The mechanisms by which chronic stress triggers changes in the immune system that promote depression and other psychiatric illnesses are now clear. This also opens up new approaches to treating depression.
In a recent study, a team including researchers from the University of Zurich (UZH) examined the underlying mechanisms of the connection between stress, changes in the peripheral immune system and psychological disorders. The results can be read in the scientific journal “Nature”.
How does stress lead to depression?
So-called psychosocial stress has profound effects on the body, including the immune system, the researchers explain. The connections between changes in the peripheral immune system and stress-related disorders such as depression have already been relatively clearly proven.
So far, however, the underlying mechanisms have remained unclear and the new study should provide more clarity, according to the research team. And the experts actually managed to identify a previously unknown mechanism through which stress changes the brain.
“We were able to show that stress increases the amount of the enzyme matrix metalloproteinase-8 (MMP-8) in the blood of mice. The same changes were also observed in patients with depression,” explains study author Flurin Cathomas in a press release.
Altered function of nerve cells
MMP-8 passes from the blood into the brain and changes the function of certain nerve cells there, which was associated with significant behavioral changes in the mice: the animals isolated themselves and avoided social contact, the researchers report.
According to the team, using animal models it was also possible to show that during stress, more so-called monocytes (a type of white blood cell) enter the brain’s vascular system, especially in the regions of the reward center.
These monocytes produce the enzyme MMP-8, which is involved in restructuring and regulating the network-like framework that surrounds nerve cells in the brain, called the extracellular matrix, the team explains.
Impaired function of neurons
“When MMP-8 penetrates from the blood into the brain tissue, it changes the matrix structure and thus disrupts the function of the neurons. “Mice affected by this process show behavioral changes similar to those of people with depression,” says Cathomas.
The researchers then removed MMP-8 from some of the mice. It turned out that the affected animals did not show any negative stress-related behavioral changes compared to mice in a control group.
In addition, blood tests on depressed people showed that the results can apparently also be transferred to humans. Increased levels of monocytes and MMP-8 in the blood were also found in depressed people compared to healthy people.
New therapeutic approaches against depression?
According to the experts, the results highlight the importance of the interaction between the immune system and the brain in mental disorders and the knowledge gained could also lead to new treatments for depression.
The study results suggest a mind-body mechanism that could be relevant not only to stress-related mental illnesses, but also to diseases of the immune and nervous systems, explains the research team.
In addition, the identification of the specific protein MMP-8 could potentially represent a starting point for the development of new treatments against depression. (as)