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bioRxiv · 10.1101/2025.03.04.641424

Physical Activity and Depressive Mood Shared the Structural Connectivity between Motor and Reward Network: a population-based study from the UK Biobank

Di, S.·Luo, N.·Shi, W.·Yang, Z.·Sui, J.·Jiang, R.·Cui, Y.·Du, Z.·Zhang, J.·Ma, Y.·Wang, H.·Chu, C.·Zhong, Y.·Li, W.·Lu, Y.·Yan, H.·Liao, J.·Zhang, D.·Calhoun, V.·Song, M.·Jiang, T.
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Abstract

BackgroundExercise has been revealed to leave a positive effect on alleviating depressive symptoms by various existing studies. However, the neural basis behind this phenomenon remains unknown, as well as its underlying biological mechanism.AimsUsing a large neuroimaging cohort from UK Biobank, this study aimed to identify structural connectivity (SC) patterns simultaneously linked with physical activity and depression, as well as its biological interpretation.Method492 participants with major depression disorder (MDD) and 535 healthy controls (HC) were extracted from the UK Biobank dataset. Partial least squares regression was first utilized to explore a replicable SC pattern simultaneously associated with physical activity and depressive mood. The neuromaps toolbox was applied to interpret the biological ontologies of the identified SC pattern. Neuroimaging-transcriptome association and enrichment analyses were conducted to explore its underlying genetic basis, pathways and cell types. The reproducibility and generalizability were tested on another independent MDD dataset (N=3,496) and bipolar disorder (BD) dataset (N=81).ResultsA SC pattern linked with exercise was identified to be both significantly correlated with depressive mood and group discriminative between MDDs and HCs, which primarily located between the motor-related regions and reward-related regions. This pattern was associated with multiple neurotransmitter receptors, such as serotonin and GABA receptors, and enriched in pathways like synaptic signaling and astrocytes cell type. The SC pattern and genetic results were also replicated in another independent MDD dataset and present commonalities with BD.ConclusionsThis study not only initially identified a reproducible shared SC pattern between physical activity and depressive mood, but also elucidated the underlying biological mechanisms, which enhanced our understanding of how exercise helps alleviate depression and may inform the development of novel neuromodulation targets.

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Di, S., Luo, N., Shi, W., Yang, Z., Sui, J., Jiang, R., Cui, Y., Du, Z., Zhang, J., Ma, Y., Wang, H., Chu, C., Zhong, Y., Li, W., Lu, Y., Yan, H., Liao, J., Zhang, D., Calhoun, V., Song, M., Jiang, T.. 2025-03-10. Physical Activity and Depressive Mood Shared the Structural Connectivity between Motor and Reward Network: a population-based study from the UK Biobank. https://doi.org/10.1101/2025.03.04.641424

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