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Josh Copperthwaite, a 17-year-old member of the running program at Mississauga’s Credit Valley Hospital, says running frees him from ‘the weight of depression.’Darren Calabrese

For the teens in Dan McGann's twice-a-week running group, exercise is therapy. That's not a metaphor: They've all been referred to the group by their doctors after being diagnosed with depression or other mental illness. McGann, a therapist, has been leading the program at Trillium Health Partners Credit Valley Hospital in Mississauga since 2006.

"Running is one of the biggest reasons I'm still standing on this earth today," says Josh Copperthwaite, a 17-year-old who first joined the group two years ago. "When you run you can leave all the bad things in your life behind you – it's just you and the road. For a few minutes out of the day, you feel free from the weight of depression that clings to your shoulders."

There's plenty of evidence that exercise really is a powerful tool for mental health – in some cases even "as effective as antidepressants," as headlines often claim. But it's not at all clear how it works. Is exercise just something that makes you feel good, like completing your to-do list or doing a good deed for a stranger, or does it have some deeper effect on the roots of depression? A recent study by Swedish researchers offers the strongest evidence yet for the latter, suggesting that – in mice, at least – physically fit muscles play a direct role in protecting the brain from stress-induced damage.

The results are just one part of a larger puzzle: "In neurobiological terms, we actually still don't know what depression is," Dr. Mia Lindskog, a researcher at the Karolinska Institute in Stockholm, noted in a statement when the study was published last month in the journal Cell. Understanding the link between muscle and brain – healthy body and healthy mind – not only gives us new insights on the nature of depression, it also enables researchers to zero in on exactly how much and what types of exercise will best fight depression – or prevent it from starting in the first place.

Researchers have proposed many different theories for how it works. One obvious candidate is the mood-boosting brain chemicals that are produced during and after exercise: Even if you don't experience the elusive "runner's high," there's little doubt that endorphins, endocannabinoids and perhaps other brain chemicals produce immediate feelings of well-being.

Another possibility is the effect of exercise-triggered growth factors, such as brain-derived neurotrophic factor, which are associated with the growth of new neurons – a key point, since depression is thought to be associated with neuron loss in certain brain areas.

"Psychosocial" factors likely also play a key role: "Exercise allows me to set goals and encourages me to live a healthier, active life," explains Sean Burdette, a 17-year-old who took part in McGann's run program last spring to help cope with severe depression and obsessive-compulsive disorder. Sticking to the routine and setting and achieving goals "has raised my confidence and allowed me to view life positively instead of thinking negatively," he says.

That's precisely what McGann was hoping for when he started the group after discovering that running helped him through a major depressive episode of his own. Exercise enables teens to take an active role in fighting for their own health, he says, rather than seeing themselves as the passive recipient of treatment.

"Each week the teen experientially, through running, learns that they do have the power and the ability to change their state by taking action," he says. "I have them complete a runners' log sheet every time they come in that records their mood before the run and then after so they can see the difference."

The Swedish study offers yet another perspective. The researchers induced depression-like behaviour in mice by subjecting them to mild stress such as loud noises and flashing lights for five weeks. The stress caused increased production of a molecule called kynurenine in the liver, which then travelled through the bloodstream to the brain. Previous studies have found that kynurenine is associated with brain inflammation and neuron death, and patients with a variety of mental illnesses tend to have elevated levels.

But when the same experiments were repeated with mice that were specially bred to be physically fit, less kynurenine made it to the brain. The reason? Exercise causes muscles to produce more of a protein called PGC-1alpha1, which in turn produces an enzyme that transforms kynurenine into a related molecule called kynurenic acid.

The two molecules sound similar, but there's a crucial difference: Kynurenic acid can't cross the blood-brain barrier, so it's unable to get into the brain and wreak havoc. As a result, the fit mice were less likely to develop depression despite exposure to the lights and noises.

In other words, explains senior co-author Dr. Jorge Ruas, a researcher at the Karolinska Institute, it's not that well-trained muscles produce a substance that helps the brain; instead, they produce a substance that purges the body of something that would otherwise harm the brain.

Ruas and his co-workers are now planning follow-up studies in human volunteers who are using exercise to treat their depression. Attacking kynurenine may also offer a new target for drug development, although it's unlikely that any pill will be able to fully replicate the effects of real-life exercise. "Physical exercise has many components which may contribute to the anti-depressant effect," Ruas says.

Dr. Guy Faulkner, head of the exercise psychology group at the University of Toronto and founding editor of the journal Mental Health and Physical Activity, agrees – and points to studies in which even mild walking, which is unlikely to be vigorous enough to send a surge of chemicals through the brain, helps alleviate depression. Whatever different mechanisms are at work during exercise, the precise combination that makes any given patient feel better is likely to be "highly individual-specific," he says.

For McGann's teens, the details of the mechanism matter less than the results. About 400 kids (and some of their parents) have gone through the program so far, with several going on to run marathons and half-marathons. Other groups have now set up similar programs across the province, many with support from a charity called Team Unbreakable.

"We have a slogan in the run group: 'Hills are our friends,'" McGann says. "In other words, the challenges in our lives become easier the more we face them. Hills become easier the more that you run them."

Alex Hutchinson blogs about exercise research at

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