Neuroanatomical variability in brain surface area and cortical volumes associated with adolescent e-cigarette use

Despite the widespread use of electronic cigarettes among adolescents, evidence on their impact on brain development remains limited. To investigate associations between e-cigarette use and brain structure, we analyzed data from Wave 4 (September 1, 2020-January 15, 2022) of the Adolescent Brain Cognitive Development (ABCD) Study. Participants aged 12-15 reported exclusive e-cigarette use (vs. non-use), and structural MRI data provided seven morphometric measures (cortical area, volume, thickness, sulcal depth, gray matter, white matter, and gray-white matter contrast) across 34 brain regions. Among 2620 adolescents with complete data, 91 (3.5%) reported e-cigarette use in the past six months. Compared to non-users, e-cigarette users showed significantly smaller total cortical surface area (B[SE] = -4501 [1449.5] mm², p = 0.002) and total brain volume (B[SE] = -12,511.2 [4695.4] mm³, p = 0.008). Regional differences in surface area were observed in the pars opercularis (B[SE] = -154.4 [51.3] mm², p = 0.003), medial orbitofrontal cortex (B[SE] = -123.8 [38.3] mm², p = 0.001), frontal pole (B[SE] = -26.3 [6.9] mm², p = 0.0001), and middle temporal gyrus (B[SE] = -269.1 [87.3] mm², p = 0.002). Smaller cortical volumes were found in the superior frontal gyrus (B[SE] = -1888.1 [688.5] mm³, p = 0.006), medial orbitofrontal cortex (B[SE] = -457.8 [136.4] mm³, p = 0.001), pars opercularis (B[SE] = -479.4 [161.0] mm³, p = 0.003), frontal pole (B[SE] = -114.0 [38.3] mm³, p = 0.003), precentral gyrus (B[SE] = -865.5 [330.1] mm³, p = 0.009), and banks of the superior temporal sulcus (B[SE] = -276.2 [103.3] mm³, p = 0.008). No significant differences were observed in cortical thickness, sulcal depth, or tissue contrast measures. The observed reductions in cortical surface area and volume may either precede or follow e-cigarette initiation, suggesting a potentially bidirectional relationship. These findings underscore the need for interventions and regulatory efforts to curb youth e-cigarette use.