Nano-selenium and the SRC family kinases pathway: Redefining gene expression dynamics in major depressive disorder based on a randomized controlled trial

<b>Background:</b> Major depressive disorder (MDD) is a prevalent psychiatric condition. Dysregulation of signaling pathways interacting with SRC family kinases has been implicated in the pathophysiology of MDD through inflammation. Nano-selenium, a nanoscale form of selenium with enhanced bioavailability, has the potential to modulate oxidative stress and inflammation, which are implicated in MDD. To the best of our knowledge, in this study, for the first time we aimed to examine whether nano-selenium supplementation would decrease c-SRC gene expression. <b>Methods:</b> This triple-blind, randomized, placebo-controlled clinical trial was conducted at Imam Khomeini Hospital Complex, Tehran, Iran. Using block randomization, fifty participants diagnosed with MDD per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria were randomly assigned to receive nano-selenium (55 µg/day, n = 25) or placebo (n = 25) for 12 weeks alongside sertraline (50 mg/day). c-SRC gene expression was assessed using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) from peripheral blood samples collected at baseline and after 12 weeks. <b>Results:</b> Twenty-one participants in each group completed the study, with an 84% retention rate in both groups. No serious adverse events were reported. There was no significant difference between groups at baseline. Post-intervention, c-SRC gene expression levels decreased in both the nano-selenium and placebo groups [median change (Q1, Q3): -0.0031, (-0.0065, -0.0005) vs. -0.0021 (-0.0085, 0), respectively; P < 0.05]; however, no significant differences were observed between the two groups (P = 0.606). <b>Conclusion:</b> Nano-selenium supplementation did not significantly modulate c-SRC gene expression. Limitations included a short duration. Future studies should explore alternative molecular pathways, higher supplementation doses, and treatment-naïve populations to better understand nano-selenium's therapeutic potential in MDD.