PhD Scientific Days 2025

Mental Health Sciences III.

Investigating TNF-Alpha and Blood-Brain Barrier Genes in Stress-Induced Depression Across Sexes

Előadó neve

Nagy Tamás

Neptun code

NCF0AL

Előadó munkahelye

Department of Pharmacodynamics

Előadó telefonszáma

+36202729066

Előadó e-mail címe

nagy.tamas96@phd.semmelweis.hu

Az előadás címe

Investigating TNF-Alpha and Blood-Brain Barrier Genes in Stress-Induced Depression Across Sexes

Szerző(k) neve és munkahelye

Tamás Nagy¹, Zsofia Gal¹, Daniel Baksa¹, Peter Petschner¹, Xenia Gonda¹, Dora Torok¹, Gabriella Juhasz¹, Gyorgy Bagdy¹

1: Department of Pharmacodynamics

Bemutatás módja

Szóbeli

Szekció

Mental Health Sciences III.

Language of the presentation

English

Preferred session

Mental Health Sciences

Összefoglaló szövege

Introduction
Major depressive disorder (MDD) is influenced by environmental stress and inflammation, potentially mediated through blood-brain barrier (BBB) dysfunction. Previous studies highlight interleukin-6 (IL-6) in this pathway, yet the involvement of tumor necrosis factor-alpha (TNF-α) remains unclear.

Aims
This study aimed to investigate whether genetic interactions between TNF-α, CLDN5, and environmental stress contribute to depressive symptoms, and whether these effects differ by sex. Specifically, we assessed main effects, gene-gene (GxG), gene-environment (GxE), and three-way (GxGxE) interactions across male and female subgroups to evaluate sex-specific pathways in stress-related depression involving blood-brain barrier integrity.

Methods
Data from UK Biobank participants were analyzed. Depressive symptoms were assessed via PHQ-9 and a Current Depressive Symptoms (CDS) composite score. Environmental stress was quantified based on significant life events. Genetic analyses involved 15 TNF SNPs and the CLDN5 functional variant rs885985. Linear regression models were stratified by sex to examine main effects, gene-gene (GxG), gene-environment (GxE), and three-way (GxGxE) interactions with depressive symptoms.

Results
No significant associations were observed between TNF variants and depressive symptoms after Bonferroni correction in either sex. Several nominally significant interactions were identified (e.g., rs3093546) within sex-stratified models, but these findings lacked robustness across phenotypes and models. Importantly, neither males nor females exhibited consistent evidence of interaction between TNF, CLDN5, and stress.

Conclusions
Sex-specific analyses do not support a significant role for TNF-α genetic variants interacting with environmental stress and BBB integrity in influencing depression risk. These findings reinforce the previously observed importance of IL-6 in stress-mediated depression and suggest that sex differences may not modify the TNF-related genetic risk within this pathway.

Funding
This study was supported by the Hungarian Academy of Sciences (MTA-SE Neuropsychopharmacology and Neurochemistry Research Group), the Hungarian Brain Research Program 3.0 (NAP2022-I-4/2022) and EKÖP-2024-163.

University

Semmelweis University

Supervisor

Gabriella Juhasz

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

6859

Start

12:15

End

12:30