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.
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.
Transgenic 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.
Stellate 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.
Ethanol 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.
Aims: To investigate whether ethnic differences in vulnerability to peer norms supportive of alcohol use is a viable, partial explanation for the ethnic differences in reported prevalence and amount of alcohol use during high school. Methods: Survey data from a sample of 680 adolescents from Project STAR (Students Taught Awareness and Resistance) of the Midwestern Prevention Project were used. Hypotheses were tested using sequential, semi-continuous growth curve models. Results: Relative to Black adolescents, White adolescents reported greater peer alcohol use during middle school and were much more likely to consume alcohol during high school. General peer norms in seventh grade and middle school growth in alcohol use norms among close friends was predictive of a greater propensity to consume alcohol in ninth grade among White adolescents. Conclusion: Lower peer norms for alcohol use among Black adolescents might better account for differences between Black and White adolescents than the possibility that White adolescents are more vulnerable to peer norms.
Aims: To assess the efficacy of the Therapeutic Workplace, a substance abuse intervention that promotes abstinence while simultaneously addressing the issues of poverty and lack of job skills, in promoting abstinence from alcohol among homeless alcoholics. Methods: Participants (n = 124) were randomly assigned to conditions either requiring abstinence from alcohol to engage in paid job skills training (Contingent Paid Training group), offering paid job skills training with no abstinence contingencies (Paid Training group) or offering unpaid job skill training with no abstinence contingencies (Unpaid Training group). Results: Participants in the Contingent Paid Training group had significantly fewer positive (blood alcohol level ≥ 0.004 g/dl) breath samples than the Paid Training group in both randomly scheduled breath samples collected in the community and breath samples collected during monthly assessments. The breath sample results from the Unpaid Training group were similar in absolute terms to the Contingent Paid Training group, which may have been influenced by a lower breath sample collection rate in this group and fewer reported drinks per day consumed at intake. Conclusion: Overall, the results support the utility of the Therapeutic Workplace intervention to promote abstinence from alcohol among homeless alcoholics, and support paid training as a way of increasing engagement in training programs.
Aims: Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood. We examine whether alcohol's social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress. Methods: Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage. Results: Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 μl; corrected P < 0.05). Conclusion: Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.
Aims: To systematically review the literature on the Chinese translations of the Alcohol Use Disorders Identification Test (AUDIT) and their cross-cultural applicability in Chinese language populations. Methods: We identified peer-reviewed articles published in English (n = 10) and in Chinese (n = 11) from 1980 to September 2009, with key words China, Chinese and AUDIT among PubMed, EBSCO, PsycInfo, FirstSearch electronic databases and two Chinese databases. Results: Five teams from Beijing, Tibet, Taiwan and Hong Kong reported their region-specific translation procedures, cultural adaptations, validity (0.93–0.95 in two versions) and reliability (0.63–0.99). These Chinese translations and short versions demonstrated relatively high sensitivity (0.880–0.997) and moderate specificity (0.709–0.934) for hazardous/harmful drinking and alcohol dependence, but low specificity for alcohol dependence among Min-Nan Taiwanese (0.58). The AUDIT and its adaptations were most utilized in workplace- and hospital-settings for screening and brief intervention. However, they were under-utilized in population-based surveys, primary care settings, and among women, adolescents, rural-to-urban migrants, the elderly and minorities. Among 12 studies from mainland China, four included both women and men, and only one in Tibet was published in English. Conclusion: There is a growing amount of psychometric, epidemiologic and treatment research using Chinese translations of the AUDIT, much of it still unavailable in the English-language literature. Given the increase in burden of disease and injury attributable to alcohol use in the Western Pacific region, the use of an internationally comparable instrument (such as the AUDIT) in research with Chinese populations presents a unique opportunity to expand clinical and epidemiologic knowledge about alcohol problem epidemics.
Aims: To evaluate sociodemographic correlates associated with transitions from alcohol use to disorders and remission in a Brazilian population. Methods: Data are from a probabilistic, multi-stage clustered sample of adult household residents in the São Paulo Metropolitan Area. Alcohol use, regular use (at least 12 drinks/year), DSM-IV abuse and dependence and remission from alcohol use disorders (AUDs) were assessed with the World Mental Health version of the Composite International Diagnostic Interview. Age of onset (AOO) distributions of the cumulative lifetime probability of each alcohol use stage were prepared with data obtained from 5037 subjects. Correlates of transitions were obtained from a subsample of 2942 respondents, whose time-dependent sociodemographic data were available. Results: Lifetime prevalences were 85.8% for alcohol use, 56.2% for regular use, 10.6% for abuse and 3.6% for dependence; 73.4 and 58.8% of respondents with lifetime abuse and dependence, respectively, had remitted. The number of sociodemographic correlates decreased from alcohol use to disorders. All transitions across alcohol use stages up to abuse were consistently associated with male gender, younger cohorts and lower education. Importantly, low education was a correlate for developing AUD and not remitting from dependence. Early AOO of first alcohol use was associated with the transition of regular use to abuse. Conclusion: The present study demonstrates that specific correlates differently contribute throughout alcohol use trajectory in a Brazilian population. It also reinforces the need of preventive programs focused on early initiation of alcohol use and high-risk individuals, in order to minimize the progression to dependence and improve remission from AUD.
Aims: Changes in glutamatergic transmission affect many aspects of neuroplasticity associated with ethanol and drug addiction. For instance, ethanol- and drug-seeking behavior is promoted by increased glutamate transmission in key regions of the motive circuit. We hypothesized that because glutamate transporter 1 (GLT1) is responsible for the removal of most extracellular glutamate, up-regulation or activation of GLT1 would attenuate ethanol consumption. Methods: Alcohol-preferring (P) rats were given 24 h/day concurrent access to 15 and 30% ethanol, water and food for 7 weeks. During Week 6, P rats received either 25, 50, 100 or 200 mg/kg ceftriaxone (CEF, i.p.), a β-lactam antibiotic known to elevate GLT1 expression, or a saline vehicle for five consecutive days. Water intake, ethanol consumption and body weight were measured daily for 15 days starting on Day 1 of injections. We also tested the effects of CEF (100 and 200 mg/kg, i.p.) on daily sucrose (10%) consumption as a control for motivated behavioral drinking. Results: Statistical analyses revealed a significant reduction in daily ethanol, but not sucrose, consumption following CEF treatment. During the post treatment period, there was a recovery of ethanol intake across days. Dose-dependent increases in water intake were manifest concurrent with the CEF-induced decreases in ethanol intake. Nevertheless, CEF did not affect body weight. An examination of a subset of the CEF-treated ethanol-drinking rats, on the third day post CEF treatment, revealed increases in GTL1 expression levels within the prefrontal cortex and nucleus accumbens. Conclusions: These results indicate that CEF effectively reduces ethanol intake, possibly through activation of GLT1, and may be a potential therapeutic drug for alcohol addiction treatment.
Aims: To clarify the role of acetate in neurochemical mechanisms of the initial (inborn) tolerance to ethanol. Methods: Rats with low and high inborn tolerance to hypnotic effect of ethanol were used. In the brain region homogenates (frontal and parietal cortex, hypothalamus, striatum, medulla oblongata) and brain cortex synaptosomes, the levels of acetate, acetyl-CoA, acetylcholine (AcH), the activity of pyruvate dehydrogenase (PDG) and acetyl-CoA synthetase were examined. Results: It has been found that brain cortex of rats with high tolerance to hypnotic effect of ethanol have higher level of acetate and activity of acetyl-CoA synthetase, but lower level of acetyl-СCoA and activity of PDG. In brain cortex synaptosomes of tolerant rats, the pyruvate oxidation rate as well as the content of acetyl-CoA and AcH synthesis were lower when compared with intolerant animals. The addition of acetate into the medium significantly increased the AcH synthesis in synaptosomes of tolerant, but not of intolerant animals. Calcium ions stimulated the AcH release from synaptosomes twice as high in tolerant as in intolerant animals. Acetate eliminated the stimulating effect of calcium ions upon the release of AcH in synaptosomes of intolerant rats, but not in tolerant animals. As a result, the quantum release of AcH from synaptosomes in the presence of acetate was 6.5 times higher in tolerant when compared with intolerant rats. Conclusion: The brain cortex of rats with high inborn tolerance to hypnotic effect of ethanol can better utilize acetate for the acetyl-CoA and AcH synthesis, as well as being resistant to inhibitory effect of acetate to calcium-stimulated release of AcH. It indicates the metabolic and cholinergic mechanisms of the initial tolerance to ethanol.
Aims: This systematic review focuses on research about macro-level gender equality and violence against women (VAW) and identifies conceptually and theoretically driven hypotheses as well as lessons relevant for alcohol research. Hypotheses include: amelioration—increased equality decreases VAW; backlash—increased equality increases VAW; and convergence—increased equality reduces the gender gap; and hypotheses that distinguish between relative and absolute status, with relative status comparing men's and women's status and absolute status measuring women's status without regard to men. Methods: Systematic review of studies published through June 2009 identified through PubMed and Web of Science, as well as citing and cited articles. Results: A total of 30 studies are included. Of 85 findings examining amelioration/backlash, 25% support amelioration, 22% backlash; and 53% are null. Of 13 findings examining convergence, 31% support and 23% are inconsistent with convergence; 46% are null. Conclusion: Neither the existence nor the direction of the equality and VAW relationship can be assumed. This suggests that the relationship between macro-level gender equality and alcohol should also not be assumed, but rather investigated through research.
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.
Aims: The aims were to provide proofs of mechanism and principle by establishing the ability of kynurenine metabolites to inhibit the liver mitochondrial low Km aldehyde dehydrogenase (ALDH) activity after administration and in vivo, and to induce aversion to alcohol. Methods: Kynurenic acid (KA), 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) were administered to normal male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring blood acetaldehyde following ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice. Results: ALDH activity was significantly inhibited by all three metabolites by doses as small as 1 mg/kg body wt. Blood acetaldehyde accumulation after ethanol administration was strongly elevated by KA and 3-HK and to a lesser extent by 3-HAA. All three metabolites induced aversion to alcohol in rats and decreased alcohol preference in mice. Conclusions: The above kynurenine metabolites of tryptophan induce aversion to alcohol by inhibiting ALDH activity. An intellectual property covering the use of 3-HK and 3-HAA and derivatives thereof in the treatment of alcoholism by aversion awaits further development.
Aims: The aims were to provide proofs of mechanism and principle by establishing the ability of the amino acid L-tryptophan (Trp) combined with the kynureninase inhibitor benserazide (BSZ) to inhibit the liver mitochondrial low Km aldehyde dehydrogenase (ALDH) activity after administration and in vivo and to induce aversion to alcohol. Methods: Trp, BSZ or both were administered to male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring acetaldehyde accumulation in blood after ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice. Results: Combined administration of Trp + BSZ, but neither compound alone, produced a strong inhibition of ALDH activity and an increase in blood acetaldehyde concentration after ethanol, and induced aversion to alcohol in rats and decreased preference in mice. Another kynureninase inhibitor, carbidopa, induced aversion to alcohol by itself, which was reversed by Trp co-administration. Conclusions: The present results establish a prior art for the use of a combination of Trp plus BSZ in the treatment of alcoholism by aversion, which merits rapid clinical development.
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.
Aims: To ascertain the views of general practitioners (GPs) regarding the prevention and management of alcohol-related problems in practice, together with perceived barriers and incentives for this work; to compare our findings with a comparable survey conducted 10 years earlier. Methods: In total, 282 (73%) of 419 GPs surveyed in East Midlands, UK, completed a postal questionnaire, measuring practices and attitudes, including the Shortened Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ). Results: GPs reported lower levels of post-graduate education or training on alcohol-related issues (<4 h for the majority) than in 1999 but not significantly so (P = 0.031). In the last year, GPs had most commonly requested more than 12 blood tests and managed 1–6 patients for alcohol. Reports of these preventive practices were significantly increased from 1999 (P < 0.001). Most felt that problem or dependent drinkers' alcohol issues could be legitimately (88%, 87%) and adequately (78%, 69%) addressed by GPs. However, they had low levels of motivation (42%, 35%), task-related self-esteem (53%, 49%) and job satisfaction (15%, 12%) for this. Busyness (63%) and lack of training (57%) or contractual incentives (48%) were key barriers. Endorsement for government policies on alcohol was very low. Conclusion: Among GPs, there still appears to be a gap between actual practice and potential for preventive work relating to alcohol problems; they report little specific training and a lack of support. Translational work on understanding the evidence-base supporting screening and brief intervention could incentivize intervention against excessive drinking and embedding it into everyday primary care practice.
Aims: To examine whether individual changes in alcohol consumption among female alcoholics under treatment are predicted by level of and changes in depression and dysfunctional attitudes. Method: A total of 120 women who were treated for alcohol addiction at the Karolinska Hospital in Stockholm (Sweden) were assessed twice over a 2-year period using the Depression scale from the Symptom Checklist-90, the Alcohol Use Inventory and the Dysfunctional Attitude Scale (DAS). Latent growth curve analysis was used. Results: Decrease in alcohol consumption, depression and dysfunctional attitude variables were found at group level. The results also showed significant individual variation in change. Changes in alcohol consumption were predicted by baseline alcohol drinking, as well as by level and changes in depression. Stronger reduction in depression was related to higher level of depression at baseline, and with reduction in dysfunctional attitudes. Different DAS sub-scales resulted in different magnitude of the model relations. Good treatment compliance was related to lower baseline level in depression, but also with higher baseline level in dysfunctional attitudes, and predicted stronger reduction in alcohol consumption. Conclusion: This paper shows the importance of incorporating both individual level and change in depression as predictors of change in alcohol consumption among subjects treated for alcohol addiction. Also, dysfunctional attitudes are both indirectly and directly related to treatment outcome. By incorporating alcohol consumption, depression and dysfunctional attitudes as targets of intervention, treatment compliance and outcome may be enhanced.
Aims: To compare the mortality of female alcoholics randomly assigned to the woman-only programme ‘Early treatment for Women with Alcohol Addiction’ (EWA) versus those who received mixed gender ‘Treatment As Usual’ (TAU). Methods: Randomized controlled trial involving 2-year follow-up by personal interview and mortality register data through 27 years of 200 women first time treated for alcohol use disorder (AUD; EWA, n = 100 and TAU, n = 100), who were consecutively recruited during 1983–1984. Data from the Causes of Death Register were used to test for mortality differences related to group interaction predictors such as age, inpatient versus outpatient status at intake and 2-year drinking outcome. Results: Significantly lower mortality was found among younger women who participated in EWA compared with those who received TAU. This difference lasted nearly 20 years after intake to treatment. For women who only needed outpatient treatment, reduced mortality was found in the EWA group, even for older women. Increased mortality was found for TAU women who did not attend the 2-year follow-up compared with those who attended; no such difference was found for EWA women. This indicates different attrition mechanisms in the two groups. Thus, previously reported treatment effects may have been underestimated. EWA was a more comprehensive programme than TAU while also being single gender. Conclusions: EWA, specifically developed to meet a broad spectrum of problems among women with AUDs, was more effective than TAU, a mixed gender programme. It was not possible to separate whether this was in part because it was a more comprehensive programme, as well as being single gender.