A Systematic Review of Circulatory microRNAs in Major Depressive Disorder: Potential Biomarkers for Disease Prognosis

Abstract

Major depressive disorder (MDD) is a neuropsychiatric disorder, which remains challenging to diagnose and manage due to its complex endophenotype. In this aspect, circulatory microRNAs (cimiRNAs) offer great potential as biomarkers and may provide new insights for MDD diagnosis. Therefore, we systemically reviewed the literature to explore various cimiRNAs contributing to MDD diagnosis and underlying molecular pathways. A comprehensive literature survey was conducted, employing four databases from 2012 to January 2021. Out of 1004 records, 157 reports were accessed for eligibility criteria, and 32 reports meeting our inclusion criteria were considered for in-silico analysis. This study identified 99 dysregulated cimiRNAs in MDD patients, out of which 20 cimiRNAs found in multiple reports were selected for in-silico analysis. KEGG pathway analysis indicated activation of ALS, MAPK, p53, and P13K-Akt signaling pathways, while gene ontology analysis demonstrated that most protein targets were associated with transcription. In addition, chromosomal location analysis showed clustering of dysregulated cimiRNAs at proximity 3p22-p21, 9q22.32, and 17q11.2, proposing their coregulation with specific transcription factors primarily involved in MDD physiology. Further analysis of transcription factor sites revealed the existence of HIF-1, REST, and TAL1 in most cimiRNAs. These transcription factors are proposed to target genes linked with MDD, hypothesizing that first-wave cimiRNA dysregulation may trigger the second wave of transcription-wide changes, altering the protein expressions of MDD-affected cells. Overall, this systematic review presented a list of dysregulated cimiRNAs in MDD, notably miR-24-3p, let 7a-5p, miR-26a-5p, miR135a, miR-425-3p, miR-132, miR-124 and miR-16-5p as the most prominent cimiRNAs. However, various constraints did not permit us to make firm conclusions on the clinical significance of these cimiRNAs, suggesting the need for more research on single blood compartment to identify the biomarker potential of consistently dysregulated cimiRNAs in MDD, as well as the therapeutic implications of these in-silico insights.

A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice

“…Fang et al [ 65 ] reported that plasma levels of miR-132 in medication-free MDD patients were 2.4-fold higher than control subjects, and that there was a positive correlation between miR-132 levels and the severity of depression, suggesting that blood levels of miR-132-5p may be a state biomarker for depression. A recent systematic review showed a list of dysregulated circulatory miRNAs in MDD patients as the most prominent miRNAs such as miR-24-3p, miR-26a-5p, miR-135a, miR-425-3p, miR-132, miR-124, and miR-16-5p [ 50 ]. In addition, miR-132 is the most frequently upregulated miRNA in MDD patients [ 49 ].…”

“…It is known that miRNAs are detected in the brain and body fluids of human. Interestingly, blood levels of miRNAs in patients with MDD are altered compared to healthy control subjects [ 49 , 50 ]. Thus, it is likely that circulatory miRNAs may be potential diagnostic and therapeutic biomarkers for depression.…”

Identification of Common Genes and Screening of Therapeutic Agents for Major Depressive Disorder and Alzheimer's Disease through Integrated Bioinformatics Approach

“…mir-16-5p can be upregulated by deposited Aβ in AD and induces neuronal injury and apoptosis of neuronal cells by directly targeting and repressing the expression of related genes (Kim et al, 2020). Furthermore, mir-16-5p has been identi ed as a potential marker of MDD (Rasheed et al, 2022). mir-1-3p played an important role in the regulation of tumor associated genes, and no studies have yet identi ed its role in the regulation of AD and MDD related genes.…”

Clinical Utility of Fluid Biomarker in Depressive Disorder

“…As an example, blood miRNA levels were shown to largely correlate with brain expression [ 55 ]. Indeed, miRNA circulating levels are a promising field of investigation [ 56 - 60 ]. Access to cerebrospinal fluid could reduce this bias [ 61 , 62 ], however feasibility is obviously a strong limitation.…”