Association Between Heroin Use and Depression: NHANES 2005-2018

Heroin use and major depression are each leading contributors to global disability and premature mortality, yet evidence for a specific association between the two remains fragmented and is often derived from small, treatment-seeking samples. We conducted a cross-sectional analysis of nationally representative data from the 2005-2018 National Health and Nutrition Examination Survey, including 19 022 US adults aged ≥ 20 years with complete information on heroin use, depression status, and relevant covariates. Clinically significant depression was defined as a PHQ-9 score ≥ 10. After multivariable adjustment for sociodemographic, behavioural, and clinical factors, including polysubstance use and chronic medical conditions, lifetime heroin use was independently associated with depression (adjusted OR = 1.85, 95% CI 1.43-2.40; p < 0.001). Subgroup analyses demonstrated that this association was robust and modified by age and smoking status, with significant interaction effects observed (p for interaction < 0.05). Restricted cubic spline analysis among participants with a history of heroin use (n = 439) revealed a non-linear relationship between age at first heroin use and depression risk (p for non-linearity = 0.032), with the highest predicted probability of depression among individuals who initiated use at or before 20.4 years of age. These findings indicate that lifetime heroin use is associated with a substantially increased risk of clinically significant depression in the general US population, particularly among younger adults and current smokers, underscoring the need for integrated screening and concurrent treatment of substance-use and mood disorders.