Use of ultra-high-risk alcohol dependence families, as was done in the present study, has both strengths and weaknesses. Use of these families to assess the impact of prenatal substance use provides a unique opportunity to hold constant the familial/genetic susceptibility for substance use disorders while examining the impact of specific prenatal exposures on offspring. On the other hand, these families are not representative of AD families in the general population. Follow-up of offspring from these multiplex families has revealed an exceptionally high rate of AD and substance use by young adulthood (Hill et al 2008; 2011). In our view, use of extreme sampling methodology that results in inclusion of multiplex families provides an efficient means for identifying risk factors that can then be taken to population samples for replication.
