Neuroscience: Pathways to Alcohol Dependence Part II — Overview of the Neuroadaptation, Risk, and Recovery

Alcohol Research & Health Volume 31, Number 4, 2009

IN THIS ISSUE

Who Is at Risk? Population Characterization of Alcohol Selfadministration In Nonhuman Primates Helps Identify Pathways to Dependence
Alcohol abuse and dependence are uniquely human disorders. However, scientists sometimes use animal models to study different aspects of alcohol abuse and dependence, including aspects that cannot be easily or ethically studied in humans. For example, studies of nonhuman primates, who share many genetic, anatomical, physiological, and behavioral characteristics with humans, can help to uncover risk factors that may either predispose a person to alcoholism or accelerate the course of alcohol addiction; these models therefore can shed light on these processes in humans in a way that other animal models cannot. In this article, Dr. Kathleen A. Grant, Mr. James Stafford, Ms. Allison Thiede, Ms. Caitlin Kiley, Ms. Misa Odagiri, and Dr. Betsy Ferguson present findings of studies analyzing drinking behaviors in populations of nonhuman primates and the neurological factors that may underlie differences in alcohol intake levels. The authors also discuss how these findings can help scientists to prevent and treat alcoholism in humans. (pp. 289–297)

The Molecular Basis of Tolerance
Tolerance is the body’s diminished response to alcohol or other drugs over the course of time and repeated exposure. This article by Drs. Andrzej Z. Pietrzykowski and Steven N. Treistman discusses the various degrees of tolerance—acute, rapid, or chronic— and how changes in tolerance induced by alcohol may affect several processes at the molecular, cellular, or behavioral level that are related to the onset of acute, rapid, or chronic tolerance. (pp. 298–309)

How Adaptation of the Brain to Alcohol Leads to Dependence: A Pharmacological Perspective
Alcohol causes both short- and long-term changes in brain chemistry. Long-term changes in some of the brain’s signaling systems have been linked to the behavioral effects of alcoholism. If a heavy drinker stops drinking suddenly, these changes can lead to the syndrome of alcohol withdrawal; additionally, they can make an alcohol-dependent person who has stopped drinking more likely to relapse. As described by Drs. Peter Clapp, Sanjiv V. Bhave, and Paula L. Hoffman, many brain chemicals are affected by both chronic exposure to alcohol and sudden cessation of alcohol consumption. Both alcohol-induced and withdrawalinduced changes to these signaling systems may lead to behavioral effects such as reinforcement, enhanced anxiety, and increased sensitivity to stress. The authors also explain how certain brain chemicals can be targeted by drugs meant to treat alcohol dependence. (pp. 310–339)

From Actions to Habits: Neuroadaptations Leading to Dependence
Overlapping cerebral networks associated with behavioral control processes such as reward-guided Pavlovian conditional responses, goal-directed instrumental actions, and stimulus-driven habits can be altered by alcohol and other drug abuse and therefore are important to the study of substance abuse. In this article, Dr. Henry H. Yin describes these networks and the mechanisms underlying reward-guided action selection and discusses their implications for alcohol addiction. (pp. 340–344)

Alcohol Dependence, Withdrawal, and Relapse
Alcohol dependence is associated with the development of physical and psychological withdrawal symptoms when alcohol use is stopped or significantly reduced. According to Dr. Howard C. Becker, fear of these withdrawal symptoms can perpetuate alcohol abuse in many alcohol-dependent people; moreover, the presence of such symptoms can trigger relapse in those who have abstained from alcohol. As Dr. Becker reports, both clinical studies and basic research studies using animal and human models have demonstrated that alcohol-related (conditioned) cues and contexts as well as stressful stimuli and events can trigger relapse. Improved understanding of the processes contributing to withdrawal and relapse may aid in the development of medications to treat alcohol dependence more effectively. (pp. 348–361)

Magnetic Resonance Imaging of the Living Brain: Evidence for Brain Degeneration Among Alcoholics and Recovery With Abstinence
Magnetic resonance imaging, or MRI, is a safe and noninvasive technology that allows scientists to examine the brain’s structure and function in real time. MRI technologies can show how the brain changes when exposed to alcohol over the short and long term, as well as how long these changes persist after a person has stopped drinking. In this article Ms. Margaret J. Rosenbloom and Dr. Adolf Pfefferbaum discuss how MRI studies, including longitudinal studies of animal models of alcoholism, can help researchers to understand how alcoholism develops and how it affects the brain. Through these studies, scientists have been able to explore specific alcohol-related changes to the brain, their duration, their effects on behavior, and the mechanisms through which the brain compensates for these changes. These studies suggest that some changes are reversed with abstinence, while others endure long after a person has stopped drinking. (pp. 362–376)

Alcohol-Related Neurodegeneration and Recovery: Mechanisms From Animal Models
Animal studies have established that alcohol can cause damage to brain cells, resulting in the loss of structure and function as well as inhibiting the production of neurons (i.e., neurogenesis), which ultimately leads to cognitive impairment. This article by Dr. Fulton T. Crews describes models of binge alcohol consumption in rats that induce changes in cognition similar to those found in human alcoholics. Findings from these animal studies provide insight into when, where, and how alcohol abuse and abstinence recovery dynamically change braincell composition, which could lead to new potential therapies for neurodegeneration, mental diseases, and alcohol use disorders. (pp. 377–388)

The Role of Selected Factors in the Development and Consequences of Alcohol Dependence
Studying the risk for developing alcoholism and the negative consequences of alcohol dependence is a complex process that requires an understanding of the various factors that may determine the degree of that risk. In this article, Rebecca Gilbertson, Robert Prather, and Dr. Sara Jo Nixon examine how gender, family history, comorbid psychiatric and substance use disorders, and age interact to influence an individual’s risk for alcoholism as well as how they interact with alcoholism to influence neurocognitive functioning following detoxification. (pp. 389–399)

Treatment Implications: Using Neuroscience to Guide the Development of New Pharmacotherapies for Alcoholism
Developing new medications to treat alcohol dependence requires a better understanding of the neuroscience of alcohol-drinking behavior. Although there are currently three approved medications for treating alcohol dependence— disulfiram, naltrexone, and acamprosate—new medications that target different neurochemical systems and that could be used either as adjunctive treatments or to treat subpopulations of drinkers are needed. In this article, Drs. Suchitra Krishnan-Sarin, Stephanie O’Malley, and John H. Krystal discuss the complex neuropharmacology of alcohol and how it can affect many different brain neurotransmitter systems. (pp. 400–407)

Glossary

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Altered White Matter Integrity in Adolescent Binge Drinkers
Alcoholism: Clinical and Experimental Research
Published Online: 21 Apr 2009

White matter integrity has been found to be compromised in adult alcoholics, but it is unclear when in the course of alcohol exposure white matter abnormalities become apparent. This study assessed microstructural white matter integrity among adolescent binge drinkers with no history of an alcohol use disorder.

Binge drinkers had lower FA than controls in 18 white matter areas (clusters ≥27 contiguous voxels, each with p < 0.01) throughout the brain, including the corpus callosum, superior longitudinal fasciculus, corona radiata, internal and external capsules, and commissural, limbic, brainstem, and cortical projection fibers, while exhibiting no areas of higher FA. Among binge drinkers, lower FA in 6 of these regions was linked to significantly greater lifetime hangover symptoms and/or higher estimated peak blood alcohol concentrations.

Binge drinking adolescents demonstrated widespread reductions of FA in major white matter pathways. Although preliminary, these results could indicate that infrequent exposure to large doses of alcohol during youth may compromise white matter fiber coherence.

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Request Reprint E-Mail: stapert@ucsd.edu
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Per capita alcohol consumption and sickness absence in Norway
The European Journal of Public Health Advance Access published online on April 15, 2009


There is only one previous study addressing the relationship between population drinking and sickness absence. That study, based on Swedish time-series data, showed a statistically significant relationship between per capita alcohol consumption and the male sickness absence rate. Estimates suggested that a 1-l increase in consumption was associated with a 13% increase in sickness absence among men. In the present study, we aim at replicating and expanding the Swedish study on the basis of data for Norway.

The results suggested that a 1-l increase in total consumption was associated with a 13% increase in sickness absence among men (P < 0.05). This corresponds to an elasticity coefficient equal to 0.62. The alcohol effect was not significant for women. Unemployment was negatively associated with the outcome for men as well as for women (P < 0.05). In the beverage-specific analyses, spirits were statistically significant for men (P < 0.05), but not beer and wine.

The present findings strengthen the conclusion from the Swedish study, that sickness absence may be added to the list of indicators of alcohol-related harm.

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Request Reprint E-Mail: totto@sofi.su.se
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Does binge drinking increase the risk of lung cancer: results from the Findrink study

The European Journal of Public Health Advance Access published online on April 15, 2009

There are controversies on the role of alcohol in lung cancer but no studies have examined the role of alcohol consumption patterns. We examined the association between binge drinking and lung cancer.

Prospective population based study of 2267 middle aged men from Finland without a history of lung cancer at baseline.

There were 65 cases of lung cancer during an average follow-up of 16.7 years. The relative risk (RR) of lung cancer for binge drinkers was 1.89 (95% CI 1.10–3.20) after adjusting for age, examination year, family history of cancer, smoking, socio-economic status (SES), leisure-time physical activity and body mass index (BMI). No increased risk was observed among non-smoking binge drinkers, RR 1.48 (95% CI 0.89–2.47). Binge drinking smokers had increased risks of lung cancer in all categories of daily smoking compared with non-binge drinking smokers. The RR were 2.70 (95% CI 1.61–4.53), 2.35 (95% CI 1.38–3.96) and 2.24 (95% CI 1.29–3.80) for those who smoked 1–19, 20–29 and 30/day, respectively.

Binge drinking is not associated with an increased risk of lung cancer among non-smokers but among smokers, it is associated with an increased risk irrespective of the number of cigarettes smoked daily. Even though the number of lung cancer cases among non-smokers was relatively small, the fact that the increased risk was limited to only smokers means that residual confounding by smoking may play a role. Larger studies are needed to clarify this association.

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Request Reprint E-Mail: Adetunji.toriola@uta.fi

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Ethanol Teratogenesis in Five Inbred Strains of Mice
Alcoholism: Clinical and Experimental Research
Published Online: 21 Apr 2009


Previous studies have demonstrated individual differences in susceptibility to the detrimental effects of prenatal ethanol exposure. Many factors, including genetic differences, have been shown to play a role in susceptibility and resistance, but few studies have investigated the range of genetic variation in rodent models.

B6 mice exposed to ethanol in utero had fetal weight deficits and digit, kidney, brain ventricle, and vertebral malformations. In contrast, 129 mice showed no teratogenesis. The remaining strains showed varying degrees of teratogenesis.

Differences among inbred strains demonstrate genetic variation in the teratogenic effects of ethanol. Identifying susceptible and resistant strains allows future studies to elucidate the genetic architecture underlying prenatal alcohol phenotypes.

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Request Reprint E-Mail: cdowning@colorado.edu
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Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence
Molecular Psychiatry (2009) 14, 501–510


Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability.

Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3'-UTR of the CHRNA3 gene and nicotine dependence.

In this study we performed a comprehensive association analysis of the CHRNA5–CHRNA3–CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence.

Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence.

These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation.

Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.

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Request Reprint E-Mail: goate@icarus.wustl.edu


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Improving public addiction treatment through performance contracting: The Delaware experiment

Health Policy Volume 87, Isue 3, pages 296-308 (September 2008

In fiscal 2002, Delaware replaced traditional cost-reimbursement contracts with performance-based contracts for all outpatient addiction treatment programs. Incentives included 90% capacity utilization and active patient participation in treatment.

One of the programs failed to meet requirements. Strategies adopted by successful programs included extended hours of operation, facility enhancements, salary incentives for counselors, and two evidence-based therapies (MI and CBT). Average capacity utilization from 2001 to 2006 went from 54% to 95%; and the average proportion of patients’ meeting participation requirements went from 53% to 70%—with no notable changes in the patient population.

We conclude that properly designed, program-based contract incentives are feasible to apply, welcomed by programs and may help set the financial conditions necessary to implement other evidence-based clinical efforts; toward the overall goal of improving addiction treatment.

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Request Reprint E-Mail: tmclellan@tresearch.org

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The Importance of Keeping Regular: Accurate Guidance to the Public on Low-Risk Drinking Levels
Alcohol and Alcoholism 2009 44(3):226-228


The aim of this study was to argue that recommendations to the general public on daily amounts for low-risk alcohol consumption must retain the word ‘regular’ in order to avoid being rejected.

Narrative review of the evidence-base for daily limits to alcohol consumption, the guidance the public actually receives in the UK and media reactions to this guidance.

Evidence for daily limits (not more than 3–4 units for men and 2–3 units for women) rests on epidemiological surveys that enquire about ‘average’ or ‘usual’ amounts of consumption and this is reflected by the use of ‘regular’ or ‘consistent’ in the UK Government's Sensible Drinking report in 1995 and in guidance currently issued by the English Department of Health. In contrast, guidance the public actually receives often omits the word ‘regular’ and implies that the limits in question are maximum daily amounts. Media reactions to this inaccurate information suggest that the general public is likely to find these recommendations incredible and to reject them.

If guidance to the public on daily drinking amounts is to stand any chance of being credible and effective, it must be accurate and must therefore retain the word ‘regular’.

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Request Reprint E-Mail: nick.heather@northumbria.ac.uk
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Explaining change and stasis in alcohol consumption
Addiction Research & Theory Published Online 10 March 2009

The term 'saturation' has often been used when alcohol consumption in a region stays the same despite there having been reason to expect an increase, e.g. after a decrease of taxation. However, the term 'saturation' has been used only descriptively, and in different ways.

We therefore propose a wider-ranging framework for understanding and explaining trends in alcohol consumption, illustrating the operation of the factors with historical or contemporary examples. In the framework, we include not only taxes and other alcohol controls, but also situational and other norms on drinking and intoxication, competing responsibilities and attractions that demand or favour sobriety, structural changes, external influences and the range of societal or cultural responses to alcohol problems.

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Request Reprint E-Mail: robin.room@sorad.su.se
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Should alcohol policies aim to reduce total alcohol consumption? New analyses of Canadian drinking patterns

Addiction Research & Theory, Volume 17, Issue 2 April 2009 , pages 135 - 151

We investigated whether high-risk drinking patterns are restricted to a few high-volume drinkers or are evenly distributed across the population to inform discussion regarding the optimal mix of targeted versus universal prevention strategies.

Drinking patterns reported in the 2004 Canadian Addiction Survey (CAS, n = 13,909) were assessed against various low-risk drinking guidelines. Under-reporting was assessed against known alcohol sales for 2004. Non-response bias due to the low response rate (47%) was investigated through comparisons with the 2002 Canadian Community Health Survey (CCHS).

Self-reported alcohol consumption for the past week and past year accounted for between 31.9% and 37.0%, respectively of official alcohol sales data. Comparisons with the 2002 CCHS suggested only limited non-response bias.

Many more respondents regularly placed themselves at risk of short-term harm (20.6%) than exceeded guidelines for avoiding long-term health problems (3.9%). Ten percent of respondents consumed more than 50% of total self-reported consumption. Most alcohol (73.4%) consumed by the sample in the previous week was drunk in excess of Canadian low-risk drinking guidelines - for 19 to 24 year olds this figure was 89.4%.

These data provide support both for universal prevention strategies (e.g. reducing economic and physical availability of alcohol) as well as targeted interventions for risky drinkers (e.g. screening and brief interventions in primary health care settings).

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Request Reprint E-Mail: timstock@uvic.ca

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Adolescent risk factors for excessive alcohol use at age 32 years. A 16-year prospective follow-up study

Social Psychiatry and Psychiatric Epidemiology 0933-7954 (Print) 1433-9285 (Online) April, 16, 2009

To examine which socioeconomic, family, personal and lifestyle risk factors in adolescence were the strongest independent predictors of excessive alcohol use in adulthood.

All the socioeconomic, family, personal, and lifestyle variables in adolescence, except parental social class in both genders and self-esteem among females, showed significant univariate associations with excessive alcohol use at age 32 years. Multivariate logistic regression analysis showed that among adolescent males, parental divorce, moderate and high level of depressive symptoms, leisure-time spent daily among friends and moderate and drunkenness-orientated drinking were the strongest predictors of excessive alcohol use in adulthood. Among females, the strongest adolescent predictors of excessive alcohol use in adulthood were drunkenness-orientated drinking and frequent smoking.

Early interventions for adolescent substance use and a set of specific psychosocial risk factors should be tailored and evaluated as methods for identifying those at high risk of and preventing excessive alcohol use in adulthood.

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Request Reprint E-Mail: taina.huurre@thl.fi

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Recovery: Linking Addiction Treatment and Communities of Recovery
Scottish Addiction Library 16 April 2009

William White and Ernest Kurtz primer for addiction professionals wanting to utilise the complementary power of mutual aid or self-help networks. Keywords: mutual aid, self-help, AA, NA, alcoholics anonymous, narcotics anonymous, recovery, recovery communities, abstinence.

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Population-based study of baseline ethanol consumption and risk of incident essential tremor

Journal of Neurology, Neurosurgery, and Psychiatry 2009;80:494-497

Recent postmortem studies have demonstrated pathological changes, including Purkinje cell loss, in the cerebellum in essential tremor (ET). Toxic exposures that compromise cerebellar tissue could lower the threshold for developing ET. Ethanol is a well-established cerebellar toxin, resulting in Purkinje cell loss.

To test whether higher baseline ethanol consumption is a risk factor for the subsequent development of incident ET.

Lifetime ethanol consumption was assessed at baseline (1994–1995) in a prospective, population-based study in central Spain of 3285 elderly participants, 76 of whom developed incident ET by follow-up (1997–1998).

In a Cox proportional hazards model adjusting for cigarette pack-years, depressive symptoms and community, the baseline number of drink-years was marginally associated with a higher risk of incident ET (relative risk, RR = 1.003, p = 0.059). In an adjusted Cox model, the highest baseline drink-year quartile doubled the risk of incident ET (RR = 2.29, p = 0.018), while other quartiles were associated with more modest elevations in risk (RR3rd quartile = 1.82 (p = 0.10), RR2nd quartile = 1.75 (p = 0.10), RR1st quartile = 1.43 (p = 0.34) vs non-drinkers (RR = 1.00)). With each higher drink-year quartile, the risk of incident ET increased an average of 23% (p = 0.01, test for trend).

Higher levels of chronic ethanol consumption increased the risk of developing ET. Ethanol is often used for symptomatic relief; studies should explore whether higher consumption levels are a continued source of underlying cerebellar neurotoxicity in patients who already manifest this disease.

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Request Reprint E-Mail: EDL2@columbia.edu

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Ethanol- and cocaine-induced locomotion are genetically related to increases in accumbal dopamine

Genes, Brain and Behavior Volume 8 Issue 3, Pages 346 - 355

Neuroanatomical research suggests that interactions between dopamine and glutamate within the mesolimbic dopamine system are involved in both drug-induced locomotor stimulation and addiction. Therefore, genetically determined differences in the locomotor responses to ethanol and cocaine may be related to differences in the effects of these drugs on this system.

To test this, we measured drug-induced changes in dopamine and glutamate within the nucleus accumbens (NAcc), a major target of mesolimbic dopamine neurons, using in vivo microdialysis in selectively bred FAST and SLOW mouse lines, which were bred for extreme sensitivity (FAST) and insensitivity (SLOW) to the locomotor stimulant effects of ethanol. These mice also show a genetically correlated difference in stimulant response to cocaine (FAST > SLOW).

Single injections of ethanol (2 g/kg) or cocaine (40 mg/kg) resulted in larger increases in dopamine within the NAcc in FAST compared with SLOW mice. There was no effect of either drug on NAcc glutamate levels.

These experiments indicate that response of the mesolimbic dopamine system is genetically correlated with sensitivity to ethanol- and cocaine-induced locomotion.

Because increased sensitivity to the stimulating effects of ethanol appears to be associated with greater risk for alcohol abuse, genetically determined differences in the mesolimbic dopamine response to ethanol may represent a critical underlying mechanism for increased genetic risk for alcoholism.

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Request Reprint E-Mail: phillipt@ohsu.edu

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High-Risk Drinking Down as Result of Broad Initiative

News & Information April, 14, 2009

Fewer UC Davis students are engaging in high-risk drinking and the community is raising expectations for responsible behavior related to alcohol and parties, according to a report on a major local effort.

The Safe Party Initiative at UC Davis began as part of a $6.9 million research project at 14 UC and California State University campuses to help combat high-risk drinking among college students in California.

Over the last four years, the UC Davis initiative showed students how to reduce alcohol-related risks at parties, fostered better relationships among students and their neighbors, and increased the visibility of law enforcement related to alcohol use.

. . . . .

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Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model

Neuroscience & Biobehavioral Reviews Article in Press, 24 March 2009

The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities.

This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential.

The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects.

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Request Reprint E-Mail: rpautassi@psyche.unc.edu.ar

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AP15
Policies for Reducing Problems Associated with Alcohol Availability

The 15th in a series of conferences on the avoidance of alcohol-related problems using public policy strategies

When?
TBA during either the second half of 2010 or first half of 2011

Where?
Washington, DC (tentative)

Why now?
The new federal administration has signaled a renewed interest in science and public health. Meanwhile, states and localities are facing increased demand for public services in the face of declining revenues. Evidence-based alcohol policy can reduce alcohol problems and resultant social costs, simultaneously generating revenue (alcohol excise taxes and other user fees) to promote public health and safety.

Who should attend?
We welcome an anticipated attendance of up to 300 participants, including community-based practitioners, public officials, and researchers from across North America and beyond.

More information
Call for abstracts, scholarship availability, exhibit opportunities, and accommodations forthcoming via silvergategroup.com/ap15. Reach Silver Gate Group staff by e-mail – tomc@silvergategroup.com.

Read More Conference Infgormation (PDF)


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Influence of a Drinking Quantity and Frequency Measure on the Prevalence and Demographic Correlates of DSM-IV Alcohol Dependence
Alcoholism: Clinical and Experimental Research Volume 33 Issue 5, Pages 761 - 771

Recent research suggests that adding a quantity/frequency alcohol consumption measure to diagnoses of alcohol use disorders may improve construct validity of the diagnoses for Diagnostic and Statistical Manual of Mental and Behavior Disorders (DSM-V).

This study explores the epidemiological impact of including weekly at-risk drinking (WAD) in the DMS-IV diagnostic definition of alcohol dependence via 3 hypothetical reformulations of the current criteria.

The sample was the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample with 43,093 adults aged >18 in the U.S interviewed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule IV. The current (DSM-IV) definition of alcohol dependence was compared with 4 hypothetical alcohol dependence reformulations that included WAD: (1) WAD added as an eighth criteria; (2) WAD required for a diagnosis; (3) adding abuse and dependence criteria together, and including WAD with a 3 of 12 symptom threshold; (4) adding abuse and dependence criteria together, and including WAD with a 5 of 12 symptom threshold.

The inclusion of at-risk drinking as an eighth criterion of alcohol dependence has a minimal impact on the sociodemographic correlates of alcohol dependence but substantially increases the prevalence of dependence (from 3.8% to 5.0%). At-risk drinking as a required criterion or as part of a diagnosis that combines abuse with dependence criteria with a higher threshold (5+ criteria) decreases prevalence and has a larger impact on sociodemographic correlates. Blacks, Hispanics, and women are less likely to be included in diagnostic reformulations that include WAD, whereas individuals with low-income and education are more likely to remain diagnosed.

Including WAD as either a requirement of diagnosis or as an additional criterion would have a large impact on the prevalence of alcohol dependence in the general population. The inclusion of a quantity/frequency requirement may eliminate false positives from studies of alcohol disorder etiology and improve phenotype definition for genetic association studies by reducing heterogeneity in the diagnosis, but may also reduce eligibility for treatment services among women and racial/ethnic minorities compared

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Request Reprint E-Mail: dsh2@columbia.edu
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Protective Effect of Vitamin E Against Ethanol-Induced Hyperhomocysteinemia, DNA Damage, and Atrophy in the Developing Male Rat Brain

Alcoholism: Clinical and Experimental Research Published Online: 9 Apr 2009

Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by clinical investigations and animal experiments. It has been posited that elevated levels of Hcy mediate DNA damage, brain atrophy, and excitotoxicity. The current study sought to elucidate the effect of vitamin E on ethanol-induced hyperhomocysteinemia, DNA damage, and atrophy in the developing hippocampus and cerebellum of rats.

The results revealed that along with a significant decrease in brain, cerebellum, and hippocampus weights in animals that received alcohol, the levels of DNA damage and Hcy significantly increased. Significant amelioration of brain atrophy and DNA damage as well as restoration of the elevated level of Hcy to that of controls were found in vitamin E-treated rats.

These findings strongly support the idea that ethanol intake by dams during pregnancy and lactation induces Hcy-mediated oxidative stress in the developing hippocampus and cerebellum of offspring rats, and that these effects can be alleviated by vitamin E as an antioxidant.

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Request Reprint E-Mail: ashirpoor@yahoo.com

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Sex Differences in Drug-Related Stress-System Changes: Implications for Treatment in Substance-Abusing Women

Harvard Review of Psychiatry, Volume 17, Issue 2 April 2009 , pages 103 - 119

Extensive research indicates that chronic substance abuse disrupts stress and reward systems of the brain. Gender variation within these stress-system alterations, including the impact of sex hormones on these changes, may influence sex-specific differences in both the development of, and recovery from, dependency.

As such, gender variations in stress-system function may also provide a viable explanation for why women are markedly more vulnerable than men to the negative consequences of drug use.

This article therefore initially reviews studies that have examined gender differences in emotional and biophysiological changes to the stress and reward system following the acute administration of drugs, including cocaine, alcohol, and nicotine.

The article then reviews studies that have examined gender differences in response to various types of stress in both healthy and drug-abusing populations. Studies examining the impact of sex hormones on these gender-related responses are also reported.

The implications of these sex-specific variations in stress and reward system function are discussed in terms of both comorbid psychopathology and treatment outcome.

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Request Reprint E-Mail: helen.fox@yale.edu

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The affordability of alcoholic beverages in the European Union: Understanding the link between alcohol affordability,consumption and harms

The European Commission (EC) commissioned RAND Europe to conduct a study on theaffordability of alcohol products across the EU, and on the potential impacts ofaffordability on harmful use of alcohol. On this basis, the study is intende to provideevidence on whether alcohol affordability could be a useful policy lever to publicauthorities seeking to reduce harmful alcohol consumption in Europe.

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Public Health Campaigns to Change Industry Practices That Damage Health: An Analysis of 12 Case Studies

Health Education & Behavior, Vol. 36, No. 2, 230-249 (2009

Industry practices such as advertising, production of unsafe products, and efforts to defeat health legislation play a major role in current patterns of U.S. ill health. Changing these practices may be a promising strategy to promote health.

The authors analyze 12 campaigns designed to modify the health-related practices of U.S. corporations in the alcohol, automobile, food and beverage, firearms, pharmaceutical, and tobacco industries.

The objectives are to examine the interactions between advocacy campaigns and industry opponents; explore the roles of government, researchers, and media; and identify characteristics of campaigns that are effective in changing health-damaging practices. The authors compared campaigns that operate at different levels of organization and use different strategies.

Findings suggest that many campaigns achieve policy or mobilization outcomes that may contribute to improved health; local campaigns may be more effective than national ones; and advocates frequently frame their campaigns on the themes of children's health and social justice.

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Request Reprint E-Mail: nfreuden@hunter.cuny.edu
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Wage Penalty of Abstinence and Wage Premium of Drinking -A misclassification bias due to pooling of drinking groups?

Several studies have found protective effects of low/moderate (hereafter “light”) alcohol consumption compared with “abstinence” on mortality, health and wage. Some of these studies have been criticised because former drinkers have been included among the abstainers, which may overstate the protective effect of light alcohol consumption. It has also been proposed, but not shown, that the commonly pooled group of light drinkers and former heavy drinkers would understate the protective effect of light drinking. We also suggest that former abstainers might cause the same effect when pooled with light drinkers.

The aim of this paper is to study whether pooled groups risk create bias in the form of misclassification and confounding. The analysis focuses on: ‘former drinker error’ (pooling of lifelong abstainers and former drinkers); ‘former abstainer error’ (pooling of former abstainers and lifelong light
drinkers); and ‘former heavy drinker error’ (pooling of light drinkers with and without history of heavy drinking). Swedish panel data were used in a multinomial logit model, presenting odds ratios when comparing the subgroups.

The results demonstrate that commonly pooled groups are heterogeneous with respect to a number of variables, which may implicate confounding. Given appropriate controls, misclassification bias is likely in the pooled group of light drinkers.

The direction of the misclassification bias, however, is to underestimate the beneficial effect of light alcohol consumption on wage and can therefore not explain the wage penalty of abstinence compared to light drinking.

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Fetal ethanol exposure increases ethanol intake by making it smell and taste better

PNAS March 31, 2009 vol. 106 no. 13 5359-5364

Human epidemiologic studies reveal that fetal ethanol exposure is highly predictive of adolescent ethanol avidity and abuse. Little is known about how fetal exposure produces these effects. It is hypothesized that fetal ethanol exposure results in stimulus-induced chemosensory plasticity. Here, we asked whether gestational ethanol exposure increases postnatal ethanol avidity in rats by altering its taste and odor.

Experimental rats were exposed to ethanol in utero via the dam's diet, whereas control rats were either pair-fed an iso-caloric diet or given food ad libitum. We found that fetal ethanol exposure increased the taste-mediated acceptability of both ethanol and quinine hydrochloride (bitter), but not sucrose (sweet). Importantly, a significant proportion of the increased ethanol acceptability could be attributed directly to the attenuated aversion to ethanol's quinine-like taste quality.

Fetal ethanol exposure also enhanced ethanol intake and the behavioral response to ethanol odor. Notably, the elevated intake of ethanol was also causally linked to the enhanced odor response. Our results demonstrate that fetal exposure specifically increases ethanol avidity by, in part, making it taste and smell better.

More generally, they establish an epigenetic chemosensory mechanism by which maternal patterns of drug use can be transferred to offspring. Given that many licit (e.g., tobacco products) and illicit (e.g., marijuana) drugs have noteworthy chemosensory components, our findings have broad implications for the relationship between maternal patterns of drug use, child development, and postnatal vulnerability.

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Request Reprint E-Mail: youngens@upstate.edu

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Health professionals add more support for pricing controls on alcohol

The Royal College of Physicians and Royal College of Nursing Survey on Alcohol Treatment Services published last week asked gastroenterologists, hepatologists, acute physicians and nurses for their expert opinion on Government policy initiatives and national strategies to tackle alcohol related harm, the provision of service for people with alcohol related health problems and the scale of alcohol related health harms in their particular clinical environment. . . . . .

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PATHWAYS TO ABSTINENCE: IMPACT OF ALCOHOLICS ANONYMOUS





-The results of the present study support the efficacy of the fellowship of Alcoholics Anonymous to promote abstinence


-In 1992 Americans with alcohol use disorders who continued to attend AA were more likely to achieve abstinence (64%) than those who dropped out of AA (37%) or those who never attended AA (16%)

-Abstinence recovery status varies as a function of increasing age and level of severity of alcohol symptoms.


-The findings suggest that a substantial portion of the "AA drop outs" attain sobriety or abstinence after a period of AA membership and maintain their abstinence without AA


- The unmet need for AA referral is concentrated in the younger age groups, 35% in the 18-29 years group and 30% in the 30-39 years age group.


Read Full KNOL
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Effectiveness of Making Alcoholics Anonymous Easier: A group format 12-step facilitation approach

Journal of Substance Abuse Treatment Article in Press 1 April 2009

Most treatment programs recommend clients attend 12-step groups, but many drop out posttreatment. The effectiveness of Making Alcoholics Anonymous [AA] Easier (MAAEZ ), a manual-guided intervention designed to help clients connect with individuals encountered in AA, was tested using an “OFF/ON” design (n = 508).

MAAEZ effectiveness was determined by comparing abstinence rates of participants recruited during ON and OFF conditions and by studying the effect of the number of MAAEZ sessions attended. At 12 months, more clients in the ON condition (vs. OFF) reported past 30-day abstinence from alcohol (p = .012), drugs (p = .009), and both alcohol and drugs (p = .045). In multivariate analyses, ON condition participants had significantly increased odds of abstinence from alcohol (odds ratio [OR] = 1.85) and from drugs (OR = 2.21); abstinence odds also increased significantly for each additional MAAEZ session received.

MAAEZ appeared especially effective for those with more prior AA exposure, severe psychiatric problems, and atheists/agnostics. MAAEZ represents an evidence-based intervention that is easily implemented in existing treatment programs.

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Request Reprint E-Mail: lkaskutas@arg.org

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Tracking Adolescent Substance Use and Abuse in North Carolina


Duke University has just launched a great website that allows policymakers and others to get information about teen aclohol and drug use in North Carolina. It pulls from multiple public information sources about teen arrests for possession by drug, emergency room visits, and much more. County data can be compared to state data, data can be examined by county on a map of North Carolina ... and that's just the start.
. . . . .


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Problemas relacionados con el consumo de alcohol en jóvenes de la provincia de Jujuy, Argentina.

Salud pública Méx [online]. 2008, v. 50, n. 4, pp. 300-307.

To examine drinking patterns and alcohol-related problems among youth in Jujuy, Argentina.

A survey was conducted in 2005 with a representative sample of 9th grade youth (12 to 17 years old) including sociodemographic and consumption data, and the AUDIT-C test.

Nine percent of girls and 11% of boys reported hazardous drinking; 12% of girls and 19% of boys reported dependence symptoms. The odds ratio for dependence symptoms (adjusted OR 0.7; 95%CI: 0.6-0.8) and for hazardous drinking (adjusted OR 0.7; 95%CI: 0.6-0.8) was significantly lower for girls compared with boys. Older age, working, and attending night school were risk factors for hazardous drinking, dependence symptoms, and harmful drinking.

A significant proportion of youth reported problematic patterns of alcohol drinking, highlighting the need to implement prevention and treatment interventions tailored to the adolescent population

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Request Reprint E-Mail: e_alderete@arnet.com.ar

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Children Living with Substance-Dependent or Substance-Abusing Parents: 2002 to 2007

Highlights:

Combined data from SAMHSA's 2002 to 2007 National Surveys on Drug Use and Health were used to provide average annualized estimates of the number of children under age 18 living with a substance abusing parent, that is, a parent who was dependent on or abused alcohol or an illicit drug.

Over 8.3 million children (11.9%) lived with at least one parent who was dependent on or abused alcohol or an illicit drug during the past year.

Of the children living with a substance abusing parent, almost 7.3 million (10.3%) lived with a parent who was dependent on or abused alcohol, and about 2.1 million (3.0%) lived with a parent who was dependent on or abused illicit drugs.

About 5.4 million children under 18 years of age lived with a father who met the criteria for past year substance dependence or abuse and 3.4 million lived with a mother who met the criteria.

Read Full Report (PDF)

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Reclaiming Futures Launches Blog Dedicated to Substance Abuse and Teens in the Juvenile Justice System

Reclaiming Futures Every Day is a professionally-staffed blog that aims to keep people informed of the latest happenings in juvenile justice and substance abuse treatment. Launched by Reclaiming Futures, an initiative of the Robert Wood Johnson Foundation, it can be found at http://blog.reclaimingfutures.org/, and is designed to help readers:

• Discuss the national challenge of helping teens break the cycle of drugs, alcohol and crime.

• Comment on new developments in teen alcohol and drug treatment and juvenile justice reform.

• Stay in touch with what's going on in the 23 communities using the proven Reclaiming Futures approach.

• Receive expert opinions and commentary from regular contributors who are leaders in the field.

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Disparity Between Tonic and Phasic Ethanol-Induced Dopamine Increases in the Nucleus Accumbens of Rats
Alcoholism: Clinical and Experimental Research Published Online: 9 Apr 2009

Dopamine concentrations in the nucleus accumbens fluctuate on phasic (subsecond) and tonic (over minutes) timescales in awake rats. Acute ethanol increases tonic concentrations of dopamine, but its effect on subsecond dopamine transients has not been fully explored.

Microdialysis samples yielded significant tonic increases in dopamine concentrations at 1 to 2 g/kg ethanol in each rat, while repeated saline infusions had no effect. When monitored with fast scan cyclic voltammetry, ethanol increased the frequency of dopamine transients in 6 of 16 recording sites, in contrast to the uniform effect of ethanol as measured with microdialysis. In the remaining 10 recording sites that were unresponsive to ethanol, dopamine transients either decreased in frequency or were unaffected by cumulative ethanol infusions, patterns also observed during repeated saline infusions. The responsiveness of particular recording sites to ethanol was not correlated with either core versus shell placement of the electrodes or the basal rate of dopamine transients. Importantly, the phasic response pattern to a single dose of ethanol at a particular site was qualitatively reproduced when a second dose of ethanol was administered, suggesting that the variable between-site effects reflected specific pharmacology at that recording site.

These data demonstrate that the relatively uniform dopamine concentrations obtained with microdialysis can mask a dramatic heterogeneity of phasic dopamine release within the accumbens.

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Request Reprint E-Mail: DLR@unc.edu
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Proopiomelanocortin Peptides Are Not Essential for Development of Ethanol-Induced Behavioral Sensitization
Alcoholism: Clinical and Experimental Research Published Online: 9 Apr 2009

Behavioral sensitization is a result of neuroadaptation to repeated drug administration and is hypothesized to reflect an increased susceptibility to drug abuse. Proopiomelanocortin (POMC) derived peptides including β-endorphin and α-melanocyte stimulating hormone have been implicated in development of behavioral sensitization and the reinforcing effects of alcohol and other drugs of abuse.

This study used a genetically engineered mouse strain that is deficient for neural POMC to directly determine if any POMC peptides are necessary for the development of ethanol-induced locomotor sensitization.

There was no significant difference in BEC between genotypes (WT = 2.11 ± 0.06; KO = 2.03 ± 0.08 mg/ml). Both WT and nPOMC-deficient mice treated repeatedly with ethanol demonstrated a significant increase in locomotor activity on test day when compared to repeated saline-treated counterparts. In addition, mice of both genotypes in the repeated saline groups showed a significant locomotor stimulant response to acute ethanol injection.

Central POMC peptides are not required for either the acute locomotor stimulatory effect of ethanol or the development of ethanol-induced locomotor sensitization. While these peptides may modulate other ethanol-associated behaviors, they are not essential for development of behavioral sensitization.

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Request Reprint E-Mail: sharpea@uthscsa.edu
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The Impact of Underage Drinking Laws on Alcohol-Related Fatal Crashes of Young Drivers
Alcoholism: Clinical and Experimental Research Published Online: 9 Apr 2009

This study used a pre- to post-design to evaluate the influence on drinking-and-driving fatal crashes of 6 laws directed at youth aged 20 and younger and 4 laws targeting all drivers..

Significant decreases in the underage fatal CIR were associated with presence of 4 of the laws targeting youth (possession, purchase, use and lose, and zero tolerance) and 3 of the laws targeting all drivers (0.08 blood alcohol concentration illegal per se law, secondary or upgrade to a primary seat belt law, and an administrative license revocation law). Beer consumption was associated with a significant increase in the underage fatal CIR. The direct effects of laws targeting drivers of all ages on adult drinking drivers aged 26 and older were similar but of a smaller magnitude compared to the findings for those aged 20 and younger. It is estimated that the 2 core underage drinking laws (purchase and possession) and the zero tolerance law are currently saving an estimated 732 lives per year controlling for other exposure factors. If all states adopted use and lose laws, an additional 165 lives could be saved annually.

These results provide substantial support for the effectiveness of under age 21 drinking laws with 4 of the 6 laws examined having significant associations with reductions in underage drinking-and-driving fatal crashes. These findings point to the importance of key underage drinking and traffic safety laws in efforts to reduce underage drinking-driver crashes.

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Request Reprint E-Mail: fell@pire.org
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IgA Immune Responses Against Acetaldehyde Adducts and Biomarkers of Alcohol Consumption in Patients with IgA Glomerulonephritis

Alcoholism: Clinical and Experimental Research Published Online: 9 Apr 2009


The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo-antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined.

In male IgAGN patients, drinking status was significantly associated with MCV, p < 0.001; CDT, p < 0.01; and γ -CDT, p < 0.05. In the reference population, all biomarkers and anti-adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti-adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self-reported ethanol intake

These data indicate high levels of IgA antibodies against acetaldehyde-derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti-adduct immune responses in IgAGN patients are warranted


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Request Reprint E-Mail: kati.kaartinen@elisanet.fi
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New Manual Teaches Strategies to Manage Depressive Symptoms in Substance Abuse Clients

Managing Depressive Symptoms in Substance Abuse Clients During Early Recovery, a new manual which offers substance abuse counselors new insights on working with clients with depressive symptoms and substance use disorders, is now available from the Substance Abuse and Mental Health Services Administration (SAMHSA).

The manual is #48 in the Treatment Improvement Protocol (TIP) series. TIPs are best-practice guidelines used for the treatment of substance use disorders, issued by SAMHSA’s Center for Substance Abuse Treatment (CSAT). This and future TIPs will be organized in a new format.

The new format consists of three parts. The parts of this TIP are:
- Part 1 - Managing Depressive Symptoms in Substance Abuse Clients During Early Recovery
- Part 2 - Managing Depressive Symptoms: An Implementation Guide for Administrators
- Part 3 - Managing Depressive Symptoms: A Review of the Literature

Read Full Manual (PDF)
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A Behavioral Economic Reward Index Predicts Drinking Resolutions: Moderation Revisited and Compared With Other Outcomes

Journal of Consulting and Clinical Psychology Volume 77, Issue 2, April 2009, Pages 219-228

Data were pooled from 3 studies of recently resolved community-dwelling problem drinkers to determine whether a behavioral economic index of the value of rewards available over different time horizons distinguished among moderation (n = 30), abstinent (n = 95), and unresolved (n = 77) outcomes.

Moderation over 1- to 2-year prospective follow-up intervals was hypothesized to involve longer term behavior regulation processes than abstinence or relapse and to be predicted by more balanced preresolution monetary allocations between short-term and longer term objectives (i.e., drinking and saving for the future).

Standardized odds ratios (ORs) based on changes in standard deviation units from a multinomial logistic regression indicated that increases on this “Alcohol-Savings Discretionary Expenditure” index predicted higher rates of abstinence (OR = 1.93, p = .004) and relapse (OR = 2.89, p < .0001) compared with moderation outcomes. The index had incremental utility in predicting moderation in complex models that included other established predictors.

The study adds to evidence supporting a behavioral economic analysis of drinking resolutions and shows that a systematic analysis of preresolution spending patterns aids in predicting moderation.

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Request Reprint E-Mail: jtucker@uab.edu

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The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption
PLoS Med 6(3)

ALDH2 Lys487 allele contributes to both the alcohol flushing response
and an elevated risk of squamous cell esophageal cancer from alcohol
consumption.

Read Full Article (PDF)
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Alcohol Treatment: Need, Utilization, and Barriers

Highlights:

SAMHSA's National Survey on Drug Use & Health defines need for alcohol treatment as meeting criteria for alcohol dependence or abuse using criteria specified in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The criteria includes symptoms such as withdrawal, tolerance, use in dangerous situations, trouble with the law, and interference in major obligations at work, school, or home during the past year. Also included are people who received treatment in a specialty substance abuse treatment facility in the past year for their alcohol use.
Based on SAMHSA's 2007 National Survey on Drug Use & Health, 7.8% (19.3 million) persons aged 12 or older needed treatment for their alcohol problem in the past year.

The majority of those who needed alcohol treatment either did not perceive the need for treatment or did not receive it. Of those who needed alcohol treatment in the past year, 8.1% received treatment at a specialty treatment facility, 4.5% did not receive treatment but felt they needed it, and 87.4% neither received nor perceived a need for alcohol treatment.

Among those who did not receive alcohol treatment but felt they needed it, only 27.9% actually made an effort to get treatment in the past year.
Combined data from SAMHSA's 2004 to 2007 National Surveys on Drug Use & Health were used to determine reasons for not receiving alcohol treatment. The most common reasons given for not receiving alcohol treatment among those who felt the need for it were: 42% were not ready to stop using alcohol and 34.5% had cost or insurance barriers.

Read Full Report (PDF)

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British teenagers amongst worst in Europe for excessive drinking - 2007 ESPAD report

The 2007 European School Survey Project on Alcohol and other Drugs (ESPAD) report was published last week. The study focuses on alcohol and drug use amongst 15 to 16 year-olds in 35 European countries and found that UK consumption for young people was highest behind only Denmark and the Isle of Man.

The report adds weight to calls for minimum pricing. Professor Martin Plant who leads the UK part of the ESPAD study said:
There is a clear scientific consensus that alcohol education and mass media campaigns have a very poor track record in influencing drinking habits. Far more effective - and cost effective - policies include using taxation to make alcohol less affordable.

. . . . .

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