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


Saturday, October 22, 2011

The dimensionality and measurement properties of alcohol outcome expectancies across Hispanic national groups

This study examines the psychometric properties of alcohol expectancies among Hispanic subgroups.

Face-to-face interviews were conducted as part of the 2006 Hispanic Americans Baseline Alcohol Survey (HABLAS), which employed a multistage cluster sample design. A total of 5,224 individuals (18 + years of age) representing four Hispanic national groups (Puerto Ricans, Cuban Americans, Mexican Americans, and South/Central Americans) were selected at random from the household population in five metropolitan areas (Miami, New York, Philadelphia, Houston, and Los Angeles).

Alcohol expectancies included 18 items covering positive (e.g., laugh more, become more talkative) and negative dimensions (e.g., become aggressive, lose control) when alcohol is consumed.

Confirmatory factor models replicated a previously proposed three-factor dimensional structure with a substantial majority of items exhibiting measurement invariance across Hispanic national group and gender.

Items covering social extroversion were an exception, showing a lack of invariance for female Cuban and South/Central Americans.

Latent mean differences across groups were detected for expectancies concerning emotional fluidity, and the pattern of differences largely mirrored known differences in alcohol consumption patterns.

Results suggest that caution should be exercised in interpreting differences in expectancies concerning social extroversion across Hispanic groups, and additional work is needed to identify indices of this construct with invariant measurement properties.

However, measures of emotional/behavioral impairment and emotional fluidity expectancies can be validly compared across gender and Hispanic national groups.

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Non-Random Mating and Convergence Over Time for Alcohol Consumption, Smoking, and Exercise: The Nord-Trøndelag Health Study

Spouses tend to have similar lifestyles. We explored the degree to which spouse similarity in alcohol use, smoking, and physical exercise is caused by non-random mating or convergence.

We used data collected for the Nord-Trøndelag Health Study from 1984 to 1986 and prospective registry information about when and with whom people entered marriage/cohabitation between 1970 and 2000.

Our sample included 19,599 married/cohabitating couples and 1,551 future couples that were to marry/cohabitate in the 14–16 years following data collection. All couples were grouped according to the duration between data collection and entering into marriage/cohabitation. Age-adjusted polychoric spouse correlations were used as the dependent variables in non-linear segmented regression analysis; the independent variable was time.

The results indicate that spouse concordance in lifestyle is due to both non-random mating and convergence. Non-random mating appeared to be strongest for smoking. Convergence in alcohol use and smoking was evident during the period prior to marriage/cohabitation, whereas convergence in exercise was evident throughout life. Reduced spouse similarity in smoking with relationship duration may reflect secular trends.

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Neighborhood, School, and Family Effects on the Frequency of Alcohol Use Among Toronto Youth

This study examines the effect of neighborhood, school, and family indicators on adolescent drinking. The Toronto Drugs, Alcohol, and Violence International (DAVI) data were collected in 2001–2002.

The sample was stratified both by region (city vs. outskirts) and by the socio-economic status of the schools. Two schools from each stratum were randomly selected and 910 students completed the survey. The survey contains extensive measures of substance use, violence, and mental health.

The study uses cluster analysis and multinomial logits to examine the variation in the effect of schools, family, and demographic indicators on alcohol use across neighborhood contexts.

Study implications and suggestions for future research are included.

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Atypical Antipsychotic Drugs and Ethanol Withdrawal Syndrome: A Review

Alcoholism and psychosis are known to have common neurochemical substrates. The aim of this review is to assess the reports involved in the effects of some atypical antipsychotic agents on the signs of ethanol withdrawal syndrome (EWS) in rats. Thus, both effectiveness of these drugs in ethanol withdrawal and the association between the drug effects and the signs have been investigated here on the same animal model.

Adult Wistar rats were used as subjects. Ethanol was given to rats by modified liquid diet technique for inducing ethanol dependence. Clozapine, olanzapine, risperidone, quetiapine and ziprasidone were the drugs tested. Effects of these drugs on the signs of ethanol withdrawal such as locomotor hyperactivity, stereotyped behavior, tremor, wet dog shakes, tail-stiffness, abnormal posture and gait, agitation and audiogenic seizures were evaluated for the first 6 h of ethanol withdrawal.

Although some beneficial effects of all the drugs on ethanol withdrawal signs were observed, olanzapine precipitated abnormal posture and gait in the animals. Effectiveness rank of the used atypical antipsychotics was as follows: risperidone = quetiapine > ziprasidone > klozapine > olanzapine.

Our results suggest that risperidone and quetiapine seem to be potent and pharmacologically more active agents on EWS in rats. Thus, these drugs may be beneficial in treatment of EWS in patients with alcoholism. Ziprasidone and clozapine also seem to be useful drugs in treatment of ethanol withdrawal.

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Ethanol Consumption Alters the Expression and Reactivity of Adrenomedullin in the Rat Mesenteric Arterial Bed

Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on arterial blood pressure, vascular reactivity to AM and the expression of AM system components in the rat mesenteric arterial bed (MAB).

Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Systolic, diastolic and mean arterial blood pressure were monitored in conscious rats. Vascular reactivity experiments were performed on isolated rat MAB. Matrix metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation were measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, CRLR (calcitonin receptor-like +receptor) and RAMP1, 2 and 3 (receptor activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively.

Ethanol consumption induced hpertension and decreased the relaxation induced by AM and acetylcholine in endothelium-intact rat MAB. Phenylephrine-induced contraction was increased in endothelium-intact MAB from ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 or the net MMP activity in the rat MAB. Ethanol consumption increased mRNA levels of pre-pro-AM and protein levels of AM in the rat MAB. Finally, no differences in protein levels or mRNA of CRLR and RAMP1, 2 and 3 were observed after treatment with ethanol.

Our study demonstrates that ethanol consumption increases blood pressure and the expression of AM in the vasculature and reduces the relaxation induced by this peptide in the rat MAB.

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Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications

The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness).

This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction.

Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.

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Transcriptional and epigenetic mechanisms of addiction

Investigations of long-term changes in brain structure and function that accompany chronic exposure to drugs of abuse suggest that alterations in gene regulation contribute substantially to the addictive phenotype.

Here, we review multiple mechanisms by which drugs alter the transcriptional potential of genes.

These mechanisms range from the mobilization or repression of the transcriptional machinery — including the transcription factors ΔFOSB, cyclic AMP-responsive element binding protein (CREB) and nuclear factor-κB (NF-κB) — to epigenetics — including alterations in the accessibility of genes within their native chromatin structure induced by histone tail modifications and DNA methylation, and the regulation of gene expression by non-coding RNAs.

Increasing evidence implicates these various mechanisms of gene regulation in the lasting changes that drugs of abuse induce in the brain, and offers novel inroads for addiction therapy.

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Pharmacogenetic approaches to the treatment of alcohol addiction

Addictive disorders are partly heritable, chronic, relapsing conditions that account for a tremendous disease burden.

Currently available addiction pharmacotherapies are only moderately successful, continue to be viewed with considerable scepticism outside the scientific community and have not become widely adopted as treatments. More effective medical treatments are needed to transform addiction treatment and address currently unmet medical needs.

Emerging evidence from alcoholism research suggests that no single advance can be expected to fundamentally change treatment outcomes.

Rather, studies of opioid, corticotropin-releasing factor, GABA and serotonin systems suggest that incremental advances in treatment outcomes will result from an improved understanding of the genetic heterogeneity among patients with alcohol addiction, and the development of personalized treatments.

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Characterization of an alcohol addiction-prone phenotype in mice

Human studies indicate that high impulsivity, novelty seeking and anxiety predispose individuals to alcohol abuse. Unclear, however, is whether the same phenotypes can be observed in laboratory animals prone to uncontrolled alcohol drinking.

To characterize a novelty-seeking trait, anxiety, impulsivity, compulsivity and the motivation for natural rewards in mice, numerous tests were performed in the automated IntelliCage learning system. The same mice then had extended access to alcohol for 70 days, followed by the evaluation of addiction-like behaviors, including (1) the motivation for alcohol in a progressive-ratio schedule of reinforcement; (2) persistent and compulsive alcohol seeking and taking during signaled ‘no alcohol’ periods and (3) when subjected to punishment; and (4) the intensity of relapse after alcohol withdrawal.

Our data suggest that high levels of anxiety-related traits (i.e. low novelty seeking, low resistance to punishment and a high level of compulsive behaviors) and high impulsivity predict addiction-like alcohol drinking in mice.

Future studies are, however, warranted to create a valid model of alcohol addiction in mice in the IntelliCage system.

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Friday, October 21, 2011

Binge drinking, drinking frequency, and risk of ischaemic heart disease: A population-based cohort study

Light-to-moderate alcohol drinking is associated with a decreased risk of ischaemic heart disease (IHD). However, drinking heavily and in binges has been suggested to increase IHD risk. This complexity makes the issue of binge drinking within the light-to-moderate alcohol range an important area for further investigation.

This population-based cohort study included 26,786 men and women who participated in the Danish National Cohort Study in 1994, 2000, and 2005. Binge drinking (defined >5 drinks/day) and risk of IHD and all-cause mortality was investigated among light-to-moderate drinkers (defined ≤21 and ≤14 drinks/week for men and women, respectively). In the entire study population, we investigated the association between drinking frequency, separately and combined with total weekly alcohol intake, and risk of IHD and all-cause mortality.

1136 individuals developed IHD during a mean follow up of 6.9 years. Among male light-to-moderate drinkers reporting occasional binge drinking, the hazard ratio (HR) of IHD was 0.81 (95% CI 0.61–1.08) compared to male light-to-moderate drinkers reporting no binge drinking. Corresponding HR for women was 0.97 (95% CI 0.54–1.76). For women drinking 5–6 days/week, the risk of IHD was lower than for women drinking 1–2 days/week (HR 0.54, 95% CI 0.32–0.90). We did not observe any patterns when looking at combinations of total weekly alcohol intake and drinking frequency.

Among light-to-moderate alcohol drinkers, binge drinking was not associated with risk of IHD and all-cause mortality. Overall, drinking frequency did not appear to be an important determinant of the risk of IHD and all-cause mortality.

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The Role of Alcohol Consumption in Female Victimization: Findings from a French Representative Sample

Alcohol is frequently related to interpersonal aggression, but information regarding the role of alcohol consumption by victims of severe aggression is however lacking.

In order to better understand the dynamic of victimization, we investigated contextual, facilitator, and psychological impact variables related to victimization in a French sample composed of 1,033 females aged 18–74 years.

The participants were recruited using quota sampling methodology, and responses were measured using Computer-Assisted Self-Interviewer. A logistic regression was conducted using a backward elimination procedure to identify the significant predictors of blows and wounds suffered in the past 24 months.

The results indicated that victims, relative to nonvictims, did binge drink significantly more often, had a higher aggression trait, and had experienced more social hardships in the past.

The study's limitations are noted.

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Transformation of the Culture of Recovery in America

For almost three centuries, people recovering from severe alcohol and other drug problems have found ways to help each other initiate and sustain their recovery journeys.

Today, recovering people, their families, and visionary professionals have responded to the stigma, criminalization, and lack of appropriate medical care associated with severe alcohol and other drug problems by creating an unprecedented growth in new structures of recovery support.

This presentation will explore recent recovery community building activities and the influence they will exert on the future of addiction treatment and recovery in America.

William White is one of the world’s best-know and most influential advocates, authors and public speakers on the subject of recovery from addiction. He has authored or coauthored more than 350 articles and monographs and fifteen books, including "Let's Go Make Some History: Chronicles of the New Addiction Recovery Advocacy Movement," "Pathways From The Culture of Addiction to the Culture of Recovery," and "Slaying the Dragon: The History of Addiction Treatment and Recovery in America" which received the McGovern Family Foundation Award for the best book on addiction recovery.

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Sexual Orientation and Substance Use Among Adolescents and Young Adults

We examined interrelationships among the 3 dimensions of sexual orientation-self-identity, sexual attraction, and sexual experience-and their associations with substance use among adolescents and young adults.

To estimate total and net associations of sexual identity, attraction, and experience with use of tobacco, drugs, and alcohol, we applied logistic regression to cross-sectional data from the National Survey of Family Growth Cycle 6.

We found a lack of concordance among the different dimensions of sexual orientation. More youths reported same-gender sexual attraction and same-gender sexual experiences than identified as lesbian, gay, or bisexual. Estimates of substance use prevalence differed significantly by gender and across dimensions of sexual orientation. Sexual experience was the most consistent predictor of substance use. Women and men with no sexual experience had the lowest odds of all forms of substance use; those reporting sexual experience with partners of both genders had the highest odds.

Our findings indicate that sexual identity was less strongly associated with substance use than sexual experience and attraction were, pointing to the need for more nuanced indicators of sexual orientation in public health studies.

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Thursday, October 20, 2011

Commissioner Dalli delivers speech at the 9th Plenary Meeting of the European Alcohol and Health Forum

Ladies and Gentlemen,

I am delighted to join this plenary meeting of the European Alcohol and Health Forum. It is my first time here, even though I have already met many of you onother occasions.

I wanted to be here with you today for two reasons: First, because our work together on alcohol-related harm is entering a crucial phase; and Second, because work on alcohol-related harm - as a risk factor for Non Communicable Diseases - has now beenput to the fore with the recent United Nations declaration. > > > > Read More

Considering the Definition of Addiction

The definition of addiction is explored. Elements of addiction derived from a literature search that uncovered 52 studies include: (a) engagement in the behavior to achieve appetitive effects, (b) preoccupation with the behavior, (c) temporary satiation, (d) loss of control, and (e) suffering negative consequences. Differences from compulsions are suggested.

While there is some debate on what is intended by the elements of addictive behavior, we conclude that these five constituents provide a reasonable understanding of what is intended by the concept.

Conceptual challenges for future research are mentioned.

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Involvement of the Beta-Endorphin Neurons of the Hypothalamic Arcuate Nucleus in Ethanol-Induced Place Preference Conditioning in Mice

Increasing evidence indicates that mu- and delta-opioid receptors are decisively involved in the retrieval of memories underlying conditioned effects of ethanol. The precise mechanism by which these receptors participate in such effects remains unclear. Given the important role of the proopiomelanocortin (POMc)-derived opioid peptide beta-endorphin, an endogenous mu- and delta-opioid receptor agonist, in some of the behavioral effects of ethanol, we hypothesized that beta-endorphin would also be involved in ethanol conditioning.

In this study, we treated female Swiss mice with estradiol valerate (EV), which induces a neurotoxic lesion of the beta-endorphin neurons of the hypothalamic arcuate nucleus (ArcN). These mice were compared to saline-treated controls to investigate the role of beta-endorphin in the acquisition, extinction, and reinstatement of ethanol (0 or 2 g/kg; intraperitoneally)-induced conditioned place preference (CPP).

Immunohistochemical analyses confirmed a decreased number of POMc-containing neurons of the ArcN with EV treatment. EV did not affect the acquisition or reinstatement of ethanol-induced CPP, but facilitated its extinction. Behavioral sensitization to ethanol, seen during the conditioning days, was not present in EV-treated animals.

The present data suggest that ArcN beta-endorphins are involved in the retrieval of conditioned memories of ethanol and are implicated in the processes that underlie extinction of ethanol-cue associations. Results also reveal a dissociated neurobiology supporting behavioral sensitization to ethanol and its conditioning properties, as a beta-endorphin deficit affected sensitization to ethanol, while leaving acquisition and reinstatement of ethanol-induced CPP unaffected.

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Endothelial Dysfunction and High Cardiovascular Risk Profile in Severe Alcoholics Improve Only Partially Following a Medium-Term Alcohol Withdrawal

Little is known about brachial artery flow-mediated vasodilatation (FMD) in active and medium-term withdrawing heavy alcoholics (HA).

FMD and some parameters of cardiovascular (CV) risk were measured in 29 HA (average alcohol intake 135, range 86 to 215 g per day) at baseline and after a 9 ± 7 months withdrawal and in 35 teetotalers.

HA showed baseline impaired maximal % FMD (8.5 ± 5.4 SD vs. 14.9 ± 7.4, <0.001 vs. teetotalers), higher systolic (SBP) and diastolic (DBP) blood pressure (+24 mm Hg, <0.001; +15 mm Hg, <0.01), uric acid (5.3 ± 1.1 vs. 4.4 ± 0.8 mg/dl, <0.05), high-sensitivity C-reactive protein (hs-CRP; 2.7 ± 2.0 vs. 1.0 ± 0.9 mg/l, <0.02), endothelin-1 (ET-1, 0.88 ± 0.36 vs. 0.37 ± 0.10 pg/ml,<0.001), asymmetric dimethylarginine (ADMA, 0.50 ± 0.21 vs. 0.41 ± 0.12 μmol/l, p < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (2.3 ± 1.1 vs. 1.2 ± 0.4, <0.001), and urinary 8-isoprostane (U8-iso-PGF2α) (237.2 ± 172.4 vs. 168.5 ± 96.6 pg/mg creatinine, <0.05). After withdrawal, SBP fell by 15 mm Hg, DBP by 11 mm Hg (p < 0.001), and hs-CRP by 0.94 mg/l (p < 0.02), all remaining still higher than teetotalers (<0.05, 0.01, 0.05 respectively). ET-1, HOMA-IR, and U8-iso-PGF2α were unchanged (p = NS vs. baseline, <0.05 to 0.001 vs. teetotalers). Maximal % FMD rose (to 10.6 ± 6.2, p < 0.04), but it still remained impaired (<0.04 vs. teetotalers). ADMA increased further to 0.64 ± 0.15 μmol/l (<0.05 vs. baseline, <0.02 vs. teetotalers).

HA show marked endothelial dysfunction (ED) and high BP, impaired insulin sensitivity, inflammation, increased oxidative stress, and elevated ET-1 and ADMA, which are unaffected or only partially reversed by a medium-term alcohol withdrawal. ED and related abnormalities persist in detoxified alcoholics, thus contributing to a greater CV morbidity and mortality.

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The Relationship Between Measures of Impulsivity and Alcohol Misuse: An Integrative Structural Equation Modeling Approach

Higher levels of impulsivity have been implicated in the development of alcohol use disorders. Recent findings suggest that impulsivity is not a unitary construct, highlighted by the diverse ways in which the various measures of impulsivity relate to alcohol use outcomes. This study simultaneously tested the following dimensions of impulsivity as determinants of alcohol use and alcohol problems: risky decision making, self-reported risk-attitudes, response inhibition, and impulsive decision making.

Participants were a community sample of nontreatment seeking problem drinkers (n = 158). Structural equation modeling (SEM) analyses employed behavioral measures of impulsive decision making (delay discounting task [DDT]), response inhibition (stop signal task [SST]), and risky decision making (Balloon Analogue Risk Task [BART]), and a self-report measure of risk-attitudes (domain-specific risk-attitude scale [DOSPERT]), as predictors of alcohol use and of alcohol-related problems in this sample.

The model fits well, accounting for 38% of the variance in alcohol problems, and identified 2 impulsivity dimensions that significantly loaded onto alcohol outcomes: (i) impulsive decision making, indexed by the DDT; and (ii) risky decision making, measured by the BART.

The impulsive decision-making dimension of impulsivity, indexed by the DDT, was the strongest predictor of alcohol use and alcohol pathology in this sample of problem drinkers. Unexpectedly, a negative relationship was found between risky decision making and alcohol problems. The results highlight the importance of considering the distinct facets of impulsivity to elucidate their individual and combined effects on alcohol use initiation, escalation, and dependence.

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Effects of Withdrawal from Chronic Intermittent Ethanol Vapor on the Level and Circadian Periodicity of Running-Wheel Activity in C57BL/6J and C3H/HeJ

Alcohol withdrawal is associated with behavioral and chronobiological disturbances that may persist during protracted abstinence. We previously reported that C57BL/6J (B6) mice show marked but temporary reductions in running-wheel activity, and normal free-running circadian rhythms, following a 4-day chronic intermittent ethanol (CIE) vapor exposure (16 hours of ethanol vapor exposure alternating with 8 hours of withdrawal). In the present experiments, we extend these observations in 2 ways: (i) by examining post-CIE locomotor activity in C3H/HeJ (C3H) mice, an inbred strain characterized by high sensitivity to ethanol withdrawal, and (ii) by directly comparing the responses of B6 and C3H mice to a longer-duration CIE protocol.

In Experiment 1, C3H mice were exposed to the same 4-day CIE protocol used in our previous study with B6 mice (referred to here as the 1-cycle CIE protocol). In Experiment 2, C3H and B6 mice were exposed to 3 successive 4-day CIE cycles, each separated by 2 days of withdrawal (the 3-cycle CIE protocol). Running-wheel activity was monitored prior to and following CIE, and post-CIE activity was recorded in constant darkness to allow assessment of free-running circadian period and phase.

C3H mice displayed pronounced reductions in running-wheel activity that persisted for the duration of the recording period (up to 30 days) following both 1-cycle (Experiment 1) and 3-cycle (Experiment 2) CIE protocols. In contrast, B6 mice showed reductions in locomotor activity that persisted for about 1 week following the 3-cycle CIE protocol, similar to the results of our previous study using a 1-cycle protocol in this strain. Additionally, C3H mice showed significant shortening of free-running period following the 3-cycle, but not the 1-cycle, CIE protocol, while B6 mice showed normal free-running rhythms.

These results reveal genetic differences in the persistence of ethanol withdrawal-induced hypo-locomotion. In addition, chronobiological alterations during extended abstinence may depend on both genetic susceptibility and an extended prior withdrawal history. The present data establish a novel experimental model for long-term behavioral and circadian disruptions associated with ethanol withdrawal.

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Randomized Controlled Trial of Mailed Personalized Feedback for Problem Drinkers in the Emergency Department: The Short-Term Impact

Evidence exists for the efficacy of emergency department (ED)-based brief alcohol interventions, but attempts to incorporate face-to-face interventions into routine ED practice have been hampered by time, financial, and attitudinal constraints. Mailed personalized feedback, which is likely to be more feasible, has been associated with reduced alcohol consumption in other settings, but its cost-effectiveness in the ED has not been examined.

The intervention was evaluated with a randomized controlled trial of patients presenting to 5 rural EDs in New South Wales, Australia. Patients aged 14 years and older were screened using the Alcohol Use Disorders Identification Test, and those scoring 8 or more were randomly allocated to the intervention or control group. Participants in the intervention group received mailed personalized feedback regarding their alcohol consumption. The control group received no feedback.

Two hundred and forty-four (80%) participants were successfully followed up at 6 weeks. A significant effect of the mailed feedback was observed only in patients with an alcohol-involved ED presentation. Among this subgroup of participants, those in the intervention group consumed 12.2 fewer drinks per week than the control group after controlling for baseline consumption and other covariates (effect size d = 0.59). The intervention was associated with an average cost of Australian $5.83 per patient, and among participants with an alcohol-involved ED presentation, an incremental cost-effectiveness ratio of 0.48.

Mailed personalized feedback is efficacious in reducing quantity/frequency of alcohol consumption among patients with alcohol-involved ED presentations. Mailed feedback has high cost-efficacy and a low absolute cost, making it a promising candidate for integration into ED care.

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Ethanol Alters Opioid Regulation of Ca2+ Influx Through L-Type Ca2+ Channels in PC12 Cells

Studies at the behavioral and synaptic level show that effects of ethanol on the central nervous system can involve the opioid signaling system. These interactions may alter the function of a common downstream target. In this study, we examined Ca2+ channel function as a potential downstream target of interactions between ethanol and μ or κ opioid receptor signaling.

The studies were carried out in a model system, undifferentiated PC12 cells transfected with μ or κ opioid receptors. The PC12 cells express L-type Ca2+ channels, which were activated by K+ depolarization. Ca2+ imaging was used to measure relative Ca2+ flux during K+ depolarization and the modulation of Ca2+ flux by opioids and ethanol.

Ethanol, μ receptor activation, and κ receptor activation all reduced the amplitude of the Ca2+ signal produced by K+ depolarization. Pretreatment with ethanol or combined treatment with ethanol and μ or κ receptor agonists caused a reduction in the amplitude of the Ca2+ signal that was comparable to or smaller than that observed for the individual drugs alone, indicating an interaction by the drugs at a downstream target (or targets) that limited the modulation of Ca2+ flux through L-type Ca2+ channels.

hese studies provide evidence for a cellular mechanism that could play an important role in ethanol regulation of synaptic transmission and behavior through interactions with the opioid signaling.

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Children with Heavy Prenatal Alcohol Exposure Exhibit Deficits when Regulating Isometric Force

Production of isometric (i.e., constant) force is an essential component of performing everyday functional tasks, yet no studies have investigated how this type of force is regulated in children with confirmed histories of heavy prenatal alcohol exposure.

Children 7 to 17 years old with heavy prenatal alcohol exposure (n = 25) and without exposure (n = 18) applied force to a load cell to generate an isometric force that matched a criterion target force displayed on a computer monitor. Two levels of target force were investigated in combination with 3 levels of visual feedback frequency that appeared on the computer monitor as a series of yellow dots. Force was maintained for 20 seconds and participants completed 6 trials per test condition.

Root-mean-square error, signal-to-noise ratio, and sample entropy indexed response accuracy, response variability, and signal complexity, respectively. The analyses revealed that in comparison with controls, children with gestational ethanol exposure were significantly less accurate and more variable in regulating their force output and generated a response signal with greater regularity and less complexity in the time domain.

Children with prenatal alcohol exposure experience significant deficits in isometric force production that may impede their ability to perform basic motor skills and activities in everyday tasks.

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The Impact of Alcohol on BCG-Induced Immunity Against Mycobacterium tuberculosis

Alcoholics are at heightened risk for developing active tuberculosis. This study evaluates chronic alcohol consumption in a murine model of vaccination with Mycobacterium bovis Bacille Calmette–Guèrin (BCG) and subsequent pulmonary infection with virulent Mycobacterium tuberculosis.

BALB/c mice were administered the Lieber–DeCarli liquid ethanol diet or pair-fed the liquid control diet for 3 weeks either before or after subcutaneous vaccination with M. bovis BCG. At least 3 weeks after BCG vaccination, groups of mice on the aforesaid diets were challenged with intratracheal infection with M. tuberculosis H37Rv. Lung mycobacterial burden, and lung and lung-associated lymph node CD4+ lymphocyte production of tuberculosis-specific interferon (IFN)-γ were assayed. Popliteal lymph node lymphocytes from both dietary regimens undergoing BCG vaccination (in the absence of M. tuberculosis infection) were also evaluated for purified protein derivative–induced IFN-γ production by ELISpot assay.

Mice begun on alcohol prior to vaccination with M. bovis BCG demonstrated impaired control of pulmonary challenge with virulent M. tuberculosis, as well as impaired lung CD4+ and popliteal lymph node T-cell IFN-γ responses. If BCG vaccination was delivered prior to initiation of alcohol feeding, the mice remained protected against a subsequent challenge with M. tuberculosis, and BCG-induced immunity was not impaired in either the lung or the popliteal lymph nodes.

Alcohol consumption blunts the development of the adaptive immune response to M. bovis BCG vaccination, which impairs the control of a secondary challenge with M. tuberculosis, but only if the alcohol exposure is begun prior to BCG vaccination. These results provide insight into mechanisms by which alcohol consumption impairs antimycobacterial immunity, including in response to vaccination and subsequent pathogenic challenge.

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In the Rat, Chronic Intermittent Ethanol Exposure During Adolescence Alters the Ethanol Sensitivity of Tonic Inhibition in Adulthood

Alcohol drinking by adolescents is a major public health concern. Adolescents tend to drink in a chronic, intermittent, that is, “binge,” pattern, and such patterns of ethanol exposure are associated with increased risk of neurotoxicity and the development of alcohol use disorders (Crews et al., 2000; Hunt, 1993). Both adolescent humans and rats are more sensitive to acute ethanol-induced memory impairment than adults (Acheson et al., 1998; Markwiese et al., 1998). Furthermore, in rats, chronic intermittent ethanol (CIE) exposure during adolescence produces a long-lasting, perhaps permanent, maintenance of the adolescent high sensitivity to ethanol’s amnestic effects (White et al., 2000a). We have previously shown that acute ethanol increases tonic inhibitory current mediated by extrasynaptic GABAA receptors more efficaciously in dentate granule cells (DGCs) from adolescent than adult rats (Fleming et al., 2007).

In this study, we determined if CIE during adolescence produced long-lasting changes in this tonic current.

Adolescent rats were subjected to a CIE exposure regimen and allowed to mature to full adulthood. Whole-cell voltage-clamp measurements of tonic inhibitory current and mean phasic current were made in vitro in hippocampal brain slices.

CIE exposure during adolescence increased the ethanol sensitivity of tonic inhibitory current mediated by extrasynaptic GABAA receptors and decreased the ethanol sensitivity of phasic, synaptic GABAA receptor-mediated current in adult DGCs.

CIE exposure during adolescence produces long-lasting changes in the function and ethanol sensitivity of extrasynaptic GABAA receptors in DGCs. These changes appear to “lock-in” and maintain the high adolescent sensitivity to ethanol in these cells. Furthermore, greater ethanol enhancement of tonic inhibition in the hippocampal formation after CIE is consistent with the greater sensitivity to ethanol-induced memory impairment after adolescent CIE. This finding represents the first demonstration of a long-term, memory-related cellular effect of CIE during adolescence, and the “lock-in” of adolescent ethanol sensitivity that these results suggest could represent a conceptual step forward in understanding the vulnerability of the adolescent brain to alcohol.

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Personality Traits and Coping Compensate for Disadvantageous Decision-making in Long-term Alcohol Abstinence

High relapse rate and extreme difficulty to maintain abstinence are core characteristics of alcohol dependence (AD). Previous studies have demonstrated a persistent decision-making (DM) deficit in AD. We aimed to reveal specific personality features and stress-coping mechanisms presumed to compensate for ineffective DM skills.

Eighty-eight unmedicated patients with AD were enrolled. Intact general cognitive status was assured by IQ above 90. Forty-three patients had an average abstinence period of 12 weeks and were currently in an inpatient treatment program (short-term abstinence group, STA) and 45 patients were abstinent for at least 3 years (long-term abstinence group, LTA). The two groups were assessed using an integrative approach combining domains of DM, temperament and character dimensions and stress-coping measures.

Both groups performed at chance level with no linear improvement tendency on the gambling task assessing DM adequacy. The LTA group scored significantly higher on scales of self-directedness and cooperativeness. In contrast, levels of harm avoidance, emotion-oriented coping and perceived stress were significantly higher in the STA group.

Our findings provide new evidence for a persistent DM deficit with no learning effect in AD. Despite the deficit, alcohol-dependent patients can achieve LTA. STA patients perceive higher levels of stress and use non-adaptive coping strategies. We propose that the more adaptive personality profile of LTA patients contributes to the compensation of the trait-like DM deficit in alcoholism. These compensatory features represent promising new targets for preventive measures and therapeutic interventions in AD.

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Alcohol brand appearances in US popular music

The average US adolescent is exposed to 34 references to alcohol in popular music daily. Although brand recognition is an independent, potent risk factor for alcohol outcomes among adolescents, alcohol brand appearances in popular music have not been assessed systematically. We aimed to determine the prevalence of and contextual elements associated with alcohol brand appearances in US popular music.

Qualitative content analysis.

We used Billboard Magazine to identify songs to which US adolescents were most exposed in 2005–07. For each of the 793 songs, two trained coders analyzed independently the lyrics of each song for references to alcohol and alcohol brand appearances. Subsequent in-depth assessments utilized Atlas.ti to determine contextual factors associated with each of the alcohol brand appearances.

Our final code book contained 27 relevant codes representing six categories: alcohol types, consequences, emotional states, activities, status and objects.

Average inter-rater reliability was high (κ = 0.80), and all differences were easily adjudicated. Of the 793 songs in our sample, 169 (21.3%) referred explicitly to alcohol, and of those, 41 (24.3%) contained an alcohol brand appearance. Consequences associated with alcohol were more often positive than negative (41.5% versus 17.1%, P < 0.001). Alcohol brand appearances were associated commonly with wealth (63.4%), sex (58.5%), luxury objects (51.2%), partying (48.8%), other drugs (43.9%) and vehicles (39.0%).

One in five songs sampled from US popular music had explicit references to alcohol, and one-quarter of these mentioned a specific alcohol brand. These alcohol brand appearances are associated commonly with a luxury life-style characterized by wealth, sex, partying and other drugs.

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Critique 059: Association of quantity of alcohol and frequency of consumption with cancer mortality

A paper from the National Institutes of Health in the United States attempts to evaluate the separate and combined effects of the frequency of alcohol consumption and the average quantity of alcohol per occasion as they relate to the risk of mortality from all cancers, as well as cancer-specific mortality. It is based on repeated administrations of the National Health Interview Survey in the United States, with a total of more than 300,000 subjects and over 8,000 deaths from cancer, and reports on total cancer deaths and deaths from lung, colorectal, prostate, and breast cancers.

For total alcohol consumption (frequency x quantity), the data indicate a significant reduction in the risk of all-site cancers (RR=0.87, CI 0.80-0.94) which, interestingly, is not emphasized by the authors and is not included in their abstract. Moderate drinking consistently shows no effect, and only heavier drinking is associated with an increase in all-site cancer risk. For site-specific cancers, an increase in risk of lung cancer was seen only for heavier drinkers, with a tendency for less cancer among light drinkers. There was no evidence of an effect of total alcohol consumption on colorectal, prostate, or breast cancer. > > > > Read More


Dr. Morris Edward Chafetz died October 14, 2011, at his home in Georgetown. Dr. Chafetz was born in Worcester, Massachusetts on April 20, 1924. He served in the Medical Corps during World War II and earned the M.D. in Psychiatry at Tufts Medical School in Boston in 1948. He served an internship in the U.S. Marine Hospital in Detroit, Michigan, 1948-49, and was named Resident Psychiatrist at the state hospital in Howard, Rhode Island, from 1949-1951. Following a stint at the Instituto Nacional de Cardiologia in Mexico City, 1951-52, Chafetz served two years as clinical and research fellow in Psychiatry at Massachusetts General Hospital as well as a research fellow in Psychiatry at Harvard Medical School, 1952-54. Chafetz was also a psychiatrist for the U.S. Coast Guard stationed in Cape May, New Jersey, in 1952. He was board certified by the American Board of Psychiatry and Neurology. During the 1970s and 1980s, Chafetz was involved with a number of national boards and conferences, among them a presidential appointment to the White House Conference for a Drug-Free America and as a member of the executive committee of the National Commission against Drunk Driving Board of Directors, as well as Chairman of its Committee on Education and Prevention. He was named Clinical Professor of Psychiatry and Behavioral Science, Medical University of South Carolina, and Adjunct Professor, Center for Metropolitan Affairs and Public Policy at the College of Charleston. He was also founding Director of the National Institute on Alcohol Abuse and Alcoholism, Alcohol, Drug Abuse, and Mental Health Administration. > > > > Read More

Wednesday, October 19, 2011

Mindfulness Is Associated With Fewer PTSD Symptoms, Depressive Symptoms, Physical Symptoms, and Alcohol Problems in Urban Firefighters

This study investigated the association between mindfulness, other resilience resources, and several measures of health in 124 urban firefighters.

Participants completed health measures of posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, physical symptoms, and alcohol problems and measures of resilience resources including mindfulness, optimism, personal mastery, and social support. The Mindful Awareness and Attention Scale (MAAS; Brown & Ryan, 2003) was used to assess mindfulness. Participants also completed measures of firefighter stress, number of calls, and years as a firefighter as control variables. Hierarchical multiple regressions were conducted with the health measures as the dependent variables with 3 levels of independent variables: (a) demographic characteristics, (b) firefighter variables, and (c) resilience resources.

The results showed that mindfulness was associated with fewer PTSD symptoms, depressive symptoms, physical symptoms, and alcohol problems when controlling for the other study variables. Personal mastery and social support were also related to fewer depressive symptoms, firefighter stress was related to more PTSD symptoms and alcohol problems, and years as a firefighter were related to fewer alcohol problems.

Mindfulness may be important to consider and include in models of stress, coping, and resilience in firefighters. Future studies should examine the prospective relationship between mindfulness and health in firefighters and others in high-stress occupations.

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Effects of adverts from a drug and alcohol prevention campaign on willingness to engage in alcohol-related risky behaviors

Behavioral willingness is conceptualized as a pathway to behavior that is non-deliberative, yet traditional measures require thoughtful deliberation to complete.

This study explored non-deliberative measures of alcohol-related willingness to complement recent work on marijuana-related willingness. The study also examined whether adverts from a field-tested drug and alcohol prevention campaign may have operated by influencing alcohol-related willingness.

Participants viewed campaign adverts or consumer adverts (control). Outcomes were reaction times to make speeded judgments about whether one would engage in risky alcohol-related behaviors.

Results showed that campaign advertisements lowered willingness to play drinking games and (for males) to drive while intoxicated.

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Preventing alcohol misuse in young people aged 9-11 years through promoting family communication: an exploratory evaluation of the Kids, Adults Togeth

Alcohol misuse by young people is an important public health issue, and has led to the development of a range of prevention interventions. Evidence concerning the most effective approaches to intervention design and implementation is limited. Parental involvement in school-based interventions is important, but many programmes fail to recruit large numbers of parents. This paper reports findings from an exploratory evaluation of a new alcohol misuse prevention programme - Kids, Adults Together (KAT), which comprised a classroom component, engagement with parents through a fun evening for families with children aged 9-11 years, and a DVD. The evaluation aimed to establish the programme's theoretical basis, explore implementation processes and acceptability, and identify plausible precursors of the intended long-term outcomes.

Documentary analysis and interviews with key personnel examined the programme's development. Classroom preparation and KAT family events in two schools were observed. Focus groups with children, and interviews with parents who attended KAT family events were held immediately after programme delivery, and again after three months. Interviews with head teachers and with teachers who delivered the classroom preparation were conducted. Follow-up interviews with programme personnel were undertaken. Questionnaires were sent to parents of all children involved in classroom preparation.

KAT achieved high levels of acceptability and involvement among both children and parents. Main perceived impacts of the programme were increased pro-social communication within families (including discussions about harmful parental alcohol consumption), heightened knowledge and awareness of the effects of alcohol consumption and key legal and health issues, and changes in parental drinking behaviours.

KAT demonstrated promise as a prevention intervention, primarily through its impact on knowledge and communication processes within families, and its ability to engage with large numbers of parents. A key programme mechanism was the classroom preparation's facilitation of parental involvement in the family fun evening. The programme also incorporated features identified in the literature as likely to increase effectiveness, including a focus on harm reduction, interactive delivery, and targeting primary-school-age children. Further research is needed to test and develop programme theory through implementation in different school contexts, and to examine potential longer-term impacts, and the feasibility of large scale delivery.

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A mathematical formula for prediction of gray and white matter volume recovery in abstinent alcohol dependent individuals

We propose a mathematical formula that predicts the trajectory of the recovery from lobar gray and white matter volume deficits in individuals with sustained abstinence from alcohol.

The formula was validated by using MRI-measured volumetric data from 16 alcohol dependent individuals who had brain scans at three time points during abstinence from alcohol.

Using the measured volumetric data of each individual from the first two time points, we estimated the individual's gray and white matter volume of the frontal, parietal and temporal lobes for the third time point using the formula. Similarly, using the measured data for the second and third time points, we estimated the first time point data for each individual.

The data predicted from the formula were very similar to the experimentally measured data for all lobes and for both gray and white matter. The intra-class correlation coefficients between the measured data and the data estimated from the formula were >
0.95 for almost all the tissues.

The formula may also be applicable in other neuroimaging studies of tissue volume changes such as white matter myelination during brain development and white matter demyelination or brain volume loss in diseases, such as Alzheimer's disease.

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Alcohol in fatal crashes involving Mexican and Canadian drivers in the USA

To determine the prevalence of alcohol involvement and impairment in fatal crashes in the USA involving Mexican and Canadian drivers.

Drivers in fatal crashes in the USA were identified during 1998 to 2008 from the Fatality Analysis Reporting System, and the prevalence of alcohol involvement and impairment (defined as blood alcohol concentrations ≥0.01 g/dl and ≥0.08 g/dl, respectively) was compared among drivers licensed in Mexico (n=687), Canada (n=598), and the USA (n=561 908).

The prevalence of alcohol involvement was 27% for US drivers, 27% for Mexican drivers, and 11% for Canadian drivers. Alcohol impairment was found in 23% of US drivers, 23% of Mexican drivers, and 8% of Canadian drivers. With adjustment for driver demographic characteristics and survival status and for crash circumstances, the prevalence of alcohol involvement was significantly lower for Canadian drivers (adjusted prevalence ratio (PR) 0.63, 95% CI 0.49 to 0.80) than for US drivers, and was similar between Mexican and US drivers (adjusted PR 0.91, 95% CI 0.81 to 1.02).

Alcohol involvement in fatal motor vehicle crashes in the USA is similarly prevalent in US and Mexican drivers, but is substantially less common in Canadian drivers

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Characteristics and behaviors of mothers who have a child with fetal alcohol syndrome

Fetal alcohol syndrome (FAS) is a leading cause of birth defects and developmental disabilities.

The objective of this study was to identify the characteristics and behaviors of mothers of children with FAS in the United States using population-based data from the FAS Surveillance Network (FASSNet). FASSNet used a multiple source methodology that identified FAS cases through passive reporting and active review of records from hospitals, specialty clinics, private physicians, early intervention programs, Medicaid, birth certificates and other vital records, birth defects surveillance programs, and hospital discharge data.

The surveillance included children born during January 1, 1995–December 31, 1997. In the four states included in our analysis – Arizona, New York, Alaska, and Colorado – there were 257 confirmed cases and 96 probable cases for a total of 353 FAS cases.

Compared to all mothers in the states where surveillance occurred, mothers of children with FAS were significantly more likely to be older, American Indians/Alaska Natives, Black, not Hispanic, unmarried, unemployed, and without prenatal care, to smoke during pregnancy, to have a lower educational level, and to have more live born children. A significant proportion of mothers (9–29%) had another child with suspected alcohol effects.

Compared to all US mothers, they were also significantly more likely to be on public assistance, to be on Medicaid at their child's birth, to have received treatment for alcohol abuse, to have confirmed alcoholism, to have used marijuana or cocaine during pregnancy, to have their baby screen positive for alcohol or drugs at birth, to have had an induced abortion, to have had a history of mental illness, to have been involved in binge drinking during pregnancy, and to have drunk heavily (7 days/week) during pregnancy.

These findings suggest that it is possible to identify women who are at high risk of having a child with FAS and target these women for interventions.

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A haplotype analysis is consistent with the role of functional HTR1B variants in alcohol dependence

Animal and human studies have suggested that the serotonergic system plays an important role in alcohol consumption and abuse, mainly due to the serotonin receptor 1B (5-HT1B) function in the mesolimbic reward pathway. Association studies between the HTR1B gene variants and alcoholism have found significant results. There is also evidence for a complex balancing regulation of the gene by two functional variants in the promoter region (rs11568817 and rs130058), which are in linkage disequilibrium.

The aim of this study is to investigate the role of the most relevant variants (rs11568817, rs130058, rs6296 and rs13212041) of the HTR1B gene in the susceptibility to alcohol dependence. The sample comprised 136 Brazilian alcoholics of European descendent and 237 controls.

The results suggest an association between a functional variant of the gene (rs11568817) and alcohol dependence (p = 0.001). In addition, this association could also be confirmed in an independent sample using imputed data from a GWAS, where marginal significant association (p = 0.03, one-tailed) with the same allele was obtained. The pattern of distribution of haplotypes was significantly different between patients and controls (p < 0.0001), which is consistent with the role of the two functional variants of the promoter region.

In conclusion, our findings point to an association between functional variants in the promoter region of the HTR1B gene and alcohol dependence, supporting previous neurobiological evidences of the involvement of HTR1B variations in alcohol-related phenotypes.

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Alcohol misuse and violent behavior: Findings from a 30-year longitudinal study

This study examined the associations between measures of alcohol abuse/dependence (AAD) and violent offending and intimate partner violence (IPV) to age 30 in a New Zealand birth cohort.

Outcomes included: measures of violent offending, violence victimization, and physical IPV perpetration and victimization. The study also used measures of AAD symptoms; and time-dynamic covariate factors including life stress, other substance use, mental health status, peer and partner substance use and offending, and unemployment. Data were analysed using conditional fixed effects regression modelling augmented by time-dynamic covariate factors to control for confounding.

Those with five or more AAD symptoms had unadjusted rates of violence outcomes that ranged from 4.10 to 11.85 times higher than those with no symptoms, but these associations did not differ by gender. Adjustment of the associations for both unobserved fixed effects and time-dynamic covariate factors reduced the magnitude of the associations for violent offending, violence victimization and IPV perpetration, with those with five or more AAD symptoms having rates of violence outcomes that were 1.91–3.58 times higher than those with no symptoms. However, control for both fixed effects and time-dynamic covariate factors reduced the associations between AAD symptoms and physical IPV victimization to statistical non-significance (IRR = 0.73, 95% CI: 0.51–1.06).

The results suggest a causal association between alcohol misuse and violent offending/victimization and IPV perpetration, with estimates suggesting that alcohol use disorder accounted for approximately 4.6–9.3% of the reported violent offending/victimization and IPV perpetration in the cohort.

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