Alcohol and Alcoholism Journal
Ethanol Increases GABAergic Transmission and Excitability in Cerebellar Molecular Layer Interneurons from GAD67-GFP Knock-in Mice
This study assessed the acute effect of ethanol on GABAergic transmission at molecular layer interneurons (MLIs; i.e. basket and stellate cells) in the cerebellar cortex. The actions of ethanol on spontaneous firing of these pacemaker neurons were also measured.
MethodsTransgenic mice (glutamic acid-decarboxylase 67-green fluorescent protein knock-in mice) that express green fluorescence protein in GABAergic interneurons were used to aid in the identification of MLIs. Parasagittal cerebellar slices were prepared and whole-cell patch-clamp electrophysiological techniques were used to measure GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs). Loose-seal cell-attached recordings were used to measure spontaneous action potential firing.
ResultsStellate cells received spontaneous GABAergic input in the form of a mixture of action potential-dependent events (sIPSCs) and quantal events (mIPSCs); ethanol increased sIPSC frequency to a greater extent than mIPSC frequency. Ethanol increased spontaneous action potential firing of MLIs, which could explain the increase in sIPSC frequency in stellate cells. Basket cells received GABAergic input in the form of quantal events only. Ethanol significantly increased the frequency of these events, which may be mediated by a different type of interneuron (perhaps, the Lugaro cell) or Purkinje cell collaterals.
ConclusionsEthanol exposure differentially increases GABA release at stellate cell vs. basket cell-to-Purkinje cell synapses. This effect may contribute to the abnormalities in cerebellar function associated with alcohol intoxication.
Ethanol Consumption Alters the Expression and Reactivity of Adrenomedullin in the Rat Mesenteric Arterial Bed
Aims: Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on arterial blood pressure, vascular reactivity to AM and the expression of AM system components in the rat mesenteric arterial bed (MAB). Methods: Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Systolic, diastolic and mean arterial blood pressure were monitored in conscious rats. Vascular reactivity experiments were performed on isolated rat MAB. Matrix metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation were measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, CRLR (calcitonin receptor-like receptor) and RAMP1, 2 and 3 (receptor activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively. Results: Ethanol consumption induced hypertension and decreased the relaxation induced by AM and acetylcholine in endothelium-intact rat MAB. Phenylephrine-induced contraction was increased in endothelium-intact MAB from ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 or the net MMP activity in the rat MAB. Ethanol consumption increased mRNA levels of pre-pro-AM and protein levels of AM in the rat MAB. Finally, no differences in protein levels or mRNA of CRLR and RAMP1, 2 and 3 were observed after treatment with ethanol. Conclusion: Our study demonstrates that ethanol consumption increases blood pressure and the expression of AM in the vasculature and reduces the relaxation induced by this peptide in the rat MAB.
Personality Traits and Coping Compensate for Disadvantageous Decision-making in Long-term Alcohol Abstinence
Aims: High relapse rate and extreme difficulty to maintain abstinence are core characteristics of alcohol dependence (AD). Previous studies have demonstrated a persistent decision-making (DM) deficit in AD. We aimed to reveal specific personality features and stress-coping mechanisms presumed to compensate for ineffective DM skills. Methods: Eighty-eight unmedicated patients with AD were enrolled. Intact general cognitive status was assured by IQ above 90. Forty-three patients had an average abstinence period of 12 weeks and were currently in an inpatient treatment program (short-term abstinence group, STA) and 45 patients were abstinent for at least 3 years (long-term abstinence group, LTA). The two groups were assessed using an integrative approach combining domains of DM, temperament and character dimensions and stress-coping measures. Results: Both groups performed at chance level with no linear improvement tendency on the gambling task assessing DM adequacy. The LTA group scored significantly higher on scales of self-directedness and cooperativeness. In contrast, levels of harm avoidance, emotion-oriented coping and perceived stress were significantly higher in the STA group. Conclusion: Our findings provide new evidence for a persistent DM deficit with no learning effect in AD. Despite the deficit, alcohol-dependent patients can achieve LTA. STA patients perceive higher levels of stress and use non-adaptive coping strategies. We propose that the more adaptive personality profile of LTA patients contributes to the compensation of the trait-like DM deficit in alcoholism. These compensatory features represent promising new targets for preventive measures and therapeutic interventions in AD.
Brief Alcohol Intervention by Newly Trained Workers Versus Leaflets: Comparison of Effect in Older Heavy Drinkers Identified in a Population Health Examination Survey: A Randomized Controlled Trial
Aims: To test if a brief motivational intervention (BMI) in a non-treatment seeking population of heavy drinkers results in a reduced alcohol intake. Methods: Screening of 12,364 participants in a Danish health examination survey led to 1026 heavy drinkers of whom 772 were included and randomized to a BMI group (n = 391) or a control group (n = 381) receiving two leaflets about alcohol. Follow-up took place after 6 and 12 months including 670 and 616 participants respectively. The outcome measure was self-reported weekly alcohol consumption. Data were analysed according to the intention-to-treat principle. We used the Motivational Interviewing Treatment Integrity 3.0 code (MITI) as a quality control of the interventions delivered. Results: The intervention effect of the BMI was –1.0 drinks/week, but the effect was not significant. The MITI analysis showed that the quality of the BMI delivered was sub-optimal, as only one of four aspects was above the recommended level for beginning proficiency. Conclusion: We found no effect of a BMI in reducing alcohol consumption. The generalizability of the study is questionable, as individuals with the lowest level of education, low income and unmarried individuals are under-represented.
Atypical Antipsychotic Drugs and Ethanol Withdrawal Syndrome: A Review
Aims: Alcoholism and psychosis are known to have common neurochemical substrates. The aim of this review is to assess the reports involved in the effects of some atypical antipsychotic agents on the signs of ethanol withdrawal syndrome (EWS) in rats. Thus, both effectiveness of these drugs in ethanol withdrawal and the association between the drug effects and the signs have been investigated here on the same animal model. Methods: Adult Wistar rats were used as subjects. Ethanol was given to rats by modified liquid diet technique for inducing ethanol dependence. Clozapine, olanzapine, risperidone, quetiapine and ziprasidone were the drugs tested. Effects of these drugs on the signs of ethanol withdrawal such as locomotor hyperactivity, stereotyped behavior, tremor, wet dog shakes, tail-stiffness, abnormal posture and gait, agitation and audiogenic seizures were evaluated for the first 6 h of ethanol withdrawal. Results: Although some beneficial effects of all the drugs on ethanol withdrawal signs were observed, olanzapine precipitated abnormal posture and gait in the animals. Effectiveness rank of the used atypical antipsychotics was as follows: risperidone = quetiapine > ziprasidone > klozapine > olanzapine. Conclusion: Our results suggest that risperidone and quetiapine seem to be potent and pharmacologically more active agents on EWS in rats. Thus, these drugs may be beneficial in treatment of EWS in patients with alcoholism. Ziprasidone and clozapine also seem to be useful drugs in treatment of ethanol withdrawal.
Mentorship for Alcohol Problems (MAP): A Peer to Peer Modular Intervention for Outpatients
Aims: This is a Stage I open pilot to develop a new intervention, Mentorship for Alcohol Problems (MAP), for individuals with alcohol-use disorders in community treatment programs. Methods: Ten mentors participated for 6 months until 30 mentees received MAP for 12 weeks. Behavioral and biological measures were conducted in addition to fidelity measures. Four focus groups were held with participants and clinician feedback surveys were completed. Results: Feasibility and acceptance data in the domains of patient interest, safety and satisfaction were promising. Mentees reduced their alcohol and substance use and the majority of mentors sustained abstinence. Fidelity measures indicated that mentors adhered to the delivery of treatment. Conclusion: MAP shows promise to be incorporated into professionally run outpatient alcohol treatment programs to assist in the reduction of alcohol and substance use.
Refractory Hypotension in a Patient with Wernicke's Encephalopathy
A 57-year-old male patient with gastric carcinoma underwent radical distal gastrectomy type II + Braun anastomosis, and received total parenteral nutrition for 10 days after surgery, followed by small amounts of semi-liquid nutrition for 3 days and liquid nutrition for 2 days. The patient developed refractory hypotension for more than 1 week in the early course of disease, and on Day 15 after surgery presented with characteristic signs of Wernicke's encephalopathy, including diplopia and mental confusion. The hypotension did not improve despite appropriate fluid replacement soon after admission. Treatment with moderate dose of thiamine for 3 months partly relieved ophthalmoplegia and confusion, but not Korsakoff syndrome. This extraordinary presentation with refractory hypotension and the unusual course of the disease encouraged us to present this case.
Do Media Messages Change People's Risk Perceptions for Binge Drinking?
Aims: The current study investigated the effect of a media health message for drinking on risk perception estimates (comparative optimism). Methods: Sixty-five young adults who regularly drink alcohol watched an anti-drinking scenario (having an accident due to drinking). There were two intervention conditions: 30 participants ‘imagined’ they were part of the scenario, and 35 ‘watched’ the scenario. They then completed four comparative optimism estimates comparing themselves to those the same age and gender with similar drinking habits. The four comparisons were of their likelihood of being involved in an accident due to drinking; having unprotected sex, when under the influence of alcohol; having a car accident due to drinking (drivers only) and developing cirrhosis. There was also a control group (n = 59) who just completed the questionnaires. Results: Both intervention groups reported significantly lower comparative optimism for accident, unprotected sex and car accident than the control group. The ‘imagine’ group reported significantly lower comparative optimism than the ‘watch’ group for accidents. Conclusions. These results highlighted that media messages can successfully change people's risk perception, and also that imagination can be a powerful tool in changing risk perceptions associated with binge drinking.
Social Norm Influences on Evaluations of the Risks Associated with Alcohol Consumption: Applying the Rank-Based Decision by Sampling Model to Health Judgments
Aims: The research first tested whether perceptions of other people's alcohol consumption influenced drinkers' perceptions of the riskiness of their own consumption. Second, the research tested how such comparisons are made—whether, for example, people compare their drinking to the ‘average’ drinker's or ‘rank’ their consumption amongst other people's. The latter untested possibility, suggested by the recent Decision by Sampling Model of judgment, would imply different cognitive mechanisms and suggest that information should be presented differently to people in social norm interventions. Methods: Study 1 surveyed students who provided information on (a) their own drinking, (b) their perceptions of the distribution of drinking in the UK and (c) their perceived risk of various alcohol-related disorders. Study 2 experimentally manipulated the rank of ‘target’ units of alcohol within the context of units viewed simultaneously. Results: In both studies, the rank of an individual's drinking in a context of other drinkers predicted perceptions of developing alcohol-related disorders. There was no evidence for the alternative hypothesis that people compared with the average of other drinkers' consumptions. The position that subjects believed they occupied in the ranking of other drinkers predicted their perceived risk, and did so as strongly as how much they actually drank. Conclusions: Drinking comparisons are rank-based, which is consistent with other judgments in social, emotional and psychophysical domains. Interventions should be designed to work with people's natural ways of information processing, through providing clients with information on their drinking rank rather than how their drinking differs from the average.
Normative Misperceptions about Alcohol Use in a General Population Sample of Problem Drinkers from a Large Metropolitan City
Aims: Heavy drinkers tend to overestimate how much others drink (normative fallacy), at least in college samples. Little research has been conducted to evaluate whether normative misperceptions about drinking extend beyond the college population. The present study explored normative misperceptions in an adult general population sample of drinkers. Methods: As part of a larger study, in Toronto, Canada, a random digit dialling telephone survey was conducted with 14,009 participants who drank alcohol at least once per month. Respondents with Alcohol Use Disorders Identification Test of eight or more (n = 2757) were asked to estimate what percent of Canadians of their same sex: (a) drank more than they do; (b) were abstinent and (c) drank seven or more drinks per week. Respondents' estimates of these population drinking norms were then compared with the actual levels of alcohol consumption in the Canadian population. Results: A substantial level of normative misperception was observed for estimates of levels of drinking in the general population. Estimates of the proportion of Canadians who were abstinent were fairly accurate. There was some evidence of a positive relationship between the respondents' own drinking severity and the extent of normative misperceptions. Little evidence was found of a relationship between degree of normative misperceptions and age. Conclusion: Normative misperceptions have been successfully targeted in social norms media campaigns as well as in personalized feedback interventions for problem drinkers. The present research solidifies the empirical bases for extending these interventions more widely into the general population.
Universal Prevention is Associated with Lower Prevalence of Fetal Alcohol Spectrum Disorders in Northern Cape, South Africa: A Multicentre Before-After Study
Prevalence of fetal alcohol spectrum disorders (FASDs) is remarkably high in several provinces of South Africa; yet population-level knowledge of the harms of maternal drinking remains low. In two heavily affected areas, we assessed effectiveness of interventions to heighten awareness of these harms and to alter social norms about drinking in pregnancy.
MethodsFASD prevalence, maternal knowledge and drinking behaviours were investigated in two Northern Cape Province towns, before and after interventions which included highlighting FASD using local media and health promotion talks at health facilities. Independently, two dysmorphologists and a neuropsychometrist examined children at 9 and 18 months.
ResultsPre-intervention maternal knowledge of alcohol harms was low and FASD prevalence 8.9% (72/809). Interventions reached high coverage and knowledge levels increased substantially. FASD prevalence was 5.7% post-intervention (43/751; P = 0.02); 0.73 lower odds, controlling for maternal age and ethnicity (95% confidence interval = 0.58–0.90). No change was detected in more severe FASD forms, but in the whole population, median dysmorphology scores reduced from 4 [inter-quartile range (IQR) = 2–7] to 3 (IQR = 1–6; P = 0.002).
ConclusionThis, the first prevention study using FASD outcomes, suggests that universal prevention might reduce FASD by ~30% and have population-level effects. This supports intensifying universal interventions where knowledge of harms of maternal drinking is low. These efforts need to be accompanied by alcohol-dependence treatment to lower more severe FASD forms.
A Brief Report on Perceptions of Alcohol and Society among Scottish Medical Students
Aims: To assess perceptions on alcohol misuse and addiction among medical students prior to in-depth training in order to determine areas of the curriculum that need to be reshaped or focused on. Methods: A questionnaire assessment of first- and second-year medical students' perceptions of alcohol misuse. Results: Students had some misconceptions about current alcohol misuse rates, including a perception that addiction is common among health professionals, that the under-25s had the fastest increasing rate of alcohol addiction and that British women had a more rapidly increasing rate of alcohol addiction than British men. Conclusion: Encouragingly, students overwhelmingly felt that alcohol addiction was something to which they could make a difference. It highlights that early education about alcohol misuse is important in terms of teaching students how to recognize hazardous and harmful drinkers and how to manage them.
Equal Discussion of Significant Findings? Possible Confirmation Bias in Study of Alcohol Advertising
Equal Discussion of Significant Findings? Not Confirmation Bias, but a Focus on the Most Significant Findings
Socio-demographic Predictors of Dimensions of the AUDIT Score in A Population Sample of Working-age Men in Izhevsk, Russia
Aims: To investigate the relationship between socio-demographic factors and alcohol drinking patterns identified through a formal analysis of the factor structure of the Alcohol Use Disorders Identification Test (AUDIT) score in a population sample of working-age men in Russia. Methods: In 2008–2009, a sample of 1005 men aged 25–59 years living in Izhevsk, Russia were interviewed and information collected about socio-demographic circumstances. Responses to the AUDIT questions were obtained through a self-completed questionnaire. Latent dimensions of the AUDIT score were determined using confirmatory factor analysis and expressed as standard deviation (SD) units. Structural equation modelling was used to estimate the strength of association of these dimensions with socio-demographic variables. Results: The AUDIT was found to have a two-factor structure: alcohol consumption and alcohol-related problems. Both dimensions were higher in men who were unemployed seeking work compared with those in regular paid employment. For consumption, there was a difference of 0.59 SDs, (95% confidence interval (CI): 0.23, 0.88) and for alcohol-related problems one of 0.66 SD (95% CI: 0.31, 1.00). Alcohol-related problems were greater among less educated compared with more educated men (P-value for trend = 0.05), while consumption was not related to education. Similar results were found for associations with an amenity index based on car ownership and central heating. Neither dimension was associated with marital status. While we found evidence that the consumption component of AUDIT was underestimated, this did not appear to explain the associations of this dimension with socio-demographic factors. Conclusions: Education and amenity index, both measures of socio-economic position, were inversely associated with alcohol-related problems but not with consumption. This discordance suggests that self-reported questions on frequency and volume may be less sensitive markers of socio-economic variation in drinking than are questions about dependence and harm. Further investigation of the validity of the consumption component of AUDIT in Russia is warranted as it appears that the concept of a standard ‘drink’ as used in the instrument is not understood.
Accuracy of Self-Reported Drinking: Observational Verification of 'Last Occasion' Drink Estimates of Young Adults
Aims: As a formative step towards determining the accuracy of self-reported drinking levels commonly used for estimating population alcohol use, the validity of a ‘last occasion’ self-reporting approach is tested with corresponding field observations of participants' drinking quantity. This study is the first known attempt to validate the accuracy of self-reported alcohol consumption using data from a natural setting. Methods: A total of 81 young adults (aged 18–25 years) were purposively selected in Perth, Western Australia. Participants were asked to report the number of alcoholic drinks consumed at nightlife venues 1–2 days after being observed by peer-based researchers on 239 occasions. Complete observation data and self-report estimates were available for 129 sessions, which were fitted with multi-level models assessing the relationship between observed and reported consumption. Results: Participants accurately estimated their consumption when engaging in light to moderate drinking (eight or fewer drinks in a single session), with no significant difference between the mean reported consumption and the mean observed consumption. In contrast, participants underestimated their own consumption by increasing amounts when engaging in heavy drinking of more than eight drinks. Conclusion: It is suggested that recent recall methods in self-report surveys are potentially reasonably accurate measures of actual drinking levels for light to moderate drinkers, but that underestimating of alcohol consumption increases with heavy consumption. Some of the possible reasons for underestimation of heavy drinking are discussed, with both cognitive and socio-cultural factors considered.
Clinical Experience with Baclofen in the Management of Alcohol-Dependent Patients with Psychiatric Comorbidity: A Selected Case Series
Aims: To illustrate the potential indications for, and adverse effects of, baclofen pharmacotherapy for alcohol dependence in patients with co-existing psychiatric illness. Methods: Audit of the files of alcohol-dependent patients treated for comorbid non-psychotic psychiatric illness in a specialist detoxification unit with integrated outpatient treatment. Files were selected of patients who had been offered treatment with baclofen because other alcohol pharmacotherapies had previously been unsuccessful in preventing relapse or were contraindicated. Results: Of the 21 selected patients, 13 attended for outpatient treatment, with follow-up periods ranging from 4 days to 27 months, and the outcomes could be rated. Prescribed baclofen doses ranged from 30 to 275 mg daily. Common side effects at lower doses included tiredness and sedation; one patient on 120 mg/day developed reversible severe back pain, and a patient taking up to 275 mg/day developed somnolence, dizziness and incontinence. Seven patients maintained significant periods of abstinence, and one patient reduced daily consumption to non-problematic levels. Two patients consumed an overdose of other central nervous system (CNS) depressants, while taking baclofen in the first week of treatment, were briefly unwell, were given emergency monitoring, but made a full recovery. Conclusion: While more than half the patients reported significant reduction in alcohol use, it is not possible to draw definite conclusions about the effectiveness of baclofen, given that it was combined with other psychiatric and alcohol treatments, and because there was no control or comparison group. We recommend caution when offering baclofen to patients with a history of recurrent overdosing or a history of other substance misuse. When prescribing in conjunction with other medications with CNS depressant action, close monitoring is recommended at initiation and during dose escalation.
The Association between Social Determinants and Drunken Driving: A 15-Year Register-based Study of 81,125 Suspects
Aims: The aim of the study was to examine the association between social background and drunken driving. Methods: A Finnish register on suspected drunken driving was combined with data on social background. There were 81,125 drivers arrested for drunken driving and 86,279 references from 1993 to 2007. Results: A low level of education, unemployment, living alone and divorce were strongly associated with drunken driving. In addition, for persons aged 15–24 years, low parental education and income, high own income and possession of a car correlated with higher odds of drunken driving. For working-aged men and women, low income was associated with a higher risk of drunken driving. For working-aged women, also possession of a car was a risk factor. Conclusions: Social factors are associated with drunken driving. In general, people with a lower social position are more prone to drive after drinking. Social differences are visible already in youth, whereas working and own income of young persons signal different risk mechanisms for youth than for working-aged people. Measures for preventing drunken driving are needed within public health policies.
Why Drivers Start Drinking and Driving--A Prospective Study Over a 6-Year Period in the GAZEL Cohort
Aims: To estimate the frequency with which a group of formerly safe drivers adopt driving while alcohol-intoxicated (DWI), and to determine the factors associated with DWI adoption. Methods: Participants were current employees or recent retirees of the French national electricity and gas company. An annual cohort questionnaire that includes two questions about overall alcohol consumption is sent each year to participants. A Driving Behaviour and Road Safety (DBRS) questionnaire was administered in 2001, 2004 and 2007. Only drivers who participated in the 2001 survey received the 2004 and 2007 questionnaires. Results: More than 462 participants ceased DWI between 2001 and 2007, while 511 adopted this behaviour for the first time. Multivariate analysis showed that the risk of adopting DWI was associated with male gender and with several changes over the preceding years: increased alcohol consumption, increased number of close friends, decreased number of close relatives and decreased attitudes in favour of strict enforcement/regulations. Conclusion: A large number of offenders stopped DWI between 2001 and 2007, concomitantly with an increased crackdown on road violations in France. But this success was compromised by the occurrence of new drunk drivers. Preventive strategies should target factors that facilitate DWI adoption—in particular, increased alcohol consumption and low acceptance of law enforcement initiatives.


