The principal goal of the original research plan was to search for reliable """"""""markers"""""""" or indicators of vulnerability for alcoholism. Families were selected because some adult siblings were alcoholic and others were not, allowing us to trace the """"""""marker"""""""" through families to determine its association with affected status. The unaffected siblings from these families who were selected through an alcoholic proband were also contrasted with siblings from control families (no first degree relatives with alcoholism). Our research during years 01-03 has suggested a number of biological indicators deserving of further study. One of these is measurement of the late components of the event-related brain potentials (e.g., P300), another is increased haplotype sharing (HLA) among concordant affected sibs in contrast to discordant sib pairs (all family members had well characterized diagnoses, e.g., Feighner Criteria). During the proposed renewal period we plan to ascertain the complete sibship, which with their spouses and children will provide us with a large number of nuclear families with which to perform segregation analysis. This analysis along with quantitative estimates of risk (10 year and lifetime) to these children (most have not entered the age of risk) for alcoholism will be determined. With this information, we can test the reliability of our putative indicators by performing correlational analyses between the estimate risk and our quantitative indicators. With follow-up during subsequent investigations, we can confirm whether or not our predictions for specific children are correct. Also, we will begin to explore the nature of the neurobehavioral deficits reported in the literature for children of alcoholics utilizing measures of vigilance, iconic memory, and neurological functioning including static ataxia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA005909-04
Application #
3109179
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1984-01-01
Project End
1990-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
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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