Dysregulation of circRNA Expression in the Peripheral Blood of Individuals With Schizophrenia and Bipolar Disorder

Abstract Circular RNA (circRNA) are head-to-tail back-spliced RNA transcripts that have been linked to several biological processes and their perturbation is evident in human diseases, including neurological disorders. There is also emerging research suggesting circRNA expression may also be altered in psychiatric and behavioural syndromes. Here, we provide a comprehensive analysis of circRNA expression in peripheral blood mononuclear cells (PBMCs) from 39 patients with schizophrenia and bipolar disorder as well as 20 healthy individuals using deep RNA-seq. We observed systematic alternative splicing leading to a complex and diverse profile of RNA transcripts including 8,762 high confidence circRNAs. More specific scrutiny of the circular transcriptome in schizophrenia and bipolar disorder, compared to a non-psychiatric control group, revealed significant dysregulation of 55 circRNAs with a bias towards downregulation. These molecules were predicted to interact with a large number of miRNAs that target genes enriched in psychiatric disorders. Further replication and cross validation to determine the specificity of these circRNAs across broader diagnostic groups and subgroups in psychiatry will enable their potential utility as biomarkers to be established.