Effects of Physical Activity on Major Depressive Disorder Risk

Findings validate a potential protective relationship between physical activity and depression and indicate the need for objective measurement of physical activity in mental health studies.

Enhancing physical activity may be an effective prevention strategy for depression, according to study findings published in JAMA Psychiatry.

Few modifiable targets have demonstrated efficacy for the prevention of depression, but physical activity is a promising intervention. Evidence suggests an association between lack of physical activity and depression, but the direction of causality is unknown. Some studies have suggested that depression reduces physical activity, but few studies have tested both directional relationships concurrently.

Karmel W. Choi, PhD, of the department of psychiatry, Massachusetts General Hospital, the department of epidemiology, Harvard T.H. Chan School of Public Health, and the Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, and colleagues, conducted a 2-sample mendelian randomization study. They used de-identified data from a recent genome-wide association study (GWAS) to examine 2 physical activity phenotypes: self-reported and objective accelerometer-based. They also drew on summary statistics from the largest and most recent GWAS for major depressive disorder (MDD).

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The combined sample size comprised 611,583 adult participants, including 377,234 in the self-reported physical activity group, 91,084 in the objective accelerometer-based group, and 143,265 in the MDD group.  The analysis found a protective association between accelerometer-based activity and MDD (odds ratio [OR] for MDD, 0.74; P =0.006), but not a statistically significant association, across all mendelian randomization methods, between MDD and accelerometer-based activity (P =.70). This suggests a protective effect of physical activity for MDD, rather than a causal effect of MDD on physical activity. No statistically significant relationship was found between self-reported activity and MDD or between MDD and self-reported activity.

The researchers noted that these findings underscore the importance of objectively assessing physical activity in epidemiologic studies of mental health, as self-report tends to be inaccurate. They also suggested that enhancing physical activity is potentially effective as a prevention strategy for depression.

Study limitations include the identification of few genome-wide significant single-nucleotide polymorphisms in some studies, the failure of common single-nucleotide polymorphisms to explain much total variance in complex traits, and the use of summary GWAS data for MDD but not for depressive symptoms in individuals with or without MDD.


Choi KW, Chen CY, Stein MB, et al. Assessment of bidirectional relationships between physical activity and depression among adults: a 2-sample mendelian randomization study [published online January 23, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.4175