ArticlePsychological medicine2026
Causal relationships between somatic movement, brain structures, and mental well-being: A multi-stage Mendelian randomization study.
Article in Psychological medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundWhile the relationships between somatic movement, mental well-being, and brain health have been well established, the causal nature and underlying mechanisms of such associations remain incompletely understood.
methodsBy applying multi-stage Mendelian randomization to multi-source summary data derived from genome-wide association studies, we examined the causal effects of 4 somatic movement measures on 2 mental well-being indices and 13 types of brain structures, followed by testing the mediating roles of brain structures in accounting for the causal associations between somatic movement and mental well-being.
resultsTwo-sample Mendelian randomization revealed that more physical activity was causally associated with greater mental well-being (life satisfaction and positive affect), while more sedentary behavior (longer leisure screen time and more sedentary behavior at work) with lower mental well-being. With respect to brain structures, sedentary behavior was causally linked to decreased volume, surface area, and local gyrification index in distributed cortical regions. Remarkably, decreased surface area of the piriform cortex was found to mediate the causal associations between sedentary behavior and lower mental well-being.
conclusionsOur findings not only complement and extend earlier reports on the associations of somatic movement with mental well-being and brain health by further resolving the causality but also help elucidate the neural mechanisms by which sedentary behavior adversely affects mental well-being.
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