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, March 2, 2013

Alcohol abuse's hidden world

What happens when you drink alcohol?

The answer, on one level, is simple - you get drunk. But the science reveals a complicated series of reactions that lie behind drinking - between chemicals and neurons, genes and environment, people and society. Understanding these factors is important. Alcohol is implicated in 47% of violent crime in the UK and is estimated to cost the economy some £21bn a year.

The Today programme asked Sally Marlow, a researcher in alcohol addiction at King's College London, to look at the challenge of tackling alcohol abuse - and how it can best be understood - she's spent time in the north east of England.

First broadcast on BBC Radio 4's Today programme on Friday 1 March 2013.

A Behavioral Genetic Investigation of Weekend Drinking Among an Adult Sample

This study examined common and unique genetic and environmental influences on weekend drinking and weekday drinking reported by US male and female adult participants (mean age = 43.9). 

Data from 96 monozygotic and 82 dizygotic twin pairs were used to estimate bivariate biometric models of daily levels of weekend and weekday drinking volume. Weekend and weekday drinking volume scores were calculated from end-of-day reports of drinking across eight days. 

As expected, more drinking occurred during weekends. Biometric models provided evidence of significant additive genetic and nonshared environmental influences on both weekend and weekday drinking. Shared environmental influences were nonsignificant. Genetic influences accounted for a greater proportion of drinking variance during weekdays than weekends (0.36 compared to 0.17). 

However, these apparent differences in heritability—proportion of total variance accounted for by genetic variance—were due to increased nonshared environmental influences on weekend days, rather than greater genetic influences. 

The study's limitations are noted.

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Friday, March 1, 2013

Experts Call for UK Wide Tough Action on Alcohol Pricing

More than 70 health organisations (PDF) from across the UK have backed a new independent alcohol strategy calling for the UK Government to prioritise Minimum Unit Pricing (MUP), amongst a set of key policies aimed at curbing the nation's drink problem.

Published today by the University of Stirling the report, Health First: An evidence-based alcohol strategy for the UK (PDF) sets out for the first time a series of no-nonsense recommendations to tackle the harm caused by excess drinking across the UK.

The strategy was developed by a group of experts independent from government and the alcohol industry under the auspices of the Alcohol Health Alliance. There was unanimous agreement from the 70 organisations that a 50p minimum price per unit of alcohol sold should be the priority.

The group urges the UK government to adopt the measure to avoid England, Northern Ireland and Wales being left behind Scotland, which has already passed legislation for a minimum unit price of 50p per unit.   > > > >  Read More

For Debate Alcohol—a universal preventive agent? A critical analysis

In observational studies, moderate drinking is associated with a reduced risk of more than twenty different diseases and health problems. However, it would be premature to conclude that there is a causal relationship.

This paper critically reviews the evidence for such associations.

It was found that reasons for questioning the causal association of moderate drinking and a reduced health risk are: the lack of dose-response relationships; the characteristics and lifestyles of today's abstainers and moderate drinkers; the lack of plausible biological mechanisms; the problems in the classification of drinking groups, and; the general limitations of observational studies.

The evidence for the harmful effects of alcohol is undoubtedly stronger than the evidence for beneficial effects.

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The Association Between Prenatal Alcohol Exposure and Behavior at 22 Years of Age

Prenatal alcohol exposure (PAE) affects central nervous system development, growth, and morphology at higher exposure levels. Little is known about the effects of PAE at lower exposure levels or in young adults. Research on children with higher levels of PAE has shown that PAE predicts behavior problems. The question remains whether these effects are permanent or ameliorated by maturation into adulthood.

These data are from a longitudinal study of PAE. Mothers were recruited from a prenatal clinic and interviewed during their fourth prenatal month, seventh month, and delivery. In the postpartum, mothers and offspring were seen at 8 and 18 months, and 3, 6, 10, 14, 16, and 22 years.

At 22 years, PAE significantly predicted behavior as measured with the adult self-report. These findings were significant controlling for covariates. Exposure at each trimester predicted increased behavior problems on the Total Score, Internalizing, Externalizing, Attention, and Critical Items scales. Use across pregnancy predicted a higher rate of behavior problems compared to no use and use in the first trimester only.

The effects were dose-response and significant at each trimester of pregnancy. However, duration across pregnancy was a better predictor than drinking during the first trimester only. Binge drinking was not a better predictor of outcome compared to average daily volume (ADV), and within categories of ADV, binge drinking did not predict more problems than nonbinge drinking. Thus, there is no safe level or safe time during pregnancy for women to drink. These data demonstrate that the effects of PAE, even at low to moderate levels, extend into young adulthood and are most likely permanent.

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he Influence of Fetal Ethanol Exposure on Subsequent Development of the Cerebral Cortex as Revealed by Magnetic Resonance Imaging

Fetal alcohol syndrome and related disorders (commonly referred to as fetal alcohol spectrum disorder, or FASD) cause significant hardships to the individuals affected. Previously, histological studies in animals have characterized developmental cerebral cortical abnormalities that result from prenatal ethanol (EtOH) exposure. Additionally, magnetic resonance imaging (MRI) studies have identified abnormalities associated with fetal EtOH exposure in the cerebral cortices of human children and adolescents. However, there is still a need to bridge the gap between human MRI studies and animal histological studies. The goal of the research presented here was to perform postmortem MRI experiments on rodents, during time periods relative to late human gestation through adulthood, to characterize anomalies associated with FASD throughout development. Additionally, by determining how histologically identified abnormalities are manifest in MRI measurements specifically during the critical early time points, neuroimaging-based biomarkers of FASD can potentially be identified at much earlier ages in humans, thus reducing the impact of these disorders.

Cerebral cortical volume, thickness, and surface area were characterized by ex vivo MRI in Long-Evans rat pups born from dams that were EtOH-treated, maltose/dextrin-treated, or untreated throughout gestation at 6 developmental time points (postnatal day [P] 0, P3, P6, P11, P19, and P60).

Brain volume, isocortical volume, isocortical thickness, and isocortical surface area were all demonstrated to be reduced following prenatal exposure to EtOH. Significant differences among the treatment groups were observed throughout the range of time points studied, allowing for a comprehensive view of FASD influenced MRI outcomes throughout development. Isocortical surface area and isocortical thickness results contributed independent information important to interpreting effects of prenatal EtOH exposure on cerebral cortical development. Additionally, regional patterns in cortical thickness differences suggested primary sensory areas were particularly vulnerable to gestational EtOH exposure.

Structural MRI measurements were in accordance with previous histological studies performed in animal models of FASD. In addition to establishing a summary of MRI outcomes throughout development in FASD, this research suggests that MRI techniques are sufficiently sensitive to detect neuroanatomical effects of fetal EtOH exposure on development of the cerebral cortex during the period of time corresponding to late gestation in humans. Importantly, this research provides a link between animal histological data and human MRI data.

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Gender, Age, and Educational Level Attribute to Blood Alcohol Concentration in Hospitalized Intoxicated Adolescents; A Cohort Study

The prevalence of adolescents hospitalized with acute alcohol intoxication, mainly because of severe reduced consciousness, is increasing. However, the characteristics of these adolescents are mainly unidentified. In this clinical research, we aimed to identify factors that attribute to higher ethanol concentration, on which targeted alcohol health interventions can be designed.

Since 2007, alcohol intoxication among adolescents has been one of the leading topics of the Dutch Pediatric Surveillance System. In the current study, we have analyzed which demographic characteristics, general alcohol use behaviors, and clinical intoxication data were related to the blood alcohol concentration (BAC) levels at hospital admittance.

A total of 2,023 adolescents with alcohol intoxication were reported, and 1,618 questionnaires were returned, of which 1,350 met our inclusion criteria.
In univariate analysis, age, gender, educational level, place of alcohol purchase, place of alcohol consumption, age of first drink, and regular alcohol use during the weekend correlated with higher BAC. After multivariate analysis, older adolescents, boys, and higher educational level significantly attributed to higher BAC at admittance.

In alcohol-intoxicated adolescents with reduced consciousness, gender, age, and also educational level correlate with BAC at admittance. Explanatory factors could be found in sensitivity to alcohol, but also in socioeconomic factors, which influence availability. Intervention strategies could be targeted more specific now for the subgroups found in this study to decrease the growing burden of adolescent alcohol intoxication, both on the societal level and on the clinical level.

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Childhood Alcohol Use May Predict Adolescent Binge Drinking: A Multivariate Analysis among Adolescents in Brazil

To test the hypothesis that first alcohol use during childhood is associated with heavy drinking patterns during adolescence and with parental drinking patterns and parental rules about alcohol consumption.

A national cross-sectional survey of 17371 high-school students. Students were drawn from 789 public and private schools in all the Brazilian state capitals using a multistage probabilistic sampling method and a self-report questionnaire. Weighted data were analyzed through logistic regression testing for differences on the associated factors for first use of alcohol during childhood. Survival analysis and Cox proportional hazard models were used to confirm results.

Among the 82% alcohol lifetime users, 11% had first used alcohol before age 12 years. The lack of perception of possible punishment by parents is associated with childhood alcohol use (OR 2.22, 95% CI 1.67-2.95). Adolescents who first used alcohol during childhood compared with those who only used alcohol at later ages are more likely to engage in binge drinking behaviors (OR 1.57, 95% CI 1.17-2.10), to have a pattern of heavy alcohol use (OR 1.98, 95% CI 1.26-3.09), and to have recently used illegal drugs (OR 1.74, 95% CI 1.39-2.16). According to hazard ratios, students with an earlier age of onset were more likely to have used tobacco and any illegal drug in the past year.

Childhood alcohol may be a risk factor for the most dangerous patterns of alcohol use in adolescence and is associated with parental alcohol use. Parental rules about child alcohol use must be clear because perception of punishment might delay the age of first alcohol use.

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Thursday, February 28, 2013

Press Release -- British children more exposed to alcohol promotion than adults

Experts call for urgent changes to "flawed" regulatory system to protect children

Children in Britain are more exposed to alcohol promotion than adults and need much stronger protection, warn experts on today.

In an editorial to coincide with publication of the UK's first independent alcohol strategy, Professor Gerard Hastings at the University of Stirling and Dr Nick Sheron at the University of Southampton argue that urgent changes to Britain's "flawed" regulatory system are needed to provide much stronger protection for children.

A new analysis conducted by the Rand Corporation for the European Commission shows, for example, that 10-15 year olds in the UK see 10% more alcohol advertising on TV than their parents do. Even more shocking, when it comes to the specific sector of alcopops, they see 50% more. > > > >  Read 

Methodology of the Youth Risk Behavior Surveillance System — 2013 Recommendations and Reports

Priority health-risk behaviors (i.e., interrelated and preventable behaviors that contribute to the leading causes of morbidity and mortality among youths and adults) often are established during childhood and adolescence and extend into adulthood. The Youth Risk Behavior Surveillance System (YRBSS), established in 1991, monitors six categories of priority health-risk behaviors among youths and young adults: 1) behaviors that contribute to unintentional injuries and violence; 2) sexual behaviors that contribute to human immunodeficiency virus (HIV) infection, other sexually transmitted diseases, and unintended pregnancy; 3) tobacco use; 4) alcohol and other drug use; 5) unhealthy dietary behaviors; and 6) physical inactivity. In addition, YRBSS monitors the prevalence of obesity and asthma among this population.

YRBSS data are obtained from multiple sources including a national school-based survey conducted by CDC as well as school-based state, territorial, tribal, and large urban school district surveys conducted by education and health agencies. These surveys have been conducted biennially since 1991 and include representative samples of students in grades 9–12. In 2004, a description of the YRBSS methodology was published (CDC. Methodology of the Youth Risk Behavior Surveillance System. MMWR 2004;53 [No RR-12]). Since 2004, improvements have been made to YRBSS, including increases in coverage and expanded technical assistance. This report describes these changes and updates earlier descriptions of the system, including questionnaire content; operational procedures; sampling, weighting, and response rates; data-collection protocols; data-processing procedures; reports and publications; and data quality. This report also includes results of methods studies that systematically examined how different survey procedures affect prevalence estimates. YRBSS continues to evolve to meet the needs of CDC and other data users through the ongoing revision of the questionnaire, the addition of new populations, and the development of innovative methods for data collection. 

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Assessing Youth Participation in AA-Related Helping: Validity of the Service to Others in Sobriety (SOS) Questionnaire in an Adolescent Sample


The positive outcomes derived from participation in Alcoholics Anonymous-related helping (AAH) found among adults has spurred study of AAH among minors with addiction. AAH includes acts of good citizenship in AA, formal service positions, public outreach, and transmitting personal experience to another fellow sufferer. Addiction research with adolescents is hindered by few validated assessments of 12-step activity among minors. This study provides psychometric findings of the “Service to Others in Sobriety (SOS)” questionnaire as completed by youths.

Multi-informant data was collected prospectively from youth self-reports, clinician-rated assessments, biomarkers, and medical chart records for youths (N = 195) after residential treatment.

Few youths (7%) did not participate in any AAH during treatment. Results indicated the SOS as a unidimensional scale with adequate psychometric properties, including inter-informant reliability (r = .5), internal consistency (alpha = .90), and convergent validity (rs = −.3 to .3). Programmatic AAH activities distinguished abstinent youths in a random half-sample, and replicated on the other half-sample. The SOS cut-point of 40 indicated high AAH participation.

The SOS appears to be a valid measure of AAH, suggesting clinical utility for enhancing treatment and identifying service opportunities salient to sobriety. 

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Increased Risk of Alcohol and Drug Use among Children from Deployed Military Families

To examine the association between military deployment of a parent and use of alcohol and drugs among children of deployed military personnel.

Observational and cross-sectional study.

Data from the 2010 Iowa [USA] Youth Survey, a statewide survey of 6th, 8th, and 11th graders, were analyzed during 2011.

Of all 6th, 8th, and 11th grade students enrolled in Iowa in 2010, 69% (n=78,240) completed the survey.

Ever drink more than a few sips of alcohol and past 30-day: binge drinking, marijuana consumption, other illegal drug use, and prescription drug misuse.

The odds of using alcohol (OR=1.44, 99.91%CI=1.21-1.70), binge drinking (OR=2.02, 99.91%CI=1.63-2.50), using marijuana (OR=2.22, 99.91%CI=1.69-2.92), using other illegal drugs (OR=3.73, 99.91%CI=2.81-4.94), and misusing prescription drugs (OR=2.51, 99.91%CI=2.00-3.16) are greater for children of currently or recently deployed parents than for children of parents who are not in the military. The magnitude of the effects is consistent across 6th, 8th, and 11th grades. Disrupted living arrangements further accentuate increased substance use, with the largest effect seen in children with a deployed parent who was not living with a parent or relative.

Children of deployed military personnel should be considered at higher risk for substance use than children of non-military citizens.

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Prevalence and Patterns of Hazardous and Harmful Alcohol Consumption Assessed Using the AUDIT among Bhutanese Refugees in Nepal

This study sought to ascertain the prevalence of hazardous and harmful alcohol consumption among Bhutanese refugees in Nepal and to identify predictors of elevated risk in order to better understand intervention need. 

Hazardous and harmful alcohol consumption was assessed using the Alcohol Use Disorder Identification Test (AUDIT) administered in a face-to-face interview in a census of two camps comprising ∼8000 refugees. 

Approximately 1/5 men and 1/14 women drank alcohol and prevalence of hazardous drinking among current drinkers was high and comparable to that seen in Western countries with longstanding alcohol cultures. Harmful drinking was particularly associated with the use of other substances including tobacco. 

Assessment of the alcohol-related needs of Bhutanese refugees has permitted the design of interventions. This study adds to the small international literature on substance use in forced migration populations, about which there is growing concern.                  

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DRD2 and ANKK1 Gene Polymorphisms and Alcohol Dependence: A Case–Control Study among a Mendelian Population of East Asian Ancestry

Dopamine receptors are extensively studied in association with alcohol dependence (AD), since they are thought to be the key neural substrate for alcohol and other drug-related reinforcement and reward behaviours. The present study aims to understand the role of dopamine receptors in susceptibility to AD with respect to three sites of DRD2 gene (-141C Ins/Del, TaqIB and TaqID) and TaqIA site of ANKK1 gene among Meiteis of Manipur, a Mendelian population of India. 

A total of 129 individuals who all met the DSM-IV criteria for AD and 286 controls were screened for four single-nucleotide polymorphisms (SNPs) -141C Ins/Del, TaqIB TaqID and TaqIA. Both AD cases and controls were unrelated up to first cousin. 

Early age of onset of alcohol consumption and smoking status were significantly associated with AD. Improvement in education and occupation statuses showed decreased risk of AD. The heterozygous and mutant homozygous conditions of ANKK1 TaqIA polymorphism were found to be significantly associated with AD (odds ratio = 2.13, 95% confidential interval 1.04–4.39, P < 0.05), whereas a borderline significance of the -141C Del allele was observed (P = 0.059). Such a trend was not observed between AD and the other polymorphism, i.e. TaqIB and TaqID. 

Individuals carrying the A1 allele of ANKK1 TaqIA polymorphism may be relatively more susceptible to AD. Interaction of both ANKK1 TaqIA and -141C Ins/Del polymorphism is likely to increase risk of AD phenotypes among Meiteis of Manipur, India.

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Heineken eyes older shoppers to grow brands

The Dutch brewer is crowdsourcing observations from fans on the consumption occasions of older shoppers using its innovation platform the Ideas Brewery.

The insight will be used to create new beer products as well as bring the marketing strategies for its lager and cider brands more in line with the specific needs of the demographic over the next year. It is hoped the company-wide initiative will encourage more older drinkers to purchase Heineken’s brands such as Amstel and Birra Moretti.

A spokeswoman for Heineken, says: “We see in many parts of the world an ageing global population which is increasingly living longer. Traditionally, our focus has been on younger consumer groups – we see potential in embracing all age groups. We are now looking for insights that can help us develop propositions that are better tailored to the specific needs of the 60+ consumer. At a later phase we will match ideas with relevant brands.”

The strategy follows the launch of the brand’s 60+ Generation challenge on the Ideas Brewery earlier this year where fans were invited to help create a documentary that celebrated the older generation. The activity is the first time Heineken has used its crowdsourcing platform, which launched last year, to target a specific demographic.  > > > >   Read More

Wednesday, February 27, 2013

Alcohol & Gambling: Alcohol Concern report explores links and reccomendations

Alcohol Concern Cymru and the Royal College of Psychiatrists (RCPysch) Wales have published a joint report on the links between alcohol misuse and gambling, exploring key policy implications and recommendations.  > > >   >  Read More 

The Impact of the Mental Health Parity and Addiction Equity Act on Inpatient Admissions > > > >

The 2008 Mental Health Parity and Addiction Equity Act (MHPAEA) sought to improve access to mental health and substance use services. The Health Care Cost Institute, Inc. (HCCI) analyzed mental health, sub-stance use, and medical/surgical inpatient per capita spending, utiliza-tion, prices, and out-of-pocket payments for individuals younger than age 65 and covered by employer-sponsored health insurance (ESI) for 2007 through 2011. During the study period, ESI per capita spending nearly doubled for behavioral health admissions and grew to 3.2 percent of in-patient spending. In 2011, mental health admissions grew by 5.9 per-cent, and substance use admissions grew by 19.5 percent. After 2009, out-of-pocket payments per admission were nearly equivalent for mental health and medical/surgical stays. In all years, out-of-pocket payments per substance use stay remained greater than out-of-pocket payments per mental health or medical/surgical admission. In this initial examina-tion, the role MHPAEA played in the changes observed in 2011 remains unclear.  > > > >  Read More

Intellectual disability: population-based estimates of the proportion attributable to maternal alcohol use disorder during pregnancy

The aim of this study was to examine the association between maternal alcohol use disorder and intellectual disability in children.

All mothers with an International Classification of Diseases (ICD) 9 and/or 10 alcohol-related diagnosis, a proxy for alcohol use disorder, recorded on the Western Australian health, mental health, and drug and alcohol data sets were identified through the Western Australian Data Linkage Unit (n=5614 non-Aboriginal; n=2912 Aboriginal). A comparison cohort of mothers without an alcohol-related diagnosis was frequency matched on maternal age within maternal Aboriginal status and year of birth of their children. Linkage with the Western Australian Midwives Notification System (1983–2001) identified all births to these mothers (n=10 664 and 7907 respectively). Linkage to the Western Australian Intellectual Disability Database and Register of Developmental Anomalies identified cases of intellectual disability with no identified genetic origin (intellectual disability) (n=1487) and fetal alcohol syndrome (n=66). Odds ratios (ORs) and 95% confidence intervals (CIs) for intellectual disability were calculated using logistic regression incorporating generalized estimating equations and used to estimate population-attributable fractions.

At least 3.8% (95% CI 2.84–4.89%) of cases of intellectual disability could be avoided by preventing maternal alcohol use disorder: 1.3% (95% CI 0.81–1.86%) in non-Aboriginal and 15.6% (95% CI 10.85–20.94%) in Aboriginal children. We observed a three-fold increase in the adjusted odds of intellectual disability in children of mothers with an alcohol-related diagnosis recorded during pregnancy (non-Aboriginal OR 2.89, 95% CI 1.62–5.18; Aboriginal OR 3.12, 95% CI 2.13–4.56), with a net excess proportion of 3.7% and 5.5% respectively. One-third (32%) of children diagnosed with fetal alcohol syndrome had intellectual disability.

Maternal alcohol use disorder is the leading known risk factor for intellectual disability with no identified genetic origin.

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Critique 104: Moderate alcohol consumption is associated with a lower risk of diabetes — 26 February 2013

We investigated the influence of different aspects of alcohol consumption on the risk of Type 2 diabetes and autoimmune diabetes in adults.  > > > >  Read More

Alcohol in Australia - Analysis and Comment

Alcohol, tobacco, and fast-food industry sponsorship of sport sends the wrong message to the population. Dean Lewins/AAP

‘As a matter of fact, I’ve got it now’: alcohol advertising and sport

Sport is generally a healthy activity that transmits important societal values, such as fairness, perseverance, and teamwork. Unfortunately, it’s also the primary vehicle for marketing alcohol to the general…
Australian studies show alcohol is considerably more likely than other drugs to be involved in violence. Aviva West

Fact check: only drugs and alcohol together cause violence

On ABC TV’s Four Corners program last night, Paul Nicolaou, chief executive officer of Australia Hotels Association New South Wales, dismissed claims that alcohol is fuelling late-night violence, arguing…
Alcohol-related violence is rising while per capita consumption is falling. Kirti Poddar

Alcohol-fuelled violence on the rise despite falling consumption

Generally speaking, if a population drinks more, then there are more heavy drinkers and more harm from alcohol (similarly if a population drinks less, there will be less harm). But this link now appears…
In decisions about alcohol policy, the effects on others, and not just on the drinker, need to be taken into account. Gaby Av

My drinking, your problem: alcohol hurts non-drinkers too

Drinking a lot of alcohol is bad for the drinker’s health, both in the short and in the long run. But drinking often affects others adversely, too. This is well recognised for drink driving, and once the…
The increasing liberalisation of alcohol normalises drinking and consumption becomes enmeshed in the daily fabric of life. Image from

Social acceptance of alcohol allows us to ignore its harms

Most of us forget that alcohol is a drug so when asked to name drug-related problems, we tend to think of illegal drugs such as cannabis or heroin. But most of us drink, and drinking is an accompaniment…
Wine became popular in Australia in the 1960s, which led to the invention of the wine cask. Flickr/Johnsyweb

A brief history of alcohol consumption in Australia

Although most Australians would probably say we’ve always been a heavy-drinking nation, the consumption of alcohol has followed a roller coaster curve since European invasion. Alcohol consumption in Australia…

How is alcohol consumption affected if we account for under-reporting? A hypothetical scenario

This study predicts the implications of under-reporting of alcohol consumption in England for alcohol consumption above Government drinking thresholds. 

Two nationally representative samples of private households in England were used: General LiFestyle survey (GLF) and Health Survey for England (HSE) 2008. Participants were 9608 adults with self-reported alcohol consumption on heaviest drinking day in the last week (HSE) and 12 490 adults with self-reported average weekly alcohol consumption (GLF). Alcohol consumption in both surveys was revised to account for under-reporting in three hypothetical scenarios. The prevalence of drinking more than UK Government guidelines of 21/14 (men/women) alcohol units a week, and 4/3 units per day, and the prevalence of binge drinking (>8/6 units) were investigated using logistic regression. 

Among drinkers, mean weekly alcohol intake increases to 20.8 units and mean alcohol intake on heaviest drinking day in the last week increases to 10.6 units. Over one-third of adults are drinking above weekly guidelines and over three-quarters drank above daily limits on their heaviest drinking day in the last week. The revision changes some of the significant predictors of drinking above thresholds. In the revised scenario, women have similar odds to men of binge drinking and higher odds of drinking more than daily limits, compared with lower odds in the original survey. 

Revising alcohol consumption assuming equal under-reporting across the population does not have an equal effect on the proportion of adults drinking above weekly or daily thresholds. It is crucial that further research explores the population distribution of under-reporting.

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Tuesday, February 26, 2013

Acute Alcohol Effects on Attentional Bias are Mediated by Subcortical Areas Associated with Arousal and Salience Attribution

Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the underlying cognitive and brain mechanisms remain unknown. 

We combined functional magnetic resonance imaging (fMRI) with performance of a dual task that probed attentional distraction by alcohol-related stimuli during ‘conflict’ processing: the Concurrent Flanker/Alcohol-Attentional bias task (CFAAT). In this task, an Eriksen Flanker task is superimposed on task-unrelated background pictures with alcohol-associated or neutral content. Participants respond to the direction of a central ‘target’ arrow and ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) ‘flanking’ arrows. Using a between-subject design, 40 healthy moderate-to-heavy social drinkers received either no alcohol (placebo), 0.4g/kg (low dose), or 0.8g/kg (high dose) of alcohol, and underwent fMRI while performing the CFAAT. 

The low alcohol dose, relative to placebo, increased response latencies on trials with alcohol-associated backgrounds and, under low cognitive load, increased the activity evoked by these pictures within a medial hypothalamic region. Under high cognitive load, the low alcohol dose, relative to placebo, elicited greater activity within a more lateral hypothalamic region, and reduced activity within frontal motor areas. 

The high alcohol dose, relative to placebo, did not reliably affect response latencies or neural responses to background images, but reduced overall accuracy under high cognitive load. This effect correlated with changes in reactivity within medial and dorsal prefrontal cortices.

These data suggest that alcohol at a low dose primes attentional bias to alcohol-associated stimuli, an effect mediated by activation of subcortical hypothalamic areas implicated in arousal and salience attribution.

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The Feasibility and Cost of Neonatal Screening for Prenatal Alcohol Exposure by Measuring Phosphatidylethanol in Dried Blood Spots

Accurate confirmation of prenatal alcohol exposure (PAE) is required as a diagnostic criterion for the majority of children adversely affected by PAE who do not manifest the physical features associated with fetal alcohol syndrome. A number of ethanol biomarkers have been used to assess PAE, often with suboptimal results. The purpose of this study was to evaluate the feasibility and cost of PAE screening in newborns by measuring phosphatidylethanol (PEth) in dried blood spot (DBS) cards.

The feasibility of collecting an additional DBS card during routine newborn screening and the background prevalence of PAE were evaluated in a de-identified sample of newborn children delivered at the University of New Mexico Hospital. Electronic orders to collect DBS cards from newborns who continue to bleed after the routine newborn screen, glucose, or hematocrit testing were initiated for all infants delivered during a 4-week time frame. Specimens were sent to a contract laboratory for PEth analysis by liquid chromatography–tandem mass spectrometry. A cost analysis was conducted to compare the cost of PAE screening by PEth in DBS versus PEth in conventional blood specimens and by meconium fatty acid ethyl esters.

From 230 collected cards, 201 (87.4%) had at least 1 full blood spot (amount sufficient for PEth analysis), and 6.5% had PEth >20 ng/ml indicative of potential PAE in late pregnancy. PAE screening by PEth in DBS is logistically simpler and less expensive compared with 2 other screening approaches.

These results indicate that screening for PAE in DBS cards is a feasible procedure and that a majority of infants have enough blood after the routine heel prick to fill an additional card. Moreover, screening by PEth analysis from DBS cards is cost-efficient. The acceptability of such screening by parents and corresponding ethical issues remain to be investigated.

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Self-Determination and Substance Use: Is Effortful Control a Mediator?

Alcohol and other drug use among college students are highly common in the United States. This study examined the relationships between 2 motivational orientations (i.e., autonomy and controlled orientations) and substance use and related problems among college students. It also examined whether effortful control mediated the relationship between these motivational orientations and substance use.

Study participants were 644 undergraduate students (67.2% female; 87.2% Caucasian) who completed a series of online questionnaires as a part of a larger longitudinal study on sleep and substance use. The mean age of participants was 23.58 (SD = 6.861).

Students with a higher autonomy orientation were more likely than their counterparts to report that they did not drink in the last 6 months. In contrast, students with a higher controlled orientation were less likely to report that they did not drink. Among those who drank in the last 6 months, effortful control significantly mediated the effects of autonomy orientation and controlled orientation on frequency of alcohol use within that time frame. Autonomy orientation positively predicted effortful control, which was associated with a decrease in the expected frequency of drinking. In contrast, controlled orientation negatively predicted effortful control, which was associated with an increase in the expected frequency of drinking. Controlled orientation also significantly predicted the presence of alcohol-related problems and illicit drug use.

Intervention and prevention programs on college drinking could incorporate education about strategies for self-control, including strategies for withstanding peer pressure and diverting one's attention to activities unrelated to substance use. Focusing on strategies of self-control may be a useful starting point for a more in-depth discussion about the motivations, values, and psychological needs satisfaction that are associated with drinking and other drug use.

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Resting-State Synchrony in Short-Term Versus Long-Term Abstinent Alcoholics

We previously reported that when compared with controls, long-term abstinent alcoholics (LTAA) have increased resting-state synchrony (RSS) of the inhibitory control network and reduced synchrony of the appetitive drive network, and hypothesized that these levels of synchrony are adaptive and support the behavioral changes required to maintain abstinence. In this study, we investigate whether these RSS patterns can be identified in short-term abstinent alcoholics (STAA).

Resting-state functional magnetic resonance imaging data were collected from 27 STAA, 23 LTAA, and 23 nonsubstance abusing controls (NSAC). We examined baseline RSS using seed-based measures.

We found ordered RSS effects from NSAC to STAA and then to LTAA within both the appetitive drive and executive control networks: increasing RSS of the executive control network and decreasing RSS of the reward processing network. Finally, we found significant correlations between strength of RSS in these networks and (i) cognitive flexibility, and (ii) current antisocial behavior.

Findings are consistent with an adaptive progression of RSS from short- to long-term abstinence, so that, compared with normal controls, the synchrony (i) within the reward network progressively decreases, and (ii) within the executive control network progressively increases.

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Intravenous Ethanol Increases Extracellular Dopamine in the Medial Prefrontal Cortex of the Long–Evans Rat

Ethanol (EtOH) affects prefrontal cortex functional roles such as decision making, working memory, and behavioral control. Yet, the pharmacological effect of EtOH on dopamine, a neuromodulator in the medial prefrontal cortex (mPFC), is unclear. Past studies exploring this topic produced conflicting outcomes; however, a handful of factors (temporal resolution, method of drug administration, estrous cycle) possibly contributed to these discrepancies. We sought to mitigate these factors in order to elucidate EtOH's pharmacological effects on mPFC dopamine in Long–Evans rats.

We administered experimental solutions via an intravenous (iv), handling-free route, monitored dopamine in the mPFC via microdialysis (10-minute samples), and used male rats to avoid estrous cycle/EtOH interactions. First, we rapidly (approximately 2.7 ml/min) or slowly (approximately 0.6 ml/min) administered 1.0 g/kg EtOH and saline infusions, showing that the experimental methods did not contribute to dopamine changes. Then, a cumulative dosing protocol was used to administer 0.25, 0.75, 1.50, and 2.25 g/kg iv EtOH doses to evaluate dose–response. Finally, we monitored dialysate EtOH levels during an oral EtOH self-administration session to compare the dialysate EtOH levels achieved during the pharmacological experiments to those seen during self-administration.

IV administration of a rapid or slow 1.0 g/kg EtOH infusion resulted in similar significant 55 ± 9 and 63 ± 15% peak dialysate dopamine increases, respectively. The 0.25, 0.75, 1.50, and 2.25 g/kg EtOH doses produced a nonsignificant 17 ± 5% and significant 36 ± 15, 68 ± 19, and 86 ± 20% peak dialysate dopamine increases, respectively. Self-administration dialysate EtOH concentrations fell within the range of concentrations noted during the EtOH dose–response curve.

These experiments show that, using experimental methods that minimize possibly confounding factors, acute iv EtOH increases extracellular dopamine in the mPFC in a dose-dependent manner, thereby clarifying EtOH's pharmacological effects on the mesocortical dopamine system.

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Nicotinic Acetylcholine Receptors are Sensors for Ethanol in Lung Fibroblasts

Chronic ethanol (EtOH) abuse in humans is known to independently increase the incidence of and mortality due to acute lung injury in at-risk individuals. However, the mechanisms by which EtOH affects lung cells remain incompletely elucidated. In earlier work, we reported that EtOH increased the expression in lung fibroblasts of fibronectin, a matrix glycoprotein implicated in lung injury and repair. This effect was blocked by α-bungarotoxin, a neurotoxin that binds certain nicotinic acetylcholine receptors (nAChRs) thereby implicating nAChRs in this process. Here, we examine the identity of these receptors.

Mouse lung fibroblasts were stimulated with EtOH (60 mM) or acetylcholine (100 to 500 μM) and evaluated for the expression of fibronectin and nAChRs. Inhibitors to nAChRs or the antioxidant N-acetyl cysteine (NAC) were used to assess changes in fibronectin expression. Animals exposed to EtOH for up to 6 weeks were used to evaluate the expression of nAChRs in vivo
First, in EtOH-treated fibroblasts, we observed increased expression of α4 and α9 nAChR subunits. Second, we found that acetylcholine, a natural ligand for nAChRs, mimicked the effects of EtOH. Dihydro-β-erythroidin hydrobromide, a competitive inhibitor of α4 nAChR, blocked the increase in fibronectin expression and cell proliferation. Furthermore, EtOH-induced fibronectin expression was inhibited in cells silenced for α4 nAChR. However, EtOH-treated cells showed increased α-bungarotoxin binding suggesting that α4 nAChR mediates the effects of EtOH via a ligand-independent pathway. Knowing there are several important cysteine residues near the ligand-binding site of α4 nAChRs, we tested the antioxidant NAC and found that it too blocked the induction of fibronectin expression by EtOH. Also, fibroblasts exposed to oxidant stress showed increased fibronectin expression that was blocked with α-bungarotoxin. Finally, we showed increased expression of α4 nAChRs in the lung tissue of mice and rats exposed to EtOH suggesting a role for these receptors in vivo

Altogether, our observations suggest that α4 nAChRs serve as sensors for EtOH-induced oxidant stress in lung fibroblasts, thereby revealing a new mechanism by which EtOH may affect lung cells and tissue remodeling and pointing to nAChRs as potential targets for intervention.

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Molecular Tolerance of Voltage-Gated Calcium Channels is Evident After Short Exposures to Alcohol in Vasopressin-Releasing Nerve Terminals

Voltage-gated calcium channels (VGCCs) in rat neurohypophysial terminals exhibit molecular tolerance to alcohol, including desensitization to the drug and increased current density, after 3 weeks of alcohol drinking. Moreover, after this time, terminals from drinking rats exhibit diminished alcohol inhibition of vasopressin (AVP) release.

We took advantage of organotypic cultures (explants) of the hypothalamo-neurohypophysial system (HNS) to extend our analysis of molecular tolerance to 2 classes of the VGCC. The isolated HNS explant allows much finer temporal resolution of molecular tolerance than do voluntary drinking paradigms. After exposure of the HNS explant to alcohol, terminals are isolated by mechanical treatment and plated in a dish. Patch clamp recording techniques are used to obtain VGCC currents, and immunohistochemistry is used to determine VGCC distribution. A release assay is used to provide functional readout of AVP release.

We show that even a brief, 1-hour exposure to a clinically relevant concentration of alcohol is sufficient to evoke similar changes to those observed after several weeks of exposure. Acute ethanol (EtOH) exposure inhibits high K+-induced AVP release from naïve terminals. However, terminals pre-exposed to 20 mM EtOH for 1 hour become tolerant to EtOH, and subsequent exposure has significantly less effect on high K+-induced AVP release. Electrophysiological recordings indicate that among different types of VGCCs present in the neuronal terminal, the L-type is the most affected by alcohol. The current density of L-type current is significantly increased (approximately 50%), while its responsiveness to alcohol is significantly diminished (approximately 50%), after brief alcohol exposure. Fluorescent imaging results were consistent with the electrophysiology and suggest that the increased current density of VGCCs after brief exposure is attributable to combined synthesis of 1.2 and 1.3 subtypes of the L-type VGCC and redistribution of channel protein into terminal plasma membrane.

These data indicate that a brief alcohol exposure affects subsequent alcohol sensitivity of VGCCs and neuropeptide release from presynaptic terminals.

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The Effects of Chronic Cigarette Smoking on Cognitive Recovery During Early Abstinence from Alcohol

Alcohol use disorders are related to neurocognitive abnormalities during early abstinence in those seeking treatment for alcohol dependence (ALC). Considerable evidence indicates that chronic cigarette smoking is associated with multiple neurocognitive deficiencies. However, very little is known about the effects of chronic smoking on neurocognitive recovery during early abstinence from alcohol. We evaluated whether cigarette smoking interferes with cognitive improvement during early abstinence from alcohol, a period thought important for maintaining long-term sobriety.

Neurocognitive functions previously shown to be adversely affected by both alcohol use disorders and chronic cigarette smoking were evaluated. We assessed 35 smoking ALC (sALC) and 34 nonsmoking ALC (nsALC) at approximately 1 and 5 weeks of monitored abstinence.

Although neither group was clinically impaired, both cross-sectional and longitudinal deficiencies were observed in sALC versus nsALC in processing speed, working memory, and auditory-verbal learning and memory. Lifetime alcohol consumption, medical, and psychiatric comorbidities did not predict neurocognitive performance or improvement across assessments. Within sALC, greater drinking and smoking severities were synergistically (more than additively) related to less improvement on visuospatial learning and memory. Former smoking status in the nsALC-mediated group differences in auditory-verbal delayed recall.

Chronic cigarette smoking appears to negatively impact neurocognition during early abstinence from alcohol. Although the cognitive deficiencies observed in this cohort were not in a clinical range of impairment, they should be considered to enhance treatment efficacy. Our findings lend support to integrating smoking cessation as well as the individual assessment of cognition into early ALC treatment. Additionally, there is a need to elucidate the effects of current and former smoking status in future reports of neurocognition.

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