Tryptophan in Alcoholism Treatment II: Inhibition of the Rat Liver Mitochondrial Low Km Aldehyde Dehydrogenase Activity, Elevation of Blood Acetaldehy

The aims were to provide proofs of mechanism and principle by establishing the ability of the amino acid L-tryptophan (Trp) combined with the kynureninase inhibitor benserazide (BSZ) to inhibit the liver mitochondrial low K_m aldehyde dehydrogenase (ALDH) activity after administration and in vivo and to induce aversion to alcohol.

Trp, BSZ or both were administered to male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring acetaldehyde accumulation in blood after ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice.

Combined administration of Trp + BSZ, but neither compound alone, produced a strong inhibition of ALDH activity and an increase in blood acetaldehyde concentration after ethanol, and induced aversion to alcohol in rats and decreased preference in mice. Another kynureninase inhibitor, carbidopa, induced aversion to alcohol by itself, which was reversed by Trp co-administration.

The present results establish a prior art for the use of a combination of Trp plus BSZ in the treatment of alcoholism by aversion, which merits rapid clinical development.


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Tryptophan in Alcoholism Treatment I: Kynurenine Metabolites Inhibit the Rat Liver Mitochondrial Low Km Aldehyde Dehydrogenase Activity, Elevate Bloo

The aims were to provide proofs of mechanism and principle by establishing the ability of kynurenine metabolites to inhibit the liver mitochondrial low K_m aldehyde dehydrogenase (ALDH) activity after administration and in vivo, and to induce aversion to alcohol.

Kynurenic acid (KA), 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) were administered to normal male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring blood acetaldehyde following ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice.

ALDH activity was significantly inhibited by all three metabolites by doses as small as 1 mg/kg body wt. Blood acetaldehyde accumulation after ethanol administration was strongly elevated by KA and 3-HK and to a lesser extent by 3-HAA. All three metabolites induced aversion to alcohol in rats and decreased alcohol preference in mice.

The above kynurenine metabolites of tryptophan induce aversion to alcohol by inhibiting ALDH activity. An intellectual property covering the use of 3-HK and 3-HAA and derivatives thereof in the treatment of alcoholism by aversion awaits further development.



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Global Actions: September 8, 2011

Key Recent Milestones

Channel Research has released a mid-term evaluation of Global Actions, capturing information learned to date from the initiatives to improve development and implementation of initiatives over the next two years. The Channel Research report includes the following key findings:

· The initiatives have been effective and efficient due to ICAP’s coordination with local stakeholders and Global Actions country managers;

· The approach is relevant and builds on the interests of local institutions and industry representatives to promote responsible consumption of beverage alcohol;

· The initiatives’ extent of influence is attributed to locally targeted efforts that make responsible positions on social issues attractive to stakeholders;

· Knowledge is disseminated in a targeted, timely manner;

· The Noncommercial Alcohol initiative has already achieved impact through quality data and high public interest in beverage alcohol regulation; and

· Self-Regulation and Drink Driving initiatives are aligned with good practice standards and should achieve impact in a three-year time frame. For more about the mid-term evaluation, please visit www.global-actions.org.

Global Actions in Focus: Self-Regulation in Argentina

The fifth Red Latinoamericana de Organismos de Autorregulación Publicitaria (CONARED) meeting will take place on September 14-16, hosted by CONARP, the Argentinean advertising self-regulatory organization. CONARED will feature speakers from the World Federation of Advertisers (WFA), the International Chamber of Commerce (ICC), and Autocontrol of Spain, with the goal of sharing international best practices and strengthening existing self-regulatory practices. The meeting will be attended by representatives from self-regulatory organizations (SROs) in four Global Actions countries, Brazil, Colombia, Mexico, and Argentina, as well as representatives from Chile, El Salvador, Paraguay, Peru, and Uruguay. ICAP, WFA, and the Argentinean Chamber of Advertisers (CAA) will also bring together stakeholders at the event for a meeting on self-regulation.

What’s Happening Next

· China: September 16-18, Drink drive training workshop for local staff in Xi’an, followed by an enhanced enforcement workshop for traffic police September 21-22. Similar workshops will take place in Nanjing on September 20-22 and September 24-25.

· Nigeria: September 20-21, Capacity-building program for the Lagos-Apapa intervention. · Mexico: September 28-29, Drink drive summit in Mexico City.

· Ukraine: World Federation of Advertisers (WFA) will be participating in a self-regulation conference in Kiev on September 30.

Ethanol Causes The Redistribution of L1 Cell Adhesion Molecule in Lipid Rafts

Fetal alcohol spectrum disorder is estimated to affect 1% of live births. The similarities between children with fetal alcohol syndrome and those with mutations in the gene encoding L1 cell adhesion molecule (L1) implicates L1 as a target of ethanol developmental neurotoxicity.

Ethanol specifically inhibits the neurite outgrowth promoting function of L1 at pharmacologic concentrations. Emerging evidence shows that localized disruption of the lipid rafts reduces L1-mediated neurite outgrowth.

We hypothesize that ethanol impairment of the association of L1 with lipid rafts is a mechanism underlying ethanol’s inhibition of L1-mediated neurite outgrowth.

In this study, we examine the effects of ethanol on the association of L1 and lipid rafts.

We show that, in vitro, L1 but not N-cadherin shifts into lipid rafts following treatment with 25 mM ethanol. The ethanol concentrations causing this effect are similar to those inhibiting L1-mediated neurite outgrowth. Increasing chain length of the alcohol demonstrates the same cutoff as that previously shown for inhibition of L1-L1 binding.

In addition, in cerebellar granule neurons (CGN) in which lipid rafts are disrupted with methyl-beta-cyclodextrin (MBCD), the rate of L1-mediated neurite outgrowth on L1-Fc is reduced to background rate and that this background rate is not ethanol sensitive.

These data indicate that ethanol may inhibit L1-mediated neurite outgrowth by retarding L1 trafficking through a lipid raft compartment.

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2011 Fetal Alcohol Canadian Expertise (FACE) Poster Competition Abstracts

12th FACE Research Roundtable

Held on September 13, 2011 - Prince Edward Island

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A Differential Approach for Examining the Behavioural Phenotype of Fetal Alcohol Research Disorders

2006, Nash and colleagues published results suggesting that individual items from the Child Behavior Checklist (CBCL) could be used as a screening tool that was highly sensitive in differentiating children with FASD from controls and children with Attention Deficit Hyperactivity Disorder (ADHD). Since many of the items referred to features of Oppositional Defiant/Conduct Disorder (ODD/CD), it was not clear whether the items reflected comorbidity with ODD/CD, or were unique to children with FASD.

The present study sought to replicate the results of our 2006 paper using a new and larger sample, which also includes a group of children diagnosed with ODD/CD.

Retrospective psychological chart review was conducted on 56 children with FASD, 50 with ADHD, 60 with ODD/CD, and 50 normal control (NC) children. Receiver operating characteristic curve (ROC) analysis of CBCL items discriminating FASD from NC was used to compare FASD to the ADHD and ODD/CD groups.

ROC analyses showed scores of a) 3 or higher on 10 items differentiated FASD from NC with a sensitivity of 98%, specificity of 42% and b) 2 or higher on 5 items reflecting oppositional behaviors differentiated FASD from ADHD with a sensitivity of 89% and specificity of 42%.

Our findings partially replicate the results of our 2006 study and additionally elucidate the behavioural differences between children with FASD and those with ODD/CD. The proposed screening tool is currently the only tool available that is empirically derived and able to differentiate children with FASD from children with clinically similar profiles.

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Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings

This report presents the first information from the 2010 National Survey on Drug Use and Health (NSDUH), an annual survey sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA). The survey is the primary source of information on the use of illicit drugs, alcohol, and tobacco in the civilian, noninstitutionalized population of the United States aged 12 years old or older. The survey interviews approximately 67,500 persons each year. Unless otherwise noted, all comparisons in this report described using terms such as "increased," "decreased," or "more than" are statistically significant at the .05 level.

Alcohol Use

• Slightly more than half of Americans aged 12 or older reported being current drinkers of alcohol in the 2010 survey (51.8 percent). This translates to an estimated 131.3 million people, which was similar to the 2009 estimate of 130.6 million people (51.9 percent).

• In 2010, nearly one quarter (23.1 percent) of persons aged 12 or older participated in binge drinking. This translates to about 58.6 million people. The rate in 2010 was similar to the estimate in 2009 (23.7 percent). Binge drinking is defined as having five or more drinks on the same occasion on at least 1 day in the 30 days prior to the survey.

• In 2010, heavy drinking was reported by 6.7 percent of the population aged 12 or older, or 16.9 million people. This rate was similar to the rate of heavy drinking in 2009 (6.8 percent). Heavy drinking is defined as binge drinking on at least 5 days in the past 30 days.

• Among young adults aged 18 to 25 in 2010, the rate of binge drinking was 40.6 percent, and the rate of heavy drinking was 13.6 percent. These rates were similar to the rates in 2009.

• The rate of current alcohol use among youths aged 12 to 17 was 13.6 percent in 2010, which was lower than the 2009 rate (14.7 percent). Youth binge and heavy drinking rates in 2010 (7.8 and 1.7 percent) were also lower than rates in 2009 (8.8 and 2.1 percent).

• There were an estimated 10.0 million underage (aged 12 to 20) drinkers in 2010, including 6.5 million binge drinkers and 2.0 million heavy drinkers.

• Past month and binge drinking rates among underage persons declined between 2002 and 2010. Past month use declined from 28.8 to 26.3 percent, while binge drinking declined from 19.3 to 17.0 percent.

• In 2010, 55.3 percent of current drinkers aged 12 to 20 reported that their last use of alcohol in the past month occurred in someone else's home, and 29.9 percent reported that it had occurred in their own home. About one third (30.6 percent) paid for the alcohol the last time they drank, including 8.8 percent who purchased the alcohol themselves and 21.6 percent who gave money to someone else to purchase it. Among those who did not pay for the alcohol they last drank, 38.9 percent got it from an unrelated person aged 21 or older, 16.6 percent from another person younger than 21 years old, and 21.6 percent from a parent, guardian, or other adult family member.

• In 2010, an estimated 11.4 percent of persons aged 12 or older drove under the influence of alcohol at least once in the past year. This percentage had dropped since 2002, when it was 14.2 percent. The rate of driving under the influence of alcohol was highest among persons aged 21 to 25 (23.4 percent).

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Implementing Brief Interventions in Health Care: Lessons Learned from the Swedish Risk Drinking Project

The Risk Drinking Project was a national implementation endeavour in Sweden, carried out from 2004 to 2010, based on a government initiative to give alcohol issues a more prominent place in routine primary, child, maternity and occupational health care.

The article describes and analyses the project. Critical factors that were important for the results are identified. The magnitude of the project contributed to its reach and impact in terms of providers’ awareness of the project goals and key messages. The timing of the project was appropriate.

The increase in alcohol consumption in Sweden and diminished opportunities for primary prevention strategies since entry to the European Union in 1995 have led to increased expectations for health care providers to become more actively involved in alcohol prevention. This awareness provided favourable conditions for this project.

A multifaceted approach was used in the project. Most educational courses were held in workshops and seminars to encourage learning-by-doing. Motivational interviewing was an integral aspect. The concept of risk drinking was promoted in all the activities.

Subprojects were tailored to the specific conditions of each respective setting, building on the skills the providers already had to modify existing work practices. Nurses were afforded a key role in the project.



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Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study

Recent clinical and laboratory studies have shown that the effects of naltrexone for alcoholism may be moderated by the Asn40Asp single-nucleotide polymorphism (SNP) of the μ-opioid receptor gene (OPRM1). Allele frequencies for this polymorphism, however, have been shown to vary substantially as a function of ethnic background, such that individuals of Asian descent are more likely to carry the minor (Asp40) allele.

The objective of this study is to test the naltrexone pharmacogenetic effects of the Asn40Asp SNP in a sample of Asian Americans. This study consists of a double-blinded, randomized, placebo-controlled laboratory trial of naltrexone. Participants (n=35, 10 females; 13 Asn40Asn and 22 Asp40 carriers) were non-treatment-seeking heavy drinkers recruited from the community. After taking naltrexone or placebo, participants completed an intravenous alcohol administration session. The primary outcome measures were subjective intoxication and alcohol craving.

Results suggested that Asp40 carriers experienced greater alcohol-induced sedation, subjective intoxication, and lower alcohol craving on naltrexone, as compared to placebo, and to Asn40 homozygotes. There results were maintained when controlling for ALDH2 (rs671) and ADH1B (rs1229984) markers and when examining the three levels of OPRM1 genotype, thereby supporting an OPRM1 gene dose response.

These findings provide a much-needed extension of previous studies of naltrexone pharmacogenetics to individuals of Asian descent, an ethnic group more likely to express the minor allele putatively associated with improved biobehavioral and clinical response to this medication.

These findings help further delineate the biobehavioral mechanisms of naltrexone and its pharmacogenetics.



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Differential Effects of Daily-Moderate Versus Weekend-Binge Alcohol Consumption on Atherosclerotic Plaque Development in Mice.

We examined the effect of daily-moderate (2 drinks/day, 7 days/week) and weekend-binge (7 drinks/day, 2 days/week) patterns of alcohol consumption on plasma lipid levels and physiological parameters of atherosclerotic plaque development.

ApoE k/o mouse were fed (1) ‘daily-moderate’ (blood alcohol content: 0.07%) or (2) ‘weekend-binge’ (blood alcohol content: 0.23%), or (3) an isocaloric cornstarch mix. Then, to induce atherosclerotic plaque formation, all groups underwent partial carotid artery ligation, started on an atherogenic diet and continued on the alcohol feeding regimen. After 2 weeks plasma lipid levels and atherosclerotic plaque formation were assessed.

While there was an increase in HDL-C levels in both binge and moderate groups, LDL-C levels were significantly decreased in the daily-moderate drinking mice and significantly elevated in the weekend-binge drinking mice. In the daily-moderate alcohol group there was a decrease in atherosclerotic plaque volume, concomitant with an increase in lumen volume and decreased macrophage accumulation, when compared to no alcohol mice. In contrast, after 4 weeks of weekend-binge alcohol there was an increase in plaque volume, concomitant with a decrease in lumen volume and increased deposition of macrophages.

These findings demonstrate for the first time a differential effect of daily-moderate vs. weekend-binge alcohol consumption on atherosclerotic plaque development and highlight the importance of patterns of alcohol consumption, as opposed to total amount consumed, in relation to the cardiovascular effects of alcohol.

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The involvement of alcohol consumption in the deaths of children and young people in New Zealand during the years 2005–2007

While it is commonly accepted that alcohol misuse is harmful, very little is known about the effects of alcohol on the lives of children in New Zealand, particularly those under the age of 16. This special report was commissioned to investigate the role that alcohol consumption plays in the deaths of children and young people in New Zealand.

This report examines 357 deaths of children and young people aged between 4 weeks and 24 years who died in New Zealand during the years 2005 to 2007. In 87 of these, the death was attributable to alcohol or alcohol clearly contributed to the death. Of these 87 deaths, 49 involved a motor vehicle, 16 involved assault and 11 were due to drowning. The majority of these deaths related to young people 15 to 24 years.

The data shows a dramatic increase in death rates for injury from age 15 years onwards; much of this relates to adolescent risk-taking behaviour for which alcohol is a precipitating factor. This report also highlights that too many young people are victims of their own drinking or victims of the drinking of others. These issues represent different parts of the same problem but require different strategies for prevention. Victims of their own drinking typically drive while intoxicated, carry out risky behaviours (eg, being an intoxicated pedestrian) or drink to the point of poisoning and death. Most victims of others’ drinking get into cars with, or are injured by, an intoxicated driver or are assaulted by people who are drunk.


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Implementation of brief interventions evaluated in Scotland

An evaluation to assess the implementation of NHS delivered alcohol brief interventions in Scotland has been released. NHS Health Scotland had a target to deliver 149,449 brief interventions across three priority settings of primary care, Accident & Emergency (A&E) and antenatal care between 2008-2011. The programme is currently within a one year extension. > > > > Read More

Genetic Polymorphisms of Genes Coding to Alcohol-Metabolizing Enzymes in Western Mexicans: Association of CYP2E1*c2/CYP2E1*5B Allele with Cirrhosis an

Alcoholic cirrhosis constitutes a major public health problem in the world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy control individuals (C) and patients with alcoholic cirrhosis (AC) from western Mexico.

Ninety C and 41 patients with AC were studied. Genotype and allele frequency were determined through polymerase chain reaction-restriction fragment length polymorphisms.

Polymorphic allele distribution in AC was 1.6%ADH1B*2, 0.0%ALDH2*2, and 19.5%CYP2E1*c2; in C: 6.1%ADH1B*2, 0%ALDH2*2, and 10.6%CYP2E1*c2. CYP2E1*c2 polymorphic allele and c1/c2 genotype frequency were significantly higher (p < 0.05 and p < 0.01, respectively) in patients with AC when compared to C. Patients with AC, carrying the CYP2E1*c2 allele, exhibited more decompensated liver functioning evaluated by total bilirubin and prothrombin time, than c1 allele carrying patients (p < 0.05). Cirrhosis severity, assessed by Child’s Pugh score and mortality, was higher in patients carrying the c2 allele, although not statistically significant.

In this study, CYP2E1*c2 allele was associated with susceptibility to AC; meanwhile, ADH1B*2 and ALDH2*2 alleles were not. CYP2E1*c2 allele was associated with AC severity, which could probably be attributed to the oxidative stress promoted by this polymorphic form. Further studies to clearly establish CYP2E1*c2 clinical relevance in the development of alcohol-induced liver damage and its usefulness as a probable prognostic marker, should be performed. Also, increasing the number of patients and including a control group conformed by alcoholic patients free of liver damage may render more conclusive results. These findings contribute to the understanding of the influence of gene variations in AC development among populations, alcohol metabolism, and pharmacogenetics.

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The Effects of Age at Drinking Onset and Stressful Life Events on Alcohol Use in Adulthood: A Replication and Extension Using a Population-Based Twin

A study by Dawson and colleagues (Alcohol Clin Exp Res 2007; 31:69) using data from National Epidemiologic Survey on Alcohol and Related Condition found earlier drinking onset age, and higher levels of past-year stressful life events (SLE) were associated with higher past-year alcohol consumption. The aims of our study were as follows: (i) to attempt to replicate this interaction; (ii) to extend it by examining sex and event dependence as potential moderators of the effect; and (iii) to estimate the roles of genetic and environmental factors in mediating the overlap of early drinking onset and SLE in their relations with alcohol consumption.

Data were from 1,382 female and 2,218 male drinkers interviewed as part of the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Regression models were used to evaluate the main and interactive effects of early drinking onset and moderate or severe past-year SLE on past-year drinking density (PYDD), a weighted quantity-frequency measure of alcohol consumption. Analyses adjusted for demographic covariates and were stratified by sex and whether SLE were independent or dependent on the person’s actions, as rated by interviewers. Structural twin models were used to estimate the degree to which early drinking onset, SLE, and their interaction accounted for additive genetic, common environmental and individual-specific variance in PYDD.

We replicated the prior finding of a main effect of higher alcohol consumption among individuals reporting earlier drinking onset. Age at drinking onset accounted for about 5% of the variation in PYDD, and this association was mostly attributable to overlapping genetic influences. Evidence for an interaction between onset age and SLE was generally weak, possibly because of lower power and other methodological differences from Dawson and colleagues’ study. However, there was some evidence consistent with an interaction of higher PYDD among early drinking men who experienced independent SLE and early drinking women with dependent SLE.

We confirmed prior findings of an association between early age at drinking onset with higher past-year drinking among young- and middle-aged adults and found limited evidence supporting a replication for higher stress-related drinking among early-onset drinkers. The association is consistent with early onset and stress-related drinking being attributable to overlapping genetic liability. Among early drinkers, our results suggest sex differences in consumption with regard to event dependence.

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The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review

The endogenous opioid system has been implicated in the pathophysiology of alcoholism as it modulates the neurobehavioral effects of alcohol.

A variant in the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received attention as a functional variant that may influence a host of behavioral phenotypes for alcoholism as well as clinical response to opioid antagonists.

This paper will review converging lines of evidence on the effect of the Asn40Asp SNP on alcoholism phenotypes, including: (i) genetic association studies; (ii) behavioral studies of alcoholism; (iii) neuroimaging studies; (iv) pharmacogenetic studies and clinical trials; and (v) preclinical animal studies.

Together, these lines of research seek to elucidate the effects of this functional polymorphism on alcoholism etiology and treatment response.

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Parent–teen communication and pre-college alcohol involvement: A latent class analysis

Although parent–adolescent communication has been identified as important in delaying the onset and escalation of alcohol use, both the strength and direction of observed associations have varied in prior research with adolescents and college students. The current study categorizes parents according to alcohol-related communication and relates these categories to other parenting factors and late adolescent alcohol involvement.

As part of a larger study, 1007 college-bound teens and their parents were assessed. Teens were asked to report on their drinking behavior, and parents were asked about the occurrence of several specific alcohol-related communications with their teen, as well as additional parenting characteristics. Profiles of parent alcohol-related communication were derived using latent class analysis. Once the best fitting solution was determined, covariates were entered predicting class membership and investigating how classes were associated with additional parenting characteristics and teen alcohol use.

A five-class solution provided the best fit to the data: Frequent, All Topics (28%); Moderate, All Topics (25%); Frequent, General Topics (25%); Frequent, Consequences and Limits (12%); and Infrequent, All Topics (10%). Covariate analyses demonstrated class differences with regard to parental modeling, monitoring, knowledge, and parent–teen relationship satisfaction, as well as for students' intentions to join fraternities/sororities and alcohol use.

Findings from the current study add to a small but growing literature supporting the continuing influence of parents in late adolescence and suggest that the frequency and specificity of parent–teen communication are potentially informative for refined parent-based preventive interventions




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Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person whose mother drank alcohol during pregnancy. Learn more about signs, treatments, and what you can do about FASDs. > > > > Read More

Alcohol Consumption at Midlife and Successful Ageing in Women: A Prospective Cohort Analysis in the Nurses' Health Study

Observational studies have documented inverse associations between moderate alcohol consumption and risk of premature death. It is largely unknown whether moderate alcohol intake is also associated with overall health and well-being among populations who have survived to older age. In this study, we prospectively examined alcohol use assessed at midlife in relation to successful ageing in a cohort of US women.

Alcohol consumption at midlife was assessed using a validated food frequency questionnaire. Subsequently, successful ageing was defined in 13,894 Nurses' Health Study participants who survived to age 70 or older, and whose health status was continuously updated. “Successful ageing” was considered as being free of 11 major chronic diseases and having no major cognitive impairment, physical impairment, or mental health limitations. Analyses were restricted to the 98.1% of participants who were not heavier drinkers (>45 g/d) at midlife. Of all eligible study participants, 1,491 (10.7%) achieved successful ageing. After multivariable adjustment of potential confounders, light-to-moderate alcohol consumption at midlife was associated with modestly increased odds of successful ageing. The odds ratios (95% confidence interval) were 1.0 (referent) for nondrinkers, 1.11 (0.96–1.29) for ≤5.0 g/d, 1.19 (1.01–1.40) for 5.1–15.0 g/d, 1.28 (1.03–1.58) for 15.1–30.0 g/d, and 1.24 (0.87–1.76) for 30.1–45.0 g/d. Meanwhile, independent of total alcohol intake, participants who drank alcohol at regular patterns throughout the week, rather than on a single occasion, had somewhat better odds of successful ageing; for example, the odds ratios (95% confidence interval) were 1.29 (1.01–1.64) and 1.47 (1.14–1.90) for those drinking 3–4 days and 5–7 days per week in comparison with nondrinkers, respectively, whereas the odds ratio was 1.10 (0.94–1.30) for those drinking only 1–2 days per week.

These data suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health status among women who survive to older ages.

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Alcohol imagery and branding, and age classification of films popular in the UK

Exposure to alcohol products in feature films is a risk factor for use of alcohol by young people. This study was designed to document the extent to which alcohol imagery and brand appearances occur in popular UK films, and in relation to British Board of Film Classification (BBFC) age ratings intended to protect children and young people from harmful imagery.

Alcohol appearances (classified as ‘alcohol use, inferred alcohol use, other alcohol reference and alcohol brand appearances’) were measured using 5-min interval coding of 300 films, comprising the 15 highest grossing films at the UK Box Office each year over a period of 20 years from 1989 to 2008.

At least one alcohol appearance occurred in 86% of films, at least one episode of alcohol branding in 35% and nearly a quarter (23%) of all intervals analysed contained at least one appearance of alcohol. The occurrence of ‘alcohol use and branded alcohol appearances’ was particularly high in 1989, but the frequency of these and all other appearance categories changed little in subsequent years. Most films containing alcohol appearances, including 90% of those including ‘alcohol brand appearances’, were rated as suitable for viewing by children and young people. The most frequently shown brands were American beers: Budweiser, Miller and Coors. Alcohol appearances were similarly frequent in films originating from the UK, as from the USA.

Alcohol imagery is extremely common in all films popular in the UK, irrespective of BBFC age classification. Given the relationship between exposure to alcohol imagery in films and use of alcohol by young people, we suggest that alcohol imagery should be afforded greater consideration in determining the suitability of films for viewing by children and young people.

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The size and burden of mental disorders and other disorders of the brain in Europe 2010

To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU.

Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY).

Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8 million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165 m vs. 2005: 82 m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (N4%), ADHD (5%) in the young, and dementia (1–30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment.

Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke.

In every year over a third of the total EU population suffers from mental disorders. The true size of “disorders of the brain” including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs.

We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.


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