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The effects on depression of exercise

The effects on depression of exercise

Posted by Steven Klayman on Oct 1st 2019

We have heard of the benefits of exercise on heart disease and weight loss but now many experts agree that exercise is one of the most powerful tools available for the prevention and management of depression. To understand how this works this article goes into the bio chemical changes that happen in the body when you’re exercising. If you don’t want to read the bio chemistry of it just exercise at least three days a week. The more cardiovascular and the longer the exercise goes the greater the benefits. In other words a stationary bike or running on the beach for an hour is going to be more beneficial than 40 minutes. However if you’re not used to doing this type of exercise build up to it slowly and gradually. This is not to discount the benefits of weight training however at this point it seems cardiovascular training produces better results for the inhibition of depression.

For example, a meta-analysis published in 2016, which looked at 23 randomized controlled trials in which exercise was used as treatment for unipolar depression, found that, compared to no intervention, exercise “yielded a large and significant effect size,” which led them to conclude, “Physical exercise is an effective intervention for depression.”

    One of the ways exercise promotes mental health is by normalizing insulin resistance. Mechanistic studies have also linked the antidepressant effects of exercise to molecular mechanisms involving:
  • Kynurenine, a neurotoxic stress chemical produced from the amino acid tryptophan
  • Myokines
  • Brain-derived neurotrophic factor (BDNF), a growth factor that regulates neuroplasticity and new growth of neurons
  • The endocannabinoid system
  • Beta endorphin, an endogenous opioid neuropeptide and peptide hormone.
  • Tryptophan is an essential amino acid required for the synthesis of serotonin, melatonin, vitamin B3 and kynurenine. While kynurenine is associated with stress and depression at higher levels, higher levels of serotonin are associated with improved mood.

To a degree, exercise will allow you to control what the tryptophan will be synthesized into. By allowing for more tryptophan to be transported into your brain, exercise raises your serotonin and inhibits conversion into kynurenine, thereby boosting mood and preventing depression. Conversely, chronic stress and low-grade inflammation makes more tryptophan available for conversion into kynurenine and less into serotonin, which has a depressive effect.

Kynurenine, in turn, is a precursor to a neurotoxic compound called quinolinic acid, as well as a neuroprotective compound called kynurenic acid. Here too, exercise — and especially endurance exercise — activates a gene that prevents kynurenine from forming quinolinic acid, and makes it form kynurenic acid instead.

Animal research has also shown that well-trained muscles have higher levels of an enzyme that helps metabolize kynurenine, thereby ridding the body of it. As noted by the authors: “Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain. We actually found the opposite: well-trained muscle produces an enzyme that purges the body of harmful substances. So in this context the muscle’s function is reminiscent of that of the kidney or the liver.”

Myokines are a type of a chemical messenger in a class called cytokines. Many of the cytokines we already know about are the kind liberated from adipose tissue, your body fat, particularly the truncal fat mass that gives you that apple-shape.

Many of these are inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1 family (IL-1), which are involved in a variety of disease states, including cancer. Interestingly, the cytokines produced by muscle tissue, which are known as myokines (“myo” being the Latin root for muscles), have anti-inflammatory effects. Myokines also increase your insulin sensitivity by improving glucose utilization inside your muscles and, acting as chemical messengers, myokines help inhibit the release of inflammatory cytokines.

Furthermore microglia in your brain secrete neurotropic substances such as BDNF in response to exercise. Interestingly, it is inflammatory cytokines that are responsible for this beneficial effect.

So, while chronic release of inflammatory cytokines can cause grave harm — and is associated with depression — the transient inflammation caused by vigorous exercise actually has beneficial impact.

Low BDNF levels have been implicated as a central component of depression, as depressed patients typically have lower levels than healthy controls. As noted in a 2013 study on the interactions between exercise, depression and BDNF levels: “[T]here is strong evidence that decreased BDNF is associated with … increased risk for depression, whereas increasing BDNF by aerobic exercise appears to … reduce depression.” Exercise is known to enhance BDNF secretion, while chronic stress reduces it. In one study, moderate and vigorous intensity cycling raised BDNF levels by an average of 32% compared to baseline.

As you might expect, duration plays an important role in how much BDNF is produced. Moderate to vigorous intensity for 40 minutes produced a more significant increase than those exercising at the same intensity for just 20 minutes.

Cannabinoid receptors in the human body were discovered in the 1990s, which in turn led to the realization that we make compounds in our body — endogenous cannabinoids — that influence these receptors. It was also discovered that the endocannabinoid system (ECS) orchestrates communication between other bodily systems, such as your respiratory, digestive, immune and cardiovascular systems.

One of the cannabinoids your body produces is called anandamide — a nod to the word “ananda,” the Sanskrit word for “bliss,” as it attaches to the same CB1 receptors that the psychoactive THC in cannabis attaches to. While runner’s high is typically attributed to the release of endorphins, running also dramatically increases anandamide in the body, and anandamide not only targets the CB1 receptor, but it also influences opioid and endorphin receptors. Not surprisingly, then, the higher an individual’s anandamide level, the better they report feeling.

Research shows people engaging in moderate intensity running or cycling increase their anandamide levels, and that the greatest increase occurs when you’re exercising at 70% to 80% of your maximum heart rate.

Exercise also triggers the release of beta endorphin, an endogenous (meaning it’s made by your body) opioid neuropeptide and peptide hormone produced in specific neurons located in your central and peripheral nervous systems. As noted in the 2008 paper, “The Runner’s High: Opiodergic Mechanisms in the Human Brain”:

    “Reductions in opioid receptor availability were identified preferentially in prefrontal and limbic/paralimbic brain structures. The level of euphoria was significantly increased after running and was inversely correlated with opioid binding in prefrontal/orbitofrontal cortices, the anterior cingulate cortex, bilateral insula, parainsular cortex, and temporoparietal regions.

    These findings support the ‘opioid theory’ of the runner's high and suggest region-specific effects in frontolimbic brain areas that are involved in the processing of affective states and mood.” And there’s a solid and ever-growing body of scientific evidence showing physical exercise is a major key in the successful treatment of depression.