Circular RNA and Neuropsychiatric Practice: A Scoping Review of the Literature and Discussion of Unmet Clinical Needs

Circular RNA (circRNA) is a recently characterized species of RNA that is highly enriched in the human brain, differentially expressed in neuropsychiatric disorders, and readily detectable in the peripheral circulation. These characteristics make circRNA an attractive candidate biomarker for neuropsychiatric illness and suggest it as a potential missing link in the understanding of the specific biological underpinnings of neuropsychiatric illness. In this scoping review, the authors summarize the literature on circRNA in neuropsychiatric disorders and add clinical context. The authors searched PubMed, PsycInfo, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials for articles describing research on circRNA and mental disorders published in or after 2012. The authors included peer-reviewed studies with substantive discussions of circRNA and mental disorders that included human participants or cell lines. Only studies written in English or with English translations were considered. Seventy-eight studies met the authors' inclusion criteria. Common and serious neuropsychiatric illnesses were well represented among these studies, including schizophrenia, major depressive disorder, and major neurocognitive disorder. Many studies identified altered circRNA levels in peripheral blood and specific brain regions that were both sensitive to and specific for neuropsychiatric disorders. Few studies discussed the role that circRNA-based diagnostic tests might play in clinical practice, and research on prognostic, therapeutic, or monitoring biomarkers was limited. Although circRNAs have the potential to change the understanding and treatment of neuropsychiatric disorders, the research field would benefit from more clinician involvement in this area to identify and address urgent clinical needs.