This proposal is designed around the premise that breaking the cycle of intergenerational alcoholism could best be achieved by intervening in the lives of high-risk children before alcohol abuse becomes entrenched in their life-styles. To accomplish this, we need a better understanding of how to identify those children at highest risk and the predictors of adverse outcome in these special populations. Neurobiological indices of familial/genetic risk appear to hold promise for discriminating high-risk (children of alcoholic parents or children from multiple affected relatives) from low-risk children and adolescents. However, to improve specificity of this potential marker, multiple predictors may be needed to explain the major portion of variance in outcome. In 1991 we initiated a study of a sample of 8-13 year olds who were children from alcoholic families. Additionally, the availability of 14-18 year olds allowed us to begin to study a small adolescent sample as well. Their families were multigenerational for alcoholism affectation and were well characterized as they had been identified through a pair of alcoholic brothers (child's father and uncle) who had led us to the full pedigree drawn for study previously (1984-1990). Results of our follow-up study to date, which currently includes 2.5 Waves, have been analyzed and important high-risk/low-risk differences revealed. Already striking differences between the risk groups are seen: (1) children from high-risk families begin drinking earlier (13.2 years old) than those from low-risk families (14.7 years old). The high-risk children drank more per occasion and were more frequently intoxicated. A survival analysis performed on data to date showed a significantly earlier onset associated with a number of the predictors from the domains of interest: high-risk status; higher scores on Extraversion, greater postural sway, and lower amplitude of the P300 component of the event-related potential. Further follow-up of this well characterized set of high-risk children appears to be essential for understanding antecedent factors that predict alcohol dependence (possibly drug dependence as well). The children have not yet moved through the two major windows of risk (adolescence and young adulthood). Moreover, for the majority of young adults, this is a time for """"""""protective"""""""" factors (e.g. marriage and employment) to ameliorate problem drinking. Little is known about the factors that discourage continued heavy drinking in young adulthood for individuals from multigenerational alcohol dependent families in which a high density of individuals are dependent on alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA005909-15
Application #
2699647
Study Section
Clinical and Treatment Subcommittee (ALCP)
Project Start
1984-01-01
Project End
2001-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
15
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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; 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
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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