Circulating microRNAs as a Novel Class of Potential Diagnostic Biomarkers in Neuropsychiatric Disorders

Abstract

Neuropsychiatric diseases, such as schizophrenia, bipolar disorder (BD), major depressive disorder (MDD) and autism spectrum disorder (ASD), are a huge burden on society, impairing the health of those affected, as well as their ability to learn and work. Biomarkers that reflect the dysregulations linked to neuropsychiatric diseases may potentially assist the diagnosis of these disorders. Most of these biomarkers are found in the brain tissue, which is not easily accessible. This is the challenge for the search of novel biomarkers that are present in various body fluids, including serum or plasma. As a group of important endogenous small noncoding RNAs that regulate gene expression at post-transcriptional level, microRNAs (miRNAs) play a crucial role in many physiological and pathological processes. Previously, researchers discovered that miRNAs contribute to the neurodevelopment and maturation, including neurite outgrowth, dendritogenesis and dendritic spine formation. These developments underline the significance of miRNAs as potential biomarkers for diagnosing and prognosing central nervous system diseases. Accumulated evidence indicates that there are considerable differences between the cell-free miRNA expression profiles of healthy subjects and those of patients. Therefore, circulating miRNAs are likely to become a new class of noninvasive, sensitive biomarkers. Despite the fact that little is known about the origin and functions of circulating miRNAs, their essential roles in the clinical diagnosis and prognosis of neuropsychiatric diseases make them attractive biomarkers. In this review we cover the increasing amounts of dataset that have accumulated in the last years on the use of circulating miRNAs and their values as potential biomarkers in most areas of neuropsychiatric diseases.

Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans

“…miRNAs, which are short, noncoding sequences that typically regulate gene expression by suppressing protein coding mRNA, have been demonstrated to be biomarkers for several psychological disorders, including schizophrenia, major depressive disorder, and bipolar disorder (Kichukova, Popov, Ivanov, & Vachev, 2016; Maffioletti et al, 2016; Schmidt, Keck, & Buell, 2015). Within the central nervous system, miRNA are considered to play a major role in gene expression regulation (Kuss & Chen, 2008; Martinetz, 2016); however, the specific role of miRNAs in PTSD remains largely unknown.…”

Long noncoding RNA and its contribution to autism spectrum disorders

“…For example, Wang et al 11 reported that hypermethylation of the enolase 2 (ENO2) gene is present in 15% of patients with ASDs. It is noteworthy that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which play important roles as transcriptional and/or posttranscriptional regulators, [12][13][14][15][16][17][18][19][20] have also been implicated in ASDs and other neurological disorders. Some prominent functional studies have shown that lncRNAs perform a wide variety of functions, including participating in the recruitment of chromatin modifying complexes, providing a scaffold for the assembly of protein complexes, modulating alternative splicing, and employing enhancer-like functions.…”

Circulating miRNA or circulating DNA—Potential biomarkers for organ transplant rejection

“…A rapid and inexpensive ddPCR has been developed that continuously monitors a patient's health status at a low cost (about one‐tenth of a new generation of sequencing methods) . Compared with the miRNA quantitation performed by ddPCR and real‐time PCR, ddPCR offers many potential advantages, including the ability to obtain absolute quantitation without external references, and has higher accuracy and improved reproducibility …”

“…39 Compared with the miRNA quantitation performed by ddPCR and real-time PCR, ddPCR offers many potential advantages, including the ability to obtain absolute quantitation without external references, and has higher accuracy and improved reproducibility. 95 With the further development of molecular biology, circulating miRNA combined with other molecular biological detection techniques may become sensitive and specific indicators of various clinical diseases with a wide range of clinical application.…”