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, February 12, 2011

Relationships Between State and Trait Anxiety Inventory and Alcohol Use Disorder Identification Test Scores Among Korean Twins and Families: The Healthy Twin Study

We explored heritabilities of the State and Trait Anxiety Inventory (STAI) and the Alcohol Use Disorders Identification Test (AUDIT), and associations including genetic and environmental correlations between the phenotypes among Korean twins and their families. 

We analyzed the data of 1,748 participants (835 men, 913 women, 656 individuals of monozygotic twins, 173 individuals of same-sexed dizygotic twins, 919 non-twin family members, age 30–79 years) from the Healthy Twin study. Heritabilities and bivariate analyses were assessed using the SOLAR package software. 

In the methods of generalized estimation equations, women in the 4th quartile of state and trait scores were 17% and 15%, respectively more likely to be hazardous alcohol users compared to women in the lower three quartiles (P < .05). 

However, there were no significant associations between these phenotypes in men. 

After adjusting for age and squared age, the heritability estimates were 0.26 in men and 0.34 in women for the state score; for the trait score, 0.35 in men and 0.31 in women; for the AUDIT score, 0.32 in men and 0.37 in women (P < .001). 

After adjusting for age and squared age, there was a significant genetic correlation between the trait score and the AUDIT score, and a significant non-genetic correlation between the state score and the AUDIT score in women, while there were no significant genetic or non-genetic correlations between these phenotypes in men. 

The STAI and AUDIT scores are heritable in Koreans and the relationships between these phenotypes may be inconsistent by sex.

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Toward a Comprehensive Developmental Model for Alcohol Use Disorders in Men

The multiple risk factors for alcohol use (AU) and alcohol use disorders (AUDs) are interrelated through poorly understood pathways, many of which begin in childhood. 

In this report, the authors seek to develop an empirical, broad-based developmental model for the etiology of AU and AUDs in men. 

We assessed 15 risk factors in four developmental tiers in 1,794 adult male twins from the Virginia population based twin registry. 

The best fitting model explained 39% of the variance in late adolescent AU, and 30% of the liability to lifetime symptoms of AUD. 

AU and AUDs can be best understood as arising from the action and interaction of two pathways reflecting externalizing genetic/temperamental and familial/social factors. 

Peer group deviance was important in each pathway. Internalizing symptoms played a more minor role. Familial/social factors were especially important influences on AU, while genetic/temperamental factors were more critical for AUDs. 

We conclude that AU and AUDs in men are complex traits influenced by genetic, family, temperamental, and social factors, acting and interacting over developmental time.

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News Release - Action needed to reduce health impact of harmful alcohol use

Wider implementation of policies is needed to save lives and reduce the health impact of harmful alcohol drinking, says a new report launched today by WHO. Harmful use of alcohol results in the death of 2.5 million people annually, causes illness and injury to many more, and increasingly affects younger generations and drinkers in developing countries. 

Harmful use of alcohol is defined as excessive use to the point that it causes damage to health and often includes adverse social consequences.   > > > >   Read More

Lifestyle, health characteristics and alcohol abuse in young adults who are non-daily smokers

Despite the decline in the prevalence of tobacco use in many countries, including Brazil, there are growing numbers of smokers who continue to smoke at a low daily rate, or less frequently (non-daily smokers). This group needs to be better characterized in order to direct preventive actions and public health policies. 

The aim here was to compare lifestyle, health characteristics and alcoholism problems among young adult smokers, non-daily smokers and non-smokers.  

This was a cross-sectional study in which volunteers from the university community and its surrounds in Santa Maria, State of Rio Grande do Sul, Brazil, were included between October 2007 and January 2008.  

Out of 1240 volunteers initially contacted in a university cafeteria, a total of 728 participants of mean age 22.45 ± 3.32 years were selected for final analysis. Data were collected using structured questionnaires.  

In general, it was observed that the non-daily smokers showed intermediate characteristics in relation to the smokers and non-smokers. However, there was a significant association between non-daily smoking and alcohol abuse. The non-daily smokers presented an odds ratio of 2.4 (95% confidence interval: 1.10-5.48) in relation to the daily smokers and an odds ratio of 3.3 (confidence interval: 1.7-6.5) in relation to the non-smokers, with regard to presenting a positive CAGE test, thereby indicating alcohol abuse or dependence.  

The study suggested that non-daily smoking and alcohol consumption were concomitant behaviors.

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When is social marketing not social marketing?

The paper aims to discuss the thorny issues of industry-funded social marketing campaigns. Can the tobacco industry be trusted to educate our children about the dangers of smoking? Is a brewer the best source of health promotion? The paper argues for transparency and critical appraisal. 

The paper looks at the issues of tobacco and alcohol in more detail, emphasises the need for caution and suggests guidelines for future practice.

The fiduciary duty of the corporation means that all its efforts – including any social marketing campaigns or corporate social responsibility – must be focused first and foremost on the success of the business and the enhancement of shareholder value; any wider public health benefits will inevitably be subjugated to this core purpose. And there is good evidence to show that the principal beneficiaries of apparently public-spirited campaigns run by tobacco and alcohol companies are the sponsors. In the hands of a corporation, then, social marketing will always transmute into commercial marketing. 

We should then proceed with our eyes wide open, alert to the danger of counterproductive outcomes, armed with independent evaluation and in the full knowledge that wherever industry-funded efforts to educate the public replace those run by objective third parties, harm will be done.

The paper, concerned with industry-sponsored social marketing, broadens the discussion beyond communications. It shows that it is necessary to consider the whole marketing mix, not simply advertising, when discussing social marketing.

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An Alcohol Training Program Improves Chinese Nurses’ Knowledge, Self-Efficacy, and Practice: A Randomized Controlled Trial

Excessive alcohol use has been associated with health, social and legal problems. Helping health care providers to manage hazardous or harmful drinkers is an important worldwide issue. Alcohol is a legal and accessible substance in Taiwan and is viewed as an acceptable drink for relieving stress and enhancing socialization in Chinese culture. These cultural factors may contribute to drinking problems being easily ignored and to lack of alcohol training programs for health care providers.
For this randomized controlled clinical trial with 1- and 3-month posttests, six hospitals were randomly selected throughout Taiwan and were randomly assigned to an experimental or control group. In these hospitals, nurses were selected from the Emergency Department, psychiatric, and gastrointestinal medical-surgical units where most patients with alcohol problems are seen. For the experimental group, nurses received a 1.5-hour alcohol training program consisting of an introduction to alcohol, factors influencing alcohol drinking, impacts of high-risk drinking on a person, as well as introduction to and practice of the Alcohol Use Disorders Identification Test and brief alcohol intervention. The program also discussed Taiwanese nurses’ perceived barriers and facilitators to intervening for problem alcohol use. Teaching strategies included lecture, discussion, demonstration, practice, role-playing, and sharing experiences. The control group did not receive any training. Data were collected at pretest, 1-month, and 3-month posttests using a self-report questionnaire on knowledge, self-efficacy, clinical practice scales, and a demographic form.
The study was completed by 395 nurses, including 191 nurses in the experimental group and 204 nurses in the control group. Knowledge scores significantly improved in the experimental group at the 1- and 3-month posttests but not for the control group. Similarly, nurses’ self-efficacy and clinical practice scores significantly improved in the experimental group at the 3-month posttest but not for the control group.
Our results suggest that the alcohol training program could be used to enhance nurses’ alcohol knowledge, self-efficacy, and clinical practice not only in Taiwan but also other countries.

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Assessing the Dimensionality of Lifetime DSM-IV Alcohol Use Disorders and a Quantity–Frequency Alcohol use Criterion in the Australian Population: a Factor Mixture Modelling Approach

With the revision of the DSM-IV underway, two important research issues currently dominate the addiction literature: (a) how can the dimensionality of DSM-IV alcohol use disorders (AUD) diagnostic criteria best be described? and (ii) should a quantity–frequency alcohol use (QF) criterion be added to the existing diagnostic criteria set in the DSM-V? The current study addressed these aims by analysing lifetime data from a recent Australian population survey. 

Data from adults screened for lifetime DSM-IV AUD in the 2007 National Survey on Mental Health and Wellbeing (NSMHWB) were analysed (n = 5409). A series of alternative factor analytic, latent class and factor mixture or ‘hybrid’ models were used to assess the dimensionality of lifetime DSM-IV AUD diagnostic criteria and a lifetime QF criterion.
Examination of the goodness-of-fit indices revealed that a one-factor or a two-factor model, a three-class latent class model or a two-factor zero-class hybrid model, were all acceptable models for the data. A simple structure one-factor model was considered to be the most parsimonious and theoretically meaningful model, given the high correlation between the abuse and dependence factors (0.874) in the two-factor model. The inclusion of the QF criterion did not enhance the fit of the one-factor model.
Incorporating both dimensional and categorical conceptions of lifetime AUD did not provide substantial gains over a simple structure unidimensional model of AUD severity. The utility of a QF use criterion in helping to diagnose AUD is questionable. These findings should be of relevance to the DSM-5 substance use disorder workgroup. 

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    Global Status report on alcohol and health 2011

    The Global status report on alcohol and health (2011) presents a comprehensive perspective on the global, regional and country consumption of alcohol, patterns of drinking, health consequences and policy responses in Member States. It represents a continuing effort by the World Health Organization (WHO) to support Member States in collecting information in order to assist them in their efforts to reduce the harmful use of alcohol, and its health and social consequences

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    Country profiles 2011

    Thursday, February 10, 2011

    COMT and ALDH2 polymorphisms moderate associations of implicit drinking motives with alcohol use

    Dual process models of addiction emphasize the importance of implicit (automatic) cognitive processes in the development and maintenance of substance use behavior. Although genetic influences are presumed to be relevant for dual process models, few studies have evaluated this possibility. 

    The current study examined two polymorphisms with functional significance for alcohol use behavior (COMT Val158Met and ALDH2*2) in relation to automatic alcohol cognitions and tested additive and interactive effects of genotype and implicit cognitions on drinking behavior. 

    Participants were college students (n = 69) who completed Implicit Association Tasks (IATs) designed to assess two classes of automatic drinking motives (enhancement motives and coping motives). 

    Genetic factors did not show direct associations with IAT measures; however, COMT and ALDH2 moderated associations of implicit coping motives with drinking outcomes. 

    Interaction effects indicated that associations of implicit motives with drinking outcomes were strongest in the context of genetic variants associated with relatively higher risk for alcohol use (COMT Met and ALDH2*1). 

    Associations of genotype with drinking behavior were observed for ALDH2 but not COMT

    These findings are consistent with the possibility that genetic risk or protective factors could potentiate or mitigate the influence of reflexive cognitive processes on drinking behavior, providing support for the evaluation of genetic influences in the context of dual process models of addiction.

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    Wednesday, February 9, 2011

    Under-reporting of foetal alcohol spectrum disorders: an analysis of hospital episode statistics

    Internationally, 0.97 per 1,000 live births are affected by foetal alcohol syndrome (FAS). However, prevalence intelligence has been limited in the UK, hindering the development of appropriate services. 

    This analysis compares hospital admissions over time, between regions and with alcohol-related admissions for adult females to assess whether established patterns (such as the North experiencing elevated harms) can be identified.

    A retrospective analysis of hospital admissions data (April 2002 to March 2008) for foetal alcohol spectrum disorder (FASD)-related conditions: foetal alcohol syndrome (dysmorphic) (n=457); foetus and newborn affected by maternal use of alcohol (n=157); maternal care for (suspected) damage to foetus from alcohol (n=285); and 322,161 women admitted due to alcohol-related conditions.

    Whilst the rate of admission for alcohol-related conditions in women aged 15-44 years increased significantly by 41% between 2002/03 and 2007/08 (p<0.0001), no such increases were seen in the numbers of FASD-related conditions (all p<0.05). Established regional rates of admission for alcohol-related conditions in women aged 15-44 years old were not associated with admission for FASD-related conditions.

    It would be expected that the North West and North East regions, known to have higher levels of alcohol harm would have higher levels of FASD-related conditions. However, this was not reflected in the incidence of such conditions, suggesting under-reporting. With incomplete datasets, intelligence systems are severely limited, hampering efforts to develop targeted interventions. Improvements to intelligence systems, practitioner awareness and screening are essential in tackling this.

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    Moderating Effects of a Craving Intervention on the Relation Between Negative Mood and Heavy Drinking Following Treatment for Alcohol Dependence

    Negative affect is a significant predictor of alcohol relapse, and the relation between negative affect and drinking has been shown to be strongly mediated by alcohol craving. Thus, targeting craving during treatment could potentially attenuate the relation between negative affect and drinking. 

    The current study is a secondary analysis of data from the COMBINE study, a randomized clinical trial that combined pharmacotherapy with behavioral intervention in the treatment of alcohol dependence. 

    Our goal in the current study was to examine whether a treatment module that targeted craving would predict changes in negative mood during the 16-week combined behavioral intervention (n = 776) and the relation among changes in mood, craving, and changes in heavy drinking during treatment and 1 year posttreatment.  

    Changes in negative mood were significantly associated with changes in heavy drinking during treatment (f2 = 0.78). Participants (n = 432) who received the craving module had significantly fewer heavy drinking days during treatment (d = 0.31), and receiving the module moderated the relation between negative mood and heavy drinking during treatment (f2 = 0.92) and 1 year posttreatment (f2 = 0.03). Moderating effects of the craving module were mediated by changes in craving during treatment. Within-subject analyses indicated significant pre- to postmodule reductions in negative mood. Additionally, postmodule craving significantly mediated the association between negative mood and heavy drinking during treatment and at posttreatment.

    The craving module of the combined behavioral intervention may weaken the relation between negative affect and heavy drinking by fostering greater decreases in craving during treatment.

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    Longitudinal association of preference-weighted health-related quality of life measures and substance use disorder outcomes

    To examine the construct validity of generic preference-weighted health-related quality of life measures in a sample of patients with a substance use disorder (SUD).
    Longitudinal (baseline and 6-month follow-up) data from a research study that evaluated interventions to improve linkage and engagement with SUD treatment.
    A central intake unit that referred patients to seven SUD treatment centers in a Midwestern US metropolitan area.
    A total of 495 individuals with a SUD.
    Participants completed two preference-weighted measures: the self-administered Quality of Well-Being scale (QWB-SA) and the standard gamble weighted Medical Outcomes Study SF-12 (SF-6D). They were also administered two clinical assessments: all seven domains of the Addiction Severity Index (ASI) and a symptom checklist based on the DSM-IV. Construct validity was determined via the relationships between disease-specific SUD and generic measures.
    In unadjusted analyses, the QWB-SA and SF-6D change scores were correlated significantly with six ASI subscale change scores, but not with employment status. 

    In adjusted repeated-measures analyses, three of seven ASI subscale scores were significant predictors of QWB-SA and 5/7 ASI subscale scores were significant predictors of SF-6D. 

    Abstinence and problematic use at follow-up were significant predictors of QWB-SA and SF-6D. Effect sizes ranged from 0.352 to 0.400 for abstinence and −0.484 to −0.585 for problematic use.
    Generic preference-weighted health-related quality of life measures show moderate to good associations with substance-use specific measures and in certain circumstances can be used in their stead. 

    This study provides further support for the use of the Quality of Well-Being scale and Medical Outcomes Study SF-12 in clinical and economic evaluations of substance use disorder interventions.

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    Substance Abuse Treatment for Older Adults in Private Centers

    By 2020, an estimated 4.4 million older adults will require substance abuse treatment compared to 1.7 million in 2000-01. 

    This study examined the availability of special services for older adults, adoption of recommended treatment approaches, and organizational characteristics of centers that offer special services. Data were collected via face-to-face interviews with administrators and/or clinical directors from a nationally representative sample of 346 private treatment centers participating in the 2006-07 National Treatment Center Study. 

    Results indicated that only 18% provided special services for older adults; age-specific recommendations were generally adopted; more older adult-specialty centers offered prescription drug addiction treatment, primary medical care, and housing assistance. 

    The proportion of patients with Medicare payment predicted availability. 

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    Alcoholics Anonymous and the Minnesota Model of Treatment in Iceland

    This study was undertaken to provide an initial characterization of the current status of patients admitted to an alcoholism treatment program in Iceland. Consistent with the Minnesota Model, 12-step facilitation has been a central component of the program since its inception. 

    Of the 94 patients assessed in this study, 67% were male and 40% had attended over 90 AA meetings prior to admission. The mean number of drinking days during the month prior to admission was 15.51 days and the mean length of hospital stay was 12.32 days. At time of hospital discharge, 39% were referred to residential treatment. 

    Significant predictors of referral to residential treatment included having attended less than 90 AA meetings prior to admission and length of stay. 

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    The 1258 G>A polymorphism in the neuropeptide Y gene is associated with greater alcohol consumption in a Mediterranean population

    Neuropeptide Y (NPY) is a neurotransmitter widely distributed in the central nervous system. Several studies have demonstrated that increases of NPY are associated with reduced alcohol intake and anxiety manifestations. The Leu7Pro polymorphism in the NPY has been associated with alcohol consumption, but evidence is scarce. 

    In the Spanish Mediterranean population, this variant is not polymorphic. 

    Thus, our aim is to identify novel functional variants in the NPY and to investigate the impact of these markers and others previously described on alcohol consumption in this population. 

    A total of 911 subjects (321 men and 590 women) from the Spanish Mediterranean population were recruited. Alcohol consumption, and demographic and lifestyle variables were measured. Nucleotide sequence determination and SNP analyses were carried out. 

    Only one exonic SNP was detected by direct sequencing (1258 G>A or rs9785023; allele frequency 0.47). From the intronic markers chosen (483 A>G or rs13235938, 2517 A>G or rs4722342, and 7065 A>G or rs4722343), only the two latter ones were polymorphic (allele frequencies 0.46 and 0.04, respectively), and none of them were associated with alcohol consumption. 

    However, the 1258 G>A SNP was associated (recessive pattern) with higher alcohol intake. This association was particularly relevant in men with high alcohol intake (59.1 ± 5.0 g/day in AA as opposed to 40.6 ± 7.5 in the G carriers, P = .022) and women with moderate alcohol intake (7.3 ± 5.5 g/day in AA as opposed to 4.6 ± 3.9 g/day in G carriers, P = .048). 

    The 1258 G>A polymorphism in the NPY is associated with higher alcohol consumption in the Mediterranean population.

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    Commentary on Lopez-Quintero et al. (2011)

    Remission and relapse – the Yin-Yang of addictive disorders


    Molecular Pathogenesis of Hepatocellular Carcinoma

    Hepatocellular carcinoma (HCC) is one of the major causes of death among cirrhotic patients, being viral hepatitis and alcohol abuse, the main risk factors for its development. 

    The introduction of highly sophisticated genomic technologies has spurred extensive research on the molecular pathogenesis of this devastating disease. 

    Several signaling cascades have been consistently found dysregulated in HCC (e.g., WNT-β-catenin, PI3K/AKT/MTOR, RAS/MAPK, IGF, HGF/MET, VEGF, EGFR, and PDGF). 

    In addition, there have been numerous molecular classifications proposed for this disease, what provides an additional hint about its genomic complexity. 

    The importance of knowing the molecular drivers of HCC is underscored by the positive results of a molecular targeted agent, sorafenib, able to improve survival in patients with advanced disease. 

    This review will briefly outline key concepts in alcohol-related hepatocarcinogenesis, and provide some insight regarding current trends in translating HCC genomics into clinical management of the disease.

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    Genetics and Alcohol: A Lethal Combination in Pancreatic Disease?

    An association between alcohol consumption and pancreatic diseases has been recognized for decades, but the absolute risk for pancreatic disease for individuals who drink alcohol is low. Other than smoking, few additional environmental factors have been identified, which suggests that genetic risk factors may be important.

    Studies in our laboratory using the Lieber-DeCarli feeding technique demonstrate that alcohol causes oxidative stress and mitochondrial damage and alters neruohormonal regulation of the pancreas after a threshold dose is exceeded, which makes the pancreas susceptible to withdrawal hypersensitivity and acute pancreatitis. 

    Alcohol also shifts cell death from apoptosis to necrosis and promotes fibrosis through anti-inflammatory immune mechanisms. Others have demonstrated that alcohol lowers the threshold for trypsin activation in acinar cells, which increases sensitivity to triggering pancreatitis. 

    In addition, we used the Lieber-DeCarli diet plus recurrent acute pancreatitis insults to develop the first animal model of chronic pancreatitis that mimics human disease. 

    Finally, our North American Pancreatitis Study 2 (NAPS2), which was built on insights from animal studies, confirmed the threshold effect predicted by Charles Lieber (>5 drinks per day and >35 drinks/week).

    These studies and others also defined distinctive roles of alcohol and genetics in the etiology and progression of chronic pancreatitis.

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    Inter-Hemispheric Functional Connectivity Disruption in Children With Prenatal Alcohol Exposure

    MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual-motor skill, verbal learning, and executive functioning. 

    The goal of this study was to determine whether inter-hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter-hemispheric functional connectivity and disrupted cognition.
    Twenty-one children with FASD and 23 matched controls underwent a 6-minute resting-state functional MRI scan as well as anatomical imaging and DTI. Using a semi-automated method, we parsed the corpus callosum and delineated 7 inter-hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right–left correlations in resting fMRI signal were computed for these sets of ROIs, and group comparisons were made. Correlations with facial dysmorphology, cognition, and DTI measures were computed.
    A significant group difference in inter-hemispheric functional connectivity was seen in a posterior set of ROIs, the para-central region. Children with FASD had functional connectivity that was 12% lower than in controls in this region. Subgroup analyses were not possible owing to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para-central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures, and Wechsler perceptual reasoning ability.
    Inter-hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para-central) that are connected by posterior callosal fiber projections. 

    We have previously shown microstructural abnormalities in these same posterior callosal regions, and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning.

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    l-cysteine Prevents Ethanol-Induced Stimulation of Mesolimbic Dopamine Transmission

    Acetaldehyde (ACD), the first metabolite of ethanol (EtOH) appears to be involved in many of the psychoactive effects of its parent compound, including EtOH-induced activation of the mesolimbic dopamine (DA) system, thereby suggesting that ACD may participate in EtOH motivational properties. 

    l-cysteine (Lcys), a thiol compound sequestering ACD, is able to prevent the behavioral effect of EtOH and ACD. 

    Here we show that the stimulatory effect of both EtOH and ACD on the mesolimbic DA system is prevented by Lcys pretreatment.
    Male Wistar rats were implanted with a microdialysis probe in the nucleus accumbens shell (NAccs), and pretreated intraperitoneally with Lcys (30 mg/kg) before intragastric administration of EtOH (1 g/kg) or ACD (20 mg/kg) or before intraperitoneal administration of morphine (2.5 mg/kg).
    Pretreatment with Lcys prevented both EtOH and ACD-induced DA release in the NAccs without influencing morphine-induced DA release, suggesting that Lcys specifically affects EtOH-induced DA release possibly through ACD sequestering.
    Our results underscore the role of ACD on EtOH-induced stimulation of DA mesoaccumbens system and support the notion that thiol compounds such as Lcys, by modulating EtOH-derived ACD bioavailability, would blunt EtOH rewarding properties.

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    Alcohol-Metabolizing Enzyme Gene Polymorphisms in the Basque Country, Morocco, and Ecuador

    Genes ADH1B and ADH1C have certain functional SNPs that are related to alcoholism. The frequencies of these polymorphisms vary between populations, so studying them in populations made up of groups with different phylogeographic origins requires an individualized analysis of each group. 

    In the Basque Country, various recently arrived foreign groups live side by side with the original Southern European population, particularly North Africans from Morocco and Hispanics from Ecuador. 

    This study sets out to examine the distribution of the frequencies of alleles that encode alcohol dehydrogenase with different metabolization rates, as higher rates make for greater susceptibility to alcoholism.
    Four SNPs: rs1229984, rs2066702, rs698, and rs1693482 using Taqman technology with a Rt-PCR were studied in a sample of 114 European individuals originating from the Basque Country, 100 North Africans from Morocco, and 109 Hispanics from Ecuador. The allele and genotype frequencies were calculated using Genepop v4.0. The most frequent haplotypes were estimated using the ELB algorithm with Arlequin v3.01. A breakdown of the complete disequilibrium commonly observed between the 2 missense polymorphisms that distinguish the common ADH1C alleles rs698 and rs1693482 was observed and confirmed by sequencing in 2 individuals from the Basque Country.
    A higher frequency of protective allele ADH1C*1 was found in the North African population group. Haplotype combinations are also studied, and the rare association of alleles ADH1B*2–ADH1C*2 was observed in the Southern European group in the Basque Country, along with an allele not hitherto described in the ADH1C locus.
    This study provides the first data published on the allele and genotype frequencies of the ADH1C locus in the Moroccan population and on the ADH1B and ADH1C loci in the Ecuadorian population. 

    The study shows differences in the distribution of the frequency of allele ADH1C*1 between the Basque Country and Moroccan populations, and a new allele not described to date.

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    Comorbid Psychiatric Diagnoses Among Individuals Presenting to an Addiction Treatment Program for Alcohol Dependence

    A retrospective patient record review was conducted to examine comorbid psychiatric diagnoses, and comorbid substance use, among 465 patients below 45 years of age, presenting to a national alcohol addiction treatment unit in Dublin, between 1995 and 2006.
    Rates were high for depressive disorder (25.3%) particularly among females (35.4%). Lifetime reported use of substances other than alcohol was 39.2%, and further analysis showed significantly higher rates of deliberate self-harm among this group. 

    Lifetime reported use of ecstasy was also significantly associated with depression in this alcohol-dependent population using logistic regression analysis. 

    Implications and limitations of the findings are discussed.

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    A retrospective patient record review was conducted to examine comorbid psychiatric diagnoses, and comorbid substance use, among 465 patients below 45 years of age, presenting to a national alcohol addiction treatment unit in Dublin, between 1995 and 2006. Rates were high for depressive disorder (25.3%) particularly among females (35.4%). Lifetime reported use of substances other than alcohol was 39.2%, and further analysis showed significantly higher rates of deliberate self-harm among this group. Lifetime reported use of ecstasy was also significantly associated with depression in this alcohol-dependent population using logistic regression analysis. Implications and limitations of the findings are discussed.

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    Imaging of alcohol-induced dopamine release in rats: Preliminary findings with [11C]raclopride PET

    Microdialysis studies report that systemic alcohol increases extracellular dopamine in the rat striatum. 

    The present study examined whether changes in striatal dopamine could be detected in rats using small animal positron emission tomography (PET). 

    PET images were acquired in 44 alcohol-naïve male Wistar and alcohol-preferring (P) rats. Subjects received up to three [11C]raclopride scans (rest, alcohol, and saline). Animals were anesthetized with isoflurane and secured on a stereotactic-like holder during all scans. Blood samples were collected from the tail or lateral saphenous vein of 12 animals 10 minutes after tracer injection for determination of blood alcohol concentration (BAC). Time activity curves were extracted from the striatum and the cerebellum and binding potential (BPND) was calculated as a measure of D2 receptor availability. 

    Wistars given 1.0g/kg alcohol (20%v/v) I.V. or 3.0g/kg alcohol (20%v/v) I.P showed significant alcohol-induced decreases in BPND.
    In P rats (given 1.5, 2.25, or 3.0 g/kg alcohol), no individual group showed a statistical effect of alcohol on BPND, but taken together, all P rats receiving I.P. alcohol had significantly lower BPND than rest or saline scans. 

    Large decreases in BPND were primarily observed in rats with BAC above 200 mg%. Also, a significant difference was found between baseline BPND of Wistars who had undergone jugular catheterization surgery for I.V. alcohol administration and those who had not. 

    These preliminary results suggest that alcohol-induced DA release in the rat striatum is detectable using small animal PET given sufficiently large cohorts and adequate blood alcohol levels.

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    KCNJ6 is Associated with Adult Alcohol Dependence and Involved in Gene × Early Life Stress Interactions in Adolescent Alcohol Drinking

    Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. 

    Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. 

    KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. 

    We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. 

    One SNP, rs2836016, was found to be associated with alcohol dependence (p=0.01, false discovery rate). 

    We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene–environment interactions. 

    In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p=0.01).
    Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. 

    We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.

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    Past Month Alcohol Use Among U.S. 8th, 10th, and 12thGraders Reaches Record Low

    The percentage of 8th, 10th, and 12thgraders reporting past month use of alcohol reached record lows* in 2010, according to data from the national Monitoring the Future study. 

    Less than one-half (41.2%) of 12thgraders reported drinking at least one sip of alcohol in the past month in 2010, compared to the peak prevalence of 72.1% in 1978. 

    Past month prevalence rates among 8th(13.8%) and 10th(28.9%) graders are also at the lowest levels since these grades were first included in the study in 1991 (see figure below). 

    In addition, binge drinking—drinking five or more drinks in a row at least once in the two weeks prior to the survey—also continues to decrease in all three grades (data not shown). For example, 23.2% of 12thgraders reported binge drinking in 2010, compared to the peak of 41.4% in 1981.

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    Tuesday, February 8, 2011

    Husbands' and wives' alcohol use disorders and marital interactions as longitudinal predictors of marital adjustment.

    In this longitudinal study, the relationships among wives' and husbands' lifetime alcoholism status, marital behaviors, and marital adjustment were tested. 

    Participants were 105 couples from the Michigan Longitudinal Study (MLS), an ongoing multimethod investigation of substance use in a community-based sample of alcoholics, nonalcoholics, and their families. 

    At baseline (T1), husbands and wives completed a series of diagnostic measures, and lifetime diagnosis of alcohol use disorder (AUD, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.), was assessed. Couples completed a problem-solving marital interaction task 3 years later at T2, which was coded for the ratio of positive to negative behaviors. Couples also completed a measure of marital adjustment at T4 (9 years after T1 and 6 years after T2). 

    Results showed that husbands' lifetime AUD predicted lower levels of their wife's positive marital behaviors 3 years later but was not related to their own or their wife's marital adjustment 9 years from baseline. 

    By contrast, wives' lifetime AUD had direct negative associations with their own and their husband's marital satisfaction 9 years later, and wives' marital behaviors during the problem-solving task predicted their own and their husband's marital satisfaction 6 years later. 

    Findings indicate that marital adjustment in alcoholic couples may be driven more by the wives' than the husbands' AUD and marital behavior. Implications for intervention with alcoholic couples were discussed. 

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    The Disguise of Sobriety: Unveiled by Alcohol in Persons with an Aggressive Personality

    This investigation examined the factor structure of eight well-validated self-report measures that assess traits that fall under the rubric of an “aggressive personality” and then determined how those factor(s) moderated the association between alcohol intoxication and aggression. 

    Participants were 518 (252 men and 266 women) healthy social drinkers between 21 and 35 years of age. Following the consumption of an alcohol or a placebo beverage, participants were tested on a laboratory aggression paradigm in which electric shocks were received from, and administered to, a fictitious opponent. Aggression was operationalized as the shock intensities and durations administered to the opponent. 

    Results demonstrated a unidimensional factor structure for the aggressive personality traits which were then combined into a latent variable. The aggressive personality variable moderated the alcohol-aggression relation. 

    Specifically, alcohol was significantly more likely to increase aggression in persons with higher, compared with lower, aggressive personality scores.

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    Differential relationships of family drinking with alcohol expectancy among urban school children

    Positive alcohol outcome expectancy has consistently been linked with problematic drinking, but there is little population-based evidence on its role on early stages of drinking in childhood. The present study seeks to understand the extent to which drinking of family members is differentially associated with the endorsement of alcohol expectancy in late childhood.

    A representative sample of 4th and 6th graders (N=2455) drawn from 28 public schools in an urban region of Taiwan completed a self-administered paper-and-pencil questionnaire. Each student provided information on alcohol expectancy, drinking experiences, and individual and family attributes. Complex survey analyses were performed to evaluate the relationship, with stratification by children's alcohol drinking history.

    An estimated 29% of the 4th graders and 43% of the 6th graders had initiated alcohol consumption (over 40% of them had drank on three or more occasions). Alcohol drinking-related differences appear in both the endorsement and the correlates of alcohol expectancy. Positive alcohol expectancy was strongly associated with family drinking, particularly the dimension of "enhanced social behaviors"; negative alcohol expectancy was inversely associated with drinking frequency. Among alcohol naive children, significant connections appear between paternal drinking and three dimensions of positive alcohol expectancy (i.e., enhanced social behaviors:betawt =0.15, promoting relaxation or tension reduction:betawt =0.18, and global positive transformation:betawt =0.22).

    Individual tailored strategies that address family influences on alcohol expectancy may be needed in prevention programs targeting drinking behaviors in children. 

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    A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway

    Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. 

    Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. 

    We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. 

    We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. 

    Additionally, we show that, as in mammals, flies reared on ethanol have altered responses to ethanol vapor exposure as adults, including increased locomotor activation, resistance to the sedating effects of the drug and reduced tolerance development upon repeated ethanol exposure. 

    We have found that the developmental and behavioral defects are largely due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression. Transgenic expression of Dilp proteins in the larval brain suppressed both the developmental and behavioral abnormalities displayed by ethanol-reared adult flies. 

    Our results thus establish Drosophila as a useful model system to uncover the complex etiology of fetal alcohol syndrome. 

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    Adult Consequences of Late Adolescent Alcohol Consumption: A Systematic Review of Cohort Studies

    Although important to public policy, there have been no rigorous evidence syntheses of the long-term consequences of late adolescent drinking.

    This systematic review summarises evidence from general population cohort studies of drinking between 15–19 years old and any subsequent outcomes aged 20 or greater, with at least 3 years of follow-up study. Fifty-four studies were included, of which 35 were assessed to be vulnerable to bias and/or confounding. The principal findings are: (1) There is consistent evidence that higher alcohol consumption in late adolescence continues into adulthood and is also associated with alcohol problems including dependence; (2) Although a number of studies suggest links to adult physical and mental health and social consequences, existing evidence is of insufficient quality to warrant causal inferences at this stage.

    There is an urgent need for high quality long-term prospective cohort studies in order to better understand the public health burden that is consequent on late adolescent drinking, both in relation to adult drinking and more broadly. Reducing drinking during late adolescence is likely to be important for preventing long-term adverse consequences as well as protecting against more immediate harms.

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