PhD Scientific Days 2022

Mental Health Sciences I. (Poster discussion will take place in the Aula during the Coffee Break)

Catenin Alpha 2 and Rumination as Potential New Targets in Treatment and Prevention of Several Psychiatric Disorders

Előadó neve

Eszlári, Nóra, PhD

Előadó munkahelye

Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University

Előadó telefonszáma

+36304902112

Előadó e-mail címe

eszlari.nora@gmail.com

Az előadás címe

Catenin Alpha 2 and Rumination as Potential New Targets in Treatment and Prevention of Several Psychiatric Disorders

Szerző(k) neve és munkahelye

Nóra Eszlári1,2, Zsolt Bagyura3, András Millinghoffer2,4, Tamás Nagy4, Gabriella Juhász1,5,6, Péter Antal4, Béla Merkely3, György Bagdy1,2,5

1 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest
2 NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest
3 Heart and Vascular Center, Semmelweis University, Budapest
4 Department of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest
5 MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest
6 SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest

Bemutatás módja

Szóbeli

Szekció

Mental Health Sciences I. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Mental Sciences

Összefoglaló szövege

Introduction
Catenin (cadherin-associated protein) alpha 2 has a key role in neuronal migration and intrauterine brain development. CTNNA2 gene encoding this protein has been associated both with psychiatric disorders and cardiovascular risk.
Aims
In our study, we tested whether the same causal pathway, endophenotype leads from CTNNA2 towards the several psychiatric symptoms and cardiovascular risk phenotypes. Our candidate endophenotype was rumination, a perseverative negative thinking style in response to depressed mood and past stress.
Methods
In a cross-sectional design, our sample consisted of 634 participants of the Budakalász Health Examination Survey. In FaST-LMM regressions, we tested the association between 274 single-nucleotide polymorphisms of CTNNA2 and Ruminative Response Scale rumination, ten Brief Symptom Inventory scores, four types of Framingham scores and body mass index. Mplus v7.4 was used to test statistical mediating role of rumination between CTNNA2 and disorder risk scores, hypothesizing direct and indirect genetic effects within the same model.
Results
Despite significant genetic effects on each phenotype, none of them survived correction for multiple testing. Rumination was significantly related to all ten psychiatric symptom scores but unrelated to cardiovascular risk phenotypes. Therefore, mediating role of rumination could be tested only towards psychiatric symptom scores. In this model, the rs17019243 polymorphism had no direct effect towards any of global severity index, somatization, obsessive-compulsive symptoms, depression, anxiety, phobic anxiety, hostility and paranoid ideation, but affected all of them only via rumination.
Conclusion
Decreased brain expression of CTNNA2 has been suggested in schizophrenic patients so far, and KO mice of this gene showed a schizophrenic sensory gating phenotype. Future studies should reveal the role of CTNNA2 expression in other psychiatric disorders that are also related to rumination, in order to pave the way for targeting the CTNNA2 protein with a trans-psychopharmacon. If CTNNA2 genetics do not imply adult expression levels that can be targeted by pharmacotherapy, CTNNA2 and rumination can become important markers in transdiagnostic psychiatric prevention.
Funding
ÚNKP-21-4-II-SE-1; 2017-1.2.1-NKP-2017-00002; 2019-2.1.7-ERA-NET-2020-00005; 2020-4.1.1.-TKP2020; TKP2021-EGA-25

University and Doctoral School

Other, please specify in the next box

Other university and doctoral school, not listed above

Semmelweis University, post-doctoral ÚNKP

Supervisor

-

Publication of my abstract

I 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

1049

Start

09:00

End

09:15

Authors (legacy)

Nóra Eszlári1,2, Zsolt Bagyura3, András Millinghoffer2,4, Tamás Nagy4, Gabriella Juhász1,5,6, Péter Antal4, Béla Merkely3, György Bagdy1,2,5

1 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest
2 NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest
3 Heart and Vascular Center, Semmelweis University, Budapest
4 Department of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest
5 MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest
6 SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest