Investigating the Relationship Between Daily Physical Activity and Depression in Individuals with and Without a BDNF Gene Variant: A Cross-sectional Analysis of the All of Us Database
Dylan Letcher1, Naima Rahim1, Matthew Phan1, Caitlyn Long1
1University of Texas Medical Branch
Objective:
This study examines the association between daily physical activity and depressive symptoms and evaluates whether the presence of a BDNF Val66Met variant moderates this relationship.
Background:
The BDNF Val66Met (rs6265) polymorphism has been linked to altered activity-dependent BDNF secretion, which may influence the antidepressant effects of physical activity. Population-based studies exploring this potential moderation effect are limited.
Design/Methods:
We conducted a cross-sectional analysis using data from the All of Us Research Program, including participants with available Fitbit step count data (≥30 days), BDNF genotype information (Met allele carriers vs. non-carriers), and Patient Health Questionnaire-9 (PHQ-9) scores. We used linear regression models to evaluate the association between average daily steps and PHQ-9 scores, with an interaction term for BDNF variant status to test moderation effects. Covariates included age, sex, race/ethnicity, income, education, and home ownership.
Results:
In a multivariable linear regression adjusting for covariates, higher daily activity was significantly associated with lower PHQ-9 score (β = -0.87, p <0.001), corresponding to a 0.24 point decrease for each additional 1,000 steps taken per day. The BDNF variant showed no independent association with PHQ-9 score (p = 0.10), and the interaction between physical activity and BDNF genotype was not significant (p = 0.59). Socioeconomic factors, including lower household income and lack of a college degree, were independently associated with higher PHQ-9 scores.
Conclusions:
This study leveraged a large, diverse cohort to investigate the relationship between physical activity, BDNF-related gene variation, and depression. Greater daily physical activity was strongly associated with lower PHQ-9 score independent of BDNF genotype. Although the BDNF polymorphism did not moderate this effect, these findings reinforce the antidepressant benefits of regular physical activity across BDNF genotypes.
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