Integration of alcohol use disorders identification and management in the tuberculosis programme in Tomsk Oblast, Russia

The European Journal of Public Health Advance Access published online on December 26, 2008

Alcohol use disorders (AUDs) among tuberculosis (TB) patients are associated with nonadherence and poor treatment outcomes.

We developed a multidisciplinary model to manage AUDs among TB patients in Tomsk, Russia.

First, we assessed current standards of care through stakeholder meetings and ethnographic work. The Alcohol Use Disorders Identification Test (AUDIT) was incorporated into routine assessment of all patients starting TB treatment. We established treatment algorithms based on AUDIT scores. We then hired specialists and addressed licensing requirements to provide on-site addictions care.

Our experience offers a successful model in the management of co-occurring AUDs among patients with chronic medical problems.

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Request Reprint E-Mail: tmathew@medicine.umsmed.edu

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ADD Bulletin 5/2008: Malawi and WHO

Invitation to an NGO Alliance for a Global Strategy

NGOs worldwide are now invited to join an information sharing network connected to the WHO process leading up to a Global Strategy on alcohol. More information on how your organization can be affiliated to the network can be found here.
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FORUT signs agreement with the Government of Malawi

The Government of Malawi and the Norwegian development NGO FORUT recently signed an agreement to cooperate on alcohol and drug prevention. The new Memorandum of Understanding is outlining the ambitions, intentions and motivation for the cooperation between the Government of the Republic of Malawi and FORUT. The parties have the common understanding that alcohol and drugs are obstacles to development and that it is important to develop evidence based alcohol policy and local prevention strategies to combat the harm of alcohol and drug.
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WHO Commission on Social Determinants of Health

Closing the gap in health inequities in a generation is the ambitious goal described in the report from the WHO Commission on Social Determinants on Health. The Commission calls on the WHO and all governments to lead global action on the social determinants of health with the aim of achieving health equity.
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Alcohol Primes the Airway for Increased Interleukin-13 Signaling
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Using an experimental model of airway fibrosis following lung transplantation, we recently showed that chronic alcohol ingestion by donor rats amplifies airway fibrosis in the recipient. Associated with alcohol-mediated amplification of airway fibrosis is increased transforming growth factor β-1(TGFβ1) and α-smooth muscle actin expression. Other studies have shown that interleukin-13 (IL-13) modulates TGFβ1 signaling during experimentally-induced airway fibrosis.

Therefore, we hypothesized that IL-13 is a component of alcohol-mediated amplification of pro-fibrotic mediators in the alcoholic lung.

Interleukin-13 expression was detected in type II alveolar epithelial cells and human bronchial epithelial cells, but not in lung fibroblasts. IL-13 expression was decreased in whole lung and type II cells in response to alcohol exposure. In all cell types analyzed, expression of IL-13 signaling receptor (IL-13Rα1) mRNA was markedly increased. In contrast, mRNA and protein expression of the IL-13 decoy receptor (IL-13Rα2) were decreased in all cells analyzed. Exposure to alcohol also increased STAT6 phosphorylation in response to IL-13 and lipopolysaccharide.

Data from multiple cell types in the pulmonary system suggest that IL-13 and its receptors play a role in alcohol-mediated activation of pro-fibrotic pathways. Taken together, these data suggest that alcohol primes the airway for increased IL-13 signaling and subsequent tissue remodeling upon injury such as transplantation.

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Request Reprint E-Mail: pmitche@emory.edu
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Alcohol Functionally Upregulates Toll-Like Receptor 2 in Airway Epithelial Cells
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Alcoholics are known to have more severe airway diseases of the lung, such as bronchitis. Little is known about why this phenomenon is observed. We hypothesized that alcohol may modulate Toll-like receptor 2 (TLR2), which regulates inflammation caused by gram-positive bacteria.

Alcohol, at biologically relevant concentrations (25 to 100 mM), caused a 2 to 3-fold time- and concentration-dependent increase in TLR2 mRNA in normal human bronchial epithelial cells and 16HBE 14o- cells. Western blots for TLR2 revealed a qualitative increase in TLR2 protein in cells exposed to 100 mM alcohol. FACS showed that TLR2 was quantitatively increased on the surface of airway epithelial cells that were exposed to alcohol. Airway cells that were primed with alcohol produced nearly twice as much IL-8 in response to 40 ng of peptidoglycan than naive cells.

Alcohol upregulates TLR2 message and protein in the airway epithelium. This leads to exaggerated inflammation in response to environmental stimuli that would normally be well tolerated in airway epithelial cells. This may be a partial explanation of why alcoholics have more severe airway disease than nonalcoholics.

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Request Reprint E-Mail: jsisson@unmc.edu
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Characterization of White Matter Microstructure in Fetal Alcohol Spectrum Disorders
Alcoholism: Clinical and Experimental Research Published Online: 22 Dec 2008

Exposure to alcohol during gestation is associated with CNS alterations, cognitive deficits, and behavior problems. This study investigated microstructural aspects of putative white matter abnormalities following prenatal alcohol exposure.

Prenatal alcohol exposure was associated with low FA in multiple cerebral areas, including the body of the corpus callosum and white matter innervating bilateral medial frontal and occipital lobes. Fewer between-group differences in MD were observed.

These data provide an account of cerebral white matter microstructural integrity in fetal alcohol spectrum disorders and support extant literature showing that white matter is a target of alcohol teratogenesis. The white matter anomalies characterized in this study may relate to the neurobehavioral sequelae associated with gestational alcohol exposure, especially in areas of executive dysfunction and visual processing deficits.

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Request Reprint E-Mail: sfryer@ucsd.edu.
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Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis

Human Molecular Genetics Advance Access published online on November 7, 2008

Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated.

This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use, and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSMIIIR criteria for AD.

There were study-wide significant associations (p<2.3x10–4) p="8.2x10–7)," p="2.7x10–6)," p="2.7x10–6)" p="8.9x10–8)">

After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (p=4.7x10–5) and suggestive associations (p<0.001)>

These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake.

The absence of study-wide significant effects on alcohol dependence results from the low p-value required when testing multiple SNPs and phenotypes.

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Request Reprint E-Mail: stuart.macgregor@qimr.edu.au
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NHS must take long term approach to tackling unhealthy lifestyles

A new report states the NHS needs to change its approach to health prevention in order to successfully impact on key health risks including alcohol misuse, obesity and smoking. 'Commissioning and behaviour change; Kicking Bad Habits', produced by the King's fund, says more work is needed to ensure NHS staff are suitably skilled to ensure people choose and maintain healthier lifestyles. A long term approach from the NHS must be delivered as the UK's unhealthy habits are deep-rooted within society and can not be addressed by short term measures. . . . . .

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Editorial: Raise Wisconsin's alcohol tax to help address issue

December 22, 2008

We know that too many people in Wisconsin drive drunk. We read about repeat drunken driving offenders almost every day.

And, as The Post-Crescent revealed in its extensive State of Drinking series last summer, Wisconsinites have a litany of other alcohol-related problems that rank high among states in the nation.

We appreciate that the Wisconsin District Attorneys Association wants to raise the state's beer and liquor taxes. This is long overdue. The beer tax hasn't been raised in almost 40 years and the tax on alcohol hasn't gone up since 1981. . . . . .

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Social anxiety disorder as a risk factor for alcohol use disorders: A prospective examination of parental and peer influences

Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 128-137

Elucidation of mechanisms underlying the high rates of alcohol use disorder (AUD) remains a pressing clinical and research concern. Despite data indicating that social anxiety disorder (SAD) may be a psychological vulnerability that increases AUD risk, no known prospective research has examined underlying mechanisms. Given the nature of SAD, social support and peer alcohol use may be implicated.

The present study set out to clarify the SAD–AUD link in several ways using a prospective dataset comprised of 1803 (47% female) young adults at T1, 1431 of whom were assessed again approximately 3 years later. First, stringent criteria were used to directly test whether SAD was a risk for AUD. Second, we examined whether social support and peer alcohol use moderated the prospective SAD–AUD link. Structured diagnostic interviews were conducted to assess DSM-IV Axis I disorders, negative life events, social support, and peer alcohol use.

Among men, Time 1 (T1) SAD was not significantly related to Time 2 (T2) AUD. Yet, among women, T1 SAD was related to T2 AUD. Further, T1 SAD was the only internalizing disorder to significantly predict T2 AUD after controlling for relevant variables (e.g., T1 depression, other anxiety, alcohol and marijuana use disorders). The SAD–AUD relation demonstrated directional specificity. Family cohesion and adverse family relations significantly moderated this relation.

Findings highlight the important role of SAD and familial support in the onset of AUD among women.

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Request Reprint E-Mail: jbuckner@lsu.edu

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Change over time in alcohol consumption in control groups in brief intervention studies: systematic review and meta-regression study

Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 107-114

Reactivity to assessment has attracted recent attention in the brief alcohol intervention literature. This systematic review sought to examine the nature of change in alcohol consumption over time in control groups in brief intervention studies.

Primary studies were identified from existing reviews published in English language, peer-reviewed journals between 1995 and 2005. Change in alcohol consumption and selected study-level characteristics for each primary study were extracted. Consumption change data were pooled in random effects models and meta-regression was used to explore predictors of change. Eleven review papers reported the results of 44 individual studies. Twenty-six of these studies provided data suitable for quantitative study.

Extreme heterogeneity was identified and the extent of observed reduction in consumption over time was greater in studies undertaken in Anglophone countries, with single gender study participants, and without special targeting by age. Heterogeneity was reduced but was still substantial in a sub-set of 15 general population studies undertaken in English language countries.

The actual content of the control group procedure itself was not predictive of reduction in drinking, nor were a range of other candidate variables including setting, the exclusion of dependent drinkers, the collection of a biological sample at follow-up, and duration of study.

Further investigations may yield novel insights into the nature of behaviour change with potential to inform brief interventions design.

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Request Reprint E-Mail: Jim.McCambridge@lshtm.ac.uk

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Acute effects of alcohol on inhibitory control and information processing in high and low sensation-seekers

Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 91-99

Sensation-seeking is a personality characteristic that has been associated with drug abuse. Some evidence suggests that sensation-seekers might experience increased rewarding effects from drugs of abuse, possibly contributing to the association between sensation-seeking and risk for drug abuse.

The present study examined the effects of three doses of alcohol (0.0 g/kg, 0.45 g/kg, and 0.65 g/kg) on inhibitory control, information processing, and subjective ratings in a group of high sensation-seekers and a group of low sensation-seekers (N = 20). Inhibitory control was measured by a cued go/no-go task and speed of information processing was assessed by the Rapid Information Processing (RIP) task.

Alcohol impaired inhibitory control and information processing. Group differences were also observed. Compared with their low sensation-seeking counterparts, high sensation-seekers demonstrated increased sensitivity to the subjective rewarding effects of alcohol and a poorer degree of inhibitory control that was further impaired by alcohol.

The findings highlight reward- and cognitive-based mechanisms by which sensation-seeking could operate to increase risk for alcohol abuse.

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Request Reprint E-Mail: fillmore@uky.edu

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Induction of brain CYP2E1 changes the effects of ethanol on dopamine release in nucleus accumbens shell

Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 83-90

CYP2E1 is an important enzyme involved in the brain metabolism of ethanol that can be induced by chronic consumption of alcohol. Recent works have highlighted the importance of this system in the context of the behavioural effects of ethanol. Unfortunately, the underlying neurochemical events for these behavioural changes, has not been yet explored.

In this work, we have started this exploration by analyzing the possible changes in the neurochemical response of the mesolimbic system to ethanol after pharmacological induction of brain CYP2E1. We have used the dopamine extracellular levels in nucleus accumbens (NAc) core and shell, measured by means of microdialysis in vivo, as an index of the effects of ethanol.

Acetone 1% in the tap water was used to induce brain CYP2E1. Efficacy of the induction protocol was assessed by immunoblotting. Intravenous administration of 1.5 g/kg of ethanol in control rats provoked a significant increase of the dopamine levels in both the core (up to 127% of baseline) and the shell (up to 122% of baseline) of the NAc. However, the same dose of ethanol in acetone-treated rats only increased the dopamine extracellular levels in the core (up to 142% of baseline) whereas dopamine levels in the shell subregion remain unaltered relative to baseline.

The results of this study indicate that induction of CYP2E1 changes the response of the mesolimbic system to ethanol in a region-dependent manner. Two hypotheses are postulated to explain the observed effects.

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Request Reprint E-Mail: lfgran@uv.es

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The Alcohol Use Disorders Identification Test revisited: Establishing its structure using nonlinear factor analysis and identifying subgroups of respondents using latent class factor analysis

Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 71-82

Previous research used principal components as well as exploratory and confirmatory factor analysis to establish continuous dimensions underlying answers to the 10-items of the Alcohol Use Disorders Identification Test (AUDIT). The majority of these studies conclude that one consumption dimension and an adverse consequences dimension explain the answers to the AUDIT sufficiently. However, most of the methods used presuppose normal answer distributions and linear relations between indicators and constructs, which are unrealistic assumptions for AUDIT answer.

First, to investigate the continuous factor analytic structure underlying the answers to all AUDIT items. Second and third, to assess the impact of consumption as well as age and gender on AUDIT consequences dimension. Fourth and fifth, to categorize respondents into subgroups based on the AUDIT consequences items and adjusting the subgroups for differences in consumption, age and gender. Sixth, to describe the subgroups with respect to further adverse consequences of drinking.

Nonlinear factor analyses suggested two continuous correlated factors reflecting the adverse consequences of alcohol use: (1) harmful alcohol use, (2) alcohol dependence (aim 1). Consumption items did not prove to be reasonable construct indicators, but adverse consequences were predicted by consumption (aim 2), and also by age and gender (aim 3). Latent class factor analysis identified four subgroups based on the AUDIT consequences items (aim 4): one not affected (66%), and three subgroups defined by either harmful (15%) or dependent (9%), or combined harmful and dependent use (10%). These groups differed also with respect to further alcohol use consequences. Adjusting the subgroups for differences in consumption, age and gender (aim 5) reduced the non-affected subgroup and increased the subgroup with harmful and dependent use.

The AUDIT items cover three separable domains, i.e. consumption, harmful and dependent use, as originally intended. Hence, assessment of alcohol use does not substitute for assessing adverse consequences, as assumed in short versions of the AUDIT comprising only the AUDIT consumption items. Further, the dimensional as well as the LCFA subgroup solution imply that the respondents cannot be ordered along a single severity dimension without loss of information.

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Request Reprint E-Mail: rist@psy.uni-muenster.de

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Alcohol use disorders in patients with obsessive–compulsive disorder: The importance of appropriate dual-diagnosis

Drug and Alcohol DependenceVolume 100, Issues 1-2, 1 February 2009, Pages 173-177

To evaluate the prevalence and clinical associated factors of alcohol use disorders (AUD) comorbidity in a large clinical sample of patients with obsessive–compulsive disorder (OCD).

Forty-seven patients (7.5%) presented AUD comorbidity. Compared to OCD patients without this comorbidity they were more likely to be men, to have received previous psychiatric treatment, to present lifetime suicidal thoughts and attempts and to have higher scores in the hoarding dimension. They also presented higher comorbidity with generalized anxiety and somatization disorders, and compulsive sexual behavior. Substance use was related to the appearance of the first O.C. symptoms and symptom amelioration.

Although uncommon among OCD treatment seeking samples, AUD comorbidity has specific clinical features, such as increased risk for suicidality, which deserve special attention from mental health professionals. Future studies focused on the development of specific interventions for these patients are warranted.

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Request Reprint E-Mail: afgentil@gmail.com

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Age of Onset and Temporal Sequencing of Lifetime DSM-IV Alcohol Use Disorders Relative to Comorbid Mood and Anxiety Disorders

Drug Alcohol Depend. 2008 April 1; 94(1-3): 234–245.

Understanding the temporal sequencing of alcohol use disorders (AUDs) nd comorbid mood and anxiety disorders may help to disentangle the etiological underpinnings of comorbidity. Methodological limitations of previous studies, however, may have led to inconsistent or inconclusive findings.

To describe the temporal sequencing of the onset of AUDs relative to the onset of specific comorbid mood and anxiety disorders using a large, nationally representative survey.

AUD onset tended to follow the onset of 2 of the 9 mood and anxiety disorders (specific and social phobia). The onset of alcohol abuse tended to precede the onset of 5 of the 9 mood and anxiety disorders (GAD, panic, panic with agoraphobia, major depression, and dysthymia), whereas the onset of alcohol dependence tended to precede the onset of only 2 of the 9 mood and anxiety disorders (GAD and panic). Lag times between primary and subsequent disorders generally ranged from 7–16 years. Comorbid individuals whose alcohol dependence came after panic with agoraphobia, hypomania, and GAD had increased risk of persistent alcohol dependence.

Alcohol abuse, but not dependence, precedes many mood and anxiety disorders. If the primary disorder does in fact play a causative or ontributing role in the development of the subsequent disorder, this role can best be described as “temporally distal.” However, in assessing the risk for persistent alcohol dependence, clinicians should not only consider the type of comorbid mood/anxiety disorder, but also the temporal ordering of these disorders.

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Association of NFKB1, which encodes a subunit of the transcription factor NF-[kappa]B, with alcohol dependence.
Human Molecular Genetics. 17(7):963-970, April 1, 2008.

A broad region on chromosome 4q has been linked to alcohol dependence (alcoholism). We hypothesized that such broad linkage regions represent the combined action of multiple genes.

Seeking to identify genes within that region that are associated with alcoholism, we have tested the association of NFKB1, located at 4q24, with alcoholism. NFKB1 encodes a 105 kDa transcription inhibitor that is cleaved to the 50 kDa DNA-binding subunit of the ubiquitous transcription factor NF-B. NF-B regulates many genes relevant to brain function, and its actions can be potentiated by ethanol; thus, NFKB1 is an excellent candidate gene for alcoholism.

Nineteen SNPs in and near NFKB1 were analyzed in a sample of 219 multiplex alcoholic families of European American descent. Family-based association analyses detected significant evidence of association with eight SNPs and marginal evidence for five more. The association was driven by the affected individuals with earlier onset of alcoholism (55% of the sample with onset 21 years). Further analysis of the age of onset as a quantitative variable provided evidence for the association of 12 SNPs in this gene.

Thus, variations in NFKB1 appear to affect the risk for alcoholism, particularly contributing to an earlier onset of the disease.

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News Release - UCSF Researchers Shed Light on Genetic Factors Behind Alcohol Dependence

By Robin Hindery

Understanding the genetic factors behind alcohol dependence — and using that information to improve treatment — has been the goal of many scientific studies. Now, a group of UCSF researchers has moved one step closer to unraveling what one called the “complicated web” of components that determine an individual’s response to alcohol and likelihood to abuse it.

In a recently published study, scientists from UCSF’s Ernest Gallo Clinic and Research Center took 367 white siblings with a family history of alcohol abuse and had each consume three alcoholic drinks over a 10-minute period at 10 a.m. . . . . .

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Molecular Genetics of Alcohol-Related Brain Damage

Alcohol and Alcoholism Advance Access published online on December 18, 2008

In the scientific literature it has been repeatedly hypothesized that there is a heritable susceptibility to thiamine deficiency comparable to other hereditary metabolic disorders.

The aim of this paper is to review the most recent knowledge on the genetic susceptibility to the development of alcohol-related Wernicke–Korsakoff syndrome (WKS).

A literature review was carried out looking at the molecular genetics studies performed in alcohol-dependent patients affected by WKS.

A genetic component in the pathogenesis of WKS has been postulated since the late seventies. Since then, very few genetic studies have been carried out on candidate genes such as thiamine-dependent enzymes, alcohol-metabolizing enzymes and GABA receptors. The findings are controversial and not conclusive. Several authors reported the important role of the thiamine transporters in the pathogenesis of the thiamine deficiency disorders. Our findings on SLC19A2 and SLC19A3 suggest a potential role of these two genes in the pathophysiology of alcohol-related thiamine deficiency but further studies need to be carried out.

The WKS may be a very complex, multifactorial disorder where the interaction of multiple genes and environment plays an important role in the pathogenesis. However, it is still plausible that megaphenic gene effects are responsible for WKS susceptibility and the thiamine transport genes are good candidates for having such a role. Further genetic studies are definitely needed to investigate the association with candidate genes or linkage with hot spot areas.

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Request Reprint E-Mail: i.guerrini@ucl.ac.uk

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Involvement of A2A receptors in anxiolytic, locomotor and motivational properties of ethanol in mice

Genes, Brain and Behavior Volume 7 Issue 8, Pages 887 - 898

We have shown previously that mice lacking the adenosine A2A receptor (A2AR) generated on a CD1 background self-administer more ethanol and exhibit hyposensitivity to acute ethanol.

We aimed to investigate if the increased propensity of A2A−/− mice to consume ethanol is associated with an altered sensitivity in the motivational properties of ethanol in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms and with an altered development of sensitization to the locomotor effects of ethanol. We also tested their sensitivity to the anxiolytic effects of ethanol.

Our results show that A2A−/− mice produced on a CD1 background displayed a reduced ethanol-induced CPP and an increased sensitivity to the anxiolytic and locomotor-stimulant effects of ethanol, but they did not show alteration in ethanol-induced CTA and locomotor sensitization.

Ethanol-induced CPP, ethanol consumption and the locomotor effects of ethanol were also tested in A2A−/− mice produced on a C57BL/6J background.

Our results emphasized the importance of the genetic background because alteration in ethanol consumption and preference, ethanol-induced CPP and locomotor-stimulant effects were not found in knockout mice produced on the alcohol-preferring C57BL/6J genetic background. Finally, the A2AR agonist, 2-p-(2-carboxyethyl)-phenylethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J mice.

In conclusion, A2AR deficiency in mice generated on a CD1 background leads to high ethanol consumption that is associated with an increased sensitivity to the locomotor-stimulant/anxiolytic effects of ethanol and a decrease in ethanol-induced CPP.

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Request Reprint E-Mail: mickael.naassila@u-picardie.fr

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Children admitted to hospital due to alcohol increasing

By Rebecca Smith, Medical Editor

17 Dec 2008

The number of children admitted to hospital due to alcohol has risen with those living in rural and isolated areas worst affected, official figures have revealed.

Almost 8,000 children under the age of 18 were admitted to hospital in 2006/7 a rise of more than five per cent in three years.

The data from the North West Public Health Observatory has calculated the alcohol-related health problems for each local authority area and found despite awareness campaigns and warnings from doctors illnesses and deaths caused by drinking continue to rise.

Areas with the highest child admissions due to drink are in rural places such as Copeland in Cumbria, the Isle of Wight, Rossendale in Lancashire, Wirral, and Halton in Cheshire.

The highest adult admissions though tended to be in major towns and cities, especially in the North West. . . . . .

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