Assessing and refining a metabolite-based distress score for use in different populations within three US cohorts
- 1Intramural Research Program, National Institute on Aging
Abstract
IntroductionPsychological distress is associated with metabolic alterations that contribute to adverse cardiometabolic outcomes across diverse populations. We previously developed a metabolite-based distress score (MDS) in predominantly White women. Because men and Black individuals suffer high rates of cardiometabolic disease, we evaluated whether the MDS is similarly associated with depression in these populations, and derived a multi-ethnic MDS (MDS-ME) among Black individuals with replications in independent samples.
MethodsData were from three U.S. cohorts, the Multi-Ethnic Study of Atherosclerosis (MESA), Womens Health Initiative (WHI), and Nurses Health Study (NHS), evaluated in 4 stages. Stages 1-3 included 2,477 White and 1,625 Black MESA participants with depression status data and plasma metabolomics assessed at baseline. Stage 1: We calculated the MDS and examined its association with depression status. Stage 2: We conducted an agnostic analysis among a 70% random subset of Black participants to identify additional relevant metabolites. Stage 3: We derived an MDS-ME in Black participants. Stage 4: We evaluated the MDS-ME using independent samples from all three cohorts.
ResultsThe previously validated 20-metabolite MDS showed stronger associations with prevalent depression in White (OR: 1.93, 95% CI: 1.71, 2.19) versus Black (OR: 1.13, 95% CI: 0.97, 1.33) MESA participants. Associations were generally similar in men and women. The MDS-ME comprised 33 metabolites, and relative to the MDS was more strongly associated with depression in Black participants (OR: 1.45; 95% CI: 1.04, 2.03), with associations also evident in White participants (OR: 1.81; 95% CI: 1.60, 2.04). The MDS-ME was similarly associated with depression in Black women in WHI and NHS.
ConclusionResults suggest that incorporating metabolites identified in Black participants enhances the utility and generalizability of the MDS across more diverse populations.
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BibTeX
@misc{huang2026assessing,
title = {{Assessing and refining a metabolite-based distress score for use in different populations within three US cohorts}},
author = {T. Huang and Y. Zhu and R. Balasubramanian and A. Roberts and C. B. Clish and J. A. Pacheco and J. Rotter and X. Guo and J. Yao and Y.-D. I. Chen and S. Rich and K. Taylor and A. Wood and W. C. Johnson and K. H. Shutta and K. Rexrode and A. H. Shadyab and S. Y. Jung and J. E. Manson and S. E. Hankinson and L. D. Kubzansky},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.26362734},
url = {https://www.medrxiv.org/content/10.64898/2026.09.10.26362734v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Assessing and refining a metabolite-based distress score for use in different populations within three US cohorts
AU - T. Huang
AU - Y. Zhu
AU - R. Balasubramanian
AU - A. Roberts
AU - C. B. Clish
AU - J. A. Pacheco
AU - J. Rotter
AU - X. Guo
AU - J. Yao
AU - Y.-D. I. Chen
AU - S. Rich
AU - K. Taylor
AU - A. Wood
AU - W. C. Johnson
AU - K. H. Shutta
AU - K. Rexrode
AU - A. H. Shadyab
AU - S. Y. Jung
AU - J. E. Manson
AU - S. E. Hankinson
AU - L. D. Kubzansky
PY - 2026
DA - 2026/09/10
PB - medRxiv
DO - 10.64898/2026.09.10.26362734
UR - https://www.medrxiv.org/content/10.64898/2026.09.10.26362734v1
AB - IntroductionPsychological distress is associated with metabolic alterations that contribute to adverse cardiometabolic outcomes across diverse populations. We previously developed a metabolite-based distress score (MDS) in predominantly White women. Because men and Black individuals suffer high rates of cardiometabolic disease, we evaluated whether the MDS is similarly associated with depression in these populations, and derived a multi-ethnic MDS (MDS-ME) among Black individuals with replications in independent samples. MethodsData were from three U.S. cohorts, the Multi-Ethnic Study of Atherosclerosis (MESA), Womens Health Initiative (WHI), and Nurses Health Study (NHS), evaluated in 4 stages. Stages 1-3 included 2,477 White and 1,625 Black MESA participants with depression status data and plasma metabolomics assessed at baseline. Stage 1: We calculated the MDS and examined its association with depression status. Stage 2: We conducted an agnostic analysis among a 70% random subset of Black participants to identify additional relevant metabolites. Stage 3: We derived an MDS-ME in Black participants. Stage 4: We evaluated the MDS-ME using independent samples from all three cohorts. ResultsThe previously validated 20-metabolite MDS showed stronger associations with prevalent depression in White (OR: 1.93, 95% CI: 1.71, 2.19) versus Black (OR: 1.13, 95% CI: 0.97, 1.33) MESA participants. Associations were generally similar in men and women. The MDS-ME comprised 33 metabolites, and relative to the MDS was more strongly associated with depression in Black participants (OR: 1.45; 95% CI: 1.04, 2.03), with associations also evident in White participants (OR: 1.81; 95% CI: 1.60, 2.04). The MDS-ME was similarly associated with depression in Black women in WHI and NHS. ConclusionResults suggest that incorporating metabolites identified in Black participants enhances the utility and generalizability of the MDS across more diverse populations.
ER -