Alcohol and Alcoholism - recent issues

Understanding and Treating Alcohol Craving and Dependence: Recent Pharmacological and Neuroendocrinological Findings

Leggio, L. — 2009-06-24

There is a substantial need for discovering innovative ways to provide more information on the neurobiology of alcohol dependence as well as to discover more effective pharmacotherapies for alcohol dependence. Current research includes exploring new pathways able to modulate alcohol craving. In particular, research shows that several neuroendocrinological pathways may be involved in the neurobiology of alcohol craving and dependence. The first part of this review examines recent clinical findings on the role of feeding-related peptides in alcohol craving and dependence. Second, this review focuses on the need to discover new medications that may prove to be safe and effective in the treatment of alcohol dependence. For example, the GABA_B receptor has been suggested as a new possible neuropharmacological target in the treatment of alcohol dependence. Accordingly, the second part of this review examines recent clinical findings on the role of the selective GABA_B receptor agonist baclofen in the treatment of alcohol-dependent subjects. These two distinct topics will be both analyzed and discussed. The final part of this review discusses possible connections between these two topics, as an example of possible interactions between psychoneuroendocrinology and neuropharmacology. These possible interactions could lead to future intriguing research aimed at understanding and treating alcohol craving and dependence.

Manganese Superoxide Dismutase (MnSOD) Polymorphism, Alcohol, Cigarette Smoking and Risk of Oesophageal Cancer

Sun, L., Konig, I. R., Homann, N. — 2009-06-24

Aims: Alcohol, tobacco smoke and Barrett's oesophagus as a consequence of gastro-oesophageal reflux are the main risk factors in oesophageal carcinogenesis. All risk factors may induce oxidative stress. Manganese superoxide dismutase (MnSOD) is one important repair enzyme for reactive oxidative stress (ROS)-induced damage. MnSOD polymorphisms in the –9 position of the signal sequence of the protein may lead to critical enzyme deficiency. The aim of the present study was to investigate the role of polymorphisms of MnSOD in patients with oesophageal cancer [n = 170, 61 patients with adenocarcinoma (AC), 109 patients with squamous cell carcinoma (SCC)] compared to heavy drinkers (n = 160) and healthy blood donors (n = 400). Methods: Genotyping was performed by PCR-RFLP analysis using genomic DNA extracted from whole blood. Results: The Ala/Ala genotype was 27.7% in cancer patients (29.5% AC, 26.6% SCC), 23.1% in patients with heavy alcohol abuse and 12.5% in the group of healthy blood donors. These results were not statistically significant after multivariate analysis controlling for age, sex, alcohol, cigarettes and interactions (odds ratio 0.92, 95% confidence interval = 0.63–1.36, for cancer patients versus heavy drinkers; odds ratio 1.02, 95% confidence interval = 0.51–2.03, for cancer patients versus blood donors; analysis by logistic regression). Subjects with an Ala/Ala genotype (81.3 g/day) had a significantly higher alcohol intake than those with Val/Ala (63.9 g/day) or Val/Val (53.8 g/day) genotype (P < 0.00001 by the Kruskal–Wallis test). Conclusions: MnSOD polymorphisms play no role in the genetic predisposition to oesophageal cancer. However, our data suggest a complex gene-to-phenotype interaction between the MnSOD genotype and alcohol misuse.

Role of the HPA Axis and the A118G Polymorphism of the {micro}-Opioid Receptor in Stress-Induced Drinking Behavior

Pratt, W. M., Davidson, D. — 2009-06-24

Aims: The present study sought to investigate the relationship between the HPA axis reactivity to stress, the endogenous opioid system and stress-induced drinking behavior. Methods: In the present study, 74 non-treatment-seeking alcohol-dependent subjects were tested under two mood conditions, neutral and stress, in separate testing sessions. Salivary cortisol measurements were obtained following stress induction and during the neutral control condition. Multiple measurements of alcohol intake, latency to access the alcohol cue and craving for alcohol were obtained during cue-availability testing. In addition, 52 of the study subjects were genotyped for the µ-opioid receptor. Results: A blunted cortisol response to stress was significantly correlated with increased alcohol intake following stress exposure compared to alcohol intake during the neutral session. There was not a clear correlation between the change in cortisol in response to stress and the change in latency to access alcohol or alcohol craving in response to stress. Carriers of the Asp40 variant of the µ-opioid receptor exhibited a dampened cortisol response to stress, higher alcohol intake and greater craving in response to stress compared to Asn40 homozygotes, although these differences were not statistically significant. Conclusions: The results of the present study indicate that a blunted biological stress response was correlated with increased drinking in response to stress. The Asp40 variant of the µ-opioid receptor may be associated with this HPA axis hyporeactivity although the small sample size used in the present study did not permit adequate evaluation of this association.

The Influence of Different Types of Alcoholic Beverages on Disrupting Highly Active Antiretroviral Treatment (HAART) Outcome

Miguez-Burbano, M. J., Lewis, J. E., Fishman, J., Asthana, D., Malow, R. M. — 2009-06-24

Aims: Studies have yielded conflicting results regarding alcohol's influence on HIV outcomes, particularly after highly active antiretroviral treatment (HAART). Discrepant findings may be related to confounding variables, including gender, patterns of alcohol abuse and type of alcohol beverage beyond the amount consumed. Methods: Using a cohort study, differences in HAART effectiveness after 24 weeks of therapy were compared as a function of amount and preference for alcohol, drinking only liquor (LI, n = 55) or only wine or beer (BW, n = 110). Given the critical role of thymus on HAART response, changes in thymus size, CD4s, naïve lymphocytes and viral loads were assessed. Results: After HAART, positive increases in both CD4s (+12 cell counts/mm³) and thymus size (+0.7 mm³) were evident in the BW group. In contrast, the LI subgroup exhibited a decline in both parameters (–4 CD4 cells/mm³ and –0.6 mm³ in thymus size). Women in the LI group exhibited significantly lower CD4 (163.4 ± 46.2) and naïve counts (178 ± 69.5) than LI men (CD4: 281.6 ± 203, P = 0.05; lymphocytes: 301.4 ± 198, P = 0.04). In adjusted regression models, the LI compared to the BW subgroup had greater odds of maintaining detectable viral loads (RR = 1.35, 95% CI 1.04–1.75; P = 0.03), increased thymus volumes (RR = 3.8, P = 0.04) and replenished naïve cells (RR = 13, P = 0.02). Conclusions: Liquor was associated with thymus deterioration and thus with poorer viro-immune outcomes after HAART. Subtyping participants by alcohol consumption patterns seems to be clinically relevant and needs to be accounted for in future studies.

Impairment of Cognitive Abilities and Decision Making after Chronic Use of Alcohol: The Impact of Multiple Detoxifications

Loeber, S., Duka, T., Welzel, H., Nakovics, H., Heinz, A., Flor, H., Mann, K. — 2009-06-24

Aims: In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. Methods: Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. Results: Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. Conclusions: Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

Thrombocytopenia in Early Alcohol Withdrawal is Associated with Development of Delirium Tremens or Seizures

2009-06-24

Aims: In several studies, possible risk factors/predictors for severe alcohol withdrawal syndrome (AWS), i.e. delirium tremens (DT) and/or seizures, have been investigated. We have recently observed that low blood platelet count could be such a risk factor/predictor. We therefore investigated whether such an association could be found using a large number of alcohol-dependent individuals (n = 334). Methods: This study is a retrospectively conducted cohort study based on data from female and male patients (>20 years of age), consecutively admitted to an alcohol treatment unit. The individuals had to fulfil the discharge diagnoses alcohol dependence and alcohol withdrawal syndrome according to DSM-IV. Results: During the treatment period, 3% of the patients developed DT, 2% seizures and none had co-occurrence of both conditions. Among those with DT, a higher proportion had thrombocytopenia. Those with seizures had lower blood platelet count and a higher proportion of them had thrombocytopenia. The sensitivity and specificity of thrombocytopenia for the development of DT during the treatment period was 70% and 69%, respectively. The positive predictive value (PPV) was 6% and the negative predictive value (NPV) was 99%. For the development of seizures, the figure for sensitivity was 75% and for specificity 69%. The figures for PPV and NPV were similar as those for the development of DT. Conclusions: Thrombocytopenia is more frequent in patients who develop severe AWS (DT or seizures). The findings, including the high NPV of thrombocytopenia, must be interpreted with caution due to the small number of patients who developed AWS. Further studies replicating the present finding are therefore needed before the clinical usefulness can be considered.

Cancer Incidence among Patients with Alcohol Use Disorders--Long-Term Follow-Up

2009-06-24

Aims: The aim of this study was to compare the cancer morbidity in a large cohort of patients with alcohol use disorders in the general Danish population. Methods: We included 15,258 men and 3552 women free of cancer when attending the Copenhagen Outpatient Clinic for Alcoholics in the period from 1954 to 1992. The cancer incidence until 1999 of the patients and the general Danish population was obtained through linkage with the Danish Cancer Registry. The incidence rates were standardized (SIR) according to sex, age and calendar time. Results: A total of 2145 men developed cancer compared to 1140.8 expected cases (SIR = 1.9; 95% confidence interval (CI) 1.8–2.0), while 601 women developed cancer compared to 239.1 expected cases (SIR = 2.5; 95% CI 2.3–2.7). Highly significant and strongly elevated incidence rates were found for cancer of the tongue, mouth, pharynx, oesophagus, liver, larynx and lung. A higher incidence rate was seen for renal cancer for both men (1.4; 1.1–1.8) and women (2.1; 1.0–3.8). The incidence of breast cancer in women was non-significantly elevated, but significantly elevated incidence rate was found for cervical cancer (1.8; 1.2–2.6). We did not observe increased incidence of colon, rectal or urinary bladder cancer. Conclusions: In conclusion, this study confirms the well-established association between high alcohol intake and cancer of the upper digestive tract and liver. In addition, the results indicate a significantly elevated occurrence of renal cancer, but not of breast cancer and colorectal cancer, in patients with alcohol use disorders.

Severity of Alcohol Dependence in Decompensated Alcoholic Liver Disease: Comparison with Heavy Drinkers without Liver Disease and Relationship to Family Drinking History

2009-06-24

Aim: The aim of this study was to compare alcohol dependence severity in patients with severe alcoholic liver disease (ALD) with that in heavy drinkers without liver disease. Methods: Short alcohol dependence data and lifetime alcohol questionnaires applied to unselected heavy alcohol drinkers (>60 units/week (M) or 40 units/week (F) for >5 years) with either (a) decompensated ALD (patients n = 136) or (b) no evidence of serious liver disease by clinical, biochemical and ultrasound evaluation (‘controls’ n = 148). Results: The SADD alcohol dependence severity score (range 0–42) in patients with ALD was >28 (severe dependence) in 36 cases (26%); slightly higher than that in heavy-drinking controls taken as a whole; similar to that in controls who were seeking healthcare but higher than that in controls who were not; and lower than that in controls who attended specialist alcohol services. In ALD patients and controls, the SADD score was higher in those with three or more heavy-drinking first-degree relatives than in those with none. In multiple regression analysis, the SADD score showed independent associations with young age, clinically manifest alcohol dependence, seeking healthcare and the presence of multiple heavy drinking relatives, but not with ALD. Conclusions: Alcohol dependence severity in patients with ALD varies and tends to be lower than that in heavy drinkers seeking treatment at alcohol treatment centres but is not as low as implied in some previous studies. Alcohol dependence severity is associated with young age and family drinking history but is not specifically associated with the development of liver disease.

Validation of the Bayesian Alcoholism Test Compared to Single Biomarkers in Detecting Harmful Drinking

Korzec, S., Korzec, A., Conigrave, K., Gisolf, J., Tabakoff, B. — 2009-06-24

Aims: Conventional tests for alcohol dependence often fail to detect hazardous and harmful alcohol use (HHAU) accurately. We previously validated the Bayesian Alcoholism Test (BAT) for the detection of HHAU among males. This uses 15 biochemical and clinical variables, including questionnaire data to calculate the probability of harmful (>80 g alcohol/day), hazardous (40–80 g/day) and ‘moderate’ (<40 g/day) drinking. Here we investigate the BAT's diagnostic performance when more limited clinical data are available. Methods: The WHO/ISBRA Collaborative Project recruited subjects from the general community and alcohol dependence treatment services. We analysed data from male drinkers: 318 alcohol dependent, 220 heavy and 712 moderate drinkers. Drinking was assessed using the Alcohol-Use Disorders and Associated Disabilities Interview Schedule. Eight of 15 markers used in the original BAT could be extracted from the WHO/ISBRA dataset. Results: Comparing harmful to moderate drinkers, the area under the ROC curve for BAT (0.90) was significantly higher than that for CDT (0.82), GGT (0.77) and AST (0.76). Comparing hazardous to moderate drinkers, the area under the ROC curve for BAT (0.78) was significantly higher than that for AST (0.65) but not significantly higher than that for CDT (0.71) and GGT (0.70). For all 1250 subjects, the amount consumed correlated significantly better with BAT (0.65) than with CDT (0.52), GGT (0.44) or AST (0.40) alone. Conclusions: The BAT is more accurate than commonly used single biological markers in detecting harmful alcohol use, even when only half the input requirements are available. Computerized record keeping increases the practicality of use of algorithms in the detection of harmful drinking.

Low-Alcohol Beers: Contribution to Blood-Ethanol Concentration and Its Elevation above the UK Legal Limit after 'Topping-up'

Badawy, A. A.-B., Morgan, C. J., Thomas, R. — 2009-06-24

Aims: The aim of this study was to establish the contribution of low-alcohol beers to blood-ethanol concentration (BEC) and to test if ‘topping-up’ with these beverages can increase BEC above the 80 mg/dl UK legal limit. Methods: Healthy male and female volunteers received a dose of ethanol designed to give a BEC of just below 80 mg/dl, and then received one pint (600 ml) of a 1% v/v alcohol beer in the fasting state or after lunch, or of a zero-alcohol or a 0.5% v/v alcohol beer after fasting. BEC was determined enzymatically and data were subjected to ANOVA. Results: Topping-up with a pint of a 1% v/v alcohol beer increased BEC >80 mg/dl in fasting subjects, contributing an extra 12–17 mg/dl, which lasted longer in males (80 min) than in females (20 min). A 0.5% v/v alcohol beer increased BEC above 80 mg/dl only in males, which lasted for 60 min. After food intake, the 1% v/v alcohol beer increased BEC above 80 mg/dl transiently only in males. Conclusions: Low-alcohol beers make a significant contribution to blood-ethanol concentration and can increase it above the UK legal limit. Their use as a ‘top-up’ should be discouraged. Low-alcohol beers have a place as a substitute for normal-strength beverages as a strategy for decreasing alcohol consumption in general and in countries where low legal alcohol limits are in force or being contemplated.

Treatment for Alcohol Dependence in Catalonia: Health Outcomes and Stability of Drinking Patterns over 20 Years in 850 Patients

Gual, A., Bravo, F., Lligona, A., Colom, J. — 2009-06-24

Aims: The aim of this study was to evaluate long-term outcomes in alcohol-dependent patients following outpatient treatment and gender differences in drinking outcome and mortality. Methods: A 20-year longitudinal prospective study was done with interim analyses at 1, 5 and 10 years. Of the original sample of 850 patients, 767 (90%) were located 20 years later and 393 of these were interviewed. 273 (32%) patients died during the intervening period and 101 (12%) no longer wished to participate in the study. Drinking status was assigned based on the 12 months prior to the follow-up interview. Results: At the 20-year follow-up, 277 (32.6%) of the 393 patients for whom drinking status could be assigned were abstinent (defined never drinking or drinking on less than occasion per month and never more than four drinks/drinking occasion.), 29 (3.4%) were controlled drinkers and 87 (10.2%) were heavy drinkers. Controlled drinking was the least stable category, with 23% continuing from year 5 to year 10 in that category, and 10% continuing in that category from year 10 to year 20. Mortality was higher (39.1%) in those who had been categorized at year 5 as heavy drinkers compared to those who had been categorized as controlled drinkers or abstinent. Abstinent patients reported fewer alcohol-related problems and better psychosocial functioning than heavy drinkers. Women achieved higher abstinence rates (47.2% versus 29.0%, P = 0.005) and had lower mortality (22.4% versus 34.5%, P = 0.03) than men. Conclusions: Over the long-term, abstinence is the most frequent and stable drinking outcome achieved and is associated with fewer problems and better psychosocial functioning. Controlled drinking is rarely achieved and sustained. Women appear to do better than men in the long term.

The Role of AA Sponsors: A Pilot Study

Whelan, P. J. P., Marshall, E. J., Ball, D. M., Humphreys, K. — 2009-06-24

Aims: The aim of this study was to explore the roles of Alcoholics Anonymous (AA) sponsors and to describe the characteristics of a sample of sponsors. Methods: Twenty-eight AA sponsors, recruited using a purposive sampling method, were administered an unstructured qualitative interview and standardized questionnaires. The measurements included: a content analysis of sponsors’ responses; Severity of Alcohol Dependence Questionnaire—Community version (SADQ-C) and Alcoholics Anonymous Affiliation Scale (AAAS). Results: Sample characteristics were as follows: the median length of AA attendance was 9.5 years (range 5–28); the median length of sobriety was 11 years (range 4.5–28); the median number of sponsees per sponsor was 1 but there was a wide range (0–17, interquartile range 3.75); and the sponsors were highly affiliated to AA (median AAAS score 8.75, range 5.5–8.75, maximum possible score 9). Past alcohol dependence scores were surprisingly low: 5 (18%) sponsors had mild, 14 (50%) moderate and 9 (32%) severe dependence according to the SADQ-C (median 26.5, range 11–56). Sponsorship roles were as follows: 16 roles were identified through the initial content analysis. These were distilled into three super-ordinate roles through a thematic analysis: (1) encouraging sponsees to work the programme of AA (doing the 12 steps and engaging in AA activity); (2) support (regular contact, emotional support and practical support); and (3) carrying the message of AA (sharing sponsor's personal experience of recovery with sponsees). Conclusions: The roles identified broadly corresponded with the AA literature delineating the duties of a sponsor. This non-random sample of sponsors was highly engaged in AA activity but only had a past history of moderate alcohol dependence.

Short Message Service (SMS) Technology in Alcohol Research--A Feasibility Study

Kuntsche, E., Robert, B. — 2009-06-24

Aim: The aim of this study was to describe the feasibility, advantages and limitations of the combined use of Internet and SMS technology to assess alcohol use, and to test whether an SMS sent in the evening (i.e. prior to a possible drinking event) changed the respondents’ assessment, made on the following day, of the number of drinks consumed. Participants: Seventy young adults (mean age 22.7) were recruited through face-to-face contacts, e-mails and Internet advertisements. Design and setting: Participants completed a baseline assessment via Internet and were randomly assigned to two conditions (with and without evening SMS). Over four weekends, both Friday and Saturday night, drinking was assessed via SMS questions sent the next day to the participants’ cell phones. Results: A high retention rate (75% in total) was obtained across all three recruitment conditions. The number of drinks indicated in the SMS survey was strongly correlated with the usual quantity assessed via Internet and did not differ depending on whether an additional SMS question was sent in the evening or not. Conclusion: The new method shares some of the advantages of conventional diaries but overcomes most of the limitations: it is easy to use, cost-effective and suitable for large-scale surveys. Application restrictions and further developments are discussed.

Autobiographical Memory in Detoxified Dependent Drinkers

Whiteley, C., Wanigaratne, S., Marshall, J., Curran, H. V. — 2009-06-24

Working Hard, Drinking Hard: On Violence and Survival in Honduras. By Adrienne Pine

Plant, M. — 2009-06-24

Breaking the Ashes. The Culture of Illicit Liquor in Sri Lanka. By Michele Ruth Gamburd

Paton, A. — 2009-06-24

Treating Drinkers and Drug Users in the Community. By Tom Waller and Daphne Rumball

Farmer, R. — 2009-06-24

Alcoholism in America from Reconstruction to Prohibition. By Sarah W. Tracy

Ritson, E. B. — 2009-06-24

Fragmented Intimacy--Addiction in a Social World. By Peter J. Adams

Paton, A. — 2009-06-24

Introduction to Special Issue 'Alcohol, Media and Message'

Chick, J. — 2009-04-20

Obituary: Charles Saul Lieber, A Tribute (13 February 1931 to 1 March 2009)

Seitz, H. K., Ishii, H., Salaspuro, M. — 2009-04-20

The Importance of Keeping Regular: Accurate Guidance to the Public on Low-Risk Drinking Levels

Heather, N. — 2009-04-20

Aim: The aim of this study was to argue that recommendations to the general public on daily amounts for low-risk alcohol consumption must retain the word ‘regular’ in order to avoid being rejected. Method: Narrative review of the evidence-base for daily limits to alcohol consumption, the guidance the public actually receives in the UK and media reactions to this guidance. Results: Evidence for daily limits (not more than 3–4 units for men and 2–3 units for women) rests on epidemiological surveys that enquire about ‘average’ or ‘usual’ amounts of consumption and this is reflected by the use of ‘regular’ or ‘consistent’ in the UK Government's Sensible Drinking report in 1995 and in guidance currently issued by the English Department of Health. In contrast, guidance the public actually receives often omits the word ‘regular’ and implies that the limits in question are maximum daily amounts. Media reactions to this inaccurate information suggest that the general public is likely to find these recommendations incredible and to reject them. Conclusion: If guidance to the public on daily drinking amounts is to stand any chance of being credible and effective, it must be accurate and must therefore retain the word ‘regular’.

Impact of Alcohol Advertising and Media Exposure on Adolescent Alcohol Use: A Systematic Review of Longitudinal Studies

Anderson, P., de Bruijn, A., Angus, K., Gordon, R., Hastings, G. — 2009-04-20

Aims: To assess the impact of alcohol advertising and media exposure on future adolescent alcohol use. Methods: We searched MEDLINE, the Cochrane Library, Sociological Abstracts, and PsycLIT, from 1990 to September 2008, supplemented with searches of Google scholar, hand searches of key journals and reference lists of identified papers and key publications for more recent publications. We selected longitudinal studies that assessed individuals' exposure to commercial communications and media and alcohol drinking behaviour at baseline, and assessed alcohol drinking behaviour at follow-up. Participants were adolescents aged 18 years or younger or below the legal drinking age of the country of origin of the study, whichever was the higher. Results: Thirteen longitudinal studies that followed up a total of over 38,000 young people met inclusion criteria. The studies measured exposure to advertising and promotion in a variety of ways, including estimates of the volume of media and advertising exposure, ownership of branded merchandise, recall and receptivity, and one study on expenditure on advertisements. Follow-up ranged from 8 to 96 months. One study reported outcomes at multiple time-points, 3, 5, and 8 years. Seven studies provided data on initiation of alcohol use amongst non-drinkers, three studies on maintenance and frequency of drinking amongst baseline drinkers, and seven studies on alcohol use of the total sample of non-drinkers and drinkers at baseline. Twelve of the thirteen studies concluded an impact of exposure on subsequent alcohol use, including initiation of drinking and heavier drinking amongst existing drinkers, with a dose response relationship in all studies that reported such exposure and analysis. There was variation in the strength of association, and the degree to which potential confounders were controlled for. The thirteenth study, which tested the impact of outdoor advertising placed near schools failed to detect an impact on alcohol use, but found an impact on intentions to use. Conclusions: Longitudinal studies consistently suggest that exposure to media and commercial communications on alcohol is associated with the likelihood that adolescents will start to drink alcohol, and with increased drinking amongst baseline drinkers. Based on the strength of this association, the consistency of findings across numerous observational studies, temporality of exposure and drinking behaviours observed, dose-response relationships, as well as the theoretical plausibility regarding the impact of media exposure and commercial communications, we conclude that alcohol advertising and promotion increases the likelihood that adolescents will start to use alcohol, and to drink more if they are already using alcohol.

Alcohol Portrayal on Television Affects Actual Drinking Behaviour

Engels, R. C. M. E., Hermans, R., van Baaren, R. B., Hollenstein, T., Bot, S. M. — 2009-04-20

Aims: Alcohol portrayal in movies and commercials is generally positive and might stimulate young people to drink. We tested experimentally whether portrayal of alcohol images in movies and commercials on television promotes actual drinking. Methods: In a naturalistic setting (a bar lab), young adult male pairs watched a movie clip for 1 h with two commercial breaks and were allowed to drink non-alcohol and alcoholic beverages. These participants were randomly assigned to one of four conditions varying on the type of movie (many versus few alcohol portrayals) and commercials (alcohol commercials present or not). Results: Participants assigned to the conditions with substantial alcohol exposure in either movies or commercials consume more alcohol than other participants. Those in the condition with alcohol portrayal in movie and commercials drank on average 1.5 glasses more than those in the condition with no alcohol portrayal, within a period of 1 h. Conclusions: This study—for the first time—shows a causal link between exposure to drinking models and alcohol commercials on acute alcohol consumption.

An Experimental Study on Imitation of Alcohol Consumption in Same-Sex Dyads

Larsen, H., Engels, R. C. M. E., Granic, I., Overbeek, G. — 2009-04-20

Aim: In order to study the role of imitation in relation to drinking, alcohol consumption among two peers was examined with experiments in a naturalistic drinking setting. Method: In a bar lab, 135 young adults (52% women) were exposed to either a non-drinking, a light-drinking or a heavy-drinking same-sex model (i.e. a confederate) in a 30-min time-out session. Instead of using a taste task (Quigley and Collins, 1999. The modeling of alcohol consumption: a meta-analytic review. J Stud Alcohol 60:90–8) in which participants were obliged to consume alcohol, in the current study, a design was used in which participants were allowed to drink alcohol but could also choose non-alcoholic beverages. Results: Craving for alcohol was included as a covariate in ANCOVAs. Results showed that the participants consumed substantially more alcohol when exposed to heavy-drinking models compared to light- and non-drinking models. Craving levels were positively related to alcohol consumption during the experiment. Conclusion: Both men and women imitated same-sex peers’ drinking behavior in an ad lib naturalistic bar setting.

Media Coverage of Celebrity DUIs: Teachable Moments or Problematic Social Modeling?

Smith, K. C., Twum, D., Gielen, A. C. — 2009-04-20

Aim: Alcohol in the media influences norms around use, particularly for young people. A recent spate of celebrity arrests for drinking and driving (DUI) has received considerable media attention. We asked whether these newsworthy events serve as teachable moments or problematic social modeling for young women. Method: Qualitative analysis of US media coverage of four female celebrities (Michelle Rodriguez, Paris Hilton, Nicole Richie and Lindsay Lohan) was conducted over the year following their DUI arrest (December 2005 through June 2008). The media sample included five television and three print sources and resulted in 150 print and 16 television stories. Results: Stories were brief, episodic and focused around glamorous celebrity images. They included routine discussion of the consequences of the DUI for the individual celebrities without much evidence of a consideration of the public health dimensions of drinking and driving or possible prevention measures. Conclusions: Our analysis found little material in the media coverage that dealt with preventing injury or promoting individual and collective responsibility for ensuring such protection. Media attention to such newsworthy events is a missed opportunity that can and should be addressed through media advocacy efforts.

A Promoter Polymorphism in the ALDH2 Gene Affects Its Basal and Acetaldehyde/Ethanol-Induced Gene Expression in Human Peripheral Blood Leukocytes and HepG2 Cells

Kimura, Y., Nishimura, F. T., Abe, S., Fukunaga, T., Tanii, H., Saijoh, K. — 2009-04-20

Aims: To assess the effect of the –360G/A polymorphism in the promoter region of the human aldehyde dehydrogenase-2 (ALDH2) gene on its transcription, basal and acetaldehyde/ethanol-induced gene expression was examined by in vivo and in vitro experiments. Methods: Human peripheral blood leukocytes were collected before and after alcohol ingestion (0.4 g/kg body weight) in 21 healthy young Japanese volunteers with a deficient phenotype of ALDH2 (⁴⁸⁷Glu/Lys), and the levels of ALDH2 mRNA were quantified by real-time RT-PCR. The transcriptional activity of the ALDH2 promoter was investigated by a reporter assay using HepG2 cells in the presence or absence of acetaldehyde/ethanol. Results: The basal level of ALDH2 mRNA was significantly higher in –360A heterozygous subjects than in –360G homozygous subjects. In all subjects, regardless of the genotype, ALDH2 mRNA increased following ethanol ingestion. The promoter activity of a reporter plasmid for –360G was significantly lower than that of a reporter plasmid for –360A. Exposure to acetaldehyde induced a significant increase in the transcriptional activity of the –360G reporter, but not the –360A reporter. Conclusions: In vivo and in vitro experiments showed that the –360G allele has lower basal transcriptional activity than the –360A allele, whereas acetaldehyde/ethanol-induced gene expression, in general, seems to be more enhanced in individuals homozygous for the –360G allele than in those with the –360A allele. Thus, the promoter polymorphism may be involved in individual differences in acetaldehyde elimination.

Activation of Liver Tryptophan Pyrrolase Mediates the Decrease in Tryptophan Availability to the Brain after Acute Alcohol Consumption by Normal Subjects

Badawy, A. A-B, Doughrty, D. M., Marsh-Richard, D. M., Steptoe, A. — 2009-04-20

Aims: We have previously suggested that acute ethanol consumption by normal subjects decreases the availability of circulating tryptophan (Trp) to the brain by activating liver Trp pyrrolase, the first and rate-limiting enzyme of the (major) kynurenine pathway of Trp degradation. The aim of the present study was to examine this hypothesis further by measuring plasma levels of kynurenine metabolites following alcohol consumption. Methods: After an overnight fast and a light breakfast, each of 10 healthy subjects received one of five drinks (placebo and doses of ethanol of 0.2, 0.4, 0.6 and 0.8 g/kg body weight in tonic water) on five different occasions. Blood samples were withdrawn 2 h later and plasma was analysed for concentrations Trp, competing amino acids (CAA) and kynurenine metabolites. Results: Along with the depletion of plasma Trp and the decrease in its availability to the brain, as expressed by the ratio of [Trp]/[CAA], plasma kynurenine was elevated by doses of ethanol of 0.2–0.8 g/kg body weight. The ratio% of [kynurenine]/[Trp], an index of the expression of Trp pyrrolase activity, was also increased by all doses of ethanol. Conclusions: We conclude that activation of liver Trp pyrrolase mediates the depletion of plasma Trp and the decrease in its availability to the brain induced by acute ethanol consumption.

Alcohol, Gestation and Breastfeeding: Selenium as an Antioxidant Therapy

2009-04-20

Aim: The aim of this paper is to study the relationship between alcohol, selenium and oxidative stress in breastfeeding rat pups exposed to ethanol during gestation and lactation. We have also studied how a Se-supplemented diet among mothers could prevent different oxidative liver disorders in the pups. Method: Pups of 21 days were randomized into four groups: control group (C), alcohol group (A), alcohol selenium group (AS) and control selenium group (CS). Alcohol was supplied to their mothers for 13 weeks (induction, reproduction, gestation and lactation periods). The selenium-supplemented diet contained 0.5 ppm as selenite. We determined serum and liver selenium by graphite-furnace atomic absorption spectrometry. We measured antioxidant enzyme activities: glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD); and lipid peroxidation (TBARS) and protein carbonyl (PC) by a spectrophotometric method in the liver. Results: In the liver of pups, exposure to ethanol provoked a decrease in selenium and GPx activity and an increase in GR and CAT activity, as well as in carbonyl groups in protein. A pups had higher Se levels and GPx activity in serum than C pups. Administering Se with alcohol balances the activities of scavenging enzymes and reduces peroxidation protein products. Conclusion: These results suggest that selenium could be effective in neutralizing the damage of ethanol consumption during gestation and lactation in pups since it repairs selenium levels in liver as well as the activity of scavenging enzymes and peroxidation protein products. In serum, Se also recovers GPx activity and increases the levels of Se that are available to other organs.

Effect of a Small Dose of Alcohol on the Endurance Performance of Trained Cyclists

Lecoultre, V., Schutz, Y. — 2009-04-20

Aim: The aim of this study was to investigate the effect of an acute small ethanol (EtOH) dose (0.5 ml EtOH/kg fat-free mass, combined with carbohydrate) in a drink on endurance performance of trained cyclists. Methods: Thirteen well-trained male cyclists took part in this study. A 60-min cycling endurance performance test (time trial) was performed in a calorimetric chamber after drinking an EtOH (30 ± 1.8 ml) or a non-EtOH control (C) drink. Results: Overall, EtOH induced a significant decrease in the average cycling power output (PO) (EtOH: 233 ± 23 W versus C: 243 ± 24 W, P < 0.01). The time course of mechanical PO showed an early decrease during the EtOH trial as compared to C (P < 0.01). Due to the lower PO, oxygen consumption, carbon dioxide production and glucose oxidation were significantly lower (P < 0.05) as compared to C. Relative to PO, heart rate response and ratings of perceived exertion (RPE) were increased by EtOH as compared to C (P < 0.05). In contrast, EtOH did not influence gross work efficiency, glycaemia and blood lactate concentration. Conclusions: These results show that the acute low dose of EtOH decreased endurance performance. An increase of cardio-vascular strain and psychobiological mechanisms may explain this decrease of endurance performance.

PAT (2009)--Revisions to the Paddington Alcohol Test for Early Identification of Alcohol Misuse and Brief Advice to Reduce Emergency Department Re-attendance

Touquet, R., Brown, A. — 2009-04-20

The Paddington Alcohol Test (PAT) has evolved over 15 years as a clinical tool to facilitate emergency physicians and nurses giving brief advice and the offer of an appointment for brief intervention by an alcohol nurse specialist. Previous work has shown that unscheduled emergency department re-attendance is reduced by ‘making the connection’ between alcohol misuse and resultant problems necessitating emergency care. The revised ‘PAT (2009)’ now includes education on clinical signs of alcohol misuse and advice on when to request a blood alcohol concentration.

The Effect of Hair Pigment on the Incorporation of Fatty Acid Ethyl Esters (FAEE)

Kulaga, V., Velazquez-Armenta, Y., Aleksa, K., Vergee, Z., Koren, G. — 2009-04-20

Aims: The objective of the current study was to determine whether FAEE incorporation is affected by hair pigmentation. Methods: Black hooded LE rats were injected intraperitoneally daily with ethanol. Prior to dosing, black and white patches of fur were shaved and analyzed for baseline levels of FAEE using an adapted extraction procedure and GCMS method. Once the shaved ‘patches’ had grown back they were re-sampled along with hair outside the ‘patches’, referred to as ‘no patch’ hair, and tested for post-treatment FAEE levels in the same manner. Blood was also sampled for pharmacokinetic analysis of ethanol. Results: Total FAEE levels were significantly higher in post-treatment hair (black and white) compared to baseline (pre-treatment) levels. Total FAEE levels were also significantly higher in post-treatment ‘patch’ hair (black and white) compared to ‘no patch’ hair. No significant differences were found between post-treatment black and white hair. The FAEE profiles were similar between black and white hair, with FAEE levels being highest for ethyl myristate, followed by ethyl stearate, palmitate, and then oleate. Conclusion: FAEE incorporation into hair does not appear to be affected by hair pigment, which is in congruence with what is known about the chemistry of drug–melanin interactions. This is important in avoiding potential bias and discrimination in the interpretation of alcohol abuse based on hair color.

Sweet Liking Phenotype, Alcohol Craving and Response to Naltrexone Treatment in Alcohol Dependence

2009-04-20

Aims: To investigate the relationship between the sweet liking/sweet disliking phenotype (a putative probe of brain opioid function), craving for alcohol and response to treatment with naltrexone in individuals with alcohol dependence. Methods: Forty individuals with alcohol dependence were enrolled in a 12-week open-label study of 50 mg of naltrexone with four sessions of motivational enhancement therapy. Prior to treatment, individuals completed a sweet preference test and the Penn Alcohol Craving Scale. Subjects were categorized as sweet liking (SL), n = 15, or sweet disliking (SDL), n = 25, via a standard sweet tasting paradigm. The sweet tasting results were blinded to the subjects and to treatment staff. SL status, pretreatment craving and their interaction were examined as predictors of frequency of abstinent days and heavy drinking days during treatment with naltrexone. Results: SL and SDL subjects achieved similar reductions in percent heavy drinking days with treatment. During treatment, SDL subjects had 48% abstinent days compared to 30% for SL subjects (P = 0.034). Pretreatment craving did not predict % heavy drinking days or % abstinent days. An interaction effect was found between the SL/SDL phenotype and pretreatment craving such that SL subjects with high craving demonstrated higher rates of percent abstinent days whereas SDL subjects with high craving demonstrated lower rates of percent abstinent days, P < 0.001. Conclusions: These findings indicate that the SL/SDL phenotype may predict variation in response to naltrexone and/or counseling treatment. Furthermore, the SL/SDL phenotype may interact with craving to provide a more robust prediction of outcome with naltrexone or counseling.

Self-Assessment of Drinking on the Internet--3-, 6- and 12-Month Follow-Ups

Koski-Jannes, A., Cunningham, J., Tolonen, K. — 2009-04-20

Aim: The aim of this work was to report on the results of a pilot study of a web-based self-assessment service (DHT) for Finnish drinkers (www.paihdelinkki.fi/testaa/juomatapatesti). Method: During the 7-month recruitment period in 2004 altogether 22,536 anonymous self-assessments were recorded in the database of this service. The study sample was recruited from the 1598 service users who also participated to a survey evaluating the DHT. Those who consented by providing required baseline data and their e-mail address (n = 343) were sent a message asking them to fill in the follow-up questions 3, 6 and 12 months later. Their self-reported use of alcohol and drinking-related problems served as the main outcome variables in this single-group follow-up study. Results: At 3, 6 and 12 months, 78%, 69% and 61% of the study participants, respectively, responded to the follow-up. The intention-to-treat (ITT) results revealed significant reductions (P < 0.001) in all the outcome measures. The reductions occurred during the first 3 months, after which the changes were non-significant. Conclusions: The results are in line with previous studies with mostly shorter follow-up periods suggesting that Internet-based self-assessment services can be useful tools in reducing excessive drinking. A randomized controlled trial would, however, increase our certainty about the causes of the observed changes.

What Was Useful about That Session? Clients' and Therapists' Comments after Sessions in the UK Alcohol Treatment Trial (UKATT)

2009-04-20

Aim: The aim of this study was to report and contrast the aspects of two therapies considered by clients and therapists to be most and least useful. Method: In the UK Alcohol Treatment Trial (UKATT), 742 clients were treated by 49 therapists with up to three sessions of motivational enhancement therapy (MET) or up to eight sessions of social behaviour and network therapy (SBNT). After each treatment session, clients and therapists were asked to independently complete two sentences, one inviting a statement about the ‘most useful’ and the other about the ‘least useful’ thing that had happened during the session. Results: The proportion of ‘most useful’ sentences completed was greater than the proportion of ‘least useful’ and equally so for MET and SBNT. The content of comments was significantly different for the two treatments: more comments on social aspects followed SBNT and more motivational comments followed MET, with larger numbers of comments following both treatments that were more general. Clients more often completed ‘most useful’ sentences than therapists and less often completed ‘least useful’ sentences. There were a number of differences in the content of their comments: notably more ‘most useful’ client comments about talking to their therapists, and more therapist comments about client engagement. Conclusions: MET and SBNT left distinct impressions on the participants immediately following treatment sessions, adding to the evidence that they are different treatments, and hence deepening the mystery about why outcomes following the two treatments were so similar [UKATT Research Team. (2005) Br Med J 331: 541–58].

Association of Average Daily Alcohol Consumption, Binge Drinking and Alcohol-Related Social Problems: Results from the German Epidemiological Surveys of Substance Abuse

Kraus, L., Baumeister, S. E., Pabst, A., Orth, B. — 2009-04-20

Aims: The present study investigates the combined effect of average volume and binge drinking in predicting alcohol-related social problems and estimates the proportion of alcohol-related harms related to specific drinking patterns that could be prevented if transferred to a low-risk drinking group. Methods: Data came from the 1997 and 2000 German Epidemiological Survey of Substance Abuse (ESA) (age: 18–59 years; response rate: 65% and 51%, respectively). The pooled sample consisted of 12,668 current drinkers. By using nine categories of average daily intake and three groups of binge drinking, individuals were grouped into 22 mutual exclusive groups. Social problems were defined as the occurrence of ‘repeated family quarrels’, ‘concern of family members or friends’, ‘loss of partner or friend’ or ‘physical fight or injury’ in relation to alcohol. Results: The effect of average daily intake is modified by binge drinking frequency such that the association was strongest in those with four or more binge drinking occasions during the last 30 days. Within each binge drinking group, adjusted relative risks (aRR) increased with alcohol intake up to a certain threshold and decreased thereafter. Overall, compared to the reference group (≤7 g ethanol/day—no binge), the population-attributable fraction (PAF) related to the other drinking groups was 71.4% (95% CI: 64.4–77.1%). Conclusions: The frequency of binge drinking occasions seems to be a better predictor of alcohol-related social problems than volume. Alcohol-related social harms especially among drinkers with moderate volume per day may be reduced by targeting prevention strategies towards episodic heavy drinkers.

Alcohol Consumption in the Country and Hospitalizations for Acute Alcohol Pancreatitis and Liver Cirrhosis during a 20-Year Period

Sand, J., Valikoski, A., Nordback, I. — 2009-04-20

Aims: Between 1970 and 1989 the incidence of pancreatitis increased in Finland in association with increased alcohol consumption. During the1990s there was a temporary decrease in alcohol consumption. We examined the trends in the amount of alcohol consumed in Finland and the incidence of hospital admissions for acute alcoholic pancreatitis and liver cirrhosis. Patients and methods: The data on hospital admissions and annual alcohol consumption between 1987 and 2007 were obtained from the Finnish National Agency for Welfare and Health. Results: Alcohol consumption increased from 8.2 litres of ethanol per inhabitant per year in 1987 to 10.5 litres in 2007, but during the economic recession in the country there was a temporary decrease in alcohol consumption between 1992 and 1994, with the lowest consumption of 8.0 litres in 1994. The incidence of hospitalizations for acute alcoholic pancreatitis in the whole population increased significantly during the study period among both men (from 57 to 69/100,000/year) and women (from 7 to 12/100,000/year). However, there was a significant decrease in hospitalizations in 1996 and 1997 correlating with alcohol consumption three years earlier. The incidence of hospitalizations due to liver cirrhosis increased in the age groups over 45 years in both genders throughout the study period. A temporary decrease was observed in 1994, when alcohol consumption was at its lowest. Interestingly, there was a trend from pancreatitis to cirrhosis during the last six years, when the hospitalizations for acute pancreatitis decreased, although the hospitalizations for liver cirrhosis increased following increased alcohol consumption. During the study period the female-to-male ratio for liver cirrhosis was twice as high as for acute alcoholic pancreatitis, but the relative portion of females increased by 50% in both diagnoses. Conclusions: In contrast to liver cirrhosis, the hospital admissions for which followed the national alcohol consumption, admissions for acute alcoholic pancreatitis ceased to show a connection with the national alcohol consumption during the past several years.

Alcohol Poisoning in Belarus: A Comparison of Urban-Rural Trends, 1990-2005

Stickley, A., Razvodovsky, Y. — 2009-04-20

Aim: The aim of this study was to investigate the occurrence of alcohol poisoning in urban and rural regions of Belarus in the post-Soviet period. Methods: All-age male and female alcohol-poisoning mortality and population data were obtained for the years 1990, 1995, 2000 and 2005 for urban and rural regions of Belarus. These data were subsequently recalculated into three age categories and directly standardized. Poisson regression models were used to assess relative changes in rural–urban alcohol-poisoning rates across time. Results: Although extremely high in comparative terms in 1990, alcohol-poisoning rates had nevertheless risen considerably amongst men and women in all age groups in both urban and rural regions by 2005. In rural regions, the rise was continuous while amongst the urban population a small reduction was recorded in 2000 after a comparatively larger rise in 1995. By 2005, although alcohol-poisoning rates were significantly higher amongst rural men and women, the levels of acute alcohol mortality were nevertheless extremely high in nearly every age group in both urban and rural locations. Conclusions: It is probable that both the level and pattern of alcohol consumption in conjunction with the increasing use of illegal alcohol underlie the extremely high alcohol-poisoning rates in contemporary Belarus, and the growing rural–urban divergence in alcohol-poisoning mortality observed in recent years. Immediate action is now required to improve the poor social and economic conditions underpinning extreme levels of acute alcohol mortality, as well as to increase the provision of alcohol treatment services, especially in rural areas.

Alcohol Consumption Behaviours and Social Mobility in Men and Women of the Midspan Family Study

Hart, C. L., Smith, G. D., Upton, M. N., Watt, G. C. M. — 2009-04-20

Aims: The aim of this study was to investigate relationships between alcohol consumption and social mobility in a cohort study in Scotland. Methods: 1040 sons and 1298 daughters aged 30–59 from 1477 families reported their alcohol consumption from which was derived: weekly units (1 UK unit being 8 g ethanol), exceeding daily or weekly limits, binge drinking and consuming alcohol on 5+ days per week. Own and father's social class were available enabling social mobility to be investigated. Results: More downwardly mobile men exceeded the weekly limit, the daily limit, were defined as binge drinkers and drank the most units per week of the four social mobility groups. Stable non-manual women were more likely to consume alcohol on 5+ days a week but very few were binge drinkers. Stable non-manual and upwardly mobile men and women were more likely to drink wine, and downwardly mobile men to drink beer. Conclusions: Downward mobility was associated with less favourable alcohol behaviours, especially in men. Wine consumption was more closely related to the social mobility groups than beer and spirits consumption. Drinking patterns could both influence and be influenced by social mobility.

The End of My Addiction. How One Man Cured Himself of Alcoholism. By Dr Olivier Ameisen

Mcintosh, C. — 2009-04-20

Publishing Addiction Science: A Guide for the Perplexed (2nd ed). By Thomas F. Babor, Kerstin Stenius, Susan Savva and Jean O'Reilly

Black, H. — 2009-04-20

Special Issue on Alcohol and Brain Damage

Chick, J., de Witte, P. — 2009-02-18

Introduction to This Issue: The Seven Ages of Man ... (or Woman)

Marshall, E. J., Guerrini, I., Thomson, A. D. — 2009-02-18

Foetal Alcohol Spectrum Disorders and Alterations in Brain and Behaviour

Guerri, C., Bazinet, A., Riley, E. P. — 2009-02-18

The term ‘Foetal Alcohol Spectrum Disorders (FASD)’ refers to the range of disabilities that may result from prenatal alcohol exposure. This article reviews the effects of ethanol on the developing brain and its long-term structural and neurobehavioural consequences. Brain imaging, neurobehavioural and experimental studies demonstrate the devastating consequences of prenatal alcohol exposure on the developing central nervous system (CNS), identifying specific brain regions affected, the range of severity of effects and mechanisms involved. In particular, neuroimaging studies have demonstrated overall and regional volumetric and surface area reductions, abnormalities in the shape of particular brain regions, and reduced and increased densities for white and grey matter, respectively. Neurobehaviourally, FASD consists of a continuum of long-lasting deficits affecting multiple aspects of cognition and behaviour. Experimental studies have also provided evidence of the vulnerability of the CNS to the teratogenic effects of ethanol and have provided new insight on the influence of risk factors in the type and severity of observed brain abnormalities. Finally, the potential molecular mechanisms that underlie the neuroteratological effects of alcohol are discussed, with particular emphasis on the role of glial cells in long-term neurodevelopmental liabilities.

Mechanisms of Neurodegeneration and Regeneration in Alcoholism

Crews, F. T., Nixon, K. — 2009-02-18

Aims: This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies. Methods: The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration. Results: Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-B proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-B transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans. Conclusions: Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans.

Biochemical and Neurotransmitter Changes Implicated in Alcohol-Induced Brain Damage in Chronic or 'Binge Drinking' Alcohol Abuse

Ward, R. J., Lallemand, F., de Witte, P. — 2009-02-18

The brain damage, which occurs after either chronic alcoholization or binge drinking regimes, shows distinct biochemical and neurotransmitter differences. An excessive amount of glutamate is released into specific brain regions during binge drinking (in excess of 4- to 5-fold of the normal basal concentration) that is not evident during periods of excessive alcohol consumption in chronic alcohol abusers. Increases in glutamate release are only observed during the initial stages of withdrawal from chronic alcoholism (~2- to 3-fold) due to alterations in the sensitivities of the NMDA receptors. Such changes in either density or sensitivity of these receptors are reported to be unaltered by binge drinking. When such excesses of glutamate are released in these two different models of alcohol abuse, a wide range of biochemical changes occur, mediated in part by increased fluxes of calcium ions and/or activation of various G-protein-associated signalling pathways. Cellular studies of alveolar macrophages isolated from these two animal models of alcohol abuse showed enhanced (binge drinking) or reduced (chronic alcoholization) lipopolysaccharide (LPS)-stimulated NO release. Such studies could suggest that neuroadaptation occurs with the development of tolerance to alcohol's effects in both neurotransmitter function and cellular processes during chronic alcoholization that delay the occurrence of brain damage. In contrast, ‘binge drinking’ induces immediate and toxic effects and there is no evidence of an increased preference for alcohol as seen after withdrawal from chronic alcoholization.

The Neuropathology of Alcohol-Related Brain Damage

Harper, C. — 2009-02-18

Excessive alcohol use can cause structural and functional abnormalities of the brain and this has significant health, social and economic implications for most countries in the world. Even heavy social drinkers who have no specific neurological or hepatic problems show signs of regional brain damage and cognitive dysfunction. Changes are more severe and other brain regions are damaged in patients who have additional vitamin B1 (thiamine) deficiency (Wernicke–Korsakoff syndrome). Quantitative studies and improvements in neuroimaging have contributed significantly to the documentation of these changes but mechanisms underlying the damage are not understood. A human brain bank targeting alcohol cases has been established in Sydney, Australia, and tissues can be used for structural and molecular studies and to test hypotheses developed from animal models and in vivo studies. The recognition of potentially reversible changes and preventative medical approaches are important public health issues.

Update of Cell Damage Mechanisms in Thiamine Deficiency: Focus on Oxidative Stress, Excitotoxicity and Inflammation

Hazell, A. S., Butterworth, R. F. — 2009-02-18

Thiamine deficiency (TD) is a well-established model of Wernicke's encephalopathy. Although the neurologic dysfunction and brain damage resulting from the biochemical consequences of TD is well characterized, the mechanism(s) that lead to the selective histological lesions characteristic of this disorder remain a mystery. Over the course of many years, various structural and functional changes have been identified that could lead to cell death in this disorder. However, despite a concerted effort to explain the consequences of TD in terms of these changes, our understanding of the pathophysiology of this disorder remains unclear. This review will focus on three of these processes, i.e. oxidative stress, glutamate-mediated excitotoxicity and inflammation and their role in selective vulnerability in TD. Since TD inhibits oxidative metabolism, a feature of many neurodegenerative disease states, it represents a model system with which to explore pathological mechanisms inherent in such maladies, with the potential to yield new insights into their possible treatment and prevention.

The Korsakoff Syndrome: Clinical Aspects, Psychology and Treatment

Kopelman, M. D., Thomson, A. D., Guerrini, I., Marshall, E. J. — 2009-02-18

Aims: The Korsakoff syndrome is a preventable memory disorder that usually emerges (although not always) in the aftermath of an episode of Wernicke's encephalopathy. The present paper reviews the clinical and scientific literature on this disorder. Methods: A systematic review of the clinical and scientific literature on Wernicke's encephalopathy and the alcoholic Korsakoff syndrome. Results: The Korsakoff syndrome is most commonly associated with chronic alcohol misuse, and some heavy drinkers may have a genetic predisposition to developing the syndrome. The characteristic neuropathology includes neuronal loss, micro-haemorrhages and gliosis in the paraventricular and peri-aqueductal grey matter. Lesions in the mammillary bodies, the mammillo-thalamic tract and the anterior thalamus may be more important to memory dysfunction than lesions in the medial dorsal nucleus of the thalamus. Episodic memory is severely affected in the Korsakoff syndrome, and the learning of new semantic memories is variably affected. ‘Implicit’ aspects of memory are preserved. These patients are often first encountered in general hospital settings where they can occupy acute medical beds for lengthy periods. Abstinence is the cornerstone of any rehabilitation programme. Korsakoff patients are capable of new learning, particularly if they live in a calm and well-structured environment and if new information is cued. There are few long-term follow-up studies, but these patients are reported to have a normal life expectancy if they remain abstinent from alcohol. Conclusions: Although we now have substantial knowledge about the nature of this disorder, scientific questions (e.g. regarding the underlying genetics) remain. More particularly, there is a dearth of appropriate long-term care facilities for these patients, given that empirical research has shown that good practice has beneficial effects.

Neuroimaging of the Wernicke-Korsakoff Syndrome

Sullivan, E. V., Pfefferbaum, A. — 2009-02-18

Aim: Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition. Methods: Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance. Results: Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion. Conclusions: Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE.

Molecular Genetics of Alcohol-Related Brain Damage

Guerrini, I., Thomson, A. D., Gurling, H. M. — 2009-02-18

Aims: In the scientific literature it has been repeatedly hypothesized that there is a heritable susceptibility to thiamine deficiency comparable to other hereditary metabolic disorders. The aim of this paper is to review the most recent knowledge on the genetic susceptibility to the development of alcohol-related Wernicke–Korsakoff syndrome (WKS). Methods: A literature review was carried out looking at the molecular genetics studies performed in alcohol-dependent patients affected by WKS. Results: A genetic component in the pathogenesis of WKS has been postulated since the late seventies. Since then, very few genetic studies have been carried out on candidate genes such as thiamine-dependent enzymes, alcohol-metabolizing enzymes and GABA receptors. The findings are controversial and not conclusive. Several authors reported the important role of the thiamine transporters in the pathogenesis of the thiamine deficiency disorders. Our findings on SLC19A2 and SLC19A3 suggest a potential role of these two genes in the pathophysiology of alcohol-related thiamine deficiency but further studies need to be carried out. Conclusions: The WKS may be a very complex, multifactorial disorder where the interaction of multiple genes and environment plays an important role in the pathogenesis. However, it is still plausible that megaphenic gene effects are responsible for WKS susceptibility and the thiamine transport genes are good candidates for having such a role. Further genetic studies are definitely needed to investigate the association with candidate genes or linkage with hot spot areas.

Proteomics Approach in the Study of the Pathophysiology of Alcohol-Related Brain Damage

Matsumoto, I. — 2009-02-18

Aims: Chronic, excessive drinking of alcohol can induce brain damage in the regions important for neurocognitive function. Some of the damage are permanent while some are appearantly reversible. It is our aim to understand the molecular mechanisms underlying alcohol-induced and/or related brain damage, particularly of that observed in ‘medically uncomplicated’ (without heptatic cirrhosis or Wernicke-Korsakoff Syndrome [WKS]) alcoholics. Methods: A high-throughput proteomics technology has been applied to several ‘alcohol-sensitive’ brain regions from uncomplicated and hepatic cirrhosis-complicated alcoholics to understand the mechanisms of alcohol-related brain damage at the level of protein expression. Results: It was clearly demonstrated that each brain region reacts in significantly different manner to chronic alcohol ingestion. Appearant abnormalities in vitamin B1 (thiamine)-related biochemical pathways were observed in several brain regions, such as the dorsolateral prefrontal cortex, genu (a frontal part of the corpus callosum) and cerebellar vermis in uncomplicated alcoholics, suggesting that the reduction of this important nutritional component might be associated with brain damage even without the signs of WKS. In addition, in the two different subregions of the corpus callosum (genu and splenium [a posterior part of the corpus callosum]) and the cerebellar vermis, significant differences in protein expression profiles between uncomplicated and complicated alcoholics with hepatic cirrhosis were identified, suggesting that hepatic factors such as ammonia have significant additive influences on brain protein expression, which might lead to the structural changes and/or damage in these brain regions. Furthermore, in the hippocampus, significant change of the level of glutamine synthetase expression was observed, suggesting once again the importance of ammonia as a cause of brain damage in this region. Conclusions: Although our data did not show any evidence of "direct" alcohol effects to induce the alteration of protein expression in association with brain damage, high-throughput neuroproteomics approaches are proven to have a potential to dissect the mechanisms of complex brain disorders.

Biomarkers in Alcohol Misuse: Their Role in the Prevention and Detection of Thiamine Deficiency

Mancinelli, R., Ceccanti, M. — 2009-02-18

In Western countries alcohol misuse is the most frequent cause of thiamine (vitamin B1) deficiency (TD) and consequent neuro-impairment. Studies have demonstrated that between 30 and 80% of alcoholics are thiamine deficient, and this puts them at risk of developing the Wernicke–Korsakoff (WK) syndrome. The relative roles of alcohol and TD in causing brain damage remain controversial and it is important to try to determine the role played by each factor. Animal studies support an additive effect of alcohol exposure and TD, and indicate the potential for interaction between alcohol and TD in human alcohol-related brain damage. Early diagnosis of alcohol-related TD is therefore an important aspect of effective intervention and treatment. Alcohol biomarkers provide a direct and indirect way of estimating the amount of alcohol being consumed, the duration of ingestion and the harmful effects that long-term alcohol use has on body functions. Appropriate use of these markers is very helpful when considering a diagnosis of alcohol-related TD.

Alcohol Withdrawal and Prolonged Hospital Stay in a Patient with Neuroimaging Abnormalities: A Case Report

Gupta, M. — 2009-02-18

A hospital stay of 30 days was required in a 47-year-old woman with alcohol withdrawal. Magnetic resonance imaging (MRI) findings revealed a focal brain stem lesion and multiple focal supracortical abnormalities. Could asymptomatic neuroimaging abnormalities predict risk of complicated alcohol withdrawal? Future clinical observations and longitudinal studies may wish to address this potential risk factor.

In vitro Neurogenesis from Neural Progenitor Cells Isolated from the Hippocampus Region of the Brain of Adult Rats Exposed to Ethanol during Early Development through Their Alcohol-Drinking Mothers

Singh, A. K., Gupta, S., Jiang, Y., Younus, M., Ramzan, M. — 2009-02-18

Aims: This study was aimed to determine whether ethanol exposure during early development altered neurogenesis in the brain of adult rats. Methods: Pregnant rats were given either ethanol-mixed or mannose-mixed (for control) rodent liquid diet ad libitum. Ethanol drinking continued during pregnancy and nursing. After weaning, the pups (AC_o: pups from control mothers, AE_o: pups from ethanol exposed mothers) received normal diet and water ad libitum for 11 weeks. Then the rats were anesthetized, their brains were collected and the hippocampal samples were processed for isolation of neural progenitor cells (NPCs). AC_o NPCs and AE_o NPCs were sequentially grown in media containing different growth factors that induced proliferation and differentiation. Results and Conclusions: Neuronal maturation was significantly delayed in ethanol-exposed rats. AC_o NPCs, up to day 7 of culture, exhibited high β-catenin-probe binding, an increase in Ca²⁺ when exposed to -amino butyric acid (GABA) and lack of response to glutamate (Glu) exposure. β-Catenin-probe binding and the stimulatory effects of GABA declined thereafter. AC_o NPCs, at culture day 29, exhibited high β-catenin-probe binding, lack of response to GABA and elevated Glu-induced increase in Ca²⁺ⁱ. Cultures of AE_o NPCs showed an amplified stimulatory effects of GABA, attenuated stimulatory effects of Glu and attenuated the delayed (culture day 29) increase in the expression of Wnt proteins and β-catenin-probe binding. This suggests a significant alteration in neurogenesis and synapse formation in adult rats exposed to ethanol at early development through their alcohol-drinking mothers.