To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, June 4, 2011

Strategies for characterizing complex phenotypes and environments: General and specific family environmental predictors of young adult tobacco dependence, alcohol use disorder, and co-occurring problems

Defining phenotypes in studies of tobacco and alcohol misuse is difficult because of the complexity of these behaviors and their strong association with each other and with other problem behaviors. The present paper suggests a strategy for addressing this issue by conceptualizing and partitioning variance in phenotypes into either general or substance/behavior-specific. The paper also applies the general or substance/behavior-specific conceptualization to environmental predictors of tobacco and alcohol misuse and other problem behaviors.

Data were drawn from the Seattle Social Development Project, a contemporary, ethnically diverse and gender-balanced longitudinal panel including 808 participants. Latent variable modeling was used to partition variance in young adult (age 24) nicotine dependence, alcohol abuse and dependence, illicit drug abuse and dependence, involvement in crime, and engagement in HIV sexual risk behavior into general problem behavior and behavior-specific variance. Similarly, measures of general, drinking-specific, and smoking-specific adolescent family environment were constructed.

Consistent with expectations, more positive general family environment during adolescence was associated with lower levels of shared variance in problem behaviors at age 24, but not with unique variance in tobacco or alcohol use disorder. Higher levels of family smoking and drinking environments during adolescence, however, were positively associated with unique variance in tobacco and alcohol use disorder, respectively, but did not predict shared variance in problem behaviors.

Results support the utility of the proposed approach. Ways in which this approach might contribute to future molecular genetic studies are discussed.

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Friday, June 3, 2011

Effects of high-profile collisions on drink-driving penalties and alcohol-related crashes in Japan

Japanese road traffic law was amended in 2002 and 2007 to increase the penalties for drink-driving in response to media coverage, publicity campaigns, and debates following high-profile alcohol-related motor-vehicle crashes in 1999 and 2006. 

To test the hypothesis that the proportion of crashes involving drink-driving started to decline before the law amendments, because of changes in social norms and driver behaviour after the high-profile crashes.

In order to assess the impact of the cases in 1999 and 2006, time-series analyses were used to examine the trends in the proportion of crashes involving drink-driving, and whether there were abrupt changes in the level or slope at the expected time points, using monthly police data for the period between January 1995 and December 2008.

In 1999, the proportion of alcohol-related fatal crashes in which the driver had a blood alcohol concentration (BAC) ≥0.5 mg/ml started to decline with a slope change of −0.09 percentage points per month (95% CI −0.15 to −0.03) but no level change, whereas there were no changes for drivers with a BAC <0.5. In 2006, the trends for drivers with a BAC ≥0.5 or <0.5 showed significant level declines of −3.1 (−5.0 to −1.2) and −1.7 (−2.5 to −0.9) percentage points, respectively, but no slope changes.

Media coverage of high-profile crashes, and subsequent publicity campaigns and debates might have altered social norms and driver behaviour, reducing the proportion of alcohol-related crashes before the introduction of more severe penalties for drink-driving. 

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Persistent Escalation of Alcohol Drinking in C57BL/6J Mice With Intermittent Access to 20% Ethanol

Intermittent access (IA) to drugs of abuse, as opposed to continuous access, is hypothesized to induce a kindling-type transition from moderate to escalated use, leading to dependence. Intermittent 24-hour cycles of ethanol access and deprivation can generate high levels of voluntary ethanol drinking in rats.

The current study uses C57BL/6J mice (B6) in an IA to 20% ethanol protocol to escalate ethanol drinking levels. Adult male and female B6 mice were given IA to 20% ethanol on alternating days of the week with water available ad libitum. Ethanol consumption during the initial 2 hours of access was compared with a short-term, limited access “binge” drinking procedure, similar to drinking-in-the-dark (DID). B6 mice were also assessed for ethanol dependence with handling-induced convulsion, a reliable measure of withdrawal severity.

After 3 weeks, male mice given IA to ethanol achieved high stable levels of ethanol drinking in excess of 20 g/kg/24 h, reaching above 100 mg/dl blood ethanol concentrations, and showed a significantly higher ethanol preference than mice given continuous access to ethanol. Also, mice given IA drank about twice as much as DID mice in the initial 2-hour access period. B6 mice that underwent the IA protocol for longer periods of time displayed more severe signs of alcohol withdrawal. Additionally, female B6 mice were given IA to ethanol and drank significantly more than males (ca. 30 g/kg/24 h).

The IA method in B6 mice is advantageous because it induces escalated, voluntary, and preferential per os ethanol intake, behavior that may mimic a cardinal feature of human alcohol dependence, though the exact nature and site of ethanol acting in the brain and blood as a result of IA has yet to be determined.

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Neurocognitive Performance, Alcohol Withdrawal, and Effects of a Combination of Flumazenil and Gabapentin in Alcohol Dependence

Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of 2 medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pretreatment AW (Anton et al., 2009). 

This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone.

Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial.

AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking.

Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains.

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Ethanol consumption and pineal melatonin daily profile in rats

It is well known that melatonin participates in the regulation of many important physiological functions such as sleep–wakefulness cycle, motor coordination and neural plasticity, and cognition. 

However, as there are contradictory results regarding the melatonin production diurnal profile under alcohol consumption, the aim of this paper was to study the phenomenology and mechanisms of the putative modifications on the daily profile of melatonin production in rats submitted to chronic alcohol intake. 

The present results show that rats receiving 10% ethanol in drinking water for 35 days display an altered daily profile of melatonin production, with a phase delay and a reduction in the nocturnal peak.

This can be partially explained by a loss of the daily rhythm and the 25% reduction in tryptophan hydroxylase activity and, mainly, by a phase delay in arylalkylamine N-acetyltransferase gene expression and a 70% reduction in its peak activity. 

Upstream in the melatonin synthesis pathway, the results showed that noradrenergic signaling is impaired as well, with a decrease in β1 and α1 adrenergic receptors' mRNA contents and in vitro sustained loss of noradrenergic-stimulated melatonin production by glands from alcohol-treated rats. 

Together, these results confirm the alterations in the daily melatonin profile of alcoholic rats and suggest the possible mechanisms for the observed melatonin synthesis modification.

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Interleukin-15 and Other Myokines in Chronic Alcoholics

Interleukin (IL)-15 is highly expressed in skeletal muscle, where it exerts anabolic effects, increasing protein content in muscle fibres and promoting muscle growth. Alcoholics frequently suffer myopathy. Therefore, we analyse the behaviour of IL-15 (and other myokines, such as IL-6, IL-8 and tumour necrosis factor α (TNF-α)) in alcoholics.
These myokines and also malondialdehyde (MDA)—a lipid peroxidation product—were determined by radioimmunoanalytic techniques in blood samples of 35 chronic alcoholics and 13 age- and sex-matched controls, and compared with body composition, nutritional status, liver function, amount of ethanol and routine biochemical variables. 

IL-15, IL-6, TNF-α, IL-8 and MDA were all higher in alcoholics than in controls; MDA and IL-6 were clearly related with liver function impairment and short-term prognosis, whereas IL-15 was higher among those who died and was related to serum bilirubin. No relation was found between IL-15 and lean mass.
IL-15 levels were higher in alcoholics than in controls, especially among those who died within 18 months after admission. They are not related with muscle mass, intensity of alcoholism or nutritional status, but only with serum bilirubin. IL-6 showed inverse correlations with liver function, intensity of alcoholism, nutritional status, left arm muscle mass and short-term mortality.

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Thursday, June 2, 2011

Cellular DNA methylation program during neurulation and its alteration by alcohol exposure

Epigenetic changes are believed to be among the earliest key regulators for cell fate and embryonic development. To support this premise, it is important to understand whether or not systemic epigenetic changes coordinate with the progression of development. We have demonstrated that DNA methylation is programmed when neural stem cells differentiate (Zhou et al.,2011). Here, we analyzed the DNA methylation events that occur during early neural tube development. 

Using immunocytochemistry, we demonstrated that the DNA methylation marks – 5-methylcytosine (5-MeC), DNA methylation binding domain 1 (MBD1), and DNA methytransferases 1 (DNMT1) were highly coordinated in temporal and spatial patterns that paralleled the progress of embryonic development. The above ontogenic program of DNA methylation was, however, subjected to environmental modification. Alcohol exposure during fetal development, which is known to cause fetal alcohol spectrum disorder, altered the density and distribution of the DNA methylation marks. The alcohol exposure (88 mM) over 6 or 44 hours at gestation day 8 (GD-8) to GD-10 altered timely DNA methylation and retarded embryonic growth. We further demonstrated that the direct inhibiting of DNA methylation with 5-aza-cytidine (5-AZA) resulted in similar growth retardation. 

We identified a temporal and spatial cellular DNA methylation program after initial erasure, which parallels embryonic maturation. Alcohol delayed the cellular DNA methylation program and also retarded embryonic growth. Since direct inhibiting of DNA methylation resulted in similar retardation, alcohol thus can affect embryonic development through a epigenetic pathway. 

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Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis

Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case–control study.  

A total of 6622 control infants and 1768 infants with birth defects delivered from 1997–2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity-frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. 

Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR = 0.92; CI: 0.78–1.08), but alcohol consumption in the second (OR = 0.65; CI: 0.47–0.92) and third trimesters (OR = 0.68; CI: 0.49–0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR = 1.50; CI: 1.15–1.96) and gastroschisis (OR = 1.40; CI: 1.17–1.67).
Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis.

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Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome

Fetal alcohol syndrome (FAS) is a common birth defect in many societies. Affected individuals have neurodevelopmental disabilities and a distinctive craniofacial dysmorphology. These latter deficits originate during early development from the ethanol-mediated apoptotic depletion of cranial facial progenitors, a population known as the neural crest. 

We showed previously that this apoptosis is caused because acute ethanol exposure activates G-protein-dependent intracellular calcium within cranial neural crest progenitors, and this calcium transient initiates the cell death. The dysregulated signals that reside downstream of ethanol's calcium transient and effect neural crest death are unknown. 

Here we show that ethanol's repression of the transcriptional effector β-catenin causes the neural crest losses. Clinically relevant ethanol concentrations (22–78 mM) rapidly deplete nuclear β-catenin from neural crest progenitors, with accompanying losses of β-catenin transcriptional activity and downstream genes that govern neural crest induction, expansion, and survival. Using forced expression studies, we show that β-catenin loss of function (via dominant-negative T cell transcription factor [TCF]) recapitulates ethanol's effects on neural crest apoptosis, whereas β-catenin gain-of-function in ethanol's presence preserves neural crest survival. Blockade of ethanol's calcium transient using Bapta-AM normalizes β-catenin activity and prevents the neural crest losses, whereas ionomycin treatment is sufficient to destabilize β-catenin. 

We propose that ethanol's repression of β-catenin causes the neural crest losses in this model of FAS. β-Catenin is a novel target for ethanol's teratogenicity. 

β-Catenin/Wnt signals participate in many developmental events and its rapid and persistent dysregulation by ethanol may explain why the latter is such a potent teratogen.

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Maternal alcohol drinking pattern during pregnancy and the risk for an offspring with an isolated congenital heart defect and in particular a ventricular septal defect or an atrial septal defect†

This cohort study examines the possible association between maternal alcohol intake, including binge drinking, during pregnancy, and the subsequent risk of having a child with an isolated congenital heart defect and, more specifically, with the isolated form of ventricular septal defect (VSD) or of an atrial septal defect (ASD).
Participants were 80,346 pregnant women who were enrolled into the Danish National Birth Cohort in 1996–2002 and gave birth to a live-born singleton without any chromosome anomalies. Twice during pregnancy these women were asked about their intake of alcohol. Few (if any) women with an excessive/abusive intake of alcohol were enrolled into the Danish National Birth Cohort.
Through linkage with the National Hospital Discharge Registry, we identified 477 infants with a diagnosis of isolated congenital heart defect registered at any time during their first 3½-years of life; they included 198 infants with a VSD and 145 with an ASD. Neither the number of episodes of binge drinking nor binge drinking during three different developmental periods was associated with VSD or ASD. Women drinking ½-1½, 2, and 3+ drinks of alcohol per week had adjusted prevalence ratios of delivering an infant with a VSD of 1.22 (95% CI = 0.90–1.66); 1.38 (95% CI = 0.83–2.28); and 1.10 (95% CI = 0.54–2.23), respectively. The test for trend was 0.29.
Prenatal exposure to low-to-moderate levels of alcohol on a weekly basis or occasional binge drinking during the early part of pregnancy was not statistical significantly associated with the prevalence of isolated VSD and ASD in offspring.

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Independent Contributions of Cortical Gray Matter, Aging, Sex and Alcoholism to K-Complex Amplitude Evoked During Sleep

The amplitude of the N550 component derived from the averaged evoked K-complex decreases with normal aging and with alcoholism. The study was designed to determine whether these declines are related to the extent of cortical or subcortical shrinkage.

26 abstinent long-term alcoholic men, 14 abstinent long-term alcoholic women, 18 control men, and 22 control women.

MRI data collected at 3T were analyzed from alcoholic and control men and women previously reported to have significantly different evoked delta activity during sleep. Segmented and parcellated MRI data collected at 3T were compared between these groups and evaluated for correlation with evoked K-complex amplitude measured at FP1, Fz, FCz, Cz, CPz, and Pz. Cortical gray matter and regional subcortical tissue volumes entered as predictors into stepwise multiple regression identified cortical gray matter as a unique significant predictor of evoked K-complex at all sites. Age added independent variance at 5 of the 6 sites, while alcoholism and sex added independent variance at frontal sites only.

These data support recent intracranial studies showing cortical generation of K-complexes by indicating that cortical, but not subcortical volume contributes to K-complex amplitude. Establishing the extent of the relation between cortical volume and K-complex amplitude provides a mechanistic understanding of sleep compromise clinically relevant to normal aging, alcoholism, and likely other conditions affecting cortical volume and integrity.

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National Public Health Task Force Recommends Against Privatization of Retail Alcohol Sales

A new report from a task force of national public health experts recommends against further privatization of retail alcohol sales.

The report, released in April, is the most definitive statement on retail alcohol privatization issued to date by U.S. public health researchers. It deserves close examination as Pennsylvania lawmakers consider a proposal to privatize state wine and spirits stores.

In a statement, the researchers wrote: “The Task Force on Community Preventive Services recommends against the further privatization of alcohol sales in settings with current government control of retail sales, based on strong evidence that privatization results in increase per capita alcohol consumption, a well-established proxy for excessive consumption.”

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News Release - College Students Respond Better to Positive Anti-Binge Drinking Messages

Binge drinking among college students has long been viewed as dangerous and destructive. Government and non-profit health organizations spend millions of dollars annually on public service announcements (PSAs) aimed at dissuading college students from hazardous drinking habits. These organizations primarily use “loss-framed”, or negative messages, to show the dangers of binge drinking. Now, University of Missouri researchers have found that “gain-framed”, or positive messages, are much more effective in convincing college students to abandon binge drinking.

Gain-framed messages portray positive reasons for avoiding risky behavior such as improved grades or more fulfilling relationships. Alternatively, loss-framed messages focus on negative consequences, such as failing school or suffering from health problems. Through in-depth interviews of college students, Joonghwa Lee, a doctoral candidate at the Missouri School of Journalism, identified four areas of interest for college students regarding the effects of binge drinking: relationships, academic success, health, and control safety.
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Deconstructing the architecture of alcohol abuse and dependence symptoms in a community sample of late adolescent and emerging adult women: An item response approach

The objective of this study was to examine the underlying factorial architecture of lifetime DSM-IV alcohol use disorder (AUD) criteria in a population-based sample of adolescent and emerging adult female twins who had ever used alcohol (n=2832; aged 18–25 years), and to determine whether thresholds and factor loadings differed by age. 

Item response modeling was applied to DSM-IV AUD criteria. Compound criteria (e.g., persistent desire or unsuccessful attempts to quit or cut down) were included as separate items. Of the remaining 16 items, tolerance and use despite physical problems were the most and least commonly endorsed items, respectively. 

Underlying the items was a single factor representing liability to AUDs. Factor loadings ranged from 0.67 for blackouts to 0.90 for time spent using/recovering from effects. 

Some items assessing different DSM-IV criteria had very similar measurement characteristics, while others assessing the same criterion showed markedly different thresholds and factor loadings. 

Compared to that of women aged 21–25 years, the threshold for hazardous use was higher in women aged 18–20 years, but lower for used longer than intended and persistent desire to cut down. 

After accounting for threshold differences, no variations in discrimination across age groups were observed. 

In agreement with the extant literature, our findings indicate that the factorial structure of AUD is unidimensional, with no support for the abuse/dependence distinction. Individual components of compound criteria may differ in measurement properties; therefore pooling information from such divergent items will reduce information about the AUD construct.

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Researchers' experience with project management in health and medical research: Results from a post-project review

Project management is widely used to deliver projects on time, within budget and of defined quality. However, there is little published information describing its use in managing health and medical research projects. We used project management in the Alcohol and Pregnancy Project (2006-2008) ( and in this paper report researchers' opinions on project management and whether it made a difference to the project.

A national interdisciplinary group of 20 researchers, one of whom was the project manager, formed the Steering Committee for the project. We used project management to ensure project outputs and outcomes were achieved and all aspects of the project were planned, implemented, monitored and controlled. Sixteen of the researchers were asked to complete a self administered questionnaire for a post-project review.

The project was delivered according to the project protocol within the allocated budget and time frame. Fifteen researchers (93.8%) completed a questionnaire. They reported that project management increased the effectiveness of the project, communication, teamwork, and application of the interdisciplinary group of researchers' expertise. They would recommend this type of project management for future projects.

Our post-project review showed that researchers comprehensively endorsed project management in the Alcohol and Pregnancy Project and agreed that project management had contributed substantially to the research. In future, we will project manage new projects and conduct post-project reviews. The results will be used to encourage continuous learning and continuous improvement of project management, and provide greater transparency and accountability of health and medical research. The use of project management can benefit both management and scientific outcomes of health and medical research projects. 

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Alcohol Dependence Is More Likely among Adults with Mental Illness than Adults without Mental Illness

Alcohol dependence is 4 times as likely to occur among adults with mental illness than adults with no mental illness (9.6 percent vs. 2.2 percent; Figure). Furthermore, the rate of alcohol dependence increases as the severity of mental illness increases. 

Providers working with individuals with either a substance use or a mental health problem may want to consider screening for a co-occurring disorder and providing an integrated treatment program.

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Alcohol policy support among mandated college students

Alcohol consumption on college campuses is high, and often dangerous. College administrators have created policies to control alcohol consumption, but student body support or opposition of specific policies has been relatively unexplored.

The current study examined the relations of alcohol policy support with gender and alcohol consumption. Mandated students (N = 229; 44% women) completed self-report assessments of alcohol policy support and alcohol consumption.

Women supported policies to a greater extent than did men, as did lighter drinkers relative to heavier drinkers. Drinks per drinking day fully mediated the relation between gender and alcohol policy support.

While alcohol policy support differs by gender, this covariation is explained by differences in alcohol consumption. Findings have implications for addressing alcohol policy support among mandated college students

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The Role of Executive Function in bridging the Intention-Behaviour Gap for Binge-Drinking in University Students

Alcohol consumption contributes to a significant proportion of disease and the high prevalence among young adults is a worldwide health concern.

To determine which aspects of executive function (EF) distinguish binge-drinkers from non binge-drinkers and to establish the role of EF in predicting behaviour. 

Self-report questionnaires, four tests of self-regulation and a behaviour measure were administered to 153 students.

The Theory of Planned Behaviour model was significant in predicting both intentions and behaviour. Although binge-drinkers and non binge-drinkers were found to differ on three of the four measures of EF, none predicted additional variance in behaviour. Planning ability and inhibition control moderated the relationship between intention and behaviour such that for individuals who intended to binge-drink, those with high planning ability or high inhibitory control were more likely to avoid doing so.

Interventions targeting binge-drinking behaviour should aim to develop planning skills and inhibitory control.

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Alcohol, Violence, and the Alcohol Myopia Model: Preliminary Findings and Implications for Prevention

This experiment provided a preliminary test of whether the Alcohol Myopia Model (AMM; Steele & Josephs, 1990) would provide a guiding framework for the prevention of alcohol-related violence. The model contends that alcohol has a “myopic” effect on attentional capacity that presumably facilitates violence by focusing attention onto more salient provocative, rather than less salient inhibitory, cues in hostile situations. 

Participants were 16 intoxicated male social drinkers who completed a laboratory task in which electric shocks were received from, and administered to, a fictitious opponent under the guise of a competitive reaction-time task while they were exposed to either violence-promoting (n = 8) or violence-inhibiting (n = 8) cues. Aggression was operationalized as the intensity and duration of shocks administered by the participant to his “opponent.” 

Despite being equally intoxicated, participants exposed to violence-inhibiting cues were dramatically less aggressive (d = 1.65) than those exposed to the violence-promoting cues.
Our data suggest that the AMM holds a great deal of promise to help develop effective prevention interventions for alcohol-related violence.

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To drink or not to drink: Motives and expectancies for use and nonuse in adolescence

Drinking motives have a prominent role in cognitive models of adolescent and adult alcohol decision-making (Cooper, Russell, Skinner, & Windle, 1992; Cooper, 1994). The complementary construct of motivation not to drink has received less attention (Epler, Sher & Piasecki, 2009). 

We examined how abstinence motives interacted with drinking motives and alcohol expectancies to predict alcohol consumption in samples of US high school students (N > 2,500). 

Nondrinking motives predicted lower rates of lifetime and current alcohol use. Motives not to drink interacted with specific drinking motives, like social and coping motives, and alcohol expectancies to predict certain aspects of drinking behavior. For example, motives not to drink had the greatest impact on youth with weaker social motivations. 

Findings highlight the distinction between motives not to drink and other alcohol-related cognitions in predicting adolescent alcohol consumption. 

This work not only supports the utility of this construct in developing models of youth alcohol-related decision-making but also has implications for prevention programming.

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Using the theory of planned behaviour and prototype willingness model to target binge-drinking in female undergraduate university students

The current study investigated whether binge-drinking in female undergraduates could be reduced by the mere measurement effect (MME), and by altering binge-drinker prototypes from the prototype willingness model (PWM). Whether willingness added to the Theory of Planned Behaviour (TPB) was also explored. 

Female undergraduates aged 17–25 (N = 122) were randomly allocated to a prototype manipulation, mere measurement, or control group, and completed two online questionnaires separated by 14–21 days. 

Controlling for past behaviour, MME group consumed less alcohol than the control group, and this effect was more extreme for those who previously consumed more alcohol. However, the prototype manipulation had no effect. 

The TPB variables were predictive of intentions and behaviour, but willingness was not.

Despite limitations, the MME could be utilised to reduce binge-drinking in female undergraduates. 

The TPB appears to model binge-drinking in female undergraduates better than the PWM, implying that binge-drinking can be a reasoned behaviour.

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Factors that influence trajectories of change in frequency of substance use and quality of life among adolescents receiving a brief intervention

This study aimed to identify factors influencing trajectories of change in two outcome domains, frequency of substance use and quality of life (QOL), among adolescents receiving a brief evidence-based intervention. 

Participants were 106 adolescents, aged 13 to 21 years, who met criteria for a substance use disorder. The adolescents received a five-session intervention and completed four assessments over 12 months. Based upon a theoretical and empirical review, five putative predictors were tested: gender, age, severity of conduct disorder, severity of depression, and peer substance involvement. 

Results of a parallel-process latent growth curve model indicated that higher peer substance involvement and conduct severity predicted higher frequency of use at baseline, whereas higher peer substance involvement and depression severity predicted poorer QOL at baseline. 

Counter to predictions, higher depression severity predicted greater improvements in QOL following substance use treatment. 

The implications of baseline risk factors on adolescents' response to intervention are discussed.

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Country Managers Convene

Global Actions on Harmful Drinking held a landmark event last week, as our country coordinators convened in Washington, DC. At the headquarters for the International Center for Alcohol Policies (ICAP;, the lead implementing organization for Global Actions, they offered updates on Global Actions efforts in partnership with local stakeholders. Highlights of the week-long event included:

  • Mario Lleras presented an overview of the road safety situation in Colombia, ICAP’s partnership with the Fondo de prevención vial, and opportunities to highlight good practices on drink driving in cities across Colombia.

  •  James Yu explained that Drink Driving initiatives in China are making progress, citing his recent meeting with local coordinators in Nanjing, Xi’an and Wuhan.

  • Lan Huong Nguyen was enthusiastic about progress in Vietnam, thanks to securing the participation of key local partners, including Vietnam’s National Traffic Safety Committee.

  • Mariana Rendon spoke of her strides in Mexico, and her plans to co-sponsor a capacity-building training summit in July while continuing to raise public awareness of Jalisco’s “Ley Salvavidas.”
  • Country manager Olanrewaju Onigbogi has set up his Global Actions Nigeria office in Lagos and discussed plans for three capacity-building workshops to be held in collaboration with the Federal Road Safety Commission (FRSC) later this year.

The Effects of Short-Term Chronic Ethanol Intoxication and Ethanol Withdrawal on the Molecular Composition of the Rat Hippocampus by FT-IR Spectroscopy

The numerous adverse effects of ethanol abuse and ethanol withdrawal on biological systems are well documented. Conversely, the understanding of the molecular mechanisms underlying these pathological effects is still incomplete. This study was undertaken to investigate the effects of short-term chronic ethanol administration and ethanol withdrawal on the molecular structure and function of hippocampal tissue, a brain region important for mnemonic processes and known to be highly susceptible to ethanol intoxication.

Ethanol was administered to adult Wistar rats by intragastric intubation for 15 days with a stepwise increase in the daily dose from 6 to 12 g/kg body weight, with the highest dose delivered for the last 2 days only. The total daily dose of ethanol was divided into 3 equal portions administered 4 hours apart. Animals were sacrificed by decapitation at 4, 24, and 72 hours after the last ethanol administration to examine potential effects of ethanol intoxication and ethanol withdrawal. Ethanol-related molecular changes were monitored by Fourier transform infrared (FT-IR) spectroscopy.

Significant changes in the hippocampal content, structure, and function of lipids, proteins, and nucleic acids were recorded under ethanol intoxication. Seventy-two hours after the cessation of ethanol administration, during the late phase of withdrawal, alterations in the macromolecules’ content and conformational changes in protein and nucleic acid structure ameliorated, while the changes in macromolecular ratios, lipid order, and dynamics aggravated.

Our results suggest that 15 days of binge-like drinking resulting in the high blood alcohol concentration (varying in the dose-dependent manner between 253 and 606 mg/dl) produced a strong physical dependence manifested mainly by the changes in lipid profiles pointing toward withdrawal-induced oxidative stress. These results show that ethanol withdrawal may cause equal to or even more severe brain damage than the ethanol itself, which should be considered when designing antialcohol therapies.

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Effects of Alcohols on Recombinant Adenylyl Cyclase Type 7 Expressed in Bacteria

Our previous studies showed that ethanol enhanced the activity of adenylyl cyclase (AC) in an isoform-specific manner and that alcohol cutoff point of AC was isoform specific. Recently, we showed that 2,3-butanediol inhibited AC type 7 (AC7) activity in a stereoisomer-specific manner and that this inhibition was also AC isoform specific. These observations strongly suggest that a major target of alcohol action on cAMP signaling is AC. We hypothesized that alcohols exhibit their effect on AC activity by direct interaction with AC proteins. However, experimental systems employed in past studies such as intact cells and membrane preparations are too complex and do not allow us to unequivocally test this hypothesis. In attempt to bypass, these complications of the membrane-bound AC, we decided to study the effect of alcohols on AC recombinant proteins expressed in bacteria.

A recombinant AC, designated as AC7sol, consisting of the C1a and C2 domains of the human AC7 was designed and expressed in bacteria. The activity of AC7sol was examined using lysate prepared from bacteria expressing AC7sol.

The activity of AC7sol was stimulated by manganese or by the α subunit of G protein that stimulates AC (G). Forskolin by itself did not stimulate the activity of AC7sol. However, in the presence of activated G, forskolin stimulated the activity of AC7sol. A series of n-alkanols including ethanol enhanced the manganese-stimulated activity of AC7sol. The alcohol cutoff point of AC7sol was pentanol. Ethanol and butanol increased Vmax and KM values of AC7sol.

These results are consistent with our hypothesis and suggest that the enhancing effect of alcohols on AC activity is because of the increase in turnover number of AC. The current study demonstrates for the first time that the effect of alcohols requires only the C1a and C2 domains of AC and no other domains of AC as well as no other mammalian proteins.

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Association of Alcohol Dehydrogenase Genes with Alcohol-Related Phenotypes in a Native American Community Sample

Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism.

The present study tested for associations between alcohol dependence and related traits and 22 single-nucleotide polymorphisms (SNPs) spanning the 7 ADH genes. Participants included 586 adult men and women recruited from 8 contiguous Native American reservations. A structured interview was used to assess DSM-III-R alcohol dependence criteria as well as a set of severe alcohol misuse symptoms and alcohol withdrawal symptoms.

No evidence for association with the alcohol dependence diagnosis was observed, but an SNP in exon 9 of ADH1B (rs2066702; ADH1B*3) and an SNP at the 5′ end of ADH4 (rs3762894) showed significant evidence of association with the presence of withdrawal symptoms (p = 0.0018 and 0.0012, respectively). Further, a haplotype analysis of these 2 SNPs suggested that the haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype (p = 0.000006).
These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence.

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Reducing the legal blood alcohol concentration limit for driving in developing countries: a time for change? Results and implications derived from a time series analysis (2001-2010) conducted in Brazil

In Brazil, a new law introduced in 2008 has lowered the blood alcohol concentration limit for drivers from 0.06 to 0.02, but the effectiveness in reducing traffic accidents remains uncertain. This study evaluated the effects of this enactment on road traffic fatalities and injuries.
Time series analysis using ARIMA modelling.
State and capital of Sao Paulo, Brazil.
Data on injuries and deaths caused by road traffic accidents in both regions were collected from January 2001 to June 2010, comprising a total of 1,417,087 injuries and 51,561 fatalities.
The new traffic law was responsible for significant reductions in traffic injuries and fatalities rates in both localities (P < 0.05). A stronger effect was observed for traffic fatalities (-7.2 and -16.0% in the average monthly rate in the State and capital, respectively) compared to traffic injuries rates (-1.8 and -2.3% in the State and capital, respectively).
Lowering the blood alcohol concentration limit in Brazil had a greater impact on traffic fatalities than injuries, with a higher effect in the capital where presumably the police enforcement was enhanced.

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Treatment outcomes of a Stage 1 cognitive-behavioral trial to reduce alcohol use among HIV-infected outpatients in western Kenya


Dual epidemics of HIV and alcohol use disorders, and a dearth of professional resources for behavioral treatment in sub-Saharan Africa, suggest the need for development of culturally relevant and feasible interventions. 

The purpose of this study was to test the preliminary efficacy of a culturally adapted 6-session gender-stratified group cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya.
Randomized clinical trial comparing CBT against a usual care assessment only control
A large HIV outpatient clinic in Eldoret, Kenya, part of the Academic Model for Providing Access to Healthcare collaboration
74 HIV-infected outpatients who were antiretroviral (ARV)-initiated or ARV-eligible and who reported hazardous or binge drinking
Percent drinking days (PDD) and mean drinks per drinking days (DDD) measured continuously using the Timeline Followback
There were 299 ineligible and 102 eligible outpatients with 12 refusals. Effect sizes of the change in alcohol use since baseline between the two conditions at the 30-day follow-up were large (d = .95, p = .0002, mean difference = 24.93 (95% CI: 12.43, 37.43) PDD; d = .76, p = .002, mean difference=2.88 (95% CI: 1.05, 4.70) DDD). Randomized participants attended 93% of the 6 CBT sessions offered. Reported alcohol abstinence at the 90-day follow-up was 69.4% (CBT) and 37.5% (usual care). Paraprofessional counselors achieved independent ratings of adherence and competence equivalent to college-educated therapists in the U.S. Treatment effect sizes were comparable to alcohol intervention studies conducted in the U.S.
Cognitive-behavioral therapy can be successfully adapted to group paraprofessional delivery in Kenya and may be effective in reducing alcohol use among HIV-infected Kenyan outpatients.

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