Alcohol Expectancies and Drinking Refusal Self‐Efficacy Mediate the Association of Impulsivity With Alcohol Misuse

Background: Recent work suggests that 2 biologically based traits convey risk for alcohol misuse: reward sensitivity/drive and (rash) impulsiveness. However, the cognitive mechanisms through which these traits convey risk are unclear. This study tested a model predicting that the risk conveyed by reward sensitivity is mediated by a learning bias for the reinforcing outcomes of alcohol consumption (i.e., positive alcohol expectancy). The model also proposed that the risk conveyed by rash impulsiveness (RI) is mediated by drinkers’ perceived ability to resist alcohol (i.e., drinking refusal self‐efficacy). Methods: Study 1 tested the model in a sample of young adults (n = 342). Study 2 tested the model in a sample of treatment‐seeking substance abusers (n = 121). All participants completed a battery of personality, cognitive, and alcohol use questionnaires and models were tested using structural equation modeling. Results: In both studies, the hypothesized model was found to provide a good fit to the data, and a better fit than alternative models. In both young adults and treatment‐seeking individuals, positive alcohol expectancy fully mediated the association between reward sensitivity and hazardous alcohol use. For treatment seekers, drinking refusal self‐efficacy fully mediated the association between RI and hazardous drinking. However, there was partial mediation in the young adult sample. Furthermore, neither trait was directly associated with the other cognitive mediator. Conclusions: The hypothesized model was confirmed on a large sample of young adults and replicated on a sample of treatment‐seeking substance abusers. Taken together, these findings shed further light on the mechanisms through which an impulsive temperament may convey risk for alcohol misuse.     

Interaction between the ADH1B*3 allele and drinking motives on alcohol use among Black college students

Background: Black young adults have lower rates of alcohol use than other racial groups. Genetic factors may protect against drinking. Specifically, the ADH1B*3 allele is present almost exclusively in Black populations and has been protective against alcohol use and alcohol use disorder. The protective effects of the ADH1B*3 allele, however, may differ as a function of alcohol-promoting cognitions. Objectives: The current study examined whether ADH1B*3 moderated relations of drinking motives with alcohol consumption among Black college drinkers. Methods: Participants were 241 undergraduate students of self-identified Black race (mean age = 20 years; 66% female) who reported consuming alcohol at least once in the past 30 days. Results: ADH1B*3 was not significantly associated with drinking motives or drinking behaviors. However, significant, albeit small, interaction effects of ADH1B*3 with drinking motives on drinking behavior were found; the presence of an ADH1B*3 allele protected against greater drinking quantity among students with high social motives (incidence rate ratio [IRR] = 0.95, 95% CI [0.92, 0.99]) and against frequent drinking among students with low coping motives (IRR = 1.06, 95% CI [1.01, 1.11]). Conclusion: These findings represent a novel demonstration of genetic modulation of alcohol-related cognitions within Black college drinkers, although replication is needed. Results represent an initial step toward better characterizing individual differences in associations of drinking motives with drinking behavior, with potential implications for interventions aimed at motivational processes in alcohol use.     

Drinking motives in female smokers: factor structure, alcohol dependence, and genetic influences

Background: Alcohol and tobacco use often co‐occur. Human and animal studies indicate that nicotine increases alcohol’s rewarding effects and the motivation to consume it. The aims of this study were to examine whether the factorial architecture of self‐reported motivations to consume alcohol differed between regular and nonregular cigarette smokers while taking into account the lifetime history of alcohol dependence and psychopathology, and to estimate the genetic and environmental influences on the motivations. Methods: Using data on 2,189 monozygotic and dizygotic female twins, we examined the factorial structure (item thresholds and factor loadings, means, and variances) of the items from the Drinking Motives Questionnaire (DMQ) in regular and nonregular smokers. Post hoc tests examined the association between the latent drinking motives factors and alcohol dependence in both groups. Twin models were fitted to the latent drinking motives factors, testing for variations in the magnitude of additive genetic, shared, and nonshared environmental influences between the groups. Results: The 4 DMQ factors (social, conformity, coping, and enhancement) were recovered in both groups, and their measurement structure was consistent across the groups. Regular smokers reported higher levels of coping, enhancement, and social motives while nonregular smokers reported higher conformity motives. Alcohol dependence was associated with higher scores on all motives in both groups; however, in a regression analysis that included all of the motives as predictor variables, only coping was significantly related to alcohol dependence. While twin models revealed evidence for substantially greater genetic influences on enhancement (h² = 0.40), coping (h² = 0.35) and social (h² = 0.37) drinking motives in regular compared to nonregular smokers, the power to statistically distinguish the 2 groups was low. Conclusions: While the measurement structure of the drinking motive factors appears to be similar across regular and nonregular smokers, regular smokers report more motivation to drink for internal affect‐related reasons and to obtain social reward. Of all the motives, coping was the most robust predictor of alcohol dependence in both the regular and the nonregular smokers. Further, genetic influences might play a larger role in drinking motives among regular smokers, which provides tentative evidence for latent genetic × smoking status interactions.     

Risky alcohol use in adolescence: the role of genetics (DRD2, SLC6A4) and coping motives

Background: Drinking to cope (i.e., drinking to forget or alleviate negative feelings) has been found to be associated with adolescents’ heavy drinking and alcohol‐related problems. Additionally, it is widely accepted that genetic factors are involved in alcohol use and dependence. Studies are only beginning to reveal, however, which specific genotypes are related to drinking behaviors, and it is unknown whether they may interact with coping motives in predicting adolescents’ risky drinking. The aim of this study was to examine relationships between the dopamine D2 receptor gene (DRD2) Taq1A polymorphism (rs1800497), a serotonin transporter gene (SLC6A4) polymorphism (5‐HTTLPR), coping motives, and adolescents’ binge drinking and alcohol‐related problems. Methods: Participants in this cross‐sectional study were 282 Dutch adolescents (mean age 17.4, 47% men) who had consumed alcohol at least once in their life. Results: Coping motives were positively related to both binge drinking and alcohol‐related problems, while DRD2 and SLC6A4 genotypes were not. DRD2, but not the SLC6A4 genotype, interacted with coping motives. The link between coping motives and alcohol outcomes was stronger among those carrying the DRD2 risk (A1) allele. Conclusions: This study extends the present literature by providing additional insight into the etiological factors of adolescent drinking behavior. An interaction between a vulnerability gene (DRD2) and a cognitive factor (coping drinking) was found to be related to adolescents’ binge drinking and alcohol‐related problems.     

ALDH2 and ADH1B interactions in retrospective reports of low-dose reactions and initial sensitivity to alcohol in Asian American college students

Background: A mechanistic model has been proposed for how alcohol‐metabolizing gene variants protect individuals from the development of alcohol use disorders, with heightened sensitivity to alcohol being an early step (endophenotype) in this model. This study was designed to determine whether possession of 2 alcohol‐metabolizing genes variations, the aldehyde dehydrogenase ALDH2*2 allele and the alcohol dehydrogenase ADH1B*2 allele, was associated with self‐reported sensitivity to alcohol at low doses and at initial use. Methods: Asian–American college students (N = 784) of Chinese and Korean descent were genotyped at the ALDH2 and ADH1B loci and assessed for lifetime alcohol symptoms following 1 or 2 drinks and level of response to alcohol during the first 5 lifetime drinking episodes. Results: Participants who had an ALDH2*2 allele were more likely to report experiencing all 6 low‐dose symptoms and having heightened initial response to alcohol. An interaction was found between ALDH2*2 and ADH1B*2, with ADH1B*2 being associated with heightened self‐reported sensitivity to alcohol only in individuals who also possessed 1 ALDH2*2 allele. Conclusions: These findings suggest the effects of ADH1B*2 may be felt more strongly in Asians who already have some heightened sensitivity to alcohol from possessing 1 ALDH2*2 allele, but who are not too sensitized to alcohol from possessing 2 ALDH2*2 alleles. These results offer additional insight into the discrepant findings that have been reported in the literature for the role of ADH1B*2 in response to alcohol and the development of alcohol‐related problems.     

A systematic evaluation and validation of subtypes of adolescent alcohol use motives: genetic and environmental contributions

Background: Alcohol use motives are closely associated with specific profiles of alcohol use and reflect a subjectively derived decisional framework based on a motivational style of responding. Adult twin studies typically estimate the heritability of alcohol use motives to be between 7 and 42%, although relatively little is known about genetic and environmental influences upon alcohol use motives in adolescence. Methods: Latent class analysis (LCA) models containing 1 through 5 classes were fitted to the data derived from 1,422 adolescent twin and siblings self‐reported alcohol use motives. Using twin models, we estimated the genetic, shared, and nonshared environmental influences to the class membership data derived from the LCA. Results: Four drinking motives classes were identified (family‐oriented, social, enhancement/social, and coping/social). The coping/social and enhancement/social classes were differentiated from the social class on measures of depression, delinquency, and aggressive behavior. Analyses indicated that nonadditive genetic factors accounted for 76% of the variance in the coping/social motives class and additive genetic influences accounted for 66% of the variance in the social motives class. There was a moderate contribution of genetic factors and shared environmental factors influencing class membership of enhancement/social motivated drinkers (28 and 20% explained variance, respectively). Substantial shared environmental influences were revealed for membership of the family‐oriented class (75%). Conclusions: Heritable influences may predispose individuals to drink to cope with negative affect, for social reasons, and to a lesser extent for enhancement. Familial environmental influences shape family‐oriented motives for drinking in adolescents.     

ALDH2*2 and peer drinking in East Asian college students

Background: The ALDH2*2 allele (A-allele) at rs671 is more commonly carried by Asians and is associated with alcohol-related flushing, a strong adverse reaction to alcohol that is protective against drinking. Social factors, such as having friends who binge drink, also contribute to drinking in Asian youth. Objectives: This study examined the interplay between ALDH2*2, peer drinking, and alcohol consumption in college students. We hypothesized that the relationship between ALDH2*2 and standard grams of ethanol per month would vary based on the level of peer drinking. Methods: Subjects (N = 318, 63.25% female) were East Asian college students in the United States who reported drinking alcohol. Data were from the freshman year of a university survey that included a saliva DNA sample. ALDH2*2 status was coded ALDH2*2(+) (A/G and A/A genotypes) and ALDH2*2(?) (G/G genotype). Peer drinking was students’ perception of how many of their friends “got drunk”. Results: Main effects of ALDH2*2(?) and having more friends who got drunk were associated with greater alcohol consumption. The ALDH2*2 × peer drunkenness interaction showed a stronger positive association with alcohol consumption for ALDH2*2(?) versus ALDH2*2(+) at increasing levels of peer drunkenness. Follow-up comparisons within each peer drunkenness level identified significantly higher alcohol consumption for ALDH2*2(?) compared to ALDH2*2(+) at the all friends got drunk level.

Conclusion: There was evidence of a stronger effect for ALDH2*2(?) compared to ALDH2*2(+) with greater alcohol use when students were more exposed to peer drinking. Findings contribute to a growing literature on the interrelationships between genetic influences and more permissive environments for alcohol consumption.     

The association of ADH and ALDH gene variants with alcohol drinking habits and cardiovascular disease risk factors

Background: Genetic variation in ethanol metabolism may have an influence on both alcohol drinking habits and the susceptibility to health effects of alcohol drinking. Such influences are likely to bias exposure‐disease associations in epidemiologic studies of health effects of alcohol drinking. In a Caucasian population, we examined the association of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genetic variants with alcohol drinking habits, biomarkers of alcohol exposure, and risk factors for cardiovascular disease. Methods: The study population consisted of 1,216 Danish men and women aged 15–77 years participating in a health examination in 1998. The health examination included a self‐administered questionnaire (alcohol drinking habits), a physical examination (blood pressure), and various blood tests [alanine aminotransferase (ALAT), erythrocyte mean corpuscular volume (E‐MCV), and lipids]. ADH and ALDH gene variants were determined by standard techniques. Data were analyzed by regression analyses adjusted for relevant confounders. Results: Self‐reported alcohol drinking was significantly associated with increasing levels of ALAT, E‐MCV, high‐density lipoprotein cholesterol, and blood pressure. The ALDH1b ala69val variant was associated with nondrinking and total alcohol intake. The ALDH2 promoter variant was associated with binge‐drinking, and the ALDH1b1 ala69val polymorphism was associated with diastolic blood pressure. We did not find any statistically significant interactions between any of the gene variants and alcohol consumption in relation to the various outcomes. Conclusions: In this Caucasian population sample, we found evidence to support that genetic variation in ethanol metabolism may influence drinking habits, but no statistically significant gene‐environment interactions. More large‐scale epidemiologic studies are needed to confirm theses results and to further investigate genetic susceptibility to the effects of alcohol drinking.     

The relationship between rs3779084 in the dopa decarboxylase (DDC) gene and alcohol consumption is mediated by drinking motives in regular smokers

Background: Motivational models of alcohol use propose that the motivation to consume alcohol is the final common pathway to its use. Both alcohol consumption and drinking motives are influenced by latent genetic factors that partially overlap. This study investigated whether drinking motives mediate the associations between alcohol consumption and 2 single‐nucleotide polymorphisms (SNPs) from genes involved in serotonin (TPH2; rs1386496) and dopamine synthesis (DDC; rs3779084). Based on earlier work showing that enhancement and coping motives were heritable in regular smokers but not in nonregular smokers, we hypothesized these motives would mediate the relationships between alcohol consumption and these SNPs in regular smokers. Methods: Drinking motives data were available from 830 young adult female twins (n = 344 regular smokers and n = 486 never/nonregular smokers). We used confirmatory factor analyses to model enhancement, coping, and alcohol consumption factors and to conduct mediation analyses in the regular smoker and never/nonregular smoker groups. Results: Our hypothesis was partially supported. The relationship between alcohol consumption and rs1386496 was not mediated by drinking motives in either group. However, in the regular smokers, the relationship between alcohol consumption and rs3779084 was mediated by enhancement and coping motives. Carriers of the rs3779084 minor allele who were regular smokers reported more motivation to consume alcohol. Given this pattern of results was absent in the never/nonregular smokers, our results are consistent with a gene × smoking status interaction. Conclusions: In regular smokers, variability at the locus marked by rs3779084 in the DDC gene appears to index biologically based individual differences in the motivation to consume alcohol to attain or improve a positive affective state or to relieve a negative one. These results could be because of increased sensitivity to the reinforcing effects of alcohol among minor allele carriers who smoke, which might be due to structural or functional differences in mesorticolimic dopamine “reward” circuitry.     

Motivational pathways from antecedents of alcohol use to consequences: a structural model of using alcohol to cope with negative affect

ABSTRACT

Background: Drinking among college-aged individuals can be problematic. The motivational model of use, which examines various cognitive factors, personal characteristics, and environmental factors, can provide a greater understanding of what contributes toward the decision to drink in these young adults. Objectives: The current study evaluates proposed paths from risk factors for alcohol use, motives for drinking, and subsequent outcomes of alcohol use, drawing from seminal research on the motivational model and drinking motives. Methods: This model was tested in a sample of 303 undergraduate drinkers (77.9% female, mean age = 19.8 years), and evaluated the potential impact of gender and pattern of use. Results: Results indicate that expectancies, maladaptive coping, and negative affect personality styles are associated with coping motives for drinking, and that coping motives are significantly related to problems associated with use. These results are similar for males and females, and among heavy and lighter drinkers. Conclusion: Findings support the role of the coping motive in problematic outcomes associated with drinking and suggest that expectancies, negative affect personality styles, maladaptive coping, and drinking motives are potential targets of prevention and intervention.     

Implicit and explicit alcohol cognitions and observed alcohol consumption: three studies in (semi)naturalistic drinking settings

Aims Dual‐process models imply that alcohol use is related to implicit as well as explicit cognitive processes. Few studies have tested whether both types of processes are related to ad libitum drinking. In a series of three studies, we tested whether both implicit and explicit alcohol‐related cognitions predicted the amount of alcohol consumed in an ad libitum (semi)naturalistic drinking situation. Design Two experimental studies used trained confederates (same‐sex peers) who consumed either alcoholic or non‐alcoholic beverages, while observing participants' drinking behaviour in a 30‐minute session. The third study involved observations of participants' alcohol use during a 45‐minute session in which participants spent time with five to seven friends. Setting A (semi)naturalistic drinking setting, a laboratory bar. Participants Participants were undergraduates recruited at Radboud University (study 1: n = 115; study 2: n = 121; study 3: n = 200). Measurements We used coding of drinking behaviour from observations, questionnaire data on positive alcohol expectancies and alcohol use patterns and implicit association tests to assess alcohol associations. Findings Implicit associations were not related to observed alcohol use, whereas explicit positive expectancies were related positively to observed alcohol use in study 1 and study 2. Conclusions Among undergraduate students in (semi)naturalistic drinking settings with peers, implicit alcohol‐related cognitions do not predict the amount of alcohol consumed.     

The enduring influence of drinking motives on alcohol consumption after fateful trauma

Objective: Drinking motives predict later levels of alcohol consumption and development of alcohol dependence, but their effects on stress‐related drinking are less clear. Proximity to the terrorist attack on the World Trade Center (WTC) on 9/11/01 was significantly associated with alcohol consumption 1 and 16 weeks after 9/11/01. We investigated the relationship between drinking motives measured a decade earlier, proximity to the WTC, and drinking after 9/11/01. This event constitutes a natural experiment for studying the effects of previously measured drinking motives on alcohol consumption after fateful trauma. Methods: Adult drinkers (N = 644) residing in a New Jersey county were evaluated for four drinking motives: coping with negative affect, for enjoyment, for social facilitation and social pressure. After 9/11/01, their exposure to the WTC attack and subsequent drinking were assessed. Poisson regression was used to assess the relationships between proximity to the WTC, drinking motives and post‐9/11/01 drinking; models were adjusted for alcohol dependence, age, gender and race. Results: Drinking to cope with negative affect predicted alcohol consumption 1 week after 9/11/01 (p = 0.04) and drinking for enjoyment predicted drinking 1 and 16 weeks after 9/11/01 (p = 0.001 and 0.01, respectively). The associations were independent of proximity to the WTC. No interactions were observed between drinking motives, proximity to the WTC or lifetime alcohol dependence. Conclusion: Drinking motives a decade earlier predicted higher alcohol consumption after fateful trauma independently from proximity to the WTC on 9/11/01. Results suggest that drinking motives constitute a robust, enduring influence on drinking behavior, including after traumatic experiences.     

MAOA Interacts With the ALDH2 Gene in Anxiety–Depression Alcohol Dependence

Background: Alcohol dependence is usually comorbid with anxiety disorder, depressive disorder, or both; this comorbidity may increase drinking behavior. We previously hypothesized that anxiety–depressive alcohol dependence (ANX/DEP ALC) was a genetically specific subtype of alcohol dependence. ANX/DEP ALC may be related to dopamine and serotonin, which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The aim of this study was to determine whether the interaction between the MAOA and the ALDH2 genes is associated with ANX/DEP ALC. Methods: We recruited 383 Han Chinese men in Taiwan: 143 ANX/DEP ALC and 240 healthy controls. The diagnosis of ANX/DEP ALC (alcohol dependence with a past or current history of anxiety, depressive disorder, or both) was made using DSM‐IV criteria. Genotypes of ALDH2 and MAOA‐uVNTR (variable number of tandem repeat located upstream) were determined using PCR‐RFLP. Results: The ALDH2, but not the MAOA‐uVNTR, polymorphism was associated with ANX/DEP ALC. After stratifying the MAOA‐uVNTR polymorphism, we found a stronger association between the ALDH2*1/*2 and *2/*2 genotypes and the controls in the MAOA‐uVNTR 4‐repeat subgroup. Logistic regression significantly associated the interaction between ALDH2 and MAOA variants with ANX/DEP ALC. Conclusion: We conclude that the MAOA and ALDH2 genes interact in ANX/DEP ALC. Although the MAOA gene alone is not associated with ANX/DEP ALC, we hypothesize that different variants of MAOA‐uVNTR polymorphisms modify the protective effects of the ALDH2*2 allele on ANX/DEP ALC in Han Chinese in Taiwan.     

Suppression of Heavy Drinking and Alcohol Seeking by a Selective ALDH-2 Inhibitor

Background: Inherited human aldehyde dehydrogenase 2 (ALDH‐2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH‐2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH‐2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However, daidzin can reduce drinking in some rodents without necessarily increasing acetaldehyde. Therefore, a selective ALDH‐2 inhibitor might affect other metabolic factors involved in regulating drinking. Methods: Aldehyde dehydrogenase 2 inhibitors were synthesized based on the co‐crystal structure of ALDH‐2 and daidzin. We tested the efficacy of a highly selective reversible ALDH‐2 inhibitor, CVT‐10216, in models of moderate and high alcohol drinking rats. We studied 2‐bottle choice and deprivation‐induced drinking paradigms in Fawn Hooded (FH) rats, operant self‐administration in Long Evans (LE), FH, and inbred P (iP) rats and in cue‐induced reinstatement in iP rats. We also assayed blood acetaldehyde levels as well as dopamine (DA) release in the nucleus accumbens (NAc) and tested possible rewarding/aversive effects of the inhibitor in a conditioned place preference (CPP) paradigm. Results: CVT‐10216 increases acetaldehyde after alcohol gavage and inhibits 2‐bottle choice alcohol intake in heavy drinking rodents, including deprivation‐induced drinking. Moreover, CVT‐10216 also prevents operant self‐administration and eliminates cue‐induced reinstatement of alcohol seeking even when alcohol is not available (i.e., no acetaldehyde). Alcohol stimulates DA release in the NAc, which is thought to contribute to increased drinking and relapse in alcoholism. CVT‐10216 prevents alcohol‐induced increases in NAc DA without changing basal levels. CVT‐10216 does not show rewarding or aversive properties in the CPP paradigm at therapeutic doses. Conclusion: Our findings suggest that selective reversible ALDH‐2 inhibitors may have therapeutic potential to reduce excessive drinking and to suppress relapse in abstinent alcoholics.     

The association between drinking motives and alcohol‐related consequences – room for biases and measurement issues?

Aims To investigate whether the predominant finding of generalized positive associations between self‐rated motives for drinking alcohol and negative consequences of drinking alcohol are influenced by (i) using raw scores of motives that may weight inter‐individual response behaviours too strongly, and (ii) predictor‐criterion contamination by using consequence items where respondents attribute alcohol use as the cause. Design Cross‐sectional study within the European School Survey Project on Alcohol and other Drugs (ESPAD). Setting School classes. Participants Students, aged 13–16 (n = 5633). Measurements Raw, rank and mean‐variance standardized scores of the Drinking Motives Questionnaire—Revised (DMQ‐R); four consequences: serious problems with friends, sexual intercourse regretted the next day, physical fights and troubles with the police, each itemized with attribution (‘because of your alcohol use’) and without. Findings As found previously in the literature, raw scores for all drinking motives had positive associations with negative consequences of drinking, while transformed (rank or Z) scores showed a more specific pattern: external reinforcing motives (social, conformity) had negative and internal reinforcing motives (enhancement, coping) had non‐significant or positive associations with negative consequences. Attributed consequences showed stronger associations with motives than non‐attributed ones. Conclusion Standard scoring of the Drinking Motives Questionnaire (Revised) fails to capture motives in a way that permits specific associations with different negative consequences to be identified, whereas use of rank or Z‐scores does permit this. Use of attributed consequences overestimates the association with drinking motives.     

Influence of Alcohol Use Experience and Motivational Drive on College Students' Alcohol-Related Cognition

Background: Cognitive processes are thought to be pivotal to risk for heavy drinking. However, few studies have examined the alcohol cue‐activated positive and negative semantic memory networks that may be pivotal to drinking behavior. Moreover, much is to be understood about the influences of cognitive processes, particularly in high‐risk drinking samples such as college students. The current study examines the sequential process of alcohol cues activating valenced semantic memory networks, and the influences of prior drinking experience and individual differences in motivational drive on this automatic (implicit) cognitive process. Methods: Participants (N = 138, 52% women) were college freshmen prescreened to represent the full range of drinking experience (i.e., current abstainers, light and heavy drinkers). Participants completed self‐reports of past month alcohol use, and individual differences in behavioral inhibition system (BIS) and behavioral approach/activation system (BAS). Alcohol cue‐elicited positive and negative semantic memory networks were assessed using a priming task. Results: Results from the priming task revealed that for light drinkers alcohol cues were equally as likely to activate positive and negative semantic memory networks, suggesting relatively neutral cue‐elicited alcohol attitudes. Conversely, for heavy drinkers, alcohol cues more readily activated positive relative to negative semantic memory networks, suggesting relatively positive cue‐elicited alcohol attitudes. Furthermore, positive alcohol cue‐elicited semantic memory networks (positive attitudes) were evident for individuals characterized by a strong BAS and weak BIS (as hypothesized) and those characterized by a weak BAS and weak BIS. Conclusions: The findings suggest that alcohol‐cue elicited positive semantic memory networks may be pivotal to risk for heavy drinking. Specifically, it is via the influence on this cognitive process that prior drinking experience and individual differences in motivational drive, respectively, may maintain and predispose individuals to risk for heavy alcohol use.     

Factors associated with the presence of multiple Lugol‐voiding lesions in patients with esophageal squamous‐cell carcinoma

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol‐voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence‐specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84–122.45: P = 0.011), presence of the ALDH2‐2 allele (OR 4.5, 95% CI 1.55–13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02–6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13–88.44: P = 0.038) and presence of the ALDH2‐2 allele (OR 4.56, 95% CI 1.4–14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2‐2 allele (OR 17.5, 95% CI 1.97–155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2‐2 allele (OR 8.85, 95% CI 1.68–46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2‐2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2‐2 allele (OR 4.0, 95% CI 0.54–29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2‐2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2‐2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.     

The subjective, rather than the disinhibiting, effects of alcohol are related to binge drinking

Background: Evidence suggests that alcohol‐related problems are associated with impulsivity and disinhibited behavior. Less certain is whether disinhibited behavior is due to an impulsive disposition or alcohol’s ability to disinhibit some people more than others. There are a range of disinhibited behaviors associated with alcohol, including excessive alcohol consumption, bingeing. The study tested whether nondependent alcohol bingers showed more disinhibition after placebo and/or alcohol relative to nonbingers and whether this was related to enhanced motivation to drink following a priming dose of alcohol. Methods: Twenty participants (10 bingers) attended the laboratory twice. Baseline measures included impulsivity, alcohol‐related cognitions, alcohol urge, and mood. Participants were preloaded with alcohol (male: 0.6 g/kg, female: 0.5 g/kg) and placebo (counterbalanced). After a 20‐minute rest, participants completed 2 impulsivity tasks (Two Choice & Time Estimation) separated by second urge and mood ratings. Results: Bingers did not show greater impulsivity characteristics but were more concerned about their drinking (p = 0.02) and ability to control drinking (p = 0.04). A priming effect was found: alcohol urge increased after alcohol but not placebo (p = 0.006). Bingers reported greater tolerance to the sedative (p = 0.05) and lightheaded (p = 0.04) effects of alcohol, relative to nonbingers. Binge status was not associated with impulsivity task performance, while preload type (alcohol/placebo) supported only marginal associations. Conclusions: Risk of binge drinking in nondependent individuals is not strongly affected by impulsive personality characteristics or alcohol’s ability to induce behavioral disinhibition. However, alcohol did lead to a priming effect and bingers were more tolerant to the sedative and lightheaded effects of alcohol relative to placebo. Risk of binge drinking is associated with the subjective effects of a priming dose of alcohol.     

Drinking expectancies and motives: a genetic study of young adult women

BACKGROUND: Constructs such as drinking expectancies (beliefs regarding the effects of alcohol) and motives (drinking alcohol to achieve a valued end) have been shown to be associated with various stages of alcohol use behaviors. However, little is known of the extent to which genetic and environmental influences contribute to individual differences in expectancies and motives. METHODS: Using data from 3,656 young adult same-sex female twins, we examined the association between measures of drinking expectancies and motives and drinking behaviors. Using twin models, we estimated the extent to which genetic, shared and non-shared environmental factors influenced individual differences in expectancies and motives and also tested whether the extent of the genetic and environmental contributions on expectancies varied across abstainers and users of alcohol. RESULTS: Expectancies predicted initiation of alcohol use. Both motives and expectancies were associated with frequency and quantity of alcohol consumption and drinks-to-intoxication. There was no evidence for heritable influences on expectancies and enhancement motives, with familial similarity for these traits being due to shared environment. Heritable influences on social, coping and conformity motives ranged from 11% to 33%. When expectancies were stratified by alcohol use, significant heritable influences (31-39%) were found for cognitive-behavioral impairment and risk-taking/negative self-perception (RT/NSP) in abstainers only, while environmental influences contributed to familial variance for other measures of expectancies in alcohol users. CONCLUSIONS: Environmental influences (both familial and individual-specific) shape alcohol expectancies, while heritable influences may predispose to motives for drinking. Individual differences in expectancies are moderated by alcohol use, suggesting that sources of individual differences in expectancies may vary in drinkers versus abstainers.     

Alcohol and Aldehyde Dehydrogenase Polymorphisms in Japanese Patients with Alcohol-Induced Chronic Pancreatitis

In order to clarify the genetic factors in alcohol-related chronic pancreatitis among Japanese, we determined the genotype of two major alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The restriction fragment-length polymorphisms of the ADH2 and the ALDH2 genes were analyzed in 47 normal subjects and 31 patients with alcoholic pancreatitis. No significant difference between the patient and control groups was found in the ADH2 genotypes. A significant genetic difference between the two groups was found in the ALDH2 locus. The frequency of the ALDH2*1 allele was found to be 0.681 and that of the ALDH2*2 allele was 0.319 in the controls, while these values were 0.935 and 0.065 in the patients, respectively. Most of the patients (27 of 31) were ALDH2*1/2*1, only four were ALDH2*1/2*2, and none of the patients were ALDH2*2/2*2. These results indicate that genetic polymorphism of the ALDH2 gene influences the risk of developing alcoholic pancreatitis in Japanese.