Aversive Reactions and Alcohol Use in Europeans

Two hundred subjects of European descent completed a questionnaire about alcohol use and reactions to alcohol. Eleven subjects (5.5%) reported that they always experienced unpleasant reactions after small amounts of alcohol, and these subjects reported significantly lower levels for quantity and frequency of habitual alcohol use, and fewer drinks in the preceding 7 days, than the other subjects. Reactions to alcohol, either genetic or acquired, can therefore be significant in determining alcohol use in non-Asian groups.     

ADH Genotypes and Alcohol Use and Dependence in Europeans

We have tested for effects of alcohol dehydrogenase ( ADH ) genotypes on self-reported alcohol consumption and symptoms of alcohol dependence, recorded on three occasions up to 15 years apart, in 377 male and female subjects of European descent. ADH2 genotype had significant effects on both consumption and dependence in the men, but not in the women. The effects of ADH3 genotype were considerably less than those of ADH2 , but significant results could be demonstrated when the combined genotypes were considered. The direction of the effects on alcohol consumption and dependence risk were consistent with reports on Asian subjects, and with the in vitro properties of ADH isoenzymes. As with previous studies on the relationship between ADH type and alcohol use, population stratification cannot be excluded as a contributing factor in these results.     

Does Psychomotor Sensitivity to Alcohol Predict Subsequent Alcohol Use?

Data from 42 male and 58 female subjects who participated in the Colorado Alcohol Research on Twins and Adoptees (CARTA) project were subjected to model-fitting analyses. The aim of the present study was to use linear structural equation models to determine whether differences in previously measured psychomotor sensitivity to alcohol predict differences in self-reported alcohol consumption over a 4-year period. LISREL model-fitting results indicate that, for male subjects, only rail walking insensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. For females, only hand steadiness sensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. The results for males support a hypothesis that would consider alcohol insensitive individuals at greater risk for alcohol abuse. The female results, however, would argue against such a hypothesis.
With only one measure of sensitivity predicting alcohol use at only one out of four time points, in both men and women, the overall results suggest that our three measures of psychomotor sensitivity to alcohol are, in general, poor predictors of alcohol consumption in this sample.     

Association between Alcohol Use and Smoking in Adolescent and Young Adult Twins: A Bivariate Genetic Analysis

The association between alcohol use and smoking was examined in a large population-based sample of Dutch twins consisting of three age groups; young adolescent twins aged 12–14 years ( n = 650 twin pairs), 15–16-years-old adolescent twins ( n = 705 twin pairs), and young adult twins aged 17–25 years ( n = 1266 twin pairs). For all three age groups, alcohol use and smoking were correlated ( r = 0.5–0.6). Adolescents and young adults who smoked were more likely to drink alcohol than nonsmokers. The relation between alcohol use and smoking was also found within a twin pair; alcohol use in one twin was correlated with smoking in the cotwin. This finding suggested that familial factors contribute to the association between alcohol and tobacco use. With a bivariate genetic model, it was examined to what extent the comorbidity was due to genetic and environmental factors that predispose to both alcohol use and smoking. The genetic analyses showed that the underlying factors that influence alcohol and tobacco use and cause their association were different for adolescent and young adult twins. Initiation of alcohol use and smoking in adolescents (aged 12–16 years) was substantially influenced by the same shared environmental features. Alcohol and tobacco use in young adults were associated due to the same genetic risk factors.     

A PC-Based Software Test for Measuring Alcohol and Drug Effects in Human Subjects

A new software-based visual search and divided-attention test of cognitive performance was developed and evaluated in an alcohol dose-response study with 24 human subjects aged 21–62 years. The test used language-free, color, graphic displays to represent the visuospatial demands of driving. Cognitive demands were increased over previous hardware-based tests, and the motor skills required for the test involved minimal eye movements and eye-hand coordination. Repeated performance on the test was evaluated with a latin-square design by using a placebo and two alcohol doses, low (0.48 g/kg/LBM) and moderate (0.72 g/kg/LBM). The data on 7 females and 17 males yielded significant falling and rising impairment effects coincident with moderate rising and falling breath alcohol levels (mean peak BrALs = 0.045 g/dl and 0.079 g/dl). None of the subjects reported eye-strain or psychomotor fatigue as compared with previous tests. The high sensitivity/variance relative to use in basic and applied research, and worksite fitness-for-duty testing, was discussed. The most distinct advantage of a software-based test that operates on readily available PCs is that it can be widely distributed to researchers with a common reference to compare a variety of alcohol and drug effects.     

Moderate Alcohol Consumption and Estrogen Levels in Postmenopausal Women: A Review

This report reviews the literature to evaluate association between moderate alcohol consumption and estrogen levels in healthy postmenopausal women. Of the eight studies available in literature on postmenopausal women who were not on estrogen therapy, two analyzed urine samples and six analyzed blood samples for estrogen levels. Of the two urine sample studies, only one reported positive association ( p < 0.05) between alcohol consumption and estrogen (estrone and estradiol) levels that increased by 16 to 20%. Of the six blood sample studies, only two– one in American women and one in European women–reported significant increases ( p < 0.05) in estradiol levels in response to alcohol consumption. In the American women study, estradiol levels increased only with wine and not with beer or whiskey. In the European women study, estradiol levels increased in Danish and Portuguese women, but not in Spanish women. Thus, further studies are required to establish correlation between moderate alcohol consumption and estrogen levels in postmenopausal women. Of the two studies on postmenopausal women who were on estrogen replacement therapy, one administered estradiol through transdermal patch (0.15 mg) and one orally (1 mg/ day). In both studies, blood estradiol levels were measured after administering a single dose of ethanol orally (0.7–0.75 g/kg of body weight). Estradiol levels were increased by 22 and 300% in the transdermal patch and oral studies, respectively. These results suggest that alcohol consumption may increase blood estradiol levels in postmenopausal women who are on estrogen replacement therapy, and this may increase the risk of breast cancer.     

Behavioral Effects and Pharmacokinetics of Low-Dose Intravenous Alcohol in Humans

Alcohol has physiological effects on the human central nervous system at blood alcohol concentrations (BACs) as low as 9 mg/dl. It is unknown, however, if humans can perceive the effects of such low doses of alcohol. Furthermore, low BACs can be difficult to measure. The purpose of this experiment was to: (1) assess the ability of humans to perceive subjective effects of low BACs; (2) measure behavioral effects of low BACs on a psychomotor performance task; and (3) test the sensitivity and accuracy of the transdermal alcohol sensor (TAS) for measuring low BACs from skin. Five men and seven women were administered single-blind intravenous infusions of ethyl alcohol in 5% dextrose/water to achieve peak BACs of 0,10,20, and 40 mg/dl. Subjective intoxication scales and a computer administered continuous performance task (CPT) were used to assess alcohol effects. BACs were estimated from skin, blood, and breath. The only alcohol-induced sensation significantly increased during the alcohol infusions was anesthesia measured by the Alcohol Sensation Scale on the descending limb of the BAC curve. The subjective positive-reinforcing stimulant and mood effects of alcohol were not reported until subjects were administered the 40 mg/dl alcohol infusion. Other measures of subjective intoxication and sedation, and the CPT were unaffected by the alcohol infusions. The TAS provided a noninvasive method for estimating BACs that was comparable with estimates obtained from blood and breath, although delayed in time.     

Alcohol Expectancies and Behavioral and Emotional Responses to Placebo Versus Alcohol Administration

Forty normal drinking males were recruited for a study of "responses to alcohol." Following the completion of an alcohol use questionnaire that included measures of expectancies of alcohol effects, subjects were randomly assigned to either receive the actual 0.6 g/kg dose of ethanol to bring their peak blood alcohol concentration (BAC) to near 0.075 g/dl or to receive a placebo dose. Neither the subject nor the tester was aware of the condition to which the subject has been assigned. Prior to dosing and at repeated 1/2-hr intervals following dosing, subjects were tested on a battery of motor coordination, perceptual speed, reaction time, and mood measures. Significant alcohol effects were found for several measures, but the only significant interaction of individual differences in expectancies of alcohol effects with alcohol dosing occurred for self-perceived intoxication. Subjects who expected more disinhibition after alcohol dosing and who were administered alcohol reported more intoxication than those expecting less disinhibition, while no expectancy effect was found for subjects administered the placebo.     

Effects of variation at the ALDH2 locus on alcohol metabolism, sensitivity, consumption, and dependence in Europeans

BACKGROUND: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the alcohol flush reaction and reduces alcohol consumption and risk of alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry. METHODS: Serial measurements of blood and breath alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an alcohol challenge study. Participants provided data on alcohol reactions, alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on alcohol metabolism and alcohol's effects. RESULTS: The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath alcohol concentration, with similar but smaller and nonsignificant effects on blood alcohol. Haplotype-related variation in responses to alcohol, and reported alcohol consumption, was small and not consistently in the direction predicted by the effects on alcohol concentrations. CONCLUSIONS: Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on alcohol sensitivity, consumption, or risk of dependence.     

Impulsivity, Sensation Seeking, and Behavioral and Emotional Responses to Alcohol

Three hundred forty-two male and female subjects from the Colorado Alcohol Research on Twins and Adoptees returned a mailed questionnaire that included the Eysenck Impulsivity-Venturesomeness-Empathy scales. These subjects had previously been tested in a procedure in which they were given a 0.8 g/kg dose of ethanol to bring their peak blood alcohol concentration (BAC) to near 0.10 g/dl, given topping doses to maintain this BAC over a 3-hr period, and repeatedly tested on a battery of diverse physiological, psychomotor, perceptual speed, and mood measures. Impulsivity was significantly correlated with higher levels of self-reported alcohol use and the occurrence of alcohol use problems in males, while both impulsivity and venturesomeness (sensation seeking) were significantly correlated with lessened motor impairment following alcohol use in males. These personality measures, however, were not significantly correlated with mood measures following initial alcohol dosing. Impulsivity and venturesomeness were uncorrelated with alcohol use and responses to alcohol in females, but as with males, impulsivity was related to the occurrence of alcohol use problems in females.     

Risk Factors for Alcohol Dependence: A Questionnaire Survey

Several factors, known to associate with alcoholism, have not been studied together earlier as determinants of alcohol dependence, and taking into account possible interactions. A representative sample of 302 male and 312 female Finns, aged 19 to 81 years, answered a computerized questionnaire in January 1996. The diagnosis of alcohol dependence was based on the ICD-10 criteria. There were 66 (10.8%) subjects with current (past 12-month) ICD-10 alcohol dependence. After adjusting for other potential correlates in logistic regression analysis, alcohol dependence was more common among subjects high on both asocial behavior and on thinking that his or her behavior is determined mainly by chance or by other people (external control) than among the rest [odds ratio (OR) 4.4; 95% confidence interval (95% Cl) 1.8–10.91. Likewise, alcohol dependence was more common among subjects who recalled that they were highly stimulated when intoxicated by alcohol (OR 3.4; 95% CI 1.9–6.0). High predisposition to anxiety associated strongly with alcohol dependence among males (OR 13.8; 95% CI 4.4–43.1), but not among females (OR 25; 95% CI 0.7–9.1). Several of the aforementioned correlates may be modifiable risk factors for alcohol dependence.     

Autistic Behaviors in Offspring of Mothers Abusing Alcohol and Other Drugs: A Series of Case Reports

Although autistic-like behaviors were described even in the earliest reports of fetal alcohol syndrome, it was only recently that fetal alcohol syndrome and autism were reported as a dual diagnosis in six school-aged children. The purpose of the present series of case reports is to describe marked autistic characteristics in three much younger children (25–36 months) with histories of prenatal exposure to alcohol and other drugs. The behavioral characteristics of these children are described and compared with current diagnostic criteria for autistic disorder. In addition, longitudinal scores on the Bayley Scales of Infant Development are provided to underscore the marked developmental delays shown by each of the children. Limitations of these case reports are discussed with suggestions for future prospective research.     

Gender Differences in Patterns of Alcohol Consumption in Spain

Gender differences in alcohol consumption components, hazardous alcohol consumption, and drinking patterns among Spaniards were analyzed. The study was conducted in the fall of 1992 on 2,500 individuals, aged 14–70 years, who lived in the region of Castile and Leon (Spain). Males drank more frequently (with a high intake of alcohol), were more likely to be hazardous drinkers, and started drinking earlier than females. Both sexes drank beer in a similar way, but not wine and spirits. Males and females gave similar reasons for drinking and showed similar patterns of "family" drinking, although sex differences in other patterns of alcohol consumption were found. The relevance of results was discussed.     

Alcohol effects during acamprosate treatment: a dose-response study in humans

BACKGROUND: Acamprosate (calcium acetyl homotaurinate) reduces alcohol intake in animals and increases abstinence rates in alcohol-dependent persons. Acamprosate's mechanism of action, however, remains poorly understood. In order to examine whether acamprosate/alcohol interactions contribute to acamprosate's efficacy, the present double-blind, placebo-controlled human laboratory study examined effects of acamprosate on the pharmacokinetics and subjective, psychomotor, and physiological effects of alcohol in heavy drinkers. METHODS: In a six-week within-subject design, participants were maintained on acamprosate (0, 2, and 4 g, p.o., double-blind, in counterbalanced order) for 11 days at each dose. Physiological, subjective, and psychomotor measures were collected daily during each dosing cycle. During each acamprosate dose condition, subjects were challenged with 0, 0.5, and 1.0 g/kg ethanol (p.o., counterbalanced order) during three separate laboratory sessions. Subjective, physiological, and psychomotor effects of alcohol, and breath alcohol levels were collected at baseline and at 30-min intervals for a 3-hr post-administration period. RESULTS: Acamprosate alone did not substantially affect subjective, physiological, or psychomotor performance measures. Acamprosate did not alter alcohol pharmacokinetics, or alcohol-induced behavioral impairment or tachycardia, and most subjective alcohol effects were also unaltered by acamprosate as well. Although a trend appeared for acamprosate to increase subjective ratings of intoxication following the lower (0.5 g/kg) alcohol dose, adjustment for individual differences in blood alcohol level eliminated this effect, suggesting the trend was not due to a central effect of acamprosate. CONCLUSIONS: Acamprosate does not alter alcohol pharmacokinetics, acute physiological or psychomotor alcohol effects, or most subjective alcohol effects.     

Variation in alcohol pharmacokinetics as a risk factor for alcohol dependence

BACKGROUND: The significant association between alcohol dehydrogenase (ADH)-2 genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence. METHODS: We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992-1993. RESULTS: Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up had higher blood and breath alcohol values after alcohol challenge than never-dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2-fold higher in men and 3-fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile. CONCLUSIONS: In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.     

Alcohol dependence and abuse diagnoses: concurrent validity in a nationally representative sample

The Alcohol Dependence Syndrome concept has had a widespread influence on the major nosological classification systems, most recently with its operationalization as DSM-IV alcohol dependence. Although many studies have provided evidence of the validity of the Alcohol Dependence Syndrome in clinical samples, little validation work has been conducted in general population samples on DSM-IV alcohol dependence or the distinction of DSM-IV alcohol dependence from DSM-IV alcohol abuse. We therefore examined the cross-sectional validity of DSM-IV alcohol dependence and abuse in 27,616 household residents who participated in a 1992 national survey on alcohol use disorders. Validity was investigated by testing the association of a set of five "criterion" variables, external to the alcohol diagnostic criteria, with dependence and abuse diagnoses. Results indicated that dependence diagnoses were significantly associated with all criterion variables when compared with those with no diagnosis and also when compared with alcohol abuse. This supported the separation of dependence from abuse. Abuse diagnoses were associated with some, but not all, criterion variables when compared with subjects with no diagnosis. This report replicates many aspects of a similar investigation in a community sample of household residents. Implications for the next steps in research are discussed.     

Behavioral Impairment Under Alcohol: Cognitive and Pharmacokinetic Factors

This study tested the hypothesis that the intensity of behavioral impairment under alcohol is related to social drinkers' expectancies about impairment and their rates of rise in blood alcohol concentration (BAC). After subjects ( n = 30) were trained on a psychomotor task, they rated the impairment they expected from alcohol and then performed the task under alcohol (0.56 g/kg) or a placebo. Alcohol impaired performance, compared with placebo. Drinkers' expectations about impairment and their rates of rise in BAC were independent, and each factor predicted a significant portion of the variance in alcohol impairment among drinkers. More intense impairment under alcohol was associated with expectations of greater impairment and with swifter rates of rise in BAC. BACs obtained by drinkers during task performance were not related to the intensity of impairment they displayed. The study shows that a pharmacological and nonpharmacological variable can each affect a drinker's behavioral impairment under alcohol, and this finding contributes to our understanding of conditions where BAC per se may be an unreliable indicator of impairment.     

Intoxication after an Acute Dose of Alcohol: An Assessment of Its Association with Alcohol Consumption Patterns By using Twin Data

We examined the hypothesis that genetically determined differences in sensitivity to alcohol explain some of the genetic variation in alcohol consumption pattern. Self-report data on average weekly alcohol consumption and self-ratings of intoxication after a standard dose of ethanol (0.75 g/kg body weight), used as an index of sensitivity, were obtained on 206 Australian twin pairs. Significant genetic covariance between weekly consumption and level of intoxication after alcohol intake was found in males, lower ratings of intoxication being associated with increased consumption. However, when direction of causation models were fitted to the male twin data, the hypothesis that decreased sensitivity was a cause of increased consumption was rejected. The major causal effect was that of weekly consumption on level of sensitivity. A similar, although nonsignificant, trend was observed in females. The strength of the association between self-report of average weekly consumption and level of intoxication after a standard dose of alcohol supports the validity of the former measure.     

Alcohol and Secobarbital Effects as a Function of Familial Alcoholism: Extended Intoxication and Increased Withdrawal Effects

Response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism have been demonstrated in previous research and are thought to be related to risk for developing alcoholism. If this is so, the pharmacological breadth of addiction risk conferred by a positive family alcoholism history might be studied by determining whether FHP subjects show different responses than FHN to drug classes other than alcohol. We have previously reported on the acute effects of ethanol as compared with secobarbital in FHP and FHN subjects and found that FHP subjects showed greater sensitivity across a variety of subjective measures than FHN subjects for both drug classes. The data reported here are based on an extended data collection period of 3 to 18 hr postingestion, following completion of the acute laboratory portion of the study. Specifically, in the present study, dose-effect timecourse functions for a variety of physiological (heart rate, blood pressure, and breath alcohol level), subjective (analog mood, drug effect, and withdrawal, Subjective High Assessment Scale (SHAS], and psychomotor measures (Digit Symbol Substitution Test and numeric recall) were examined in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg daily) and ethanol (1 g/kg daily). FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. FHP subjects reported more extended intoxication and greater withdrawal effects following both ethanol and the high dose of secobarbital than did FHN subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in Alcohol Expectancy Between Aggressive and Nonaggressive Social Drinkers

Previous reports have shown that drinkers with aggressive personalities not only hold the strongest beliefs that alcohol facilitates aggressive behavior, but they also display the greatest increases in laboratory aggression after receiving alcohol. Given that several studies have demonstrated that a portion of the behavioral and subjective effects of alcohol are due to psychological expectancy, this study explored whether aggressive drinkers have elevated intoxication expectancies from laboratory beverages with unknown alcohol content. The rates of aggressive responses emitted in a money subtraction aggression model under baseline conditions were used to select an aggressive group and a nonaggressive group, each with five male and five female participants. Subjects then ingested and rated each of three placebo (1 ml alcohol) beverages administered hourly during a subsequent laboratory visit, and rated a series of three 0.35 g/kg of alcohol beverages the following day. Whereas nonaggressive subjects clearly discriminated the relative alcohol content of alcohol and placebo drinks, aggressive subjects gave progressively elevated shot equivalent ratings to placebo drinks, similar to their ratings of alcohol doses. However, despite similar self-reported drinking histories, aggressive subjects reported anticipating only half the intoxication from the alcohol doses (and in fact achieved a lower peak breath alcohol concentration) than was expected by nonaggressive subjects.