Diagnosis of schizophrenia is currently dependent on symptom-based criteria and lacks objective indicators. In this study, the authors investigated whether circulating miRNA can serve as a diagnostic biomarker for schizophrenia.
Global plasma miRNAs were profiled in a test cohort of 164 schizophrenia patients and 187 control subjects, using Solexa sequencing, TaqMan Low Density Array, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The captured miRNAs were then validated by qRT-PCR assays in an independent cohort of 400 schizophrenia patients, 213 control subjects, and 162 patients with nonschizophrenia psychiatric disorders; the 400 schizophrenia patients underwent a 12-month follow up study of regular treatment with an atypical antipsychotic (risperidone and aripiprazole).
The global plasma miRNA screening revealed eight miRNAs that were up-regulated in schizophrenia, as revealed by both assay platforms. The qRT-PCR analysis showed the up-regulation of miR-130b and miR-193a-3p in schizophrenia but not in nonschizophrenia disorders.
The up-regulation of miR-130b and miR-193a-3p is a state-independent biomarker for schizophrenia, and these two miRNAs could be used to develop a diagnostic tool for schizophrenia.
FIGURE 1. Scheme for Schizophrenia-Associated Plasma miRNA Discovery and Validation Workflow – a qPCR=quantitative polymerase chain reaction; TLDA=TaqMan Low Density Array; sRNA-seq=small RNA sequencing. The plasma samples from the discovery group of 150 case subjects and 150 control subjects were pooled and extracted (A). RNA from each pool was then subjected to genome-wide miRNA analysis using TLDA and small RNA sequencing (B). miRNAs in common between the two techniques were then reanalyzed in individual qPCR reactions (C). The two miRNA molecules that remained significant through individual sample reactions were then validated in a large cohort using qPCR (D). Using the same qPCR, the authors then analyzed a subgroup of participants who were in remission (>6 months) after treatment with atypical antipsychotics (E). Samples designated nonschizophrenia psychiatric disorders were also analyzed and had levels similar to those of the control group (F).