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All That Stress Could Be Making You Depressed, Too

A new study may provide new insight into how stress changes our brains for the worse

There’s a popular saying: Before you diagnose yourself with depression, you should check to make sure you’re not just surrounded by assholes.

The funny thing about it is that it’s wrong: Being surrounded by assholes is actually very stressful, and stress and depression are closely linked.

What’s more, depression is so bad for us that it may actually cause inflammation in our brains. Or is it the other way around? Does stress cause inflammation, then depression?

Science hasn’t been exactly clear on this. We know that taken together, stress, inflammation and depression create a toxic trifecta of awful in our heads. What we don’t know is the exact order of the triggers.

A new study in mice may provide some clues. Conducted in Japan at Kobe University Graduate School of Medicine, researchers surrounded mice with assholes to find out what happened to their brains. Or in more scientific terms, they used “repeated social defeat stress” — what you might call a mouse-on-mouse fight club — and found a clear pattern.

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The brains of mice who were constantly bullied by bigger, more aggressive mice released cytokines, or proteins that mark stress in the immune system, Forbes reported. And the results suggest there’s an immune response that goes something like this: stress, then inflammation, then depression. If that’s the way it works in human brains, too, then this could change the way we medicate depression.

Multiple areas of the brain are jacked up by depression, but here, the inflammation messed with neurons in the prefrontal cortex, which is an important actor in depression. When we feel bad about something, the amygdala is activated. In not-depressed people, the prefrontal cortex breezes in and charmingly advises the amygdala it to cool its jets. But in people with depression, the prefrontal cortex suddenly becomes your most paranoid friend, overreacting to every stimulus, telling the amygdala to bust out the conspiracy theories.

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But that’s not all it does: Previous research shows that the hippocampus shrinks in people with depression; in one study, hippocampuses in women with depression were 9 to 13 percent smaller. (They’re also smaller in very stressed-out rats.)

And all this stress and overactivity can damage the brain over time if it’s not treated. While that’s not news, what’s becoming clearer here, Forbes notes, is that depression should be thought of as a subtler form of other neurodegenerative diseases like Parkinson’s and Alzheimer’s.

In one Canadian study of patients with major depressive disorder, brain scans found that those with untreated depression for over a decade had 30 percent more proteins in the brain indicating inflammation and stress, progressively worsening over time and possibly in need of a range of therapies for different stages.

Speaking of therapies: Existing antidepressants are focused on neurotransmitters and upping serotonin or dopamine, but a researcher on the mice inflammation study told Forbes that this revelation “could lead to the development of new antidepressant medication targeting innate immune molecules.”

That’s highly promising news for prefrontal cortexes everywhere, and maybe, someday, for those mice too.