Alcohol and Alcoholism - current issue

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