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Saturday, March 15, 2008
European Journal of Pharmacology
Article in Press, Corrected Proof 14 Feb 2008
Effects of the opioid receptor antagonist naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) on operant ethanol self-administration alone and in combination with the non-competitive NMDA antagonist memantine (0.5 and 1 mg/kg, i.p.) were studied in rats.
Acute administration of naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) inhibited ethanol self-administration in a dose-dependent manner. Memantine (1.0 mg/kg) significantly enhanced the effects of naltrexone at 0.1 mg/kg, failing per se to inhibit ethanol consumption.
Thus, low, sub-effective dose of memantine in combination with low doses of naltrexone blocked the reinforcing properties of ethanol in rats.
It is suggested that the combination of sub-effective doses of memantine and naltrexone may have therapeutic value in the treatment of alcoholism particularly in a subgroup of alcoholic patients who have high sensitivity to the adverse side effects of naltrexone.
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Alcoholism: Clinical and Experimental Research, Early Online, 13 Mar 2008
The D1 dopamine receptor has been involved in a number of brain functions, including motor control, inattentive symptoms and reward and reinforcement mechanisms. Indeed, DRD1 antagonists may reduce cocaine-seeking behavior and the acquisition of cocaine-cue associations. The D1.1/r4532 marker of the DRD1 gene has been associated with a large set of phenotypes including addictive behaviors, but none with alcohol dependence per se.
We analyzed a population of 134 patients with alcohol dependence, also assessing more homogeneous (severe) phenotypes, comparing this sample with a healthy control population, assessing two SNPs within the DRD1 gene in order to depict the role of DRD1 polymorphisms and haplotypes.
The T allele of the rs686 polymorphism within DRD1 gene was significantly more frequent in patients with alcohol dependence (p = 0.0008), with a larger excess for patients with severe dependence (p = 6 × 10−6), and even more for patients with severe complications such as withdrawal seizures (p = 7 × 10−7). A specific haplotype rs686*T-rs4532*G within the DRD1 gene was significantly more precisely associated with alcohol dependence in our sample (p = 5 × 10−6).
Even though chance finding cannot be ruled out, convergent evidence is given that the DRD1 gene is a susceptibility gene in alcohol dependence, regarding the fact that relying on more homogeneous phenotypes (i.e., more severe patients) and more informative genetic markers (i.e., haplotypes) reinforce the initial association.
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Alcoholism: Clinical and Experimental Research, Online early, 13 Mar 2008
Repeated alcohol administration alters nucleus accumbens (NAC) basal glutamate content and sensitizes the capacity of alcohol to increase NAC extracellular glutamate levels. However, the relevance of alcohol-induced changes in NAC glutamate for alcohol drinking behavior is under-investigated.
While strain differences were not apparent for NAC basal levels of dopamine, serotonin or γ-amino butyric acid (GABA), repeated alcohol treatment elevated NAC basal glutamate content only in B6 mice. Strain differences in both the acute and the sensitized neurochemical responses to 2 g/kg alcohol were observed for all neurotransmitters examined. While the alcohol-induced rise in NAC dopamine and glutamate levels sensitized in B6 mice, a sensitization was not observed in D2 animals. Moreover, B6 mice exhibited a sensitized serotonin and GABA response to alcohol followed repeated treatment, whereas neither tolerance nor sensitization was observed in D2 animals. An intra-NAC APDC infusion reduced alcohol intake in both B6 and D2 mice by approximately 50%. In contrast, TBOA infusion elevated alcohol intake selectively in B6 mice.
These data indicate an active role for NAC glutamate in regulating alcohol consumption in mice and support the hypothesis that predisposition to high alcohol intake involves genetic factors that facilitate alcohol-induced adaptations in glutamate release within the NAC.
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Alcoholism: Clinical and Experimental Research, Early Online, 13 Mar 2008
Prospective studies have not previously examined whether a family history of alcoholism and drinking motives conjointly predict a diagnosed DSM-IV alcohol abuse or dependence in adults, despite a large literature that each is associated with alcohol consumption.
The focus of this study is the conjoint, prospective examination of these risk factors in a 10-year longitudinal study of adults who were at-risk drinkers at baseline.
Prospective, population-based cohort of drinkers aged 18 or older from a Northeastern U.S. area initially evaluated for history of alcohol use disorders and drinking motives in 1991 to 1992. New onset dependence was studied in those who never met the criteria for alcohol dependence at baseline (n = 423), and new onset abuse was studied in those who never met the criteria for alcohol abuse at baseline (n = 301) and who did not develop dependence during the follow-up.
Family history significantly interacted with 2 baseline drinking motives in predicting new onsets of DSM-IV alcohol dependence: drinking to reduce negative affect (OR 3.38; 95% CI 1.05, 10.9) and drinking for social facilitation (OR 3.88; CI 1.21, 12.5). Effects were stronger after conditioning the drinking motives on having a positive family history of alcoholism. In contrast, in predicting new onsets of alcohol abuse, drinking motives did not have direct effects or interact with family history.
Those who drank to reduce negative affect or for social facilitation at baseline were at greater risk of alcohol dependence 10 years later if they also had a family history of alcoholism.
These results suggest an at-risk group that can be identified prior to the development of alcohol dependence.
Further, the findings suggest utility in investigating the interaction of drinking motives with measured genetic polymorphisms in predicting alcohol dependence.
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Alcoholism: Clinical and Experimental Research, Early Online, 13 Mar 2008
Alcohol-related motor vehicle crashes kill approximately 17,000 Americans annually and were associated with more than $51 billion in total costs in 2000. Relatively little is known about the drinking patterns of alcohol-impaired (AI) drivers in the United States.
2006 Behavioral Risk Factor Surveillance System (BRFSS) was analyzed for alcohol consumption and self-reported AI driving among U.S. adults aged ≥18 years for all states. Alcohol consumption was divided into 4 categories: binge/heavy, binge/nonheavy, nonbinge/heavy, and nonbinge/nonheavy. Binge drinking was defined as ≥5 drinks for men or ≥4 drinks for women on one or more occasions in the past month, and heavy drinking was defined as average daily consumption of >2 drinks/day (men) or >1 drink/day (women). The prevalence of AI driving was examined by drinking pattern and by demographic characteristics. Logistic regression analysis was used to assess the association between drinking patterns and AI driving.
Five percent of drinkers were engaged in AI driving during the past 30 days. Overall, 84% of AI drivers were binge drinkers and 88% of AI driving episodes involved binge drinkers. By drinking category, binge/nonheavy drinkers accounted for the largest percentage of AI drivers (49.4%), while binge/heavy drinkers accounted for the most episodes of AI driving (51.3%). The adjusted odds of AI driving were 20.1 (95% CI: 16.7, 24.3) for binge/heavy, 8.2 (6.9, 9.7) for binge/nonheavy, and 3.9 (2.4, 6.3) for nonbinge/heavy drinkers, respectively.
There is a strong association between binge drinking and AI driving. Most AI drivers and almost half of all AI driving episodes involve persons who are not heavy drinkers (based on average daily consumption).
Implementing effective interventions to prevent binge drinking could substantially reduce AI driving.
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Alcoholism: Clinical and Experimental Research, Online early, 13 Mar 2008
Brain imaging studies have revealed abnormal function in the prefrontal cortex (PFC) of alcoholics that may contribute to the impulsive behavior and lack of control over drinking that characterizes this disorder. Understanding how ethanol affects the physiology of PFC neurons may help explain this loss of control and lead to better treatments for alcohol addiction.
In a previous study from this laboratory, we showed that ethanol inhibits complex patterns of persistent activity (known as "up-states") in medial PFC (mPFC) neurons in a reversible and concentration-dependent manner.
In deep-layer mPFC pyramidal neurons, ethanol reversibly attenuated electrically evoked N-methyl-d-aspartate-type glutamate receptor (NMDAR)-mediated EPSCs. Significant inhibition was observed at concentrations as low as 22 mM, equivalent to a blood ethanol concentration (0.1%) typically associated with legal limits for intoxication. In contrast to NMDA responses, neither evoked nor spontaneous EPSCs mediated by α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-type glutamate receptor were affected by ethanol at concentrations as high as 88 mM, a concentration that can be fatal to non-tolerant individuals. At similar concentrations, ethanol also had little effect on spontaneous or evoked IPSCs mediated by a-type γ-aminobutyric acid receptor. Finally, mPFC neurons showed little evidence of GABAR-mediated tonic current and this was unaffected by ethanol.
Together, these results suggest that NMDAR-mediated processes in the mPFC may be particularly susceptible to disruption following the acute ingestion of ethanol.
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American Journal of Epidemiology 2008 167(6):684-691;
The objective of this study was to assess the association between different types of alcoholic beverages and 34-year incidence of dementia.
Among a random sample of 1,462 women aged 38–60 years and living in Göteborg, Sweden, in 1968–1969, 164 cases of dementia were diagnosed by 2002. At baseline as well as in 1974–1975, 1980–1981, and 1992–1993, the frequency of alcohol intake, as well as other lifestyle and health factors, was recorded and related to dementia with Cox proportional hazard regression, by use of both baseline and updated covariates.
Wine was protective for dementia (hazard ratio (HR) = 0.6, 95% confidence interval (CI): 0.4, 0.8) in the updated model, and the association was strongest among women who consumed wine only (HR = 0.3, 95% CI: 0.1, 0.8).
After stratification by smoking, the protective association of wine was stronger among smokers. In contrast, consumption of spirits at baseline was associated with slightly increased risk of dementia (HR = 1.5, 95% CI: 1.0, 2.2). Results show that wine and spirits displayed opposing associations with dementia.
Because a protective effect was not seen for the other beverages, at least part of the association for wine may be explained by components other than ethanol.
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The Sydney Morning Herald
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Friday, March 14, 2008
By Mika Ono Benedyk
Scripps Research Institute investigators Marisa Roberto and George Koob are launching a new international conference, "Alcoholism and Stress: A Framework for Future Treatment Strategies," to be held in Volterra, Italy, Tuesday, May 6 to Thursday, May 8, 2008.
"This conference is the first international meeting of its kind," said Roberto. "Its primary purpose is to establish an international effort among both basic researchers and clinicians to develop preventive strategies and pharmacotherapeutic remedies."
Roberto notes that the growing health burdens of alcohol addiction and stress-related disorders affect the worldwide population, demanding novel treatment strategies and new advances in biomedical research.
The meeting will provide a platform for the world's preeminent scientists in alcoholism and stress research to present their latest findings through symposia, posters, discussions, and plenary lectures. Presentations will represent research in molecular and cellular biology, biobehavioral and clinical alcohol research, and epidemiology. An area of emphasis for the conference will be translational research for future treatment strategies.
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PLoS ONE 3(3): e1769.
While the phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is typically known to regulate cell growth and survival, emerging evidence suggest a role for this pathway in regulating the behavioural responses to addictive drugs.
To investigate whether PI3K contributes to patterns of risky alcohol drinking in human, we investigated genetic variations in PIK3R1, encoding the 85 kD regulatory subunit of PIK, in 145 family trios consisting of 15–16 year old adolescents and their parents.
Screening for mutations in exons, exon-intron boundaries and regulatory sequences, we identified 14 single nucleotide polymorphisms (SNPs) in the PIK3R1 gene region from exon 1 to the beginning of the 3′ untranslated region (UTR). These SNPs defined haplotypes for the respective PIK3R1 region. Four haplotype tagging (ht)SNPs (rs706713, rs2302975, rs171649 and rs1043526), discriminating all haplotypes with a frequency ≥4.5% were identified.
These htSNPs were used to genotype adolescents from the “Mannheim Study of Risk Children” (MARC). Transmission disequilibrium tests in these adolescents and their parents demonstrated sex-specific association of two SNPs, rs2302975 and rs1043526, with patterns of risky alcohol consumption in male adolescents, including lifetime prevalence of drunkenness (p = 0.0019 and 0.0379, respectively) and elevated maximum amount of drinking (p = 0.0020 and 0.0494, respectively), as a measure for binge drinking pattern.
Our findings highlight a previously unknown relevance of PIK3R1 genotypes for alcohol use disorders and might help discriminate individuals at risk for alcoholism.
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Birth Defects Research (Part A), Early View 12 Mar 2008
Our objective was to estimate the mortality rate in subjects with fetal alcohol spectrum disorders (FASD) and their siblings whose FASD status was unknown.
We used the state FASD Registry to link subjects with FASD to a North Dakota birth certificate. We were able to link 304 of 486 cases (63%). We used the birth certificates to identify the mother and children born to the mother (siblings). We then searched for death certificates for both the FASD cases and their siblings. We then calculated the annual and age-adjusted mortality rates for the siblings of the Registry cases and compared them with mortality rates from North Dakota.
The FASD case mortality rate was 2.4%, with a 4.5% mortality rate for their sibings, accounting for 14% of all deaths when compared to the North Dakota residents matched by age and year of death. The sibling deaths accounted for 21.5% of all cause mortality matched by age and year of death. The age-standardized mortality ratios were 4.9 for the FASD cases and 2.6 for their siblings whose FASD status was unknown.
Mortality rates for FASD cases and their siblings were increased and represent a substantial proportion of all cause mortality in North Dakota. Prevention of FASD may be a useful strategy to decrease mortality.
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Addiction 103 (4) , 598–603
To describe trends of responses to the Cut-down, Annoyed, Guilt, Eye-opener (CAGE) questionnaire during a period of declining alcohol consumption, in a country with no temperance history.
The proportion of subjects giving at least two positive answers has increased by 4.2 times; the biggest increase was observed for the Guilt question (4.8 times) and the smallest for the Eye-opener question (2.6 times). Several increases were higher for women than for men: 12.9 times versus 3.3 times for two or more positive answers, 9.8 times versus 3.8 times for the Guilt question. Increases did not vary consistently by age.
These paradoxical trends do not support the use of CAGE in general population surveys. They confirm previous reports suggesting that CAGE was sensitive to community temperance level. They might reflect the emergence of a temperance movement in France, with stronger impact among women. This movement might be responsible for the fall in alcohol consumption.
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Alcohol and Alcoholism Advance Access published online on March 13, 2008
Subtyping in alcohol dependence has become an important issue as studies have proposed different neurobiological mechanisms in alcoholism in the recent years.
Studies have shown that alcohol dependence reflects a wide range of different phenotypes, including psychological, social, and neurobiological factors. Different ways of subtyping have been proposed in the last decades, one of them being Lesch's typology of alcohol dependence.
Recent investigations have shown that different subtypes of Lesch's typology are associated with specific neurobiological factors which may have important implications for clinical practice.
This applies in particular for genetic and neuroendocrinological factors, differences in the regulation of NMDA receptor-mediated glutamatergic neurotransmission, and in response to acamprosate and naltrexone treatment.
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Friday 14 March 2008
Department of Health (National)
Sixty thousand new doctors will be specifically trained in the next ten years to identify and treat people who are drinking too much, Public Health Minister Dawn Primarolo will announce today.
Medical schools have been allocated £650,000 to do a scoping exercise next financial year to see how alcohol misuse training can be added to the curriculum.
The findings will enable a first tranche of medical schools to make the necessary changes - and test them - before full roll out. Within three years, every medical school in the country will have alcohol training on the curriculum.
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The ISAJE Board is pleased to announce the first winner of the ISAJE/WHO Young Scholars Award. Dr Jaeuk Hwang, a research scientist from Seoul National University Hospital, Korea, receives the award for a paper published in Drug and Alcohol Dependence on decreased cerebral blood flow in former methamphetamine users. Dr Hwang wins travel support to attend an international scientific meeting of his choice.
International Society of Addiction Journal Editors (ISAJE)
World Health Organization (WHO)
Purpose of the award
The award scheme aims to provide appropriate recognition for the contributions to addiction science of young scholars from developing countries and to promote their involvement in research and publication in the field.
Eligibility for the award
The criteria for eligibility will be as follows:
- The applicant should be less than 35 years old
- He/she should be the lead author of the published paper being submitted for the award
- He/she should hold a current academic or research position in a low or middle income country (as defined by the World Bank); or should have held such a position at the time the research for the paper was being carried out
- The research reported should have been carried out predominantly in a low or middle income country
- The paper should be based on a topic of relevance to the country or region of origin, or should have broad implications for the field of addiction research
- The paper submitted for the award should have been published either online or in print form in a peer-reviewed scholarly journal between 1 July 2007 and 30 June 2008.
Current Drug Abuse Reviews, Volume 1, 2008, Pp. 42-46
To assess the incidence of hangover we: (1) reviewed the experimental and survey literature; (2) performed secondary analyses on two large population surveys; and (3) calculated the incidence of hangover among young adults participating in several randomized trials we conducted on the aftereffects of heavy drinking.
Survey data included adults admitted for alcohol detoxification, community adults who ever got “tipsy” or “high”, adolescents in high school who ever drank heavily, adults who drank heavily in the past 12 months, and university students. Most of the experimental trials brought participants to intoxication.
The consistency of findings across study designs, populations, and referenced time period suggests that around 23% of the population may be resistant to hangover.
Since propensity for hangover may affect drinking patterns, further research on the consequences and predictors of hangover insensitivity is warranted.
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Current Drug Abuse Reviews, Volume 1, 2008, Pp. 36-41
Research into the cognitive consequences of chronic excessive alcohol use continues to grow. Despite this, little research has investigated what impact excessive alcohol use might have upon everyday remembering.
An important aspect of everyday remembering is prospective memory (PM), which refers to the cognitive ability of remembering to carry out an intended action at some future point in time.
The majority of the studies which have focused on what impact excessive alcohol use has upon PM in teenagers and young adults have consistently found that the excessive drinkers reported more lapses in their short term (e.g., forgetting to lock one’s door upon leaving home) and long term (e.g., forgetting to post a letter on time) aspects of everyday PM, when compared to low-dose alcohol users or non-users.
It is concluded from this review that PM deficits should be added to the growing list of neuropsychological sequelae associated with excessive alcohol use. The magnitude of the effects of alcohol on PM depends upon the amount of alcohol consumed and how long one has been drinking.
Major limitations of these studies include their reliance upon the use of self-report measures of PM, the issue of polydrug use complicating the picture, the need to control for the co-morbidity of other conditions - such as depression, and better drug-screening methods.
Therefore, further studies need to employ objective measures alongside self-report measures of PM, incorporate better controls for the use of other drugs and mood states, as well as extending the focus of the research to study what effect different patterns of alcohol use might have upon PM, e.g., what impact binge drinking has upon everyday PM.
These findings have educational and applied relevance within the alcohol field.
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Current Drug Abuse Reviews, Volume 1, 2008, Pp. 20-35
Expectancy Theory has offered much in the way of understanding alcohol use and abuse, and has contributed greatly to prevention and treatment initiatives.
However although many cognitive-behavioural treatment approaches are based on expectancy constructs, such as outcome expectancies and self-efficacy, high relapse rates imply that expectancy theory may be too narrow in scope, and that additional variables need to be examined if a comprehensive understanding of drinking behaviour, and better treatment outcomes, are to be achieved.
We suggest that the coping strategies an individual employs present one such set of variables that have largely been neglected from an expectancy framework. Although coping skills training is routinely used in prevention and treatment of alcohol problems, coping research has suffered from a poor theoretical framework.
In this paper we review the existing research relating expectancies, self-efficacy and coping to drinking behaviour and propose a model which explains both social and dependent drinking, by incorporating coping into an expectancy theory framework.
We also outline research and clinical implications of the proposed model.
[Full Text Article]
Current Drug Abuse Reviews, Volume 1, 2008, Pp. 3-8
The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence (addiction) is reviewed.
Although the role of AcH in EtOH addiction has been controversial, there are data showing a relationship. AcH can be formed in the brain tissues through the peroxidatic activity of catalase and by oxidation via other oxidizing enzymes such as cytochrome P-4502E1.
Significant formation of AcH occurs in vitro in brain tissue at concentrations of EtOH that can be achieved by voluntary consumption of EtOH by rodents. AcH itself possesses reinforcing properties, which suggests that some of the behavioral pharmacological effects attributed to EtOH may be a result of the formation of AcH, and supports the involvement of AcH in EtOH addiction.
Modulation of aldehyde dehydrogenase (ALDH) and brain catalase activity can change EtOH-related addictive behaviors presumably by changing AcH levels. Moreover, some condensation reaction products of AcH may promote some actions of EtOH and its consumption.
On the basis of the findings, it can be concluded that AcH may mediate some of the CNS actions of EtOH including tolerance and dependence, although further exploration the involvement of AcH in EtOH addiction is warranted.
[Full Text Article]
10 March 2008
The families, parents, local communities and police at the local level have been dealing with the problem of binge drinking for a long, long time. Families, parents, local communities know that binge drinking is a problem right across the country. What we find is that families and local police and communities have been trying to do their bit to turn this problem around, and today the Australian Government is putting up its hand to partner with them to try, to try to turn this problem around.
If you look at some of the figures, we have a big challenge on our hands. There is a 2005 survey by the Australian Secondary Students, of Australian Secondary Students Alcohol and Drug Survey. And it found that in a given week, approximately one in ten, that is 168,000 young people aged 12 to 17, reported binge drinking or drinking at risky levels. For 16 and 17 year olds, one in five drank at risky levels. In an earlier survey, 13 per cent of 18 to 20 year olds drank 13 or more standard drinks each time they visited a club, 83 per cent left the club as the driver of a vehicle and 70 per cent of males and 30 per cent of females believed that drinking was an important tradition at their club.
Ultimately, this, of course, is a question of personal responsibility. But what we propose to do is to, as the Australian Government, to do what we can to partner with parents and local communities and with families and with local police and sporting organisations to try and turn this problem around.
Therefore, we’re announcing today a $53 million program, which has three parts to it.
A $14.4 million investment in community level initiatives to confront the culture of binge drinking, particularly in sporting organisations. This funding, in particular, would be dedicated to sporting clubs to assist them in developing local codes of conduct in relation to binge drinking. The Government will also take sporting organisations actions on this question into account in the possible future consideration of grants to such sporting organisations.
Secondly, the question of personal responsibility. $19.1 million to support innovative early intervention and diversion programs for young people under the age of 18. That is where young people are found binge drinking, to provide funding and support to assist to turn those young people around.
The possible initiatives there range anything from requiring young people to participate in educational and/or diversionary activities. Or even to allow the authorities to confiscate alcohol and to provide formal warnings. Our objective under this program is to have a major pilot project up and running in each state capital of Australia during the course of 2008. We need to learn how this can work effectively at a community level.
The third part of this new national binge drinking strategy is this: $20 million over two years in a hard hitting television, radio and internet campaign that confronts young people with the costs and consequences of binge drinking.
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Eur Addict Res 2008;14:71-81
To compare acute negative consequences for people who drink a given amount of alcohol on few occasions (concentrators) per week in comparison with the consequences for people who drink the same amount on more days in a week (spreaders).
To investigate whether these associations are cross-culturally stable.
Analysis is based on general population surveys of adults conducted in 7 European countries.
It appeared that more drinking occasions in many countries lead to more consequences independent of the volume consumed.
Risky single-occasion drinking was to be associated with higher risks for immediate health consequences and legal problems, accidents and fights. Among older respondents the same frequency pattern appeared, with the exception of immediate health consequences among women.
Hence, more regular drinking seemed to have more beneficial effects on older individuals compared to younger ones, which may be related to the different drinking situation: younger people mostly drinking outside the home. Amongst the younger people, frequent drinking seemed to be associated with more acute consequences.
Cultural and methodological variations must be taken into account. Even so, it is concluded that the credibility of these findings is strengthened by differences in the methods of the surveys.
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Thursday, March 13, 2008
World J Gastroenterol 2008 March 7; 14(9): 1444-1449
To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males.
Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink-years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively).
There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2*1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2 + *2/*2) and CYP2E1 (*c1/*c2 + *c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively.
The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1) + ADH1B (*1/*2 + *2/*2), ALDH2 (*1/*1) + CYP2E1 (*c1/*c2 + *c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction.
In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.
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Neuropsychopharmacology (2008) 33, 1084–1096;
While women are more vulnerable than men to many of the medical consequences of alcohol abuse, the role of sex in the response to ethanol is controversial. Neuroadaptive responses that result in the hyperexcitability associated with withdrawal from chronic ethanol likely reflect gene expression changes.
We have examined both genders for the effects of withdrawal on brain gene expression using mice with divergent withdrawal severity that have been selectively bred from a genetically heterogeneous population.
A total of 295 genes were identified as ethanol regulated from each gender of each selected line by microarray analyses. Hierarchical cluster analysis of the arrays revealed that the transcriptional response correlated with sex rather than with the selected withdrawal phenotype. Consistent with this, gene ontology category over-representation analysis identified cell death and DNA/RNA binding as targeted classes of genes in females, while in males, protein degradation, and calcium ion binding pathways were more altered by alcohol.
Examination of ethanol-regulated genes and these distinct signaling pathways suggested enhanced neurotoxicity in females. Histopathological analysis of brain damage following ethanol withdrawal confirmed elevated cell death in female but not male mice. The sexually dimorphic response was observed irrespective of withdrawal phenotype.
Combined, these results indicate a fundamentally distinct neuroadaptive response in females compared to males during chronic ethanol withdrawal and are consistent with observations that female alcoholics may be more vulnerable than males to ethanol-induced brain damage associated with alcohol abuse.
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Neuropsychopharmacology (2008) 33, 1071–1083
Specific pharmacological treatments are currently not available to address problems resulting from fetal ethanol exposure, described as Fetal Alcohol Syndrome or Fetal Alcohol Spectrum Disorders (FASD).
The present study evaluated the therapeutic effects of aniracetam against cognitive deficits in a well-characterized and sensitive FASD Sprague–Dawley rat model. Ethanol, administered orally at a moderate dose (4 g/kg/24 h; 38% v/v) during the entire course of pregnancy, caused severe cognitive deficits in offspring. Furthermore, both progeny genders were affected by a spectrum of behavioral abnormalities, such as a delay in the development of the righting reflex, poor novelty seeking behavior, and high anxiety levels in female rats.
Cognitive disabilities, monitored in adult rats by a two-way active avoidance task, correlated well with a significant reduction of AMPA (-amino-3 hydro-5 methyl-isoxazole propionic acid) receptor-mediated miniature excitatory postsynaptic responses (mEPSCs) in the hippocampus.
Administration of aniracetam for 10 days (post-natal days (PND) 18–27), at a dose of 50 mg/kg reversed cognitive deficits in both rat genders, indicated by a significant increase in the number of avoidances and the number of 'good learners'.
After the termination of the nootropic treatment, a significant increase in both amplitude and frequency of AMPA receptor-mediated mEPSCs in hippocampal CA-1 pyramidal cells was observed. Significant anxiolytic effects on PND 40 also preceded acquisition improvements in the avoidance task.
This study provides evidence for the therapeutic potential of aniracetam in reversing cognitive deficits associated with FASD through positive post-natal modulation of AMPA receptors.
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Wednesday, March 12, 2008
Journal of Gastroenterology and Hepatology 23 (s1) , S2–S8
The aim of the present review was to: (i) highlight epidemiological and other studies that have generated important data on the harmful patterns of drinking that increase the risk for chronic diseases, including alcohol dependence, and on the mechanisms by which alcohol produces and, in some instances, may protect against damage; and (ii) discuss a conceptual basis for quantifying risk criteria for alcohol-induced chronic disease based on the quantity, frequency, and pattern of drinking.
The relationship between heavy drinking and risk for adverse health conditions such as alcoholic liver disease (ALD), dementia, and alcohol dependence is well known. However, not everyone who drinks chronically develops ALD or dementia, and the major risk factors for disease development and the mechanisms by which this occurs have remained unclear.
Large-scale, general population-based studies have provided the evidence by which quantifying the frequency of a pattern of high-risk drinking can be related directly to risk and the severity of alcohol dependence. Cellular and molecular biology studies have identified the major pathways of alcohol metabolism and how genetics and the environment can interact in some individuals to further increase the risk of organ damage.
Extant databases should allow scientists and clinicians jointly to develop the framework for quantifying the drinking patterns that increase the risk of alcohol-induced organ pathologies, to develop clinical practice guidelines, such as those used to diagnose other common complex diseases (e.g. diabetes and hypertension), and to propose future studies for refining such guidelines.
Attention must be paid to comorbid conditions such as hepatitis B and C infections, HIV, obesity, and environmental exposures other than alcohol.
Developing trait and state biomarkers is critical to the process of discovery and to fulfilling the promise of personalized medicine.
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Nordic Journal of Psychiatry 12 Mar 2008
Although drinking patterns in women have received increased attention, few studies have focused on middle-aged women.
Drinking patterns were investigated in a population sample of 513 Swedish women aged 50-59, and analysed in relation to social situation, and mental and physical health.
Abstainers and occasional drinkers had lower levels of education and more often regular medical control compared with weekly drinkers. Furthermore, abstainers more often had disability pension. Among women drinking alcohol, 56.6% affirmed binge drinking within the last year and 39.4% within the last month. Binge drinkers did not differ in terms of social situation, mental or physical health, compared with other drinkers.
Drinking to relieve tension was affirmed by 7.2%. These women had more mental symptoms and less contact with friends compared with other drinkers; furthermore, they were more often binge drinkers.
Binge drinking was common and health and social consequences of this drinking pattern in middle-aged women need to be further explored.
Women drinking to relieve tension may need intervention for both drinking habits and mental health.
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By Nick Triggle
Health reporter, BBC News
Public health chiefs have welcomed the tax rises on alcohol, but said there is still a way to go before it starts influencing drinking habits.
Chancellor Alistair Darling announced excise duty on beer, wine and spirits would rise by 6% above inflation - the biggest monetary rise since the 1970s.
It comes after the levy has struggled to keep pace with inflation since Labour came to power.
But experts said it was still not enough to make a "real difference".
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Reclaiming Futures® changed the way juvenile courts in 10 pilot sites help teens with drug and alcohol problems. A new national dissemination program supported by a grant from the Robert Wood Johnson Foundation is spreading the Reclaiming Futures approach to up to six new communities this year through a learning collaborative that shares resources, improves data collection and utilization and promotes new standards of practice. No grant funds will be awarded, but successful applicants will receive a technical assistance package valued at $180,000.
Want to become a Reclaiming Futures site in 2008? Join us for a live one-hour web conference at 1:30pm EDT, on Thursday, March 20.
This session offers an excellent opportunity to talk to the staff of the Reclaiming Futures National Program Office about the current call for proposals and learn more about the selection process. See below for instructions on how to joining the web conference. The proposal deadline is April 1, 2008.
Frequently asked questions and answers about the Reclaiming Futures application process are posted on our website. Don't see an answer to your question? Please contact Jim Carlton at 503-725-8954 or by email at email@example.com.
The complete call for proposals is available at www.rwjf.org/cfp/reclaimingfutu
Instructions for March 20
To take part in the free web conference, visit rwjf.webex.com a few minutes before the meeting start time. The meeting number is 577 407 494. The password is reclaiming.
Once you're logged-in, you'll get a "Join Teleconference" pop-up form. The first field asks you to "select a phone." Please ignore that box and go the next (and last) box which simply asks for your "Number." Type in your telephone number, including area code, and click "submit." You will receive a phone call immediately thereafter connecting you to the audio portion.
Note: If you do not have a direct line (if you have an extension in your number) this call back feature will not work. In this case close the "Join Teleconference" window and manually dial 866-469-3239. You will then be asked for a meeting number. The meeting number is: 577 407 494
If you encounter difficulty getting into the meeting, please call Tech Support: 1-866-863-3904. After you're connected choose option #4. Then choose option #1.
- Simon Bowers
- Wednesday March 12 2008
Excise duty on alcohol is to rise by 6% above inflation from midnight on Sunday in an effort to curb Britain's steadily creeping boozing habit, the chancellor has revealed.
Duty on beer will rise by 4p a pint, cider by 3p a pint, wine by 14p a bottle and spirits by 55p a bottle. After that, duties will continue to rise by 2% above inflation for each of the next four years.
The rise is a huge blow for Britain's pub industry which is suffering its worst trading period in working memory. Already suffering in the wake of smoking ban laws, pub trade has been steadily losing ground to supermarkets offering deeply discounted promotions on multi-packs of beer.
Rob Hayward, chief executive of the British Beer and Pub Association (BBPA) said: "The government is punishing all beer drinkers rather than punishing the minority of drunken hooligans.
"Its policy is fuelling Britain's binge drinking problem by driving people away from beer, out of the pub into the arms of the deep discounting supermarkets."
But the British Medical Association gave the chancellor's move a warm welcome. Dr Vivienne Nathanson, the BMA's head of science and ethics, said: "These tax increases may be unpopular with some members of the public but we hope that they will look at the wider issue and recognise that the UK has a real problem on its hands regarding alcohol misuse. Tough action is needed."
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12 March 2008
Stability and opportunity: Building a strong sustainable future
Alcohol Duty Rates
As incomes have risen, alcohol has become increasingly more affordable. A 6 per cent increase in all alcohol duty rates will come into effect on 17 March 2008. This will add 4 pence to the price of a pint of beer, 55 pence to the price of a bottle of spirits and 14 pence to the price of a bottle of wine. In order to ensure that alcohol duties keep pace with rising incomes alcohol duty rates will increase by 2 per cent above the rate of inflation in future years.
Tuesday, March 11, 2008
Drug and Alcohol Dependence . Article in Press, Corrected Proof, 7 Mar 2008
Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, in particularly in those with marked withdrawal symptoms. The common C677T transition on the methylenetetrahydrofolate reductase (MTHFR) gene influences homocysteinemia.
Our objective was to study the prevalence of the MTHFR C677T polymorphism in alcohol-dependent subjects and the influence of this polymorphism on symptoms associated with alcoholism.
MTHFR C677T polymorphism was determined in 93 control subjects and 242 alcohol-dependent subjects. Serum homocysteine, folate and vitamin B12 levels together with hepatic biological parameters were determined in the control and alcohol-dependent subjects.
Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, particularly in those with marked withdrawal symptoms. Alcohol-dependent subjects showed a significant decrease in MTHFR 677TT prevalence (9%, 21/242) compared to controls (18%, 17/93) (p <>p <>
MTHFR 677TT genotype could play a protective role against alcohol dependence. Moreover, when subjects with MTHFR 677TT genotype become dependent to alcohol, they seem to constitute a subgroup of alcoholic patients with a decreased risk for developing neurotoxic withdrawal symptoms and hepatic toxicity.
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Those filled with despair at the prevalence of binge drinking in 21st-century Britain cannot say they were not warned - Sir Walter Raleigh cautioned over the dangers of alcohol more than 400 years ago.
The one-time favourite of Queen Elizabeth I even wrote a little-known treatise on the matter, warning future generations - and his son, also called Walter, in particular - that excessive alcohol consumption "transformeth a Man into a Beast" and was "a bewitching and infectious Vice" which destroyed health and led to premature ageing.
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Alcoholism: Clinical and Experimental Research, OnlineEarly Articles
11 Mar 2008
U.S. epidemiologic surveys have consistently found higher lifetime prevalence of alcohol dependence among younger subjects than among older groups. Because lifetime prevalence is cumulative, such patterns are suggestive of strong secular trends; i.e., more-recently born subjects have developed more disease in a shorter period of time than their elders. However, it remains unclear whether such patterns truly reflect secular trends or are confounded by age-dependent factors such as differential recall, differential mortality, and other effects.
Using data from 2 large, national epidemiological surveys, a repeated cross-sectional analysis was conducted to compare lifetime prevalence of alcohol dependence across temporally adjacent birth cohorts surveyed at the same age, thus enabling estimates of cross-cohort differences while controlling for age-related factors.
In contrast with results from single cross-sectional analyses, there were few significant cross-cohort differences among groups of men compared at similar ages. On the other hand, women born between 1954 and 1963 were at 1.2-fold higher odds for lifetime drinking, and those who drank were at 1.5-fold higher odds for lifetime alcohol dependence, compared with the immediately preceding birth cohort (1944 to 1953). The 1944 to 1953 cohort was also at elevated odds for lifetime drinking compared with their predecessors (1934 to 1943). These results were largely due to changes among White and Hispanic women.
These results suggest that there have been substantial secular increases in drinking and alcohol dependence among women, but not men. Analyses of single cross-sectional studies may tend to over-estimate secular trends by failing to account for age-dependent effects. Nonetheless, secular increases in drinking and alcohol dependence among women are evident after taking age-related factors into account.
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Monday, March 10, 2008
Alcoholism: Clinical and Experimental ResearchOnlineEarly Articles 6 Mar 2008
The development of alcohol dependence (AD) involves transitions through multiple stages of drinking behaviors and is shaped by both heritable and environmental influences.
We attempted to capture this dynamic process by characterizing genetic and environmental contributions to the rate at which women progressed through 3 significant transitions along the pathway to AD: nonuse to initiation, initiation to onset of first alcohol-related problem, and first problem to onset of AD.
Heritable influences were found for rate of progression across all 3 transitions, accounting for 30 to 47% of the variance in transition times. Shared environmental contributions were evident only in rate of progression from nonuse to initiation (i.e., age at first drink). Heritable contributions to the rate of movement through successive drinking milestones were attributable to a common factor, whereas environmental influences were transition-specific.
The current study is unique in its use of a genetically informative design to document the rate of movement between drinking milestones in a female sample and to examine genetic contributions to multiple transition times over the course of AD development.
Results indicate that an earlier report of heritability for males in rate of progression from regular drinking to AD generalizes to women and to other alcohol stage transitions. Findings also suggest the need to consider stage-specific environmental contributions to alcohol outcomes in developing interventions.
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