Stress influences the brain and psyche via the immune system

Chronic stress has considerable consequences on our body. For example, many stress-related psychiatric illnesses, such as depression, are associated with changes in the immune system. However, the mechanisms underlying how these changes affect the brain remain largely unknown.

An international research team led by the University of Zurich (UZH), University Psychiatric Hospital Zurich (PUK) and the Icahn School of Medicine at Mount Sinai, New York, has discovered a new mechanism. Their study is published in Nature.

“We were able to show that stress increases the amount of matrix metalloproteinase-8 (MMP-8), an enzyme present in the blood of mice. The same changes were seen in patients suffering from depression,” explains author Flurin Cathomas. MMP-8 travels from the blood to the brain, where it alters the functioning of certain neurons. In affected mice, this leads to behavioral changes: they withdraw and avoid social contact.

According to Cathomas, the results are novel in two respects: “First, they indicate a new ‘mind-body mechanism,’ which could be relevant not only for stress-related mental illnesses, but also for other illnesses that affect both the immune and nervous systems. systems.” Second, says the psychiatrist, the identification of the specific protein MMP-8 could be a potential starting point for developing new treatments for depression.

Changes in the brain extracellular matrix

Researchers were able to use animal models to show that stress increases the migration of a specific type of white blood cell called monocytes into the brain’s vasculature, particularly in reward center regions. These monocytes produce MMP-8. MMP-8 is involved in restructuring and regulating the network-like framework that surrounds neurons in the brain, called the extracellular matrix.

“If MMP-8 enters brain tissue from the blood, it changes the structure of the matrix and thus disrupts the functioning of neurons. Mice affected by this process show behavioral changes similar to those observed in humans suffering of depression.” said Cathomas.

To prove that MMP-8 was actually responsible for the behavioral changes, the researchers removed the MMP-8 gene from some mice. Compared to control mice, these animals did not exhibit negative stress-related behavioral changes.

“Blood analyzes of patients with depression indicate that the results from mouse models are also relevant to humans: monocytes and MMP-8 were increased in the blood of people with depression compared to healthy participants.”

Many more studies are needed before the results can be implemented in clinical practice. Nevertheless, says Cathomas, “Our work once again demonstrates the importance of the interaction between the immune system and the brain in the development of psychiatric disorders. This knowledge is already integrated into psychiatric treatment today.”

In PUK’s special integrative care department led by Cathomas, clinicians adopt a holistic mind-body approach based on the latest scientific findings when treating their patients.

The research team is currently planning clinical studies to study the extent to which the immune system can be influenced by stimulating certain areas of the brain. They will also examine whether changes in depressed patients’ immune system cells influence their behavior.