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, April 30, 2011

Alcohol use and misuse within the military: A review

Traditionally alcohol has been used by the military to cope with the intense stress of battle but also as a way of mediating the transition from the heightened experience of combat to routine safety. 
The use of alcohol has divided medical opinion. Some doctors viewed it as wholly harmful to both social and occupational function and to health, while others argued that alcohol had a specific role in lifting morale, aiding unit cohesion and protecting soldiers from adjustment disorders. 
Although alcoholism has always been identified as incompatible with military service, the effects of habitual heavy drinking among military personnel are less well understood. 
Recent studies have suggested that young single males and those who have undergone particularly stressful experiences are at greatest risk of misusing alcohol. 
These associations, observed in the aftermath of recent conflicts in Iraq and Afghanistan, have again raised questions about the place of alcohol in military culture.
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Combining best evidence: A novel method to calculate the alcohol-attributable fraction and its variance for injury mortality

The alcohol-attributable fraction for injury mortality is defined as the proportion of fatal injury that would disappear if consumption went to zero. Estimating this fraction has previously been based on a simplistic view of drinking and associated risk. 

This paper develops a new way to calculate the alcohol-attributable fraction for injury based on different dimensions of drinking, mortality data, experimental data, survey research, new risk scenarios, and by incorporating different distributions of consumption within populations. For this analysis, the Canadian population in 2005 was used as the reference population. 

Binge drinking and average daily consumption were modeled separately with respect to the calculation of the AAF. The acute consumption risk was calculated with a probability-based method that accounted for both the number of binge drinking occasions and the amount of alcohol consumed per occasion. The average daily consumption was computed based on the prevalence of daily drinking at various levels. These were both combined to get an overall estimate. 3 sensitivity analyses were performed using different alcohol consumption parameters to test the robustness of the model. Calculation of the variance to generate confidence limits around the point estimates was accomplished via Monte Carlo resampling methods on randomly generated AAFs that were based on the distribution and prevalence of drinking in the Canadian population. 

Overall, the AAFs decrease with age and are significantly lower for women than men across all ages. As binge drinking increases, the injury mortality AAF also increases. Motor vehicle collisions show the largest relative increases in AAF as alcohol consumption is increased, with over a 100% increase in AAF from the lowest to highest consumption category. Among non-motor vehicle collisions, the largest change in total AAF occurred both for homicide and other intentional injuries at about a 15% increase in the AAF from the lowest to the highest binge consumption scenarios. 

This method combines the best available evidence to generate new alcohol-attributable fractions for alcohol-attributable injury mortality. Future research is needed to refine the risk function for non-motor vehicle injury types and to investigate potential interactions between binge drinking and average volume of alcohol consumption.

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Impact of the 1994 Alcohol Production and Sales Deregulation Policy on Traffic Crashes and Fatalities in Japan

Many studies have demonstrated a strong relationship between alcohol availability and traffic crashes involving alcohol-impaired drivers. 

The present analysis focuses on the evaluation of the impact of alcohol availability on the Japanese population by comparing fatal and nonfatal motor vehicle crash rates before and after implementation of the alcohol deregulation policy in 1994. 

Poisson regression with robust standard error was used to model the before-to-after change in incidence rate ratios (IRRs) in the population. To control for potential confounders, per capita alcohol consumption, unemployment rate, and vehicle miles travelled (VMT) were also added to the model. The exponents of the fitted coefficients are equivalent to the IRRs.  

Implementation of the policy deregulating alcohol sales and production did not appear to increase traffic fatalities and other traffic crashes in Japan. In the overall study results, nighttime fatalities were reduced statistically significantly by 6% since the implementation of the alcohol deregulation policy in 1994. 

Contrary to previous research, the findings of this study demonstrated lower rates of fatalities and higher compliance with alcohol-related driving legislation. Further well-designed, nonaligned studies on alcohol availability and traffic fatalities in other countries are urgently needed. 

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Association between Alcohol Consumption and Cancers in the Chinese Population—A Systematic Review and Meta-Analysis

consumption is increasing worldwide and is associated with numerous cancers. This systematic review examined the role of alcohol in the incidence of cancer in the Chinese population.
Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Cohort and case-control studies on the effect of alcohol use on cancers in Chinese were included. Study quality was evaluated using the Newcastle- Ottawa Scale. Data were independently abstracted by two reviewers. Odds ratios (OR) or relative risks (RR) were pooled using RevMan 5.0. Heterogeneity was evaluated using the Q test and I-squared statistic. P,.01 was considered statistically significant.

Pooled results from cohort studies indicated that alcohol consumption was not associated with gastric cancer, esophageal cancers (EC) or lung cancer. Meta-analysis of case-control studies showed that alcohol consumption was a significant risk factor for five cancers; the pooled ORs were 1.79 (99% CI, 1.47–2.17) EC, 1.40 (99% CI, 1.19–1.64) gastric cancer, 1.56 (99% CI, 1.16–2.09) hepatocellular carcinoma, 1.21 (99% CI, 1.00–1.46) nasopharyngeal cancer and 1.71 (99% CI, 1.20–2.44) oral cancer. Pooled ORs of the case-control studies showed that alcohol consumption was protective for female breast cancer and gallbladder cancer: OR 0.76 (99% CI, 0.60–0.97) and 0.70 (99% CI, 0.49–1.00) respectively. There was no significant correlation between alcohol consumption and lung cancer, colorectal cancer, pancreatic cancer, cancer of the
ampulla of Vater, prostate cancer or extrahepatic cholangiocarcinoma.  Combined results of case-control and cohort studies showed that alcohol consumption was associated with 1.78- and 1.40-fold higher risks of EC and gastric cancer but was not
significantly associated with lung cancer.

Health programs focused on limiting alcohol intake may be important for cancer control in China. Further studies are needed to examine the interaction between alcohol consumption and other risk factors for cancers in Chinese
and other populations.

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Friday, April 29, 2011

The Nature and Extent of Flavored Alcoholic Beverage Consumption among Underage Youth: Results of a National Brand-Specific Survey

Flavored alcoholic beverages are popular among underage drinkers. Existing studies that assessed flavored alcoholic beverage use among youth relied upon respondents to correctly classify the beverages they consume, without defining what alcohol brands belong to this category. 
The aim is to demonstrate a new method for analyzing the consumption of flavored alcoholic beverages among youth on a brand-specific basis, without relying upon youth to correctly classify brands they consume.
Using a prerecruited Internet panel developed by Knowledge Networks, we measured the brands of alcohol consumed by a national sample of youth drinkers, aged 16–20 years, in the United States. The sample consisted of 108 youths who had consumed at least one drink of an alcoholic beverage in the past 30 days. We measured the brand-specific consumption of alcoholic beverages within the past 30 days, ascertaining the consumption of 380 alcohol brands, including 14 brands of flavored alcoholic beverages. 
Measuring the brand-specific consumption of flavored alcoholic beverages was feasible. Based on a brand-specific identification of flavored alcoholic beverages, nearly half of the youth drinkers in the sample reported having consumed such beverages in the past 30 days. Flavored alcoholic beverage preference was concentrated among the top four brands, which accounted for almost all of the consumption volume reported in our study.  
These findings underscore the need to assess youth alcohol consumption at the brand level and the potential value of such data in better understanding underage youth drinking behavior and the factors that influence it.

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Prevalence of alcohol-related problems among the Slavs and Arabs in Belarus: a university survey

Alcohol abuse is a major problem among students in Belarus. Alcohol-related problems might vary among students of different cultural backgrounds.

To examine the different patterns in alcohol use and related problems among students of different cultural groups – the Slavs and Arabs, in major Belarusian universities.

1465 university students (1345 Slavs and 120 Arabs) from three major universities in Minsk, Belarus, were administered the Alcohol Use Disorders Identification Test, the Cut, Annoyed, Guilty and Eye questionnaire, and the Michigan Alcohol Screening Test, including other alcohol-related questions.

Overall, 91.08% (n = 1225) Slavs and 60.83% (n = 73) Arabs were alcohol users. A total of 16.28% (n = 219) Slavs and 32.50% (n = 39) Arabs were identified as problem drinkers. Different patterns of alcohol use and related problems were characterized for the Slavs and Arabs. The level of alcohol-related problems was higher among the Arabs, compared to the Slavs. 

Significant differences in the pattern of alcohol use and related problems exist among the students of various cultural groups – the Slavs and Arabs in Minsk, Belarus.

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CC Grand Rounds Lecture: (1) Fetal Alcohol Syndrome: Etiology, Epidemiology, and Advances in Diagnosis (2) Nicotine Pharmacology Versus Nicotine Addiction: Different Sites, Different Mechanisms

CC Grand Rounds Lecture: (1) Fetal Alcohol Syndrome: Etiology, Epidemiology, and Advances in Diagnosis (2) Nicotine Pharmacology Versus Nicotine Addiction: Different Sites, Different Mechanisms
Wednesday, April 27, 2011

(1) Kenneth R. Warren, PhD, Acting Director, NIAAA 
(2) Elliot A. Stein, PhD, Chief, Neuroimaging Research Branch, Intramural Research Program, NIDA

Total Running Time: 01:03:48


Membership in Alcoholics Anonymous (AA) in Japan results in societal disjunction, the divorcing of oneself from family, friends, co-workers, and others. 
AA meetings and meeting dialogues over the course of fieldwork highlight the social marginalization experienced by AA members of the Central Group in Tokyo. 
Members are thwarted by ideological frustrations with AA and an inability to consume alcohol that clashes with societal expectations and find expression in sobriety group meetings. 
They are caught between AA’s advocacy of a new and “joyous” life devoid of alcohol that rarely matches their daily experiences of being viewed as bearers of a shameful esoteric instead of a bested personal struggle.
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Press Release - Adult-supervised drinking in young teens may lead to more alcohol use, consequences

Allowing adolescents to drink alcohol under adult supervision does not appear to teach responsible drinking as teens get older. In fact, such a “harmminimization” approach may actually lead to more drinking and alcohol-related consequences, according to a new study in the May 2011 issue of the Journal of Studies on Alcohol and Drugs.  > > > >  Read More

Thursday, April 28, 2011

Hazardous Drinking Is Associated with a Lower Risk of Coronary Heart Disease: Results from a National Representative Sample

This analysis assesses the 12-month prevalence of coronary heart disease (CHD) in individuals according to their category of alcohol use. 

The 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions study (the NESARC, n = 43,093) identified 16,147 abstinent individuals, 15,884 moderate consumers, 9,578 hazardous drinkers—defined as exceeding sex-specific weekly limits established by the World Health Organization, and 1,484 alcohol-dependent subjects. Diagnoses were generated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version. 

Both moderate and hazardous drinking were associated with decreased odds of CHD when compared with abstinence, whereas odds of CHD were not significantly different between alcohol-dependent and abstinent participants. 

A moderate or even a hazardous consumption of alcohol is associated with a decreased likelihood of CHD after controlling for sociodemographic, psychiatric, and addictive risk factors. 

Our study shows that alcohol may have cardioprotective effects not only in moderate drinkers, but also in individuals with patterns of use traditionally considered as hazardous.

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Effects of Drinking on Hospital Stays and Emergency Room Visits Among Older Adults

To evaluate whether alcohol drinking influences emergency room (ER) visits or hospital admissions among adults aged 65 and older.  

Data from two independent national surveys are used to estimate multivariate logit models that quantify the relationship between drinking and ER visits and hospital admissions. The authors distinguish between ER visits linked to a hospital admission for that individual and ER visits not linked to an admission.  

The authors find no significant effects of alcohol consumption on either ER visits or hospital admissions among older adults. These findings occur in both data sets, and for both men and women. Distinguishing between different types of ER visits makes no difference.  

Analysis of two large and nationally representative data sets suggests that among older adults drinking alcohol, or even heavily drinking alcohol, does not raise or lower the risk of a hospital admission or the risk of an ER visit. 

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Current drinking and health-risk behaviors among male high school students in central Thailand

Alcohol drinking is frequently related to behavioral problems, which lead to a number of negative consequences. This study was to evaluate the characteristics of male high school students who drink, the drinking patterns among them, and the associations between current drinking and other health risk behaviors which focused on personal safety, violence-related behaviors, suicide and sexual behaviors.

A cross-sectional study was conducted to explore current alcohol drinking and health-risk behaviors among male high school students in central Thailand. Five thousand one hundred and eighty four male students were classified into 2 groups according to drinking in the previous 30 days (yes = 631, no = 4,553). Data were collected by self-administered, anonymous questionnaire which consisted of 3 parts: socio-demographic factors, health-risk behaviors and alcohol drinking behavior during the past year from December 2007 to February 2008.

The results showed that the percent of current drinking was 12.17. Most of them were 15-17 years (50.21 %). Socio-demographic factors such as age, educational level, residence, cohabitants, grade point average (GPA), having a part time job and having family members with alcohol/drug problems were significantly associated with alcohol drinking (p< 0.05). Multiple logistic regression analysis, after adjusting for socio-demographic factors, revealed that health-risk behavioral factors were associated with current alcohol consumption: often drove after drinking alcohol (OR = 3.10, 95 % CI = 1.88-5.12), often carried a weapon (OR = 3.51, 95 % CI = 2.27-5.42), often got into a physical fight without injury (OR = 3.06, 95 % CI = 1.99-4.70), dating violence (OR = 2.58, 95 % CI = 1.79-3.71), seriously thought about suicide (OR = 2.07, 95 % CI = 1.38-3.11), made a suicide plan (OR = 2.10, 95 % CI = 1.43-3.08), ever had sexual intercourse (OR = 5.62, 95 % CI = 4.33-7.29), alcohol or drug use before last sexual intercourse (OR = 2.55, 95 % CI = 1.44-4.53), and got someone pregnant (OR = 3.99, 95 % CI = 1.73-9.25).

An increased risk of health-risk behaviors, including driving vehicles after drinking, violence-related behaviors, sad feelings and attempted suicide, and sexual behaviors was higher among drinking students that led to significant health problems. Effective intervention strategies (such as campaign mentioning the adverse health effects and social consequences to the risk groups, and encouraging parental and community efforts to prevent drinking) among adolescents should be implemented to prevent underage drinking and adverse consequences.

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Chronic Ethanol Consumption in Mice Alters Hepatocyte Lipid Droplet Properties

Hepatosteatosis is a common pathological feature of impaired hepatic metabolism following chronic alcohol consumption. Although often benign and reversible, it is widely believed that steatosis is a risk factor for development of advanced liver pathologies, including steatohepatitis and fibrosis. The hepatocyte alterations accompanying the initiation of steatosis are not yet clearly defined.

Induction of hepatosteatosis by chronic ethanol consumption was investigated using the Lieber-DeCarli (LD) high fat diet model. Effects were assessed by immunohistochemistry and blood and tissue enzymatic assays. Cell culture models were employed for mechanistic studies.

Pair feeding mice ethanol (LD-Et) or isocaloric control (LD-Co) diets for 6 weeks progressively increased hepatocyte triglyceride accumulation in morphological, biochemical, and zonally distinct cytoplasmic lipid droplets (CLD). The LD-Et diet induced zone 2-specific triglyceride accumulation in large CLD coated with perilipin, adipophilin (ADPH), and TIP47. In LD-Co-fed mice, CLD were significantly smaller than those in LD-Et-fed mice and lacked perilipin. A direct role of perilipin in formation of large CLD was further suggested by cell culture studies showing that perilipin-coated CLD were significantly larger than those coated with ADPH or TIP47. LD-Co- and LD-Et-fed animals also differed in hepatic metabolic stress responses. In LD-Et but not LD-Co-fed mice, inductions were observed in the following: microsomal ethanol-oxidizing system [cytochrome P-4502E1 (CYP2E1)], hypoxia response pathway (hypoxia-inducible factor 1 alpha, HIF1α), endoplasmic reticulum stress pathway (calreticulin), and synthesis of lipid peroxidation products [4-hydroxynonenal (4-HNE)]. CYP2E1 and HIF1 α immunostaining localized to zone 3 and did not correlate with accumulation of large CLD. In contrast, calreticulin and 4-HNE immunostaining closely correlated with large CLD accumulation. Importantly, 4-HNE staining significantly colocalized with ADPH and perilipin on the CLD surface.

These data suggest that ethanol contributes to macrosteatosis by both altering CLD protein composition and inducing lipid peroxide adduction of CLD-associated proteins.

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Role of Snail Activation in Alcohol-Induced iNOS-Mediated Disruption of Intestinal Epithelial Cell Permeability

Chronic alcohol use results in many pathological effects including alcoholic liver disease (ALD). ALD pathogenesis requires endotoxemia. Our previous studies showed that increased intestinal permeability is the major cause of endotoxemia, and that this gut leakiness is dependent on alcohol stimulation of inducible nitric oxide synthase (iNOS) in both alcoholic subjects and rodent models of alcoholic steatohepatitis. The mechanism of the alcohol-induced, iNOS-mediated disruption of the intestinal barrier function is not known.

We have recently shown that alcohol stimulates activation of the transcription factor Snail and biomarkers of epithelial mesenchymal transition. As activated Snail disrupts tight junctional proteins, we hypothesized that activation of Snail by iNOS might be one of the key signaling pathways mediating alcohol-stimulated intestinal epithelial cell hyperpermeability.

We measured intestinal permeability in alcohol-fed C57BL/6 control and iNOS knockout (KO) mice, and measured Snail protein expression in the intestines of these mice. We then examined intestinal epithelial permeability using the Caco-2 cell model of the intestinal barrier ± small interfering RNA (siRNA) inhibition of Snail. We assessed Snail activation by alcohol in Caco-2 cells ± inhibition of iNOS with L-NIL or siRNA. Finally, we assessed Snail activation by alcohol ± inhibition with siRNA for p21-activated kinase (PAK1).
Our data show that chronic alcohol feeding promotes intestinal hyperpermeability in wild-type BL/6, but not in iNOS KO mice. Snail protein expression was increased in the intestines of alcohol-treated wild-type mice, but not in iNOS KO mice. siRNA inhibition of Snail significantly inhibited alcohol-induced hyperpermeability in Caco-2 cell monolayers. Alcohol stimulation of SnailpS246 activation was blocked by inhibition of iNOS with L-NIL or with siRNA. siRNA inhibition of PAK1 significantly inhibited alcohol-mediated activation of Snail in Caco-2 cells.

Our data confirmed our prior results and further demonstrated that alcohol-induced gut leakiness in rodents and intestinal epithelial cell monolayers is iNOS dependent. Our data also support a novel role for Snail activation in alcohol-induced, iNOS-mediated intestinal hyperpermeability and that PAK1 is responsible for activation of Snail at Ser246 with alcohol stimulation. Identification of these mechanisms for alcohol-induced intestinal hyperpermeability may provide new therapeutic targets for prevention and treatment of alcohol-induced leaky gut, endotoxemia, and endotoxin-associated complications of alcoholism such as ALD.

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Characterization of South African Adolescents With Alcohol Use Disorders but Without Psychiatric or Polysubstance Comorbidity

Individuals who begin drinking during early adolescence and exhibit externalizing pathology and disinhibitory/dysregulatory tendencies are more vulnerable to developing alcohol use disorders (AUDs) in adulthood. Previous research has focused on in-treatment populations with substantial comorbid psychopathology and polysubstance use. Here, we characterize a unique sample of treatment-naïve adolescents without such comorbidity to help identify vulnerable youth who may benefit from early intervention.

We compared externalizing propensity, disinhibitory characteristics, and school performance in adolescents with AUDs (but without comorbid psychopathology or other substance use; n = 70) to those of demographically matched controls (n = 70). Within the AUD group, we compared measures of substance use and the disinhibitory syndrome between boys and girls with differing severity of externalizing propensity.
Adolescents with AUDs demonstrated more externalizing propensity and disinhibitory personality traits (impulsivity, novelty seeking, and excitement seeking), poorer self-monitoring and response inhibition, more bullying and sexual risk-taking behavior, poorer first-language performance, and greater use of alcohol, cannabis, and nicotine (p < 0.05). Within the AUD group, participants with higher externalizing propensity began drinking earlier, more frequently, and for a longer duration than those with lower externalizing symptoms (p < 0.05). Disinhibitory features (personality, cognition, and behavior) were, however, not stronger in those with higher externalizing propensity.

We suggest that the constructs of externalizing propensity and disinhibitory syndrome are useful in characterizing treatment-naïve adolescents with AUDs but without comorbid psychopathology or polysubstance use. 

These results support the importance of these constructs in understanding adolescent AUDs, even when the frank externalizing diagnoses of childhood (oppositional defiant disorder and conduct disorder) are excluded.

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Topography, power, and current source density of theta oscillations during reward processing as markers for alcohol dependence

Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol-dependent individuals are quite rare. 

The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task, which involved outcomes of either loss or gain of an amount (10 or 50¢) that was bet. 

Event-related theta band (3.0–7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200–500 ms) was compared across groups and outcome conditions. 

Additionally, behavioral data of impulsivity and task performance were analyzed. 

The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current source density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition when compared with controls who manifested stronger and focused midline sources. 

Furthermore, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures.

A strong association between reduced anterior theta power and impulsive task-performance was observed. 

It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing, and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control. 

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Receiving an Alcohol Enquiry from a Physician in Routine Health Care in Sweden: A Population-Based Study of Gender Differences and Predictors

Research has shown that the provision of brief interventions in the health care system is effective for reducing hazardous drinking. 

Using a telephone-administered questionnaire, this study provides a population-based investigation on the extent to which physicians address patients’ alcohol habits in the Swedish health care system, whether there are gender differences in the extent to which patients receive questions about alcohol, and predictors for receiving such questions.

Data were obtained from monthly telephone surveys with around 72,000 people in 2006–2009.

Having received an alcohol enquiry was defined as having been asked about one’s drinking habits by a physician in any health care visit in the last 12 months. 

Fourteen percent of the total population had received an alcohol enquiry, but there were considerable gender differences: for hazardous drinkers, 13% of the women and 17% of the men had received an alcohol enquiry; among those with sensible alcohol consumption, 10% of women and 15% of men had received an alcohol enquiry. 

Patients were more likely to have received an alcohol enquiry if they had self-reported alcohol-related problems, were hazardous drinkers and/or daily smokers. 

Some of the alcohol enquiry predictors differed by gender; social class was an important predictor for women but not for men.

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Summary report of the 7th Meeting of the Science Group of the Alcohol and Health Forum

Please click here to access the summary report of the7th Meeting of the Science Group of the European Alcohol and Health Forum that took place in Brussels on 25 October 2011.

A review of public opinion towards alcohol controls in Australia

Increasing concern about the negative impact of alcohol on the Australian community has renewed calls for tighter regulatory controls. This paper reviews levels of and trends in public support for liquor control regulations, regulation of alcohol promotions, and alcohol pricing and taxation reforms in Australia between 1998 and 2009.

Six electronic databases and twenty public health and alcohol organisation websites were searched for research literature, reports and media releases describing levels of public support for alcohol controls. Only studies which randomly selected participants were included.

Twenty-one studies were included in the review. The majority of the Australian public support most proposed alcohol controls. Levels of support are divided between targeted and universal controls.

Implementation of targeted alcohol policies is likely to be strongly supported by the Australian public, but universal controls are liable to be unpopular. Policy makers are provided with insights into factors likely to be associated with higher public support.

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Prodynorphin CpG-SNPs associated with alcohol dependence: elevated methylation in the brain of human alcoholics

The genetic, epigenetic and environmental factors may influence the risk for neuropsychiatric disease through their effects on gene transcription. Mechanistically, these effects may be integrated through regulation of methylation of CpG dinucleotides overlapping with single-nucleotide polymorphisms (SNPs) associated with a disorder. 

We addressed this hypothesis by analyzing methylation of prodynorphin (PDYN) CpG-SNPs associated with alcohol dependence, in human alcoholics. 

Postmortem specimens of the dorsolateral prefrontal cortex (dl-PFC) involved in cognitive control of addictive behavior were obtained from 14 alcohol-dependent and 14 control subjects. Methylation was measured by pyrosequencing after bisulfite treatment of DNA. DNA binding proteins were analyzed by electromobility shift assay. 

Three PDYN CpG-SNPs associated with alcoholism were found to be differently methylated in the human brain.

In the dl-PFC of alcoholics, methylation levels of the C, non-risk variant of 3′-untranslated region (3′-UTR) SNP (rs2235749; C > T) were increased, and positively correlated with dynorphins. 

A DNA-binding factor that differentially targeted the T, risk allele and methylated and unmethylated C allele of this SNP was identified in the brain. 

The findings suggest a causal link between alcoholism-associated PDYN 3′-UTR CpG-SNP methylation, activation of PDYN transcription and vulnerability of individuals with the C, non-risk allele(s) to develop alcohol dependence.

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Behavioral profiling of multiple pairs of rats selectively bred for high and low alcohol intake using the

Genetic aspects of alcoholism have been modeled using rats selectively bred for extremes of alcohol preference and voluntary alcohol intake. These lines show similar alcohol drinking phenotypes but have different genetic and environmental backgrounds and may therefore display diverse behavioral traits as seen in human alcoholics.

The multivariate concentric square field™ (MCSF) test is designed to provoke exploration and behaviors associated with risk assessment, risk taking and shelter seeking in a novel environment.

The aim was to use the MCSF to characterize behavioral profiles in rat lines from selective breeding programs in the United States (P/NP, HAD1/LAD1, HAD2/LAD2), Italy (sP/sNP) and Finland (AA/ANA). 

The open field and elevated plus maze tests were used as reference tests. 

There were substantial differences within some of the pairs of selectively bred rat lines as well as between all alcohol-preferring rats. 

The most pronounced differences within the pairs of lines were between AA and ANA rats and between sP and sNP rats followed by intermediate differences between P and NP rats and minor differences comparing HAD and LAD rats.

Among all preferring lines, P, HAD1 and HAD2 rats shared similar behavioral profiles, while AA and sP rats were quite different from each other and the others. 

No single trait appeared to form a common ‘pathway’ associated with a high alcohol drinking phenotype among all of the alcohol-preferring lines of rats.

The marked behavioral differences found in the different alcohol-preferring lines may mimic the heterogeneity observed among human alcoholic subtypes.

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A Drosophila model for alcohol reward

The rewarding properties of drugs contribute to the development of abuse and addiction. 

We developed a new assay for investigating the motivational properties of ethanol in the genetically tractable model Drosophila melanogaster.

Flies learned to associate cues with ethanol intoxication and, although transiently aversive, the experience led to a long-lasting attraction for the ethanol-paired cue, implying that intoxication is rewarding. 

Temporally blocking transmission in dopaminergic neurons revealed that flies require activation of these neurons to express, but not develop, conditioned preference for ethanol-associated cues. 

Moreover, flies acquired, consolidated and retrieved these rewarding memories using distinct sets of neurons in the mushroom body.
Finally, mutations in scabrous, encoding a fibrinogen-related peptide that regulates Notch signaling, disrupted the formation of memories for ethanol reward. 

Our results thus establish that Drosophila can be useful for understanding the molecular, genetic and neural mechanisms underling the rewarding properties of ethanol.

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Parents’ perceptions of their children’s alcohol consumption: LJMU report

A survey in Wirral secondary schools amongst parents and their children (aged 11-17 years) investigated the influences of parental drinking and perceptions of alcohol consumption.  > > > >   Read More

'Under the influence: what we know about binge-drinking' interim report

An interim report on binge drinking has been released by Demos:

By 'binge-drinking', the report refers not to the Government definition of drinking twice the recommended guidelines on one occasion, but as "young adults that drink to extreme excess, often in an intentionally reckless and very public way, putting themselves and others at risk of harm."   > > > >  Read More

Problem Drinking and Low-Dose Naltrexone-Assisted Opioid Detoxification

The influence of alcohol use on opioid dependence is a major problem that warrants a search for more effective treatment strategies. The addition of very-low-dose naltrexone (VLNTX) to methadone taper was recently associated with reduced withdrawal intensity during detoxification. In a secondary analysis of these data, we sought to determine whether problem drinking affects detoxification outcomes and whether symptoms are influenced by VLNTX use.  

Opioid-dependent patients (N = 174) received naltrexone (0.125 or 0.250 mg/day) or placebo in a double-blind, randomized design during methadone-based, 6-day inpatient detoxification. Alcohol consumption was assessed at admission using the Addiction Severity Index and self-report. Outcome measures were opioid withdrawal intensity, craving, and retention in treatment. 

Problem drinking–opioid dependent patients (n = 79) showed episodic heavy alcohol use and reported increased subjective opioid withdrawal intensity (p = .001), craving (p = .001), and significantly lower rate of retention in treatment (p = .02). Individuals with problem drinking and opioid dependence who were treated with VLNTX (n = 55) showed reduced withdrawal (p = .05) and a lower rate of treatment discontinuation (p = .03), resuming alcohol intake in smaller numbers the day following discharge (p = .03). Treatment effects were more pronounced on anxiety, perspiration, shakiness, nausea, stomach cramps, and craving. There were no group differences in use of adjuvant medications and no treatment-related adverse events.
Heavy drinking is associated with worse opioid detoxification outcomes. The addition of VLNTX is safe and is associated with reduced withdrawal symptoms and better completion rate in these patients. Further studies should explore the use of VLNTX in detoxification and long-term treatment of combined alcohol–opioid dependence and alcohol dependence alone. 

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Wednesday, April 27, 2011

Motivational Interviewing for Incarcerated Adolescents: Effects of Depressive Symptoms on Reducing Alcohol and Marijuana Use After Release

Motivational interviewing to reduce alcohol and marijuana use among incarcerated adolescents was evaluated.  

Adolescents (N = 162, 84% male; M = 17.10 years old) were randomly assigned to receive motivational interviewing or relaxation training, with follow-up assessment 3 months after release.

Compared with those who received relaxation training, adolescents who received motivational interviewing had lower rates of alcohol and marijuana use at follow-up, with some evidence for moderating effects of depression. At low levels of depression, adolescents who received motivational interviewing had lower rates of use. Adolescents who received relaxation training and who had high levels of depressive symptoms early in incarceration showed less use at follow-up than those low in depressive symptoms who received relaxation training.  
  This brief motivational interviewing intervention during incarceration reduces alcohol and marijuana use after release. In addition, depressive symptoms early in incarceration should be considered in treating these adolescents, but more work is needed to extend follow-up period and account for the impact of depression on outcomes.

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Field Trial of Alcohol-Server Training for Prevention of Fetal Alcohol Syndrome

An alcohol-server training program to prevent fetal alcohol syndrome was developed, implemented, and evaluated in a comparison study of public drinking establishments in New Mexico and Oregon.  

The management and serving staffs of 148 establishments licensed for on-premise alcohol sales in the two states studied were trained to discourage alcohol consumption by pregnant customers. Pre- and post-tests of server responses to pregnant-appearing "pseudo-patron" actors ordering alcohol in experimental (n = 148) and comparison (n = 183) establishments were a key method of evaluating the efficacy of this intervention.  

Within-group chi-square analyses compared rates of service refusal at baseline with 1-month, 6-month, and 12-month follow-up points for both the trained (experimental) and the comparison establishments. No differences were found between experimental and comparison establishments at baseline at either site, but significant differences were found for New Mexico at each posttraining measurement point. In Oregon, the refusal rate at baseline increased from 1.5% at baseline to 8.3% at 1 month, which only approached significance. In New Mexico, at baseline the refusal rate was 8.6%, and it rose to 39.2% at 6 months (p < .0001, odds ratio = 6.83) and remained high at 28.2% at 12 months (p < .001, odds ratio = 4.15). No similarly significant gains were recorded at control establishments.  

Supplemental responsible beverage service training for alcohol servers to aid in the prevention of fetal alcohol exposure can be effective in reducing the serving of alcohol to visibly pregnant women, with robust effects continuing over the subsequent year in the New Mexico establishments.

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Evaluation of Two Web-Based Alcohol Interventions in the U.S. Military

The U.S. military has traditionally had high rates of alcohol misuse and alcohol-related problems, necessitating effective treatment programs that minimize participant burden. Web-based interventions have shown promise as efficient treatment options for college students and adults but have not been widely evaluated in the military. This study evaluated the efficacy of two web-based alcohol interventions originally created for civilians and then adapted for U.S. military personnel.  

Two web-based alcohol interventions, Alcohol Savvy and Drinker's Check-Up, were adapted for use among military populations. The interventions were evaluated using a convenience sample of 3,070 active-duty military personnel at eight installations. Following a baseline survey, participants were assigned to one of three treatment conditions: (a) Alcohol Savvy, (b) Drinker's Check-Up, or (c) control (no program participation). Follow-up surveys were completed by 1,072 participants 1 month following baseline and by 532 participants 6 months following baseline.
At 1-month follow-up, participants who completed the Drinker's Check-Up intervention had significant reductions in multiple measures of alcohol use relative to controls. Positive outcomes were found for average number of drinks consumed per occasion, frequent heavy episodic drinker status, and estimated peak blood alcohol concentration. These reductions in alcohol use at the 1-month follow-up were maintained at the 6-month follow-up. There were no statistically significant changes in alcohol use for participants who completed Alcohol Savvy.  

This study expands the literature on the effectiveness of web-based treatment for alcohol misuse. Findings indicate that web-based programs (Drinker's Check-Up in particular) can significantly decrease several indicators of alcohol use in U.S. military personnel. 

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Alcohol Screening and Changes in Problem Drinking Behaviors in Medical Care Settings: A Longitudinal Perspective

Although the effect of alcohol assessment in medical settings has received attention, the longitudinal study of such efforts has been restricted to studying a single assessment/intervention dose. Such interventions can be recurrent and have effects on subsequent problem drinking.  

A sample of problem drinkers in the general population (n = 672) and with admissions to chemical-dependency programs (n = 926) was interviewed at baseline and 1, 3, 5, and 7 years later. At each wave, respondents were asked about their drinking, their medical visits, and the intensity of the medical contact (whether during the visit they were asked about their drinking and, if so, whether they received or were referred to alcohol treatment)

Rates of problem drinking declined over time, from 48% at the 1-year follow up to 38% at the 7-year follow-up. Problem drinkers were more likely at each wave to receive or be referred to treatment. Alcohol and drug severity increased with more intensive medical-contact types over time. Predicting subsequent problem drinking status from prior intensity of medical contact, odds of problem drinking at subsequent waves decreased with time, age, and prior drug severity while increasing with volume and alcohol severity. Odds of problem drinking were lower among prior problem drinkers receiving assessment and treatment/referral, compared with the assessed-only group. Examined separately, this effect was found only for those drinkers with lower volumes (average < 0.5 drinks/day).  

Alcohol assessment may be effective in reducing problem drinking but may be most effective among the non-heaviest drinkers. 

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Heavy Episodic Drinking in Early Adulthood and Outcomes in Midlife

This study assessed to what extent drinking patterns of young adults persist into midlife and whether frequent heavy episodic drinking as a young adult is associated with educational attainment, labor market, and health outcomes at midlife. 

 Using the National Longitudinal Survey of Youth 1979, we grouped individuals into three baseline drinking categories using data on the number of occasions they consumed six or more drinks on one occasion from the 1982–1984 surveys. Categories were frequent heavy episodic drinker, occasional heavy episodic drinker, and other drinker/abstainer. We used propensity score matching to compare baseline drinking groups on midlife alcohol consumption, educational attainment, and labor market and health outcomes.

Frequent heavy episodic drinkers substantially reduced alcohol consumption between baseline and follow-up 25 years later. However, they were much more likely to abuse alcohol and be alcohol dependent in 1994 and be heavy episodic drinkers at the 25-year follow-up compared with the other drinking groups. After matching, there was little indication that being in a higher consumption baseline alcohol group was adversely associated with years of schooling completed by middle age, the probability of being employed, earnings conditional on being employed in midlife, and health problems in midlife. Results on the probability of surviving to follow-up were mixed. 

Frequent heavy episodic drinking at ages 17–25 years was associated with higher rates of alcohol dependence and abuse at a 10-year follow-up and alcohol consumption 25 years following baseline but not with other study outcomes at midlife. Lack of differences in outcomes at midlife may be because of decreased heavy episodic drinking among the heaviest baseline drinkers.

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Developing a Genetically Informative Measure of Alcohol Consumption Using Past-12-Month Indices

The goal of this study was to develop a factor score derived from measures of past-12-month alcohol consumption.  

Data were drawn from two studies — the Adult and Family Development Project (N = 734) and the Missouri Adolescent Female Twin Study (N = 3,787). Data on four indices of alcohol consumption (quantity, frequency, frequency of drinking to intoxication, and frequency of five or more drinks/day) were factor analyzed, and differences in factor loadings across gender, race/ethnicity, and study were tested. Correlations between these factors were computed across three assessments and between parent and offspring self-reports. Finally, using the classical twin design, variance in the past-12-month alcohol consumption factor was decomposed into additive genetic (A), shared environmental (C), and nonshared environmental (E) influences, and the extent to which these factors overlap with those influencing lifetime heaviest drinking were examined.  

Factor loadings across all groups were high (.69–.95), with some evidence for differing factor loadings across gender, race/ethnicity, and study. The across-wave correlations for the factor ranged from .22 to .62. The within-wave correlation between parental and offspring drinking was .25, suggesting the importance of familial influences, which genetic analyses attributed to both additive genetic (31%) and shared environmental (17%) factors. The overlap between genetic influences on past-12-month and lifetime heaviest drinking was 0.97.  

A factor score derived from past-12-month drinking measures is heritable and is largely influenced by those genetic factors that influence heaviest drinking, at least in young adults. It also shows moderate across-wave stability. This will allow for large- and small-scale genomic studies to use past-12-month drinking measures in data analysis of similar cohorts.

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