Diet quality and depressive symptoms in older adults, assessing the effect modification by genetic predisposition and low-grade inflammation: a target trial emulation
6 affiliations
- 1Deakin Institute for Mental and Physical Health and Clinical Translation (Deakin IMPACT), School of Medicine, Deakin University and Barwon Health, Geelong, VIC Australia
- 2College of Medicine and Health Sciences, Debre Markos University, Debre Markos, Ethiopia
- 3School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC Australia
- 4Department of Cardiology, University Heart & Vascular Center, Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- 5German Center for Cardiovascular Research (DZHK), Partner Site, Hamburg/Kiel/Lübeck, Hamburg, Germany
- 6Biostatistics Unit, Faculty of Health, Deakin University, Geelong, VIC Australia
Abstract
Longitudinal studies have shown an association between diet quality and depression. However, reverse causality, unmeasured confounding, and selection bias remained important limitations. We aim to examine the relationship between diet quality and depression in older adults while addressing these issues and explore modification role of genetic predisposition to depression and low-grade inflammation. We emulated a target trial of dietary interventions using data from the ASPREE cohort. An ultra-processed food (UPF) index and an anti-inflammatory diet measure were extracted from a food frequency questionnaire to quantify diet quality. Depressive symptoms were assessed annually with a Center for Epidemiologic Studies-Depression 10-item score of ≥8. A polygenic score was derived using the latest Psychiatric Genomics Consortium data for major depression. Systemic inflammation was assessed using circulating high-sensitivity C-reactive protein. Inverse probability treatment weighting was applied to balance measured confounders. The effects of diet quality on depressive symptoms were estimated using generalised estimating equations. 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, 95% CI: 0.86–1.00). Genetic predisposition or low-grade inflammation did not modify the observed associations. Higher diet quality is associated with a lower risk of depressive symptoms, independent of genetic predisposition or low-grade inflammation, which may support dietary interventions as a modifiable lifestyle strategy for mental health promotion and prevention in older adults.
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BibTeX
@article{mengist2026diet,
title = {{Diet quality and depressive symptoms in older adults, assessing the effect modification by genetic predisposition and low-grade inflammation: a target trial emulation}},
author = {Belayneh Mengist and Najmeh Davoodian and Mojtaba Lotfaliany and Julie A. Pasco and Bruno Agustini and Malcolm Forbes and Wolfgang Marx and Chenglong Yu and Johannes T. Neumann and Paul Lacaze and Alice J. Owen and John J. McNeil and Robyn L. Woods and Michael Berk and Mohammadreza Mohebbi},
journal = {Molecular Psychiatry},
year = {2026},
month = jul,
doi = {10.1038/s41380-026-03762-6},
url = {https://doi.org/10.1038/s41380-026-03762-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Diet quality and depressive symptoms in older adults, assessing the effect modification by genetic predisposition and low-grade inflammation: a target trial emulation
AU - Belayneh Mengist
AU - Najmeh Davoodian
AU - Mojtaba Lotfaliany
AU - Julie A. Pasco
AU - Bruno Agustini
AU - Malcolm Forbes
AU - Wolfgang Marx
AU - Chenglong Yu
AU - Johannes T. Neumann
AU - Paul Lacaze
AU - Alice J. Owen
AU - John J. McNeil
AU - Robyn L. Woods
AU - Michael Berk
AU - Mohammadreza Mohebbi
PY - 2026
DA - 2026/07/17
JO - Molecular Psychiatry
DO - 10.1038/s41380-026-03762-6
UR - https://doi.org/10.1038/s41380-026-03762-6
AB - Longitudinal studies have shown an association between diet quality and depression. However, reverse causality, unmeasured confounding, and selection bias remained important limitations. We aim to examine the relationship between diet quality and depression in older adults while addressing these issues and explore modification role of genetic predisposition to depression and low-grade inflammation. We emulated a target trial of dietary interventions using data from the ASPREE cohort. An ultra-processed food (UPF) index and an anti-inflammatory diet measure were extracted from a food frequency questionnaire to quantify diet quality. Depressive symptoms were assessed annually with a Center for Epidemiologic Studies-Depression 10-item score of ≥8. A polygenic score was derived using the latest Psychiatric Genomics Consortium data for major depression. Systemic inflammation was assessed using circulating high-sensitivity C-reactive protein. Inverse probability treatment weighting was applied to balance measured confounders. The effects of diet quality on depressive symptoms were estimated using generalised estimating equations. 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, 95% CI: 0.86–1.00). Genetic predisposition or low-grade inflammation did not modify the observed associations. Higher diet quality is associated with a lower risk of depressive symptoms, independent of genetic predisposition or low-grade inflammation, which may support dietary interventions as a modifiable lifestyle strategy for mental health promotion and prevention in older adults.
SN - 1359-4184
SN - 1476-5578
ER -