Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

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Saturday, February 2, 2008

Alcohol misuse general information

About alcohol misuse issues and initiatives.

'Stop pushing alcohol on developing world'
Published: 28 Jan 08



Sweden needs to do more to prevent alcohol and tobacco companies from exploiting countries in the developing world, says Left Party member of parliament Kent Persson.

The major international alcohol and tobacco companies are currently engaged in a tough fight to reach new markets. The tobacco companies are being squeezed in the West by a reduction in the use of tobacco, so they have turned their eyes to developing countries to sell their products. When they look at billions of the world's poorest people what they see is a lot of potential customers.

It is against this background that the European Commission is forcing developing countries to open their markets to alcohol and tobacco. The Commission is using the World Trade Organization (WTO) to force through policies to open borders.

Using the GATS agreement on trade in services, they are trying to prevent WTO members from creating laws protecting public health - including on alcohol and tobacco. The position that WTO members should be forced to liberalize the trade in and marketing of alcohol is having a similar effect.
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Friday, February 1, 2008

Roles of the Nucleus Accumbens and Amygdala in the Acquisition and Expression of Ethanol-Conditioned Behavior in Mice
The Journal of Neuroscience, January 30, 2008, 28(5):1076-1084



Although progress has been made identifying the neural areas underlying the primary reinforcing effects of ethanol, few studies have examined the neural areas mediating ethanol-induced conditioned effects.

Previous work using the conditioned place preference (CPP) procedure implicates the ventral tegmental area (VTA) (Bechtholt and Cunningham, 2005), but the downstream neural areas modulating the conditioned rewarding effects of ethanol have not been identified. Although the nucleus accumbens (Acb) and the amygdala (Amy), which both receive dopamine innervation from the VTA, have been implicated in the primary reinforcing effects of ethanol, the roles these areas play in ethanol-conditioned behaviors are unknown.

In the present set of experiments, we use the CPP procedure along with selective electrolytic lesions to examine the neural areas underlying the acquisition and expression of ethanol conditioned behavior.

In the acquisition experiment, male DBA/2J mice received bilateral lesions of the Acb or Amy before CPP training. In the expression experiments, mice received bilateral lesions of the Acb, Acb shell, Acb core, and Amy, or unilateral lesions of the Amy after training but before testing. Lesions of the Acb and Amy before training disrupted acquisition and expression of ethanol CPP.
However, when given after training, only lesions of the Amy disrupted expression, whereas lesions of the Acb core facilitated loss of responding, of ethanol CPP.

For the first time, these results demonstrate the role of the Acb and Amy in the acquisition and expression of ethanol-induced conditioned reward.

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Request Reprint E-Mail: gremelc@ohsu.edu
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Age of Alcohol Use Initiation, Suicidal Behavior, and Peer and Dating Violence Victimization and Perpetration Among High-Risk, Seventh-Grade Adolescents
PEDIATRICS Vol. 121 No. 2 February 2008, pp. 297-305

We examined the cross-sectional associations between reports of an early age of alcohol use initiation and suicidal ideation, suicide attempts, and peer and dating violence victimization and perpetration among high-risk adolescents.

In our study, 35% of students reported alcohol use initiation before 13 years of age (preteen alcohol use initiators). Students who reported preteen alcohol use initiation reported involvement in significantly more types of violent behaviors (mean: 2.8 behaviors), compared with nondrinkers (mean: 1.8 behaviors). Preteen alcohol use initiation was associated significantly with suicide attempts, relative to nondrinkers, controlling for demographic characteristics and all other potential confounders.

Early alcohol use is an important risk factor for involvement in violent behaviors and suicide attempts among youths. Increased efforts to delay and to reduce early alcohol use among youths are needed and may reduce both violence and suicide attempts.


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Request Reprint E-Mail: mswahn@cdc.gov
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Media resistance skills and drug skill refusal techniques: What is their relationship with alcohol use among inner-city adolescents�
Addictive Behaviors Volume 33, Issue 4, April 2008, Pages 528-537


Past research related to alcohol advertising examined whether underage adolescents were targets of the alcohol industry and what impact such adverting had on adolescent drinking.

The purpose of this study was to longitudinally examine the impact of media resistance skills on subsequent drinking among adolescents residing in inner-city regions of New York City. The study also tested whether drug skill refusal techniques (knowing how to say no to alcohol and other drugs) mediated the relationship between media resistance skills and adolescent drinking.

A panel sample of baseline, one-year and two-year follow-ups (N = 1318) from the control group of a longitudinal drug abuse prevention trial participated.

A series of structural equations models showed that media resistance skills directly negatively predicted alcohol use 2 years later and that drug skill refusal techniques mediated this effect.

Baseline media resistance skills were associated with one-year drug skill refusal techniques, which in turn negatively predicted two-year alcohol use.

These findings provided empirical support for including media resistance skills and drug skill refusal techniques in alcohol prevention programs.

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Request Reprint E-Mail: jepstein@med.cornell.edu
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The effect of gestational ethanol exposure on voluntary ethanol intake in early postnatal and adult rats.
Behavioral Neuroscience. 2007 Dec Vol 121(6) 1306-1315


Clinical and epidemiological studies provide strong data for a relationship between prenatal ethanol exposure and the risk for abuse in adolescent and young adult humans. However, drug-acceptance results in response to fetal exposure have differed by study, age at evaluation, and experimental animal.

In the present study, the authors tested whether voluntary ethanol intake was enhanced in both the infantile and adult rat (15 and 90 days of age, respectively), as a consequence of chronic fetal drug experience. Experimental rats were exposed in utero by administering ethanol to a pregnant dam in a liquid diet during gestational Days 6-20.

Compared with those for isocaloric pair-fed and ad lib chow control animals, the results for experimental animals demonstrated that fetal exposure significantly increased infantile affinity for ethanol ingestion without affecting intake patterns of an alternative fluid (water). Heightened affinity for ethanol was absent in adulthood. Moreover, the results argue against malnutrition as a principal factor underlying the infantile phenomenon.

These data add to a growing literature indicative of heightened early postnatal acceptance patterns resulting from maternal use or abuse of ethanol during pregnancy


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Request Reprint E-Mail: youngens@upstate.edu
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Experience-induced fetal plasticity: The effect of gestational ethanol exposure on the behavioral and neurophysiologic olfactory response to ethanol odor in early postnatal and adult rats.
Behavioral Neuroscience. 2007 Dec Vol 121(6) 1293-1305


Human fetal ethanol exposure is strongly associated with ethanol avidity during adolescence. Evidence that intrauterine olfactory experience influences chemosensory-guided postnatal behaviors suggests that an altered response to ethanol odor resulting from fetal exposure may contribute to later abuse risk.

Using behavioral and neurophysiological methods, the authors tested whether ethanol exposure via the dam's diet resulted in an altered responsiveness to ethanol odor in infant and adult rats.

Compared with controls, (a) fetal exposure tuned the neurophysiologic response of the olfactory epithelium to ethanol odor at some expense to its responsiveness to other odorants in infantile rats--this effect was absent in adults; (b) the neural effect in infantile rats was paralleled by an altered behavioral response to ethanol odor that was specific to this odorant--this effect was also absent in adults; and (c) a significant component of the infantile behavioral effect was attributable to ethanol's effect on the olfactory neural modality.

These data provide evidence for an important relationship between prenatal ethanol experience and postnatal behavioral responsiveness to the drug that is modulated or determined by olfactory function.

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Reprint Request E-Mail:
youngens@upstate.edu
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Alcohol Use and Risk of HIV infection among Men Who Have Sex with Men
AIDS and Behavior, OnlineFirst, 31 January 2008

In the United States, men who have sex with men (MSM) currently represent more than 50% of those living with HIV and over 70% of HIV+ men.

Male-to-male sexual contact has been identified as the predominant route of transmission among this sub-group, which underscores the need for research that targets risk factors associated with risky sex-related HIV acquisition. Along these lines, research has shown that one potentially important predictor variable for risky sex among MSM is alcohol use.

The major aim of this paper is to review and integrate empirical evidence on the association of alcohol use and risky sex among MSM.

A summary of the quantitative research is provided first, followed by a critique of the reviewed literature, a discussion of the consistency of the existing empirical evidence with predictions of current theories, and finally, recommendations for future research designed to evaluate alcohol-related sexual risk in MSM.

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Request Repint E-Mail: sewoolf@syr.edu
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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 GABAB 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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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 GABAB 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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Inhibition of N-Type Calcium Channels by Activation of GPR35, an Orphan Receptor, Heterologously Expressed in Rat Sympathetic Neurons
JPET 324:342-351, 2008

GPR35 is a G protein-coupled receptor recently "de-orphanized" using high-throughput intracellular calcium measurements in clonal cell lines expressing a chimeric G-protein {alpha}-subunit. From these screens, kynurenic acid, an endogenous metabolite of tryptophan, and zaprinast, a synthetic inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase, emerged as potential agonists for GPR35.

To investigate the coupling of GPR35 to natively expressed neuronal signaling pathways and effectors, we heterologously expressed GPR35 in rat sympathetic neurons and examined the modulation of N-type (CaV2.2) calcium channels. In neurons expressing GPR35, calcium channels were inhibited in the absence of overt agonists, indicating a tonic receptor activity.

Application of kynurenic acid or zaprinast resulted in robust voltage-dependent calcium current inhibition characteristic of Gβ{gamma}-mediated modulation. Both agonist-independent and -dependent effects of GPR35 were blocked by Bordetella pertussis toxin pretreatment indicating the involvement of Gi/o proteins. In neurons expressing GPR35a, a short splice variant of GPR35, zaprinast was more potent (EC50 = 1 µM) than kynurenic acid (58 µM) but had a similar efficacy (approximately 60% maximal calcium current inhibition). Expression of GPR35b, which has an additional 31 residues at the N terminus, produced similar results but with much greater variability. Both GPR35a and GPR35b appeared to have similar expression patterns when fused to fluorescent proteins.

These results suggest a potential role for GPR35 in regulating neuronal excitability and synaptic release.

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Request Reprint E-Mail: sikeda@mail.nih.gov
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Alcohol habits in Sweden during 1997-2005 measured with the AUDIT
Nordic Journal of Psychiatry, Volume 61, Issue 6 2007 , pages 466 - 470




This study aimed to describe changes in Swedish alcohol habits during a period of "harmonization" with European Union alcohol policy.


Results were somewhat diverse, but significant changes in alcohol habits occurred among two subgroups of the population: for women and the age group between 28 and 60 years, AUDIT scores peaked in 2001.

The results are discussed in relation to the changes made in Swedish alcohol policy during the investigation period.


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Request Reprint E-Mail: hakan.kallmen@gamma.telenordia.se
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Update on College Drinking Research
November 2007



College drinking research remains a high priority for NIAAA, and ongoing projects continue to yield important new information. This bulletin summarizes these recent findings with updated statistics, analysis, and recommendations.

Download Full Bulletin (PDF)
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Alcohol Alerts
No. 73: Underage Drinking--Highlights From The Surgeon General's Call to Action To Prevent and Reduce Underage Drinking (2007)

In March 2007, the Acting Surgeon General of the United States issued a Call to Action To Prevent and Reduce Underage Drinking. The National Institute on Alcohol Abuse and Alcoholism’s (NIAAA’s) Underage Drinking Research Initiative provided much of the scientific foundation for that document. The Call to Action highlights the nature and extent of underage drinking and its consequences. It suggests a new, more comprehensive and developmentally sensitive approach to understanding, preventing, and reducing underage drinking. Importantly, the Call to Action emphasizes that everyone has a role in preventing and reducing underage drinking—parents, schools, communities, colleges and universities, the health care system, the criminal and juvenile justice systems and law enforcement, and governments and policymakers. Later in 2007, the Surgeon General also issued three separate guides—for families, educators, and communities—based on the Call to Action.

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Prevalence and the Factors Associated with Binge Drinking, Alcohol Abuse, and Alcohol Dependence: A Population-Based Study of Chinese Adults in Hong Kong
Alcohol and Alcoholism Advance Access published online on January 29, 2008


To examine the patterns of drinking, the relationship between binge drinking, alcohol abuse, and dependence, and the sociodemographic factors associated with problem drinking among Hong Kong Chinese.

The age-adjusted prevalence amongst men for binge drinking was 14.4% with 5.3% of males being alcohol abusers and 2.3% dependent on alcohol. The corresponding figures for women were all lower at 3.6%, 1.4%, and 0.7%, respectively. Younger age groups showed the highest prevalence of these drinking problems.

Among male binge drinkers, 18.7% were also alcohol abusers and 12.3% were alcohol dependent. Among female binge drinkers, 16% reported alcohol abuse and 9.9% reported dependence. Male binge drinkers were less likely to be older, less likely to be students but more likely to be employed in the service industry. Female binge drinkers were less likely to be over 60 years of age or married but more likely to be smokers. In both genders, smoking was significantly associated with the likelihood of binge drinking (OR = 3.6–12.3), alcohol abuse (OR = 3.0–12.1), and dependence (OR = 5.2–20.6).

Although binge drinking has been well tolerated in Chinese culture, it is strongly associated with alcohol abuse and dependence in both genders in Hong Kong. Our findings suggest that prevalence of problematic alcohol consumption warrants greater promotion of alcohol harms awareness.

Higher rates of heavy drinking in younger-aged individuals may reflect changing lifestyle behaviors and herald higher future levels of alcohol-related health and social problems.


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Request Reprint E-Mail:
siangriffiths@cuhk.edu.hk
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Alcohol Consumption, Abstaining, Health Utility, and Quality of Life – A General Population Survey in Finland
Alcohol and Alcoholism Advance Access published online on February 1, 2008


To examine the associations between alcohol consumptionand utility-based health-related quality of life (HRQoL), subjective quality of life (QoL), self-rated health (SRH), and mental distress.

Negative associations between alcohol and well-being were observed on several measures for women consuming more than 173 g and men more than 229 g per week. Former drinkers scored worst on most measures, even in comparison to the highest drinking decile. For men, all statistically significant associations between moderate drinking and well-being disappeared when sociodemographic factors and former drinkers were controlled for. For women, moderate alcohol use associated with better SRH and EQ-5D as compared to abstainers. However, the possible health utility benefits associated with moderate alcohol consumption were of clinically insignificant magnitude.

Failure to separate former drinkers and other abstainers produces a significant bias favoring moderate drinkers. As the possible health utility benefits of moderate alcohol use were clinically insignificant, it suffices to investigate mortality, when estimating the public health impact of moderate alcohol consumption using quality-adjusted life years.


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Request Reprint E-Mail: samuli.saarni@helsinki.fi

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Hippocampal Volume Loss in Patients with Alcoholism is Influenced by the Consumed Type of Alcoholic Beverage
Alcohol and Alcoholism Advance Access published online on January 31, 2008

The individual extent of structural brain tissue changes in patients with alcohol dependence is influenced by genetic factors, gender, age and possibly a dose/duration-effect.

Aim of the present study was to investigate different types of alcoholic beverages with regard to hippocampal volume loss in patients suffering from alcoholism.

There was a significant difference in hippocampal volumes between patients consuming different beverages with the smallest volumes in the wine group, followed by the spirits group. Furthermore, patients with a preferred spirits consumption showed significantly higher plasma homocysteine levels. Linear regression analyses revealed an association of homocysteine and hippocampal volume only in the group of patients preferring spirits .

Homocysteine-mediated excitotoxicity may be an important pathophysiological mechanism in ethanol-related brain damage, particularly in patients consuming wine and spirits. The extent of brain atrophy in beer consuming patients seems to be more moderate.


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Request Reprint E-Mail: julia.wilhelm@uk-erlangen.de

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Paternal Alcoholism and Youth Substance Abuse: The Indirect Effects of Negative Affect, Conduct Problems, and Risk Taking
Journal of Adolescent Health Volume 42, Issue 2, February 2008, Pages 198-200


This longitudinal study followed 200 adolescents into early adulthood to explore the potential mediating roles that hostility, sadness, conduct problems, and risk-taking play in the relationship between paternal alcoholism and substance abuse.

Results indicated that paternal alcoholism predicted hostility; in turn, hostility predicted risk taking, which predicted substance abuse.


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Request Reprint E-Mail: ohanness@udel.edu
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Thursday, January 31, 2008

WOMEN'S HEALTH
Cocktails and Consequences


November 24, 2007

Studies on the benefits of moderate alcohol consumption abound, but many apply more to men than women. Here are five factors women should consider before they drink.

You could forgive the average woman for being confused about how much alcohol she should be drinking, or even whether she should be drinking at all. Headlines over the last decade have linked moderate alcohol consumption to everything from a higher risk of breast cancer to a lower risk of dementia. Even the notion that pregnant women should never drink may be debatable. Just this month, a British study suggested that binge drinking—on a very occasional basis—might not be harmful to the fetus (though researchers cautioned that more investigation was needed).

As doctors continue to sort through the contradictory evidence, one thing remains certain: decisions about drinking are more loaded for women than for men. "The benefits of alcohol are going to vary by individual, depending on genes and lifestyle," explains Samir Zakhari, director of metabolic research at the National Institute of Alcoholism and Alcohol Abuse. "But the risks--which we know much more about—those clearly vary by gender, and are much higher for women." Here's what we know—and don't—about how alcohol affects the female body:
. . . . . .

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Lifetime prevalence of psychiatric disorders in South Africa
The British Journal of Psychiatry
(2008) 192: 112-117

Data on the lifetime prevalence of psychiatric disorders in South Africa are of interest, not only for the purposes of developing evidence-based mental health policy, but also in view of South Africa's particular historical and demographic circumstances.

Lifetime prevalence of DSM–IV/CIDI disorders was determined for anxiety disorders (15.8%), mood disorders (9.8%), substance use disorders (13.4%) and any disorder (30.3%). Lifetime prevalence of substance use disorders differed significantly across ethnic groups. Median age at onset was earlier for substance use disorders (21 years) than for anxiety disorders (32 years) or mood disorders (37 years).

In comparison with data from other countries, South Africa has a particularly high lifetime prevalence of substance use disorders. These disorders have an early age at onset, providing an important target for the planning of local mental health services.


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Request Reprint E-Mail: dan.stein@uct.ac.za
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Tobacco and hazardous or harmful alcohol use in Thailand: Joint prevalence and associations with socioeconomic factors
Addictive Behaviors , Volume 33, Issue 4, April 2008, Pages 503-514


This study estimates the individual and joint prevalence of cigarette smoking and alcohol misuse, and examines the association between these risks and socioeconomic factors in Thailand.

The self-reported data on cigarette and alcohol use are from a 2004 nationally representative cross-sectional survey of 39 290 individuals aged 15 and over. Substantially more men than women were current smokers (45.8% vs. 2.3%; p <>p <>p < href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VC9-4R2964F-2&_user=10&_coverDate=04%2F30%2F2008&_rdoc=11&_fmt=summary&_orig=browse&_srch=doc-info%28%23toc%235949%232008%23999669995%23679284%23FLA%23display%23Volume%29&_cdi=5949&_sort=d&_docanchor=&_ct=11&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=e3df841c53fb31e74dd62a68e7559b11">Read Full Abstract


Request Reprint E-Mail: rawap@mahidol.ac.th
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Methods for testing theory and evaluating impact in randomized field trials: Intent-to-treat analyses for integrating the perspectives of person, place, and time
Drug and Alcohol Dependence, Article in Press, Corrected Proof 22 Jan 2008

Randomized field trials provide unique opportunities to examine the effectiveness of an intervention in real world settings and to test and extend both theory of etiology and theory of intervention.

These trials are designed not only to test for overall intervention impact but also to examine how impact varies as a function of individual level characteristics, context, and across time. Examination of such variation in impact requires analytical methods that take into account the trial's multiple nested structure and the evolving changes in outcomes over time.

The models that we describe here merge multilevel modeling with growth modeling, allowing for variation in impact to be represented through discrete mixtures—growth mixture models—and nonparametric smooth functions—generalized additive mixed models. These methods are part of an emerging class of multilevel growth mixture models, and we illustrate these with models that examine overall impact and variation in impact.

In this paper, we define intent-to-treat analyses in group-randomized multilevel field trials and discuss appropriate ways to identify, examine, and test for variation in impact without inflating the Type I error rate. We describe how to make causal inferences more robust to misspecification of covariates in such analyses and how to summarize and present these interactive intervention effects clearly.

Practical strategies for reducing model complexity, checking model fit, and handling missing data are discussed using six randomized field trials to show how these methods may be used across trials randomized at different levels.


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Request Reprint E-Mail: hbrown@health.usf.edu

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Hepatic Safety of Once-Monthly Injectable Extended-Release Naltrexone Administered to Actively Drinking Alcoholics
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

Hepatoxicity has been reported with oral naltrexone. Hepatic safety data were examined from a 6-month study evaluating the efficacy and safety of a now available extended-release formulation of naltrexone (XR-NTX) in patients with alcohol dependence.

There were no significant differences in alanine aminotrasferase, aspartate aminotransferase, or bilirubin levels between the study groups at study initiation or at subsequent assessments. Gamma-glutamyltransferase in the XR-NTX 380 mg group was lower compared with placebo at weeks 4, 8, 12, and 20. Both high (>3 times the upper limit of normal) liver chemistry tests (LCTs) and hepatic-related adverse events were infrequent in all study groups. In patients who were drinking heavily throughout the study, obese subjects, or those taking nonsteroidal anti-inflammatory drugs, there was no increase in frequency of high LCTs or hepatic-related adverse events in patients receiving XR-NTX (either dose) compared with placebo.

Extended-release formulation of naltrexone does not appear to be hepatotoxic when taken at the recommended clinical doses in actively drinking alcohol-dependent patients.


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Request Reprint E-Mail: mrl@medicine.wisc.edu
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Chronic Ethanol Consumption Decreases Murine Langerhans Cell Numbers and Delays Migration of Langerhans Cells as Well as Dermal Dendritic Cells
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration.

Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application.

Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect.

These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration.


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Request Reprint E-Mail: annette-schlueter@uiowa.edu

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Association of the Ε2 Allele of Apoe Gene to Hypertriglyceridemia and to Early-Onset Alcoholic Cirrhosis
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

The diverse incidence of alcoholic cirrhosis around the world and the fact that not all alcoholic drinkers develop liver disease indicates that genetic and environmental factors play an important role in the development of liver cirrhosis. Lipids participate in early stages of alcoholic cirrhosis. Therefore variations in the plasma lipid profile due to primary (genetic) or secondary (environmental) dyslipidemia could affect the development of liver disease.

The aim of this study was to analyze the lipid profile and apolipoprotein E (APOE) polymorphism in patients with alcoholic liver cirrhosis (AC) and determine the risk associated with genotype polymorphism with the onset of alcoholic cirrhosis.

A statistically significant increase of the APOE*2 allele and genotypes 2/2, 2/3, and 2/4 was present in AC patients compared to C group. A hyperlipidemic state characterized by increased levels of triglycerides and apolipoprotein B (APOB) and a decrease of high density lipoprotein-cholesterol (HDL-c) was detected in young-aged patients (31.2 ± 6.2 years old vs. 46.3 ± 12.5 years old). In this group, hypertriglyceridemia was closely associated to APOE*2 allele and to an early onset of liver cirrhosis. By contrast, APOE*4 allele was associated with a longer duration of alcohol intake (>20 years) in the non-H group.

This study shows the association of hypertriglyceridemia and APOE allele with the early onset of alcoholic liver cirrhosis, and the interaction between environmental factors, such as duration of alcohol abuse and amount of alcohol intake, and genetic factors (APOE*2 allele) on the hypertriglyceridemic process.


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Request Reprint E-Mail: apanduro@prodigy.net.mx and biomomed@cencar.udg.mx
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Diffusion Tensor Measures of the Corpus Callosum in Adolescents With Adolescent Onset Alcohol Use Disorders
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

In adults, myelination injury is associated with alcoholism. Maturation of the corpus callosum is prominent during adolescence. We hypothesized that subjects with adolescent-onset alcohol use disorders (AUD; defined as Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence or abuse) would have myelination mircostructural differences compared to controls.

Measures of rostral body fractional anisotropy (FA) were higher in the AUD group than in the control group. Compared to controls, mean diffusivity (MD) was lower, while FA was higher, in the AUD group in the isthmus region. Anterior corpus callosum mircostructural development differed in adolescents with AUD, as age was positively (not negatively) associated with rostrum MD and age was negatively (not positively) associated with rostrum FA. There were sex by group interactions in that control females had higher posterior midbody FA when compared to female adolescents with AUD.

Lower MD and higher FA values in the AUD group suggest pre-morbid vulnerability for accelerated prefrontal and temporo-parietal myelin maturation that may enhance the risk for adolescent AUD. Significant (and opposite to developmentally expected) correlations were seen between anterior corpus callosum MD and FA measures and age in the AUD group, suggesting neurotoxic effects of alcohol on adolescent corpus callosum microstructure. As seen in adults, female adolescents with AUD may be especially vulnerable to corpus callosum mircostructural injury.

Further diffusion tensor imaging studies of corpus callosum maturation in children at familial risk for alcoholism, and in those with AUD, need to be done to elucidate these mechanisms.


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Request Reprint E-Mail: debel002@mc.duke.edu
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Face Processing in Chronic Alcoholism: A Specific Deficit for Emotional Features
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

It is well established that chronic alcoholism is associated with a deficit in the decoding of emotional facial expression (EFE). Nevertheless, it is still unclear whether this deficit is specifically for emotions or due to a more general impairment in visual or facial processing. This study was designed to clarify this issue using multiple control tasks and the subtraction method.

Alcoholic patients had a preserved performance for visuo-spatial and facial identity processing, but their performance was impaired for visuo-motor abilities and for the detection of complex facial aspects. More importantly, the subtraction method showed that alcoholism is associated with a specific EFE decoding deficit, still present when visuo-motor slowing down is controlled for.

These results offer a post hoc confirmation of earlier data showing an EFE decoding deficit in alcoholism by strongly suggesting a specificity of this deficit for emotions. This may have implications for clinical situations, where emotional impairments are frequently observed among alcoholic subjects.


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Request Reprint E-Mail: pierre.maurage@uclouvain.be

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Family History of Alcoholism Is Associated With Lower 5-HT2A Receptor Binding in the Prefrontal Cortex
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008


5-Hydroxytryptophan (5-HT2A) receptor involvement in alcoholism is suggested by less 5-HT2A binding in alcohol preferring rats, association of a 5-HT2A receptor gene polymorphism with alcohol dependence and reduced alcohol intake with 5-HT2A antagonists.

We sought to determine postmortem whether 5-HT2A receptors are altered in the prefrontal cortex (PFC) of alcoholics.

5-HT2A binding decreased with age [Brodmann areas (BA) 9, 46 gyrus; r = −0.381, −0.334, p <>n = 23) had less 5-HT2A binding throughout PFC than subjects without (n = 21) a family history of alcoholism (p <>2A receptor binding in alcoholics without a family history of alcoholism (n = 7) did not differ from controls without a family history of alcoholism (n = 14). There was no association between alcoholism or alcohol rating and genotype. There was an association between genotype and the total amount of 3H-ketanserin binding in BA46 with the TT genotype having more binding (TT>TC≈CC).

Lower 5-HT2A receptor binding in the PFC of cases with a family history of alcoholism suggests a genetic predisposition to alcoholism. Alcohol abuse by itself did not have a significant effect on PFC 5-HT2A binding and as 5-HT2A binding in alcoholics is not different from controls and antagonists may be therapeutic, fewer receptors may result in downstream developmental effects on the brain resulting in a predisposition to alcoholism


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The Effect of Acute Ethanol Intoxication on Salivary Proteins of Innate and Adaptive Immunity
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens.

In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems.

At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased , in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session.

The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher , when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively).

Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens.


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Alcohol, Psychological Dysregulation, and Adolescent Brain Development
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

While adolescent alcohol consumption has been asserted to adversely alter brain development, research in human adolescents has not yet provided us with sufficient evidence to support or refute this position.

Brain constituents actively developing during adolescence include the prefrontal cortex, limbic system areas, and white matter myelin. These areas serving cognitive, behavioral, and emotional regulation may be particularly vulnerable to adverse alcohol effects. Alternatively, deficits or developmental delays in these structures and their functions may underlie liability to accelerated alcohol use trajectories in adolescence.

This review will describe a conceptual framework for considering these relationships and summarize the available studies on the relationships among risk characteristics, alcohol involvement and brain development during this period. The cross-sectional designs and small samples characterizing available studies hamper definitive conclusions.

This article will describe some of the opportunities contemporary neuroimaging techniques offer for advancing understanding of adolescent neurodevelopment and alcohol involvement.


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Alcohol Availability and Neighborhood Characteristics in Los Angeles, California and Southern Louisiana
Journal of Urban Health, Online First 29 January 2008


The objective of this study was to examine the associations between alcohol availability types and community characteristics in randomly selected census tracts in Southern California and Southeastern Louisiana.

Outlet shelf space and price by beverage type was collected from all off-sale alcohol outlets in 189 census tracts by trained research personnel.

Three aspects of alcohol availability at the census tract level were considered—outlets per roadway mile, shelf space, and least price by beverage type.

In multivariate analyses controlling for state, male unemployment rate was inversely associated with total shelf space (p = 0.03) and distilled spirit shelf space (p = 0.05). Malt liquor shelf space was inversely associated with percent White (p = 0.02). Outlets per roadway mile was positively associated with household poverty (p < 0.0001), whereas percent African American was inversely associated with outlets per roadway mile (p = 0.03).

Beverage-specific least prices were not associated with any socioeconomic or demographic community characteristics.

Alcohol availability types, but not least price, were associated with some community characteristics.

More research exploring how alcohol availability types vary by community and their relationship to alcohol-related harms should be conducted.


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Impact of Hurricanes Katrina and Rita on Substance Use and Mental Health

Jan 31, 2008

Highlights:

  • Data are presented on substance use and mental health problems before and after Hurricanes Katrina and Rita among adults aged 18 or older who lived in the Gulf State Disaster Area and for adults living in the rest of the United States. Estimates of substance use and mental health problems before Hurricanes Katrina and Rita were based on SAMHSA's National Survey on Drug Use and Health (NSDUH) from July 2004 through June 2005. Estimates for the post hurricane period were based on NSDUH data from January 2006 through December 2006.
  • Based on SAMHSA's National Survey on Drug Use and Health, the impact of Hurricanes Katrina and Rita on substance use and mental health was primarily found among persons who were displaced from their homes.

    Substance Use:

  • Adult Gulf State Disaster Area residents who were displaced from their homes for 2 weeks or longer had significantly higher rates of past month use of illicit drugs, marijuana, and cigarettes than those who were not displaced.
  • Adult Gulf State Disaster Area residents who were displaced from their homes for less than 2 weeks had significantly higher rates of past month binge alcohol use than those who were not displaced.
  • Mental Health Problems:

  • Adult Gulf State Disaster Area residents who were displaced from their homes for 2 weeks or longer had significantly higher rates of serious psychological distress, major depressive episode, and unmet need for mental health treatment or counseling in 2006 than those who were not displaced.
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Analysis of Single Nucleotide Polymorphisms and Haplotypes in the Neuropeptide Y Gene: No Evidence for Association With Alcoholism in a German Population Sample
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

Several lines of evidence from animal and electrophysiological studies indicate that the neuropeptide Y (NPY) gene is involved in the pathophysiology of alcohol dependence. Recent studies have provided evidence for an association between a Leu7Pro polymorphism, as well as 2 promoter single nucleotide polymorphisms (SNPs) in the NPY gene (G-602T, T-399C) and alcohol dependence.

The aim of the present study was to analyze these variants in a large sample of the Munich Gene Bank of Alcoholism.

Neither single SNP-, nor haplotype analysis could detect significant associations with alcohol dependence. Additionally we could not detect any relation to Cloninger’s Type 1/2 or Babor’s Type A/B classification, to withdrawal symptoms, to the age of onset or to the amount of alcohol intake.

In conclusion, our results suggest that the analyzed SNPs, as well as the corresponding haplotypes of the NPY gene are unlikely to play a major role in the pathophysiology of alcohol dependence in the investigated sample from the German population. Further analyses are needed to confirm the present results.


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The Effect of Alcohol Intake on Cardiovascular Disease and Mortality Disappeared After Taking Lifetime Drinking and Covariates Into Account
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008

Current alcohol intake has been associated with cardiovascular morbidity and mortality. The effect of past and lifetime drinking has received less attention.

In the present study, the impact of current, past and lifetime drinking on cardiovascular events and all-cause mortality has been assessed. Secondly, the effect of accounting for covariates within these relationships has been studied.

During follow-up, 679 men and 397 women had a cardiovascular event and 330 men and 204 women died. Current drinking was associated with lower risks of cardiovascular events (women) and all-cause mortality (men and women) compared with never drinkers. The relationships were strongest for alcohol intake measured with the Weekly Recall.

Lifetime alcohol intake and alcohol intake in the distant past did not seem to be related to all-cause mortality or cardiovascular events. Adjustments for covariates weakened the relationships.

Potential positive effects of drinking seem to be of a transient nature, as lifetime drinking and drinking in the past could not be related to all-cause mortality or cardiovascular events. The alleged benefits of current drinking at baseline diminished with increasing methodological quality and rigor.


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Metacognitive beliefs about alcohol use: Development and validation of two self-report scales
Addictive Behaviors Volume 33, Issue 4, April 2008, Pages 515-527



The goal of this research was to develop clinical assessment tools of positive and negative metacognitive beliefs about alcohol use.

In Study 1 we constructed two scales and conducted preliminary factor analyses. Studies 2 and 3 investigated the predictive validity and temporal stability of the scales. Study 4 examined the factor structure, predictive validity and classification accuracy of the scales in a clinical sample.

The Positive Alcohol Metacognitions Scale (PAMS) and the Negative Alcohol Metacognitions Scale (NAMS) were shown to possess good psychometric properties, as well as predictive validity and classification accuracy, in both clinical and community populations.

The scales may aid future research into problem drinking and facilitate clinical assessment and case formulation.


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Request Reprint E-Mail: M.Spada@roehampton.ac.uk __________________________________________________________________