A Systematic Single Nucleotide Polymorphism Screen to Fine-Map Alcohol Dependence Genes on Chromosome 7 Identifies Association With a Novel Susceptibility Gene ACN9
Biological Psychiatry Article in Press, Corrected Proof 27 December 2007

Chromosome 7 has shown consistent evidence of linkage with a variety of phenotypes related to alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) project.

With a sample of 262 densely affected families, a peak logarithm of odds (LOD) score for alcohol dependence of 2.9 was observed at D7S1799. The LOD score in the region increased to 4.1 when a subset of the sample was genotyped with the Illumina Linkage III panel for the Genetic Analysis Workshop 14 (GAW14).

To follow up on this linkage region, we systematically screened single nucleotide polymorphisms (SNPs) across a 2 LOD support interval surrounding the alcohol dependence peak.

The SNPs were selected from the HapMap Phase I CEPH data to tag linkage disequilibrium bins across the region. Across the 18-Mb region, genotyped by the Center for Inherited Disease Research (CIDR), 1340 SNPs were analyzed. Family-based association analyses were performed on a sample of 1172 individuals from 217 Caucasian families.

Eight SNPs showed association with alcohol dependence at p < .01. Four of the eight most significant SNPs were located in or very near the ACN9 gene. We conducted additional genotyping across ACN9 and identified multiple variants with significant evidence of association with alcohol dependence.

These analyses suggest that ACN9 is involved in the predisposition to alcohol dependence. Data from yeast suggest that ACN9 is involved in gluconeogenesis and the assimilation of ethanol or acetate into carbohydrate.

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Request Reprint E-Mail: ddick@vcu.edu

Fetal Alcohol Syndrome Prevention Using Community-Based Narrowcasting Campaigns
Health Promotion Practice, Vol. 9, No. 1, 93-103 (2008)

Preventing fetal alcohol syndrome (FAS) by encouraging pregnant women to abstain from drinking alcohol competes with commercial alcohol marketing.

Two FAS-prevention campaigns using a narrowcast approach among young women of childbearing age in two disadvantaged Southern California communities are compared. The design, implementation process, and degree to which campaigns reached the priority populations are the focus of this article.

Formative research shows that young women in disadvantaged communities receive mixed messages about dangers of drinking during pregnancy. A social norms approach using positive role models was the most acceptable message strategy based on materials pretesting.

Differences in campaign implementation and distribution strategies between communities were documented through program monitoring. Survey research indicated the more viable messaging and implementation strategies.

Findings show that low-cost community campaigns are feasible; however, variations in messaging, distribution strategies, and saturation levels determine whether such campaigns succeed or fail to reach priority populations.

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Request Reprint E-Mail: dglik@ucla.edu
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Examining the effect of linkage disequilibrium between markers on the Type I error rate and power of nonparametric multipoint linkage analysis of two-generation and multigenerational pedigrees in the presence of missing genotype data
Genetic Epidemiology Volume 32, Issue 1 , Pages 41 - 51

Because most multipoint linkage analysis programs currently assume linkage equilibrium between markers when inferring parental haplotypes, ignoring linkage disequilibrium (LD) may inflate the Type I error rate.

We investigated the effect of LD on the Type I error rate and power of nonparametric multipoint linkage analysis of two-generation and multigenerational multiplex families.

Using genome-wide single nucleotide polymorphism (SNP) data from the Collaborative Study of the Genetics of Alcoholism, we modified the original data set into 30 total data sets in order to consider six different patterns of missing data for five different levels of SNP density. To assess power, we designed simulated traits based on existing marker genotypes. For the Type I error rate, we simulated 1,000 qualitative traits from random distributions, unlinked to any of the marker data.

Overall, the different levels of SNP density examined here had only small effects on power (except sibpair data). Missing data had a substantial effect on power, with more completely genotyped pedigrees yielding the highest power (except sibpair data). Most of the missing data patterns did not cause large increases in the Type I error rate if the SNP markers were more than 0.3 cM apart.

However, in a dense 0.25-cM map, removing genotypes on founders and/or founders and parents in the middle generation caused substantial inflation of the Type I error rate, which corresponded to the increasing proportion of persons with missing data.

Results also showed that long high-LD blocks have severe effects on Type I error rate.


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Request Reprint E-Mail: hokim@snu.ac.kr or jebw@mail.nih.gov
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Hospitals admit 500 binge drinkers a day
By James Kirkup and Caroline Gammell

31/12/2007

An epidemic of binge drinking has fuelled a dramatic increase in the number of people being hospitalised after drinking to excess, The Daily Telegraph can disclose.

The number of alcohol-related hospital admissions has increased by almost a third in just two years as 24-hour drinking laws and the greater availability of cheap alcohol lead to increased consumption.

More than 500 people a day are now being admitted to hospitals in England after drinking too much.

In some parts of the country excess drinking is the cause of almost one in 20 hospital admissions.

The figures come just two weeks after official statistics showed that nearly 13 million Britons were drinking too much because they did not appreciate the increasing strength of alcoholic drinks or the trend for larger measures.

The latest figures obtained by The Daily Telegraph are part of official data recording alcohol-related admissions to NHS hospitals in England. They show a 31 per cent rise in just two years.
. . . . . . .

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Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings.
Biochemical Pharmacology Volume 75, Issue 1, 1 January 2008, Pages 34-56

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials.

Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome.

Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious.

Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study.

Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision.

Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials.

Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic.

As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.

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Request Reprint E-Mail: bankolejohnson@virginia.edu
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Computational models of ethanol-induced neurodevelopmental toxicity across species: Implications for risk assessment
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Early View Published online 26 December 2007

Computational, systems-based approaches can provide a quantitative construct for evaluating risk in the context of mechanistic data. Previously, we developed computational models for the rat, mouse, rhesus monkey, and human, describing the acquisition of adult neuron number in the neocortex during the key neurodevelopmental processes of neurogenesis and synaptogenesis.

Here we apply mechanistic data from the rat describing ethanol-induced toxicity in the developing neocortex to evaluate the utility of these models for analyzing neurodevelopmental toxicity across species.

Our model can explain long-term neocortical neuronal loss in the rodent model after in utero exposure to ethanol based on inhibition of proliferation during neurogenesis.

Our human model predicts a significant neuronal deficit after daily peak BECs reaching 10-20 mg/dl, which is the approximate BEC reached after drinking one standard drink within one hour. In contrast, peak daily BECs of 100 mg/dl are necessary to predict similar deficits in the rat.

Our model prediction of increased sensitivity of primate species to ethanol-induced inhibition of proliferation is based on application of in vivo experimental data from primates showing a prolonged rapid growth period in the primate versus rodent neuronal progenitor population.

To place our predictions into a broader context, we evaluate the evidence for functional low-dose effects across rats, monkeys, and humans.

Results from this critical evaluation suggest subtle effects are evident at doses causing peak BECs of approximately 20 mg/dl daily, corroborating our model predictions.

Our example highlights the utility of a systems-based modeling approach in risk assessment.

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Request Reprint E-Mail: faustman@u.washington.edu
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GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence.
Journal of Psychiatric Research
Volume 42, Issue 3, February 2008, Pages 184-191

Gamma-aminobutyric acid (GABA) A receptors are believed to mediate some of the physiological and behavioral actions of ethanol. Recent studies have suggested that genetic variants of the GABA-A receptor alpha2 subunit gene (GABRA2) are associated with alcohol dependence.

The aim of this study is to confirm and extend the role of GABRA2 haplotypes in the liability to alcohol dependence.

One genetic variant was detected to significantly differ between alcohol-dependent subjects and controls. Two common 8 SNP haplotypes and their complementary alleles were identified containing this SNP and were present in 89.9% of controls and 93.4% of the alcohol-dependent individuals.

One of the haplotypes (T-C-A-C-A-T-T-C) was significantly associated with alcohol dependence and characteristics of alcohol withdrawal and severity of alcohol dependence (delirium tremens, withdrawal seizures).

These findings support and extend the three previous studies implicating a GABA-A receptor subunit as contributing to the genetic risk for alcohol dependence. Possible implications of these findings are discussed.

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Request Reprint E-Mail: michael.soyka@med.uni-muenchen.de
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News Release - Researchers Show that Fibrosis can be Stopped, Cured and Reversed

December 27, 2007

Modified Protein Developed by UC San Diego Researchers May Lead to First Cure for Cirrhosis of the Liver

University of California, San Diego researchers have proven in animal studies that fibrosis in the liver can be not only stopped, but reversed. Their discovery, to be published in PLoS Online on December 26, opens the door to treating and curing conditions that lead to excessive tissue scarring such as viral hepatitis, fatty liver disease, cirrhosis, pulmonary fibrosis, scleroderma and burns.
. . . . . .

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A Ribosomal S-6 Kinase–Mediated Signal to C/EBP-β Is Critical for the Development of Liver Fibrosis
PLoS ONE 2(12): e1372

In response to liver injury, hepatic stellate cell (HSC) activation causes excessive liver fibrosis. Here we show that activation of RSK and phosphorylation of C/EBPβ on Thr217 in activated HSC is critical for the progression of liver fibrosis.

Chronic treatment with the hepatotoxin CCl₄ induced severe liver fibrosis in C/EBPβ^+/+ mice but not in mice expressing C/EBPβ-Ala217, a non-phosphorylatable RSK-inhibitory transgene. C/EBPβ-Ala217 was present within the death receptor complex II, with active caspase 8, and induced apoptosis of activated HSC.

The C/EBPβ-Ala217 peptides directly stimulated caspase 8 activation in a cell-free system. C/EBPβ^+/+ mice with CCl₄-induced severe liver fibrosis, while continuing on CCl₄, were treated with a cell permeant RSK-inhibitory peptide for 4 or 8 weeks. The peptide inhibited RSK activation, stimulating apoptosis of HSC, preventing progression and inducing regression of liver fibrosis.

We found a similar activation of RSK and phosphorylation of human C/EBPβ on Thr266 (human phosphoacceptor) in activated HSC in patients with severe liver fibrosis but not in normal livers, suggesting that this pathway may also be relevant in human liver fibrosis.

These data indicate that the RSK-C/EBPβ phosphorylation pathway is critical for the development of liver fibrosis and suggest a potential therapeutic target.

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The DRAM, 3(11) - Childhood Sexual Abuse, Age of First Drink, and Onset of Alcohol Dependence
December 26, 2007

Studies linking childhood sexual abuse (CSA) to higher likelihood of alcohol dependence (AD) later in life (i.e., Dinwiddie et al., 2000; Fergusson, Horwood, & Lynskey, 1996; Kendler et al., 2000; Kilpatrick et al., 2000; Molnair, Buka, & Kessler, 2001; Nelson et al., 2002) might lack adequate control for environmental and genetic factors that influence the relationship between CSA and AD.

These studies are also inconclusive because an earlier age of first drink is associated with later AD regardless of CSA status (DeWit, 2000).

This week’s DRAM reviews a study that controls for the influence of environmental and genetic characteristics, as well as the influence of drinking at an early age using a sample of twins
. . . . . .

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Let’s Raise a Glass to Fairness

By DAVID LEONHARDT
Published: December 26, 2007


“We are fortunate to be living in a time when there is a lot of good wine from around the world,” Philip Cook was telling me the other day.
. . . . .
The main cause of this golden age of inexpensive wine is the obvious one: globalization. Once confined to a small part of Europe, the making (and exporting) of great wine is now done across the globe.

But there is also another factor that gets less attention. Since the early 1990s, the federal tax on wine — $1.07 a gallon — hasn’t budged. The taxes on beer and liquor haven’t changed either, which means that, in inflation-adjusted terms, alcohol taxes have been steadily falling.

Each of the three taxes is now effectively 33 percent lower than it was in 1992. Since 1970, the federal beer tax has plummeted 63 percent. Many states taxes have also been falling.

At first blush, this sounds like good news: who likes to pay taxes, right? But taxes serve a purpose beyond merely raising general government revenue. Taxes on a given activity are also supposed to pay the costs that activity imposes on society. And for all that is wonderful about wine, beer and liquor, they clearly bring some heavy costs.
. . . . .

Mr. Cook, besides being a wine lover, has been thinking about the costs and benefits of alcohol for much of his career, and he has come up with a blunt way of describing the problem. “Do you think we should be subsidizing alcohol?” he asks. “Because that’s what we’re doing.”

. . . . And if it were somehow possible to tax only those people who were going to drive drunk in the future, it would be a wonderful idea. (Then again, we might just want to take away their driver’s licenses.) Barring clairvoyance, though, raising alcohol taxes from their current lows seems to be the fairest solution.

Mr. Cook has written a wonderful little book, “Paying the Tab,” making this case. In it, he draws on history, political philosophy and straight economics to point out that higher alcohol taxes would fit squarely in the American tradition.
. . . . .

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News Release - Cognitive, genetic clues identified in imaging study of alcohol addiction
University of North Carolina at Chapel Hill
Public release date: 25-Dec-2007

People with clinical addictions know first-hand the ravages the disease can take on almost every aspect of their lives. So why do they continue addictive behaviors, even after a period of peaceable abstinence"

Some answers appear rooted in regions of the brain active during decision making.

"It's perhaps not just that people are slaves to pleasure, but that they have trouble thinking through a decision," said Charlotte Boettiger, an assistant professor of psychology at the University of North Carolina at Chapel Hill, and lead author of a study in the December issue of the Journal of Neuroscience that took a novel tack in addiction imaging research.

"Our data suggest there may be a cognitive difference in people with addictions," Boettiger said. "Their brains may not fully process the long-term consequences of their choices. They may compute information less efficiently."

The study also found that a variant of the COMT gene, which controls the level of the neurotransmitter dopamine in the cortex, was associated with a tendency to make impulsive decisions and with high activity in certain brain areas during decision making.
. . . . .

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Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158^Val/Val Genotype
The Journal of Neuroscience, December 26, 2007, 27(52):14383-14391


The tendency to choose lesser immediate benefits over greater long-term benefits characterizes alcoholism and other addictive disorders. However, despite its medical and socioeconomic importance, little is known about its neurobiological mechanisms.

Brain regions that are activated when deciding between immediate or delayed rewards have been identified (McClure et al., 2004, 2007), as have areas in which responses to reward stimuli predict a paper-and-pencil measure of temporal discounting (Hariri et al., 2006). These studies assume "hot" and "cool" response selection systems, with the hot system proposed to generate impulsive choices in the presence of a proximate reward. However, to date, brain regions in which the magnitude of activity during decision making reliably predicts intertemporal choice behavior have not been identified.

Here we address this question in sober alcoholics and non-substance-abusing control subjects and show that immediate reward bias directly scales with the magnitude of functional magnetic resonance imaging bold oxygen level-dependent (BOLD) signal during decision making at sites within the posterior parietal cortex (PPC), dorsal prefrontal cortex (dPFC), and rostral parahippocampal gyrus regions.

Conversely, the tendency of an individual to wait for a larger, delayed reward correlates directly with BOLD signal in the lateral orbitofrontal cortex. In addition, genotype at the Val158Met polymorphism of the catechol-O-methyltransferase gene predicts both impulsive choice behavior and activity levels in the dPFC and PPC during decision making.

These genotype effects remained significant after controlling for alcohol abuse history.

These results shed new light on the neurobiological underpinnings of temporal discounting behavior and identify novel behavioral and neural consequences of genetic variation in dopamine metabolism.

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Request Reprint E-Mail: cab@unc.edu
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Doctors may soon offer what alcoholics need (if not what they want)

By Melissa Healy, Los Angeles Times Staff Writer
December 24, 2007

British songstress Amy Winehouse, who croons "no, no, no" to rehab, has a lot of American company this time of year -- both in her heavy-drinking ways and her unwillingness to spend weeks in a specialized facility to get sober.

But experts say there may be new hope for rehab refuseniks like Winehouse and an estimated 5.7 million alcoholics in the United States who are not in treatment -- hope that could be as close as the family doctor.

New research and a growing arsenal of medications have set the stage for a major shift in the treatment of alcoholism, from specialized clinic to the "primary care office setting," the Journal of the American Medical Assn. reported in its Dec. 5 issue.
. . . . . .
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Network Support for Drinking: An Application of Multiple Groups Growth Mixture Modeling to Examine Client-Treatment Matching
J. Stud. Alcohol Drugs 69: 21-29, 2008


The current study re-examined the Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) hypothesis that individuals with high network support for drinking would have the best treatment outcomes if they were assigned to twelve-step facilitation (TSF).

Drinking consequences, as measured by the Drinking Inventory of Consequences, was the primary outcome measure. Growth mixture models with multiple groups were used to estimate the drinking consequence trajectories of 952 outpatients during the 12 months following treatment for each of the three Project MATCH treatment conditions. Growth factors within latent trajectory classes were regressed on network support for drinking to assess whether treatment condition moderated the relationship between network support for drinking and drinking consequences over time.

Three latent classes were identified, representing low (n = 154, 16.2%), medium (n = 400, 42%), and high (n = 398, 41.8%) levels of drinking consequences. Classes did not differ across treatment groups. Greater network support for drinking predicted more drinking consequences over time but only for clients assigned to cognitive-behavioral therapy and motivational enhancement therapy, not TSF.

This study provides further support for one of the original Project MATCH matching hypotheses: Clients with social networks supportive of drinking had better outcomes immediately after treatment if they were assigned to TSF.

Because the original Project MATCH studies found this matching effect only at the 3-year follow-up, these results add validity to the network support for drinking matching effect.

The study also provides additional evidence that accounting for heterogeneity in alcohol treatment outcomes is important for accurately estimating treatment effectiveness.

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Request Reprint E-Mail: jwu24@uic.edu
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Alcohol Consumption in Australia: A Snapshot, 2004-05


This article provides an overview of the level, prevalence and type of alcohol consumption; the health status, risk factors and demographic characteristics of those who drink alcohol at risky or high risk levels; as well as information on mortality and health costs.

This article uses data from the 2004-05 National Health Survey (NHS), the 2004-05 National Aboriginal and Torres Strait Islander Health Survey (NATSIHS) and the Causes of Death Collection.

This article also draws on measures of alcohol consumption from the Apparent Consumption of Alcohol Collection, which uses excise and import trade administrative data to produce an indirect measure of consumption of alcohol, based on a population aged 15 years or more (ABS 2006a).

Data from the 2004 National Drug Strategy Household Survey (NDSHS) are also used in this article (AIHW 2005a).

Both short and long term risk of harm were measured in the 2004-05 NHS (footnote 1). Unless otherwise stated, this article presents NHS information on alcohol consumption for long term risk of harm. Survey respondents were categorised as drinking alcohol at low, risky or high risk levels based on the guidelines of the National Health and Medical Research Council (NHMRC) (footnote 2).

Data were collected in the 2004-05 NHS from those aged 18 years and over, and from those aged 14 and over (with a small sample from 12-13 year olds) in the 2004 NDSHS.

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HIDDEN MARKOV MODELS FOR ALCOHOLISM TREATMENT TRIAL DATA
University of Pennsylvania and Syracuse University


In a clinical trial of a treatment for alcoholism, the usual response variable of interest is the number of alcoholic drinks consumed by each subject each day. Subjects in these trials are typically volunteers who are alcoholics, and thus are prone to erratic drinking behaviors, often characterized by alternating periods of heavy drinking and abstinence. For this reason, many statistical models for time series that assume steady behavior over time and white noise errors do not fit alcohol data well.

In this paper, we propose to describe subjects' drinking behavior using a Hidden Markov model (HMM) for categorical data, where the counts of drinks per day are summarized as a categorical variable with three levels, as is the convention in alcohol research.

We compare the HMM's properties to those of other models, focusing on out-of-sample prediction error as well as interpretability; to do this, we analyze data from a clinical trial of the drug Naltrexone using each model.

The HMM performs at a level comparable to the other models with respect to out-of-sample prediction error, and contains unique features that allow for useful clinical interpretations.

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Alcohol Drinking Patterns and Prevalence of Alcohol-Abuse and Dependence in the Israel National Health Survey
Isr J Psychiatry Relat Sci Vol 44 No. 2 (2007) 126–135


Coexistence of disparate religious/cultural mores with regard to alcohol drinking within the changing social milieu of Israel provides an informative environment for investigation of alcohol consumption patternsand alcohol-related mental disorders.

Half of the 4,859 respondents reported any alcohol consumption in the year prior to interview; 5% drink 3 ormore times weekly. DSM-IV criteria for alcohol abuse or dependence (lifetime) were met by 4.3% of respondents. Significantly higher rates were found among males (AOR, adjusted odds ratio=7.3), younger adults (AOR=5.0), immigrants from the former Soviet Union (AOR=2.0), and those who were never married (AOR=1.6).

Under-reporting remains a potential concern in health behavior surveys, particularly in the face of opposing religious norms.

The lifetime prevalence of alcohol abuse in Israel is identical to other European countries while drinking levels are considerably lower, suggesting a biological sensitivity alongside socio-cultural factors.

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The impact of smoking bans on alcohol demand
The Social Science Journal Volume 44, Issue 4, 2007, Pages 664-676

Although many studies find that smoking bans reduce cigarette demand, arguments can be made for smoking bans also affecting alcohol demand.

Accordingly, in this paper we address the determinants of state-level alcohol demand, which we treat as a function of various economic and demographic variables, as well as smoking bans.

Results reveal that smoking bans reduce the demand for beer and spirits. Furthermore, smoking bans tend to intensify the complementary relationship between cigarettes and alcohol, which suggests that smoking bans have altered consumer demographics in the alcohol market.

We also find the nature of the smoking ban matters, as bans specific to restaurants and bars lead to larger reductions in beer and spirits consumption, but increase the demand for wine.

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Request Reprint E-Mail: cgallet@csus.edu

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The Application of Machine Learning Techniques as an Adjunct to Clinical Decision Making in Alcohol Dependence Treatment
Substance Use & Misuse, Volume 42, Issue 14 December 2007 , pages 2193 - 2206



With few exceptions, research in the addictive sciences has relied on linear statistics and methodologies. Addiction involves a complex array of nonlinear behaviors.

This study applies two machine learning techniques, Bayesian and decision tree classifiers, in the assessment of outcome of an alcohol dependence treatment program. These nonlinear approaches are compared to a standard linear analysis.

Seventy-three alcohol-dependent subjects undertaking a 12-week cognitive-behavioral therapy (CBT) program and 66 subjects undertaking an identical program but also prescribed the relapse prevention agent Acamprosate were employed in this study.

Demographic, alcohol use, dependence severity, craving, health-related quality of life, and psychological measures at baseline were used to predict abstinence at 12 weeks.

Decision trees had a 77% predictive accuracy across both data sets, Bayesian networks 73%, and discriminant analysis 42%.

Combined with clinical experience, machine learning approaches offer promise in understanding the complex relationships that underlie treatment outcome for abstinence-based alcohol treatment programs.

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Request Reprint E-Mail: jason.connor@uq.edu.au
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Difficulties in emotion regulation and impulse control in recently abstinent alcoholics compared with social drinkers
Addictive Behaviors Volume 33, Issue 2, February 2008, Pages 388-394

Early abstinence from chronic alcohol dependence is associated with increased emotional sensitivity to stress-related craving as well as changes in brain systems associated with stress and emotional processing.

The aim of the current study was to examine potential difficulties in emotion regulation during early alcohol abstinence using the recently validated Difficulties of Emotion Regulation Scale (DERS).

Recently abstinent treatment-seeking alcohol abusers (n = 50) completed the DERS during their first week of inpatient treatment and at discharge (5 weeks later). These responses were compared to a group of social drinkers (n = 62).

Compared with social drinkers, alcohol-dependent patients reported significant differences in emotional awareness and impulse control during week 1 of treatment. Significant improvements in awareness and clarity of emotion were observed following 5 weeks of protracted abstinence. However, significant difficulties with impulse control persisted until discharge.

Findings from the DERS indicate protracted stress-related impulse control problems in abstinent alcoholics, which may contribute to increased relapse vulnerability

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Request Reprint E-Mail: helen.fox@yale.edu
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Asking patients about their drinking A national survey among primary health care physicians and nurses in Sweden
Addictive Behaviors Volume 33, Issue 2, February 2008, Pages 301-314

To investigate the extent to which Swedish primary health care (PHC) general practitioners (GPs) and nurses discuss alcohol issues with their patients, their reasons for and against addressing alcohol issues, their perceived importance of these issues, and factors that could facilitate increased alcohol intervention activity among the PHC professionals.

Fifty percent of the GPs and 28% of the nurses stated that they “frequently” discussed alcohol with their patients. The two most common reasons for asking patients about their drinking were that the GPs and nurses considered it part of their routines and the belief that the patient had alcohol-related symptoms.

GPs said that improved opportunities for referral to specialists and provision of more knowledge about counselling techniques for use when alcohol-related symptoms are evident were the most important facilitators to increased intervention activity.

Concerning the nurses, 93% stated that more time devoted to health-oriented work could facilitate increased alcohol intervention activity.

The findings highlight a considerable gap between the recognition of the significance of the alcohol problem and Swedish PHC intervention activity.

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Request Reprint E-Mail: mahol@ihs.liu.se

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Does gender moderate associations among impulsivity and health-risk behaviors�
Addictive Behaviors Volume 33, Issue 2, February 2008, Pages 252-265

The present study explores the relations among gender, impulsivity and three health-risk behaviors relevant to young adults (tobacco use, alcohol problems and gambling problems) in a sample of 197 college-age individuals. We sought to determine whether impulsivity is associated with health-risk behaviors in the same ways for men and women.

For tobacco use and gambling problems, men were at higher risk than women, and impulsivity was not significantly associated with higher risk.

Higher levels of motor impulsivity in men accounted for a significant amount of the gender difference in risk for alcohol problems. That is, impulsivity as measured by the Barratt Impulsiveness Scale (version 11), mediated the association between gender and risk for alcohol problems.

For impulsivity as measured by Stop Signal Reaction Time (i.e. response inhibition), gender moderated the association between impulsivity and alcohol problems. Specifically, lower levels of impulsivity were associated with greater risk for alcohol problems in both men and women, but the effect was stronger in men.

We speculate that this seemingly paradoxical result might be the result of coping drinking to deal with negative affect associated with behavioral overcontrol.

These findings suggest that prevention efforts might well focus on identifying individuals at high risk for alcohol problems, especially males, by assessing response inhibition.

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Request Reprint E-Mail: scottstoltenberg@bhsu.edu

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Beyond the “Binge” threshold: Heavy drinking patterns and their association with alcohol involvement indices in college students
Addictive Behaviors Volume 33, Issue 2, February 2008, Pages 225-234

Despite its ubiquity, the term “Binge” drinking has been controversial. Among other things, the grouping of drinkers into a single risk category based on a relatively low threshold may not capture adequately the nature of problem drinking behaviors.

The present study is an initial examination of the utility of delineating heavy drinkers into three groups; those who typically drink below the traditional “Binge” cutoff (less than 4+/5+ drinks per occasion for women/men), those who met traditional “Binge” drinking criteria, and a higher “Binge” cutoff of 6+/7+ (women, men). We examined differences in drunkenness, drinking frequency, and unique types of alcohol problems.

We found that the standard 4+/5+ drink “Binge” cutoff distinguishes drinkers across some but not all indices of alcohol involvement. “Binge” drinkers differed from their “Non-Binge” counterparts on eBAL, but for other indicators (drinking frequency, total alcohol consequences), only “Heavy Binge” drinkers differed significantly from “Non-Binge” drinkers.

Importantly, “Heavy Binge” drinkers experienced higher levels of those specific consequences associated with more problematic alcohol involvement.

Findings suggest that not all “Binge” drinkers drink alike, are equally drunk, or experience similar consequences. As such, there may be utility in distinguishing among heavy drinkers, in order to focus appropriately on those at greatest risk for different types of consequences.

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Request Reprint E-Mail: JPRead@buffalo.edu
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Approach to the genetics of alcoholism: A review based on pathophysiology
Biochemical Pharmacology Volume 75, Issue 1, 1 January 2008, Pages 160-177


Alcohol dependence is a common disorder with a heterogenous etiology. The results of family, twin and adoption studies on alcoholism are reviewed.

These studies have revealed a heritability of alcoholism of over 50%. After evaluating the results, it was epidemiologically stated that alcoholism is heterogenous complex disorder with a multiple genetic background.

Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcoholism. Strategies for gene identification are introduced to the reader, including family-based and association studies.

The susceptibility genes that are in the focus of this article have been chosen because they are known to encode for underlying mechanisms that are linked to the pathophysiology of alcoholism or that are important for the pharmacotherapeutic approaches in the treatment of alcohol dependence. Postulated candidate genes of the metabolism of alcohol and of the involved neurotransmitter systems are introduced.

Genetic studies on alcoholism examining the metabolism of alcohol and the dopaminergic, GABAergic, glutamatergic, opioid, cholinergic and serotonergic neurotransmitter systems as well as the neuropeptide Y are presented.

The results are critically discussed followed by a discussion of possible consequences.

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Request Reprint E-Mail: michael.koehnke@friedrich-petersen-klinik.de
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Key Role of Ethanol-Derived Acetaldehyde in the Motivational Properties Induced by Intragastric Ethanol: A Conditioned Place Preference Study in the Rat
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 21 December 2007

Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), is produced peripherally by gastric and hepatic alcohol dehydrogenase (ADH) and centrally by brain catalase. In spite of the aversive properties classically ascribed to ACD, it has recently been suggested that ACD might mediate some of the motivational effects of EtOH. Accordingly, the relative role of ACD in the positive motivational properties of EtOH ingested is increasingly becoming the matter of debate.

Thus, we studied the ability of intragastrically administered EtOH, ACD and EtOH-derived ACD to induce conditioned place preference (cpp) in rats.

Both, EtOH and ACD dose-dependently induced cpp; further, while EtOH-induced cpp was prevented by the administration of 4-MP and by DP, ACD-induced cpp was unaltered by 4-MP administration and prevented by DP. Both pretreatments did not interfere with morphine-induced cpp indicating that 4-MP and DP specifically modulate the motivational properties of EtOH and ACD.

The ability of 4-MP and DP to decrease EtOH-induced cpp suggests that a reduction of ACD levels is crucial in depriving EtOH from its motivational properties as indexed by the cpp procedure. In addition, this conclusion is supported by the inefficacy of 4-MP in preventing ACD-induced cpp, and by its blockade observed after administration of the selective ACD sequestrating agent DP.

The present results underscore the role of EtOH-derived ACD in EtOH-induced motivational properties as well as its abuse liability.

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Request Reprint E-Mail: apeana@uniss.it
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Acculturation, Drinking, and Alcohol Abuse and Dependence Among Hispanics in the Texas-Mexico Border
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 21 December 2007

Acculturation has been linked to an increased prevalence of alcohol-related problems. However, most of the research has been conducted with Hispanic populations in metropolitan areas of the United States, none of which is on the U.S.–Mexico border.

This study examines the association between acculturation, heavy episodic drinking, and DSM-IV alcohol abuse and dependence among Hispanics in the Texas–Mexico border.

The study used data from a survey conducted (2002 to 2003) along the Texas–Mexico border and included 472 male and 484 female Hispanic adults from El Paso, the Rio Grande Valley, and colonias. Based on the Acculturation Rating Scale for Mexican Americans-II scale, respondents were coded into 4 acculturation categories: "very Mexican oriented,""Mexican bicultural,""Anglo bicultural," or "very Anglo/Anglicized.".

Acculturation was related to lower rates of alcohol use disorders among men and a higher frequency of heavy episodic drinking among women. Multivariate analyses indicate that men who report heavy episodic drinking and those who are "very Mexican,""bicultural Mexican," or "bicultural Anglo" are more at higher risk for alcohol abuse and/or dependence compared with "very Anglo/Anglicized" men. For women, acculturation level did not predict alcohol disorders.

Statistical analyses included testing for bivariate associations and multivariate logistic regression predicting heavy episodic drinking alcohol abuse or dependence.

This study suggests that acculturation has different effects on drinking for men and women. This finding needs some attention as literature also indicates that women drink more and may develop more alcohol-related problems as they acculturate. This increase in women’s drinking is probably because of U.S. society’s more liberal norms governing female drinking. The "bimodal" distribution of risk, in which only men in "very Anglo" group are at a lower risk than the others, may be unique to the Border.

The association between acculturation and alcohol use disorders does not appear to be linear and the effect of acculturation is not uniform on individuals’ drinking behavior.

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Request Reprint E-Mail: Raul.caetano@UTSouthwestern.edu
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A Comparison of Results From an Alcohol Survey of a Prerecruited Internet Panel and the National Epidemiologic Survey on Alcohol and Related Conditions
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 21 December 2007

Given today’s telecommunications environment, random digit dial (RDD) telephone surveys face declining response rates and coverage, and increasing costs. As an alternative to RDD, we surveyed participants in a randomly recruited standing Internet panel supplemented with a randomly sampled telephone survey of nonpanel members for a study of associations between onset of alcohol use and later alcohol-related problems.

The purpose of this paper was to compare results from our survey with results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a face-to-face probability sample survey of 43,093 adults, with a focus on associations between demographics, age of drinking onset, and alcohol dependence.

Demographic and drinking characteristics from our survey of 4,021 ever-drinkers between the ages of 18 and 39 years were compared with the characteristics of 11,549 similarly aged ever-drinkers from the NESARC. Weighted analyses accounting for sampling design compared these 2 samples on drinking characteristics over the past year and during a respondent’s heaviest period of drinking, and in multivariate models examining associations between demographics, age of drinking onset, and lifetime alcohol dependence.

Participants in the supplemented Internet panel were similar to the national population of 18- to 39-year-old ever drinkers on gender, education, and race/ethnicity, while adults who were aged 18 to 25 years were under-represented in the Internet panel. The supplemented Internet panel reported higher rates of moderate risk drinking over the past 12 months, lifetime high-risk drinking, and lifetime (ever) alcohol dependence. Estimates of the associations between alcohol dependence and age of drinking onset, risky drinking, and family history of alcohol problems did not significantly differ between the supplemented Internet sample and the NESARC survey.

Randomly recruited Internet-based panels may provide an alternative to random digit dial telephone surveys and in-person surveys for some studies of factors associated with alcohol-related problems

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Request Reprint E-Mail: tch@bu.edu
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DSM-IV Criteria Endorsement Patterns in Alcohol Dependence: Relationship to Severity
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 21 December 2007

In DSM-IV, the diagnostic threshold for alcohol dependence (AD) is met when a patient presents with at least 3 of 7 criteria. We have computed the predictive value for each individual DSM-IV AD criterion, and examined subtypes of AD criteria endorsement patterns and their associated severity indicators for community-dwelling AD individuals.

We utilized data from the 2001 to 2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Positive predictive values (PPV) for DSM-IV AD were computed for each of the individual criteria. Patterns of criteria endorsements were identified by latent class analysis (LCA). Sociodemographic status, age of onset and duration of AD, patterns of drinking, and drinking treatment history, were conditional on DSM criteria endorsement clusters, as indicators of the respondents’ clinical severity.

At the individual criterion level, the single criterion with the greatest PPV was D7—"Activities given up" with 95% of drinking individuals who endorsed this DSM criterion correctly diagnosed as having DSM-IV AD. In addition to D7, only D5—"Physical/Psychological problems", and D6—"Time spent" had a PPV for AD substantially >50%. The LCA of AD endorsement patterns yielded a 6-cluster solution. The most common response pattern (34.5% of those with AD) was endorsement of 5 criteria: D1—"Quit/Control," D2—"Larger/Longer," D3—"Tolerance," D4—"Withdrawal," and D5—"Physical/Psychological problems." The most severe cluster (14%) was comprised of those who were likely to endorse 7/7 criteria. Cluster 1 (8.3%) did not include an endorsement of withdrawal, despite a heavy pattern of alcohol consumption. Unmarried status was associated with more severe criteria endorsement patterns.

The present findings indicate a Guttman-like scaling of endorsement which yielded associations with severity for some of the concurrent indicators included in the analysis. However, severity measures did not always increase with DSM-IV AD criterion endorsement counts. Although endorsement of 6/7 or 7/7 criteria was associated with greater severity across a variety of indicators, fewer criteria were randomly associated with these measures. These data do not support the use of AD symptom counts as a phenotypic dependent variable. At least 2 extant diagnostic criteria showed relatively low PPV for AD, indicating a need for further assessment of these criteria with new symptoms or re-wording of the current symptom items.

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Requst Reprint E-Mail: mossh@mail.nih.gov

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Distinct Mechanisms of Ethanol Potentiation of Local and Paracapsular GABAergic Synapses in the Rat Basolateral Amygdala
JPET 324:251-260, 2008

Converging lines of behavioral and pharmacological evidence suggest that GABAergic synapses in the basolateral amygdala (BLA) may play an integral role in mediating the anxiolytic effects of ethanol (EtOH).

Since anxiety is thought to play an important role in the development of, and relapse to, alcoholism, elucidating the mechanisms through which EtOH modulates GABAergic synaptic transmission in the BLA may be fundamental in understanding the etiology of this disease.

A recent study in mice has shown that principal cells within the BLA receive inhibitory input from two distinct types of GABAergic interneurons: a loosely distributed population of local interneurons and a dense network of paracapsular (pcs) GABAergic cells clustered along the external capsule border.

Here, we sought to confirm the presence of these two populations of GABAergic synapses in the rat BLA and evaluate their ethanol sensitivity.

Our results suggest that rat BLA pyramidal cells receive distinct inhibitory input from local and pcs interneurons and that EtOH potentiates both populations of synapses, albeit via distinct mechanisms. EtOH enhancement of local inhibitory postsynaptic currents (IPSCs) was associated with a significant decrease in paired-pulse ratio (PPR) and was significantly potentiated by the GABA_B receptor antagonist SCH 50911 [(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid], consistent with a facilitation of GABA release from presynaptic terminals. Conversely, EtOH enhancement of pcs IPSCs did not alter PPR and was not enhanced by SCH 50911 but was inhibited by blockade of noradrenergic receptors.

Collectively, these data reveal that EtOH can potentiate GABAergic inhibitory synaptic transmission in the rat BLA through at least two distinct pathways.


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Request Reprint E-Mail: jweiner@wfubmc.edu
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Alcohol Use, Depressive Symptoms and the Receipt of Antiretroviral Therapy in Southwest Uganda
AIDS and Behavior Online First 30 October 2007

Alcohol use and depressive symptoms are associated with reduced access to antiretroviral therapy (ART) in the developed world. Whether alcohol use and depressive symptoms limit access to ART in resource-limited settings is unknown.

This cross-sectional study examined the association between alcohol use, depressive symptoms and the receipt of ART among randomly selected HIV-positive persons presenting for primary health care services at an outpatient HIV clinic in Uganda. Depressive symptoms were defined by the Hopkins Symptom Checklist and alcohol use was measured through frequency of consumption questions. Antiretroviral use was assessed using a standardized survey and confirmed by medical record review. Predictors of ART use were determined via logistic regression.

Among 421 HIV-infected patients, factors associated with the receipt of ART were having at least primary education, having an opportunistic infection in the last 3 months, and not drinking within the last year.


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Request Reprint E-Mail: priscilla.martinez@medisin.uio.no
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Alcohol Use, Intimate Partner Violence, Sexual Coercion and HIV among Women Aged 15–24 in Rakai, Uganda
AIDS and Behavior Online First 7 Dec 2007

Disinhibition due to alcohol may induce intimate partner violence and sexual coercion and increased risk of HIV infection.

In a sample of 3,422 women aged 15–24 from the Rakai cohort, Uganda, we examined the association between self-reported alcohol use before sex, physical violence/sexual coercion in the past and prevalent HIV, using adjusted odds ratios (Adj OR) and 95% confidence intervals (95% CI).

During the previous year, physical violence (26.9%) and sexual coercion (13.4%) were common, and alcohol use before sex was associated with a higher risk of physical violence/sexual coercion.

HIV prevalence was significantly higher with alcohol consumption before sex (Adj OR = 1.45, 95% CI: 1.06–1.98) and especially when women reported both prior sexual coercion and alcohol use before sex (Adj OR = 1.79, 95% CI: 1.25–2.56).

Alcohol use before sex was associated with physical violence and sexual coercion, and both are jointly associated with HIV infection risk in young women.

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Request Reprint E-Mail: i.zablotska@unsw.edu.au
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A Daily Process Investigation of Alcohol-involved Sexual Risk Behavior Among Economically Disadvantaged Problem Drinkers Living with HIV/AIDS
AIDS and Behavior Online First 11 Dec 2007

Alcohol use is believed to increase sexual risk behavior among people living with HIV/AIDS (PLWHA). As drinking and sexual risk acts often occur in the same social contexts, this association is difficult to confirm.

In this study, electronic daily diaries were completed by 116 PLWHA over 5 weeks. This yielded a total of 1,464 records consisting of data pertaining to discrete occasions of anal and vaginal sex. Simultaneous within- and between-person multilevel analyses were conducted, including situational variables (partner type, partner serostatus, partner drinking) and individual difference variables (gender, level of alcohol dependence).

The resulting model explains 27.5% of the variance and reveals that interactions among these situational and individual difference variables predict changes in the estimated rate of unprotected sex (US).

Also, in defined contexts, the amount of alcohol consumed prior to sex significantly affects the rate of US among members of the sample.

Implications are discussed.

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Request Reprint E-Mail: william.barta@uconn.edu
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Mental Health & Substance Use: dual diagnosis

the conference

For the person experiencing co-existing mental health and substance use problems life presents many challenges. Their needs, often complex and multifaceted, extend beyond simply a mental health and substance use problem. For clinicians and services working with this group, this also presents many challenges. To effectively and creatively deliver care and services to meet the needs of individuals experiencing co-existing problems, professionals need to continually update knowledge and skills.

This one day conference explores some of the issues facing clients, professionals and services. It provides an insight into current thinking and latest developments in the field from a variety of perspectives: policy, practice and training. The conference draws together some of the UK’s leading clinicians, researchers and educators to consider how we meet the challenge, now and in the future, providing a thought provoking day.

In addition, the conference has the pleasure of hosting the UK launch of the new, international Taylor and Francis journal Mental Health and Substance Use: dual diagnosis and an opportunity to meet the Editor and members of the Advisory Board. All delegates will receive a year’s subscription to the journal and a copy of the first issue in their welcome pack.

Conference Flyer

Proposed Programme

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