Abstract
Background: Several longitudinal studies have found an association between diet quality and depression (1,2). However, the extent to which this association can be explained by reverse causality, unmeasured confounding and selection bias requires further investigation. In this study, we designed a target trial emulation to investigate the long-term association between diet quality and the risk of depressive symptoms in older adults, while accounting for a broad range of confounders. Additionally, we examined the modifying role of genetic predisposition to depression and low-grade inflammation.
Methods: Data were obtained from the ASPirin in Reducing Events in the Elderly (ASPREE) extended follow-up cohort in Australia from 2012 to 2022. We emulated a target trial of diet intervention using a prespecified protocol. The ultra-processed food (UPF) index, according to the NOVA classification, and an anti-inflammatory diet measure, based on a validated dietary inflammation score, were extracted from a food frequency questionnaire to quantify diet quality. Presence of depressive symptoms was assessed annually using the Center for Epidemiologic Studies-Depression 10-item scale (CES-D 10) score of ≥8. A polygenic score (PGS) was derived using the latest Psychiatric Genomics Consortium data for major depression. Systemic inflammation was assessed using circulating high-sensitivity C-reactive protein (CRP). Inverse probability treatment weighting was applied to balance measured confounders, including socio-demographics, comorbidities, medications, genetic predisposition and low-grade inflammation. The effects of diet quality on depressive symptoms were estimated using generalised estimating equations. Effect modification was investigated using interaction analysis.
Results: A total of 7220 participants (52.7% female), aged >70 years, were followed for a median of 5.7 years. High UPF consumption was associated with a higher risk of depressive symptoms (RR: 1.12, 95% CI: 1.03-1.21), while an anti-inflammatory diet was associated with lower depressive symptoms (RR: 0.93, 0.86-1.00). Genetic predisposition or low-grade inflammation did not modify the association between diet quality and depressive symptoms.
Conclusions: Higher diet quality is associated with a lower risk of depressive symptoms, independent of genetic predisposition or low-grade inflammation, which may support dietary intervention as a modifiable strategy for the prevention and promotion of mental health in older adults.