Journal Article

Impact of Nano-Selenium supplementation on the JAK/STAT signaling pathway in major depressive disorder: a Triple-Blind, randomized controlled trial

Dehkordi, Pegah Khosravian, Amini, Ali, Mohammadzadeh, Morteza, Shidfar, Farzad, Noormohammadi, Morvarid, Etesam, Farnaz

2025

Overview

Background Major depressive disorder (MDD) is a prevalent mental health condition, wherein the JAK/STAT signaling pathway serves as a potent cellular mechanism implicated in its pathophysiology. Increased expression of JAK2, STAT3, and subsequently IDO1 genes appears to be linked to depressive symptoms. With their antioxidant capabilities and improved absorption due to the nano formula, selenium nanoparticles could potentially modulate this molecular pathway. This study aimed to assess the impact of nano-selenium supplementation on the expression of JAK2, STAT3, and IDO1 genes in patients with MDD. Methods A triple-blind, randomized, placebo-controlled trial was conducted at the Psychosomatic Clinic of Imam Khomeini Hospital Complex. A total of 50 participants, newly diagnosed with MDD were randomized to either a nano-selenium (55 µg/day) or placebo group for 12 weeks. All participants were receiving their standard treatment (sertraline 50 mg/day). Blood samples were collected at baseline and post-intervention to measure the gene expression using RT-qPCR. Results At the end of the study, both groups showed reductions in JAK2 and STAT3 relative gene expression after 12 weeks ( P  < 0.05). Although the reduction was more in the nano-selenium group, the between-group differences were not statistically significant. Conclusions This study is the first to examine nano-selenium as a novel potential adjunct treatment for MDD. Though the degree of reduction in JAK2 and STAT3 levels was greater within the nano-selenium group, it appears that additional investigations are needed to elucidate its effects. Trial registration The research received approval from the Research Ethics Committees of Iran University of Medical Sciences (Approval ID: IR IUMS.REC.1402.206, dated 2023-06-13) and was duly registered with the Iranian Registry of Clinical Trials (IRCT; registration number: IRCT20091114002709N62, dated 2023-07-29). Graphical Abstract This research represents the first human trial investigating the effects of the nano-selenium formulation on the expression of a key signaling pathway associated with major depressive disorder.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Analysis / Bioavailability / Care and treatment / Clinical trials / Depressive disorder / Depressive Disorder, Major - drug therapy / Depressive Disorder, Major - genetics / Diagnosis / Dietary Supplements / Double-Blind Method / Eating behavior / Enzymes / Female / Gene expression / Genes / Genetic aspects / Health aspects / Humans / Inflammation / Janus kinase 2 / Janus Kinase 2 - drug effects / Janus Kinase 2 - genetics / Janus Kinase 2 - metabolism / Kinases / Major depressive disorder / Male / Medical ethics / Medicine / Medicine & Public Health / Mental depression / Mental disorders / Mental health / Middle Aged / Nanoparticles / Nanoparticles - administration & dosage / Oxidative stress / Placebos / Psychiatry / Psychotherapy / Randomized controlled trial / Selenium / Selenium - administration & dosage / Selenium - pharmacology / Sertraline / Signal transduction / Signal Transduction - drug effects / STAT proteins / Stat3 protein / STAT3 Transcription Factor - drug effects / STAT3 Transcription Factor - genetics / STAT3 Transcription Factor - metabolism / Statistical analysis / Trace elements