Shaping the stress response


March 08, 2021

Not only since the Covid-19 pandemic does stress form a part of everyday life and so being able to cope with it appropriately is crucial. Biologically, this means that the stress response must switch on and off correctly when needed, otherwise stress can become detrimental to mental health. Understanding the biological underpinnings of stress and stress-related disorders is the research focus of Dr. Mathias Schmidt’s research group at the Max Planck Institute of Psychiatry in Munich.

Research has shown that the stress response is orchestrated by the so-called hypothalamic-pituitary-adrenal (HPA) axis, which ultimately controls the release of the stress hormone cortisol. Cortisol then in turn mediates the body’s response to the stressor. It was previously known that a protein called FKBP5 is an essential regulator of the HPA axis as it alters the binding affinity of the receptor for cortisol. Not surprisingly, FKBP5 is a well-known risk factor for many stress-related disorders, including psychiatric and metabolic disorders. Higher levels of FKBP5 are generally associated with higher stress hormone levels and as such, FKBP5 is critical in switching off the stress response.

Although FKBP5 was known to be an important regulator of stress, little was known about the exact mechanisms that give it this power, nor the location in the brain that is crucial for its action to regulate the stress response. In this study, the Max Planck scientists used state-of-the-art mouse models where FKBP5 was either missing or over-expressed in the brain region orchestrating the stress response in the hypothalamus. Joint first authors Lea Brix and Alexander Häusl, both PhD students in Schmidt’s research group, explain “Previous data in this field came from animal models where the FKBP5 was deleted throughout the whole body. Here, for the first time, we were able to identify the brain region centrally responsible for FKBP5’s function in regulating the stress response”.

The findings from this precise manipulation were recently published in the well-renowned journal Molecular Psychiatry. The scientists hope that the gained understanding of FKBP5’s exact role in the stress response will enable a more targeted approach to the treatment and prevention of stress-related disorders and boost the further development of FKBP5 inhibitors as an exciting new treatment option.

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