The concept that exercise is an effective treatment for depression is not new. The Cochrane Collaboration, an enormous network of scientific experts around the world recently published (Rimer et al July 2012) a review of 28 articles studying the effects of exercise on depression symptoms with a total of 1101 participants. They showed that exercise significantly improved symptoms of depression, although modestly, but the benefits were long lasting.

Since we know that depression is a ‘condition of the brain’, what may be more interesting is studying the effects of exercise on the depressed (or stressed) brain. How does exercise affect the depressed brain? Is there is a level of exercise that is optimal in treating the harmful effects of stress and depression. What type of exercise (running, walking, strength training etc) is best?

In my previous post ‘Chronic stress and depression is bad for your brain’, I talked about how chronic stress activates the body’s hypothalamic-pituitary-adrenal (HPA) axis. Stress disrupts the delicate balance of neurotransmitters and other molecules in the brain, signaling the hypothalamus to release hormones which in turn signal the pituitary to activate the adrenal glands in the abdomen, just above the kidneys, to produce cortisol. Cortisol is not the bad guy- but prolonged high levels of cortisol disrupt the body’s homeostasis, weaken the immune system and impair memory ( However, it is important to appreciate that the relationship between chronic stress and depression, cortisol and the neuroimmune response has not been completely mapped out. I will try to explain now how exercise fits in.

The key battleground between chronic stress on one side and exercise on the other is the neuroimmune system.  The neuroimmune system acts as the gatekeeper between the nervous system and the immune system. The nervous system especially the brain and spinal cord have a very privileged position in that they are separated and protected from infection and inflammatory cells circulating in the body (within the blood vessels). In animal studies, chronic stress and depression disrupts this balance and increases inflammation and production of free radicals within the brain as well as blunts the production of beneficial neurotrophins. Exercise on the other hand seems to work in the opposite direction: reducing inflammation, increasing anti-oxidant activity and enhancing production of neurotrophins (Refer to my post “Neurotrophins are brain fertilizers’).

One of the first studies examining how exercise could protect the brain from the harmful effects of stress was published in Neuroscience in 2004 (Adlard & Cotman). Rats were randomized to 3 weeks of running wheel exercise or to regular housing and then underwent a stressful event (enclosed in a small tube for 2 hours). They found that exercise protected the brain against the stress-induced decrease in the neurotrophin, BDNF.

Nakajima et al (2010 Behav. Brain Res.) showed that in rats receiving chronic severe immobilization stress (12 hours/day, 6 days/week for 5 weeks), there was accumulation of brain cell damage (lipid peroxidation), loss of the natural neurogenesis (growth of new neurons in the brain) and impaired cognitive function. Exposure to exercise between the exposures to immobilization stress reduced the severity of the harmful effects of stress.

Most of the research in the field is consistent with the concept that exercise is a potential treatment to reverse or limit the neuroimmune mechanisms related to stress-associated depression. The jury is out regarding the intensity, duration and type of exercise required but the general trend is a moderate (fast walking), regular (almost every day) approach.