Abstract
BACKGROUND: Despite the importance of understanding the long-term outcome for children of alcohol dependent (AD) women, the available literature is largely based on offspring of AD fathers and few have utilized prospective designs that include child, adolescent and young adult assessments. Multiplex AD families in which multiple cases of AD are present provide an ideal setting for understanding developmental variants of the adult phenotype. METHOD: Offspring from multiplex AD families identified through the mother or control families were evaluated multiple times during childhood and followed to young adulthood. Familial risk status and the presence of specific child/adolescent disorders were used as predictors of substance use disorder outcome by young adulthood. RESULTS: Offspring who were members of maternal multiplex families had elevated rates of child and young adulthood disorders. High risk offspring of alcohol dependent women were at increased risk for externalizing (Conduct Disorder and ADHD) and internalizing disorders (Major Depressive Disorder (MDD) and Anxiety Disorders). By young adulthood, offspring from these multiplex families had significantly greater odds of developing alcohol abuse or dependence (odds ratio [OR] = 3.63 [CI 1.36-9.64]) and drug abuse or dependence (OR = 4.23 [CI 1.73-10.32]). The prospective design of the study revealed that specific childhood disorders (Conduct Disorder, ADHD, MDD) increased the odds of subsequent development of substance use disorder (SUD). CONCLUSIONS: Multiplex familial risk for alcohol dependence is a significant predictor of substance use disorders by young adulthood. Familial risk and an earlier childhood disorder may set the stage for later development of SUD.