Abstract
To date, diagnosis of schizophrenia is still based on clinical interviews and careful observations, which is subjective and variable, and can lead to misdiagnosis and/or delay in diagnosis. As early intervention in schizophrenia is important in improving outcomes, objective tests that can be used for schizophrenia diagnosis or treatment monitoring are thus in great need. MicroRNAs (miRNAs) negatively regulate target gene expression and their biogenesis is tightly controlled by various factors including transcription factors (TFs). Dysregulation of miRNAs in brain tissue and peripheral blood mononuclear cells (PBMNCs) from patients with schizophrenia has been well documented, but analysis of the sensitivity and specificity for potential diagnostic utility of these alternations is limited. In this study, we explored the TF-miRNA-30-target gene axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring. Using bioinformatics analysis, we retrieved all TFs that control the biogenesis of miRNA 30 members as well as all target genes that are regulated by miRNA-30 members. Further, reverse transcription-quantitative PCR analysis revealed that the early growth response protein 1 (EGR1) and miR-30a-5p were remarkably downregulated, whereas neurogenic differentiation factor 1 (NEUROD1) was significantly upregulated in PBMNCs from patients in acute psychotic state. Antipsychotics treatment resulted in the elevation of EGR1 and miR-30a-5p but the reduction of NEUROD1. Receiver operating characteristic analysis showed that the EGR1-miR-30a-5p-NEUROD1 axis possessed significantly greater diagnostic value than miR-30a-5p alone. Our data suggest the EGR1-miR-30a-5p-NEUROD1 axis might serve as a promising biomarker for diagnosis and treatment monitoring for those patients in acute psychotic state.
Highlights
Schizophrenia is a debilitating mental disorder with an overall prevalence estimate of ~ 4.0 per 1000 people.[1,2] This major psychotic disorder is characterized by early adulthood onset and complex clinical symptoms related to neurocognitive and neurophysiological dysfunction
As early intervention in schizophrenia is important in improving outcome,[13,14] objective tests that can be used for schizophrenia diagnosis or medication response monitoring are in great need to enable effective treatment.[12,15,16]
Study subjects Preliminary data from 10 patients and 10 controls showed that the levels of early growth response protein 1 (EGR1) and miR-30a-5p within each group were distributed with a respective s.d. of ~ 2.0 and if the true difference in the patient and control means is ~ 1.5 as observed in the preliminary study, according to the analysis with the Power and Sample Size Program, we would need to study at least 29 cases and 29 controls to be able to reject the null hypothesis that the means of the patient and control groups are equal with a probability of 0.8
Summary
Schizophrenia is a debilitating mental disorder with an overall prevalence estimate of ~ 4.0 per 1000 people.[1,2] This major psychotic disorder is characterized by early adulthood onset and complex clinical symptoms related to neurocognitive and neurophysiological dysfunction. Diagnosis of schizophrenia is based on clinical interviews and careful observations. These descriptive methods are subjective and variable, which can lead to delay in diagnosis and/or misdiagnosis.[12] As early intervention in schizophrenia is important in improving outcome,[13,14] objective tests that can be used for schizophrenia diagnosis or medication response monitoring are in great need to enable effective treatment.[12,15,16]
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