Sugar-sweetened beverage consumption and incident depression: an exploratory multi-omics analysis of candidate biological mediators.

Abstract

BACKGROUND: Depression is a leading cause of mental and physical disability globally, with its onset and progression influenced by a complex interplay of dietary, psychological, and biological factors. Recent research suggests a link between sugar-sweetened beverage (SSB) consumption and depression risk, although the potential biological pathways underlying this association remain poorly understood. METHODS: This study utilized data from 192,045 participants in the UK Biobank to examine the prospective association between SSB consumption and incident depression using Cox proportional hazards models. SSBs were defined as the sum of five beverage categories assessed via the Oxford WebQ 24-hour dietary recall. Directional consistency of the association was further examined across three external supporting datasets encompassing diverse populations: NHANES, YRBSS, and the Lianyungang Municipal School Health and Risk Factor Surveillance Study Dataset. We further investigated whether proteins, metabolites, inflammatory markers, and brain imaging phenotypes may serve as candidate mediators statistically consistent with mediation of the SSB-depression association. RESULTS: High SSB consumption was associated with an 18% higher risk of incident depression compared with non-consumers (HR = 1.18; 95% CI: 1.11-1.25), with consistent directional associations observed across external supporting datasets. A plasma proteomic signature comprising 229 proteins was constructed using elastic net regularization and was associated with an increased risk of incident depression. Exploratory mediation analyses identified 72 proteins, 36 metabolites, and 5 inflammatory markers as candidate mediators, with IL1RN showing the strongest protein-level candidate mediating effect (9.6%), and Unsaturation and neutrophil count showing the strongest metabolite- and inflammatory marker-level effects, respectively. CONCLUSIONS: This study provides preliminary evidence that proteins, metabolites, and inflammatory markers may serve as candidate mediators statistically consistent with mediation of the association between SSB consumption and incident depression. These findings are exploratory and hypothesis-generating, and future experimental studies are needed to validate these candidate pathways and assess their potential as targets for dietary interventions in depression prevention.