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. 2025 Dec 1:390:119889.
doi: 10.1016/j.jad.2025.119889. Epub 2025 Jul 11.

Body mass index mediates the relationship between depression and triglyceride levels: Evidence from a large national cohort

Bhaavyaa B Shah  1 , Michael L Thomas  2 , Michael J McCarthy  3 , Alejandro D Meruelo  4
Affiliations

Body mass index mediates the relationship between depression and triglyceride levels: Evidence from a large national cohort

Bhaavyaa B Shah et al. J Affect Disord. .

Abstract

Background: Major Depressive Disorder (MDD) is linked to adverse metabolic outcomes, including elevated triglycerides and body mass index (BMI). However, mechanisms underlying this relationship-and their variation by age or sex-remain unclear.

Methods: Using data from over 200,000 participants in the All of Us Research Program, we examined associations between MDD (defined by SNOMED-coded diagnoses), BMI, and lipid biomarkers (triglycerides, HDL, LDL). Causal mediation analyses tested whether BMI mediated the MDD-triglyceride relationship, adjusting for age, sex, and alcohol intake. Sex differences and age-stratified effects (ages 25, 45, 65) were also explored.

Results: Individuals with MDD had higher BMI and triglyceride levels than those without (BMI SMD = 0.234; triglycerides SMD = 0.195; both p < 0.001). BMI significantly mediated the MDD-triglyceride association (ACME = 5.46, 95 % CI [2.95, 8.17], p < 0.001), accounting for 34.1 % of the total effect. The direct effect was not statistically significant (ADE = 10.55, p = 0.084). Mediation effects were consistent across sexes. Stronger mediation was observed at older ages (e.g., ACME = 6.07 at age 65, p < 0.001) but not at younger ages (e.g., ACME = 5.09 at age 25, p = 0.076). Multiple imputation analyses confirmed these findings (ACME = 3.71, 95 % CI [3.09, 4.33], p < 0.001; proportion mediated = 24.9 %). HDL and LDL levels differed modestly by MDD status.

Conclusions: BMI partially mediates the relationship between MDD and triglycerides, particularly in older adults. These results support integrating metabolic risk management into mental health care.

Keywords: Body mass index; Depression; HDL cholesterol; LDL cholesterol; Mediation analysis; Triglycerides.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

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