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Exercise -> serotonin -> antidepressant

November 14th, 2011

It’s well-established that exercise can be a powerful tool against depression (as Gretchen Reynolds wrote about in the New York Times a few months ago). What’s less clear is how and why it might help. A new study inĀ  Medicine & Science in Sports & Exercise, from researchers at the University of Sherbrooke, offers some evidence for the theory that exercise can boost serotonin levels in the brain. This, of course, is pretty much the same as what the most common antidepressants (SSRIs: selective serotonin reuptake inhibitors) do.

The study was pretty straightforward. They had 19 men with an average age of 64 perform a 60-minute bout of exercise at moderate intensity (average HR 129 beats per minute, 68% VO2max). Then they measured several proxies of serotonin production, since it’s very difficult to directly measure neurotransmitters in the brain. The result: levels of tryptophan — the key precursor which is converted into serotonin — roughly doubled.

Is this a surprise? There was previous evidence in studies of rodents and younger humans that exercise boosted tryptophan availability, but it wasn’t clear whether the same effect would occur in older adults. This is particularly important because we become increasingly susceptible to depression as we age, suggesting that some of the mechanisms that help us ward off depression stop working quite as well.

Of course, one of the problems with “prescribing” exercise as a depression treatment (as Reynolds notes) is that once you’re depressed, it can be extremely difficult to summon the motivation needed to maintain a regular exercise program. Still, this study suggests that exercise might help to prevent depression in the first place, particularly as you get older.

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  1. Seth Leon
    November 14th, 2011 at 22:55 | #1

    It seems a little curious to me that a population with mean age=64 would only be at 68% Vo2max with an average HR of 129. I’m only 48 (at least for another 60 days :) but my HR at 68% Vo2 max is <120. By age 64 it will be substantially lower.

    This seems to be a population with a quite hi Vo2max HR for age.

  2. alex
    November 14th, 2011 at 23:13 | #2

    Are you sure of your numbers, Seth? Just plugging into the first calculator that came up on Google, I get these “standard” numbers:

    64-year-old at 129 bpm: 79% of HRmax, 65% of VO2max
    48-year-old at 120 bpm: 69% of HRmax, 49% of VO2max

  3. Seth Leon
    November 14th, 2011 at 23:54 | #3

    My mistake, I was using HR Max.

    Thanks!

  4. alex
    November 15th, 2011 at 00:32 | #4

    Ah, that makes sense then. And happy advance birthday!

  5. November 17th, 2011 at 15:21 | #5

    Just curious, what was the bout of exercise they were performing? If it was running, was it on the treadmill or done outdoors? The reason I ask is because I find that when I run on treadmills I become depressed. Not seriously. But it is very depressing to think of even stepping a foot on a treadmill.

  6. Chi
    November 17th, 2011 at 17:49 | #6

    This is kinda interesting.

    A review shows no effect from exercise against depression:
    http://www.ncbi.nlm.nih.gov/pubmed/18843656

    A causality study among twins shows no relation between exercise and depression:
    http://www.ncbi.nlm.nih.gov/pubmed/18678794

    No effect is to be expected from SSRI’s antidepressants for the majority:
    http://www.ncbi.nlm.nih.gov/pubmed/20051569

    Yet, we read the NY times, we rad Spark (the book) as if it were true and we’re discussing the effect of excercise on tryptophan, like it matters ;-)

  7. alex
    November 17th, 2011 at 19:49 | #7

    Thanks for the links, Chi. It’s a good point to bear in mind that we’re dealing with uncertain theories at this point.

    You say: “A review shows no effect from exercise against depression.”

    Here’s the what the study you linked to for that statement says:

    “For the 23 trials (907 participants) comparing exercise with no treatment or a control intervention, the pooled SMD was -0.82 (95% CI -1.12, -0.51), indicating a large clinical effect… The effect of exercise was not significantly different from that of cognitive therapy…

    Exercise seems to improve depressive symptoms in people with a diagnosis of depression, but when only methodologically robust trials are included, the effect sizes are only moderate and not statistically significant.”

    While the review definitely concludes that more evidence and better-designed trials are needed, I’d disagree that you can fairly sum up their findings as “showing no effect from exercise against depression.”

    You also linked to another study, saying: “A causality study among twins shows no relation between exercise and depression.”

    I think it’s important to distinguish logically between two statements:

    (A) Depression is caused by a lack of exercise.
    (B) Adding exercise can reduce symptoms of depression.

    The twin study is evidence that (A) is not true, but it has no bearing whatsoever on (B). It’s like asking whether red hair is caused by dye: a population study might show that the occurrence of red hair isn’t significantly correlated with the presence of any particular chemicals, but that doesn’t mean that you can’t dye your hair red.

  8. Chi
    November 17th, 2011 at 21:16 | #8

    Thanks Alex for responding and for your great blog by the way! When I have a chance to read some it, I enjoy it.

    The authors were right to separate the quality trials from the rest for a re-analysis. Most of the trials had poor methodology (e.g. lack of intention to treat [ITT] analysis, multiple imputation for missing data, and lac of blinded assessments). Some of the lower quality trials for example had controlgroups doing nothing. Increasing the effect of the placebo, which is pretty strong as one the well controlled study suggests: http://www.ncbi.nlm.nih.gov/pubmed/17846259. So the suggestion of a large clinical effect from all the studies combined is not surprising, but it does not mean much.

    The three quality trials combined showed some effect, but not significant, so that’s leaves a lot to chance. Not corrected in this review was the confounding effect of achievement, attention and autonomy. All happen to have an arguable effect on depression symptoms. If they have a causal effect, exercise would merely be a vessel. The fact that exercise is not superior to CBT, strengthens this idea.

    As for the twin study, you are right that we should separate the two statements. I should have been more clear about it and thank you for pointing that out. I mentioned it, because Ratey (Spark) mentions the previous study (also twins) from the same group as evidence that exercise is important. The previous study was however not designed to discover causality, as the authors clearly state in the article. It shows that the whole idea that exercise is crucial for emotional health is not well grounded.

    I kinda jumped on it, just to make a point. Something you picked up on immediately. I feel that the whole serotonin, endorphin and even the cannabinoid CB1 receptor mechanisms as an explanation for the effect is jumping the gun. Let’s establish an effect first, shall we ;-)

    So, I do feel we need more and better studies, but ones that also includes variables of achievement, attention and even increased autonomy. And while we’re at it, why don’t we try to control the confounding variable of outdoor in nature of exercise in the gym. The effect of a green environment on mood is well documented, but not corrected in this review.

    Thanks again, just my 2 cts!

  1. November 17th, 2011 at 15:09 | #1
  2. December 5th, 2011 at 15:02 | #2