OBJECTIVE: Alcoholism is a complex disorder that demonstrates genetic heterogeneity. Genetic linkage studies of alcohol dependence also suffer from the probability that many individuals who inherit an enhanced risk never develop the clinical syndrome. Thus, studies of genetic influences in alcohol abuse or dependence would benefit from the identification of characteristics of an individual that are associated with the probability of developing the disorder. A reduced responsivity to alcohol has been reported to characterize almost 40% of sons of alcoholics and to predict future alcohol abuse or dependence a decade later. This study explores the existence of this characteristic in a more heterogeneous sample that is part of a genetic pedigree study of families of alcoholics. METHOD: Eighteen to 30 year old subjects who were sons of alcohol dependent fathers and who were drinkers but not alcohol dependent were selected from pedigrees of alcoholics at all six sites of the Collaborative Study on the Genetics of Alcoholism (COGA) study. Family history negative controls matched on demography and substance use histories were selected for each subject. Data were obtained on 20 pairs of high-risk and low-risk men (40 subjects) following a challenge with 0.72 g/kg (0.9 ml/kg) of ethanol. Evaluations included measures of subjective feelings of intoxication and body sway, and changes in cortisol, ACTH and prolactin. RESULTS: The data corroborate a lower level of intensity of response to alcohol in the sons of alcoholics especially as measured by changes in cortisol, with similar but less robust changes in subjective feelings and other measures. CONCLUSIONS: The results expand upon earlier studies by using a more heterogeneous population of men at high alcoholism risk. The data highlight the possible usefulness of the reduced response to alcohol as an adjunct to future linkage analyses.
RCT Entities:
OBJECTIVE: Alcoholism is a complex disorder that demonstrates genetic heterogeneity. Genetic linkage studies of alcohol dependence also suffer from the probability that many individuals who inherit an enhanced risk never develop the clinical syndrome. Thus, studies of genetic influences in alcohol abuse or dependence would benefit from the identification of characteristics of an individual that are associated with the probability of developing the disorder. A reduced responsivity to alcohol has been reported to characterize almost 40% of sons of alcoholics and to predict future alcohol abuse or dependence a decade later. This study explores the existence of this characteristic in a more heterogeneous sample that is part of a genetic pedigree study of families of alcoholics. METHOD: Eighteen to 30 year old subjects who were sons of alcohol dependent fathers and who were drinkers but not alcohol dependent were selected from pedigrees of alcoholics at all six sites of the Collaborative Study on the Genetics of Alcoholism (COGA) study. Family history negative controls matched on demography and substance use histories were selected for each subject. Data were obtained on 20 pairs of high-risk and low-risk men (40 subjects) following a challenge with 0.72 g/kg (0.9 ml/kg) of ethanol. Evaluations included measures of subjective feelings of intoxication and body sway, and changes in cortisol, ACTH and prolactin. RESULTS: The data corroborate a lower level of intensity of response to alcohol in the sons of alcoholics especially as measured by changes in cortisol, with similar but less robust changes in subjective feelings and other measures. CONCLUSIONS: The results expand upon earlier studies by using a more heterogeneous population of men at high alcoholism risk. The data highlight the possible usefulness of the reduced response to alcohol as an adjunct to future linkage analyses.
Authors: Geoff Joslyn; Gerry Brush; Margaret Robertson; Tom L Smith; Jelger Kalmijn; Marc Schuckit; Raymond L White Journal: Proc Natl Acad Sci U S A Date: 2008-12-08 Impact factor: 11.205