterns in both peripheral blood mononuclear cells (PBMCs) and brain tissues
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