Network Science Laboratory | Maria Ercsey-Ravasz | TINS
English | Română

Reward-stress interactions as neural substrate for resilience and vulnerability in mental health: A translational large-scale project


Funding: project code ERANET-NEURON-2-RESIST-D, contract 22/2024 from the State Budget of Romania: Program 5.8 - European and International Cooperation, Subprogram 5.8.1. - Horizon Europa, ERANET (UEFISCDI).

Abstract

The overarching goal of this translational project is to investigate the neurobehavioral responses to rewards and to acute stress as key neurobiological mechanisms underlying individual differences in the risk of developing depressive symptoms at different ages (young and older adults) after early life stress experiences (ELS), a well- documented environmental risk factor for psychopathology. We hypothesize that an imbalance between striatal sensitivity to reward and amygdala reactivity to stress may constitute a predictor for the development of psychopathological symptoms resp. for resilience. Our multi-modal project combines A) preclinical models of ELS and stress exposure on reward-related and depression-like behaviors in rats and mice (WP 1); B) fMRI and EEG studies in human participants at risk, using existing datasets and cohorts of individuals exposed to ELS (such as the Mannheim Psychoepidemiological Center cohort, an accelerated cohort study of 700 children, juveniles and young adults with varying degrees of ELS exposure), and extending them with targeted data collection in young and older adults exposed to ELS (WP2), in combination with HPA axis, genetic, and ecological momentary assessment measures; C) Studies in a sample of currently depressed participants (WP3); and D) computational analysis of brain network properties using fMRI and EEG data collected under WP2 and WP3, to unravel their relation to different stress measures (WP4), and ultimately provide the foundation for a common FAIR database to probe our overarching hypotheses using large-scale analyses (WP5). This multi- modal translational approach combining neurobiological, behavioral, genetic and neuro-endocrine data, and measures from everyday life to increase ecological validity, is highly innovative and brings a bench-to bedside methodology with direct clinical implications. Targeting specific and well-defined mechanisms of interest will support the identification of biomarkers and advance towards a transdiagnostic and dimensional approach of psychopathology, making it possible to transfer our framework to other mental disorders. We expect our project to lead to the identification of evidence-based behavioral markers, that will be validated in a clinical group of depressed participants and associated with specified neural mechanisms. Such biomarkers should be easily accessible and transferable in clinical settings (i.e. behavioral measures of reward and stress reactions). Creating a database with large samples of individuals at risk and individuals with current depression will allow defining norms for behavioral results and increase their interest for clinical use. This can lead to the development of tailored preventive interventions in individuals at higher risk or to specific treatments for patients with depressive symptoms and ELS exposure. Our project has therefore a strong clinical relevance. The creation of a FAIR database specific for ELS available in open-access after the end of project will be an important deliverable. The identification of neural and genetic biomarkers will be highly valuable for clinical purposes as well as for dissecting neurobiological mechanisms. The introduction of a developmental, life-time perspective is cutting-edge, especially in the context of ELS and depression, and we strongly believe that it will yield major advances in the understanding of depression in a life-long perspective, sparkling important new insight for the understanding of late-life depression and the long-term effects of ELS.
Our consortium includes a very strong and multidisciplinary group of investigators, each of them being a specialist in his / her field, and all with excellent research and publication records. We are therefore convinced that our project will lead to major high-impact publications on neurobiological mechanisms of vulnerability and resilience in mental health, and thus pave the way to novel clinical perspectives in the management of patients.

Research team

Dr. Mária M. Ercsey-Ravasz, principal investigator.
Dr. Eng. Raul C. Mureșan, scientific researcher gr. I.

[Curriculum Vitae]
Dr. Eng. Vlad V. Moca, senior researcher.
Dr. Zsolt I. Lázár, senior researcher.
Dr. Botond Molnár, researcher.
Dr. Eng. Levente Varga, researcher.
Dr. István Tóth, researcher.
Máté Józsa, research assistant.
Balázs Péntek, research assistant.
András Rusu, research assistant.

Objectives

The overarching goal of this translational project is to investigate neurobehavioral and biopsychological factors mediating the relationship between well-known environmental risks factor, such as ELS and the development of depressive symptoms at different ages (young adults and older adults). We will specifically focus on the neurobehavioral responses to rewards and to acute stress.  Our main hypothesis is that an imbalance between the striatal sensitivity to reward and the amygdala reactivity to stress may constitute a predictor for the development of psychopathological symptoms resp. for resilience.
For this the Parteners will provide existing datasets and collect new data and we will analyze functional brain networks extracted from EEG and fMRI data to unravel their relation to different stress measures.

Expected results

  • Reports about the properties of functional networks in humans with ELS.

  • Conclusions regarding our hypothesis, and the potential role of striatal sensitivity to reward and the amygdala reactivity to stress.

  • Identifying functional network properties (e.g. special role of certain areas) that are related to certain stress measures.



The project coordinator, Dr. Chantal Martin Soelch starts the June 19, 2024 meeting of the consortium in Fribourg for the project launch.



The consortium members discuss the details of the experiments, the questionnaires that will be used, the measures and methodologies etc. Dr. Maria Ercsey-Ravasz from TINS can be seen on the left side of the picture.



Photo of consortium members at the University of Fribourg, 19.06.2024.


Scientific reports

  • Overview of results (in Romanian).
     [pdf]


Dissemination

Scientific articles:

  • Ichim A.M., Bârzan H., Moca V.V., Nagy-Dăbâcan A., Ciuparu A., Hapca A., Vervaeke K., Mureșan R.C. (2024) The gamma rhythm as a guardian of brain health. eLife, 13, e100238.
    https://doi.org/10.7554/eLife.100238
    [Open access link]

  • Bulcsu Sandor, Andras Rusu, Karoly Denes, Maria Ercsey-Ravasz, Zsolt Lazar, „Measuring dynamical phase transitions in time series”, under review in Physical Review Letters.

  • Balazs Pentek, Maria Ercsey-Ravasz, „The exponential distance rule based network model predicts topology and reveals functionally relevant properties of the Drosophila projectome”, under review in Network Neuroscience.

  • Levente Varga, Balazs Pentek, Botond Molnar, Laura Perez-Cervera, Mohamed Kotb Selim, Antonio Díaz-Parra, David Moratal, Wolfgang H. Sommer, Santiago Canals, Raul C. Mureșan, Vasile V. Moca*, Maria Ercsey-Ravasz*, “Protocol to study brain dynamics through a hierarchy of complex correlation patterns defining a robust functional architecture”, under review in STAR Protocol.


Presentations at international conferences:

  • Andras Rusu, Karoly Denes, Zsolt Lazar, Maria Ercsey-Ravasz, Bulcsu Sandor, „Application of dynamical entropies in measuring complexity if time-series”, International conference: Dynamic Days 2024, poster, iulie 2024.


Media dissemination, presentations for the general public, etc.: