Abstract
Schizophrenia is a complex and heterogenous psychiatric disorder characterized by positive, negative, and cognitive symptoms. Our previous study identified three subgroups of schizophrenia patients based on plasma microRNA (miRNA) profiles. The present study aims to (1) verify the reproducibility of the miRNA-based patient stratification and (2) explore the pathophysiological pathways linked to the symptoms using plasma miRNAs. We measured levels of 376 miRNAs in plasma samples of schizophrenia patients and obtained their Positive and Negative Syndrome Scale (PANSS) scores and the Brief Assessment of Cognition in Schizophrenia (BACS) scores. The plasma miRNA profiles identified similar subgroups of patients as in the previous study, suggesting miRNA-based patient stratification is potentially reproducible. Our multivariate analysis identified optimal combinations of miRNAs to estimate the PANSS positive and negative subscales and BACS composite scores. Those miRNAs consistently enriched 'inflammation' and 'NFκB1' according to miRNA set enrichment analysis. Our literature-based text mining and survey confirmed that those miRNAs were associated with IL-1β, IL-6, and TNFα, suggesting that exacerbated positive, negative, and cognitive symptoms are associated with high inflammation. In conclusion, miRNAs are a potential biomarker to identify patient subgroups reflecting pathophysiological conditions and to investigate symptom-related molecular mechanisms in schizophrenia.