Certain tribes of Native Americans have very high rates of alcoholism and other alcohol related disease when compared to Euroamericans, African Americans, and Asian American samples. These ethnic differences in rates of alcoholism are thought to reflect a combination of sociocultural and biological factors. Within the biological realm few studies have evaluated whether ethnic and/or racial diversities exist in physiological markers of alcoholism risk. Recent data do suggest that there is genetic diversity in biologic sensitivity to alcohol among ethnic groups. The source of the differences in alcohol sensitivity results, in part, from genetic differences in metabolic factors, i.e., polymorphisms of the genes that regulate alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), as well as inborn differences in brain cellular responses to alcohol. The overall objective of the proposed studies is to extend our previous investigations, which evaluated risk factors for the development of alcoholism as well as biological responses to alcohol and placebo challenge. Our studies suggest that Native American men have a quantitatively different response to alcohol than Euro- American and Asian American men using subjective (feelings of intoxication) as well as objective (EEGs, ERPs, cardiovascular responsivity, hormone levels) measures of intoxication. We believe that this diversity in level of response to alcohol may, in part, account for their increased risk for the development of alcoholism. In order to explore this further, these studies will be extended to Native American women age 18-25 years who will be tested for biologic response to alcohol and placebo using a modification of the same alcohol challenge protocol from our previous studies. Our preliminary studies in Native Americans ages 8-11 years will also be extended in order to determine whether specific risk factors might be present in young boys and girls prior to any alcohol exposure. A follow-up study of both the children and young adults will be carried out to deter-mine if factors identified at the initial interview are predictive of the development of alcohol- related life problems. Additionally, 18-50 year old Native American adult sibling-pairs and family members with and without alcohol dependence will be assessed using a structured diagnostic interview (SSAGA). These assessments will serve as the basis for future genetic analyses. These studies have the potential to verify whether Native Americans have any specific biological or behavioral factors that may help to explain the high risk for alcoholism within the tribes evaluated. The identification of such variables may potentially be useful in the development of specific prevention and treatment programs for this population as well as other Native American tribes.
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