# Aspirin use and risk of depression: a cross-sectional study

**Authors:** Runa A, Huan Yu, Kun Wang, Ruotong Yang, Huairong Wang, Liuyan Zheng, Jingxian Wu, Yiqun Wu

PMC · DOI: 10.3389/fphar.2026.1721286 · Frontiers in Pharmacology · 2026-02-20

## TL;DR

This study found that aspirin use is linked to a lower risk of depression, especially mild cases, based on data from a large health survey.

## Contribution

The study provides new evidence on the inverse association between aspirin use and depression risk, with variation by depression severity.

## Key findings

- Aspirin use was inversely associated with depression (OR = 0.69; 95% CI: 0.55, 0.86; p < 0.01).
- The association was significant for mild depression (OR = 0.65; 95% CI: 0.51, 0.83; p < 0.001) but not for moderate and severe depression.
- The relationship between aspirin use and depression varied by depression severity and aspirin dose.

## Abstract

The association between aspirin use and depression risk remains controversial.

Based on the National Health and Nutrition Examination Survey (NHANES) database from the 2011 to 2018, a cross-sectional study was designed. Depression was estimated using Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression models were used to assess the association between aspirin use and depression, adjusting for sociodemographic, lifestyle, and clinical covariates. To explore potential heterogeneity, we stratified the analysis by depression severity and aspirin dose categories.

A total of 4,887 participants with a mean age of 65.5 years were included. Of the participants, 1,421 (29%) were identified to be with depression. Aspirin use was inversely associated with the depression (OR = 0.69; 95% CI: 0.55, 0.86; p < 0.01). For depression of different severity, aspirin use was inversely significantly associated with “Mild depression” (OR = 0.65; 95% CI: 0.51, 0.83; p < 0.001) while not significant associated with “Moderate and severe depression”.

Aspirin use was inversely associated with depression, particularly mild depression, and the association differed by depression severity and aspirin dose. The clinical benefits and risks of aspirin should be carefully considered.

## Linked entities

- **Chemicals:** aspirin (PubChem CID 2244)
- **Diseases:** depression (MONDO:0002050)

## Full-text entities

- **Genes:** COX8A (cytochrome c oxidase subunit 8A) [NCBI Gene 1351] {aka COX, COX8, COX8-2, COX8L, MC4DN15, VIII}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, MYSM1 (Myb like, SWIRM and MPN domains 1) [NCBI Gene 114803] {aka 2A-DUB, 2ADUB, BMFS4}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** MDD (MESH:D003865), functional impairment (MESH:D003072), gastrointestinal bleeding (MESH:D006471), chronic diseases (MESH:D002908), inflammatory cytokines (MESH:D000080424), congestive heart failure (MESH:D006333), renal impairment (MESH:D007674), Depression (MESH:D003866), obesity (MESH:D009765), bleeding (MESH:D006470), bipolar depressive symptoms (MESH:D001714), stroke (MESH:D020521), overweight (MESH:D050177), monoaminergic dysfunction (MESH:D006331), Mental Disorders (MESH:D001523), kidney failure (MESH:D051437), heart attack (MESH:D009203), cardiovascular disease (MESH:D002318), infection (MESH:D007239), diabetes (MESH:D003920), hepatopathy (MESH:D020754), cancer (MESH:D009369), angina (MESH:D000787), vascular dysfunction (MESH:D002561), hemorrhagic stroke (MESH:D000083302), Inflammatory (MESH:D007249), arthritis (MESH:D001168), HPA axis dysregulation (MESH:C566610), pain (MESH:D010146), hypertension (MESH:D006973), coronary heart diseases (MESH:D003327)
- **Chemicals:** tryptophan (MESH:D014364), Alcohol (MESH:D000438), N-Acetylcysteine (MESH:D000111), 5-hydroxytryptamine (MESH:D012701), Aspirin (MESH:D001241), cortisol (MESH:D006854), homocysteine (MESH:D006710)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12963233/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963233/full.md

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Source: https://tomesphere.com/paper/PMC12963233