A metabolite-based distress score (MDS), originally developed in predominantly White women using 20 plasma metabolites, showed striking racial disparity in performance: an odds ratio of 1.93 for detecting prevalent depression in White MESA participants versus a non-significant 1.13 in Black participants across a combined sample of 4,102 individuals. Expanding the panel to 33 metabolites via an agnostic discovery phase in Black participants produced a multi-ethnic MDS (MDS-ME) that meaningfully improved detection in Black adults (OR: 1.45) while preserving strong performance in White adults (OR: 1.81), with replication in Women's Health Initiative and Nurses' Health Study cohorts.
This finding sits at a critical intersection of metabolomics, mental health equity, and cardiometabolic research. Psychological distress is a known upstream driver of cardiovascular risk, yet biomarker tools developed in homogeneous cohorts routinely underperform in populations with the highest disease burden. The MDS-ME's expanded metabolite panel likely captures population-specific metabolic perturbations — potentially reflecting differences in stress physiology, gut microbiome composition, or dietary patterns — though the specific added metabolites are not detailed in the abstract. Importantly, performance remained comparable between men and women, addressing a secondary equity concern. Limitations include the observational, cross-sectional design at baseline, which precludes causal inference, and the OR of 1.45 in Black participants, though improved, still lags the White cohort performance. As a preprint not yet peer-reviewed, the metabolite identities and effect stability require independent validation before clinical translation.