Seminar - What is Addiction Neuroethics?

Professor Wayne Hall Seminar

Where:

UQCCR Main Auditorium Level 2 (Ground floor)

When:

Starts: Thursday, April 22, 2010 - 12:00 PM

Ends: Thursday, April 22, 2010 - 1:00 PM

Professor Wayne Hall is an NHMRC Australia Fellow in addiction neuroethics at the University of Queensland Centre for Clinical Research. He was formerly: Professor of Public Health Policy in the School of Population Health (2005-2010) and Director of the Office of Public Policy and Ethics at the Institute for Molecular Bioscience (2001-2005) at the University of Queensland; and Director of the National Drug and Alcohol Research Centre at UNSW (1994-2001). He has advised the World Health Organization on: the health effects of cannabis use; the effectiveness of drug substitution treatment; the scientific quality of the Swiss heroin trials; the contribution of illicit drug use to the global burden of disease; and the ethical implications of genetic and neuroscience research on addiction.. In 2001 he was identified by the Institute for Scientific Analysis as one of the world's most highly cited social scientists in the past 20 years. He was awarded an NHMRC Australia Fellowship in 2009 to research the public health, social policy and ethical implications of genetic and neuroscience research on drug use and addiction

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Onset Drinking: How It Is Related Both to Mother's Drinking and Mother–Child Relationships

Employing the National Longitudinal Survey of Youth (NLSY) as a sample of adolescents and their mothers, the present study connected the onset of adolescents’ drinking to certain posited risk and protective factors characterizing their families.

Via event history analysis and the discrete-time method, the data analysis involved more than 6,331 pair-interview-year units.

The results show that both peer influences and mother's daily alcohol consumption enhance the risk that an adolescent aged between 10 and 14 years will begin drinking.

At the same time, the quality of a mother's relationship with her child is an important posited protective factor delaying onset drinking.

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Request Reprint E-Mail: clo@ua.edu


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Prevalence and Correlates of At-Risk Drinking Among Older Adults: The Project SHARE Study.

At-risk drinking, excessive or potentially harmful alcohol use in combination with select comorbidities or medication use, affects about 10% of elderly adults and is associated with higher mortality. Yet, our knowledge is incomplete regarding the prevalence of different categories of at-risk drinking and their associations with patient demographics.

To examine the prevalence and correlates of different categories of at-risk drinking among older adults. DESIGN: Cross-sectional analysis of survey data. SUBJECTS: Current drinkers ages 60 and older accessing primary care clinics around Santa Barbara, California (n = 3,308).

At-risk drinkers were identified using the Comorbidity Alcohol Risk Evaluation Tool (CARET). At-risk alcohol use was categorized as alcohol use in the setting of 1) high-risk comorbidities or 2) high-risk medication use, and 3) excessive alcohol use alone. Adjusted associations of participant characteristics with at-risk drinking in each of the three at-risk categories and with at-risk drinking of any kind were estimated using logistic regression.

Over one-third of our sample (34.7%) was at risk. Among at-risk individuals, 61.9% had alcohol use in the context of high-risk comorbidities, 61.0% had high-risk medication use, and 64.3% had high-risk alcohol behaviors. The adjusted odds of at-risk drinking of any kind were decreased and significant for women (odds ratio, OR = 0.41; 95% confidence interval: 0.35-0.48; p-value < 0.001), adults over age 80 (OR = 0.55; CI: 0.43-0.72; p < 0.001 vs. ages 60-64), Asians (OR = 0.40; CI: 0.20-0.80; p = 0.01 vs. Caucasians) and individuals with higher education levels. Similar associations were observed in all three categories of at-risk drinking.

High-risk alcohol use was common among older adults in this large sample of primary care patients, and male Caucasians, those ages 60-64, and those with lower levels of education were most likely to have high-risk alcohol use of any type. Our findings could help physicians identify older patients at increased risk for problems from alcohol consumption.

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Request Reprint E-Mail: abarnes2@gmail.com


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The effects of minimum legal drinking age 21 laws on alcohol-related driving in the United States

To examine trends in alcohol consumption and alcohol-related crashes among people younger than 21 in the United States and to review evidence on the effects of minimum legal drinking age (MLDA) laws.

Trends in alcohol-related crashes and alcohol consumption among young people were examined, and studies on the effects of lowering and raising the drinking age were reviewed.

MLDA laws underwent many changes during the 20th century in the United States. Since July 1988, the MLDA has been 21 in all 50 states and the District of Columbia. Surveys tracking alcohol consumption among high school students and young adults found that drinking declined since the late 1970 s, and most of the decline occurred by the early 1990 s. These were the years when states were establishing, or reinstating, a MLDA-21.

Among fatally injured drivers ages 16–20, the percentage with positive BACs declined from 61% in 1982 to 31% in 1995, a bigger decline than for older age groups; declines occurred among the ages directly affected by raising MLDAs (ages 18–20) and among young teenagers not directly affected (ages 16–17).

Almost all studies designed specifically to gauge the effects of drinking age changes show MLDAs of 21 reduce drinking, problematic drinking, drinking and driving, and alcohol-related crashes among young people. Yet many underage people still drink, many drink and drive, and alcohol remains an important risk factor in serious crashes of young drivers, especially as they progress through the teenage years. Stepped-up enforcement of MLDA and drinking and driving laws can reduce underage drinking.

Recent efforts to lower MLDAs to 18 and issue licenses to drink upon completion of alcohol education have gained local and national media attention. There is no evidence that alcohol education can even partially replace the effect of MLDA-21.

The cause and effect relationship between MLDAs of 21 and reductions in highway crashes is clear. Initiatives to lower the drinking age to 18 ignore the demonstrated public health benefits of MLDAs of 21.

Lowering the drinking age to 18 will increase highway crash deaths among young people.

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Request Reprint E-Mail: amccartt@iihs.org

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“Everyone Deserves Services No Matter What”: Defining Success in Harm-Reduction-Based Substance User Treatment

This article reports qualitative interview data from a study of participant-generated outcomes of two harm reduction programs in the United States.

We address the question:“What does success in harm-reduction-based substance user treatment look like?”

Providers in this study understood harm reduction to adhere to notions of “any positive change,” client centeredness, and low-threshold services.

Participants reported changes in demarginalization, engagement in the program, quality of life, social functioning, changes in substance use, and changes in future goals and plans.

The nature of these changes is difficult to articulate within traditional notions of success (i.e., abstinence, program completion, etc.).

We conclude that participants in harm reduction programs experience tangible positive changes but that legitimation of these changes calls for a reconceptualization of “outcomes” and“success” in the current context of substance user treatment and research.

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Request Reprint E-Mail: hsophialee@gmail.com.

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Cohabitation, Gender, and Alcohol Consumption in 19 Countries: A Multilevel Analysis

We used an ecological paradigm and multilevel analytic techniques to analyze gender-specific relationships of cohabitation (versus marriage) to drinking in 19 countries (n = 32,922) and to“heavy episodic drinking” (HED) in 17 countries (n = 24,525) in surveys (1996–2004) from Gender, Alcohol, and Culture: An International Study.

Cohabitation was associated with elevated risk of HED among drinkers of both genders, controlling for age, education, and societal characteristics. The association between cohabitation and HED tended to be stronger for female drinkers than for male drinkers. HED was more prevalent among younger drinkers, especially among younger women in countries with higher per capita gross domestic product.

Cross-culturally, cohabiters deserve special attention in prevention efforts for hazardous drinking, considering both individual-level and societal factors.

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Request Reprint E-Mail: youliqing@hotmail.com

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“Alcohol is Something That Been With Us Like a Common Cold”: Community Perceptions of American Indian Drinking

This study examined tribal members’ perspectives on alcohol, risk factors, consequences, and community responses.

Focus groups were conducted with five American Indian tribes between 1997 and 2001. Participants were knowledgeable of the cultural lives of their reservation communities.

Although there was agreement regarding the pervasiveness of heavy drinking, participants reported different opinions about the meaning of alcohol and appropriate intervention strategies.

Three dilemmas were identified, suggesting that community ambivalence may serve as a barrier to reducing problem drinking. Implications, limitations, and future research directions are discussed.

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Request Reprint E-Mail:

nyuan@email.arizona.edu.

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The Effect of Alcohol Treatment on Social Costs of Alcohol Dependence: Results From the COMBINE Study

The COMBINE (combined pharmacotherapies and behavioral intervention) clinical trial recently evaluated the efficacy of pharmacotherapies, behavioral therapies, and their combinations for the treatment of alcohol dependence.

Previously, the cost and cost-effectiveness of COMBINE have been studied. Policy makers, patients, and nonalcohol-dependent individuals may be concerned not only with alcohol treatment costs but also with the effect of alcohol interventions on broader social costs and outcomes.

To estimate the sum of treatment costs plus the costs of health care utilization, arrests, and motor vehicle accidents for the 9 treatments in COMBINE 3 years postrandomization.

Multivariate results show no significant differences in mean costs between any of the treatment arms as compared with medical management (MM) + placebo for the 3-year postrandomization sample. The median costs of MM + acamprosate, MM + naltrexone, MM + acamprosate + naltrexone, and MM + acamprosate + combined behavioral intervention were significantly lower than the median cost for MM + placebo.

The results show that social cost savings are generated relative to MM + placebo by 3 years postrandomization, and the magnitude of these cost savings is greater than the costs of the COMBINE treatment received 3 years prior.

Our study suggests that several alcohol treatments may indeed lead to reduced median social costs associated with health care, arrests, and motor vehicle accidents.

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Request Reprint E-Mail: gaz rti.org

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PhenX consensus measures for Phenotypes and eXposures

PhenX is a three year project led by RTI International and funded by the National Human Genome Research Institute (NHGRI) to contribute to the integration of genetics and epidemiologic research PhenX has prioritized 21 research domains related to complex diseases and environmental exposures Consensus building is being used to develop a recommended minimal set of high priority measures for use in Genome-wide Association Studies (GWAS) and other large-scale genomic research efforts High priority measures will maximize benefits of future research by enabling cross-study comparisons and analysis Selection and specification of the measures are driven by the scientific community via the PhenX Steering Committee, Working Groups and community consensus. The PhenX Toolkit presents the selected high priority measures to the scientific community

PhenX Toolkit Release Notes

PhenX Home Site _______________________________________

Alcohol-Induced Neurodegeneration, Suppression of Transforming Growth Factor-β, and Cognitive Impairment in Rats: Prevention by Group II Metabotropic

Glutamatergic neurotransmission has been implicated in mechanisms of alcohol-induced neurodegeneration and cognitive impairment, but the underlying mechanism remains unknown.

Here, we examined whether the group II metabotropic glutamate receptor agonist LY379268 prevents neuronal death and learning deficits in a rat model of binge-like exposure to alcohol.

Following 4-day binge alcohol exposure concurrent with LY379268 or vehicle treatment, Fluoro-Jade B and transforming growth factor-β (TGF-β) staining were carried out, and reversal learning in the Morris water maze was assessed.

Fluoro-Jade B staining indicating neurodegeneration was most extensive in the ventral hippocampus and the entorhinal cortex (EC). LY379268 was potently neuroprotective in the EC but not in the dentate gyrus of the hippocampus.

In parallel, binge alcohol exposure suppressed TGF-β expression in both the EC and dentate gyrus, whereas LY379268 increased TGF-β in the EC only.

Finally, neuroprotective effects of LY379268 were accompanied by prevention of deficits in spatial reversal learning.

Our data support a neuroprotective role for group II metabotropic glutamate receptor agonists and TGF-β in alcohol-induced neurodegeneration.

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Request Reprint E-Mail: markus.heilig@mail.nih.gov

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Metabotropic Glutamate Receptor 5 Activity in the Nucleus Accumbens Is Required for the Maintenance of Ethanol Self-Administration in a Rat Genetic Mo

Systemic modulation of Group I and II metabotropic glutamate receptors (mGluRs) regulate ethanol self-administration in a variety of animal models. Although these receptors are expressed in reward-related brain regions, the anatomical specificity of their functional involvement in ethanol self-administration remains to be characterized.

This study sought to evaluate the functional role of Group I (mGluR5) and Group II (mGluR2/3) in mesocorticolimbic brain regions in ethanol self-administration.

Alcohol-preferring (P) rats, a genetic model of high alcohol drinking, were trained to self-administer ethanol (15% v/v) versus water in operant conditioning chambers. Effects of brain site-specific infusion of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and the mGluR2/3 agonist were then assessed on the maintenance of self-administration.

Microinjection of the mGluR5 antagonist MPEP in the nucleus accumbens reduced ethanol self-administration at a dose that did not alter locomotor activity. By contrast, infusion of the mGluR2/3 agonist LY379268 in the nucleus accumbens reduced self-administration and produced nonspecific reductions in locomotor activity.

The mGluR5 involvement showed anatomical specificity as evidenced by lack of effect of MPEP infusion in the dorsomedial caudate or medial prefrontal cortex on ethanol self-administration.

To determine reinforcer specificity, P-rats were trained to self-administer sucrose (.4% w/v) versus water, and effects of intra-accumbens MPEP were tested. The MPEP did not alter sucrose self-administration or motor behavior.

These results suggest that mGluR5 activity specifically in the nucleus accumbens is required for the maintenance of ethanol self-administration in individuals with genetic risk for high alcohol consumption.

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Request Reprint E-Mail: chodge@med.unc.edu

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Serotonin 1B Receptor Imaging in Alcohol Dependence

Although animal models suggest that alcohol dependence (AD) is associated with elevations in the number of serotonin 1B receptors (5-HT_1BR), 5-HT_1BR levels have not been investigated in people with AD. The selective 5-HT_1BR antagonist radioligand, [¹¹C]P943, permits in vivo assessment of central 5-HT_1BR binding potential (BP_ND) with positron emission tomography. Because of its central role in AD, we were particularly interested in ventral striatal 5-HT_1BR BP_ND values.

Twelve medication-free, recently abstinent (at least 4 weeks) patients with AD (mean age 35.2 ± 10.2 years, 5 women) and 12 healthy control subjects (HC) (mean age 30.6 ± 9.2 years, 5 women) completed [¹¹C]P943 positron emission tomography on a high-resolution research tomograph. Individual magnetic resonance imaging scans were collected to exclude individuals with anatomical abnormalities and for coregistration. Imaging data were analyzed with a multilinear reference tissue model.

Ventral striatal 5-HT_1BR BP_ND values (2.01 ± .57% and 1.55 ± .09%, respectively; 29% between-group difference, p = .006) were increased in AD compared with HC subjects. No influence of demographic or clinical variables or amount of injected radiotracer was observed.

This study provides the first evidence that AD in humans is, like in rodent models, associated with increased levels of ventral striatal 5-HT_1BRs.

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Request Reprint E-Mail: alexander.neumeister@mssm.edu

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Press Release - Remembering the good times helps alcoholics stay sober

Recovering alcoholics who focus on positive experiences in their past may be more successful in managing their addiction. This is the finding of a study by Sarah Davies and Professor Gail Kinman of the University of Bedfordshire that was presented on the 16th April 2010, at the British Psychological Society’s Annual Conference in Stratford-upon-Avon.

A hundred and one members of Alcoholics Anonymous (53 per cent male) completed questionnaires that assessed the extent to which they were oriented towards the past, present or future, and whether this orientation was mostly positive or negative. They were also asked about their spiritual experiences, level of abstinence, compulsion to drink and anxiety.

The results showed that problem drinkers who were oriented towards the past and who had a positive view of their previous life experiences were more likely to be successful in managing alcohol dependency than those with a more negative focus on the past. Participants who held a present hedonistic orientation (focusing on having fun in the here and now) also tended to experience stronger compulsions to drink alcohol.

High levels of spirituality were also found to be a protective factor in helping recovering alcoholics stay sober and manage the anxiety associated with addiction and withdrawal. . . . . .

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Estimated effect of alcohol pricing policies on health and health economic outcomes in England: an epidemiological model

Although pricing policies for alcohol are known to be effective, little is known about how specific interventions affect health-care costs and health-related quality-of-life outcomes for different types of drinkers. We assessed effects of alcohol pricing and promotion policy options in various population subgroups.

We built an epidemiological mathematical model to appraise 18 pricing policies, with English data from the Expenditure and Food Survey and the General Household Survey for average and peak alcohol consumption. We used results from econometric analyses (256 own-price and cross-price elasticity estimates) to estimate effects of policies on alcohol consumption. We applied risk functions from systemic reviews and meta-analyses, or derived from attributable fractions, to model the effect of consumption changes on mortality and disease prevalence for 47 illnesses.

General price increases were effective for reduction of consumption, health-care costs, and health-related quality of life losses in all population subgroups. Minimum pricing policies can maintain this level of effectiveness for harmful drinkers while reducing effects on consumer spending for moderate drinkers. Total bans of supermarket and off-license discounting are effective but banning only large discounts has little effect. Young adult drinkers aged 18–24 years are especially affected by policies that raise prices in pubs and bars.

Minimum pricing policies and discounting restrictions might warrant further consideration because both strategies are estimated to reduce alcohol consumption.

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Request Reprint E-Mail: r.purshouse@sheffield.ac.uk

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CRF-1 Antagonist and CRF-2 Agonist Decrease Binge-Like Ethanol Drinking in C57BL/6J Mice Independent of the HPA Axis

Recent evidence suggests that corticotropin-releasing factor (CRF) receptor (CRFR) signaling is involved in modulating binge-like ethanol consumption in C57BL/6J mice.

In this report, a series of experiments were performed to further characterize the role of CRFR signaling in binge-like ethanol consumption.

The role of central CRFR signaling was assessed with intracerebroventricular (i.c.v.) infusion of the nonselective CRFR antagonist, α-helical CRF_9–41 (0, 1, 5, 10 μg/1 μl). The contribution of central CRF type 2 receptor (CRF₂R) signaling was assessed with i.c.v. infusion of the selective CRF₂R agonist, urocortin (Ucn) 3 (0, 0.05, 0.1, or 0.5 μg/1 μl). The role of the hypothalamic–pituitary–adrenal (HPA) axis was assessed by pretreating mice with intraperitoneal (i.p.) injection of (1) the corticosterone synthesis inhibitor, metyrapone (0, 50, 100, 150 mg/kg) or (2) the glucocorticoid receptor antagonist, mifepristone (0, 25, 50 mg/kg), and (3) by using radioimmunoassay to determine whether binge-like ethanol intake influenced plasma corticosterone levels. Finally, we determined whether the ability of the CRF₁R antagonist, CP-154,526 (CP; 0, 10, 15 mg/kg, i.p.), to blunt binge-like drinking required normal HPA axis signaling by comparing the effectiveness of CP in adrenalectomized (ADX) and normal mice.

Results showed that i.c.v. infusion of a 1 μg dose of α-helical CRF_9–41 significantly attenuated binge-like ethanol consumption relative to vehicle treatment, and i.c.v. infusion of Ucn 3 dose-dependently blunted binge-like drinking.

On the other hand, metyrapone nonselectively reduced both ethanol and sucrose consumption, mifepristone did not alter ethanol drinking, and binge-like drinking did not correlate with plasma corticosterone levels.

Finally, i.p. injection of CP significantly attenuated binge-like ethanol intake in both ADX and normal mice.

Together, these results suggest that binge-like ethanol intake in C57BL/6J mice is modulated by CRF₁R and CRF₂R signaling, such that blockade of CRF₁R or activation of CRF₂R effectively reduces excessive ethanol intake.

Furthermore, normal HPA axis signaling is not necessary to achieve binge-like drinking behavior.


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Request Reprint E-Mail: thiele@unc.edu

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Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts

Twin studies provide strong evidence that there is a shared genetic liability that predisposes to a number of different psychiatric outcomes related to behavioral disinhibition. Further, alcohol dependence comorbid with other disinhibitory disorders is particularly heritable. Chromosome 2p14-2q14.3 has been linked to multiple psychiatric conditions related to behavioral undercontrol.

In the Collaborative Study on the Genetics of Alcoholism (COGA), we previously reported linkage to this region with alcohol dependence (AD), suicide attempts (SUI), and conduct disorder (CD).

In this study, we follow-up on these previous reports of linkage by combining the phenotypes in analyses that jointly consider the presence of multiple conditions.

Linkage analyses of the combined phenotype of AD with CD or SUI results in a maximum LOD score of 5.4 in this region. In addition to this primary linkage peak, independent samples have reported linkage to other alcohol-related phenotypes across chromosome 2. Accordingly, we followed-up these linkage signals by testing for association with SNPs across chromosome 2 in a case-control sample, in which a subset of the cases consisted of alcohol-dependent probands from the linkage sample.

We find evidence of association with the combined AD with CD or SUI phenotype, with 23 genes surviving permutation testing. The number of associated genes across the chromosome may explain the persistent linkage findings reported on chromosome 2 across a number of independent studies of alcohol and disinhibitory phenotypes.

Further, none of the genes were located directly under the primary COGA linkage peak, which has implications for association tests following-up linkage peaks.

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Request Reprint E-Mail: ddick@vcu.edu

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Will Increasing Alcohol Availability By Lowering the Minimum Legal Drinking Age Decrease Drinking and Related Consequences Among Youths?

Alcohol use health consequences are considerable; prevention efforts are needed, particularly for adolescents and college students. The national minimum legal drinking age of 21 years is a primary alcohol-control policy in the United States.

An advocacy group supported by some college presidents seeks public debate on the minimum legal drinking age and proposes reducing it to 18 years.

We reviewed recent trends in drinking and related consequences, evidence on effectiveness of the minimum legal drinking age of 21 years, research on drinking among college students related to the minimum legal drinking age, and the case to lower the minimum legal drinking age.

Evidence supporting the minimum legal drinking age of 21 years is strong and growing. A wide range of empirically supported interventions is available to reduce underage drinking. Public health professionals can play a role in advocating these interventions.

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Request Reprint E-Mail: tfnelson@umn.edu .

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Genome-wide gene expression analysis identifies K-ras as a regulator of alcohol intake

Adaptations in the anterior cingulate cortex (ACC) have been implicated in alcohol and drug addiction.

To identify genes that may contribute to excessive drinking, here we performed microarray analyses in laser microdissected rat ACC after a single or repeated administration of an intoxicating dose of alcohol (3g/kg).

Expression of the small G protein K-ras was reduced following both single and repeated alcohol administration.

We also observed that voluntary alcohol intake in K-ras heterozygous null mice (K-ras^+/-) did not increased after withdrawal from repeated cycles of intermittent ethanol vapor exposure, unlike in their wild-type littermates.

To identify K-ras regulated pathways, we then profiled gene expression in the ACC of K-ras^+/-, heterozygous null mice for the K-ras negative regulator Nf1 (Nf1^+/-) and wild-type mice following repeated administration of an intoxicating dose of alcohol.

Pathway analysis showed that alcohol differentially affected various pathways in a K-ras dependent manner – some of which previously shown to be regulated by alcohol - including the insulin/PI3K pathway, the NF-kB, the phosphodiesterases (PDEs) pathway, the Jak/Stat and the adipokine signaling pathways.

Altogether, the data implicate K-ras-regulated pathways in the regulation of excessive alcohol drinking after a history of dependence.

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Request Reprint E-Mail: psanna@scripps.edu

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The Evolution of Drinking Motivations Among Korean Women With Alcohol Dependence

Our purpose in conducting this study was to explore increases in alcohol problems among women in South Korea.

Qualitative data were collected from 10 women in treatment for alcohol dependence using in-depth interviews.

The grounded theory analysis revealed three phases of drinking behavior that were driven by certain motivations: (1) positive experiences, (2) coping with negative emotions, and (3) needing alcohol to function.

The findings suggest that the increased occurrence of alcohol dependence among Korean women may be associated with shifting expectations about women's alcohol use and conflicts between their traditional and modern gender roles in the rapidly changing society.

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Request Reprint E-Mail: wkim5@buffalo.edu


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Developing choice in peer-support How alcohol services can support SMART Recovery

From 2008 to 2010 Alcohol Concern managed a project that aimed to establish and develop new peer-support groups for problem drinkers based on the SMART Recovery model. The Department of Health funded the project which worked with SMART Recovery UK and six services in England which acted as pilot sites.

This manual aims to provide guidance to alcohol services and others working with alcohol misusing clients as to how they can help the establishment and development of SMART Recovery groups in their area.

The manual is based on learning from the Alcohol Concern SMART Recovery project and includes a description of how the project developed, along with discussion on what worked well in the project and what worked less well.

The project was based on a peer-led model, with service users taking on the role of SMART meeting facilitators. However, professionals facilitate some SMART groups.

The project was focused on alcohol as opposed to other substances but SMART Recovery benefits people with any addictive substance or behaviour. Therefore the experience and advice in this manual is applicable to those working with all substance misusing clients.

Read Full Manual (PDF)

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Heritability of MMPI-2 Scales in the UCSF Family Alcoholism Study

The current study evaluated the heritability of personality traits and psychopathology symptoms assessed by the Minnesota Multiphasic Personality Inventory 2nd Edition (MMPI-2) in a family-based sample selected for alcohol dependence.

Participants included 950 probands and 1,204 first-degree relatives recruited for the University of California at San Francisco (UCSF) Family Alcoholism Study.

Heritability estimates for MMPI-2 scales ranged from .25 to .49. When alcohol dependence was used as a covariate, heritability estimates remained significant but generally declined. However, when the MMPI-2 scales were used as covariates to estimate the heritability of alcohol dependence, the scales measuring antisocial behavior, depressive symptoms, and addictive behavior led to moderate increases in the heritability of alcohol dependence.

This suggests that the scales may explain some of the non-genetic variance in the alcohol dependence diagnosis in this population when used as covariates, and thus may serve to produce a more homogeneous and heritable alcohol-dependence phenotype.

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Request Reprint E-Mail: igizer@unc.edu


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Liberal Democrats manifesto: support for minimum pricing principle and below cost ban

The Liberal Democrats have released their 2010 election manifesto, outlining their proposals for alcohol policy:

"We will...reduce the ill health and crime caused by excessive drinking. We support a ban on below-cost selling, and are in favour of the principle of minimum pricing, subject to detailed work to establish how it could be used in tackling problems of irresponsible drinking. We will also review the complex, ill-thought-through system of taxation for alcohol to ensure it tackles binge drinking without unfairly penalising responsible drinkers, pubs and important local industries." . . . . .

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Conservative manifesto: ban 'below cost' sales and tax drinks that cause anti-social behaviour

The Conservatives have launched their 2010 election manifesto, sticking to previously announced measures proposed to crack down on the causes of anti-social drinking including cheap, strong drinks. The manifesto states:

"Under Labour’s lax licensing regime, drink-fuelled violence and disorder are a blight on many communities. We will overhaul the Licensing Act to give local authorities and the police much stronger powers to remove licences from, or refuse to grant licences to, any premises that are causing problems. In addition, we will:

• allow councils and the police to shut down permanently any shop or bar found persistently selling alcohol to children;
  
• double the maximum fine for under-age alcohol sales to £20,000;
• raise taxes on those drinks linked to antisocial drinking, while abolishing Labour’s new ‘cider tax’ on ordinary drinkers;
  
• ban off-licences and supermarkets from selling alcohol below cost price; and,
• permit local councils to charge more for latenight licences to pay for additional policing. . . . . .

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Labour manifesto: support declared for pubs & treatment investment hints?

The current Labour Government has released their 2010 election manifesto as the May 6th election looms close. A quick word search finds alcohol-related topics receiving a few mentions:

• Crime is down by more than a third; violent crime is down by over 40 per cent, and the risk of being a victim of crime is the lowest since 1981. But people are still worried about binge drinking, problem families and anti-social behaviour. We are committed to tackling these problems, not talking them up to run Britain down. (p.36)
• To tackle the binge drinking which can leave people reluctant to venture into town centres at night, we have banned irresponsible promotions and strengthened police and council powers to close down rowdy pubs and clubs, cracking down on under-age and public drinking. We have brought in a right to petition local authorities to end 24-hour licensing where problems arise. (p.40)
• The local pub and social club are also hubs of community life. Too many pubs have closed that could have been sustained by local people. We will support pubs that have a viable future with a new fund for community ownership in 2010-11. Councils must take full account of the importance of pubs to the local community when assessing proposals that change their use, and we will make it more difficult to demolish pubs... (p.52) . . . . .
  

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The role of alcohol and other drugs in road deaths and serious injuries

The total number of people killed on Australian roads in 2006 was 1601, with a further 31 204 people suffering serious injuries. Many factors are believed to contribute to traffic accidents, including drug and alcohol use, fatigue and speed.

This paper examines the impact of alcohol and other drug use, including various pharmaceuticals, on road deaths and injuries. It also outlines a number of strategies that are currently being implemented to minimise and reduce the number of drivers who consume drugs.

Prevention strategies include current education activities in schools, advertising campaigns and information provided by health professionals.

Detecting drug driving, and treatment and education following the loss of licence due to drug driving, are also discussed.

All of these approaches work together to reduce the number of individuals who drive under the influence of drugs.

In addition to a review of relevant literature, the views of key informants who have professional experience in a range of fields (alcohol and other drug service delivery, road safety and research) were sought to inform this paper.

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Mozambique: Worst Addiction in Country is to Alcohol

The number of people undergoing treatment in Mozambique for alcohol and drug addiction rose from about 1,500 in 2008 to 2,100 in 2009, according to the government's interim spokesperson, Deputy Foreign Minister Henrique Banze.

He told reporters that on Tuesday the government received and approved the annual report on drug consumption and trafficking produced by the Central Office for the Fight against Drug Addiction.

The report indicates that the most problematic drug in the country is alcohol. The number of people treated for alcoholism rose from 896 in 2008 to around 1,100 last year. Such figures vastly underestimate the problem, since the majority of alcoholics do not seek medical care. . . . . .

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Association between alcohol consumption and cognitive impairment in Southern Chinese older adults

There is limited data on the effects of alcohol consumption on cognitive impairment in Chinese populations.

To investigate the association between alcohol consumption and the risk of cognitive impairment in Southern Chinese older adults in Hong Kong.

This was a cross-sectional study of 314 Chinese older participants, aged 65 years or over. Participants' socio-demographic, co-morbid diseases, alcohol drinking habits, and Mini Mental State Examination (MMSE) for cognitive function were obtained by a face-to-face interview. Participants were categorized into normal cognitive and cognitively impaired groups by education-adjusted MMSE cut-off scores.

The mean (SD) age of the participants was 79.9 (6.5) years. The average weekly alcohol consumption in the cognitively impaired group was significantly higher than that of the normal cognition group [mean (SD): 861.89 (673.03) versus 241.21 (276.26) grams per week respectively; p <>t-test]. Drinkers with light to moderate alcohol consumption were associated with higher MMSE scores than non-drinkers and heavy drinkers. Logistic regression analyses showed that heavy drinkers (>400 g alcohol for men and >280 g for women) were associated with an increased risk of cognitive impairment (OR = 4.99, 95%CI = 1.8-13.82), while light drinkers and moderated drinkers (<400 or =" 0.32," ci =" 0.12-0.86;" or =" 0.17," ci =" 0.06-0.51,">

Heavy alcohol consumption is associated with an increased risk of cognitive impairment while light to moderate alcohol consumption is associated with reduced risk among Southern Chinese older adults in Hong Kong. Read Full Abstract Request Reprint E-Mail: lwchu@hkuccc.hku.hk ________________________________________

Moderate Red Wine Consumption and Cardiovascular Disease Risk: Beyond the “French Paradox”

The term French paradox was coined in 1992 to describe the relatively low incidence of cardiovascular disease in the French population, despite a relatively high dietary intake of saturated fats, and potentially attributable to the consumption of red wine.

After nearly 20 years, several studies have investigated the fascinating, overwhelmingly positive biological and clinical associations of red wine consumption with cardiovascular disease and mortality.

Light to moderate intake of red wine produces a kaleidoscope of potentially beneficial effects that target all phases of the atherosclerotic process, from atherogenesis (early plaque development and growth) to vessel occlusion (flow-mediated dilatation, thrombosis). Such beneficial effects involve cellular signaling mechanisms, interactions at the genomic level, and biochemical modifications of cellular and plasma components.

Red wine components, especially alcohol, resveratrol, and other polyphenolic compounds, may decrease oxidative stress, enhance cholesterol efflux from vessel walls (mainly by increasing levels of high-density lipoprotein cholesterol), and inhibit lipoproteins oxidation, macrophage cholesterol accumulation, and foam-cell formation.

These components may also increase nitric oxide bioavailability, thereby antagonizing the development of endothelial dysfunction, decrease blood viscosity, improve insulin sensitivity, counteract platelet hyperactivity, inhibit platelet adhesion to fibrinogen-coated surfaces, and decrease plasma levels of von Willebrand factor, fibrinogen, and coagulation factor VII. Light to moderate red wine consumption is also associated with a favorable genetic modulation of fibrinolytic proteins, ultimately increasing the surface-localized endothelial cell fibrinolysis.

Overall, therefore, the “French paradox” may have its basis within a milieu containing several key molecules, so that favorable cardiovascular benefits might be primarily attributable to combined, additive, or perhaps synergistic effects of alcohol and other wine components on atherogenesis, coagulation, and fibrinolysis. Conversely, chronic heavy alcohol consumption and binge drinking are associated with increased risk of cardiovascular events.

In conclusion, although mounting evidence strongly supports beneficial cardiovascular effects of moderate red wine consumption (one to two drinks per day; 10-30 g alcohol) in most populations, clinical advice to abstainers to initiate daily alcohol consumption has not yet been substantiated in the literature and must be considered with caution on an individual basis.

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Request Reprint E-Mail: giuseppe.lippi@univr.it

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Characteristics of Problem Drinking in an Urban South American Indigenous Population

This 2002 Medcen Foundation-funded study explored characteristics of problem drinking among 211 urban Venezuelan Native Americans of Arawak origin.

Prevalence of problem drinking using Alcohol Use Disorders Identification Tests was 88.5% among men and 17.3% among women. Periodic binge drinking was marked by loss of control, failure to meet obligations, and alcohol-related trauma.

Focus group participants noted that previous occasional binge drinking by men has been replaced by frequent male and female heavy weekend drinking, violence, and death.

Limitations and implications are discussed.

Awareness of high levels of problem drinking and desire for assistance present compelling mandates for community intervention efforts.

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Request Reprint E-Mail: seale.paul@mccg.org

Ethanol Blocks Long-Term Potentiation of GABAergic Synapses in the Ventral Tegmental Area Involving μ-Opioid Receptors

It is well documented that ethanol exposure alters GABA (γ-aminobutyric acid)-releasing synapses, and ethanol addiction is associated with endogenous opioid system.

Emerging evidence indicates that opioids block long-term potentiation in the fast inhibitory GABA_A receptor synapses (LTP_GABA) onto dopamine-containing neurons in the ventral tegmental area (VTA), a brain region essential for reward-seeking behavior. However, how ethanol affects LTP_GABA is not known.

We report here that in acute midbrain slices from rats, clinically relevant concentrations of ethanol applied both in vitro and in vivo prevents LTP_GABA, which is reversed, respectively, by in vitro and in vivo administration of naloxone, a μ-opioid receptor (MOR) antagonist.

Furthermore, the blockade of LTP_GABA induced by a brief in vitro ethanol treatment is mimicked by DAMGO ([D-Ala², N-MePhe⁴, Gly-ol]-enkephalin), a MOR agonist. Paired-pulse ratios are similar in slices, 24 h after in vivo injection with either saline or ethanol.

Sp-cAMPS, a stable cAMP analog, and pCPT-cGMP, a cGMP analog, potentiates GABA_A-mediated inhibitory postsynaptic currents in slices from ethanol-treated rats, indicating that a single in vivo ethanol exposure does not maximally increase GABA release, instead, ethanol produces a long-lasting inability to generate LTP_GABA.

These neuroadaptations to ethanol might contribute to early stage of addiction.

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Request Reprint E-Mail: ye@umdnj.edu

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Sober living houses for alcohol and drug dependence: 18-Month outcomes

A major challenge facing many individuals attempting to abstain from substances is finding a stable living environment that supports sustained recovery.

Sober living houses (SLHs) are alcohol- and drug-free living environments that support abstinence by emphasizing involvement in 12-step groups and social support for recovery. Among a number of advantages, they are financially self-sustaining and residents can stay as long as they wish. Although SLHs can be used as housing referrals after inpatient treatment, while clients attend outpatient treatment, after incarceration, or as an alternative to treatment, they have been understudied and underutilized.

To describe outcomes of SLH residents, we interviewed 245 individuals within 1 week of entering SLHs and at 6-, 12-, and 18-month follow-up. Eighty-nine percent completed at least one follow-up interview. Outcomes included the Addiction Severity Index (ASI), Brief Symptom Inventory (BSI), and measures of alcohol and drug use. Covariates included demographic characteristics, 12-step involvement, and substance use in the social network.

Regardless of referral source, improvements were noted on ASI scales (alcohol, drug, and employment), psychiatric severity on the BSI, arrests, and alcohol and drug use. Substance use in the social network predicted nearly all outcome measures. Involvement in 12-step groups predicted fewer arrests and lower alcohol and drug use.

Residents of SLHs made improvements in a variety of areas. Additional studies should use randomized designs to establish causal effects of SLHs.

Results support the importance of key components of the recovery model used by SLHs: (a) involvement in 12-step groups and (b) developing social support systems with fewer alcohol and drug users.

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Request Reprint E-Mail: dpolcin@arg.org

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Extended-release naltrexone for treatment of alcohol dependence in primary care

The feasibility of using extended-release injectable naltrexone (XR-NTX) to treat alcohol dependence in routine primary care settings is unknown.

An open-label, observational cohort study evaluated 3-month treatment retention, patient satisfaction, and alcohol use among alcohol-dependent patients in two urban public hospital medical clinics.

Adults seeking treatment were offered monthly medical management (MM) and three XR-NTX injections (380 mg, intramuscular). Physician-delivered MM emphasized alcohol abstinence, medication effects, and accessing mutual help and counseling resources.

Seventy-two alcohol-dependent patients were enrolled; 90% (65 of 72) of eligible subjects received the first XR-NTX injection; 75% (49 of 65) initiating treatment received the second XR-NTX injection; 62% (40 of 65), the third.

Among the 56% (n = 40) receiving three injections, median drinks per day decreased from 4.1 (95% confidence interval = 2.9–6) at baseline to 0.5 (0–1.7) during Month 3.

Extended-release naltrexone delivered in a primary care MM model appears a feasible and acceptable treatment for alcohol dependence.

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Request Reprint E-Mail: joshua.lee@med.nyu.edu

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Barriers and facilitators for alcohol treatment for women: Are there more or less for rural women?

Among women at-risk for problems drinking, treatment seeking can be hindered by a complex array of issues such as a lack of transportation, social stigma, denial, fear of losing children, and reluctance of primary care physicians to refer women.

This study describes the barriers/facilitators and need for treatment among a community sample of rural and urban women at-risk drinkers. Data for this study were assembled from the baseline sample of individuals who participated in a large probability sample of rural and urban at-risk drinkers (N = 733) from six Southern states: Alabama, Arkansas, Georgia, Louisiana, Mississippi, and Tennessee.

Men and women differed on perceived barriers/facilitators and need for alcohol treatment. Women differed from men on measures of treatment affordability, accessibility, acceptability and report of social support, illness severity, comorbidities, and demographic characteristics.

Rural women differed from urban women on measures of treatment affordability and accessibility and report of illness severity and comorbidities.

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Request Reprint E-Mail: jsmall@uams.edu

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Molecular Mechanisms of Ethanol-Induced Pathogenesis Revealed by RNA-Sequencing

Acinetobacter baumannii is a common pathogen whose recent resistance to drugs has emerged as a major health problem. Ethanol has been found to increase the virulence of A. baumannii in Dictyostelium discoideum and Caenorhabditis elegans models of infection.

To better understand the causes of this effect, we examined the transcriptional profile of A. baumannii grown in the presence or absence of ethanol using RNA-Seq. Using the Illumina/Solexa platform, a total of 43,453,960 reads (35 nt) were obtained, of which 3,596,474 mapped uniquely to the genome.

Our analysis revealed that ethanol induces the expression of 49 genes that belong to different functional categories. A strong induction was observed for genes encoding metabolic enzymes, indicating that ethanol is efficiently assimilated.

In addition, we detected the induction of genes encoding stress proteins, including upsA, hsp90, groEL and lon as well as permeases, efflux pumps and a secreted phospholipase C. In stationary phase, ethanol strongly induced several genes involved with iron assimilation and a high-affinity phosphate transport system, indicating that A. baumannii makes a better use of the iron and phosphate resources in the medium when ethanol is used as a carbon source.

To evaluate the role of phospholipase C (Plc1) in virulence, we generated and analyzed a deletion mutant for plc1. This strain exhibits a modest, but reproducible, reduction in the cytotoxic effect caused by A. baumannii on epithelial cells, suggesting that phospholipase C is important for virulence.

Overall, our results indicate the power of applying RNA-Seq to identify key modulators of bacterial pathogenesis.

We suggest that the effect of ethanol on the virulence of A. baumannii is multifactorial and includes a general stress response and other specific components such as phospholipase C.

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