Antibiotic exposure and depression incidence: A cohort study of the Korean population.

• Positive duration-dependent associations between antibiotic exposure and the incidence of depression were consistently found in large, nationally representative database. • The number of antibiotic classes to which one is exposed during the exposure period was also positively associated with the incidence of depression. • This association remained consistent after controlling for behavioral factors, chronic comorbidity, and antibiotic indications, including infectious diseases. • The effects of specific antibiotic classes were analyzed in stratified analyses, and the effects varied by antibiotic class. • This observational study contributes to the growing body of evidence supporting the link between gut microbiota dysbiosis and depression using a population-based database. Recent research highlights the crucial role of the gut-brain axis in understanding depression etiologies. While burgeoning studies suggest an association between disruptions in gut microbiota and the development of depression, limited longitudinal studies have investigated this link. To address this gap, we conducted a retrospective cohort study using National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data in South Korea, involving 199,144 individuals aged 40–79. We examined the impact of cumulative antibiotic exposure (2004–2008) on subsequent depression incidence (2009–2013) by conducting Cox proportional hazards regressions. Our findings show an increasing depression risk with extended antibiotic exposure after adjusting for comorbidities and behavioral covariates. A broader antibiotic spectrum was associated with a higher depression risk. These trends persisted after adjusting for the original antibiotic indications. In conclusion, our study highlights the duration-dependent association between antibiotic exposure and increased depression risk, offering insights into depression etiologies and relevant novel therapeutic tools, and advocating for heightened antibiotic stewardship considering their impact on mental health. [ABSTRACT FROM AUTHOR]