Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future

Abstract

Neuropsychiatry disorders are common health problems affecting approximately 1% of the population. Twin, adoption, and family studies have displayed a strong genetic component for many of these disorders; however, the underlying pathophysiological mechanisms and neural substrates remain largely unknown. Given the critical need for new diagnostic markers and disease-modifying treatments, expanding the focus of genomic studies of neuropsychiatric disorders to include the role of non-coding RNAs (ncRNAs) is of growing interest. Of known types of ncRNAs, microRNAs (miRNAs) are 20–25-nucleotide, single-stranded, molecules that regulate gene expression through post-transcriptional mechanisms and have the potential to coordinately regulate complex regulatory networks. In this review, we summarize the current knowledge on miRNA alteration/dysregulation in neuropsychiatric disorders, with a special emphasis on schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). With an eye toward the future, we also discuss the diagnostic and prognostic potential of miRNAs for neuropsychiatric disorders in the context of personalized treatments and network medicine.

Dysregulation of miRNA and its potential therapeutic application in schizophrenia

“…Since then, there are numerous reports that revealed the roles of various miRNA in neuronal development and differentiation. The important functional roles of miRNA in neurogenesis, neuroprotection, survival, and pathogenesis of neuropsycho‐disorders have been also extensively studied and reviewed . In addition, alterations of miRNA are reported to be associated with many neuropsychiatric diseases.…”

“…The important functional roles of miRNA in neurogenesis, neuroprotection, survival, and pathogenesis of neuropsycho-disorders have been also extensively studied and reviewed. 7,[44][45][46][47][48][49] In addition, alterations of miRNA are reported to be associated with many neuropsychiatric diseases. For This phenotype is significantly rescued by transfection of miRNAs obtained from embryonic mouse midbrain, suggesting that miRNAs play essential roles in midbrain dopamine neuronal differentiation and survival.…”

MicroRNAs as biomarkers for psychiatric disorders with a focus on autism spectrum disorder: Current progress in genetic association studies, expression profiling, and translational research

“…The investigation of the role of miRNAs in normal and abnormal development of the central nervous system (CNS) revealed that more than half of all identified miRNAs were expressed in the brain and are involved in several biological processes in CNS development, including cell proliferation, cell differentiation, synaptogenesis, synaptic plasticity, and apoptosis [Alural, Genc, & Haggarty, ; Reschke & Henshall, ] and mutations in miRNA‐related genes and abnormal expression of miRNAs were found to be associated with several neurodegenerative diseases [Nelson, Wang, & Rajeev, ], including Alzheimer's Disease and Parkinson's Disease.…”

“…Abnormal expression of miRNAs has been reported in various tissues from patients with psychiatric disorders. Results regarding miRNA‐related genetic variants and abnormal expression of miRNAs have recently been reviewed for schizophrenia, bipolar disorder, and major depressive disorder [Alural et al, ; Hommers, Domschke, & Deckert, ] and, in spite of limitations such as population heterogeneity for genetic association studies and tissue specificity for expression profiling studies, point to several consistent findings (e.g. hsa‐miR‐137 for schizophrenia).…”

“…miRNAs are present in diverse biological fluids, including cerebrospinal fluid (CSF), blood, saliva, and urine. Therefore, miRNAs could be potential noninvasive biomarkers for the diagnosis, prognosis, and treatment responses for psychiatric disorders and may have applications in precision medicine in the future [Alural et al, ; Santulli, ; Stoicea et al, ]. Due to the fact that miRNAs are small in size, traditional RNA isolation procedures can be inefficient in the recovery of these molecules; special care should be considered prior to RNA extraction to enhance capture.…”