Anhedonia, a hallmark of depression, is associated with environmental exposure to volatile organic compounds in U.S. adults from NHANES

Background and Aim: Environmental exposure to volatile organic compounds (VOCs) is linked to depressive disorder, examined as a unitary outcome. Symptom-specific observations are scarce. Anhedonia, a representative phenotype in depression, has unique biology from negative valences. Here, we aim to investigate associations between urinary metabolites of VOCs (UVOCs) and anhedonia. Methods: We analyzed 5,084 adults from five cycles of National Health and Nutrition Examination Survey (NHANES) over a decade. Anhedonia was assessed by the first item of the Patient Health Questionnaire-9. Fifteen UVOCs included were selected based on their importance by multivariate logistic regression, elastic net, and random forest models. Dose-response relationships were examined by generalized additive models and restricted cubic splines. Mixed exposure was evaluated by environmental risk score and weighted quantile sum regression. Mechanisms were explored by mediation analysis. Results: We found six UVOCs with strong links to anhedonia: four positive (MHBMA3, DHBMA, MA, 3HPMA) and two inverse (2MHA, 2HPMA). Positively associated UVOCs exhibited J-shaped dose-response relationships with anhedonia, while inversely associated ones showed reverse patterns. Mixed exposure was positively connected to anhedonia, with DHBMA (metabolite of 1,3-butadiene) still contributing the most. A nomogram was developed for risk estimation based on UVOC concentrations. Mechanistically, white blood cells and neutrophils acted as detrimental mediators, lymphocytes and monocytes as protective ones, whereas albumin showed suppression effects. Conclusions: We report the symptom-specific associations between certain VOC exposure and anhedonia. These findings may propose environmental predictors of anhedonia and advance precision approaches in psychiatric epidemiology.