More Evidence That Physical Activity Keeps Depression at Bay

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In my mind, aerobic exercise is an antidepressant. Every day, when I lace up my sneakers to go for a jog, I visualize a cascade of feel-good neurotransmitters (e.g., endocannabinoids, dopamine) along with a smorgasbord of mood-boosting endogenous hormones such as adrenaline and endorphin flooding my body and brain.

As someone who has been prone to major depressive disorder (MDD) since adolescence, I stumbled on the ability of regular physical activity to keep my depression at bay in 1983. Over the past four decades, I've fine-tuned "prescriptive doses” of moderate-to-vigorous physical activity (MVPA) combined with high-intensity interval training (HIIT) that effectively lower my odds of having another major depressive episode.

An original investigation (Choi et al., 2019) conducted by researchers at Harvard Medical School (HMS) reaffirms that higher levels of physical activity and lower risk of depression go hand-in-hand.

The paper, “Assessment of Bidirectional Relationships Between Physical Activity and Depression Among Adults,” was published January 23 in the journal JAMA Psychiatry.

The research team who conducted this two-sample Mendelian randomization study was led by Karmel W. Choi, PhD, who is currently a postdoctoral fellow at the Harvard T.H. Chan School of Public Health and Harvard Medical School’s Massachusetts General Hospital (MGH). The study’s senior author was Jordan Smoller, MD, ScD, director of the MGH Psychiatric and Neurodevelopmental Genetics Unit and a professor of Psychiatry at HMS.

The research question formulated by Choi and co-authors at the outset of this study was, “Does physical activity have a potential causal role in reducing risk for depression?” To answer this question, the researchers identified gene variants from the results of a global consortium of large-scale genome-wide association studies (GWAS) and used something called a Mendelian randomization approach, which makes it possible to study the causal effects of non-genetic factors.

After analyzing a massive amount of data, Choi and colleagues identified robust evidence of a protective relationship between physical activity and the risk of depression.

The authors write, “Higher levels of physical activity (indexed by objective accelerometer data) were linked to reduced odds for major depression.” These findings support the hypothesis that prescribing daily and weekly amounts of physical activity may be an effective strategy for preventing depression.

"On average, doing more physical activity appears to protect against developing depression,” Choi said in a statement. “Any activity appears to be better than none; our rough calculations suggest that replacing sitting with 15 minutes of a heart-pumping activity like running, or with an hour of moderately vigorous activity, is enough to produce the average increase in accelerometer data that was linked to a lower depression risk.”

After reading about this research earlier today, I was curious to learn more directly from the first author. In an email, I asked how the study advances our understanding of the two-way relationship between regular physical activity and major depressive disorder. Choi responded:

“Something we hear a lot is that exercise and mood are related. What we don’t know for sure is whether being physically active can actually improve emotional wellbeing or [we just] move less when we feel sad or depressed. It’s possible that both explanations are true, but we don’t know for sure. Using advances from genetic research, our study provides unique and novel support for the idea that physical activity has an important role in reducing risk for depression."

I also asked whether Choi had any practical advice for people who are currently experiencing debilitating depressive symptoms and are interested in incorporating more physical activity into their daily routine.

“Our study looked at physical activity as a way to prevent depression. But the good news from other research is that even if you are already feeling depressed, physical activity helps too. Finding ways to get active is something we often brainstorm with patients who are feeling depressed. I would say: Start somewhere – remember that something is better than nothing at all. Start small – don’t jump into 1 hour of aerobics, but begin with a few minutes of light walking or stretching, and build from there. Do it with others – this not only keeps you on track but also has the added boost of social connection. And don’t wait till you feel like it – when you move first, the good feelings often follow. Of course, this doesn’t replace the importance of seeing a medical provider to discuss effective treatment options for depression.”

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The paper was accompanied by an editorial, "A Mendelian Randomization Approach for Assessing the Relationship Between Physical Activity and Depression,” written by Adam Mourad Chekroud from the Department of Psychiatry at Yale University (who was not involved in the study). Chekroud sums up the significance of the recent paper in his editorial:

“There is a large and growing need to better manage the burden of major depression. Antidepressants are not universally effective, and many patients undergo a trial-and-error process to find the right regimen. Psychological therapies are about equally effective and can be expensive and difficult to access. Reducing the number of individuals who develop depression would be ideal, but identifying robust protective factors that are modifiable has proven challenging. Physical exercise has emerged as a key opportunity. In large cross-sectional studies (1) individuals who exercise report significantly better mental health. In large prospective cohort studies (2), individuals who exercise are less likely to develop depression. In randomized clinical trials (3), people who were assigned to exercise groups had greater depressive symptom reduction than those who were not. Individuals with depression who are taking antidepressants and exercise more are significantly more likely to recover than those who exercise less (4). Case closed, perhaps?”

In closing, Choi says, “More work needs to be done to figure out how best to tailor recommendations to different kinds of people with different risk profiles.” Her team is currently investigating just how much physical activity is necessary to benefit specific at-risk groups, such as those who are genetically predisposed to clinical depression or anyone who feels overwhelmed by stressful life circumstances.