PhD Scientific Days 2024

Mental Health Sciences III.

The Role of NAD+/SIRT1 Pathway in Human Depression

Előadó neve

Ms. Torok, Dora

Neptun code

NXSU2H

Előadó munkahelye

Department of Pharmacodynamics

Előadó telefonszáma

06705695093

Előadó e-mail címe

torok.dora@phd.semmelweis.hu

Az előadás címe

The Role of NAD+/SIRT1 Pathway in Human Depression

Szerző(k) neve és munkahelye

Dora Torok¹, Sandor Krause², Kinga Gecse¹, Zsofia Gal¹, Nora Eszlari¹, Mate Csikos¹, Gyorgy Bagdy¹, Xenia Gonda², Gabriella Juhasz¹, Peter Petschner¹

1: Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary
2: Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Mental Health Sciences III.

Language of the presentation

Hungarian

Preferred session

Mental Health Sciences

Összefoglaló szövege

Introduction
A recent study demonstrated that rodents exposed to early life stress (ELS) showed changes in fat tissue composition and exhibited depression-like phenotype. Decreased SIRT1 expression in the reward-related nucleus accumbens (NAc) was a key component of this alteration. Specifically, male rodents exhibited ELS-induced increased adiposity and behavioral changes, whereas these effects were not detected in females.
Aim
Our aim was to translate these findings into humans using a population genetic approach and brain imaging data in UK Biobank and a small Hungarian cohort.
Methods
We calculated polygenic risk score (PRS) for the NAD+/SIRT1 pathway genes (Ngenes = 20) for the UK Biobank cohort (application number 1602) with LDpred2 for the total population and sex-separated subpopulations (Nmales = 46,581, Nfemales = 59,073). We tested the interaction of PRS and ELS on current depressive symptom score with linear regressions with R (v.4.1.2) and investigated whether body fat percentage mediates the interacting effect with mediation analysis using lavaan (v. 0.6-12). We also investigated the effect of the PRS - ELS interaction on functional connectivity of the NAc in the Hungarian cohort (N = 102).
Results
Our findings suggest that interaction between PRS-ELS contributes to depression only in males (beta = 2.9275, p = 0.0002). Additionally, this interaction influences sex-dependent functional connectivity of the NAc with the middle frontal gyrus and triangular part of the inferior frontal gyrus (p = 0.0139). The observed interaction effect is independent of body fat percentage in adults, indicating that the investigated depressogenic genetic effects are not mediated through adiposity.
Discussion
All our analyses revealed that males with higher PRS for NAD+/SIRT1 and exposed to early life stress are more susceptible to depression, and higher PRS for NAD+/SIRT1 and ELS can lead to changes in reward processes related to NAc in a sex-dependent manner. These findings translate previous animal findings and pave the way for targeted, functional testing of the NAD+/SIRT1 pathway and ELS in depression in humans aiming to reveal novel biomarkers and discover new therapies.
Funding
This study was supported by the following funding: SE 250+ Excellence Award, ÚNKP-23-3-I-SE-73, TKP2021-EGA-25, ERAPERMED2019-108, NAP2022-I-4/2022.

University

Semmelweis University

Supervisor

Peter Petschner

Publication of my abstract

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

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8113

Start

17:15

End

17:25