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. This study aimed to identify serum metabolites associated with symptoms of depression or anxiety in Hispanic/Latino adults and to develop and assess metabolite risk scores (MRSs) of these phenotypes. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we conducted a metabolome-wide association study of 768 metabolites with depression and anxiety symptoms. We used two separate assay batches measured from baseline samples collected between June 2008 and July 2011 for discovery (batch 1: n=4,002 adults) and replication (batch 2: n=2,178 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 metabolite risk score (MRS) weights. In analyses adjusted for age, sex, field center and Hispanic/Latino background, we identified five metabolites with 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 MRSs developed in this study may facilitate earlier and more objective screening of individuals for depression and anxiety apart from traditional risk factors.