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 13, 2007

Revealed: huge leap in alcohol casualties

· Hospital emergency admissions soar
· North-south division in drinks crisis

Denis Campbell and Jamie Doward
Sunday October 14, 2007
The Observer

The shocking extent of England's binge-drinking culture is laid bare today with new official figures showing an alarming increase in emergency hospital admissions owing to alcohol abuse.

Previously unpublished NHS data obtained by The Observer reveals that the number of people who had to be taken to hospital over the past five years has risen sharply in every region of the country.

The figures, obtained from patient entry records kept by every hospital, come two years after the government relaxed the licensing laws to permit 24-hour drinking and have led critics to demand strong measures to reduce high levels of alcohol-related harm.
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Serotonergic anti-depressants and ethanol withdrawal syndrome: a review
Alcohol and Alcoholism Advance Access published online on October 12, 2007

Alcoholism and depression are known to have common neurochemical substrates. The serotonergic system has great importance in both depression and alcoholism-related central mechanisms.

The aim of this review is assessing the reports from our laboratory which is involved in the effects of some anti-depressant agents that interact with the serotonergic system's signs of ethanol withdrawal syndrome in rats. Thus, both effectiveness of antidepressants in ethanol withdrawal and the relationship between the drug's effects and the signs have been investigated here on the same animal model.

Some beneficial effects of fluoxetine, tianeptine, HPE, escitalopram and venlafaxine on ethanol withdrawal signs were observed. Effectiveness ranking of the used anti-depressants was as follows: fluoxetine = tianeptine > HPE > escitalopram > venlafaxine.

Our results suggest that tianeptine and fluoxetine seem to be potent and pharmacologically active agents on ethanol withdrawal syndrome in rats. Thus, these anti-depressants may be useful in treatment of ethanol withdrawal syndrome in patients with alcoholism.

In addition to serotonergic effects, interactions with nitrergic, glutamatergic, and adenosinergic systems may also provide a significant contribution to the beneficial effects of these drugs on ethanol withdrawal syndrome.

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An evaluation of National alcohol screening day
Alcohol and Alcoholism Advance Access published online on October 13, 2007

Although National Alcohol Screening Day (NASD) became the USA's largest and most visible community-based intervention targeting risky drinking over the past decade, its utility in identifying individuals who are at risk for alcohol problems and in catalyzing behaviour change has not been tested in studies including untreated controls.

The purpose of this study was to assess changes in alcohol use three months following NASD participation using a quasi-experimental pretest-posttest control group design.

Significant decreases in the typical number of drinks consumed per occasion were observed among at-risk drinkers in the intervention group relative to controls in the 3 months following NASD. At-risk NASD participants averaged approximately 5.6 fewer drinks per week than at-risk controls.

Findings suggest that exposure to a brief screening program with provision of feedback can result in significant reductions in alcohol consumption among risky drinkers.

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Typologies of alcohol consumption in adolescence: predictors and adult outcomes
Alcohol and Alcoholism Advance Access published online on October 12, 2007

Data from the 1970 British Cohort Study were used to examine the effects of alcohol expectancies, norms, and openness of communication with parents on typologies of adolescent alcohol use and the subsequent risk of adult alcohol misuse from adolescent use.

Four adolescent drinking typologies were defined by frequency and quantity of alcohol consumption at age 16.

Positive alcohol expectancies predicted all types of adolescent alcohol use in young men and women. Norms affected frequency of alcohol use over quantity, while openness of communication with parents affected quantity of alcohol use. All men who drank alcohol in adolescence were at risk of alcohol misuse (defined by the CAGE questionnaire) in adulthood, whereas the risk for women was limited to frequent drinkers.

Drinking typologies were useful for understanding the mechanisms of adolescent alcohol use. Early prevention may be required to reduce alcohol related problems in later life.

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Friday, October 12, 2007

Human Molecular Genetics Advance Access published online on October 6, 2007

Seven alcohol metabolising enzymes are encoded by the human alcohol dehydrogenase (ADH) gene cluster on chromosome 4q22-23. One of these genes, ADH7, is uniquely expressed in the stomach mucosa and can influence metabolism of alcohol before its absorption into the blood. However, the contribution of ADH7to the overall genetic variation in alcohol oxidation in vivo is unknown.

Data on in vivo alcohol metabolism were obtained for 206 Australian twin pairs of Caucasian ancestry, following ingestion of a standard dose (0.75g. kg–1body weight) of alcohol. Twenty-five single nucleotide polymorphisms that cover the ADH7 encoding region were genotyped.

The patterns of linkage disequilibrium among these SNPs identified a recombinational hotspot within intron 7 of the ADH7 gene. A model for the absorption and elimination of alcohol from the body led to the identification of haplotypes associated with inter-individual variation in the early stages of alcohol metabolism. These are within a 35kb DNA tract contained in the region 5' of intron 7 in the ADH7 gene.

The region accounts for 18% of the linkage for alcohol concentration associated with the ADH region, or approximately 11% of the genetic variance.

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Smoking and alcoholism target genes associated with plasticity and glutamate transmission in the human ventral tegmental area
Human Molecular Genetics Advance Access published online on October 10, 2007

Drugs of abuse including nicotine and alcohol elicit their effect by stimulating the mesocorticolimbic dopaminergic system. There is a high incidence of nicotine dependence in alcoholics. To date only limited data is available on the molecular mechanism underlying the action of alcohol and nicotine in the human brain.

This study utilised gene expression screening to identify genes sensitive to chronic alcohol abuse within the ventral tegmental area of the human brain. Alcohol-responsive genes encoded proteins primarily involved in structural plasticity, neurotransmitter transport and release. In particular, genes involved with brain-derived neurotrophic factor signalling and glutamatergic transmission were found to be affected.

The possibility that glutamate transport was a target of chronic alcohol and/or tobacco abuse was further investigated in an extended case set by measurement of mRNA and protein expression. Expression levels of vesicular glutamate transporters SLC17A6 and SLC17A7 were robustly induced by smoking, an effect that was reduced by alcohol co-exposure. Glutamatergic transmission is vital for the control of the ventral tegmental area and may also be critical to the weighting of novelty and importance of a stimulus, an essential output of this brain region.

We conclude that enduring plasticity within the ventral tegmental area may be a major molecular mechanism for the maintenance of smoking addiction and that alcohol, nicotine and co-abuse have distinct impacts on glutamatergic transmission with important implications for the control of this core mesolimbic structure.

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Genetics of Lesch's typology of alcoholism.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, In Press, Accepted Manuscript, Available online 22 September 2007,

It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Lesch's typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups.

The aim of the present study was to evaluate a possible genetic background of Lesch's typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Lesch's typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients.

The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR.

No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small.

The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.

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Comparing alcohol consumption in central and eastern Europe to other European countries
Alcohol and Alcoholism 2007 42(5):465-473

To give an overview of the volume of alcohol consumption, beverage preference, and patterns of drinking among adults (people 15 years and older) in central and eastern Europe (Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia) and to compare it to southern and western Europe, Russia and Ukraine.

Average consumption in central and eastern Europe is high with a relatively large proportion of unrecorded consumption ranging from one litre in Czech Republic and Estonia to 10.5 l in Ukraine. The proportion of heavy alcohol consumption (more than 40 g of pure alcohol per day) among men was the lowest in Bulgaria (25.8%) and the highest in Czech Republic (59.4%). Among women, the lowest proportion of heavy alcohol consumption was registered in Estonia (4.0%) and the highest in Hungary (16.0%).

Patterns of drinking are detrimental with a high proportion of binge drinking, especially in the group of countries traditionally drinking vodka. In most countries, beer is now the most prevalent alcoholic beverage.

Other studies suggest that the population drinking levels found in central and eastern Europe are linked with higher levels of detrimental health outcomes. Known effective and cost-effective programs to reduce levels of risky drinking should, therefore, be implemented, which may, in turn, lead to a reduction of alcohol-attributable burden of disease.

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No changes in neocortical cell volumes or glial cell numbers in chronic alcoholic subjects compared to control subjects
Alcohol and Alcoholism 2007 42(5):400-406

To study if the total glial cell population in the neocortex is intact in subjects with a history of severe alcohol abuse compared to control subjects. Further, to investigate whether the cortical nerve cell nuclei and nerve cell perikarya volumes are the same in chronic alcoholic subjects as in the control subjects.

We found the mean neuronal cell volumes to be unaffected by severe alcohol abuse (p = 0.84) and a normal total number of glial cells (p = 0.39) in chronic alcoholic subjects compared to control subjects.

Only glial cells and dendritic/synaptic changes have so far been reported in stereological studies of the brains of alcoholic subjects. We thus have increasing evidence that it may be possible for some individuals to return to their previous cognitive abilities after cessation of alcohol which may give hope and encouragement for chronic alcoholic subjects to stop the abuse.

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Compliance with Aftercare Treatment, Including Disulfiram, and Effect on Outcome in Alcohol-Dependent Patients
Alcohol and Alcoholism Advance Access published online on September 18, 2007

To delineate the features of treatment compliance with which predicted outcome during aftercare treatment in a series of patients that completed an inpatient program at the Lisbon Regional Alcohology Centre (CRAS).

Survival analysis revealed that, after 6 months of follow-up, 39.2% of the patients had attained total abstinence of alcohol ingestion; 71% of the relapses on alcohol consumption occurred within the first 3 months.

The median number of days taking disulfiram was significantly related to the number of days of abstinence. Demographic variables, pre-treatment variables, attendance at AA meetings, AGs and outpatient appointments were not significant predictors of outcome.

Consistently taking disulfiram is associated with good outcome, but this may reflect committment to abstinence as well as a treatment effect.

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How do public health policies tackle alcohol-related harm: a review of 12 developed countries
Alcohol and Alcoholism 2007 42(5):492-499

To identify how current public health policies of 12 developed countries assess alcohol-related problems, the goals and targets that are set and the strategic directives proposed.

All the countries studied state that alcohol causes substantial harm to individual health and family well-being, increases crime and social disruption, and results in economic loss through lost productivity. All are concerned about consumption of alcohol by young adults and by heavy and problem drinkers. Few aim to reduce total consumption. Only five of the countries set specific targets for changes in drinking behaviour. Countries vary in their commitment to intervene, particularly on taxation, drink-driving, the drinking environment and for high-risk groups. Australia and New Zealand stand out as having coordinated intervention programmes in most areas.

Policies differ markedly in their organization, the goals and targets that are set, the strategic approaches proposed and areas identified for intervention. Most countries could improve their policies by following the recommendations in the World Heath Organization's European Alcohol Action Plan.

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Self-reported never-drinkers in England 1994–2003: Characteristics and trends in adults aged 18–54 years
Alcohol and Alcoholism Advance Access published online on October 12, 2007

This paper describes prevalences, time-trends and characteristics of self-reported never-drinkers, during the period 1994–2003, focussing particularly on white adults aged 18–54.

The overall proportion of white, female never-drinkers was 5.5%, rising monotonically with age. Proportions among men were much lower, with the lowest proportion (1.1%) in the 30–54 age group. Odds of never-drinking increased by 3% per year in those aged 30–54, a trend not explained by any covariates. Smaller increases were seen among those aged 18–29. Never-drinking was strongly associated with living with another adult and with lower qualification. The association with qualification increased over time among young women, and the association with living with another adult increased among men aged 30–54.

Never-drinkers are a significant minority in England, whose prevalence rose, between 1994 and 2003, among adults aged under 55 years. The prevalence varies considerably by age, sex, and social characteristics, and the social discrepancies in never-drinking appear to be widening.

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Thursday, October 11, 2007

The Readiness to Change and Insight in Alcohol dependent Patient
J Korean Med Sci. 2007 Jun;22(3):453-458.

This study was performed to investigate the effect of insight on the readiness to change in alcoholism.

The patients' readiness to change was classified into precontemplation, contemplation, and action stage through the readiness to change questionnaire. The state of the patients' insight was measured through the Hanil alcohol insight scale.

Fourteen patients (10.7%) were in the stage of precontemplation, 65 (49.6%) in contemplation and 52 (39.7%) in action stage. The insight score of the patients in precontemplation stage was significantly lower (p<0.001) than that of others.

On the basis of the precontemplation stage, multinomial logistic regression analysis for the control of the differences in the patients' characteristics among each stage of the readiness to change showed that the possibility of contemplation and action stage went up 1.231 (p<0.01)>

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Still the king of alcohol in Japan

Staff writer

The unbearably hot and humid summer is peak beer season in Japan. Here are some facts about the nation's beer market and its taxes, as well as regulations related to the alcoholic beverage:

How many beer products does Japan produce, and how much is consumed? How does Japan compare with other countries?

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Young Australians and alcohol: the acceptabllity of ready-to-drink (RTD) alcoholic beverages among 12-30-year-olds
Addiction 102 (11), 1740–1746.

Concern has been expressed regarding the influence of the newer premixed alcohols, known as ready-to-drinks (RTDs), on adolescent alcohol use as a result of their sweet and milky flavours. Use of these flavours may reduce the natural barrier of the often strong and unpleasant flavour of alcohol to early experimentation and regular and heavy use.

To determine the acceptability and alcohol detectability of a range of alcoholic and non-alcoholic beverages to young adolescents and young adults.

The acceptability of alcohol increased with age; however, chocolate ‘Mudshake’, and to a lesser extent watermelon ‘Breezer’, had acceptability scores more like their soft drink base than their alcohol component. There were no significant differences in the ability to detect the presence of alcohol in the RTDs across age or beverage types.

Public policy makers and others concerned with preventing early initiation to alcohol use and binge drinking among adolescents should be aware that when using milk as a base for an RTD, particularly with an alcoholic base such as vodka, the drink may have high acceptance with young adolescents and equal palatability to milk, even though the presence of alcohol is not completely masked. Further research with a wider range of RTDs is required.

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Arrest-Related Deaths in the United States, 2003-2005
Bureau of Justice Statistics (October 2007, NCJ 219534)

Presents the first findings from the law enforcement collection of the Deaths in Custody Reporting Program (DCRP), which is the largest resource of information ever collected on arrest-related deaths.

The report provides counts of all arrest-related deaths reported by State authorities in over 40 States, over a three-year period (2003-2005), by cause of death and characteristics of the deceased. It also includes all manners of death during an arrest, including homicides (both those by officers and other persons), suicides, alcohol or drug intoxication deaths, accidental injuries, and fatal medical problems.

The report presents counts of deaths by cause for each State. Appendix tables provide details on the circumstances surrounding arrest-related deaths including the criminal offenses for which the arrest attempt was made; the use of weapons or other behavior by the arrest subject; and use of weapons and restraint devices by officers involved in the arrest.

The report also presents comparative counts of law enforcement homicides from DCRP and counts of justifiable homicides by police, collected by the FBI’s Supplementary Homicide Reports program.

Highlights include the following:

  • Homicides by law enforcement officers made up 55% (1,095) of all deaths during arrests by State and local agencies. Eleven homicides were committed by other persons present at the scene.
  • No other cause of death was reported half as often as homicide. Drug and alcohol intoxication accounted for 13% of all deaths, followed by suicides (12%), accidental injuries (7%), and illness or natural causes (6%).
  • Three-quarters of the law enforcement homicides reported to DCRP involved arrests for a violent crime. Except for suicides (51%), violent offenders were involved in less than 30% of all other causes of death. Public-order offenders accounted for 8% of homicides, followed by property (4%) and drug offenders (2%).
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Long-term behavior in treated alcoholism: Evidence for beneficial carry-over effects of abstinence from smoking on alcohol use and vice versa.
Addictive Behaviors
Volume 32, Issue 12, December 2007, Pages 3093-3100

Co-dependence of alcohol and nicotine is quite frequent. Research results on the mutual influence one drug has on the other – i.e., on the further course of the dependence – has been inconclusive.

Our primary aim is to investigate the natural course of smoking behavior in a long term follow-up study with alcohol-dependent patients who completed an inpatient treatment program.

Our results show that being a non-smoker at treatment entry is a predictor for alcohol abstinence 7 years later. The rate of non-smokers among the abstinent patients increased by 32%.

Potential explanations for our findings lie in carry-over effects. Skills and insights gained in treatment of alcohol dependence could be instrumental in coping with smoking behavior as well. Non-smokers may have more functional coping abilities from the beginning.

We conclude that it is warranted and recommendable to explore the willingness of alcohol-dependent patients to quit smoking and to offer them treatment options addressing this point.

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A Brief Scale for Measuring Helping Activities in Recovery: The Brief Helper Therapy Scale
Substance Use & Misuse, Volume 42, Issue 11 September 2007 , pages 1767 - 1781

Helping others is evident in the philosophy of Alcoholics Anonymous, and is emphasized in formal treatment. However, helping among recovering alcoholics has not been studied, in part because of a lack of helping measures.

This study developed a Brief Helper Therapy Scale to capture helping among individuals with varying lengths of recovery. The 26-item long version of the Helper Therapy Scale was developed from qualitative interviews (n = 21) and item analysis of responses from 200 recovering alcoholics with differing lengths of recovery. Three subscales assessed Recovery, Life, and Community Helping. This brief version was created using an iterative process of item analysis designed to yield good internal consistency and representation of different types of helping. Helping was assessed as a continuous measure of how much time had been spent on each activity in the past week.

The resulting 9-item Brief Helper Therapy Scale demonstrated strong internal consistency (alpha = 0.83), but did not correlate well with psychological and spirituality measures used to assess construct validity. The Brief Helper Therapy Scale can be completed in about 5 minutes. Those in early recovery reported move involvement in recovery helping, with service in AA a notable exception. Those with the longest recovery focused more on community helping.

Findings suggest that persons more stable in recovery move beyond a singular focus on recovery helping and demonstrate that people in recovery do contribute to society - potentially dispelling some of the stigma associated with alcoholism.

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2007 Pre-Budget Report and Comprehensive Spending Review

Press notice 03: Public Service Agreements

9 October 2007

Public Service Agreements

The Government today announces a reformed performance management framework which places increased emphasis on a new relationship with public sector professionals and includes a smaller, streamlined set of 30 new PSAs articulating the Government’s highest priority outcomes for the CSR07 period.

Each PSA is underpinned by a single Delivery Agreement shared across all contributing departments and developed in consultation with delivery partners and frontline workers.

. . . . . . .

"25) A new PSA to reduce the harm caused by Alcohol and Drugs which will drive further improvement in the level of effective treatment for drug users, for the first time extending this to focus on alcohol misuse, thereby reducing the harm to communities as a result of associated crime, disorder and anti-social behaviour."

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October Washington Report

October 2007

In this issue…

Federal Developments
  • TTB Proposes Nutrition Labels for Alcoholic Beverages
  • Federal Alcohol Tax Update
  • STOP Act Appropriations Fall Short

Advocacy News
  • Campaign for a Family-Friendly Nationals Stadium
  • Global Strategy Efforts at the WHA

Mark Your Calendars
  • Alcohol Policy 14 Conference

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Statement of the National Institute on Alcohol Abuse and Alcoholism on Topiramate Clinical Trial by Johnson, et al. JAMA 10/10/07

Wednesday, October 10, 2007

Contact: 301-443-3860

The promising results of the topiramate treatment study reported by Johnson, et al in the October 10, 2007 issue of the Journal of the American Medical Association represent another development in ongoing efforts to expand and improve treatment options for individuals with alcohol dependence (alcoholism). Topiramate significantly reduced drinking among alcohol dependent individuals. And unlike previous studies with other medications, participants were currently drinking when they entered the study.
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Predictors of suicide attempters in substance-dependent patients: a six-year prospective follow-up
Clinical Practice and Epidemiology in Mental Health
2007, 3

This is a six-year prospective follow-up of a former cross sectional study of suicide attempters in a sample of treatment-seeking substance-dependent patients.

The aims were to explore the frequency of patients with new suicide attempts (SA) during the six-year observation period, and to explore the predictive value of lifetime Axis I and II disorders, measured at index admission, on SA in the observation period, when age, gender and substance-use variables, measured both at admission and at follow-up, were controlled for.

The prevalence of patients with SA between T1 and T2 was 19% (30/160), with no difference between sexes or between patient type (alcohol-dependent versus poly-substance-dependent). Sober patients also attempted suicide. At the index admission, lifetime eating disorders, agoraphobia with and without panic disorder, and major depression were significantly and independently associated with SA.

Prospectively, only lifetime dysthymia increased the risk of SA during the following six years, whereas lifetime generalized anxiety disorder reduced the risk of SA. Individually, neither the numbers of Axis I and Axis II disorders nor the sum of these disorders were independently related to SA in the observation period. Substance use measured at T1 did not predict SA in the follow-up period, nor did harmful use of substances at follow-up or in the preceding year.

A high prevalence of SA was found six years later, both in patients still abusing substances and in sober patients. To prevent SA, treatment of both affective disorders and substance abuse is important.

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Withdrawal From Intermittent Ethanol Exposure Increases Probability of Burst Firing in VTA Neurons In Vitro
J Neurophysiol
98: 2297-2310, 2007

Changing the activity of ventral tegmental area (VTA) dopamine neurons from pacemaker to burst firing is hypothesized to increase the salience of stimuli, such as an unexpected reward, and likely contributes to withdrawal-associated drug-seeking behavior. Accordingly, pharmacological, behavioral, and electrophysiological data suggest an important role of the VTA in mediating alcohol-dependent behaviors. However, the effects of repeated ethanol exposure on VTA dopamine neuron ion channel function are poorly understood.

Consistent with a role for SK in regulation of burst firing, NMDA applied during firing facilitated the transition to bursting in ethanol-treated but not saline-treated animals; NMDA consistently induced bursting only in saline-treated animals when SK was inhibited. Also, enhanced bursting in ethanol-treated animals was not a result of differences in NMDA-induced depolarization.

Further, Ih was also reduced in ethanol-treated animals, which delayed recovery from hyperpolarization, but did not account for the increased NMDA-induced bursting in ethanol-treated animals.

Finally, repeated ethanol exposure and withdrawal also enhanced the acute locomotor-activating effect of cocaine (15 mg/kg, ip).

Thus withdrawal after repeated ethanol exposure produced several alterations in the physiological properties of VTA dopamine neurons, which could ultimately increase the ability of VTA neurons to produce burst firing and thus might contribute to addiction-related behaviors.

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Letter to the FDA urging action against a campaign promoting the unapproved use of Topamax for treating alcoholics (HRG Publication #1825)

October 9, 2007

Andrew von Eschenbach, MD, Commissioner
US Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Dear Dr. von Eschenbach:

I urge you to immediately stop the illegal and dangerous promotional campaign by Ortho-McNeil Janssen-funded researchers for the unapproved use of Topamax (topiramate) for treating alcoholics (the drug is only approved for treating seizure disorders and migraines).

In a study to be published in tomorrow’s Journal of the American Medical Association, funded entirely by the company, researchers from the company and from the University of Virginia find only a modest improvement in the percentage of days of heavy drinking in people using Topamax compared with people using a placebo. Both groups also got a weekly 15 minute intervention by a trained nurse to promote compliance.

But accompanying the study, in an embargoed press kit distributed by the University of Virginia on behalf of the researchers, is a question and answer sheet asking “Can my doctor prescribe me topiramate for alcohol dependence?” The answer is, essentially, yes: “Since topiramate is currently FDA-approved for seizures and migraines, it is available to your doctor to prescribe it to you off-label.” This clearly violates the prohibition on off-label promotion, as patients are being explicitly urged/promoted to ask their doctor for topiramate to treat their serious alcohol addiction.
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Guidance for First Responders in Violent Situations Involving Alcohol: An Annotated Bibliography.

As part of its program of activities on violence, ICAP has developed an annotated bibliography of sources of guidance for first responders in situations involving alcohol and violence.

These reports aim to enhance the capabilities of first responders, namely police, emergency room staff, public health care providers, shelter staff, and others to prevent, prepare for, and respond to incidents of violence.

The document summarizes relevant resources on violence and highlights instances where alcohol is specifically referenced.
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Wednesday, October 10, 2007

The alcohol industry: taking on the public health critics
BMJ 2007;335:671 (29 September)

Views & reviews
Review of the week

The worldwide alcohol industry is flying high. With economic growth, changes in lifestyles, and the erosion of traditional customs and mores in many developing countries, the commercial production and consumption of alcohol has been booming. New competition within the industry has seen unparalleled growth, especially in the Asia Pacific region. And the party has only just begun. Some marketing organisations predict major growth in the cognac, whisky, and other spirits niches as Chinese markets continue to expand. The one cloud on the horizon is the public health sector. The alcohol industry wants to learn and avoid the mistakes that other industries have made; thus it has examined carefully the current state of the tobacco industry, the ever tightening regulation of smoking in public places, and the falling prevalence of smoking in developed countries.

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Confusion over advice on alcohol for pregnant women

· Standards body guideline permits glass of wine a day
· Draft contradicts official policy of abstinence

Sarah Boseley, health editor
Thursday October 11, 2007
The Guardian

Pregnant women face more confusion about the safety of drinking alcohol after draft guidelines published yesterday suggested a glass a day does no harm.

The draft from the government's standards-setting body, the National Institute for Healthcare and Clinical Excellence (Nice), runs directly counter to official government advice. In May, the Department of Health urged women to abstain completely from alcohol during pregnancy.

But Nice's preliminary recommendation on antenatal care - now out to consultation - says that pregnant women should limit their intake to "less than one standard drink (1.5 units or 12g of alcohol) per day and if possible avoid alcohol in the first three months of pregnancy". It says women should be told that binge drinking can be harmful to the foetus.
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Appeal for under 21 alcohol ban

Off-licences in areas of Sunderland have been urged not to sell alcohol to those under 21 at weekends.

The move comes after complaints about drink-related disorder in the Plains Farm, Silksworth, Doxford Park and Farringdon area.

So far 10 off-licences in the areas have pledged not to sell booze to people under 21 on Friday and Saturday.

Northumbria Police are urging a further nine off-licences in the area to sign up to the challenge 21 campaign.

It is illegal for those aged under 18 to purchase alcohol.
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A daily tipple is safe for pregnant women
By Laura Clout


Pregnant women may drink a small glass of wine every day without harming their unborn child, new guidance suggests.

The advice, from the National Institute of Clinical Excellence, recommends that women should consume no more than 1.5 units of alcohol a day — roughly equal to a 125ml glass of wine.

However, this contradicts the recently updated advice from the Department of Health, which urges pregnant women not to drink at all.
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Addiction 102 (11), 1699–1700.

Substance use disorders are among the leading public health challenges worldwide, with alcohol use alone accounting for approximately 4% of the global disease burden . Neither the investment in biomedical addiction research, nor health service provision in this area adequately reflect the magnitude of the problem. In fact, the view of substance use disorders as medical conditions much similar to other chronic, relapsing disorders is still not widely accepted. Ultimately, this can only change if research elucidates the pathophysiology of drug seeking behavior, and points to effective, mechanism-based treatments.

Linking genetics and brain functions subserving motivation and emotion will be key for changes to occur. In this issue, Prof Schumann provides a good illustration of current developments . Cleverly chosen intermediate phenotypes, and integration between levels of complexity are beginning to provide us with a hope of reaching a mechanistic understanding that goes beyond traditional statistical association studies. The role of genetic variation at the SERT and COMT loci, and their interaction, for processing of negative affective stimuli described by Prof Schumann provides a model for this kind of paradigm. The IMAGEN project Prof Schumann describes offers the promise of applying this type of approach directly to substance use disorders. In some ways, the IMAGEN project follows in the footsteps of the Collaborative on the Genetics of Alcoholism (COGA) in the US. They both show the value of collaborative efforts that standardize assessment methodologies across a number of sites, enabling them to collect populations that simply cannot be recruited by a single institution. A key lesson from COGA is the importance of a sustained, long-term commitment. These ambitious projects simply take time to provide a return on the investment.
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Addiction 102 (11), 1697–1699.

Professor Schumann, in his Okey lecture, beautifully outlined recent research findings combining genetics and brain imaging to discover biological aspects of vulnerability to addiction . This is cutting-edge research that will move the field forward to more precise diagnosis and more specific treatment. Of course, understanding vulnerability can lead to the best possible ‘treatment’, which is prevention of the development of addictive disorders.

The exciting findings discussed by Schumann form part of the advancing edge of knowledge about the biological underpinnings of the drug abuse disorders that we treat. He points out carefully that environment also plays an important role, but the role of genes is unfolding and should influence the development of more effective biological treatments .
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Addiction 102 (11), 1696–1697.

In his paper, Gunter Schumann provides an excellent review of the progress and perspectives of an approach that tries to link genetic variance with heritable biological phenotypes (‘endophenotypes’) rather than complex disease categories .

In complex disorders such as alcohol dependence, it may be extremely complicated to identify the multitude of genetic interactions that dispose a certain individual to develop addictive behaviour, while Schumann and collaborators successfully discovered a gene that interacts with circumscribed phenotypes such as glutamate transporter expression, excessive alcohol intake and acamprosate response . This discovery may help to elucidate individual differences in medication response and thus help to establish individually tailored treatment algorithms in alcohol-dependent patients.

However, while such studies have helped substantially to shed light on previously unknown genotype–phenotype interactions, studies with other genes have yielded controversial results.
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Okey Lecture 2006: identifying the neurobiological mechanisms of addictive behaviour
Addiction 102 (11), 1689–1695

Substance use disorders are extremely costly to the individual and to society, and a substantial proportion of patients do not respond to the therapies offered. To improve existing treatments a better understanding of the neurobiological and genetic basis of addictive behaviour and substance use disorder is warranted. The aim of this lecture is to develop a model of integrated translational addiction research which may result in the establishment of individualized therapeutic approaches for patients with substance use disorders.

The genetic basis of substance use disorders is characterized by a contribution of multiple genes to the clinical phenotype. This genetic complexity is based on poly/oligogenicity and genetic heterogeneity, two parallel mechanisms which are present to varying extents in different substance use disorders. To disentangle the complexity and to identify the genetic and neurobiological basis of addictions an integrated, translational approach involving (functional) genetic analyses, animal behavioural experimentation and neuroimaging studies is proposed.

Examples of this approach are provided by describing a line of work which identified the relevance of circadian rhythm genes in regulating alcohol drinking behaviour in animal models and humans, as well as a complementary approach using endophenotypes in human gene-neuroimaging studies where the effect of single and combined genetic variations on processing of aversive emotional stimuli in the limbic system was demonstrated.

While the combination of genetic, behavioural and neuroimaging analyses are shown to be useful tools to address oligogenicity and genetic heterogeneity in substance use disorders, the clinical relevance of this approach needs to be developed further. Thus, two current major research projects, the European integrated project ‘IMAGEN’ and the NIHR-Biomedical Research Centre ‘Mental Health’ in the United Kingdom, which potentially integrate our proposed research strategy with clinically relevant outcomes, will be discussed.

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International Research Collaboration on Alcohol and Alcoholism (U01)

Release Date: October 9, 2007
Program Announcement (PA) Number: PAR-08-004

  • The National Institute on Alcohol Abuse and Alcoholism (NIAAA) invites applications for the purpose of fostering international collaborations between alcohol research investigators within the United States and investigators located at non-United States laboratories and performance sites.
  • The program is intended to facilitate, through international collaborations, advancements in the understanding of alcohol problems and the clinical and public health approaches to their solutions.
  • Applications are invited across the full spectrum of alcohol research from basic science to clinical, public health and health services research
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Paternal alcoholism predicts the occurrence but not the remission of alcoholic drinking: a 40-year follow-up
Acta Psychiatrica Scandinavica 116 (5), 386–393.

To test the effects of father's alcoholism on the development and remission from alcoholic drinking by age 40.

High Risk subjects were significantly more likely than Low Risk subjects to develop alcohol dependence (31% vs. 16%), but not alcohol abuse (17% vs. 15%). More subjects with alcohol abuse were in remission at age 40 than subjects with alcohol dependence. Risk did not predict remission from either alcohol abuse or alcohol dependence.

Familial influences may play a stronger role in the development of alcoholism than in the remission or recovery from alcoholism.

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Tuesday, October 9, 2007

A genomic imprinting test for ordinal traits in pedigree data
Genetic Epidemiology Early View 5 October 2007

Genomic imprinting can lead maternally and paternally derived alleles with identical nucleotide sequences to function differently and has been found to affect the complex inheritance of a variety of human disorders.

Statistical methods that differentiate the parent-of-origin effects on human diseases are available for binary traits and continuous traits. However, numerous common diseases are measured on discrete ordinal scales. Imprinting may also contribute to the complex genetic basis of these traits.

In a previous study, we proposed a latent variable model and developed computationally efficient score statistic to test linkage of ordinal traits for any size pedigree while adjusting for non-genetic covariates.

In this study, we extend the latent variable model to incorporate parent-of-origin information and further develop a score statistic for testing the imprinting effect in linkage analysis. We evaluated the properties of our test statistic using simulations.

We then applied our method to the Collaborative Study on the Genetics of Alcoholism and found a novel locus on chromosome 18 that shows a strong signal for imprinting. In addition, we identified two loci on chromosomes 3 and 4 significantly (p<0.0001) linked with alcoholism.

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Pill Helps Alcoholics Taper Off Drinking

Published: October 9, 2007

CHICAGO (AP) -- A migraine pill seems to help alcoholics taper off their drinking without detox treatment, researchers report, offering a potential option for a hard-to-treat problem. The drug, Topamax, works in a different way than three other medications already approved for treating alcoholism.

Experts said the drug is likely to appeal to heavy drinkers who would rather seek help from their own doctors, rather than enter a rehab clinic to dry out. The drug costs at least $350 a month, plus the price of doctor's visits.

But side effects are a problem, and it's unclear whether the findings will make a dent in an addiction that affects millions of Americans.

Addiction specialists not involved in the study said the findings are promising, although side effects such as trouble concentrating, tingling and itching caused about one in five people to drop out of the study. Drowsiness and dizziness are also problems.
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Topiramate for Treating Alcohol Dependence
A Randomized Controlled Trial
JAMA. 2007;298:1641-1651.

Hypothetically, topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol's reinforcing effects through facilitation of {gamma}-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system.

To determine if topiramate is a safe and efficacious treatment for alcohol dependence.

Treating all dropouts as relapse to baseline, topiramate was more efficacious than placebo at reducing the percentage of heavy drinking days from baseline to week 14 .

Prespecified mixed-model analysis also showed that topiramate compared with placebo decreased the percentage of heavy drinking days and all other drinking outcomes .

Adverse events that were more common with topiramate vs placebo, respectively, included paresthesia taste perversion , anorexia , and difficulty with concentration .

Topiramate is a promising treatment for alcohol dependence.

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