Alcohol and Alcoholism - current issue

Addictions Biology: Haplotype-Based Analysis for 130 Candidate Genes on a Single Array

2008-08-23

Aims: To develop a panel of markers able to extract full haplotype information for candidate genes in alcoholism, other addictions and disorders of mood and anxiety. Methods: A total of 130 genes were haplotype tagged and genotyped in 7 case/control populations and 51 reference populations using Illumina GoldenGate SNP genotyping technology, determining haplotype coverage. We also constructed and determined the efficacy of a panel of 186 ancestry informative markers. Results: An average of 1465 loci were genotyped at an average completion rate of 91.3%, with an average call rate of 98.3% and replication rate of 99.7%. Completion and call rates were lowered by the performance of two datasets, highlighting the importance of the DNA quality in high throughput assays. A comparison of haplotypes captured by the Addictions Array tagging SNPs and commercially available whole-genome arrays from Illumina and Affymetrix shows comparable performance of the tag SNPs to the best whole-genome array in all populations for which data are available. Conclusions: Arrays of haplotype-tagged candidate genes, such as this addictions-focused array, represent a cost-effective approach to generate high-quality SNP genotyping data useful for the haplotype-based analysis of panels of genes such as these 130 genes of interest to alcohol and addictions researchers. The inclusion of the 186 ancestry informative markers allows for the detection and correction for admixture and further enhances the utility of the array.

Association Between the Stin2 VNTR Polymorphism of the Serotonin Transporter Gene and Treatment Outcome in Alcohol-Dependent Patients

2008-08-23

Aims: The aim of this study was to investigate the potential association between functional polymorphisms of dopaminergic [dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3) and dopamine transporter (SLC6A3)] and serotonergic [serotonin 2A receptor (HTR2A) and serotonin transporter (SLC6A4)] genes and treatment outcome in alcohol-dependent patients. Methods: A total of 90 Spanish Caucasian alcohol-dependent outpatients (ICD-10 criteria) were enrolled in the study. The association between genotypes and drinking outcomes was measured over 6 months of treatment. Biomarkers of alcohol consumption, as well as alcohol consumption and its consequences, craving, disability and quality of life, were assessed. Based on those measures, we created a composite secondary measure to globally assess treatment outcome in alcoholism. Results: No association was found between DRD2, DRD3, SLC6A3 or HTR2A gene variants and treatment outcome. However, SLC6A4 STin2 12/12 carriers showed poor 6-month time point treatment outcome [32.8% in the good outcome group versus 64.0% in the poor outcome group, ² (df) = 7.20 (1), corrected P = 0.042, OR (95% CI) = 0.27 (0.10–0.72)]. Nevertheless, independent analysis of each treatment group reveals that the excess of 12/12 carriers in the poor outcome group was only found in the naltrexone-treated group [24.1% versus 64.7% ² (df) = 7.41 (1), corrected P = 0.042, OR (95% CI) = 0.17 (0.05–0.64)]. In the whole sample, the L-10 repeats haplotype (5-HTTLPR-STin2 VNTR) is associated with good outcome (LRT = 3.88, df = 1, P = 0.049). Conclusions: Our findings suggest that functional polymorphism of the SLC6A4 gene may have an influence on treatment outcome in alcohol-dependent patients.

Interleukin-10 Gene Polymorphism is Associated with Alcoholism but not With Alcoholic Liver Disease

Marcos, M., Pastor, I., GonzAlez-Sarmiento, R., Laso, F. J. — 2008-08-23

Aims: To determine whether the functional polymorphism –592C>A of the interleukin (IL)-10 gene (IL10) influences the development of alcoholic liver disease or alcoholism in alcoholic Spanish subjects. Methods: The –592C>A IL10 polymorphism was analyzed by the polymerase chain reaction and digestion with restriction enzymes in 257 male alcoholics [161 without alcoholic liver disease and 96 with alcoholic liver cirrhosis (ALC)] and 100 male healthy controls. Results: We found no association between the –592C>A IL10 polymorphism and ALC. Meta-analysis combining this result and data from previous studies failed also to show any significant association between this polymorphism and alcoholic liver disease. However, the frequency of allele A carriers (CA and AA genotypes) was significantly higher in alcoholic patients (defined as patients with abuse or dependence of alcohol) than in healthy controls. Conclusion: The –592C>A IL10 polymorphism is not related to the risk of ALC. Nevertheless, our study shows that alcoholism is associated with an excess of allele A carriers in alcoholic patients.

The Drosophila Homolog of jwa is Required for Ethanol Tolerance

Li, C., Zhao, X., Cao, X., Chu, D., Chen, J., Zhou, J. — 2008-08-23

Aims: Alcohol abuse poses a serious public health problem, and repeated ingestion can produce tolerance, leading to dependence and addiction. However, the mechanisms underlying alcohol tolerance and addiction are not fully understood. Drosophilae have been employed as a suitable model to study the molecular mechanisms underlying ethanol tolerance. JWA, a newly identified microtubule-binding protein, was shown to regulate cell stress responses, transportation of intracellular excitatory amino acids, and the MAPK signal transduction pathway. The JWA mouse homologue addicsin, was postulated to play a role in the development of morphine tolerance and dependence. This study was designed to determine whether JWA participates in ethanol tolerance in Drosophila. Methods: The jwa homologous gene in Drosophila, CG10373 (djwa) was cloned and the anti-djwa and cDNA-djwa transgenic fly strains, which exhibit a reduced and elevated djwa expression respectively were constructed. Real-time PCR was used to measure the djwa levels in the resulting fly strains. Rapid tolerance experiments including inebriation exposure and recovering assay were employed. Results: The djwa and the human jwa genes share a significant sequence similarity. Their genomic nucleotide and deduced amino acid sequence identities are 41.4% and 53.6%, respectively. In inebriation tests, the wild type w¹¹¹⁸ flies and the cDNA-djwa flies acquired ethanol tolerance after several exposures whereas the anti-djwa flies did not. Conclusions: The JWA genes are evolutionarily conserved. The djwa function is required for acquiring ethanol tolerance in Drosophila. JWA is likely a novel molecule playing an important role in ethanol tolerance and drug addiction. Our results present a new direction for research related to alcohol tolerance and addiction.

Alcohol Induces Relaxation of Rat Thoracic Aorta and Mesenteric Arterial Bed

Ru, X.-C., Qian, L.-B., Gao, Q., Li, Y.-F., Bruce, I. C., Xia, Q. — 2008-08-23

Aims: The aim of this study was to investigate the effect of alcohol on rat artery and its underlying mechanism. Methods: The tension of isolated Sprague-Dawley rat thoracic aortic rings and the pressure of rat mesenteric arterial beds perfused with different concentrations of alcohol (0.1–7.0) were measured. Results: At resting tensions, alcohol caused a concentration-dependent relaxation on endothelium-denuded aortic rings precontracted with KCl (6x10^–2 mol/L) or phenylephrine (PE, 10^–6 mol/L), and this effect was most evident on rings at a resting tension of 3 g. Alcohol induced much less vasodilation on endothelium-intact rings. Alcohol inhibited the CaCl₂-induced contraction of endothelium-denuded aortic rings precontracted with KCl or PE. Incubation of rings with dantrolene (5x10^–5 mol/L), a ryanodine receptor blocker, or 2-aminoethyl diphenylborinate (7.5x10^–5 mol/L), an IP₃ receptor blocker, attenuated the vasodilating effect of alcohol on rings precontracted with PE. Alcohol also concentration-dependently relaxed rat mesenteric arterial beds precontracted with KCl (6x10^–2 mol/L) or PE (10^–5 mol/L), which was more potent on endothelium-denuded than on endothelium-intact beds. Conclusions: Alcohol has a vasodilating effect on rat artery depending on the resting tension. Both extracellular and intracellular Ca²⁺ mobilization of vascular smooth muscle cells are involved in the vascular effect of alcohol.

Lipid Metabolism in Ethanol-Treated Rat Pups and Adults: Effects of Folic Acid

Ojeda, M. L., Delgado-Villa, M. J., Llopis, R., Murillo, M. L., Carreras, O. — 2008-08-23

Aims: In this study we determined whether a folic acid-supplemented diet could change hyperlipaemia provoked by chronic ethanol intake in adult and pup rats. Methods: Animals were randomized into eight groups (four adults and four pups): control groups, water and basic diet; alcohol groups, 20% ethanol and basic diet; alcohol folic acid groups, 20% ethanol and diet supplemented with folic acid; control folic acid groups, water and folic acid-supplemented diet. We determined serum and liver total cholesterol (Chol), HDL, triglycerides (TG), phospholipids (PL) and bile acids (BA) levels in all of the groups. Hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity was also measured in the livers. Results: Ethanol-fed rats have higher serum HDL and PL levels in pups and higher serum LDL, TG and PL levels in adults than controls and supplemented animals with or without alcohol ingestion. Ethanol provokes an increase in hepatic Chol and BA, and a decrease in hepatic TG and PL in pups; in adults it also provokes an increase in hepatic Chol and BA and a significant increase in HMG-CoA reductase activity. Alcohol intake plus folic acid supplementation has no effects on these values except BA levels that were significantly higher, in both pups and adult rats, than in the control group. Conclusion: Despite the fact that alcohol intake provokes different lipid alterations in adults and in pups whose mothers drank ethanol, folic acid contributes to the alleviation of these adverse effects reducing HMG-CoA reductase activity in adult rats and, except BA levels, to normalizing lipids values due to the fact that folic acid acts as a choleretic compound. We can therefore assume that folic acid supplementation reduces alcohol-induced hypercholesterolaemia by decreasing synthesis and increasing catabolism.

Relationships Between Alcohol-Related Memory Association and Changes in Mood: Systematic Differences Between High- and Low-Risk Drinkers

Kelly, A. B., Masterman, P. W. — 2008-08-23

Heavy alcohol use is common in undergraduates and is associated with health-risk behaviors, negative consequences, and increased risk for future alcohol dependence. Alcohol-related memory associations (AMAs) and mood changes are independently related to student drinking, but more research on how these variables interact is needed. Aims: To examine (i) how AMAs predict drinking behavior after accounting for depression, and (ii) how changes in negative and positive mood predict AMAs among low- and high-risk drinkers. Methods: Positive and negative moods were manipulated using a musical mood induction procedure immediately prior to completion of memory association measures. A bootstrapped structural equation model was tested, permitting a sampling distribution free of the requirement of normality. Results: Negative mood changes predicted AMAs in high-risk drinkers but not in low-risk drinkers, and the opposite was found for positive mood changes. Conclusion: The negative mood–AMA association appeared related to risky drinking, and these subtle implicit cognitive processes may warrant a special focus in intervention programs for high-risk drinkers.

Influence of Liver Biopsy on Abstinence in Alcohol-Dependent Patients

2008-08-23

Background: Liver biopsy indication for the evaluation of alcoholic liver disease is controversial. Our aim was to investigate the influence of the biopsy on the patients’ motivation for abstinence. Methods: We retrospectively analysed, in a population of 324 patients hospitalized for alcohol withdrawal, the impact of liver biopsy on the following clinical outcomes: rapid loss to follow-up (immediately after hospital discharge), early relapse (< 3 months) and long-lasting abstinence (> 12 months). The biopsy was performed in 136 patients who had liver enzymes perturbations. Hepatic lesions were graded as mild (isolated steatosis and/or non-bridging fibrosis), moderate (bridging fibrosis and/or moderate alcoholic hepatitis) or severe (cirrhosis and/or marked alcoholic hepatitis) in 66 (48%), 41 (30%) and 29 (21%) cases, respectively. Results: In univariate analysis, patients who had a liver biopsy were less likely to be rapidly lost to follow-up (12% versus 27%, P = 0.003) but had a lower rate of long-term abstinence (20% versus 34%, P = 0.025). In multivariate analysis, age was the only factor significantly associated with clinical outcome: older patients had higher rate of long-term abstinence (OR = 1.041; P = 0.010). Among patients who had a biopsy, those with severe hepatic lesions had a lower rate of rapid relapse than those with moderate or mild lesions (32% versus 68% and 56%, P = 0.018) but the rate of long-term abstinence was similar in the three groups. Conclusion: This observational study does not support the notion that liver biopsy has a significant influence on the maintenance of alcohol abstinence in patients with alcoholic liver disease.

Circadian Phenotype in Patients with the Co-Morbid Alcohol Use and Bipolar Disorders

Hatonen, T., Forsblom, S., Kieseppa, T., Lonnqvist, J., Partonen, T. — 2008-08-23

Aims: Alcohol misuse is associated with bipolar disorder. Abnormalities in the circadian clockwork play a role in the pathogenesis of bipolar disorder. Alcohol intake is likely to affect the circadian phenotype. We aimed at analysing the behavioural trait of the preference to morning or evening hours for the daily activities in bipolar disorder patients with or without the co-morbid alcohol use. Methods: Our nationwide sample of families included patients with bipolar disorder born during 1940–1969 having at least one hospitalization due to bipolar disorder during 1969–1991 and their first-degree relatives. All the 148 participants were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders and assessed using the Morningness–Eveningness Questionnaire whose factor matrix applying for the maximum likelihood principle was calculated for the first time. Results: Patients with the co-morbid alcohol use disorder were more of the morning type as compared with patients with bipolar disorder only. Conclusions: Co-morbid patients preferred more the morning hours for their daily activities, indicative of alcohol consumption having an effect on the circadian clock.

Automated Measurement of Carbohydrate-Deficient Transferrin Using the Bio-Rad %CDT by the HPLC Test on a VariantTM HPLC System: Evaluation and Comparison with Other Routine Procedures

Schellenberg, F., Mennetrey, L., Girre, C., Nalpas, B., Pages, J. C. — 2008-08-23

Aims: In this study, we evaluated the new %CDT by the HPLC method (Bio-Rad, Germany) on a Variant^TM HPLC system (Bio-Rad), checked the correlation with well-known methods and calculated the diagnostic value of the test. Methods: Intra-run and day-to-day precision values were calculated for samples with extreme serum transferrin concentrations, high trisialotransferrin and interfering conditions (haemolysed, lactescent and icteric samples). The method was compared with two routine procedures, the %CDT TIA (Bio-Rad, Hercules, CA, USA) and the Capillarys^TM CDT (Sebia, France). A total of 350 clinical sera samples were used for a case-control study. Results: Precision values were better in high CDT and medium CDT pools than in low CDT pools. The serum transferrin concentration had no effect on CDT measurement, except in samples with serum transferrin <1 g/L. Haemolysis was the only interfering situation. The method showed high correlation (r² > 0.95) with the two other methods (%CDT TIA and CZE %CDT). The global predictive value of the test was >0.90 at 1.9% cut-off. Conclusions: These results demonstrate that the %CDT by the HPLC test is suitable for CDT routine measurement; the results from the high-throughput Variant^TM system are well correlated with other methods and are of high diagnostic value.

Validation and Comparison of Alcohol-Screening Instruments for Identifying Hazardous Drinking in Hospitalized Patients in Taiwan

2008-08-23

Aim: The aim of this study was to validate the Mandarin Chinese version of different screening instruments and compare their performances for identifying hazardous drinkers in Taiwan.Methods: We compared the performance of the Mandarin Chinese versions of AUDIT, AUDIT-C (AUDIT items 1, 2 and 3), AUDIT-4 (AUDIT items 1, 2, 3 and 10), AUDIT-3 (AUDIT item 3), TWEAK, SMAST and CAGE to detect hazardous drinking in hospitalized patients in Taiwan. The results of the test instruments were blindly compared with the reference standard Schedule for Clinical Assessments in Neuropsychiatry (SCAN).Results: Of 404 patients evaluated, 100 were identified as having a hazardous drinking pattern. All screening instruments showed acceptable sensitivities (ranging from 85 to 93%) and specificities (ranging from 72 to 92%), but AUDIT and its short forms performed consistently better than the other instruments.Conclusions: The Mandarin Chinese versions of AUDIT and its derivatives perform well in screening hospitalized Taiwanese patients for hazardous drinking.

Using the Temperament and Character Inventory (TCI) to Predict Outcome after Inpatient Detoxification during 100 Days of Outpatient Treatment

Arnau, M. M., Mondon, S., Santacreu, J. J. — 2008-08-23

Aims: The aim was to evaluate TCI (Temperament and Character Inventory) scales in identifying personality traits for predicting adherence to outpatient treatments and the relapse of alcohol consumption by alcoholic patients. Methods: Follow-up of 89 alcoholic patients during the 100-day outpatient treatment after their release from the hospital detoxification unit. The detoxification treatment and the follow-up take place in the same hospital unit. Results: Of the patients, 34.8% abandoned the treatment and 31.5% relapsed. The patients who abandoned treatment had lower scores on the Cooperativeness scale. The length of time until the abandonment of the treatment was greater for those with scores >50 for the Self-directedness or Cooperativeness scales. Patients with scores >50 on the Persistence scale were more often abstinent; however, they took the same time to relapse. Conclusions: Higher scores on the TCI personality scales of Persistence, Self-directedness and Cooperativeness predict a better therapeutic evolution, especially with regard to adherence during outpatient treatment after detoxification.

Alcohol Abuse Among English and French Psychiatric Referrals from Accident and Emergency Departments

Sarfraz, M. A., Landron, S., Klugman, A. — 2008-08-23

Patterns of Alcohol Consumption and Related Behaviour in Great Britain: A Latent Class Analysis of the Alcohol Use Disorder Identification Test (AUDIT)

Smith, G. W., Shevlin, M. — 2008-08-23

Aims: Attempts have been made to develop typologies to classify different types of alcoholism. However, limited research has focused on classifications to describe general patterns of alcohol use in general population samples. Methods: Latent class analysis was used to create empirically derived behaviour clusters of alcohol consumption and related problems from the Alcohol Use Disorder Identification Test (AUDIT) based on data from a large stratified multi-stage random sample of the population of Great Britain. Multinomial logistic regression was performed to describe these resultant classes using both demographic variables and mental health outcomes. Results: Six classes best described responses in the sample data. Three were heavy consumption groups, one with multiple negative consequences, one experiencing alcohol-related injury and social pressures to cut down and an additional class with memory loss. There was one moderate class with few negative consequences, and finally two mild consumption groups, one with alcohol-related injury and social pressure to cut down and one with no associated problems. Conclusions: Alcohol use in Great Britain can be hypothesized as reflecting six distinct classes, four of which follow a continuum of increased consumption leading to increased dependence and related problems and two that do not. Differences between alcohol use classes are apparent with reduced risk of depressive episode in moderate classes and an increased risk of anxiety disorders for the highest consumers of alcohol.

Patterns of Binge Drinking at an International Nightlife Resort

Tutenges, S., Hesse, M. — 2008-08-23

Aims: The aim of this study was to compare the patterns of substance use in young Danes while holidaying in the Bulgarian holiday resort of Sunny Beach (SB) to their patterns of substance use in Denmark. Methods: Data were collected from visitors to SB in 2007 (n = 1011). Information on alcohol and drug use was surveyed using a short questionnaire. Findings: Most individuals surveyed were regular drinkers in Denmark, and the use of most illicit drugs was rare. Patterns of substance use in SB revealed heavy drinking was common, both in adolescents and young adults. Conclusions: International nightlife resorts provide a context for excess in drug use and alcohol use. Alcohol poses a potentially severe threat to the short- and long-term health of young tourists, but little attention has been paid to form interventions targeting binge drinking in nightlife resorts.

How should Alcohol Dependence be Treated? The Public View

de Toledo Piza Peluso, E., Blay, S. L. — 2008-08-23

Aims: The aim of this study was to assess public preferences on sources of help and treatment, and perception of prognosis for alcohol dependence. Method: A household survey was administered in 2002 to a probabilistic sample of 500 individuals, all residents of the city of São Paulo, Brazil, with ages ranging from 18 to 65. A vignette in colloquial language describing an individual with alcohol dependence (according to DSM-IV and ICD-10 criteria) was presented together with a structured questionnaire with questions about the vignette. Results: The public considered the help of lay people, self-help groups and psychologists the most useful. Medical professionals were viewed less favourably. The treatments and activities most recommended were psychotherapy and general activities, such as physical activities, keeping the mind busy and attending church services. Medical treatments were seen as more harmful than helpful. The more important determinants were identification of alcohol dependence as mental illness, religion and number of years of school completed. Prognosis with treatment was viewed as favourable. Conclusion: These results may indicate that the public needs to receive more information on the full range of treatments options, especially those related to professional or formal treatment.

Out of It--How Cocaine Killed My Brother. By Clare Campbell, Hodder, and Stoughton

Marshall, S. M. — 2008-08-23

Beat the Booze--A Comprehensive Guide to Combating Drink Problems in All Walks of Life. By Edmund Tirbutt and Helen Tirbutt

Aveyard, P. — 2008-08-23

Peer-Group and Price Influence Students Drinking along with Planned Behaviour

Jamison, J., Myers, L. B. — 2008-08-23

Prevention of "Risky" Drinking among Students at a Brazilian University

2008-08-23