Given that use of alcohol often begins during adolescence (23,24) and that significant numbers of adolescents describe themselves as regular binge drinkers (consuming at least 4–5 drinks per occasion of use (25)), the possibility of alcohol-induced neurotoxicity and interference with normal patterns of brain and behavioral development is disturbing (26). The limited work that has been done to characterize alcohol’s effects on these processes has focused on comparisons of non-using teens with teens who are self-reported binge drinkers and who often report use of other drugs of abuse. Recent findings suggest alterations in major white matter tracts in teens who report heavy drinking as compared to those who do not (26-36). Dose-response associations are difficult to establish in such studies, so it is unknown whether alcohol exerts deleterious effects based on cumulative exposure or if damage occurs at some dose threshold. As in all studies of substance abusing humans, cause-effect associations are difficult to establish, because most studies are cross-sectional, and baseline status is difficult to verify. That is, it may be that other neurobiologically-based trait factors (e.g. sensation seeking:
