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. 2025 Aug 12;25(1):785.
doi: 10.1186/s12888-025-07213-4.

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

Morvarid Noormohammadi  1   2 , Farnaz Etesam  3 , Ali Amini  4 , Pegah Khosravian Dehkordi  5 , Morteza Mohammadzadeh  6 , Farzad Shidfar  7   8
Affiliations

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

Morvarid Noormohammadi et al. BMC Psychiatry. .

Abstract

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).

Keywords: Depressive disorder; Randomized controlled trial; Selenium; Trace elements.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the Research Ethics Committee of Iran University of Medical Sciences (Approval ID: IR.IUMS.REC.1402.206, dated 2023-06-13) and registered with the Iranian Registry of Clinical Trials (IRCT registration number: IRCT20091114002709N62, dated 2023-07-29). Written informed consent was obtained from all participants prior to their enrollment in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT 2010 flow diagram
Fig. 2
Fig. 2
Mean fold changes (± SE) in JAK2, STAT3, and IDO1 gene expression in the patients receiving placebo + sertraline and those receiving nano-selenium + sertraline. No statistical analysis was applied in this figure; data were visualized using GraphPad Prism for illustrative purposes only
See this image and copyright information in PMC

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