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

Text of the abstract

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