The Schmidt Lab

Stress is part of everyday life. Everybody is exposed to stressful experiences and the body's stress response is adaptive and helps to deal successfully with stressful situations. So why is stress also a major risk factor for psychiatric and metabolic disorders? And why are some people resilient to stress, while others are vulnerable and become sick? These are the questions my lab is aiming to unravel.

Adverse experiences are an inevitable part of life and shape the physiology and behavioral responses of an individual. Stress exposure at various developmental time windows can improve resilience to stressful life events by preparing the individual for future challenges. However, chronic, uncontrollable or unpredictable stress exposure, as for example experienced by many during the worldwide Covid19 pandemic, can also increase disease vulnerability, significantly contributing to disease risk. While it is clear that the difference between stress vulnerability and resilience is grounded in the specific genetic and epigenetic background in concert with previous life experiences, the underlying mechanisms are still largely unknown. Consequently, it is not possible to predict with reasonable certainty whether an individual will respond to a future challenging situation with an adaptive or maladaptive stress response.

My group investigates the interplay of early experiences during different stages of development with genetic predisposition in shaping stress resilience. Our main focus lies on stress-related psychiatric disorders, like mood or anxiety disorders. Recently, our interests have expanded to include the interplay of the brain stress system with metabolic (dys)regulation. In addition to gaining mechanistic insight into disease-relevant processes related to stress vulnerability, we also strive to carry out highly translational research. For this purpose, an important aspect is the utilization of pharmacological interventions, which may be applicable in humans.

Overall, the work in our lab can be broken down to the following specific aims:

• Establishment and further improvement of valid animal models and behavioral readouts for stress-induced disorders, that carry a high translational value

• Study the interaction of genetic risk factors identified in both preclinical and clinical studies with stress exposure on disease-relevant endophenotypes, with a focus on psychiatric disorders and metabolic disorders

• Understand the interplay of early-life stress exposures with later environmental challenges in adulthood on individual stress vulnerability and resilience

• Utilization of disease-relevant animal models and endophenotypes for the pharmacological validation of novel treatment targets of stress-related psychiatric and metabolic disorders

• Probe the molecular mechanism of stress vulnerability and enhancement of stress resilience by precise genetic or pharmacological manipulations

• Identification of biomarkers predicting future individual stress vulnerability