MicroRNAs as potential biomarkers for diagnosis of major depressive disorder and influence of antidepressant treatment

We performed a PubMed search for microRNA biomarkers in major depressive disorder (MDD) and found 25 original research articles on studies performed with human patients and published January 2019 to September 2023. These included 6 studies with whole blood, 13 with blood plasma, and 6 with blood serum. In the studies that had validated preliminary findings, potential candidate biomarkers for MDD could be miR-16–2, pmiR-chr11, miR-1275 in whole blood; miR-125a-5p, let-7e-5p, miR-134, −1180–3p, −19b-3p in blood plasma. Nine of the studies had investigated the changes in microRNA expression of MDD patients receiving treatment. Among these, one study had treated treatment-resistant depression patients by psychotherapy which resulted in an upregulation of miR-29a in whole blood of treatment responders compared to non-responders. A downregulation of miR-4707–3p occurred in blood plasma collected before treatment of MDD patients undergoing remission with selective serotonin reuptake inhibitor (SSRI) compared to MDD patients not undergoing remission with SSRI treatment. Also, an upregulation of plasma miR-6068 before treatment was found in MDD patients undergoing remission with mirtazapine compared to MDD patients treated with mirtazapine and not undergoing remission. In another study, MDD patients were treated with mirtazapine for 4 weeks and decreased plasma levels of miR-1237–5p, −4271, -4484 occurred in the remission group of patients compared to levels at baseline (0 week). Dysregulated levels of plasma miR-23a-3p, −16–5p, −146a-5p, −21–5p, and −30b-5p were identified in clinical trials for the comparison between MDD patients who remitted with duloxetine and those who did not in samples collected before treatment initiation. Upregulation of miR-483–5p and −3151–5p in MDD SSRI treatment responders was found in blood plasma collected before treatment. After 8 weeks of antidepressant therapy, plasma miR-134 levels did not significantly change in non-response MDD patients, while in the partial-response and response MDD patients, plasma miR-134 levels were significantly higher than at baseline. These studies show that certain microRNAs measured before treatment can predict early responses to antidepressant administration, and certain microRNAs were dysregulated in patients undergoing remission with antidepressants and could serve as biomarkers. Further studies are warranted with adolescents and young adults having MDD and consideration should be given to using animal models of depression to investigate the effects of suppressing or overexpressing specific microRNAs.