Plasma microRNA Levels After Electroconvulsive Therapy in Treatment-Resistant Depressed Patients

Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD), even though the molecular mechanisms underlying its efficacy remain largely unclear. This study aimed, for the first time, to analyze plasma levels of miRNAs, key regulators of gene expression, in TRD patients undergoing ECT to investigate potential changes during treatment and their associations with symptom improvement. Methods: The study involved 27 TRD patients who underwent ECT. Plasma samples were collected at baseline (T0) and 1 month after the last ECT session (T1), and miRNA analysis was conducted by qRT-PCR. We also performed gene prediction of miRNAs differentially expressed and KEGG pathway analysis. Results: miR-95-3p, miR-194-5p, miR-324-3p, miR-195-5p, miR-19b-3p, miR-30c-5p, let-7i-5p, and miR-497-5p were nominally downregulated at T1. Changes in miR-324-3p and miR-30c-5p levels between T0 and T1 significantly correlated with symptom improvement. Among the predicted miRNA target genes of these 2 miRNAs, we noticed the presence of VEGF and SIRT1, whose expression regulation has been associated with the ECT mechanism of action in previous studies. Conclusions: The study's most relevant results are related to the correlation between reductions in miR-30c-5p and miR-324-3p and the improvement of symptoms in response to ECT, positioning these miRNAs as promising candidates for further studies. These findings support and extend previous clinical and preclinical research indicating a role of miRNAs in ECT mechanism of action. However, no significant effects in ECT miRNA modulation were observed, highlighting the need for future replications in broader samples to confirm these results.