Abstract
Omics signatures for psychiatric conditions have been under-investigated. In this study, we used data from a representative observational cohort study of Hispanic/Latino adults to identify serum metabolites associated with symptoms of depression or anxiety and to develop and assess metabolite risk scores (MRSs) of these phenotypes. We conducted a metabolome-wide association study of 768 metabolites with depression and anxiety symptoms, using two separate assay batches measured from baseline samples collected between June 2008 and July 2011 for discovery (batch 1: n = 4002 adults) and replication (batch 2: n = 2178 adults). We estimated the associations via survey-based generalized linear regression, and applied Least Absolute Shrinkage and Selection Operator (LASSO) regression for metabolite selection and for obtaining MRS weights. In analyses adjusted for age, sex, field center and Hispanic/Latino background, we identified five metabolites of replicated associations with depression symptoms and six metabolites with anxiety symptoms. Key pathways related to the identified metabolites included arginine and proline, vitamin A, phospholipid, fatty acid and tyrosine metabolism. MRSs were associated with higher depression symptom score (1.07 points, 95% CI: 0.67 – 1.46, per 1 SD increase in depression MRS) and anxiety symptom score (1.05 points, 95% CI: 0.67 – 1.43, per 1 SD increase in anxiety MRS) in the replication dataset. Our study supports the associations between serum metabolites and symptoms of depression and anxiety in Hispanic/Latino adults. The developed MRSs may facilitate earlier and more objective screening of individuals for depression and anxiety apart from traditional risk factors.
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The authors thank the staff and participants of HCHS/SOL for their important contributions.
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TS discloses support for the research of this work from National Heart, Lung, and Blood Institute (NHLBI) [Grant No. R01HL161012] and National Institute on Aging (NIA) [Grant No. R01AG80598]. BY discloses support for HCHS/SOL metabolomics profiling from Junior League of Houston (JLH) Foundation (Houston, Texas) and from NHLBI [Grant No. R01HL141824]. HCHS/SOL is a collaborative study supported by contracts from the NHLBI to the University of North Carolina [HHSN268201300001I/N01-HC-65233], University of Miami [HHSN268201300004I/N01-HC-65234], Albert Einstein College of Medicine [HHSN268201300002I/N01-HC-65235], University of Illinois at Chicago [HHSN268201300003I/N01- HC-65236 Northwestern Univ], and San Diego State University [HHSN268201300005I/N01-HC-65237]. The following Institutes/Centers/ Offices have also contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements.
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The contents of this study have been approved by the institutional review board (IRB) at Beth Israel Deaconess Medical Center under the protocol (No. 2025D000897). The HCHS/SOL study was approved by IRBs at each field center, where all participants provided written informed consent, and by the non-biomedical IRB at the University of North Carolina at Chapel Hill, to the HCHS/SOL Data Coordinating Center. All methods and analyses of HCHS/SOL participants’ materials and data were carried out in accordance with human subject research guidelines and regulations.
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Qiu, X., Zhang, Y., Purushotham, Y. et al. Serum metabolites associated with depression and anxiety in the Hispanic Community Health Study/Study of Latinos. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-04058-7
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DOI: https://doi.org/10.1038/s41398-026-04058-7
