Genetic factors influencing alcohol dependence.

Plentiful data from both animal and human studies support the importance of genetic influences in substance abuse and dependence (Bierut et al., 1998; Tsuang et al., 1998; Kendler et al., 2003). This review summarizes the evidence supporting such genetic influences, places them into perspective regarding animal and human studies, discusses the importance of both genes and environment, and highlights some specific genes of interest regarding the vulnerabilities for problems associated with alcohol use disorders. A long history of repetitive heavy use of alcohol exists across generations as well as the high prevalence of alcohol-related problems in Western societies. Moreover, the information offered here addresses the importance of more general issues regarding genetics and gene expression related to alcohol abuse and dependence.

A 5-year prospective evaluation of DSM-IV alcohol dependence with and without a physiological component.

BACKGROUND: The DSM-III-R removed tolerance and withdrawal as required elements for a diagnosis of alcohol dependence. Although this practice was continued in DSM-IV, the more recent manual asked clinicians to note whether physiological aspects of withdrawal (tolerance and withdrawal) had ever been experienced. Few studies have determined the prognostic meaning of a history of a physiological component to DSM-IV alcohol dependence. METHODS: Face-to-face structured interviews were used to evaluate the course of alcohol, drug, and psychiatric problems during the subsequent 5 years for 1094 alcohol-dependent men and women. These subjects had been classified into subgroups at the time of initial interview regarding evidence of tolerance or withdrawal, and all evaluations were based on DSM-IV criteria. At baseline, the application of DSM-IV diagnostic guidelines resulted in 649 (59.3%) individuals having a history of an alcohol withdrawal syndrome, with or without tolerance (group 1); 391 (35.7%) with histories of tolerance but not withdrawal (group 2); and 54 (4.9%) with no lifetime histories of tolerance or withdrawal (group 3). RESULTS: During the 5-year follow-up, both the broad (group 1 plus 2 versus group 3) and narrow (group 1 versus group 2 plus group 3) definitions of physiological dependence were associated with more alcohol and drug problems. However, for most items, this differential primarily reflected differences between groups 1 and 3, with a less impressive effect by group 2. Although no group differences were noted for the rate of independent major depressive episodes, substance-induced depressions did differentiate among groups, a finding also most closely related to the distinction between groups 1 and 3. CONCLUSIONS: These data support the prognostic importance of noting the presence of a physiological component in alcohol dependence and indicate the potential relevance of limiting the definition of a physiological component to withdrawal.

A five-year prospective study of diagnostic orphans for alcohol use disorders.

OBJECTIVE: One consequence of the DSM-IV diagnostic system for substance abuse and dependence is that there are individuals who might endorse one or two of the criterion items for dependence but not meet criteria for abuse. These persons have been referred to as "diagnostic orphans." The aim of the analyses presented here is to further understanding about this potentially important group. METHOD: The DSM-IV categorical approach was used to determine alcohol-related diagnoses for 439 young adult men. Structured face-to-face follow-up interviews were administered 5 years later. RESULTS: At the beginning of the evaluation period, 14.6% (n = 64) of the men were alcohol dependent, 18.2% (n = 80) fulfilled criteria for alcohol abuse, 16.4% (n = 72) did not meet criteria for an alcohol use disorder but endorsed one or two of the dependence criteria and 50.8% (n = 223) reported none of the dependence items. At the initial interview, and again 5 years later, the diagnostic orphans reported alcohol and drug use histories that fell between the histories of those with dependence and those with no alcohol-related difficulties. The orphans were most similar to the men with abuse, although they had lower quantities and frequencies of alcohol use, endorsed fewer additional alcohol-related problems and reported less involvement with drugs compared with that group. CONCLUSIONS: Although the diagnostic orphans were more similar to the subjects with alcohol abuse than they were to those with dependence or no diagnosis, the data do not necessarily support combining the orphans with those with abuse. These diagnostic orphans do, however, constitute an important group that carries an enhanced risk for alcohol use disorders and should be closely followed.

A comparison of alcohol-induced and independent depression in alcoholics with histories of suicide attempts.

OBJECTIVE: Alcohol-dependent men and women are at high risk for two types of major depressive episodes and for suicide attempts. The aim of this study is to compare the characteristics of two groups: (1) alcohol-dependent subjects with histories of suicide attempts and independent mood disorders and (2) a similar population of alcoholics with histories of self harm but who have only experienced alcohol-induced depressions. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism (COGA), semistructured detailed interviews were administered to 371 alcohol-dependent individuals (62% women) with histories of suicide attempts and major mood disorders. Of the total, 145 (39.1%) had ever had an independent depressive episode and 226 (60.9%) had experienced only alcohol-induced depressions. Information was obtained about socioeconomic characteristics, suicidal behavior, independent and induced psychiatric conditions, and aspects of alcohol dependence. RESULTS: Univariate and multivariate comparisons revealed that alcohol-dependent individuals with a history of suicide attempts and independent depression had a higher number of suicide attempts, were less likely to have been drinking during their most severe attempt, and were more likely to have an independent panic disorder. Univariate analyses indicated that these subjects reported a less severe history of alcohol dependence. CONCLUSIONS: The results indicate that a distinction between independent and alcohol-induced mood disorders in alcoholics with a history of suicide attempts may be useful.

Mood and anxiety symptoms among 140 children from alcoholic and control families.

OBJECTIVE: Children of alcoholics have been reported to have elevated levels of internalizing symptoms, including anxiety and depression. However, many studies have not adequately controlled for the influence of independent (i.e. not substance-induced) parental mood or anxiety disorders and other factors. The present evaluations assess the relationships of the family histories of alcohol use disorders and independent mood and anxiety disorders to internalizing symptoms in children of alcoholic and nonalcoholic subjects. METHOD: A behavioral checklist and a structured interview were administered to the parents of 140 children aged 7-18 years. The fathers of these offspring had been recruited 15 years previously from a university population to participate in a prospective study of 453 men from alcoholic and nonalcoholic families. RESULTS: While a higher score for one of four measures of internalizing symptoms in the children was found to relate to a higher density of alcoholic relatives, this pattern was more robust in children of parents with mood or anxiety disorders. In a hierarchical regression, the family history of alcohol use disorders did not add significantly to the prediction of any of the four internalizing scores in the children after considering the impact of a family history of independent mood and anxiety disorders. CONCLUSIONS: The results indicate that internalizing symptoms in children of alcoholics were more strongly influenced by a positive family history of mood and anxiety disorders than the family history of alcohol use disorders.

Comparison of 3190 alcohol-dependent individuals with and without suicide attempts.

INTRODUCTION: Suicidal behaviors are often seen in alcohol-dependent individuals. The aim of this study is to identify and confirm risk factors for suicide attempts in a large, family-based sample of alcoholics. METHODS: Semistructured, detailed interviews were administered to 3190 alcohol-dependent individuals as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Information about suicidal behavior, socioeconomic characteristics, psychiatric comorbidity, substance use disorders, and characteristics of alcohol dependence were obtained from alcohol-dependent probands, controls, and their relatives. RESULTS: As determined by both univariate comparison and multivariate logistic regression analysis, alcohol-dependent individuals with a history of suicide attempts were found to have a significantly more severe course of alcohol dependence and a higher prevalence of both independent and substance-induced psychiatric disorders and other substance dependence. First-degree relatives of subjects with suicide attempts showed a significantly higher rate of suicide attempts, even after controlling for additional relevant diagnoses. CONCLUSION: These results support the hypothesis that alcohol-dependent individuals with a history of suicide attempts are more severely impaired. Screening and subsequent treatment of alcohol use disorder, psychiatric comorbidity, and substance use disorders among alcoholics may be crucial in preventing suicide attempts and completions.

A measure of the intensity of response to alcohol in a military population.

Heavy drinking and associated problems are relatively common in young men, including those in a military setting. This article explores characteristics of alcohol intake and associated difficulties and their relationship to a self-report of the usual intensity of response to alcohol in a sample of U.S. Marines. Two questionnaires related to demography and alcohol use histories, along with a simple, 12-item self-report measure of the usual number of drinks to experience an effect (the Self-Rating of the Effects of Alcohol, SRE) were administered to 1320 U.S. Marines. The sample had an average age of 22 years, 78% were Caucasian, and 92% were enlisted personnel. The relationships and correlations among drinking characteristics and problems and the usual number of drinks for an effect were determined. These subjects drank an average of 6 days per month, consuming an average of almost six drinks per drinking day, and reported more than three times per month in which they consumed six or more drinks per occasion. Consistent with studies of other populations, the SRE measures of intensity of response to alcohol showed a positive correlation with both drinking practices and problems, with the latter remaining significant even after controlling for recent drinking practices. The prodigious level of alcohol intake and associated problems, along with the SRE scores, indicate that the Marine Corps personnel are at especially high risk for alcohol-related life problems. These data also support the potential usefulness of the SRE both in identifying individuals likely to have more severe alcohol profiles and in educating individuals regarding their levels of risk for alcohol abuse and dependence.

Correlates of unpredicted outcomes in sons of alcoholics and controls.

OBJECTIVE: Several risk factors for alcohol abuse and dependence have been identified, including a family history of the disorder and a low response to alcohol. However, not everyone with these attributes develops an alcohol use disorder and some alcoholics have neither characteristic. This article evaluates factors that might have contributed to unexpected outcomes, in a prospective study of sons of alcoholics and controls. METHOD: 411 men with complete data at baseline (Time 1 or T1) and at 15-year (Time 15 or T15) follow-ups were studied using the level of response (LR) to alcohol, the family history (FH) of alcoholism, and additional alcohol and drug-related experiences at T1. T15 data included the development of alcohol abuse or dependence, along with the 15-year functioning in six domains for the subject, as well as the characteristics of his spouse. The men were divided into groups based on the presence of two major risk factors, low LR and FH, after controlling for several other characteristics, including antisocial personality disorder. RESULTS: Rates of alcohol use disorders increased across Group 1 (family history negative [FHN] and no low LR), Group 2 (either family history positive [FHP] or low LR, but not both) and Group 3 (both FHP and low LR). After controlling for FH and LR for Group 1, only T1 drinking quantity and T15 positive alcohol expectancies related to a diagnosis, but explained only 12% of the variance. The results improved to R2's of 0.26 and 0.36 for Groups 2 and 3, with additional predictors including the T1 history of alcohol problems and T15 measures of poor coping mechanisms, higher drinking in the environment and less nurturance in the social support system. CONCLUSIONS: Procedures aimed at discouraging earlier heavier drinking, altering attitudes toward alcohol early in life, teaching appropriate coping methods and developing support systems might help individuals carrying multiple risk factors to become more resilient.

The clinical course of alcohol dependence associated with a low level of response to alcohol.

AIMS: To evaluate the clinical course of specific alcohol-related life problems and the risk for dependence on illicit drugs in individuals with relatively low and high levels of response (LR) to alcohol earlier in life. SUBJECTS: From among 439 men who were part of the 15-year follow-up of sons of alcoholics and controls, 108 were identified as having fulfilled criteria for DSM-III-R alcohol dependence. MEASURES: The LR to alcohol was originally evaluated following the consumption of 0.61 g/kg of ethanol at age 20 by determining the levels of change in subjective feelings of intoxication, body sway and several hormones such as cortisol. From the 453 original subjects, 450 completed a face-to-face 10-year follow-up evaluation, and 439 completed the 15-year protocol. FINDINGS: A comparison of the clinical course of 50 alcohol-dependent men with clearly low LR values at age 20 with that for 42 individuals whose LR scores were above the median revealed few differences. Those with a low LR had a slightly earlier age of onset of alcohol dependence (24.8 +/- 3.41 vs. 26.6 +/- 4.48 years), and this finding was unrelated to the presence of an alcohol-dependent father. Otherwise the members of the two groups demonstrated a similar course of alcohol dependence. There was no relationship between a low LR at age 20 and either the pattern of substances used or the rate of dependence on illicit drugs. CONCLUSIONS: The results indicate that for this sample a low LR to alcohol, while associated with a high risk for alcohol dependence, was not related to most aspects of the course of alcohol problems once dependence developed.

Five-year clinical course associated with DSM-IV alcohol abuse or dependence in a large group of men and women.

OBJECTIVE: The prognostic validity of the DSM-IV diagnoses of alcohol abuse and alcohol dependence was evaluated by examining the 5-year clinical course associated with those diagnoses in a large group of predominantly blue-collar men and women. METHOD: Personal semistructured interviews were carried out 5 years after an initial evaluation with 1,346 (75%) of the approximately 1,800 men and women participating in the Collaborative Study on the Genetics of Alcoholism who were eligible for follow-up. RESULTS: About two-thirds of the 298 subjects with DSM-IV alcohol dependence at baseline maintained that diagnosis during the 5-year study period. Fifty-five percent of the 288 subjects with DSM-IV alcohol abuse at baseline continued to meet one or more of the 11 DSM-IV abuse/dependence criteria, and 3.5% went on to meet the criteria for dependence at follow-up. Among the 760 subjects with no alcohol diagnosis at baseline, 2.5% met the criteria for alcohol dependence and 12.8% for alcohol abuse at follow-up. Baseline characteristics that predicted the occurrence of any of the 11 DSM-IV abuse/dependence criteria during the 5-year interval included male gender, lack of marital stability, presence of several of the criteria for dependence, and history of illicit drug use. CONCLUSIONS: The data suggest that over 5 years the DSM-IV diagnosis of alcohol dependence predicts a chronic disorder with a relatively severe course, while DSM-IV alcohol abuse predicts a less persistent, milder disorder that does not usually progress to dependence.

A genome-wide search for genes that relate to a low level of response to alcohol.

BACKGROUND: The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified. METHODS: A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences. RESULTS: Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores > or = 2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample. CONCLUSIONS: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.

A preliminary evaluation of the potential usefulness of the diagnoses of polysubstance dependence.

OBJECTIVE: The concept of polysubstance dependence (PD) has been defined several ways over the years. However, few clinicians and researchers appear to use this label in a manner consistent with any of the major diagnostic manuals. This article evaluates the prevalence and characteristics associated with PD in participants in a large collaborative study. METHOD: In DSM-IV, PD characterizes people who do not meet criteria for dependence on any one substance but, when all drugs of abuse are considered have experienced three or more of the seven dependence items across the substances. In this study, structured face-to-face interviews were administered to 8,834 men and women as part of the Collaborative Study on the Genetics of Alcoholism. The 198 subjects (2.2%) with a slightly expanded concept of the DSM-IV disorder were compared with men and women with dependence on alcohol, marijuana or stimulants, subjects with substance abuse and those with no substance use disorder. RESULTS: In this dataset, compared with subjects with a specific substance dependence, those with PD were slightly more educated and less likely to be divorced or separated, and they had fewer substance-related problems. At the same time, those with PD had more substance problems than did subjects who only met criteria for abuse. These basic conclusions were unchanged among the subset of 59 subjects who met the more restricted, classical DSM-IV PD criteria. CONCLUSIONS: The data indicate that, while relatively rare, subjects with PD might differ in potentially important ways from those with dependence or abuse on specific drugs. A large prospective study of a group with carefully defined PD is needed.

A comparison of correlates of DSM-IV alcohol abuse or dependence among more than 400 sons of alcoholics and controls.

BACKGROUND: Alcohol dependence and abuse are defined as separate disorders. However, relatively few data are available about whether the same characteristics predict both syndromes. METHODS: Complete data were available from the 15 year follow-up of 411 men who originally had been evaluated from a university population at about age 20. Both baseline data gathered prospectively and the retrospective ratings in six domains of life functioning were analyzed for their relationship to the development of alcohol abuse or dependence during the follow-up. RESULTS: Baseline characteristics of a family history of substance use disorders, the quantity and frequency of drinking, the history of alcohol-related problems, and the level of response to alcohol all predicted future alcohol abuse or dependence, but only an alcoholic second-degree relative or a first-degree drug-dependent family member differentially predicted dependence. Logistic regression analyses revealed that similar baseline characteristics combined to predict dependence and, separately, abuse. When the domains of functioning during the 15 years were included, positive alcohol expectancies, poor coping mechanisms, low level of social support, and drinking in the environment contributed to both dependence and abuse, although the relationship was stronger for dependence. CONCLUSIONS: The predictors and correlates of alcohol abuse and dependence in this group of men were similar. Further research in additional populations and on other drugs is needed to determine if the two syndromes overlap sufficiently to be combined.

A bootstrapped commingling analysis of platelet monoamine oxidase activity levels corrected for cigarette smoking.

Monoamine oxidase (MAO) activity levels have been suggested as a possible biological marker for alcohol dependence and abuse, as well as for schizophrenia and other psychiatric conditions. Using platelet MAO activities in the Collaborative Study on the Genetics of Alcoholism data set, we applied bootstrapping methods as a novel way to test for admixture in families. This bootstrapping involved resampling in family units and hypothesis testing of the resampled datasets for commingling in the distribution of MAO activity levels. Prior to commingling analysis, we used linear models to find covariates of greatest effect on MAO activity levels. While an alcoholism diagnosis was significant in men (n = 1151, P < 0.0001) and women (n = 1254, P = 0.0003), the effect lost significance after controlling for cigarette smoking, indicating alcoholism and smoking behavior to be highly confounded. When smoking histories were compared, former smokers had levels (mean = 7.1) closer to those who never smoked (mean = 7.0) than to current smokers (mean = 5.4). Furthermore, current daily smoking and time since smoking cessation were significantly related to MAO levels, indicating smoking probably has a direct effect on MAO levels, rather than the reverse. These results suggest that studies using MAO levels as a biological marker should consider smoking as an important covariate. Finally, admixture was found in MAO levels controlled for smoking and sex, possibly indicating a major genetic locus; this confirms previous evidence for admixture.

The 5-year clinical course of high-functioning men with DSM-IV alcohol abuse or dependence.

OBJECTIVE: One goal of diagnostic criteria is to predict the course of clinically relevant future problems. This study evaluated the ability of the DSM-IV categories of alcohol abuse and alcohol dependence to predict the onset and cessation of the 11 DSM-IV abuse/dependence criterion items. METHOD: The DSM-IV categorical approach was used to determine alcohol diagnoses for 435 highly educated young adult men, who constituted 97.3% of the 447 men appropriate for this study. Structured face-to-face follow-up interviews were administered 5 years later. RESULTS: At the beginning of the study, 14.5% (N=63) of the subjects were alcohol dependent, 18.2% (N=79) reported alcohol abuse, and 67.4% (N=293) carried no alcohol diagnosis. Across these three diagnostic groups, 68.3%, 46.8%, and 15.4%, respectively, experienced at least one of the 11 DSM-IV abuse/dependence criterion items over the next 5 years. Only 11.4% of those who reported alcohol abuse went on to develop alcohol dependence. In addition to their diagnosis, characteristics that predicted subsequent problems with alcohol included a family history of alcoholism, higher levels of alcohol intake and a greater number of alcohol problems in the 10 years preceding the diagnosis, and a history of drug use. CONCLUSIONS: Even in this highly educated and high-functioning group of men, alcohol abuse and dependence predicted the onset and cessation of alcohol-related problems.

Behavioral symptoms and psychiatric diagnoses among 162 children in nonalcoholic or alcoholic families.

OBJECTIVE: People with alcoholic relatives have high rates of alcohol abuse and dependence as adults, but their patterns of problems earlier in life are less clear. Many studies have not controlled for parental disorders other than alcoholism or for parents' socioeconomic status and general life functioning. The authors' goal was to conduct a study controlling for such factors. METHOD: Personal structured interviews and a behavioral checklist were administered to the parents of 162 children 7 years old or older whose fathers had participated in the 15-year follow-up of 453 sons of alcoholics with no history of antisocial personality disorder and sons of nonalcoholic comparison subjects originally selected from a university population. RESULTS: There was no significant relationship between a family history of alcoholism and childhood diagnoses of conduct, oppositional, or attention deficit disorders or with behavioral checklist summary scores. However, children with alcoholic relatives apparently have a slightly higher risk for drug abuse or dependence than those without alcoholic relatives. CONCLUSIONS: Once familial antisocial disorders and familial socioeconomic status are controlled for, a family history of alcoholism does not appear to relate to childhood externalizing disorders.

Clinical characteristics and family histories of alcoholics with stimulant dependence.

OBJECTIVE: While much is known about the clinical patterns and family histories of individuals with alcoholism or stimulant (cocaine and amphetamine) dependence, there are few data that describe men and women with concomitant alcohol and stimulant dependence. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were administered to 3,882 (2,432 male) DSM-III-R defined alcohol and/or stimulant dependent subjects. The characteristics and family histories of four groups were compared: Group 1 (26%), with the onset of alcohol before stimulant dependence; Group 2 (10%), with alcohol dependence simultaneously with or after stimulant dependence; Group 3 (58%), with alcohol dependence only; Group 4 (6%), with stimulant dependence only. RESULTS: Individuals with concomitant alcohol and stimulant dependence (Groups 1 and 2) reported more general life problems (e.g., marital instability), a higher rate of antisocial personality disorder and more substance-induced mood disorders, additional drug dependencies and substance-related difficulties than those with dependence on one substance only. People with alcohol dependence before stimulant dependence had the most severe clinical patterns. In addition, alcohol dependence and stimulant dependence were found to breed true in families of subjects with these concomitant disorders. The major findings were confirmed with logistic regression analyses, and were independent of ASPD and gender. CONCLUSIONS: It is important for clinicians to be aware of the severe clinical characteristics of patients with concomitant alcohol and stimulant dependence. In addition, the data consistent with drug-specific heritability in this heterogeneous population may be useful to researchers.

Genetics of the risk for alcoholism.

This paper reviews the literature on the importance of genetic influences in the development of alcohol abuse and dependence (alcoholism). The alcohol use disorders are fairly typical of most complex genetic conditions in that multiple genetic influences combine together to explain approximately 40% to 60% of the risk. One useful approach for identifying specific genes related to alcoholism involves identifying a population in which known genetic factors are controlled and using genome scan and/or case-control, association approaches to search for specific genes. Several characteristics, or endophenotypes, have been identified as both genetically influenced and contributing toward the risk for alcoholism, including alcohol-metabolizing enzymes, the low level of response to alcohol, and electrophysiological measures. The potential importance of each of these characteristics is reviewed, and data relating to the search for specific genetic material for each endophenotype are presented. These findings are placed in the perspective of the impact that they are likely to have on both prevention and treatment efforts in the alcohol field.

Response to alcohol in daughters of alcoholics: a pilot study and a comparison with sons of alcoholics.

Drinking, but not alcohol-dependent, 18-29-year-old daughters of alcoholics (n = 38) from the Collaborative Study on the Genetics of Alcoholism were compared to 75 family-history-positive (FHP) men from the same families, and 68 family-history-negative (FHN) male controls. Subjects received 0.75 ml/kg of ethanol (for women), 0.9 ml/kg of ethanol (for men), and placebo, each of which was consumed over 8 min on different occasions. The breath-alcohol concentrations (BrAC) and reactions to alcohol [using the Subjective High Assessment Scale (SHAS) and body sway measures] were evaluated over 210 min. The results indicate that, despite slightly higher BrAC values for the FHP men, on the SHAS the FHP women and the FHP men demonstrated significantly lower scores than the FHN male controls, although the values for FHP men and women did not differ. On body sway, the FHP men showed evidence of less alcohol-related increases than FHN men, and there was a trend in the same direction for FHP women, but only early in the session (e.g. at 60 min). Pilot data for 11 FHN women revealed higher scores for both SHAS and body sway at 60 min, compared to FHP women, but, perhaps reflecting the small number of subjects, the family history differences were not significant. Overall, the results in FHP women resemble those for FHP men, and suggest that a low level of response to alcohol might also be a characteristic of daughters of alcoholics.