Altered frontostriatal white matter microstructure is associated with familial alcoholism and future binge drinking in adolescence

Abstract

Adolescence is a time of significant neurobiological development, including changes in white matter microstructure. Familial alcoholism and adolescent binge-drinking have both been associated with altered white matter microstructure; however, the temporal nature of these effects, and their interaction, is unclear. Using diffusion-weighted imaging and voxel-wise multilevel modeling, the effects of familial alcoholism and future binge-drinking on white matter microstructural development were assessed in 45 adolescents, who went on to binge-drink (but were alcohol-naive at baseline), and 68 adolescents, who remained largely alcohol-naive, all with varying degrees of familial alcoholism. Both future binge-drinking and familial alcoholism were associated with altered frontostriatal white matter microstructure early in adolescence, prior to alcohol use. While several binge-drinking-related effects persisted throughout adolescence (in the posterior limb of the internal capsule, superior corona radiata, and cerebellar peduncles), the association between familial alcoholism and altered white matter microstructure dissipated across adolescence in all regions. There were no white matter regions identified where future binge-drinking or familial alcoholism were significantly associated with emergent or exacerbated alterations in white matter microstructure. Altogether, these findings suggest that alterations in frontostiatal white matter microstructure, some of which are associated with familial alcoholism, may be used to predict which adolescents are more likely to go on and engage in alcohol use. Meanwhile, a reduction in family history-related associations with altered white matter microstructure by late-adolescence is encouraging for future prevention work targeted at at-risk youth.

Fig. 1

Effects of future binge-drinking status and family history density (FHD) on fractional anisotropy (FA). a Regions where future binge-drinking status (orange), FHD (blue) or both (green) were associated with altered FA. b In the posterior limb of the internal capsule and cerebellar peduncle, future binge-drinking status was associated with persistently greater FA with age. c In the superior frontal gyrus, greater FHD was associated with reduced FA in early-adolescence, but not late-adolescence. d In a smaller region of the cerebellar peduncle, future binge-drinking status was associated with persistently greater FA, and FHD was associated with reduced FA in early-adolescence but not late-adolescence. e In the splenium of the corpus callosum, early in adolescence, future binge-drinking status was associated with greater FA, while greater FHD was associated with reduced FA, effects that both dissipated by late-adolescence

Fig. 2

Effects of future binge-drinking status and family history density (FHD) on mean diffusivity (MD). a Regions of the brain where future binge-drinking status was persistently (orange) and transiently (yellow) associated with altered MD, and regions where both future binge-drinking status and FHD were associated with altered MD (green). b In the superior corona radiata and posterior limb of the internal capsule, future binge-drinking status was associated with persistently greater MD. c In the superior frontal gyrus, precentral gyrus, and superior longitudinal fasciculus, future binge-drinking status was associated with greater MD in early-adolescence but not late-adolescence. d In the thalamus, future binge-drinking status was associated with greater MD throughout adolescence, while greater FHD was associated with less MD in early-adolescence but not late-adolescence. e In the superior frontal gyrus, greater FHD was associated with lower MD in future binge-drinking adolescence, and greater MD in control adolescence, early in adolescence; however, this effects dissipated by late-adolescence

Fig. 3

Frontostriatal regions identified in whole-brain analysis. Out of approximately 13,000 voxels shown to have associations between family history density (FHD) and/or future binge-drinking status and fractional anisotropy (red) or mean diffusivity (blue), only 287 voxels (~2.2%; green) had alterations in both