Breaking the cycle of intergenerational transmission of alcohol dependence from women alcoholics to their offspring through intervention requires identification of relevant mediating and moderating risk/protective factors. Because we need a better understanding of how to identify those children at highest risk, study of offspring of parents with the most severe form of the disorder is needed. A """"""""double proband"""""""" methodology was first developed in our laboratory to select families with more severe cases of male alcoholism (early onset, high familial aggregation). Using a double proband methodology to identify a severe form of alcoholism in women, we have now completed recruitment of a sample of mothers and their offspring for longitudinal follow-up and successfully followed children with good retention (80% at the fourth annual visit). To date, offspring of these women alcoholics have shown significantly earlier onset to begin regular drinking, and have an earlier onset of depressive disorders, conduct disorders and """"""""any psychiatric disorder."""""""" The first goal of the renewal effort is to model psychiatric outcome by age 18 through identification of important interactions between a quantified estimate of familial risk, neurobiological indicators (e.g., P300 developmental trajectories), prenatal use of alcohol/drugs in mothers, and a number of environmental factors including the mothers' continued use of alcohol/drugs. Establishing which predictors influence the age of onset to begin drinking, a variable that is highly correlated with alcohol dependence outcome in national surveys will be determined using a similar set of environmental and familial/genetic predictors. Finally, a young-adult follow-up involving participants for whom multiple waves of child/adolescent data has been collected will enable us to study the effect of these factors on outcome, including substance dependence by young adulthood. Young adulthood has been identified as a period of considerable importance in that many individuals """"""""mature out"""""""" of abusive patterns of use while others may go on to severe problems. Studying these young adults will also allow us to capture changes in drinking and drug use during young adulthood and concomitant environmental changes (e.g., marriage, first career-related job) during this period as they relate to risk status and its interaction with other familial/genetic and other environmental factors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA008082-17
Application #
7343248
Study Section
Special Emphasis Panel (ZRG1-SNEM-4 (02))
Program Officer
Chiapella, Page
Project Start
1990-01-01
Project End
2010-08-14
Budget Start
2008-02-01
Budget End
2010-08-14
Support Year
17
Fiscal Year
2008
Total Cost
$635,308
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Hill, Shirley Y; Rompala, Gregory; Homanics, Gregg E et al. (2017) Cross-generational effects of alcohol dependence in humans on HRAS and TP53 methylation in offspring. Epigenomics 9:1189-1203
Sharma, Vinod K; Hill, Shirley Y (2017) Differentiating the Effects of Familial Risk for Alcohol Dependence and Prenatal Exposure to Alcohol on Offspring Brain Morphology. Alcohol Clin Exp Res 41:312-322
O'Brien, Jessica W; Hill, Shirley Y (2017) Neural predictors of substance use disorders in Young adulthood. Psychiatry Res Neuroimaging 268:22-26
Hill, Shirley Y; Lichenstein, Sarah D; Wang, Shuhui et al. (2016) Volumetric Differences in Cerebellar Lobes in Individuals from Multiplex Alcohol Dependence Families and Controls: Their Relationship to Externalizing and Internalizing Disorders and Working Memory. Cerebellum 15:744-754
Hill, Shirley Y; Sharma, Vinod; Jones, Bobby L (2016) Lifetime use of cannabis from longitudinal assessments, cannabinoid receptor (CNR1) variation, and reduced volume of the right anterior cingulate. Psychiatry Res Neuroimaging 255:24-34
Hill, Shirley Y; Jones, Bobby L; Steinhauer, Stuart R et al. (2016) Longitudinal predictors of cannabis use and dependence in offspring from families at ultra high risk for alcohol dependence and in control families. Am J Med Genet B Neuropsychiatr Genet 171B:383-95
Hill, Shirley Y; Jones, Bobby L; Zezza, Nicholas et al. (2015) ACN9 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families. Am J Med Genet B Neuropsychiatr Genet 168B:179-87
Hill, Shirley Y; O'Brien, Jessica (2015) Psychological and Neurobiological Precursors of Alcohol Use Disorders in High Risk Youth. Curr Addict Rep 2:104-113
O'Brien, Jessica W; Hill, Shirley Y (2014) Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families. Alcohol Clin Exp Res 38:2952-61
O'Brien, Jessica W; Lichenstein, Sarah D; Hill, Shirley Y (2014) Maladaptive decision making and substance use outcomes in high-risk individuals: preliminary evidence for the role of 5-HTTLPR variation. J Stud Alcohol Drugs 75:643-52

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