Summary: Physical activity can help reduce incidents of depressive episodes in those with genetic risk factors for depression.

Source: Mass General

Increased levels of physical activity can significantly reduce the odds of depression, even among people who are genetically predisposed to the condition, according to a new study from researchers at Massachusetts General Hospital (MGH). In a paper published in the journal Depression and Anxiety, the team reported that individuals who engaged in at least several hours of exercise each week were less likely to be diagnosed with a new episode of depression, even in the face of high genetic risk for the disorder.

Drawing on genomic and electronic health record data from nearly 8,000 participants in the Partners Healthcare Biobank, the new study is the first to show how physical activity can influence depression despite genetic risk. Researchers followed patients who filled out a survey about their lifestyle habits (including physical activity) when they enrolled in the Biobank. They then mined millions of electronic health record data points over the next two years and identified people who received diagnoses related to depression. They also calculated genetic risk scores for each participant, combining information across the entire genome into a single score that reflects a person’s inherited risk for depression.

What they found was that people with higher genetic risk were more likely to be diagnosed with depression over the next two years. Significantly, though, people who were more physically active at baseline were less likely to develop depression, even after accounting for genetic risk. In addition, higher levels of physical activity were protective for people even with the highest genetic risk scores for depression.

“Our findings strongly suggest that, when it comes to depression, genes are not destiny and that being physically active has the potential to neutralize the added risk of future episodes in individuals who are genetically vulnerable,” says Karmel Choi, PhD, of MGH and the Harvard T.H. Chan School of Public Health, and lead author of the study. “On average, about 35 additional minutes of physical activity each day may help people to reduce their risk and protect against future depression episodes.”

The researchers found that both high-intensity forms of activity, such as aerobic exercise, dance and exercise machines, and lower-intensity forms, including yoga and stretching, were linked to decreased odds of depression. Overall, individuals could see a 17 percent reduction in odds of a new episode of depression for each added four-hour block of activity per week.

Depression represents the leading cause of disability worldwide. Despite its massive health burden, strategies to combat depression remain limited and the public’s understanding of robust and modifiable protective factors is incomplete. “We provide promising evidence that primary care and mental health providers can use to counsel and make recommendations to patients that here is something meaningful they can do to lower their risk even if they have a family history of depression,” says Choi.

Senior author Jordan Smoller MD, added, “In general our field has been lacking actionable ways of preventing depression and other mental health conditions. I think this research shows the value of real-world healthcare data and genomics to provide answers that can help us to reduce the burden of these diseases.”

Beyond physical activity, the MGH team continues to leverage the Partners Biobank and other large-scale studies to explore modifiable ways that individuals might reduce their risk of depression. “We believe there may be many factors could be part of an overall strategy for improving resilience and preventing depression,” emphasizes Choi. “The magnitude of depression around the world underscores the need for effective strategies that can impact as many people as possible.”

Funding: The study was supported in part by the National Institute of Mental Health and National Human Genome Research Institute as well as the Demarest Lloyd Jr. Foundation.

Choi is a clinical and research fellow at Massachusetts General Hospital and the Harvard T.H. Chan School of Public Health. Senior author Smoller is associate chief for research in the MGH Department of Psychiatry and professor of psychiatry at Harvard Medical School.

About this neuroscience research article

Source:

Mass General

Media Contacts:

Noah Brown – Mass General

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The image is in the public domain.

Original Research: Closed access

“Physical activity offsets genetic risk for incident depression assessed via electronic health records in a biobank cohort study”. Karmel Choi et al.

Depression and Anxiety doi:10.1002/da.22967.

Abstract

Physical activity offsets genetic risk for incident depression assessed via electronic health records in a biobank cohort study

Background

Physical activity is increasingly recognized as an important modifiable factor for depression. However, the extent to which individuals with stable risk factors for depression, such as high genetic vulnerability, can benefit from the protective effects of physical activity, remains unknown. Using a longitudinal biobank cohort integrating genomic data from 7,968 individuals of European ancestry with high‐dimensional electronic health records and lifestyle survey responses, we examined whether physical activity was prospectively associated with reduced risk for incident depression in the context of genetic vulnerability.

Methods

We identified individuals with incident episodes of depression, based on two or more diagnostic billing codes for a depressive disorder within 2 years following their lifestyle survey, and no such codes in the year prior. Polygenic risk scores were derived based on large‐scale genome‐wide association results for major depression. We tested main effects of physical activity and polygenic risk scores on incident depression, and effects of physical activity within stratified groups of polygenic risk.

Results

Polygenic risk was associated with increased odds of incident depression, and physical activity showed a protective effect of similar but opposite magnitude, even after adjusting for BMI, employment status, educational attainment, and prior depression. Higher levels of physical activity were associated with reduced odds of incident depression across all levels of genetic vulnerability, even among individuals at highest polygenic risk.

Conclusions

Real‐world data from a large healthcare system suggest that individuals with high genetic vulnerability are more likely to avoid incident episodes of depression if they are physically active.

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