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.


Saturday, October 4, 2008

Effects of Heavy Drinking, Binge Drinking, and Family History of Alcoholism on Regional Brain Metabolites
Alcohol Clin Exp Res. 2004 April; 28(4): 650–661.

The main goals are to investigate the effects of chronic active heavy drinking on N-acetylaspartate (NAA) and other metabolites throughout the brain and to determine whether they are affected by family history (FH) of alcoholism and long-term drinking pattern.

Forty-six chronic heavy drinkers (HD) and 52 light drinkers (LD) were recruited from the community and compared on measures of regional brain structure using magnetic resonance imaging and measures of common brain metabolites in gray matter (GM) and white matter (WM) of the major lobes, subcortical nuclei, brainstem, and cerebellum using short–echo time magnetic resonance spectroscopic imaging. Regional atrophy-corrected levels of NAA, myoinositol (mI), creatine, and choline-containing metabolites were compared as a function of group, FH of alcoholism, and bingeing.

Frontal WM NAA was lower in FH-negative HD than FH-positive HD and tended to be lower in women than men. Creatine-containing metabolites in parietal GM were higher in HD than LD. FH-negative compared with FH-positive HD also had more mI in the brainstem and tended to have lower NAA and more mI in frontal GM. Although parietal GM NAA was not significantly lower in HD than LD, it was lower in non–binge drinkers than bingers. Frontal WM NAA was lower in HD than LD, with the difference driven by a small number of women, FH-negative HD, and older age. Lower frontal WM NAA in HD was associated with lower executive and working memory functions and with lower P3b amplitudes at frontal electrodes.

Community-dwelling HD who are not in alcoholism treatment have brain metabolite changes that are associated with lower brain function and are likely of behavioral significance. Age, FH, and binge drinking modulate brain metabolite abnormalities. Metabolite changes in active HD are less pronounced and present with a different spatial and metabolite pattern than reported in abstinent alcoholics.

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Romania defies Commission by lifting alcohol duties
Published: Friday 3 October 2008

The lower chamber of the Romanian Parliament has unanimously voted to eliminate excise duty on traditional home-brewed hard drinks, despite the very fact that it is required to collect excise on home-brewed alcohol under the terms of its EU accession treaty.

The vote to amend fiscal law took place last week. It eliminates excise duty on homemade pure alcohol up to a maximum quantity of 250 litres per household. The main homebrews in Romania are palinca and tuica (pronounced 'tsuica'), which has a lower alcohol content. The law will allow Romanians to produce up to 500 litres of palinca and 750 litres of tuica per year.

The European Commission declined to comment at this stage, because the adopted texts had not yet been obtained in Brussels today (3 October). But provisions in Bulgaria and Romania's Treaty of Accession to the EU state that lower excise duties (up to 50%) may only be introduced for 50 litres of pure alcohol per household in the case of Romania and 30 litres for Bulgaria. Above these quantities, the same minimum excise duty must apply as for all other alcohol produced in the Union: that is, 550 euros per hectolitre.

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Actin depolymerization contributes to ethanol inhibition of NMDA receptors in primary cultured cerebellar granule cells
Alcohol Volume 42, Issue 7, November 2008, Pages 525-539

We have previously reported that a 30 s ethanol (10 and 100 mM) pre-exposure significantly enhanced EtOH inhibition of N-methyl-d-aspartate (NMDA-induced currents)-induced peak currents in primary cultured cerebellar granule cells (CGCs).

The purpose of this study was to determine if intracellular factors play a role in ethanol pre-exposure-enhanced inhibition of NMDA-induced currents and if so, to identify the intracellular target(s) mediating this effect.

Ethanol pre-exposure-enhanced inhibition was reduced when ethanol was present intracellularly prior to the initiation of the pretreatment protocol. Similar to results acquired with the whole-cell configuration, ethanol pre-exposure-enhanced inhibition of NMDA-induced currents was also observed in the perforated patch-clamp mode.

Collectively, these results suggest an intracellular target not easily dialyzed from the cell. Perturbation of the actin cytoskeleton was responsible for the ethanol pre-exposure-enhanced inhibition of NMDA-induced currents was supported by the observation that the intracellular presence of the actin stabilizer phalloidin prevented ethanol pre-exposure-enhanced inhibition. Similar to the effects of ethanol, the depolymerizing agent latrunculin A inhibited NMDA-induced currents after a 30 s pretreatment exposure with full recovery of receptor function after washout of the drug.

Furthermore, latrunculin A occluded the enhanced inhibition of NMDA-induced currents by ethanol pre-exposure for both 10 and 100 mM ethanol. The microtubule depolymerizing agent taxol had no affect on ethanol pretreatment-enhanced inhibition of NMDA-induced currents. Confocal microscopy with phalloidin-FITC indicated that F-actin filaments in neurites were depolymerized after a 30 s treatment of either latrunculin A or 100 mM ethanol.

Our observations indicate that ethanol inhibition of NMDAR function may involve perturbation of the actin cytoskeleton.

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Neuropeptide Y suppresses ethanol drinking in ethanol-abstinent, but not non–ethanol-abstinent, Wistar rats
Alcohol Volume 42, Issue 7, November 2008, Pages 541-551

In outbred rats, increases in brain neuropeptide Y (NPY) activity suppress ethanol consumption in a variety of access conditions, but only following a history of ethanol dependence. NPY reliably suppresses ethanol drinking in alcohol-preferring rats, and this effect is augmented following a period of ethanol abstinence.

The purpose of this experiment was to examine the effects of NPY on two-bottle choice ethanol drinking and feeding in Wistar rats that had undergone chronic ethanol vapor exposure, cycles of ethanol abstinence, or both. Ethanol-drinking Wistar rats were given 6 weeks of access to 15% (vol/vol) ethanol and water followed by either: two cycles of 1 week ethanol vapor exposure and 2 weeks with no ethanol; two cycles of 1 week ethanol bottle availability and 2 weeks with no ethanol; or 2 weeks of ethanol vapor exposure. Rats were infused intracerebroventricularly with one of four NPY doses (0.0, 2.5, 5.0, or 10.0 μg) following the ethanol exposure patterns described above, and tested for ethanol drinking and feeding in a two-bottle choice situation.

NPY dose dependently increased food intake regardless of ethanol exposure history, but suppressed ethanol drinking only in rats that underwent cycles of ethanol access and ethanol abstinence.

These results support the notion that dysregulation of brain NPY systems during chronic intermittent ethanol exposure is important in the motivational drive for subsequent relapse to ethanol drinking.

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Effect of naltrexone during extinction of alcohol-reinforced responding and during repeated cue-conditioned reinstatement sessions in a cue exposure style treatment
Alcohol Volume 42, Issue 7, November 2008, Pages 553-563

The ability of alcohol-related cues to promote craving can be attenuated independently by giving the opioid antagonist naltrexone (NTX) or by subjecting alcohol-dependent patients to a cue exposure treatment. The effects of cue exposure treatment may be enhanced if conducted in the presence of NTX.

The purpose of these experiments was to determine if NTX given during extinction of responding for alcohol in rats would alter cue-conditioned reinstatement of responding and to determine if NTX, paired with repeated cue-conditioned reinstatement, would reduce subsequent cue-conditioned reinstatement or reacquisition of self-administration in the absence of NTX. Rats lever pressed for alcohol in the presence of an olfactory cue. Visual and auditory stimuli were presented during alcohol delivery. In the first experiment, rats were injected with saline or 3 mg/kg NTX prior to extinction sessions followed by cue-conditioned reinstatement tests. In the second experiment, extinction was followed by cue-conditioned reinstatement sessions presented twice per week. The rats received saline or NTX (3 and 10 mg/kg) prior to several sessions. All rats received reinstatement tests with and without a pretreatment of NTX followed by reacquisition of alcohol self-administration.

NTX had no effect on responding during extinction or on subsequent cue-conditioned reinstatement. Only 10 mg/kg NTX reduced responding during the twice weekly reinstatement sessions. The twice weekly NTX treatment had no effect on subsequent cue-conditioned reinstatement in the absence of NTX. Reacquisition of responding for alcohol was reduced in the group receiving saline during repeated reinstatement sessions, whereas this effect was blocked in the NTX group.

These findings support the notion that NTX given during a brief abstinence period (i.e., extinction) has minimal effects on future sensitivity to alcohol cues and alcohol consumption.

NTX given during the repeated alcohol cue exposure does not alter the subsequent incentive value of alcohol cues in the absence of NTX or enhance the beneficial effects of cue exposure treatment.

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Ethanol impairs calcium homeostasis following CCK-8 stimulation in mouse pancreatic acinar cells
Alcohol Volume 42, Issue 7, November 2008, Pages 565-573

Alcohol consumption has long been associated with cell damage, and it is thought that it is involved in approximately 40% of cases of acute pancreatitis.

In the present study, we have investigated the early effects of acute ethanol exposure on cholecystokinin octapeptide (CCK-8)-evoked calcium (Ca2+) signals in mouse pancreatic acinar cells. Cells were loaded with fura-2 and the changes in fluorescence were monitorized using a spectrofluorimeter.

Our results show that stimulation of cells with 1 nM CCK-8 led to a transient increase in [Ca2+]c, which consisted of an initial increase followed by a decrease of [Ca2+]c toward a value close to the prestimulation level. In the presence of 50 mM ethanol, CCK-8 lead to a greater Ca2+ mobilization compared to that obtained with CCK-8 alone. The peak of CCK-8-evoked Ca2+ response, the “steady-state level” reached 5 min after stimulation, the rate of decay of [Ca2+]c toward basal values and the total Ca2+ mobilization were significantly affected by ethanol pretreatment. Thapsigargin (Tps) induced an increase in [Ca2+]c due to its release from intracellular stores. After stimulation of cells with CCK-8 or Tps in the presence of 50 mM ethanol, a greater [Ca2+]c peak response, a slower rate of decay of [Ca2+]c, and higher values of [Ca2+]c were observed.

The effects of ethanol might result from a delayed or reduced Ca2+ extrusion from the cytosol toward the extracellular space by plasma membrane Ca2+adenosine triphosphatase (ATPase), or into the cytosolic stores by the sarcoendoplasmic reticulum Ca2+-ATPase. Participation of mitochondria in Ca2+ handling is also demonstrated.

The actions of ethanol on CCK-8 stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.

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Wine intake, ABO phenotype, and risk of ischemic heart disease and all-cause mortality: the Copenhagen Male Study—a 16-year follow-up
Alcohol Volume 42, Issue 7, November 2008, Pages 575-582

The association of alcohol intake with ischemic heart disease (IHD) and all-cause mortality may depend on ABO phenotype.

We tested this hypothesis in a 16-year follow-up of 3,022 Caucasian men aged 53–74 years without overt cardiovascular disease. Potential risk factors and confounders included were ABO phenotypes, alcohol intake (wine, beer, and spirits), tobacco smoking history, leisure-time physical activity, social class, and age.

During 16 years, 1985–1986 to end of 2001, 197 subjects (6.5%) died due to IHD, and 1,204 (39.8%) from all causes. Among non-O phenotypes (A, B, and AB) significantly fewer men who died due to IHD were wine consumers, 43.9% versus 55.7%, P < .01; with respect to all-cause mortality corresponding figures were 47.0% versus 60.1%, P < .001. No difference was found among men with phenotype O. Among men with phenotype A, compared to alcohol abstainers, in Cox analysis, the hazard ratio (HR) (95% confidence limit) for men drinking up to 8 beverages/wk was 0.5 (0.3–1.02), and among men consuming >8 beverages/wk (the highest quintile) the HR was 0.3 (0.2–0.8), P < .01. Among men with phenotype O, the association of wine intake with IHD mortality was slightly and not significantly U-shaped.

The difference in the predictive role of wine intake between phenotype O and phenotype A men was supported in a statistical test for interaction. A similar association was found for all-cause mortality.

The results suggest that the effect of wine intake on IHD and all-cause mortality among middle-aged and elderly men may depend on ABO phenotypes.

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Interactions between alcohol intake and the polymorphism of rs708272 on serum high-density lipoprotein cholesterol levels in the Guangxi Hei Yi Zhuang population
Alcohol Volume 42, Issue 7, November 2008, Pages 583-591

Both alcohol consumption and the polymorphism of the cholesteryl ester transfer protein (CETP) TaqIB gene (rs708272) influence plasma high-density lipoprotein cholesterol (HDL-C) levels. However, their interactions on serum HDL-C levels is not well known.

The present study was undertaken to detect the interactions between alcohol consumption and the rs708272 polymorphism on serum lipid levels in the Guangxi Hei Yi Zhuang population. Genotyping of the rs708272 in 342 nondrinkers and 416 drinkers aged 15–70 years was performed by polymerase chain reaction and restriction fragment length polymorphism. Interactions between rs708272 genotype and alcohol consumption was assessed using a cross-product term between genotypes and the aforementioned factor. Statistical significance was evaluated with analysis of co-variance.

The frequency of B1 allele was 65.8% in nondrinkers and 64.7% in drinkers (P > .05), respectively. The frequencies of B1B1, B1B2, and B2B2 genotypes were 45.0%, 41.5%, and 13.5% in nondrinkers, and 41.3%, 46.6%, and 12.0% in drinkers (P > .05), respectively.

The levels of HDL-C and apolipoprotein (Apo) AI in nondrinkers were higher in B2B2 genotype than in B1B1 genotype (P < .05 for each), whereas triglyceride (TG) levels in drinkers were higher in B1B1 genotype than in B1B2 genotype (P < .05).

The levels of TG, HDL-C, Apo AI in B1B1 genotype, and HDL-C and Apo AI in B1B2 genotype were higher in drinkers than in nondrinkers (P < .05–.01), whereas the levels of low-density lipoprotein cholesterol (LDL-C) and Apo B in B2B2 genotype, and the levels of LDL-C in B1B1 genotype were lower in drinkers than in nondrinkers (P < .05–.01).

The levels of HDL-C were positively correlated with female sex and genotype in nondrinkers (P < .001 for each), and were positively associated with age and alcohol consumption in drinkers (P < .005 and < .01, respectively).

This study suggests that the B1 carriers benefited more from alcohol consumption than the B2 carriers in increasing serum HDL-C and Apo AI levels, and lowering LDL-C levels.

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Associations of alcohol consumption with blood pressure, lipoproteins, and subclinical inflammation among Turks
Alcohol Volume 42, Issue 7, November 2008, Pages 593-601

Gender-related impact of alcohol consumption on blood pressure (BP), serum lipoprotein profile, and C-reactive protein (CRP) concentrations was evaluated prospectively.

Alcohol drinking status was assessed as abstainers and categories of light, moderate, and heavy (daily >40 ml ethanol) intake. Mean age of the 3,443 men and women who were followed up for a mean of 7.4 years was 47.6 ± 12 years. In each multivariable linear or logistic regression analysis, alcohol drinking status was adjusted for age, sex, smoking status, and physical activity.

Among men, drinking was significantly associated positively with low-density lipo protein (LDL) cholesterol, apolipoprotein (apo) B, systolic and diastolic BP, and with CRP in a log-linear manner exhibiting features of a threshold at heavy drinking. With respect to response of serum triglycerides to light-to-moderate drinking, whereas men exhibited a significant increase, women exhibited a decline (P < .05). Lower BPs (P < .03) and CRP levels (P = .032) were observed in female drinkers than abstainers and, as distinct from men, no increases in LDL cholesterol and apoB were noted.

Heavy drinking tended to protect the sexes against the risk of developing low high-density lipoprotein cholesterol levels in prospective multi adjusted analyses.

Sex modulates response of cardiometabolic risk variables to moderate alcohol consumption among Turks. Only women respond with lower triglycerides and CRP, whereas men show a log-linear positive association of drinking categories with BP, LDL cholesterol, apoB, and CRP.

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Increased mortality among women who drank alcohol during pregnancy
Alcohol Volume 42, Issue 7, November 2008, Pages 603-610

Women giving birth to children with fetal alcohol syndrome have a higher risk of early mortality. However, the risk of increased mortality associated with drinking at lower levels during pregnancy has not been evaluated previously.

Accordingly, mortality at 20 years post recruitment was examined in a sample (N = 570) of women recruited between 1980 and 1986, who drank more than 1 ounce of absolute alcohol per week (oz AA/wk) during pregnancy and compared to that in abstainers from the same low socioeconomic, African-American population.

Using data from archival information and state mortality records, Cox proportional hazards survival models were constructed to determine whether alcohol use, cigarette use, infant birth weight, infant dysmorphia, and alcohol use and abuse by the woman's own mother (family history positive) were associated with increased risk for mortality.

At follow-up (in 2003), 9.5% of the sample had died, with the rate for controls being 3.6%, for those alcohol users who stopped during pregnancy, 12.7%, and for the alcohol users who continued drinking throughout pregnancy, 12.5%. Thus, women using alcohol in pregnancy, whether they stopped or continued to use, were significantly (χ2 (2) = 12.1, P < .01) more likely than abstainers to have died before follow-up. Nondrinkers' mortality rate was lower than that of other women from this low-income, high-risk population, whereas the drinkers' rate was 2.7 times higher. In a multivariate analysis, factors contributing to mortality risk included alcohol use and cigarette smoking, but not infant birth weight. Drinking at any level during pregnancy should be regarded as a risk factor for the mother as well as for offspring. Health care professionals working with such women should provide counseling and support for abstinence. Read Full Abstract

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Commentary: Alcohol poisoning in Russia: implications for monitoring and comparative risk factor assessment
International Journal of Epidemiology,
Advance Access published online on September 29, 2008

Zaridze and colleagues1 demonstrated in their large autopsy study that, in recent years, alcohol has been a main underlying determinant of mortality in Russia. They also shed light on the role of drinking patterns, as a substantial part of death certificates with unspecified cardiovascular causes of death (i.e. disease categories labelled ‘other’ or ‘not classified’) had lethal, or potentially lethal, concentrations of ethanol in blood. These unspecified cardiovascular causes of death, together with external causes of death also markedly impacted by alcohol, were identified as. .

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Friday, October 3, 2008

Press Release - Alcohol and Violence: No Simple Solutions

ICAP Seeks to Identify and Promote Good Practice in the Prevention of Violence

WASHINGTON, DC, 2 SEPTEMBER 2008 – The International Center for Alcohol Policies announces the release of, “Alcohol and Violence: Exploring Patterns and Responses,” a report that discusses the association between alcohol and violence.

Given that there is no simple causative relationship between alcohol consumption and violence, the report approaches this complex topic through the disciplines of anthropology, clinical psychology, human rights law, gender, and public health. Patterns of violence at the societal level are explored in “Sociocultural Factors that Foster or Inhibit Alcohol related Violence” and at the individual level in “The Role of Drinking Patterns and Acute Intoxication in Violent Interpersonal Behaviors.”

“Working with Culture to Prevent Violence and Reckless Drinking” looks at alcohol and violence from a gender perspective and identifies strategies used to respond to analogous social problems. This paper offers some promising opportunities for future action.

“Practical Responses: Communications Guidelines for First Responders in Cases of Alcohol-related Violence” presents international guidelines for enhanced communication among first responders (police, emergency room staff, social workers) to alcohol-related violence, particularly between the health and law enforcement sectors

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Treatment of alcohol dependence in patients with co-morbid major depressive disorder - predictors for the outcomes with memantine and escitalopram medication
Substance Abuse Treatment, Prevention, and Policy 2008, 3:20

Alcohol dependence comorbid with major depressive disorder poses a major challenge in the clinical setting. The results in the treatment with selective serotonin re-uptake inhibitors have been conflicting. Thus, we compared in alcohol-dependent patients with co-morbid major depressive disorder the selective serotonin re-uptake inhibitor escitalopram to a compound that acts on different transporter system and may reduce craving, the glutamate receptor antagonist memantine.

The completion rate was high in both groups, especially among the patients who had been abstinent at the beginning of the study. However, among those patients who were not abstinent at baseline, 47% in both groups discontinued the study. Numbers of abstinent days were high in both groups throughout the study. In the second half of the study, significantly more abstinent days were found in the memantine group. Alcohol consumption measured by the AUDIT QF (quantity-frequency) score was significantly reduced in both groups, as was the craving for alcohol measured by the OCDS. Lower OCDS scores were observed with memantine, reaching significance at the one month measure. Early age at first alcohol intoxication predicted poor treatment outcomes in patients treated with escitalopram, and the same was seen with the early onset of the first depressive episode. The same predictive effects were not found in patients treated with memantine.

Our results indicate that both memantine and escitalopram are useful adjunct medications for the treatment of alcohol dependence co-morbid with major depression. Memantine was at least as effective with regard to drinking as escitalopram. We believe that a direct comparison of memantine, with the commonly used escitalopram, can provide useful information for clinicians on the treatment of alcohol dependency co-morbid with MDD.

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Addiction Equity Victory! Congress passed Wellstone-Domenici bill and President signed it into law today

Victory! Thanks to all of your incredible advocacy, Congress approved the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act and the President immediately signed it into law.

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SNP defiant after alcohol bill setback

Published Date: 03 October 2008
ALEX Salmond is preparing to defy the Scottish Parliament and continue with his plans to raise the age for buying off-sales alcohol to 21 – despite its overwhelming rejection by MSPs last night.

A spokesman for the First Minister said Mr Salmond still believed that raising the age limit was the right approach and the policy is expected to be included in legislation when it is brought before parliament, either later this year or early next.
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News Release - Public hearing on ways of reducing harmful use of alcohol

2 OCTOBER 2008 | GENEVA -- Each year, more than two million people die from alcohol-related causes. WHO was asked by its Member States in May at the World Health Assembly to develop a global strategy to combat the harmful use of alcohol. All parties with an interest in reducing the harmful use of alcohol are now invited to share their views in a public hearing being organized by WHO. The one-month web-based hearing will run between 3 and 31 October.

"The harmful use of alcohol is a leading risk factor for premature death and disability in the world. Every year at least 2.3 million people die from alcohol-related causes," says Dr Ala Alwan, Assistant Director-General of WHO's Noncommunicable Diseases and Mental Health Cluster. "This web-based public hearing is broad and inclusive and will provide an opportunity for everyone, including the public, to present their views on effective strategies to reduce the burden resulting from the harmful use of alcohol."

Contributions will be posted on a WHO web site dedicated to the hearing. The submissions can form a part of the documentation to be considered and discussed at the round table meetings with economic operators from the alcohol industry (planned for 6 November 2008), and NGOs and health professionals (planned for 24-25 November 2008), as well as at regional technical consultations with Member States (planned to take place between January and April 2009).

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Thursday, October 2, 2008

The DRAM Vol. 4(8) - Falling off the Recovery Wagon: Drinking Trajectories

Understanding the drinking behavior that can occur immediately after a lapse from abstinence can help individuals prepare for obstacles as they work their way toward a more stable recovery. Using data from the Relapse Replication and Extension Project (RREP), researchers examined the behavior of recovering individuals from an alcohol-related disorder following an initial post-treatment lapse (Witkiewitz & Masyn, 2008).

Witkiewitz & Masyn’s results suggest that lapses can lead to multiple drinking trajectories and that successful recovery is affected by coping skills. Further, a family history of addiction and many years of alcohol related problems do not affect individuals’ post lapse recovery. The three trajectories indicate that both lapse and lapse recovery have to be addressed early and comprehensively in an individual’s treatment so that any possible future relapse is offset by a plan for recovery.
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Involvement of Amygdala Dopamine and Nucleus Accumbens NMDA Receptors in Ethanol-Seeking Behavior in Mice
Neuropsychopharmacology advance online publication 1 October 2008

Although progress has been made identifying neural mechanisms underlying ethanol's primary reinforcing effects, few studies have examined the mechanisms mediating ethanol-induced conditioned effects. A recent lesion study suggests that expression of ethanol-conditioned behaviors depends upon an intact amygdala and nucleus accumbens core. However, specific mechanisms within these nuclei are unknown.

In the present experiments, we used site-specific microinfusions of dopamine and NMDA receptor antagonists to examine the roles of accumbens and amygdala in the expression of ethanol conditioned place preference (CPP) in mice. In experiments 1 and 2, a D1/D2/D3 receptor antagonist (flupenthixol) was infused into accumbens or amygdala before testing, whereas experiment 3 used pretest infusions of an NMDA antagonist (AP-5) to examine the role of intra-accumbens NMDA receptors.

Dopamine antagonism of accumbens was without effect, but intra-amygdala infusions of flupenthixol blocked CPP expression. Moreover, this effect was dependent upon dopamine antagonism within the basolateral nucleus but not the central nucleus of the amygdala. Antagonism of NMDA receptors in accumbens also blocked CPP expression.

The present findings suggest that expression of the ethanol-conditioned response depends upon amygdala dopamine and accumbens NMDA receptors. These are the first studies in any species to show a role for amygdala dopamine receptors and the first studies in mice to implicate accumbens NMDA receptors in ethanol-induced conditioned effects.

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Neuropsychological Study of FASD in a Sample of American Indian Children: Processing Simple Versus Complex Information
Alcoholism: Clinical and Experimental Research Published Online: 1 Oct 2008

Although a large body of literature exists on cognitive functioning in alcohol-exposed children, it is unclear if there is a signature neuropsychological profile in children with Fetal Alcohol Spectrum Disorders (FASD).

This study assesses cognitive functioning in children with FASD from several American Indian reservations in the Northern Plains States, and it applies a hierarchical model of simple versus complex information processing to further examine cognitive function. We hypothesized that complex tests would discriminate between children with FASD and culturally similar controls, while children with FASD would perform similar to controls on relatively simple tests.

Many of the neuropsychological tests produced results consistent with a hierarchical model of simple versus complex processing. The complexity of the tests was determined "a priori" based on the number of cognitive processes involved in them. Multidimensional scaling was used to statistically analyze the accuracy of classifying the neurocognitive tests into a simple versus complex dichotomy. Hierarchical logistic regression models were then used to define the contribution made by complex versus simple tests in predicting the significant differences between children with FASD and controls.

Complex test items discriminated better than simple test items. The tests that conformed well to the model were the Verbal Fluency, Progressive Planning Test (PPT), the Lhermitte memory tasks, and the Grooved Pegboard Test (GPT). The FASD-grouped children, when compared with controls, demonstrated impaired performance on letter fluency, while their performance was similar on category fluency. On the more complex PPT trials (problems 5 to 8), as well as the Lhermitte logical tasks, the FASD group performed the worst.

The differential performance between children with FASD and controls was evident across various neuropsychological measures. The children with FASD performed significantly more poorly on the complex tasks than did the controls.

The identification of a neurobehavioral profile in children with prenatal alcohol exposure will help clinicians identify and diagnose children with FASD.

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Drinking Before 15 Boosts Risk of Later Alcohol Abuse

Study suggests delaying imbibing as late as possible, until 18 or older, is best

THURSDAY, Oct. 2 (HealthDay News) -- Having that first drink before age 15 puts the imbiber at a higher risk for developing an alcohol problem later in life, a new report suggests.

"The key finding of this study was that people who started drinking before age 15, and to a lesser extent those who started drinking at ages 15 to 17, were more likely to become alcohol-dependent as adults than people who waited until 18 or older to start drinking," corresponding study author Deborah A. Dawson, a staff scientist at the National Institute on Alcohol Abuse and Alcoholism said in a news release from the institute.
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Working Together to Reduce Harm - The Substance Misuse Strategy for Wales 2008-2018

Press Release - New 10 year plan to reduce the harm caused by drugs and alcohol

Reducing the harm caused by alcohol, drugs and other substances is at the centre of a new ten year strategy launched today (Wednesday 1 October 2008) by the Minister for Social Justice and Local Government, Dr Brian Gibbons.

‘Working Together to Reduce Harm’ sets out how the Welsh Assembly Government and partner organisations will work to reduce the damage caused to individuals, their families and society from substance misuse.

Speaking at the launch of the strategy at the West Glamorgan Council on Alcohol and Drug Abuse in Swansea, Dr Gibbons said:

The misuse of drugs, alcohol or other substances is still one of the most devastating ways in which individuals can harm themselves, their families and the communities they live in.

This strategy sets out a clear agenda for the next ten years. It is a route map for all agencies in Wales to work together to make a real difference to reduce harm and to improve lives.

The strategy aims to educate and prevent substance misuse, improve services for substance misusers, support and protect families and tackle the availability of illicit drugs and the inappropriate availability of alcohol.
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Not All Drinks Are Created Equal: Implications for Alcohol Assessment in India
Alcohol and Alcoholism Advance Access published online on October 1, 2008

There is sparse literature on drink alcohol content in developing countries. This study documented detailed information on drink sizes and ethanol content of alcoholic beverages consumed in three different parts of India.

Data primarily from formative phases of studies on alcohol use patterns in the states of Delhi, Rajasthan and Goa are reported. Participant observation and semi-structured interviews with key informants and drinking respondents were used to assess different beverage types and to empirically measure actual drink sizes as poured. Investigation of ethanol content included the use of biochemical analyses, the alcoholmeter and the Analox Analyser AM3. Respondents interviewed in the post-formative phase in one study were also asked to define the volume of their drinks by indicating pour levels in select drinking vessels.

A wide range of alcoholic drinks were documented that varied in ethanol concentration across and within sites. Drink sizes, particularly for high-strength beverages, varied both by study site and respondent, with pours of distilled spirits on average being larger than standard measures.

Estimates of both mean volume of alcohol consumption and heavy drinking amounts are influenced by variability in alcohol concentration and respondent-defined pour sizes. The variation in drink alcohol content found across Indian states indicates that prior to conducting quantitative surveys, preliminary work on sources of drink alcohol content variation should be undertaken to tailor measurement tools to specific beverages and drinking practices observed. Recommendations for alcohol research in developing countries are provided.

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The Alcoholic Phenotypes among Different Multidimensional Typologies: Similarities and Their Classification Procedures
Alcohol and Alcoholism Advance Access published online on October 1, 2008

This detailed cross-sectional analysis, obtained from a sample of alcohol-dependent patients, attempts to compare multiple methods that have been created to classify or subtype alcoholics.

The sample comprised 318 alcohol-dependent patients recruited from the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital in Lisbon (Portugal). All subjects were evaluated during the outpatient therapeutical programme for operationalized criteria, reported by each alcoholism typology.

Regarding concordance agreement (kappa values) for the three type I/II classifications, von Knorring versus Sullivan yielded the higher rate of agreement, followed by von Knorring versus Gilligan and Gilligan versus Sullivan criteria. Chi-square comparisons showed a significant overlap between Babor type A and Cloninger type I of von Knorring and Sullivan. Over-two-type classifications showed the following significant positive relations: Lesch type I versus NETER heredopathic subtype; Lesch type II versus NETER anxiopathic subtype and Babor type A; Lesch type III versus NETER tymopathic subtype; Lesch type IV versus Cloninger type II of von Knorring and Sullivan criteria; and NETER adictopathic subtype versus Cloninger type II of von Knorring, Sullivan and Gilligan criteria.

There is a significant overlap across many of the multivariate alcoholic subtypes purposed, in which much of the concordance is a function of common characteristics in subtype operationalization. Commonalities among these different subtyping classification systems offers the possibility of identifying important dimensions that better differentiate individuals among problem drinker's populations.

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Haplotypic Variants in DRD2, ANKK1, TTC12, and NCAM1 are Associated With Comorbid Alcohol and Drug Dependence
Alcoholism: Clinical and Experimental ResearchPublished Online: 1 Oct 2008

Each gene in the chromosome 11q23 cluster of NCAM1, TTC12, ANKK1, and DRD2 is functionally linked to dopamine in brain. Many association studies of DRD2 and substance dependence (SD), including alcohol dependence (AD) and drug dependence (DD), have been reported; the results have been inconsistent. Recent association studies have considered this cluster more comprehensively, examining the association of SD with several risk variants mapped to the other genes in the cluster. Because comorbid AD with DD (AD+DD) is common, we hypothesized that heterogeneity of the SD diagnoses studied might have contributed to the inconsistency of prior results.

For AD+DD, the risk regions centered on TTC12 exon 3 [optimal individual haplotype simulated p (poihs) = 0.000015], and another extended from ANKK1 exon 8 to DRD2^C957T (poihs = 0.0028), in both samples. NCAM1 exon 12 markers showed global significance in both designs, but were significant for specific haplotypes (poihs = 0.0029) only for the family sample. For AD-only, NCAM1 intron 14 to 18 and the junction of ANKK1 and DRD2 were associated globally. Population stratification was excluded as the basis for these results. Linkage disequilibrium contrast tests supported selection at TTC12 exon 3 and ANKK1 exon 2.

We conclude that variants in TTC12 exon 3, NCAM1 exon 12, and the two 3'-ends of ANKK1 and DRD2 co-regulate risk for comorbid AD and DD.

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Effects of Alcoholism Typology on Response to Naltrexone in the COMBINE Study
Alcoholism: Clinical and Experimental Research Published Online: 1 Oct 2008

This study investigated whether subgroups of alcohol-dependent patients responded differently to naltrexone versus placebo in the NIAAA COMBINE study. In particular, the A versus B and the Early Onset versus Late Onset typologies were examined. Relative to Type A alcoholics, Type B alcoholics are characterized by greater severity, earlier onset, stronger family history, more childhood risk factors (e.g., conduct disorder), and greater frequency of comorbid psychiatric and substance use disorders.

Among those receiving MM without CBI, Type A alcoholics had better drinking outcomes with naltrexone than placebo, whereas medication condition did not influence outcomes significantly in the Type Bs. Age of onset was not significantly related to outcome. For those receiving CBI, no significant effects were found for either typology.

In this sample, the beneficial effects of opioid antagonism were limited to Type A alcoholics receiving treatment in a MM model. Future studies should investigate the relationship between clinically relevant genotypes, phenotypes such as typologies, and treatment response. More work is also needed to develop practical algorithms for phenotypic assignment.

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Age at First Drink and the First Incidence of Adult-Onset DSM-IV Alcohol Use Disorders
Alcoholism: Clinical and Experimental Research Published Online : 1 Oct 2008

Existing studies of the association between age at first drink (AFD) and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of control and designs that may inflate associations by failure to control for duration of exposure to risk.

This study examined associations between AFD (ages <15 class="i">n = 22,316), controlling for duration of exposure, family history, and a wide range of baseline and childhood risk factors.

After adjusting for all risk factors, the incidence of dependence was increased for AFD < 15 years (OR = 1.38) and for women only with AFD at ages 15 to 17 (OR = 1.54). The incidence of abuse was increased at AFD <15 and 15 to 17 years (OR = 1.52 and 1.30, respectively).

Most dependence criteria showed significant associations with AFD, but hazardous drinking and continued drinking despite interpersonal problems were the only abuse criteria to do so. All associations were nonsignificant after controlling for volume of consumption, except that AFD at all ages <18 combined was associated with a reduced likelihood of impaired control, and AFD at ages 15 to 17 was associated with lower odds of drinking more/longer than intended among heavy-volume drinkers.

In a population of low-risk drinkers that excluded those with positive family histories, personality disorders, and childhood risk factors, there were strong associations between early AFD (<18) or =" 3.79)" or =" 2.71),">

There is a robust association between AFD and the risk of AUD that appears to reflect willful rather than uncontrolled heavy drinking, consistent with misuse governed by poor decision-making and/or reward-processing skills associated with impaired executive cognitive function (ECF).

Additional research is needed to determine causality in the role of impaired ECF, including longitudinal studies with samples of low-risk adolescents.

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Wednesday, October 1, 2008

Botswana President Wants Alcohol Consumption Cut to Curb AIDS

By Joseph Balise

Oct. 1 (Bloomberg) -- Alcohol consumption in Botswana, where the government plans to implement a 30 percent levy on beer, wine and spirits, needs to be curbed to prevent the spread of HIV, President Ian Khama said.

``We have long been aware of its role in promoting the spread of HIV, as well as the significant contribution to anti- social, risky and criminal behavior,'' Khama said in a speech to mark the country's independence from Britain 42 years ago.

Botswana has the world's second-highest number of adults living with HIV, the virus that causes AIDS, with 24 percent of people infected, according to the United Nations AIDS Agency. Swaziland has the world's highest rate, with 26 percent carrying the virus.

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News Release - New National Poll Reveals Public Attitudes on Substance Abuse, Treatment and the Prospects of Recovery

Finds some significant differences in perceptions among various population groups.

Nearly half of American adults report knowing someone in recovery from the use or abuse of alcohol or drugs, according to survey results announced today by the Substance Abuse and Mental Health Services Administration (SAMHSA).

A large majority of Americans believe that people in recovery from substance addictions can live productive lives and contribute to their community, the report also said.


European Alcohol and Health Forum


European Alcohol and Health Forum: commitments for action by Forum members

In line with the process described in the Charter establishing the European Alcohol and Health Forum the members of the European Alcohol and Health Forum have made a series of commitments aimed at reducing alcohol-related harm. A complete overview of the 101 commitments introduced so far is contained in the following document (770 KB)

An analysis of the 79 commitments received until April 2008 is contained in the Summary Report on Commitments made by members of the European Alcohol and Health Forum. A new summary report, covering all current 101 commitments, will be published after the 3rd plenary meting of the European Alcohol and Health Forum on 13 November 2008.

Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes
Genes, Brain and Behavior Volume 7 Issue 7, Pages 705 - 713

Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics).

This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol.

Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess 'choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment.

High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting.

The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes.

Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals.

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Tuesday, September 30, 2008

Nick Clegg wants new law to fix drink prices

By James Kirkup, Political Correspondent
26 Sep 2008

A legally enforced minimum price for alcohol should be set to tackle Britain's binge-drinking culture, the Liberal Democrats have said.

Nick Clegg, the Lib Dem leader said it should be made illegal for shops to sell alcohol at a loss.

Branding big supermarkets "irresponsible" for aggressively promoting alcohol sales, Mr Clegg told the Sheffield Alcohol Conference that many big stores are selling drinks at a price that does not even cover their own costs for duty and VAT.

Mr Clegg said: "It is unacceptable for retailers, especially big supermarkets, to run a coach and horses through alcohol duties in order to sell alcohol well below its cost. The immediate effect of below-cost alcohol is to tempt people to buy a lot more alcohol than would otherwise be the case.

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Modeling gene-by-environment interaction in comorbid depression with alcohol use disorders via an integrated bioinformatics approach
BioData Mining 2008, 1:2

Comorbidity of Major Depressive Disorder (depression) and Alcohol Use Disorders (AUD) is well documented. Depression, AUD, and the comorbidity of depression with AUD show evidence of genetic and environmental influences on susceptibility. We used an integrated bioinformatics approach, mining available data in multiple databases, to develop and refine a model of gene-by-environment interaction consistent with this comorbidity.

We established the validity of a genetic model via queries against NCBI databases, identifying and validating TNF (Tumor Necrosis Factor) and MTHFR (Methylenetetrahydrofolate Reductase) as candidate genes. We used the PDG-ACE algorithm (Prioritizing Disease Genes by Analysis of Common Elements) to show that TNF and MTHFR share significant commonality and that this commonality is consistent with a response to environmental exposure to ethanol. Finally, we used MetaCore from GeneGo, Inc. to model a gene-by-environment interaction consistent with the data.

TNF Alpha Converting Enzyme (TACE) activity is suppressed by ethanol exposure, resulting in reduced TNF signaling. TNF binds to TNF receptors, initiating signal transduction pathways that activate MTHFR expression. MTHFR is an essential enzyme in folate metabolism and reduced folate levels are associated with both AUD and depression. Integrating these pieces of information our model shows how excessive alcohol use would be expected to lead to reduced TNF signaling, reduced MTHFR expression, and increased susceptibility to depression.

The proposed model provides a novel hypothesis on the genetic etiology of comorbid depression with AUD, consistent with established clinical and biochemical data. This analysis also provides an example of how an integrated bioinformatics approach can maximize the use of available biomedical data to improve our understanding of complex disease.

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Monday, September 29, 2008

Interventions in the alcohol server setting for preventing injuries
Cochrane Database of Systematic Reviews, Issue 3, 2008

Injuries are a significant public health burden and alcohol intoxication is recognised as a risk factor for injuries. There is increasing attention on supply-side interventions, which aim to modify the environment and context within which alcohol is supplied and consumed.

To quantify the effectiveness of interventions implemented in the server setting for reducing injuries.

One NRS investigated server training and estimated a reduction of 23% in single vehicle night-time crashes in the experimental area (controlled for crashes in the control area). Another NRS examined the impact of a drink driving service, and reported a reduction in injury road crashes of 15% in the experimental area, with no change in the control; no difference was found for fatal crashes. One NRS investigating the impact of a policy intervention, reported that pre-intervention the serious assault rate in the experimental area was 52% higher than the rate in the control area. After intervention, the serious assault rate in the experimental area was 37% lower than in the control.

The only RCT targeting the server setting environment with an injury outcome compared toughened glassware (experimental) to annealed glassware (control) on number of bar staff injuries; a greater number of injuries were detected in the experimental group (relative risk 1.72, 95% CI 1.15 to 2.59). A NRS investigating the impact of a intervention aiming to reduce crime experienced by drinking premises; found a lower rate of all crime in the experimental premises (rate ratio 4.6, 95% CI 1.7 to 12, P = 0.01), no difference was found for injury (rate ratio 1.1. 95% CI 0.1 to 10, P = 0.093).

The effectiveness of the interventions on patron alcohol consumption is inconclusive. One randomised trial found a statistically significant reduction in observed severe aggression exhibited by patrons. There is some indication of improved server behaviour but it is difficult to predict what effect this might have on injury risk.

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News Release - Drinking alcohol before 15 years of age is risky for later alcohol problem

  • Researchers have known that age of first drink (AFD) is associated with the later development of alcohol-use disorders (AUDs).
  • New findings show that an early AFD, before the age of 15, is especially risky for later AUDs.
  • Experts recommend delaying the onset of drinking behavior as late as possible, until 18 or older

It may seem like a minor point, but it matters when someone takes their first drink of alcohol relative to later development of alcohol problems. A new study of the relationship between age at first drink (AFD) and the risk of developing alcohol-use disorders (AUDs) during adulthood has found that the risk is greatest when AFD occurs before the age of 15.

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