A Mass General psychiatrist and his team used gene research to discover that engaging in physical activity could help prevent depression.

Jordan W. Smoller, MD, ScD, is associate chief for research for the Massachusetts General Hospital Department of Psychiatry and director of the Psychiatric and Neurodevelopmental Genetics Unit. In a recent interview, he discussed his team’s research involving the possible links between physical activity and depression.

Why did your team decide to study the relationship between physical activity and depression?

Depression is a huge public health issue that affects so many families. It’s the leading cause of disability worldwide and we have a whole range of treatments that can be effective. What we know very little about, though, is how to prevent depression.

There is a real need, and a growing interest, in identifying strategies one might take to reduce risk and promote resilience.

The best-known risk factors are things we cannot easily change, like our genetic background, family history or traumatic events that occurred early in our lives. So, there is a real need, and a growing interest, in identifying strategies one might take to reduce risk and promote resilience. Prior studies have suggested that depression is associated with reduced physical activity, but those studies have not been able to determine whether increasing physical activity could actually reduce the risk of developing depression. Maybe it’s just that people who are depressed are less active.

Our research was designed to answer that question: Can physical activity help prevent depression?

What did your research find?

The team, led by myself and Karmel Choi, PhD, found that physical activity has a causal protective effect on the risk of depression — with about 26 percent reduction in risk for people who tend to be more physically active. Interestingly, we also looked the other way, that is, does depression cause a lower level of physical activity? We didn’t find evidence for that in this study.

Jordan W. Smoller, MD, ScD
Jordan W. Smoller, MD, ScD

Our study has some limitations. The study was of people of European ancestry, so we don’t know how this generalizes to other groups, including racial and ethnic minorities. And, though it tells us that there seems to be a causal connection between physical activity and depression, the study did not look into how this occurs at a biological level.

How did you conduct your study?

We used a very large data resource, the UK Biobank, which has genetic and clinical information on hundreds of thousands of people. We took advantage of a new method of testing, called Mendelian randomization, a kind of natural experiment related to our genes.

And, we looked at two ways of measuring physical activity: A questionnaire where people reported physical activity, which relied on memory and truthful answers, and an accelerometer, a fitness tracker that objectively recorded activity levels, such as steps taken.

Mendelian randomization has only been around a few years and allows us to draw conclusions that are similar to what we can get from a controlled, randomized trial, the gold standard of research. It can help establish a cause-and-effect relationship because our genes are assigned to us before birth and not confounded by things that happen in our lives.

Because we know there are genetic variations associated with increased levels of physical activity, we looked at people with higher levels of activity based on their genes, to see if they were less likely to develop depression. When we looked at accelerometer measurements, the objective measure, we saw a 26-percent reduction in the risk of depression for people who were likely to be more physically active.

If you replace an hour of sitting with an hour of moderate activity, you would see the protective effect on depression.

How will your research help patients?

As a rough guide, we estimate, on average, if you replace 15 minutes of sitting, with 15 minutes of high-intensity activity, such as running, or replace an hour of sitting, with an hour of moderate activity, such as walking, you would see the protective effect on depression risk that we observed.

I had, at times, talked to patients about exercise, but this research has changed my thinking. Now, I routinely recommend physical activity when my patients can do it. It’s a recommendation I can feel good about because it has a broad range of health benefits and not many downsides.The big challenge is that getting people to increase their physical activity can be difficult. I tell my patients they do not have to work out in a gym, they can try yoga, walking, team sports or any way of increasing activity.

I think that for mild depression, physical activity might be an effective option to consider, right up front. There is also promising evidence that increasing physical activity might help people with anxiety.

Depression and deaths by suicide are increasing and patients have difficulty accessing health care. The more we can do to empower people to take care of their own health, the better.

How did philanthropy help this study?

This research was funded by Tangley Lloyd and the Demarest Lloyd Jr. Foundation. Mrs. Lloyd is very interested in identifying risk factors for depression. Philanthropy changed the course of our research and has led to discoveries that might help a great many people.

To support Dr. Smoller and his colleagues in the Psychiatric and Neurodevelopmental Genetics Unit, please contact us.