Alcohol and Alcoholism - current issue

GABA and Glutamate Overflow in the VTA and Ventral Pallidum of Alcohol-Preferring AA and Alcohol-Avoiding ANA Rats after Ethanol

Kemppainen, H., Raivio, N., Nurmi, H., Kiianmaa, K. — Wed, 03 Feb 2010 09:43:28 PST

Aims: Earlier findings suggest that dopaminergic neurons are probably not critically involved in ethanol self-administration behavior and in the differential intake of ethanol by the alcohol-preferring AA (Alko Alcohol) and non-preferring ANA (Alko Non-Alcohol) rat lines selected for differential ethanol intake. The purpose of the present study was, therefore, to clarify the role of GABAergic and glutamatergic afferents and efferents with the mesolimbic dopamine system in the control of ethanol intake as well as in differential intake of ethanol by AA and ANA rats. Methods: The effects of an acute dose of ethanol (1 or 2 g/kg i.p.) on the levels of GABA and glutamate in the ventral pallidum and the ventral tegmental area of AA and ANA rats were monitored with in vivo microdialysis. The concentrations of GABA and glutamate in the dialysates were determined with a high performance liquid chromatography system using fluorescent detection. Results: Ethanol significantly decreased the extracellular levels of GABA in the ventral pallidum but not in the ventral tegmental area. The ANA rats were more sensitive than the AA rats to the suppressive effect of ethanol on pallidal GABA levels. Ethanol did not have any effect on the concentrations of glutamate in either rat line. Conclusions: The suppressive effect of ethanol on the extracellular levels of GABA in the ventral pallidum suggests a role for pallidal GABAergic transmission in the control of ethanol consumption.

Alcohol Intake and Systemic Markers of Inflammation--Shape of the Association According to Sex and Body Mass Index

Oliveira, A., Rodriguez-Artalejo, F., Lopes, C. — Wed, 03 Feb 2010 09:43:28 PST

Aims: To assess the association of alcohol intake with high-sensitivity C-reactive protein (hs-CRP), uric acid and leukocyte count in blood, and whether sex and body mass index (BMI) modify these associations.

Methods: Individuals aged ≥18 years were randomly selected from the population of Porto, Portugal (70% of participation). A total of 840 women and 490 men with reliable information on inflammatory markers and alcohol intake, obtained from a validated food frequency questionnaire, were studied. Associations and their respective trends were estimated from generalized linear models, with adjustment for potential confounders. Analyses were stratified by sex and BMI.

Results: In women, adjusted hs-CRP levels (mg/l) were 2.69 in non-drinkers, 2.25 in drinkers of >0–15 g alcohol/day, 2.32 in drinkers of >15–30 g alcohol/day and 3.18 in drinkers of >30 g alcohol/day (P-value for the quadratic trend <0.001). In men, the association between alcohol intake and hs-CRP was positive and linear (P-value for the linear trend = 0.014). Alcohol intake was also positively and linearly associated with uric acid in each sex. Body weight modified these associations, which remained statistically significant only in normal-weight (BMI <25 kg/m²) women and overweight (BMI ≥25 kg/m²) men for hs-CRP, and in normal-weight individuals for uric acid. No significant association between alcohol intake and leukocyte count was found.

Conclusions: The association of alcohol intake with hs-CRP was J-shaped in women but positive and linear-shaped in men. Alcohol intake was directly associated with uric acid in men and women. BMI modifies the effect of alcohol on hs-CRP and uric acid levels in each sex.

Methanol Levels in Saliva--A Non-Invasive Parameter That May Be Useful in Detection of Alcohol Intoxication

Heberlein, A., Lenz, B., Degner, D., Kornhuber, J., Hillemacher, T., Bleich, S. — Wed, 03 Feb 2010 09:43:28 PST

Non-invasive screening parameters proving alcohol intoxication are necessary especially in forensic contexts. Results obtained by common measurement methods like the ethanol breath analyzer may be falsified by several parameters like hypoventilation. Therefore, we undertook a pilot study investigating the usefulness and applicability of methanol levels measured in saliva. Our results show that methanol levels in saliva are closely linked to ethanol levels in saliva (r = 0.971, P < 0.0001, t = 5.622, P = 0.000) as well as to ethanol levels in serum (r = 0.786, P = 0.001, t = –1.106, P = 0.058). Therefore, methanol levels measured in saliva might be applicable in order to increase the validity of other non-invasive measurement methods like the ethanol breath analyzer.

Initial Preference for Drinking Goal in the Treatment of Alcohol Problems: I. Baseline Differences Between Abstinence and Non-Abstinence Groups

Wed, 03 Feb 2010 09:43:28 PST

Aims: To compare baseline characteristics of clients initially preferring abstinence with those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (UKATT) and to identify predictors of goal preference from client characteristics present before the preference was stated.

Methods: From discussions with clients entering the trial (N = 742), screeners noted whether clients were aiming for abstinence ‘probably yes’ or ‘probably no’. Differences between the two groups thus formed were explored by univariate comparisons among client characteristics recorded at baseline assessment and by logistic regression analysis with pre-existing characteristics as independent variables.

Results: Across all UKATT sites, 54.3% of clients expressed a preference for abstinence and 45.7% for non-abstinence. In univariate comparisons, clients preferring abstinence were significantly (P < 0.01) more likely to: (i) be female, (ii) be unemployed, (iii) report drinking more heavily but less frequently, (iv) have been detoxified in the 2 weeks prior to assessment, (v) report more alcohol problems, (vi) be in the action stage of change, (vii) report greater negative expectancies of drinking, (viii) report greater mental and physical ill-health, (ix) report less social support for drinking and (x) be more confident of their ability to resist heavy drinking in tempting situations. In the logistic regression model, the strongest predictors of goal preference were gender, drinking pattern, recent detoxification and social support for drinking.

Conclusion: The implications of these findings for service delivery are best considered in conjunction with findings from a companion paper reporting treatment outcomes associated with each goal preference.

Initial Preference for Drinking Goal in the Treatment of Alcohol Problems: II. Treatment Outcomes

Wed, 03 Feb 2010 09:43:28 PST

Aims: To compare treatment outcomes between clients preferring abstinence and those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (the United Kingdom Alcohol Treatment Trial) and to interpret any differential outcome in light of baseline differences between goal preference groups outlined in an accompanying paper.

Methods: Outcomes at 3 and 12 months’ follow-up were recorded both in categorical terms (abstinence/non-problem drinking/much improved/somewhat improved/same/worse) and on continuous measures (percent days abstinent, drinks per drinking day/dependence score).

Results: Clients initially stating a preference for abstinence showed a better outcome than those stating a preference for non-abstinence. This superior outcome was clearer at 3 months’ follow-up but still evident at 12 months’ follow-up. The better outcome consisted almost entirely in a greater frequency of abstinent days, with only a modest benefit in drinking intensity for goal abstainers that disappeared when baseline covariates of goal preference were controlled for. Type of successful outcome (abstinence/non-problem drinking) was related to initial goal preference, with clients preferring abstinence more likely to obtain an abstinent outcome and those preferring non-abstinence a non-problem drinking outcome.

Conclusion: The client’s personal drinking goals should be discussed in assessment at treatment entry and as a basis for negotiation. Clinicians should be prepared to identify and support goal change as an unexceptional part of the treatment process that need not jeopardize good outcome.

An Open Trial of Gabapentin in Acute Alcohol Withdrawal Using an Oral Loading Protocol

Bonnet, U., Hamzavi-Abedi, R., Specka, M., Wiltfang, J., Lieb, B., Scherbaum, N. — Wed, 03 Feb 2010 09:43:28 PST

Aims: Anticonvulsants are increasingly being advocated for the treatment of acute alcohol withdrawal syndrome (AWS) to avoid the addictive properties of established medications. Because earlier works showed that moderate gabapentin doses were too low to clearly ameliorate severe AWS, we tested a higher gabapentin entry dose. Methods: Inpatients (n = 37) with severe alcohol withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-AR) score ≥15 points) were given gabapentin 800 mg, and if their symptom score reduced within 2 h, they were termed ‘early responders’ and were then treated for 2 days with 600 mg gabapentin q.i.d. (i.e. a total of 3200 mg in the first 24 h) before beginning a taper. Results: Twenty-seven (73%) were early responders (baseline CIWA-AR improved from 17.3 ± 2.6 to 8.0 ± 3.6 points). In the remaining 10 patients, baseline CIWA-AR deteriorated within 2 h (from 20.1 ± 4.6 to 21.5 ± 4.65 points). These patients were switched to clomethiazole (n = 4) or clonazepam (n = 6), which is the usual treatment. Three of the ‘early responders’ worsened in the next 36 h and were then reclassified and treated as ‘non-responders’. Among them, two developed an epileptic seizure. Conclusion: Oral 800 mg gabapentin (loaded up to 3200 mg in the first 24 h) is helpful only in reducing less severe and less complicated acute AWS.

Supervised Disulfiram in Relapse Prevention in Alcohol-Dependent Patients Suffering From Comorbid Borderline Personality Disorder--A Case Series

Wed, 03 Feb 2010 09:43:28 PST

Aims: Disulfiram is widely used to prevent alcoholic relapse. However, due to the intended adverse reaction with ethanol, some believe that its use is dangerous for patients with personality disorders or psychiatric comorbidities because of their increased risk of impulsivity or suicidal behaviour. We examined the safety and efficacy in relapse prevention of a series of alcoholics with borderline personality disorder (BPD).

Methods: Case history study of patients diagnosed with BPD, prescribed disulfiram in a dose of 1.5–2.5 g/week, supervised by a physician in up to three brief contacts per week.

Results: Two out of eight patients remained completely abstinent during the supervised disulfiram therapy over a mean period of 9.25 months. Adherence to treatment was 18.44 ± 21.78 months. The first relapse occurred after 1.38 ± 1.41 months. The cumulated time of abstinence was 16.88 ± 20.48 months. The overall tolerability was considered to be high; dizziness and fatigue appeared in all patients at the beginning of the therapy but did not persist. No serious adverse events or ethanol–disulfiram interactions were observed. No suicidal behaviour was reported.

Conclusions: Although case observations should be interpreted with caution, supervised disulfiram seems to deserve further investigation in patients with comorbid BPD, for whom it appears to help prevent alcoholic relapse.

Analysis of the Factors Determining Survival of Alcoholic Withdrawal Syndrome Patients in a General Hospital

Monte, R., Rabunal, R., Casariego, E., Lopez-Agreda, H., Mateos, A., Pertega, S. — Wed, 03 Feb 2010 09:43:28 PST

Aim: To investigate the clinical variables associated with the risk of dying and the causes of death during the course of alcoholic withdrawal syndrome (AWS) in a general hospital. Methods: Cohort study of AWS patients admitted to Xeral Hospital in Lugo, Spain between 1987 and 2003. The characteristics of patients who died were contrasted with those who survived. The different clinical, epidemiological and biochemical variables reflective of alcohol consumption habits, basal health status and presentation features of the syndrome and its complications were all recorded. Results: There were 539 episodes of hospitalization for AWS in 436 patients (mean age 45.0, SD 12.0, 91.3% males), 71.1% of whom presented with delirium tremens. A total of 29 patients died, yielding a 6.6% mortality rate (95% confidence interval, CI: 4.2–9.1%). Eighteen patients (62%) died after being admitted to the intensive care unit (ICU). The following independent variables were associated with the risk of dying in a multivariate logistic regression model: cirrhosis [odds ratio (OR) 4.8 (95% CI 1.5–14.6), P = 0.006]; presenting with delirium tremens at diagnosis [OR 3.5 (95% CI 1.3–8.9), P = 0.008]; the existence of an underlying chronic pathology other than liver disease [OR 2.5 (95% CI 1–6.1), P = 0.01]; and the need for orotracheal intubation [OR 2.9 (95% CI 1.1–7.9), P = 0.03], especially if pneumonia requiring ICU is added [OR 8 (95% CI 3–21.3), P < 0.001]. Receiver operating characteristic analysis revealed an area under the curve of 0.818 (95% CI 0.742–0.894). Conclusions: The factors determining survival after admission to a general hospital for alcoholic withdrawal syndrome depend on the intensity of clinical manifestations (delirium tremens, ICU, orotracheal intubation) and the presence of associated comorbidity.

Causal Considerations on Alcohol and HIV/AIDS -- A Systematic Review

Shuper, P. A., Neuman, M., Kanteres, F., Baliunas, D., Joharchi, N., Rehm, J. — Wed, 03 Feb 2010 09:43:28 PST

Aim: The study aimed to explore the possible causal nature of the association between alcohol consumption and HIV/AIDS.

Methods: A review based on meta-analyses and reviews was conducted according to standard epidemiological criteria to distinguish causality from association, examining (i) the potential impact of alcohol on the incidence of HIV and (ii) alcohol's impact on worsening the disease course. Results: In terms of incidence of HIV, although we found a consistent and strong association with consumption, there was not enough evidence for a causal connection. In particular, it is not clear whether personality traits such as sensation seeking or sexual compulsivity and psychiatric disorders such as antisocial personality disorder impact both alcohol consumption and risky sex, subsequently creating an association between both behaviors. In terms of worsening the disease course of HIV/AIDS, we found enough evidence for a causal impact of alcohol. Alcohol affects the immune system, thus contributing to a worsened course of HIV/AIDS. In addition, alcohol negatively impacts on behaviors that include support seeking and medication adherence. Conclusions: A randomized controlled clinical trial targeted toward at-risk HIV-negative individuals who live in areas with high HIV prevalence is suggested to test the effects of proven effective alcohol interventions on HIV incidence.

In Alcohol-Dependent Drinkers, What Does the Presence of Nicotine Dependence Tell Us About Psychiatric and Addictive Disorders Comorbidity?

Le Strat, Y., Ramoz, N., Gorwood, P. — Wed, 03 Feb 2010 09:43:28 PST

Aim: To examine the pattern of psychiatric comorbidity associated with nicotine dependence among alcohol-dependent respondents in the general population.

Methods: Drawn from a US national survey of 43,000 adults The (National Epidemiologic Survey on Alcohol and Related Conditions) who took part in a face-to-face interview, data were examined on the 4782 subjects with lifetime alcohol dependence, and comparisons were made between those with and those without nicotine dependence.

Results: Nicotine dependence was reported by 48% of the alcohol-dependent respondents. They reported higher lifetime rates of panic disorder, specific and social phobia, generalized anxiety disorder, major depressive episode, manic disorder, suicide attempt, antisocial personality disorder and all addictive disorders than those without nicotine dependence. After controlling for the effects of any psychiatric and addictive disorder, alcohol-dependent subjects with nicotine dependence were more than twice as likely as non-nicotine-dependent, alcohol-dependent subjects to have at least one other lifetime addiction diagnosis (adjusted odds ratio 2.36; 95% confidence interval 2.07–2.68).

Conclusions: Nicotine dependence represents a general marker of psychiatric comorbidity, particularly of addictive comorbidity. It may be used as a screening measure for psychiatric diagnoses in clinical practice as well as in future trials.

The Effect of Alcohol Consumption on Later Obesity in Early Adulthood -- A Population-based Longitudinal Study

Pajari, M., Pietilainen, K. H., Kaprio, J., Rose, R. J., Saarni, S. E. — Wed, 03 Feb 2010 09:43:28 PST

Aims: The study aimed to determine whether alcohol use during late adolescence contributes to the weight gain from adolescence to young adulthood or risk of obesity or waist circumference at young adulthood.

Methods: A population-based, longitudinal study of 5563 Finnish twins born in 1975–1979 and surveyed at ages 16 (T1), 17 (T2), 18 (T3) and 23–27 (T4) years. Drinking habits, height and weight were self-reported at T1, T2, T3 and T4; waist circumference was self-measured at T4. As potential confounders, we used smoking, diet, physical activity, place of residence, socio-economic status and parents' body mass index (BMI).

Results: Compared to the reference group (drinking once to twice per month), the BMI increase from T3 to T4 was less among abstaining men (–0.62 kg/m², (95% CI –1.04, –0.20)) and among women in those drinking less than monthly (–0.38 kg/m², (–0.71, –0.04)). In women, at least weekly drinking was associated with larger waist circumference (Beta 1.55 cm, (0.48, 2.61)), but this became statistically non-significant after adjusting for potential confounders. In a multilevel model for change, drinking frequency was not associated with weight change in women; in men, a negative association was seen, but it was statistically non-significant after adjusting for potential confounders.

Conclusions: These results from a population-based study with a large set of confounding variables suggest that alcohol use during adolescence has at most a minor effect on weight gain or development of abdominal obesity from adolescence to young adulthood.

Prevalence and Determinants of Binge Drinking in Middle Age in a Transitional Post-communist Country: A Population-based Study in Tirana, Albania

Burazeri, G., Kark, J. D. — Wed, 03 Feb 2010 09:43:28 PST

Aims: To assess the prevalence and determinants of binge drinking in the middle-age population of transitional post-communist Albania, for which data were previously unavailable. Methods: A population-based sample aged 35–74 years, interviewed and examined in Tirana in 2003–2006, included 450 men and 235 women for whom data on alcohol intake were collected (65.5% response). Multivariable-adjusted logistic regression was used to assess the association of drinking patterns with sociodemographic, socioeconomic and psychosocial characteristics and coronary risk factors. Results: Age-standardized to the 2005 census, 9.2% (95% confidence interval, CI = 6.5–11.9%) and 10.3% (95% CI = 7.4–13.1%) of men reported two to three or more annual episodes of drunkenness and hangovers, respectively. In women, the prevalence of both these markers of binging was 1.4% (95% CI = 0–3.1%). Among men, 8.9% (95% CI = 6.2–11.6%) reported drinking ≥60 g alcohol per session. In multivariable-adjusted models in men, binge drinking was related to low educational level (odds ratio, OR = 1.8, 95% CI = 1.0–3.3), financial loss in the pyramid collapse (OR = 1.6, 95% CI = 1.0–2.5) and religiosity (inversely) in both Muslims and Christians (OR = 0.2, 95% CI = 0.1–0.4). Conclusions: Among men in this transitional Southeast European country, social disadvantage and financial stress appear to promote alcohol abuse (which is rare in women), and traditionalism may be protective.

Alcohol Use Among Female Sex Workers and Male Clients: An Integrative Review of Global Literature

Li, Q., Li, X., Stanton, B. — Wed, 03 Feb 2010 09:43:28 PST

Aims: To review the patterns, contexts and impacts of alcohol use associated with commercial sex reported in the global literature. Methods: We identified peer-reviewed English-language articles from 1980 to 2008 reporting alcohol consumption among female sex workers (FSWs) or male clients. We retrieved 70 articles describing 76 studies, in which 64 were quantitative (52 for FSWs, 12 for male clients) and 12 qualitative. Results: Studies increased over the past three decades, with geographic concentration of the research in Asia and North America. Alcohol use was prevalent among FSWs and clients. Integrating quantitative and qualitative studies, multilevel contexts of alcohol use in the sex work environment were identified, including workplace and occupation-related use, the use of alcohol to facilitate the transition into and practice of commercial sex among both FSWs and male clients, and self-medication among FSWs. Alcohol use was associated with adverse physical health, illicit drug use, mental health problems, and victimization of sexual violence, although its associations with HIV/sexually transmitted infections and unprotected sex among FSWs were inconclusive. Conclusions: Alcohol use in the context of commercial sex is prevalent, harmful among FSWs and male clients, but under-researched. Research in this area in more diverse settings and with standardized measures is required. The review underscores the importance of integrated intervention for alcohol use and related problems in multilevel contexts and with multiple components in order to effectively reduce alcohol use and its harmful effects among FSWs and their clients.

Healthcare and Medical Graduates of 2009: Their Reactions to Four Key Proposals in the Scottish Government's Strategy for Tackling Alcohol Misuse

Gill, J. S., Gibson, C., Nicol, M. — Wed, 03 Feb 2010 09:43:28 PST

Aims: This study compares the views of final year medical, and nursing and allied health professional (NAHP) students in relation to four governmental proposals impacting on the sale and purchase of alcohol. Methods: Against a background of political will to address alcohol abuse in Scotland and moves within the National Health Service promoting a shifting of professional roles, self-completed questionnaires were administered in spring 2009 through course websites and lectures to final year medical and NAHP students. Results: Questionnaires were returned by 406 NAHPs and 121 medical students. Over three quarters of all students agreed with the proposed change to reduce the drink driving limit to 50 mg/100 ml blood. Less support was evident for the raising of the minimum legal purchase age for off-sales (37%), the banning of below cost price promotions of alcohol (47%) and minimum retail pricing (37%). However, there were differences between the NAHP and medical students in the case of the final two proposals; over 60% of the medical students agreed they would have a positive impact. For NAHPs, figures were 41% and 31%, respectively. Conclusions: Support for four key proposals outlined by the Scottish Government to address alcohol misuse varied. Only the suggestion to lower the drink driving limit received backing overall and within students in these professions. Effectiveness of proposed restrictions on the price of alcohol was less well regarded except by medical students. Evident gaps in knowledge around health guidelines, and the finding that almost half of NAHPs disagreed that they had the appropriate knowledge to advise patients about responsible drinking advice and alcohol misuse problems, suggest a need for improved undergraduate education and continued professional development with respect to public health aspects of alcohol use.

Use and Barriers to Use of Screening and Brief Interventions for Alcohol Problems Among Norwegian General Practitioners

Nygaard, P., Paschall, M. J., Aasland, O. G., Lund, K. E. — Wed, 03 Feb 2010 09:43:28 PST

Aims: To investigate the use and the obstacles to use of screening and brief interventions (SBI) for alcohol misuse among Norwegian general practitioners (GP). Methods: A questionnaire with 68 questions about the use and barriers to use of SBI in general practice was mailed to 2000 randomly selected Norwegian GPs. Results: The survey response rate was 45%. There was a much higher prevalence of using interventions (mean = 4.47 on a seven-point Likert scale) than of screening for alcohol problems (mean = 2.10 on a seven-point Likert scale). Regression models showed that knowledge and self-efficacy were the main predictors for GPs’ use of screening instruments and use of interventions, respectively, in particular with regard to use of screening. However, GPs’ views of their relationship with their patients, and structural factors were significant predictors. Conclusions: (i) Norwegian GPs do not necessarily see the link between screening for alcohol problems and conducting interventions. (ii) Factors on at least three levels, i.e. personal, social and structural, play significant roles for understanding the problems related to implementing the use of SBI in general practice. (iii) Training GPs in the use of SBI is important but may not increase GPs’ use of SBI due to social and structural barriers.

Biomarkers for Detecting Thiamine Deficiency--Improving Confidence and Taking a Comprehensive History are also Important

Thomson, A. D., Marshall, E. J., Guerrini, I. — Wed, 03 Feb 2010 09:43:28 PST

Disulfiram, an Option for the Treatment of Pathological Gambling?

Mutschler, J., Buhler, M., Grosshans, M., Diehl, A., Mann, K., Kiefer, F. — Wed, 03 Feb 2010 09:43:28 PST

Aim: Pathological gambling and comorbid alcohol dependence often occur in combination. Disulfiram is one of the proven drugs for alcohol dependence. In addition to its inhibiting acetaldehyde dehydrogenase, disulfiram inhibits dopamine β-hydroxylase and may thereby increase dopamine and decrease norepinephrine cerebral concentrations. Because there may be common neurochemical substrates and neuronal circuits for pathological gambling and addiction, we wished to explore the effect of disulfiram in gambling. Method: We describe the outcome of a patient with alcohol dependence and pathological gambling treated with disulfiram D. Results: During treatment with disulfiram, the patient reported that his desire to gamble disappeared entirely. Follow-up indicated that he has not gambled for >12 months. Conclusions: Although uncontrolled case observations should be interpreted with caution, disulfiram deserves further investigation in pathological gambling.