Direct and Indirect Associations of Widespread Individual Differences in Brain White Matter Microstructure With Executive Functioning and General and Specific Dimensions of Psychopathology in Children.

ABSTRACT

BACKGROUND: Executive functions (EFs) are important partly because they are associated with risk for psychopathology and substance use problems. Because EFs have been linked to white matter microstructure, we tested the prediction that fractional anisotropy (FA) and mean diffusivity (MD) in white matter tracts are associated with EFs and dimensions of psychopathology in children younger than the age of widespread psychoactive substance use. METHODS: Parent symptom ratings, EF test scores, and diffusion tensor parameters from 8588 9- to 10-year-olds in the ABCD Study (Adolescent Brain Cognitive Development Study) were used. RESULTS: A latent factor derived from EF test scores was significantly associated with specific conduct problems and attention-deficit/hyperactivity disorder problems, with dimensions defined in a bifactor model. Furthermore, EFs were associated with FA and MD in 16 of 17 bilateral white matter tracts (range ß = .05; SE = .17; through ß = -.31; SE = .06). Neither FA nor MD was directly associated with psychopathology, but there were significant indirect associations via EFs of both FA (range ß = .01; SE = .01; through ß = -.09; SE = .02) and MD (range ß = .01; SE = .01; through ß = .09; SE = .02) with both specific conduct problems and attention-deficit/hyperactivity disorder in all tracts except the forceps minor. CONCLUSIONS: EFs in children are inversely associated with diffusion tensor imaging measures in nearly all tracts throughout the brain. Furthermore, variance in diffusion tensor measures that is shared with EFs is indirectly shared with attention-deficit/hyperactivity disorder and conduct problems.