Heterogeneity and Individuality: microRNAs in Mental Disorders

Abstract

MicroRNAs are about 22 nucleotide long single-stranded RNA molecules, negatively regulating gene expression of a single gene or a gene network. In neural tissues, they have been implicated in developmental and neuroplasticity-related processes, such as neurogenesis, differentiation, apoptosis and long-term potentiation. Their molecular mode of action is reminiscent of findings of genome-wide association studies in mental disorders, unable to attribute the risk of disease to a specific gene, but rather to multiple genes, gene-networks and gene-environment interaction. As such, microRNAs are an attractive target for research. Here, we review clinical studies conducted in humans on microRNAs in mental disorders with a particular focus on schizophrenia, bipolar disorder, major depressive disorder and anxiety disorders. The majority of clinical studies have focused on schizophrenia. The most robust finding has been reported for rs1625579 located in MIR137HG, which was associated with schizophrenia on a genome-wide level. Concerning bipolar disorder, major depression and anxiety disorders, promising results have been published, but only a considerably smaller number of clinical studies is available and genome-wide association studies did not suggest a direct link to microRNAs so far. Expression of microRNAs as biomarkers of mental disorders and treatment response is currently emerging with preliminary results. Larger-scaled genetic and functional studies along with translational research are needed to enhance our understanding of microRNAs in mental disorders. These studies will aid in disentangling the complex genetic nature of these disorders and possibly contribute to the development of novel, individualized diagnostic and therapeutic approaches.

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

“…As regards, for example, their genetic and epigenetic underpinnings, and differences in personality (Castro et al, 2012;Hommers et al, 2014;Kas et al, 2011b;Reale et al, 2007;Verheij and Cools, 2008). Inter-individual differences can provide a lot of usually neglected yet important information and, mirroring ethological work, their analysis in the course of long-term, longitudinal studies commencing in development would be of particular interest (Clutton-Brock and Sheldon, 2010;Kas et al, 2011a).…”

Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis

“…Gene variation in microRNA-binding sites may cause expression of many genes to differ, further supporting a key regulatory role for microRNA (Kim & Bartel, 2009;Hommers et al, 2015). Recent studies suggest that functional SNPs occurring in miRNA sequences or binding sites of miRNAs, namely the miRNA-SNPs, are associated with susceptibility to various diseases, which highlights a new paradigm for genetic susceptibility (Chen et al, 2013).…”

Recent developments in understanding the mechanism and functions of microRNAs

“…miRNAs also regulate the development of nervous system and neural miRNAs like miR-124, miR-132, miR-134 and miR138 have been shown to be involved in the synaptic development and synapse maturation [55,56]. Various other nervous disorders like bipolar disorder, schizophrenia, and anxiety disorders have also been associated with miRNA expression [57].…”