Long-term ambient benzene exposure, acceleration of biological aging, and risk of incident psychiatric disorders: A cohort study in the UK Biobank.

BACKGROUND: How long-term ambient benzene exposure affects mental health, and through what biological mechanisms, remains unclear. We aimed to investigate associations between ambient benzene and risks of single and multiple psychiatric disorders (MPD), and explore biological aging as a potential mediator. METHODS: In a historical cohort of 410,207 UK Biobank participants, annual ambient benzene concentrations were estimated at residential addresses using 1 × 1 km spatial grids. Accelerated biological aging was assessed using PhenoAge acceleration. Cox models were used to evaluate associations between benzene exposure and nine psychiatric outcomes identified using ICD-10 codes from linked health records, adjusting for confounders. Bootstrap-based mediation analysis examined the mediating role of accelerated PhenoAge. RESULTS: Over 14.80 years of median follow-up, 64,270 participants developed psychiatric disorders. Each interquartile range increase in benzene was significantly associated with elevated risks of any psychiatric disorder (hazard ratio [HR] 1.040, 95% confidence interval [CI] 1.028-1.053) and MPD (HR 1.062, 1.039-1.086), along with mood disorders, major depressive disorder, anxiety disorders, and sleep disorders, most showing significant linear trends across exposure quartiles. Nonlinear dose-response patterns indicated disproportionately steeper risks at lower concentrations. Age and urbanicity were significant effect modifiers, with stronger associations among younger and rural participants. Accelerated PhenoAge significantly mediated the benzene-psychiatric associations, accounting for 7.85% (95% CI 5.57%-11.12%) for any psychiatric disorder and 17.26% (9.01%-80.54%) for MPD, with similar mediation observed for anxiety, substance use, and sleep disorders. CONCLUSION: Long-term ambient benzene exposure is associated with higher risks of psychiatric disorders, partly through accelerated biological aging. These findings support the refinement of benzene emission standards and monitoring policies.