Key result
Physical activity is associated with a specific structural connectivity pattern between motor and reward networks, which is significantly lower in individuals with major depressive disorder compared to healthy controls (Cohen's d -0.23).
Why the study?
Exercise alleviates depressive symptoms, but the underlying neural basis and biological mechanisms remained unknown.
Does physical activity associate with specific structural connectivity patterns that correlate with depressive mood in patients with major depressive disorder?
Observational (n=1,027)
Yes
Does physical activity associate with specific structural connectivity patterns that correlate with depressive mood in patients with major depressive disorder?
Physical activity is associated with a specific structural connectivity pattern between motor and reward networks that correlates with reduced depressive mood.
Answers are grounded in this paper and cite their sources.
May link exercise benefits in depression to specific connectivity patterns; hypothesis-generating from observational data, needs prospective validation.
Background Exercise 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. Aims Using 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. Method 492 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). Results A 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. Conclusions This 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 et al. (2025) conducted an observational in Major Depressive Disorder (n=1,027). Physical activity vs. Healthy controls was evaluated on Structural connectivity latent component (sc-LC) score (Cohen's d -0.23, p=2.1e-4). Physical activity is associated with a specific structural connectivity pattern between motor and reward networks, which is significantly lower in individuals with major depressive disorder compared to healthy controls (Cohen's d -0.23).
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