A further limitation of the study is the myriad of factors associated with familial risk status. Familial risk encompasses not only the overall genetic susceptibility for AD and other SUD, but also can include correlated endophenotypes of risk such as cognitive alteration as indexed by P300 amplitude (Hill et al 2009b) that appear to alter this vulnerability. Additionally, offspring with multiplex familial AD risk often grow up in a family where the nuclear and extended family is affected with Substance Use Disorders. Importantly, alcohol and drug dependent mothers often fail to stop their use of substances during pregnancy so that these effects may contribute to increase risk for offspring psychopathology. Although analysis of these exposures is beyond the scope of the present report, separate genetic and exposure conditions appear to contribute to childhood disorders (Hill et al 2000b). Although it difficult to distinguish between genetically mediated factors and those as a result of familial environmental effects in family-based studies, the observations presented here suggest that intergeneration transmission of psychopathology through the maternal line places offspring at very high risk for
