Serum metabolites associated with depression and anxiety in the Hispanic Community Health Study/Study of Latinos

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.