Researchers at Sweden's Karolinska Institute published a neat study in the journal Cell last week that may shed some light on how and why exercise fights depression (press release here). It's fairly complicated stuff (to me, at least), and it's a mouse study -- but I think it's interesting enough to be worth taking a closer look at.
It's fairly well established that exercise is an effective countermeasure to depression, but it's not clear why. Is it something to do with the cardiovascular system? Psychosocial factors related to getting out and exercising? Is there some chemical produced in the brain during exercise that fights depression (that would have been my guess), or a chemical produced in the muscles that then travels to the brain? Turns out it's none of the above.
Depression is very complex and multi-faceted, so there are likely lots of different factors involved. But the particular pathway identified in the new study is sort of the opposite of the chemical-produced-in-the-brain hypothesis. Instead, it appears that there's a chemical called kynurenine produced mainly in the liver in response to stress that then travels to the brain, where it's linked to (among other things) neuroinflammation, cell death, and depression. Exercise causes your muscles to increase levels of a protein called PGC-1alpha1, which in turn leads to higher levels of an enzyme that converts kynurenine into kynurenic acid -- and the key difference is that kynurenic acid is unable to cross the blood-brain barrier, so (unlike kynurenine) it can't get into your brain and wreak havoc.
So the short version is: stress produces kynurenine which may lead to depression, but exercise helps you convert kynurenine into a harmless substance, leaving you more resilient to stress-induced depression. The study includes this nifty "graphical abstract" to illustrate the process:
KYN is kynurenine, KYNA is kynurenic acid. Yeah, it didn't really help me understand it either; for what it's worth, the press release I linked to at the top is pretty good.
The study itself tested the hypothesis in a bunch of different ways. By exposing mice to mild stress (noises, flashing lights, etc.) over several weeks, they were able to induce depressive behavior; but genetically engineered mice with high levels of PGC-1alpha1 didn't develop depression. They were also able to induce depression by simply injecting kynurenine into the mice, show that exercise increases levels of the enzyme that converts kynurenine to kynurenic acid, and several other key steps in the pathway.
In the end, well, it's a mouse study. How well does this translate to humans, and how generalizable is stress-induced depression? I really don't know. But it's certainly an interesting possibility. I'd always assumed that exercise's mental health benefits were partly from the social benefits of simply getting out and doing something, and partly from the direct feel-good effects of, say, endorphins and other brain chemicals. But this suggests it may play a more fundamental and direct role in making the brain more resistant to problems in the first place.
Thanks to Tim Caulfield for pointing the study out!
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