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EV0588

Leisure-time physical activity and specific depressive symptoms: dose–response and Mendelian randomization analysis

RECREATIONAL PHYSICAL ACTIVITY AND SPECIFIC SYMPTOMS OF DEPRESSION: A DOSE–RESPONSE AND MENDELIAN RANDOMIZATION ANALYSIS

At least 300 minutes of leisure-time physical activity per week was associated with a less densely connected depressive symptom network, while Mendelian randomization indicated that genetically predicted activity reduced the risk of depression, anhedonia, and sleep problems.

The aim was to examine symptom-specific effects of exercise that may be obscured by total depression scores and to jointly evaluate activity dose, symptom network topology, and genetic evidence. Using NHANES 2005–2020 data, N = 22,947 participants were divided into low (less than 150 minutes per week, N = 14,408), moderate (150–300 minutes per week, N = 2,572), and high (at least 300 minutes per week, N = 5,967) activity groups. Network analysis was performed using EBICglasso, with stability assessed through 1,000 bootstrap resamples and the network comparison test (NCT); Mendelian randomization (MR) used the inverse-variance weighted (IVW) estimator as the primary method, alongside MR-Egger, weighted median/mode methods, and sensitivity analyses. Compared with low activity, high activity was associated with a significant structural difference in the symptom network (P = 0.02) and lower global connectivity strength (global strength decreased from 3.75 to 3.56; P<0.01). Direct connections in the network were concentrated in the symptoms of anhedonia (DPQ010), depressed mood (DPQ020), fatigue (DPQ040), and appetite changes (DPQ050). In the Mendelian randomization analysis, the IVW odds ratio (OR) was 0.215 for depression (95% confidence interval, CI 0.066–0.695; P = 0.010), 0.757 for anhedonia (95% CI 0.612–0.938; P = 0.011), and 0.709 for sleep problems (95% CI 0.557–0.903; P = 0.005). No significant signal was detected for the other seven PHQ-9 domains. In conclusion, genetically predicted leisure-time physical activity was associated with a lower risk of depression, and protective effects in the anhedonia and sleep domains were replicated across both methods. The main limitations were the cross-sectional, self-reported nature of the NHANES data and the possibility that the MR instruments may not fully capture real-world exercise patterns.

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