Differential Expression of tRNA-Derived Small RNA Markers of Antidepressant Response and Functional Forecast of Duloxetine in MDD Patients

Abstract

<p>Background/Objectives: Duloxetine, despite being a leading treatment option for major depressive disorder (MDD), exhibits a relatively low adequate response rate when used as a monotherapy, and the fundamental molecular mechanisms remain largely elusive. tRNA-derived small RNA (tsRNA) is a particularly interesting and new class of molecules that is becoming increasingly noticeable for investigation. Methods: We integrated small RNA sequencing with bioinformatics approaches to dissect the expression profiles of tsRNAs and decipher their functional roles post-duloxetine treatment. Subsequently, molecular docking experiments were carried out to validate the potential functions. Results: Ten tsRNAs significantly changed in the duloxetine response group after an 8-week therapy. Correlation analyses revealed that these tsRNAs predominantly interacted with miRNAs across multiple biological pathways and processes, such as the ECM-receptor interaction and B cell activation. Molecular docking analysis corroborated the binding capabilities of duloxetine with key proteins associated with ECM1 and BAFF, respectively. Conclusions: The identified changes in tsRNAs can precisely mirror the response of duloxetine in MDD treatment, offering novel insights into the underlying mechanisms of duloxetine action.</p>