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Gene-Physical Activity Interplay in Depression: Candidate-Gene Interactions, Polygenic Susceptibility, Lifestyle
James Chmiel1, Marta Kopańska2
1Faculty of Physical Culture and Health, Institute of Physical Culture Sciences, University of Szczecin, 71-065 Szczecin, Poland.
Journal of Clinical Medicine
|July 15, 2026
Summary
Regular physical activity appears protective against depression, regardless of genetic predisposition. Objective activity measures strengthen this link, though depression can also reduce physical activity, suggesting a feedback loop for interventions.
Area of Science:
- Behavioral Science
- Genetics
- Epidemiology
Background:
- Depression is complex, influenced by genetics and environment.
- Physical activity is linked to lower depression risk, but causality is debated.
- Understanding gene-environment interplay is crucial for depression research.
Purpose of the Study:
- To systematically review gene-physical activity interactions in depression.
- To synthesize evidence from candidate-gene, polygenic risk score (PRS), lifestyle, and Mendelian randomization (MR) studies.
- To clarify the causal relationship between physical activity and depression.
Main Methods:
- PRISMA-aligned systematic search and narrative synthesis.
- Inclusion of 27 studies examining genetic susceptibility, physical activity, and depression.
- Analysis across diverse methodologies including genome-wide association studies (GWAS) and MR.
Main Results:
- Higher physical activity is associated with lower depression risk across genetic risk levels.
- Objective physical activity measures (accelerometer) show stronger protective effects than self-report.
- Evidence suggests a bidirectional relationship: depression can reduce physical activity.
Conclusions:
- Physical activity is broadly protective against depression, independent of genetic risk.
- Accurate measurement of physical activity and consideration of confounding factors are vital.
- Future research should focus on diverse populations and objective activity assessment.
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