Moderate Food Preferences and Depression with Grey Matter as a Potential Mediator: A Large-Scale Longitudinal Study

Background: While stable dietary patterns and hedonic responses in food preferences are associated with depression, whether neurobiological mechanisms mediate this relationship remains unknown. This study therefore investigates the food preference–depression associations and their potential neurostructural mediation. Methods: Over 140,000 participants were included in a longitudinal study and cross-sectional. We employed Cox regression models to examine the relationships between food preferences and depression. Half-longitudinal mediation analysis and cross-lagged models estimated the mediating roles of brain grey matter and prospective relationships with depressive symptoms. Results: We found protective effects of moderate salty, bitter and spicy preferences against depression, especially in overweight and obese participants. Further, brain structure demonstrated widespread positive correlations with both food preferences and depressive symptoms. The mediation analysis identified volumes of peripheral cortical grey matter, ventricular cerebrospinal fluid, and grey and white matter as potential mediators in the relationships between salty preferences and depression. Of these, cross-lagged models revealed the distinct directional relationships between the volume of grey matter in the VI cerebellum (vermis)/lateral occipital cortex inferior division (right) and depression, indicating that their mutual influences are mediated through different neural mechanisms. Conclusions: Moderate, but not extreme, liking of specific tastes (spicy, bitter, or salty) reflects healthier mental states. The structure of brain grey matter may mediate the relationship between salty preference and depression; also, the cerebellum together with lateral occipital regions may potentially serve as potential emotional correlates. Further neurobiological investigations are needed to confirm this pathway and inform novel therapeutic strategies for depressive disorders.