Objective Depression is considered as a common mental illness worldwide affecting around 350 million people. Chronic stress is a major risk factor for its development. Interestingly, individuals can differ in the way of coping with chronic stress and are either prone (vulnerable) or resistant (resilient) to develop depression. High anxiety-trait is a vulnerability factor to develop stress-induced depression. Furthermore, it was also linked with mitochondrial dysfunction in the nucleus accumbens and in the establishment of social hierarchies in rodents. These observations suggest an important role of mitochondria in the vulnerability to develop stress-induced depression. The glucocorticoid receptor that is activated upon stress was recently shown to regulate mitochondrial function and gene transcription. Our own data show that expression of the glucocorticoid receptor is altered in animals with high anxiety-trait correlating with the expression of several mitochondrial genes. Thus, our central hypothesis is that vulnerability to develop depression is caused by a glucocorticoid receptor-mediated dysfunction of mitochondria in the nucleus accumbens. This project will address this idea in the mouse model showing considerable individual differences in stress-induced psychopathology-like behavior. We will first examine the role of the glucocorticoid receptor in vulnerability to stress-induced depression by performing comprehensive behavioral studies. We will then evaluate the impact of the glucocorticoid receptor on mitochondrial function and structure. Lastly, we will apply a pharmacological approach aiming to mitigate stress-induced depression caused by physiological changes given by the glucocorticoid receptor. This will lead to the understanding of the contribution of the glucocorticoid receptor in the nucleus accumbens to define vulnerability and resilience to develop stress-induced depression, and might lead to novel therapeutics for counteracting stress-induced depression. Fields of science social sciencespsychologybehavioural psychology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Net EU contribution € 187 419,60 Address Batiment ce 3316 station 1 1015 Lausanne Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 187 419,60