Can physical activity reduce the risk of depression?

Relation

Choi K, Zheutlin A, Karlson R, et al. Physical activity offsets genetic risk for depression assessed in a biobank cohort study using electronic health records [published online November 5, 2019].Press down fear. doi:10.1002/da.22967

Study objective

To determine whether physical activity is associated with genetic risk for depression and to assess the level of physical activity associated with risk

Draft

Cohort study – non-interventional observational study

Participant

Participants were patients from the Partners Biobank, an ongoing virtual cohort study of patients in the Partners HealthCare hospital system. Survey data on self-reported physical activity and the necessary genomic data were available from a total of 11,615 participants.

The final study included 7,968 participants of European descent with a mean age of 59.9 years and 57% female. All participants had no depression diagnoses (based on billing codes) in the 1 year prior to survey completion.

Case versus control status was defined as 2 or more depression-related billing codes in the 2-year study period after initial self-report surveys compared to those without. Those with only 1 code were removed from the study.

Study parameters assessed

Polygenic risk was determined using a large genome-wide association study meta-analysis. Participants were divided into 3 groups: low risk, medium risk and high risk.

Physical activity levels were based on self-report surveys of different types of activities performed weekly and the average number of hours spent in physical activities. Levels of physical activity were divided into quintiles based on the average number of hours of activity: 0.1 hour, 1.1 hour, 3.2 hours, 6 hours, and 11.6 hours. The calculated metabolic equivalent of task hours (MET) was highly correlated with total hours of physical activity, so researchers used total hours as the primary analytical variable, considering actionable recommendations.

Jogging and running showed the strongest associations with effects on the occurrence of depression.

The researchers compared the incidence of depression (based on billing codes) across polygenic risk groups for 2 years after conducting the survey.

Key insights

In general, the 2-year prevalence of incident depression was higher among those in the lowest physical activity groups and lower among those who exercised the most. Overall, approximately 8% of the entire cohort (n = 7,968) met criteria for depression in the 2 years following the physical activity survey. The 2 lower quintiles of physical activity (0.1 hour and 1.1 hours) had above average levels of depression (10% and 9.5%, respectively), while the 3 upper quintiles of physical activity (3.2 hours, 6 hours and 11.6 hours) had below average incident depression (6.5%, 7.2% and 6.2%, respectively).

Similarly, the prevalence of depression was lower among more physically active individuals (reporting at least 3.2 hours per week) within each polygenic risk group. The following is a comparison of the percent incidence of depression per polygenic risk category for quintiles 1 to 2 (0 to 1.1 hours per week) versus quintiles 3 to 5 (≥ 3.2 hours per week):

• Gruppe mit geringem Risiko 8,7 % gegenüber 5,6 %
• Gruppe mit mittlerem Risiko 9,1 % gegenüber 6,5 %
• Risikogruppe 12,7 % gegenüber 8,1 %

Ultimately, those with the highest polygenic risk of depression who exercised had a lower incidence of depression than their inactive, low-risk counterparts. Not surprisingly, those who were very physically active and in the lowest polygenic risk group fared best, with the lowest incidence of depression (5.6%).

These results remained even after adjusting for potential confounders such as body mass index (BMI), education level, employment status, and previous depression. Both low- and high-intensity subgroups showed positive effects on depression incidence. Jogging and running showed the strongest associations with effects on the occurrence of depression.

Practice implications

The effects of exercise on preventing or treating depression have been widely studied and are well established.^1-3However, this study appears to be one of the first to prospectively evaluate whether physical activity may have a protective effect on the occurrence of depression in individuals at increased genetic risk for the disease. The key finding of this study remains that even with increased polygenic risk, exercise – a modifiable behavioral factor – can have a dose-dependent inverse effect on depression risk.

Although this particular body of research has not examined the mechanism by which exercise exerts its effects, several possible mechanisms have been suggested in the literature. Studies suggest that the effects of exercise on depression may be due to the increased hippocampal neurogenesis seen with exercise as well as the anti-inflammatory effects.^4.5There is evidence that the acute inflammation resulting from an exercise session can boost the body's natural anti-inflammatory release of cytokines, leading to the inhibition of pro-inflammatory cytokines linked to depression.⁶This neuroinflammatory hypothesis is supported by literature supporting the use of omega-3 fatty acid supplements in the treatment and prevention of depression.⁷The International Society for Nutritional Psychiatry Research now recognizes the evidence base for the use of omega-3 fatty acids, having published official practice guidelines for the safe and effective use of omega-3 supplements in the treatment and prevention of major depressive disorder.⁷

The authors of the current study generally concluded that individuals who engage in 3 or more hours of physical activity per week have a lower prevalence of depression. With gradual increases in weekly physical activity, results continued to improve, leading to a general recommendation of 45 minutes of additional activity daily to achieve a significant reduction in depression risk. These results were consistent across individuals within each polygenic risk group, such that physical activity appeared to be associated with reduced depression incidence regardless of baseline risk. Both higher and lower intensity exercise have been associated with these benefits; The most important marker appears to be time spent in physical activity. Combining these data with previously established evidence, we see that the most effective recommendation for depression is moderate to vigorous aerobic exercise performed 3 to 5 days per week for at least 6 months.^6.8

Depression is the leading cause of disability worldwide and is associated with significant morbidity and mortality as a cause or consequence of many other diseases.¹An increased genetic risk of the disease can cause a feeling of helplessness in those with a family history of it. This is one of the key areas where research into preventative and protective interventions can be incredibly helpful. At a minimum, literature such as this study can help combat the false assumption that genetic risks and disease outcomes are unmodifiable. Additionally, exercise and physical activity are known to prevent and treat an endless list of other health conditions, so the positive benefits of supporting the use of exercise as a medical recommendation are abundant.

Perhaps the most important outcome of this study will be to encourage healthcare providers and healthcare professionals not to shy away from using physical activity as a core treatment recommendation. It is a well-known phenomenon that health care providers have an inherent bias against viewing exercise as a viable treatment option for depression, even though evidence shows that its effectiveness is equivalent to that of antidepressants.²As more and more studies are published, it is only a matter of time before official recommendations recognize exercise for what it is - a natural antidepressant.

Study Restrictions

Although promising and exciting, the work of Choi et al. some limitations in generalizing the conclusions they reached. The observational and non-interventional design only allows the assumption of an associative relationship, although there are previous intervention studies that show the positive effects of exercise on depression. Furthermore, data collection based on electronic health record (EHR) codes and self-reported surveys from a relatively homogeneous group of highly educated individuals of European descent also limits the ability to generalize these results to other socioeconomically or genetically diverse populations. However, the data collected and conclusions form a study design that future researchers can investigate.