The association of lifetime alcohol use with measures of abdominal and general adiposity in a large-scale European cohort

The relation between lifetime use of alcohol and measures of abdominal and general adiposity is unknown.

Among 99 381 men and 158 796 women of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, means of waist circumference (WC), waist-to-hip-ratio (WHR) and body mass index (BMI), and odds ratios (OR) for a larger WC than predicted for a given BMI (WClp=positive residuals of gender specific linear regression of BMI on WC) across categories of average lifetime use of alcohol (total, from wine and from beer) were calculated, all adjusted for socio-demographic, lifestyle and health factors.

WC, WHR and BMI in men using lifetime 6 g/d alcohol were 95.1 cm, 0.942 and 27.3 kg/m², and 96.2 cm, 0.961 and 28.3 kg/m² when using >96 g/d. WC and WHR in women was 83.2 cm and 0.813 for 6 g/d, and 84.6 cm and 0.830 for >60 g/d, whereas BMI deviated only slightly with the lowest BMI (26.7 kg/m²) observed for >6–24 g/d. Compared with 6 g/d, OR for a WClp in both genders increased steadily across categories of alcohol use (up to 1.40 (95% confidence interval 1.32, 1.49) in men using >60 g/d and 1.63 (1.54, 1.73) in women using >24 g/d), though increase was higher for alcohol from beer than from wine (P for difference between beer and wine<0.001 (men) and=0.002 (women)).

Lifetime alcohol use is positively related to abdominal and general adiposity in men, possibly following the male weight gain pattern; in women, it is positively related only to abdominal adiposity. In this context, beer may contribute additionally to abdominal adiposity.

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Request Reprint E-Mail:    bergmann@dife.de

Development and Validation of the Alcohol Identity Implicit Associations Test (AI-IAT)

Alcohol identity is the extent to which an individual perceives drinking alcohol to be a defining characteristic of his or her self-identity. Although alcohol identity might play an important role in risky college drinking practices, there is currently no easily administered, implicit measure of this concept. 

Therefore we developed a computerized implicit measure of alcohol identity (the Alcohol Identity Implicit Associations Test; AI-IAT) and assessed its reliability and predictive validity in relation to risky college drinking practices.

One hundred forty-one college students completed the AI-IAT. Again 3- and 6-months later, we administered the AI-IAT and indices of engagement in risky college drinking practices. A subset of participants also completed the previously-validated implicit measure of alcohol identity. 

Scores on the AI-IAT were stable over time, internally consistent, and positively correlated with the previously-validated measure of alcohol identity. 

Baseline AI-IAT scores predicted future engagement in risky college drinking practices, even after controlling for standard alcohol consumption measures. 

We conclude that the AI-IAT reliably measures alcohol identity, a concept that appears to play an important role in risky college drinking practices.


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Request Reprint E-Mail:   hgray@challiance.org  

Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASDs) are a group of conditions that can occur in a person whose mother drank alcohol during pregnancy. Learn more about signs, treatments, and what you can do about FASDs.  > > > >  Read More

Is unhealthy substance use associated with failure to receive cancer screening and flu vaccination? A retrospective cross-sectional study

To compare cancer screening and flu vaccination among persons with and without unhealthy substance use. 

The authors analysed data from 4804 women eligible for mammograms, 4414 eligible for Papanicolou (Pap) smears, 7008 persons eligible for colorectal cancer (CRC) screening and 7017 persons eligible for flu vaccination. All patients were screened for unhealthy substance use. The main outcome was completion of cancer screening and flu vaccination. 

Among the 9995 patients eligible for one or more of the preventive services of interest, 10% screened positive for unhealthy substance use. Compared with women without unhealthy substance use, women with unhealthy substance use received mammograms less frequently (75.4% vs 83.8%; p<0.0001), but Pap smears no less frequently (77.9% vs 78.1%). Persons with unhealthy substance use received CRC screening no less frequently (61.7% vs 63.4%), yet received flu vaccination less frequently (44.7% vs 50.4%; p=0.01). In multivariable analyses, women with unhealthy substance use were less likely to receive mammograms (adjusted odds ratio 0.68; 95% CI 0.52 to 0.89), and persons with unhealthy substance use were less likely to receive flu vaccination (adjusted odds ratio 0.81; 95% CI 0.67 to 0.97). 

Unhealthy substance use is a risk factor for not receiving all appropriate preventive health services. 

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Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis

Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals.
 
To investigate whether alcohol is involved in the pathogenesis of NASH, the expression of inflammation, fibrosis and alcohol metabolism related genes in the liver tissues of NASH patients and normal controls (NCs) were examined by microarray (NASH, n = 7; NC, n = 4) and quantitative real-time PCR (NASH, n = 6; NC, n = 6). Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and
cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1 and ADH4 in NASH livers (NASH, n = 9; NC, n = 4).

The augmented activity of all the available genes of the pathways for alcohol catabolism suggest that 1) alcohol concentration was elevated in the circulation of NASH patients; 2) there was a high priority for the NASH livers to scavenge alcohol from the circulation. Our data is the first human evidence that suggests alcohol may contribute to the development of NAFLD.



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Binge-Pattern Alcohol Exposure during Puberty Induces Long-Term Changes in HPA Axis Reactivity

Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. 

Our previous studies showed that binge-pattern ethanol (EtOH) treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis, as manifested by alterations in corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP), and corticosterone (CORT) during this time period. 

Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. 

In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. 

The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. 

Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

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Delivering alcohol screening and alcohol brief interventions within general dental practice: rationale and overview of the evidence

Alcohol consumption and affordability in the UK has increased over the last 50 years and is associated with a range of adverse oral health outcomes, the most serious of which, oral cancer, is also increasing in incidence. 

Despite this, routine screening and intervention relating to alcohol consumption within general dental practice remains uncommon. 

This review of the literature describes the background and outlines the evidence base for undertaking alcohol screening and delivering brief interventions in general dental practice.

Consideration will be given to the rationale for, and range of issues related to, introducing this into general dental practice.

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Request Reprint E-Mail:  t.dyer@sheffield.ac.uk    

Knock down of GCN5 histone acetyltransferase by siRNA decreases ethanol-induced histone acetylation and affects differential expression of genes in human hepatoma cells

We have investigated whether Gcn5, a histone acetyltransferase (HAT), is involved in ethanol-induced acetylation of histone H3 at lysine 9 (H3AcK9) and has any effect on the gene expression. 

Human hepatoma HepG2 cells transfected with ethanol-metabolizing enzyme alcohol dehydrogenase 1 (VA 13 cells) were used.

Knock down of Gcn5 by siRNA silencing decreased mRNA and protein levels of general control nondepressible 5 (GCN5), HAT activity, and also attenuated ethanol-induced H3AcK9 in VA13 cells. 

Illumina gene microarray analysis using total RNA showed 940 transcripts affected by GCN5 silencing or ethanol. 

Silencing caused differential expression of 891 transcripts (≥1.5-fold upregulated or downregulated). Among these, 492 transcripts were upregulated and 399 were downregulated compared with their respective controls. 

Using a more stringent threshold (≥2.5-fold), the array data from GCN5-silenced samples showed 57 genes differentially expressed (39 upregulated and 18 downregulated). Likewise, ethanol caused differential regulation of 57 transcripts with ≥1.5-fold change (35 gene upregulated and 22 downregulated). 

Further analysis showed that eight genes were differentially regulated that were common for both ethanol treatment and GCN5 silencing. 

Among these, SLC44A2 (a putative choline transporter) was strikingly upregulated by ethanol (three fold), and GCN5 silencing downregulated it (1.5-fold). The quantitative real-time polymerase chain reaction profile corroborated the array findings. 

This report demonstrates for the first time that (1) GCN5 differentially affects expression of multiple genes, (2) ethanol-induced histone H3-lysine 9 acetylation is mediated via GCN5, and (3) GCN5 is involved in ethanol-induced expression of the putative choline transporter SLC44A2.


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Request Reprint E-Mail:  shuklasd@health.missouri.edu   

Discrimination and alcohol-related problems among college students: A prospective examination of mediating effects

Discrimination is a risk factor for health-risk behaviors, including alcohol abuse. Far less is known about the mechanisms through which discrimination leads to alcohol-related problems, particularly during high-risk developmental periods such as young adulthood.

The present study tested a mediation model using prospective data from a large, diverse sample of 1539 college students. This model hypothesized that discrimination would be associated with established cognitive (positive alcohol expectancies) and affective (negative affect and coping motives) risk factors for alcohol-related problems, which would account for the prospective association between discrimination and alcohol problems.

Structural equation modeling indicated that discrimination was associated cross-sectionally with negative affect and more coping motives for drinking, but not with greater alcohol expectancies. Coping motives mediated the prospective relationship between discrimination and alcohol-related problems. Additionally, results indicated significant indirect effects from discrimination to alcohol-related problems through negative affect and coping motives. These associations were evident for multiple groups confronting status-based discrimination, including women, racial/ethnic minorities, and lesbian/gay/bisexual individuals.

This study identified potential affective mechanisms linking discrimination to alcohol-related problems. Results suggest several avenues for prevention and intervention efforts with individuals from socially disadvantaged groups.


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Request Reprint E-Mail:  lynsay.ayer@uvm.edu

Drinking and stress: An examination of sex and stressor differences using IVR-based daily data

Research on the relation of stress to alcohol consumption is inconsistent regarding the direction of effects, and this association has been shown to vary by sex and type of stress. We sought to build upon the stress–drinking literature by examining the direction of the stress–drinking association over time as well as sex and stressor differences using daily data.

246 heavy drinking adults (67% men) aged 21–82 reported daily stress levels and alcohol consumption over 180 days using Interactive Voice Response (IVR). Baseline daily hassles were examined as an alternative measure of stress. Generalized estimating equations (GEEs) were conducted to test the stress–drinking association accounting for alcohol dependency at baseline and sex and stressor type as moderators.

IVR daily stress predicted increased alcohol consumption the following day, whereas baseline level of daily hassles did not. Examining the opposite direction of effects, IVR ratings of daily alcohol consumption predicted decreased next-day stress. Stress predicted higher alcohol consumption the next day for men but there was no significant association for women. For both sexes, drinking predicted decreased stress the next day, but this effect was stronger for women.

This study generally supported the drinking to cope and self-medication hypotheses, with findings that increased stress led to increased drinking. The time-varying relation between stress and alcohol appears to be sex- and measure-specific, however. Therefore, interventions targeted at stress management found to be effective for one sex should not be presumed to be applicable to the other.


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Request Reprint E-Mail:   lynsay.ayer@uvm.edu 

Evaluating the validity and utility of scaling alcohol consumption indices alongside AUD symptoms in treatment-seeking adolescents

Current initiatives to update diagnostic criteria for alcohol use disorders (AUDs) have stimulated dialogue about the usefulness of indicators of alcohol consumption in the diagnosis of AUDs.

This study used Rasch model analyses to examine the properties of alcohol consumption descriptors and AUD symptoms among 3382 treatment-seeking adolescents, aged 12–18 years, in the DATOS-A (United States Department of Health and Human Services, 1993–1995) baseline assessment, and evaluated the predictive validity of different scoring methods (with and without alcohol consumption) for 12-month alcohol involvement.

Rasch model analyses supported the unidimensionality of indices of alcohol consumption and AUD symptoms. Test information functions showed that adding consumption items provides further information at all points of the alcohol involvement severity spectrum. Combining AUD symptoms with indices of alcohol consumption provided better prediction of alcohol involvement after treatment than either AUD symptom counts or DSM-IV dependence diagnosis alone. Differential item functioning (DIF), however, was observed for select items. Generally, indices of drinking “too much too fast” were more severe for females, African Americans and Hispanics, while the opposite was true for items measuring “too much too often”. For age, “too much too often” items were more severe for the younger (12–14 years) age group, and AUD symptoms were more severe for the older (15–18 years) age group.

Indices of alcohol consumption can be validly scaled along with AUD symptoms in this population, and their inclusion provides statistical measurement advantages. Nevertheless, caution is necessary in using consumption items in measuring alcohol involvement due to DIF observed across sex, race and age.


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Request Reprint E-Mail:   bhoeppner@partners.org   

Genetic moderators and psychiatric mediators of the link between sexual abuse and alcohol dependence

This study used a case–control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that might affect treatment planning.

A case–control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes.

The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities.

Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women.


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Request Reprint E-Mail: William.Copeland@duke.edu   

Alcohol Use Trajectories and Problem Drinking Over the Course of Adolescence: A Study of North American Indigenous Youth and Their Caretakers

This study investigated the links between alcohol use trajectories and problem drinking (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition abuse/dependence) using five waves of data from 727 North American Indigenous adolescents between 10 and 17 years from eight reservations sharing a common language and culture. 

Growth mixture models linking fundamental causes, social stressors, support, and psychosocial pathways to problem drinking via alcohol use trajectories over the early life course were estimated. 

Results indicated that 20 percent of the adolescents began drinking at 11 to 12 years of age and that another 20 percent began drinking shortly thereafter. These early drinkers were at greatly elevated risk for problem drinking, as were those who began drinking at age 13. 

The etiological analysis revealed that stressors (e.g., perceived discrimination) directly and indirectly influenced early and problem alcohol use by decreasing positive school attitudes while increasing feelings of anger and perceived delinquent friendships. 

Girls were found to be at risk independently of these other factors. 

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Request Reprint E-Mail:   j.e.cheadle@gmail.com 

RISKY SINGLE OCCASION DRINKING RESEARCH: THE FOUR STAGES OF ENLIGHTENMENT

We are grateful for the comments of our highly esteemed  colleagues.

First, they raise concerns about the name and definition of the underlying concept [1,2].While the sociology of research of binge drinking is interesting [2], our aim
was much more modest: we have been trying to clarify a concept which could help research to better interpret the myriad of empirical findings. With this objective in mind
and to avoid confusion, we prefer the term risky single occasion drinking (RSOD) in order to separate it from more chronic heavy drinking. Second, to define the cut-off for RSOD.   > > > >   Read More

MUSINGS ON NEW AUSTRALIAN GUIDELINES FOR REDUCING THE RISK FROM SINGLE OCCASION DRINKING

Gmel et al. [1] draw our attention to several important issues in relation to our understanding of ‘risky single
occasion drinking’ (RSOD), its consequences and the literature
on which it is based. I, for one, am appreciative of their efforts to make sense of this literature. The questions I raise at the end of this commentary arise from reflections,
inspired by the paper, on recent past events around Australia’s national drinking (alcohol) guidelines.   > > > >   Read More

RISKY SINGLE DRINKING OCCASIONS OR ACUTE ALCOHOL INTOXICATIONS?

Gmel et al. [1] deserve recognition for raising a key issue that tends to be forgotten. The fact that alcohol is a drug, the effects of which are mainly deletereous to human health, does not preclude us from analysing how different drinking patterns may produce different types of harm.
Clinicians have known for many years that daily heavy drinkers tend to present with a series of chronic physical  diseases, while heavy episodic drinkers are more prone
to present with higher levels of behavioural disturbances which often lead to traumas and injuries.
> > > >    Read More

BETWEEN SYMBOLS AND TECHNICALITIES – A CONCEPT OF BINGE DRINKING

Gmel et al. [1] approach a concept of binge drinking from a technical perspective. They indicate that risky single occasion drinking (RSOD) or binge drinking measures may include or hide heavy volume drinking, which is very likely to overestimate the association between RSOD and chronic complications. In other words, they claim rightly that a certain proportion of those classified as bingers are also chronic high-volume drinkers. The latter 

is often not considered in numerous studies showing the detrimental effects of binge or risky single-occasion drinking. While discussing these major questions, the authors show numerous examples of conceptual confusion with regard to definition of a drink and various cut-off levels applied in different countries and/or in different studies, which is very likely to produce miscommunication within a research world and between research and the ‘real’ world.
> > > >  Read More

THE CHALLENGE OF DISTINGUISHING HIGH-VOLUME AND FREQUENT RISKY DRINKING

The review of risky single-occasion drinking (RSOD) by Gmel et al. [1] is comprehensive and provocative. It
addresses concerns that fall into two domains, those that hamper international comparisons and those that are problematic within, as well as across, countries. As examples of the former, disparate approaches to defining standard drinks and drinking occasions may be warranted based on cross-country variation in beverage container sizes and temporal drinking patterns; however, these disparities make comparisons across countries difficult. In contrast, the lack of distinction between frequent RSOD and high-volume consumption exemplifies a conceptual problem that poses challenges within as well
as across countries.   > > > > Read More

Brief Interventions in Dependent Drinkers: A Comparative Prospective Analysis in Two Hospitals

To investigate whether brief interventions (BIs) delivered by a dedicated Alcohol Specialist Nurse (ASN) to non-treatment-seeking alcohol-dependent patients in an acute hospital setting are effective in reducing alcohol consumption and dependence.  

A prospective cohort control study in two acute NHS Hospital Trusts in the North West England, one of which provided BI (university teaching hospital—test site) while the other did not (district general hospital—control site), including follow-up BIs. Subjects were alcohol-dependent patients aged ≥18 years.  

A total of 100 patients were recruited at each site. No differences were found between the groups in the baseline demographic parameters or medical co-morbidities. At the test site, further sessions were sometimes offered, and 46 patients received more than one intervention (median 4, mean 6.3 and maximum 20). At 6 months, alcohol consumption (P < 0.0001), Alcohol Use Disorders Identification Tool (AUDIT) score (P < 0.0001) and Severity of Alcohol Dependence Questionnaire score (P = 0.0001) were significantly lower at the test site than the control site. Outcomes were found to be independent of both the baseline level of dependence and medical co-morbidity. 

BI delivered by a dedicated ASN for non-treatment-seeking alcohol-dependent individuals, who often have significant medical co-morbidities, seem to be effective in an acute hospital setting. This study provides a framework to inform the design of a future randomized controlled trial. 


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Request Reprint E-Mail:  lynno@liv.ac.uk 

Supervised Disulfiram in the Treatment of Alcohol Use Disorder: A Commentary

This commentary discusses the systematic review “The efficacy of disulfiram for the treatment of alcohol use disorder (AUD)” by Jørgensen and colleagues (2011, Alcohol Clin Exp Res ). The main focus of the commentary is on long-term effects, long-term use, and psychotherapeutic application of supervised disulfiram.

A brief qualitative overview is given of previous and recent clinical studies on disulfiram in alcoholism treatment.

The alcohol deterrent disulfiram is an effective pharmacological adjunct to the treatment of AUD when it is administered as supervised low-dose disulfiram and is integrated in comprehensive biopsychosocial alcoholism therapy. However, the assumed underlying psychological effects of psychotherapeutic disulfiram application have never been properly investigated. Prospective long-term follow-up studies are rare and suggest that long-term effects of disulfiram are associated with long-term use and/or integration of the medication in cognitive behavior therapy.

Evidence from decades of research suggests psychological effects as principal mode of action of supervised disulfiram. Future randomized controlled trials are needed that investigate psychological actions and long-term outcomes of this alcohol deterrent.


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Request Reprint E-Mail: henning.krampe@charite.de  

Chronic Alcohol Ingestion Exacerbates Lung Epithelial Barrier Dysfunction in HIV-1 Transgenic Rats

Alcohol abuse and HIV-1 infection frequently coexist, and these individuals are at high risk for serious lung infections and respiratory failure. Although alcohol ingestion and HIV-1 transgene expression have been shown to independently cause oxidative stress and disrupt alveolar epithelial barrier function in experimental models, their interactive effects have not been examined.

In this study, we determined that chronic alcohol ingestion (12 weeks) exacerbated the already significant defects in alveolar epithelial paracellular permeability and lung liquid clearance in HIV-1 transgenic rats.

Further, immunocytochemical analyses of tight junction protein expression in primary alveolar epithelial cells showed that occludin and zonula occludens-1 localization within the plasma membrane was more disrupted than in either condition alone, consistent with the observed defects in epithelial barrier function.

Interestingly, expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), the transcription factor required to activate the antioxidant-response element, was decreased in primary alveolar epithelial cells isolated from HIV-1 transgenic rats. In parallel, exposing lung epithelial cells in vitro to either alcohol or the HIV-related protein gp120 also decreased Nrf2 expression.

Importantly, treatment with procysteine, which increases thiol antioxidants including glutathione, improved tight junction protein localization in the plasma membrane and restored alveolar epithelial barrier function in alcohol-fed HIV-1 transgenic rats.

These results provide novel evidence that HIV-related proteins and alcohol together causes more barrier dysfunction in the lung epithelium than either stress alone. However, these significant effects on the alveolar barrier can be mitigated by augmenting the thiol antioxidant pool, a strategy with potential clinical applications in subjects who are highly vulnerable to lung disease because of coexistent alcohol abuse and HIV infection.


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Request Reprint E-Mail:  xfan@emory.edu 

Interaction Between Family History of Alcoholism and Locus of Control in the Opioid Regulation of Impulsive Responding Under the Influence of Alcohol

Naltrexone (NTX) is an opioid antagonist indicated for the treatment of alcoholism, which is not universally effective. Thus, identifying individual predictors of NTX’s behavioral effects is critical to optimizing its therapeutic use. Moreover, given the high rate of relapse during treatment for alcoholism, understanding NTX’s behavioral effects when combined with moderate ethanol intake is important. Our previous study of abstinent alcoholics and control subjects showed that a more internal Locus of Control score predicted increased impulsive choice on NTX (Mitchell et al., 2007, Neuropsychopharmacology 32:439–449). Here, we tested whether this predictive relationship remains in the context of moderate alcohol intake.

In this study, we tested the effect of acute NTX (50 mg) on impulsive choice, motor inhibition, and attentional bias after ingestion of moderate ethanol (∼0.3 g/kg, n = 30 subjects). Subjects included those recruited from a pool of ∼1,200 UC Berkeley undergraduates on the basis of scores on the Barratt Impulsiveness Scale (BIS).

Impulsive choice was positively correlated with breath alcohol concentration in placebo sessions. Locus of Control was again the sole predictor of NTX’s effect on decision making among subjects with a family history of alcoholism. We also found a weak interaction between BIS scores and NTX’s effect on impulsive choice.

Our results reinforce the predictive relationship between Locus of Control and NTX’s effect on decision making in those with a family history of alcoholism, suggesting a possible biological basis to this relationship.


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Request Reprint E-Mail:  cab@unc.edu 

The Association Between the SLC6A3 VNTR 9-Repeat Allele and Alcoholism—A Meta-Analysis

Dopamine transporter gene (SLC6A3) represents a promising candidate involved in the development of alcoholism. 

This study aimed to explore the association between the 9-repeat allele (A9) of a 40-bp variable number tandem repeat (VNTR) polymorphism in the 3′ un-translated region (3′ UTR) of the SLC6A3 gene and alcoholism.

The SLC6A3 VNTR was genotyped by PCR in unrelated Mexican Americans including 337 controls and 365 alcoholics. Pearson’s chi-square test or Fisher’s exact test was used to compare the genotype and allele distribution. Meta-analyses were performed for population-based case–control association studies of the SLC6A3 VNTR polymorphism with alcoholism. Data were analyzed under random effect models with the Comprehensive Meta-analysis (v.2) statistical software package.

In Mexican Americans, no significant difference was found in allele and genotype distribution between controls and alcoholics or between controls and alcoholics with alcohol withdrawal seizure (AWS) or delirium tremens (DT) (unadjusted p > 0.05). A total of 13 research articles were included in the meta-analyses.

No significant difference of the SLC6A3 VNTR A9 was noted between controls and alcoholics at the genotypic and allelic level when all ethnic populations, only Caucasian populations, or only Asian populations were considered (p > 0.05).

Significant associations were observed between SLC6A3 VNTR A9 and alcoholics with AWS or DT at the genotypic as well as allelic level when all ethnic populations or only Caucasian populations were considered (p < 0.05, OR 1.5–2.1).

Meta-analyses suggest a possible association between the SLC6A3 VNTR A9 and alcoholic subgroup with AWS or DT.


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Request Reprint E-Mail:   ywan@kumc.edu  

Motivational interviewing for substance abuse

There are 76.3 million people with alcohol use disorders worldwide and 15.3 million with drug use disorders. Motivational interviewing (MI) is a client-centred, semi-directive method for enhancing intrinsic motivation to change by exploring and resolving ambivalence. The intervention is used widely, and therefore it is important to find out whether it helps, harms or is ineffective.

To assess the effectiveness of motivational interviewing for substance abuse on drug use, retention in treatment, readiness to change, and number of repeat convictions.

We searched 18 electronic databases, 5 web sites, 4 mailing lists, and reference lists from included studies and reviews. Search dates were November 30, 2010 for Cochrane Library, Medline, Embase and PsychINFO.

Randomized controlled trials with persons dependent or abusing substance. Interventions were MI or motivational enhancement therapy. The outcomes were extent of substance abuse, retention in treatment, motivation for change, repeat conviction.

Three authors independently assessed studies for inclusion, and two authors extracted data. Results were categorized into (1) MI versus no-treatment control, (2) MI versus treatment as usual, (3) MI versus assessment and feedback, and (4) MI versus other active treatment. Within each category, we computed meta-analyses separately for post-intervention, short, medium and long follow-ups.

We included 59 studies with a total of 13,342 participants. Compared to no treatment control MI showed a significant effect on substance use which was strongest at post-intervention SMD 0.79, (95% CI 0.48 to 1.09) and weaker at short SMD 0.17 (95% CI 0.09 to 0.26], and medium follow-up SMD 0.15 (95% CI 0.04 to 0.25]). For long follow-up, the effect was not significant SMD 0.06 (95% CI-0.16 to 0.28). There were no significant differences between MI and treatment as usual for either follow-up post-intervention, short and medium follow up. MI did better than assessment and feedback for medium follow-up SMD 0.38 (95% CI 0.10 to 0.66). For short follow-up, there was no significant effect . For other active intervention there were no significant effects for either follow-up.

There was not enough data to conclude about effects of MI on the secondary outcomes.


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Request Reprint E-Mail:  geir.smedslund@diakonsyk.no   

New variable selection methods for zero-inflated count data with applications to the substance abuse field

Zero-inflated count data are very common in health surveys. This study develops new variable selection methods for the zero-inflated Poisson regression model.
 

Our simulations demonstrate the negative consequences which arise from the ignorance of zero-inflation. 

Among the competing methods, the one-step SCAD method is recommended because it has the highest specificity, sensitivity, exact fit, and lowest estimation error. The design of the simulations is based on the special features of two large national databases commonly used in the alcoholism and substance abuse field so that our findings can be easily generalized to the real settings. 

Applications of the methodology are demonstrated by empirical analyses on the data from a well-known alcohol study. 

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Request Reprint E-Mail:   buu@umich.edu

Artificial Sweeteners, Caffeine, and Alcohol Intoxication in Bar Patrons

Previous laboratory research on alcohol absorption has found that substitution of artificially sweetened alcohol mixers for sucrose-based mixers has a marked effect on the rate of gastric emptying, resulting in elevated blood alcohol concentrations. Studies conducted in natural drinking settings, such as bars, have indicated that caffeine ingestion while drinking is associated with higher levels of intoxication. 

To our knowledge, research has not examined the effects of alcohol mixers that contain both an artificial sweetener and caffeine, that is, diet cola. Therefore, we assessed the event-specific association between diet cola consumption and alcohol intoxication in bar patrons. We sought to determine whether putative increases in blood alcohol, produced by accelerated gastric emptying following diet cola consumption, as identified in the laboratory, also appear in a natural setting associated with impaired driving.

We conducted a secondary analysis of data from 2 nighttime field studies that collected anonymous information from 413 randomly selected bar patrons in 2008 and 2010. Data sets were merged and recoded to distinguish between energy drink, regular cola, diet cola, and noncaffeinated alcohol mixers.

Caffeinated alcohol mixers were consumed by 33.9% of the patrons. Cola-caffeinated mixed drinks were much more popular than those mixed with energy drinks. A large majority of regular cola-caffeinated mixed drink consumers were men (75%), whereas diet cola-caffeinated mixed drink consumers were more likely to be women (57%). 

After adjusting for the number of drinks consumed and other potential confounders, number of diet cola mixed drinks had a significant association with patron intoxication (β = 0.233, p < 0.0001). Number of drinks mixed with regular (sucrose-sweetened) cola and energy drinks did not have significant associations with intoxication (p > 0.05).

Caffeine’s effect on intoxication may be most pronounced when mixers are artificially sweetened, that is, lack sucrose which slows the rate of gastric emptying of alcohol. Risks associated with on-premise drinking may be reduced by greater attention given to types of mixers, particularly diet colas.


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dennis.thombs@unthsc.edu

Ethanol-Induced Microphthalmia is Not Mediated by Changes in Retinoic Acid or Sonic Hedgehog Signaling During Retinal Neurogenesis

Microphthalmia (reduced eye size), generally accompanied by vision defects, is a hallmark of fetal alcohol spectrum disorder (FASD) in humans. In zebrafish, embryonic ethanol exposure over the time of retinal neurogenesis also results in microphthalmia. This microphthalmia is in part the consequence of reduced retinal cell differentiation, including photoreceptors.

Here we pursue 2 signaling pathways implicated in other aspects of FASD pathogenesis: retinoic acid (RA) and Sonic hedgehog (Shh).

We evaluated markers for RA and Shh signaling within the eyes of embryos treated with ethanol during the period of retinal neurogenesis. We also performed rescue experiments using administration of exogenous RA and microinjection of cholesterol, which augments Shh signaling.

Using sequential or co-treatments, RA did not rescue ethanol-induced microphthalmia at any concentration tested. In addition, RA itself caused microphthalmia, although the underlying mechanisms were distinct from those of ethanol. Interestingly, RA treatment appeared to recover photoreceptor differentiation in a concentration-dependent manner. This may be an independent effect of exogenous RA, as ethanol treatment alone did not alter RA signaling in the eye. Cholesterol injection also did not rescue ethanol-induced microphthalmia at any concentration tested, and ethanol treatments did not alter expression of shh, or of ptc-2, which is normally regulated by Shh signaling.

Together these findings indicate that, during the time of retinal neurogenesis, effects of ethanol on eye development are likely independent of the RA and Shh signaling pathways. 

These studies suggest that FASD intervention strategies based upon augmentation of RA or Shh signaling may not prevent ethanol-induced microphthalmia.


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Commentary: Will Analyzing the Epigenome Yield Cohesive Principles of Ethanol Teratology?

This commentary discusses the impact of the manuscript by Zhou et al., titled “Alcohol Alters DNA Methylation Patterns and Inhibits Neural Stem Cell Differentiation,” published in the April 2011 issue of Alcoholism: Clinical and Experimental Research (volume 35, issue 4, pages 1–12). 

In this manuscript, the authors present intriguing evidence from a genome scale analysis of promoter DNA methylation patterns in a class of neural crest stem cells associated with dorsal root ganglia, showing that ethanol essentially prevents epigenetic programming associated with neural stem cell differentiation. 

This manuscript presents several interesting and novel pieces of data and raises important questions for future research. 

The implications of these data for our understanding of the etiology of fetal alcohol spectrum disorders are discussed.

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