School of Medicine Publications and Presentations

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Physical activity is correlated with, and effectively treats various forms of psychopathology. However, whether biological correlates of physical activity and psychopathology are shared remains unclear. Here, we examined the extent to which the neural and genetic architecture of physical activity and mental health are shared. Using data from the UK Biobank (N = 6389), we applied canonical correlation analysis to estimate associations between the amplitude and connectivity strength of subnetworks of three major neurocognitive networks (default mode, DMN; salience, SN; central executive networks, CEN) with accelerometer-derived measures of physical activity and self-reported mental health measures (primarily of depression, anxiety disorders, neuroticism, subjective well-being, and risk-taking behaviors). We estimated the genetic correlation between mental health and physical activity measures, as well as putative causal relationships by applying linkage disequilibrium score regression, genomic structural equational modeling, and latent causal variable analysis to genome-wide association summary statistics (GWAS N = 91,105–500,199). Physical activity and mental health were associated with connectivity strength and amplitude of the DMN, SN, and CEN (r’s ≥ 0.12, p’s < 0.048). These neural correlates exhibited highly similar loading patterns across mental health and physical activity models even when accounting for their shared variance. This suggests a largely shared brain network architecture between mental health and physical activity. Mental health and physical activity (including sleep) were also genetically correlated (|rg| = 0.085–0.121), but we found no evidence for causal relationships between them. Collectively, our findings provide empirical evidence that mental health and physical activity have shared brain and genetic architectures and suggest potential candidate subnetworks for future studies on brain mechanisms underlying beneficial effects of physical activity on mental health.


This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publication Title

Translational psychiatry



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Mentor/PI Department

Office of Human Genetics



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