Two competing possibilities emerge from the literature regarding the role of AAU in the expression of adolescent P300 amplitude. On one hand, P300 amplitude has been proposed as an endophenotype, or genetically transmitted biological marker, for alcoholism. This theory predicts that P300 amplitude relates to risk for alcohol misuse due to common genetic processes independent of manifested AAU. On the other hand, evidence suggests that neurodevelopment is sensitive to AAU and P300 amplitude reduction may index the neurotoxic effects of alcohol on adolescent brain development. This theory predicts that the G-E influences underlying P300 amplitude would change as AAU increases. If so, then the clinical utility of P300 amplitude as an alcoholism endophenotype would vary in populations where AAU is prevalent. Additionally, the mechanisms by which alcohol use impacts adolescent brain development would be better understood. To address these possibilities, we utilized recently developed biometric methods capable of quantifying variability in the G-E interplay underlying P300 amplitude in a large epidemiological twin sample. We reasoned that increasing levels of early alcohol use would disrupt G-E interplay underlying P300 amplitude if AAU related to P3AR differently as a function of AAU.
