Study uncovers link between stress and depression

The intricate connection between stress and its impact on both the body and mind has long intrigued scientists.

Chronic stress, known to have far-reaching consequences on our overall health, is often associated with mental disorders such as depression. Yet, the underlying mechanisms governing how these changes affect the brain have remained largely elusive.

However, a groundbreaking study led by researchers from the University of Zurich (UZH), in collaboration with the University Hospital of Psychiatry Zurich (PUK) and the Icahn School of Medicine at Mount Sinai, New York, has shed new light on this complex interplay.

The study, spearheaded by first author Flurin Cathomas, focused on a key enzyme called matrix metalloproteinase-8 (MMP-8), found in the blood of both mice and humans. It was observed that stress triggers a surge in MMP-8 levels, particularly evident in individuals grappling with depression. Remarkably, MMP-8 doesn’t confine itself to the bloodstream but traverses into the brain, where it disrupts the functioning of certain neurons, leading to behavioral changes reminiscent of depressive symptoms.

Cathomas emphasizes the novelty of these findings on two fronts. Firstly, they unveil a novel “body-mind mechanism,” potentially relevant not only to stress-related mental illnesses but also to other conditions affecting the immune and nervous systems. Secondly, the identification of MMP-8 opens doors to exploring new avenues for treating depression.

Further insights emerged from the researchers’ experiments with animal models, revealing how stress prompts the migration of specific white blood cells, known as monocytes, into the brain’s vascular system. These monocytes, in turn, produce MMP-8, which plays a crucial role in reshaping the extracellular matrix surrounding neurons. Disruption of this matrix structure interferes with neuronal functioning, mirroring behaviors seen in individuals with depression.

To validate MMP-8’s role in driving behavioral changes, the researchers genetically modified mice to lack the MMP-8 gene. Remarkably, these mice did not exhibit stress-induced negative behaviors, underscoring the enzyme’s pivotal role in depressive symptoms.

The relevance of these findings extends beyond the realm of animal models, with blood analyses of depressed patients revealing elevated levels of monocytes and MMP-8. This underscores the potential translatability of the study’s findings to human contexts.

While further clinical studies are warranted before implementing these findings in practice, Cathomas emphasizes the importance of integrating insights from immune-brain interactions into psychiatric treatments. Efforts are underway to explore how stimulating certain brain areas may influence the immune system and, subsequently, impact the behavior of patients with depression.