Early nicotine initiation and white matter integrity: Associations from late childhood to mid-adolescence

Nicotine use is increasing in prevalence among adolescents and emerging adults in the United States. While young adulthood nicotine use has been linked to alterations in white matter tissue brain structure, little is known about late childhood nicotine initiation and its associations with white matter microstructural development. In this study, nicotine initiators (ages 9-16, n = 556) were compared on white matter regions-of-interest (ROIs) to sociodemographically matched peers (n = 556) using a subsample of the Adolescent Brain Cognitive Development (ABCD) Study (baseline to year-4 follow-up). Fractional anisotropy and mean diffusivity metrics were examined across 11 diffusion tensor imaging ROIs. Linear mixed-effects models examined nicotine initiation while controlling for prenatal nicotine exposure, parental history of problematic alcohol/drug use, and other substance use initiation. Findings indicated nicotine initiation-by-age effects for widespread cortical and subcortical fractional anisotropy ROIs, which maintained significance after multiple comparison correction and conducting sensitivity analyses covarying for pubertal staging. These ROIs did not correlate with any dose-dependent (e.g., lifetime use days) measurements among the nicotine initiators. Additionally, no significant findings were observed for mean diffusivity, or exploratory interactions with sex. Overall, neurodevelopmental effects of nicotine use on white matter integrity may appear early and are associated with trajectories of white matter development, yet continued investigations of nicotine initiation and escalation across the lifespan and its relationships with structural neuroimaging outcomes are needed.