Impact of stress on brain energy metabolism

The experience of stressful events plays an essential role in numerous mental disorders. This is particularly important in light of recent alarming global events (e.g., Covid-19 pandemic, climate change, escalation of conflicts, increased living costs), which further increased the prevalence of these disorders. However, certain individuals are more vulnerable to stressful situations than others, suggesting that protective mechanisms seem to exist. Furthermore, some but not all persons who initially respond to stress eventually habituate upon repeated stress exposure. This research project specifically aims to identify regions and networks of the human brain, which are driving individual differences in the response to acute stress and its habituation. The investigation will focus on brain energy metabolism as it is considerably increased during stress exposure, particularly in a specific area of the prefrontal cortex of the brain. On the other hand, the so-called salience network, which is responsible for filtering relevant stimuli and for managing interactions with other brain networks, represents a main hub of the stress response. Together, these brain regions and networks are also highly implicated in the pathophysiology and treatment of major depressive disorder. This project will combine non-invasive state-of-the-art functional and molecular neuroimaging techniques to characterize the acute response to stress and habituation effects. Healthy volunteers will undergo two brain imaging sessions while completing a stressful task as well as additional stress exposure between the scans to induce potential habituation. Energy metabolism and network connectivity will be assessed with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The project is expected to yield new insights into the processing of and adaptation to stress exposure. Particularly the difference between individuals that respond and habituate to stress versus those who do not, is of major clinical relevance. Knowledge on the specific changes in brain energy metabolism and network connectivity that relate to the stress response may provide potential biological markers for the individual vulnerability to stress. This in turn could serve for the implementation of preventive approaches or early interventions for persons who are at risk to develop mental disorders, thus taking us one step closer to personalized medicine.