This project began in 1978 with the aim of testing the relationship between a low level of response to alcohol and the alcoholism risk. During the subsequent ten years, 453 drinking but not alcohol dependent sons of alcoholic fathers and family history negative controls were evaluated through a series of increasingly complex research paradigms. These each measured the levels of changes in subjective feelings and physiological responses to clinically relevant intoxicating doses of alcohol. By 1988, the data had consistently demonstrated that a low level of response to alcohol (or the need for larger amounts of alcohol to have an effect) characterized about 40 percent of the sons of alcoholics, but was only seen in less than 10 percent of the controls. During the next five years, subjects were followed to determine whether the low level of response to alcohol at approximately age 20 predicted alcohol abuse or dependence. All 453 men were located, and personal interviews were carried out with the subject and an additional informant for 450. The data demonstrated that the low response to alcohol was a potent predictor of future alcoholism, explaining the majority of the ability of a family history of alcoholism to predict severe alcohol problems. The most recent five year protocol, which began in 1994, located all of the original subjects, interviewed subjects and their spouses, and tested how six additional areas of life functioning relate to a family history of alcoholism and the level of response to alcohol in predicting (or protecting from) severe alcohol problems. These additional domains included levels of boredom susceptibility, work stress, expectations of the effects of alcohol, and so on. During the five years beginning in 1999 subjects will be reevaluated, extensive data gathered regarding the personal and family histories of the spouse, and detailed information will be obtained regarding their projected 555 sons and daughters. The offspring will offer information regarding how the level of response to alcohol and additional important domains relate to the family histories of both the original subjects and their spouses in predicting the initiation of alcohol use, alcohol problems, substance-related problems, and mental health problems in the next generation.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
Project #
Application #
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Witt, Ellen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Veterans Medical Research Fdn/San Diego
San Diego
United States
Zip Code
Schuckit, Marc A (2018) A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity. Alcohol Clin Exp Res 42:822-835
Gonçalves, Priscila Dib; Schuckit, Marc A; Smith, Tom L (2017) Drinking Status Between Ages 50 and 55 for Men From the San Diego Prospective Study Who Developed DSM-IV Alcohol Abuse or Dependence in Prior Follow-Ups. J Stud Alcohol Drugs 78:512-520
Schuckit, Marc A; Smith, Tom L; Heron, Jon et al. (2015) Latent trajectory classes for alcohol-related blackouts from age 15 to 19 in ALSPAC. Alcohol Clin Exp Res 39:108-16
Schuckit, Marc A (2014) A brief history of research on the genetics of alcohol and other drug use disorders. J Stud Alcohol Drugs Suppl 75 Suppl 17:59-67
Schuckit, Marc A; Smith, Tom L; Kalmijn, Jelger A (2014) The patterns of drug and alcohol use and associated problems over 30 years in 397 men. Alcohol Clin Exp Res 38:227-34
Schuckit, Marc A; Smith, Tom L (2013) Stability of scores and correlations with drinking behaviors over 15 years for the Self-Report of the Effects of Alcohol Questionnaire. Drug Alcohol Depend 128:194-9
Trim, Ryan S; Schuckit, Marc A; Smith, Tom L (2013) Predictors of initial and sustained remission from alcohol use disorders: findings from the 30-year follow-up of the San Diego Prospective Study. Alcohol Clin Exp Res 37:1424-31
Schuckit, Marc A; Smith, Tom L; Kalmijn, Jelger (2013) Relationships among independent major depressions, alcohol use, and other substance use and related problems over 30 years in 397 families. J Stud Alcohol Drugs 74:271-9
Schuckit, Marc A; Smith, Tom L; Kalmijn, Jelger et al. (2012) Comparison across two generations of prospective models of how the low level of response to alcohol affects alcohol outcomes. J Stud Alcohol Drugs 73:195-204
Schuckit, Marc A; Smith, Tom L; Trim, Ryan S et al. (2012) Sex differences in how a low sensitivity to alcohol relates to later heavy drinking. Drug Alcohol Rev 31:871-80

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