Translational Research in Psychiatry

Mood and anxiety disorders, including major depression, panic disorder and post-traumatic stress disorder, have a high life-time prevalence and account for more disability than most other diseases worldwide as they are associated with significant morbidity, mortality and increased medical comorbidities. However, the efficacy of currently available treatment options is still unacceptably low and this is likely due to our lack of in-depth understanding of the pathophysiology of these disorders.

A detailed understanding of the pathophysiology of mood and anxiety disorders on the molecular, cellular and circuit level would allow treatments that are indeed targeted to the biological mechanisms responsible for the disease state. It has become increasingly clear that the currently used diagnostic categories possibly include patients with similar symptoms but distinct underlying biology. Such novel, biology-based diagnostic categories are likely to transcend our current symptom-based diagnoses. On the one hand, the same pathophysiologic mechanism could account for a number of diverse symptoms that are presently classified into different diagnostic categories with distinct treatment recommendations. Such patients may, however, benefit from the same treatment, despite being currently classified as suffering from different disorders. On the other hand, patients within the same symptom-based diagnosis could be categorized into biologically distinct subgroups and could benefit from distinct treatments.

A main focus of our department lies on stress- and adverse life event-related psychiatric disorders. Exposure to adverse life events or stress is the most robust risk factor for mood and anxiety disorders but also other psychiatric and medical disorders. A better understanding of the adaptive as well as mal-adaptive molecular, cellular and circuit level factors influencing our response to stress will be important to define pathophysiological mechanisms of stress-related psychiatric disorders. For this, we propose to follow the trajectory of molecular, cellular and system changes leading to the development of or resilience to psychiatric symptoms following exposure to adverse life events and to investigate how such trajectories are moderated by genetic, epigenetic, environmental and developmental factors.

The overarching aim of our department research is to contribute to a new, biology-based taxonomy of psychiatric disease and to develop treatments and preventive strategies targeted at the underlying biological trajectories based on such mechanistic understanding. Our current projects include the following interlinked topics:

• Genetic and epigenetic factors underlying risk and resilience to adverse life events
• FKBP5 - a novel target for stress-related disorders
• Biomarker-based approaches for a new taxonomy of disease
• Transdiagnostic, multilevel characterization of psychiatric patients to identify common biological signatures
• Characterization of molecular, cellular and system trajectories of risk and resilience following exposure to adverse life events across development

These projects are supported by the Project Groups of: