Although long-term longitudinal studies are in agreement that P300 amplitude is associated with familial risk for alcohol dependence, there is some variation in the emphasis that has been placed on whether reduction in P300 amplitude is an endophenotype exclusively or predominantly representing an externalizing behavioral dimension that, in turn, increases the risk for a variety of antisocial behaviors (Carlson et al., 2007; Carlson and Iacono, 2008; Krueger et al., 2002; Kruger et al., 2005; Patrick et al., 2006) including alcohol dependence and substance use disorder. Alternatively, P300 reduction may be an endophenotype that reflects an overall greater likelihood of experiencing child/adolescent psychopathology which, in turn, elevates the risk for subsequent alcohol dependence or substance use disorders. Longitudinal follow up of offspring at ultra high risk for alcohol dependence through their membership in multiplex families has demonstrated an increase in both externalizing and internalizing disorders in comparison to low risk controls (Hill et al., 2008).
