There is increasing interest in the concept of endophenotypes - defined by Gottesman and Gould77 as a measurable index of liability to a phenotype that is often assumed to be more proximal to the biological underpinnings of the behavior. Endophenotypes are not only associated with disease (or behavior) but are transmitted in families (i.e. heritable) of affected individuals and while they may co-segregate with disease, they are never a consequence of it. A wide variety of endophenotypes have been identified as indices of externalizing behavior. P300, for instance, reflects human cognitive ability to respond to ‘oddball’ stimuli. In a study of adolescent twins, reduced P300 was noted in the unaffected co-twins of twins who developed alcohol dependence during early adulthood.78 Other commonly used endophenotypes for the study of substance use (and other psychopathology) include behavioral sensitivity (for alcohol, measured using sway scores of subjective high assessment scales)79 and EEG activity (e.g. beta wave patterns)80.
