Gender differences in the relationship between white matter organization and adolescent substance use disorders

Few studies have focused on the neurobiological correlates of adolescent-onset substance use disorders (SUDs), particularly with respect to white matter development and organization. This study investigated microstructural white matter characteristics associated with SUDs during the adolescent developmental period. Twenty-four case adolescents (ages 14-18) entering treatment for SUDs and 12 sex- and age-matched control adolescents with no psychopathology were compared. Diffusion tensor imaging data were collected and analyzed using the whole-brain tract-based spatial statistics (TBSS) method. In order to comprehensively characterize diffusivity characteristics, we first studied fractional anisotropy (FA), and within regions that differed in FA, other indicators of microstructure, including the axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). A large cluster of significantly lower FA values was found in cases compared to controls in the superior longitudinal fasciculus (SLF). Within this cluster, AD and RD were also significantly different between the groups, while MD was not significantly different. For FA, a significant group by sex interaction was found; females with SUD exhibited lower FA than males with SUD, while control females exhibited higher FA than control males. These results indicated significantly lower white matter integrity in the superior longitudinal fasciculus region of association cortex, and assessed using multiple indicators of diffusion. These findings suggest that the disruption of normal white matter development due to substance exposure may be more severe in females than in males.