Circulating hsa-let-7e-5p and hsa-miR-125a-5p as Possible Biomarkers in the Diagnosis of Major Depression and Bipolar Disorders

BACKGROUND: Evidence shows that microRNAs (miRNAs) could play a key role in the homeostasis and development of major depressive disorder and bipolar disorder. The present study is aimed at investigating the changes in circulating miRNA expression profiles in a plasma of patients suffering from major depressive disorder (MDD) and bipolar disorder (BD) to distinguish and evaluate these molecules as biomarkers for mood disorders. METHODS: A study enrolled a total of 184 subjects: 74 controls, 84 MDD patients, and 26 BD patients. Small RNA sequencing revealed 11 deregulated circulating miRNAs in MDD and BD plasma, of which expression of 5, hsa-miR-139-3p, miRNAs hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-125a-5p, and hsa-miR-483-5p, were further verified using qPCR. miRNA gene expression data was evaluated alongside the data from clinical assessment questionnaires. RESULTS: hsa-let-7e-5p and hsa-miR-125a-5p were both confirmed upregulated: 0.75-fold and 0.25-fold, respectively, in the MDD group as well as 1.36-fold and 0.68-fold in the BD group. Receiver operating curve (ROC) analysis showed mediocre diagnostic sensitivity and specificity of both hsa-let-7e-5p and hsa-miR-125a-5p with approximate area under the curve (AOC) of 0.66. ROC analysis of combined miRNA and clinical assessment data showed that hsa-let-7e-5p and hsa-miR-125a-5p testing could improve MDD and BD diagnostic accuracy by approximately 10%. CONCLUSIONS: Circulating hsa-let-7e-5 and hsa-miR-125a-5p could serve as additional peripheral biomarkers for mood disorders; however, suicidal ideation remains the major diagnostic factor for MDD and BD.