MicroRNA and Posttranscriptional Dysregulation in Psychiatry

Abstract

Psychiatric syndromes, including schizophrenia, mood disorders, and autism spectrum disorders, are characterized by a complex range of symptoms, including psychosis, depression, mania, and cognitive deficits. Although the mechanisms driving pathophysiology are complex and remain largely unknown, advances in the understanding of gene association and gene networks are providing significant clues to their etiology. In recent years, small noncoding RNA molecules known as microRNA (miRNA) have emerged as potential players in the pathophysiology of mental illness. These small RNAs regulate hundreds of target transcripts by modifying their stability and translation on a broad scale, influencing entire gene networks in the process. There is evidence to suggest that numerous miRNAs are dysregulated in postmortem neuropathology of neuropsychiatric disorders, and there is strong genetic support for association of miRNA genes and their targets with these conditions. This review presents the accumulated evidence linking miRNA dysregulation and dysfunction with schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorders and the potential of miRNAs as biomarkers or therapeutics for these disorders. We further assess the functional roles of some outstanding miRNAs associated with these conditions and how they may be influencing the development of psychiatric symptoms.

Encoded Hydrogel Microparticles for Sensitive and Multiplex microRNA Detection Directly from Raw Cell Lysates

“…It has been shown that many diseases including a variety of cancers, 1−3 psychiatric syndromes, 4 diabetes, 5 and cardiovascular diseases 6,7 correlate to dysregulation of these small RNAs. With a high value, miRNAs have gained increasing popularity as potential novel biomarkers in disease diagnosis and prognosis.…”

Biomarkers for bipolar disorder: current insights

“…One level of posttranscriptional gene regulatory mechanism associated with BD involves microRNAs (miRNAs). 101 miRNAs are small noncoding RNA molecules that play an important role in regulating gene expression via complementary binding to the 3′-untranslated region of a specific mRNA molecule. 102 Genetic variations in miRNA binding sites could alter gene expression, which could modulate neuronal development and plasticity.…”

“…A recent review that assessed a wide variety of differentially regulated miRNA reported, on postmortem examination, an upregulation of seven miRNAs and a downregulation of eight miRNAs in the dorsolateral prefrontal cortex of patients with BD in comparison to controls (Table 1). 101,105 Another study also validated gene expression using quantitative realtime polymerase chain reaction (qRT-PCR) and reported that patients with BD presented a trend toward decreased miRNA expression levels, specifically in 19% of miRNAs that were analyzed in the prefrontal cortex (Table 1). 106 More recently, a negative correlation was found between miRNA expression and their gene targets, 105 suggesting that miRNA may act to negatively regulate gene expression.…”

The Limitations of Genetic Testing in Psychiatry

“…Histone modification and DNA methylation in response to experience, inflammation, the illness, and the medications used to treat it can induce or suppress multiple genes, and genotype itself can affect methylation of regulatory sites that leads to epigenetic changes in brain development [51]. Micro-RNAs and short interfering RNAs are short, noncoding posttranslational regulators of gene expression that target hundreds of mRNA transcripts to influence gene networks [27,52,53]. The expression of genes for CYP450 enzymes is altered by promoter methylation, micro-RNAs associated with inflammation and other illnesses [27], and some medications [54], resulting in an altered CYP450 phenotype.…”