Science is gradually piecing together the vexing brain puzzle that connects depression and inflammation, and an important new piece just fell into place. Researchers using a mouse model have discovered how stress triggers an immune response in the brain that leads to inflammation and ultimately depression – and the implications for humans could eventually be big.
Clues linking inflammation and depression have been appearing in studies for the better part of a decade, but the “how and why” hasn’t been easy to identify. For example, while it’s now clear that depression and brain-tissue inflammation often appear in tandem, it’s not clear whether depression leads to inflammation or the other way around.
The latest study may provide part of the answer. Researchers found that by genetically manipulating particular immune receptors in the brains of mice, they could control how their brains reacted to stress. When they allowed the mice brains to be affected by repeated bouts of stress, they were able to witness an immune response that triggered the release of cytokines – proteins that serve as a marker of inflammation in both mice and humans. That inflammatory response, in turn, led to “the atrophy and impaired response of neurons in the medial prefrontal cortex [part of the brain's executive control center], causing depressive behavior.”
In other words, the researchers were able to observe a series of falling dominoes starting with stress, leading to inflammation, leading to depression, all playing out through an immune response in the brain.
“These findings demonstrate the importance of neural inflammation caused by the innate immune system for stress-induced depression,” said lead researcher Professor Tomoyuki Furuyashiki at the Kobe University Graduate School of Medicine in Japan.
Results from a study earlier this year showed that more than a decade of untreated depression is linked to higher levels of inflammation in the human brain, which suggests that depression is a type of neurodegenerative disease not unlike Parkinson’s and Alzheimer’s. The latest study suggests that the missing piece to more fully understand that connection is how the brain responds to high levels of stress, which could be the initial immune-system trigger.
For humans who suffer from stress-induced depression, this new understanding could lead to meds that target the brain’s immune response instead of neurotransmitters like serotonin and dopamine, which are targeted by today’s standard-issue antidepressants.
“This [study] could lead to the development of new antidepressant medication targeting innate immune molecules,” said Dr. Furuyashiki.
As with all studies involving animal models, it’s important to note that what applies to mice doesn’t necessarily apply to humans. Mice and humans obviously experience different types of stress and react in different ways. What’s promising about the latest study, however, is that comparable biological mechanisms are involved – the same brain tissue, the same immune response and the same inflammatory markers.
So while this puzzle isn’t nearly complete, these results are a meaningful piece helping to fill out more of the overall picture. Most importantly, they could bring us closer to finding ways of treating treatment-resistant depression, which afflicts up to 40% of all depression patients.
The study was published in the journal Neuron.