The Case For Measuring Quality In Mental Health And Substance Abuse Care

Over the past decade, efforts to measure and improve quality have permeated health policy and health care generally but have barely penetrated mental health and substance abuse care. 

We review barriers and recent activities in these areas and propose a short list of quality measures to engage the policy and practice community in a discussion about how best to evaluate the care of people with these conditions. 

Quality measures could include, for example, screening, brief intervention, and referral for alcohol abuse. 

Because proposing a list is only a first step, we suggest other elements of a broader strategy to bring mental health and substance use care into the mainstream of health care quality improvement. 

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Request Reprint E-Mail:   pincush@pi.cpmc.columbia.edu  

Most Adults with Alcohol Problems Do Not Recognize Their Need for Treatment

According to the National Survey on Drug Use and Health, an overwhelming majority of adults aged 21 to 64 in the United States with substantial alcohol problems—those meeting diagnostic criteria for either alcohol abuse disorder or alcohol dependence disorder—do not perceive a need for treatment of their disorder. 



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Scotland news and updates: AFS release new Manifesto; SNP still seek minimum price; national brief interventions target met

Alcohol Focus Scotland (AFS) have launched a new Manifesto which calls for the new Scottish Parliament to take decisive steps to reduce the harm caused by alcohol by:

• Increasing the price and reducing the availability of alcohol
• Specifically targeting supermarkets for increased regulation
• Banning alcohol sports sponsorship
• Reducing drink driving limits to 50mg
• Awareness raising campaign on the harm alcohol causes to others
• Improved treatment and support services for people in need

See here for the full 8 calls to action. The Scottish National Party (SNP) recently announced they would revive their plans for a minimum price if they win the Scottish national elections on May 5th. A senior police officer has also backed the measure.

NHS Scotland have also recently met the national 3 year target to deliver nearly 150,000 brief interventions by March 2011. See this Alcohol Information Scotland page for previous reports.

The Impact of Alcohol Outlet Density on the Geographic Clustering of Underage Drinking Behaviors within Census Tracts

The regulation of alcohol outlet density has been considered as a potential means of reducing alcohol consumption and related harms among underage youth. 

Whereas prior studies have examined whether alcohol outlet density was associated with an individual’s alcohol consumption and related harms, this study examines whether it is related to the co-occurrence, or clustering, of these behaviors within geographic areas, specifically census tracts.

The Enforcing Underage Drinking Laws Randomized Community Trial provided cross-sectional telephone survey data in 2006 and 2007 from 10,754 youth aged 14 to 20 from 5 states residing in 1,556 census tracts. The alternating logistic regression approach was used to estimate pairwise odds ratios between responses from youth residing in the same census tract and to model them as a function of alcohol outlet density.

Riding with a drinking driver, making an alcohol purchase attempt, and making a successful alcohol purchase attempt clustered significantly within census tracts with the highest off-premise alcohol outlet density while frequent drinking clustered within census tracts with the greatest on-premise density. Driving after drinking and experiencing nonviolent alcohol-related consequences clustered marginally within census tracts with the greatest on-premise and off-premise alcohol outlet density, respectively.

Although youth primarily receive alcohol from social sources, commercial alcohol access is geographically concentrated within census tracts with the greatest off-premise outlet density. A potentially greater concern is the clustering of more frequent drinking and drinking and driving within census tracts with the greatest on-premise outlet density which may necessitate alternative census tract level initiatives to reduce these potentially harmful behaviors.



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Request Reprint E-Mail:    brebouss@wfubmc.edu  

Alterations of Brain-Derived Neurotrophic Factor Serum Levels in Patients with Alcohol Dependence

Alcohol dependence is a chronic relapsing disorder characterized by repetitive alcohol drinking patterns and a loss of control over alcohol consumption. Recent studies have hypothesized that dysregulations in brain neurotrophic support regulated by neurotrophins may be involved in the vulnerability to dependence and in the brain damage caused by chronic alcohol consumption. The neurotrophin brain-derived neurotrophic factor (BDNF) plays a pivotal role in neurodevelopment and in the maintenance of adult brain homeostasis through the regulation of neurogenesis and neuronal plasticity. The role of BDNF and its signaling in the mechanisms of alcohol dependence has been well documented in studies of animal models, but a few studies have been conducted in human peripheral tissues. 

On the basis of this rationale, we compared BDNF levels in both serum and plasma in alcohol-dependent patients and healthy volunteers.

Thirty-seven patients with a principal diagnosis of alcohol dependence were recruited. In parallel, a control group of 37 unrelated volunteers matched for gender and age was enrolled. Serum and plasma BDNF levels were measured by ELISA.

A significant reduction in BDNF serum levels was observed in the patient group compared to healthy subjects (p = 0.028). On the contrary, no difference in BDNF plasma levels was evident between patients and controls.

In conclusion, our data show an alteration of BDNF peripheral content in patients with alcohol dependence, suggesting the involvement of this neurotrophin in this psychopathology.


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Request Reprint E-Mail:  rzanardini@fatebenefratelli.it   

Toll-Like Receptor 4 Mediates Alcohol-Induced Steatohepatitis Through Bone Marrow-Derived and Endogenous Liver Cells in Mice

Excessive alcohol intake causes an increase in intestinal permeability that induces translocation of gut-derived lipopolysaccharide (LPS) to the portal vein. Increased LPS in the portal vein stimulates Kupffer cells through Toll-like receptor (TLR) 4 in the liver. Activated TLR4 signaling in Kupffer cells induces various inflammatory mediators including TNF-α, IL-1β, and reactive oxygen species, resulting in liver injury. Hepatic stellate cells (HSCs) also express TLR4. 

This study investigates whether TLR4 on bone marrow (BM)-derived cells, including Kupffer cells, or non–BM-derived endogenous liver cells, including HSCs, contributes to the progression of alcohol-induced steatohepatitis and fibrogenesis in mice.

TLR4 BM chimera (wild-type [WT] mice with TLR4^−/− BM or TLR4^−/− mice with WT BM) were generated by the combination of liposomal clodronate injection with whole body irradiation and BM transplantation, followed by treatment with intragastric alcohol feeding.

WT mice transplanted with WT BM exhibited liver injury, steatosis, inflammation, and a fibrogenic response. Conversely, TLR4^−/− mice with TLR4^−/− BM displayed less steatosis, liver injury, and inflammation. Notably, steatosis, macrophage infiltration, and alanine aminotransferase levels in both TLR4-chimeric mice showed intermediate levels between WT mice transplanted with WT BM and TLR4^−/− mice transplanted with TLR4^−/− BM. Hepatic mRNA expression of fibrogenic markers (collagen α1(I), TIMP1, TGF-β1) and inflammatory cytokines (IL-1β, IL-6) were markedly increased in WT mice with WT BM, but there was less of an increase in both TLR4-chimeric mice and in TLR4^−/− mice transplanted with TLR4^−/− BM.

TLR4 signaling in both BM-derived and non–BM-derived liver cells is required for liver steatosis, inflammation, and a fibrogenic response after chronic alcohol treatment.


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Request Reprint E-Mail:  ekseki@ucsd.edu   

Acute Ethanol Disrupts Photic and Serotonergic Circadian Clock Phase-Resetting in the Mouse

Alcohol dependence is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol dependence on the circadian timing system.

In this study, we extend previous work in C57BL/6J mice to: (i) characterize the suprachiasmatic nucleus (SCN) pharmacokinetics of acute systemic ethanol administration, (ii) explore the effects of acute ethanol on photic and nonphotic phase-resetting, and (iii) determine if the SCN is a direct target for photic effects.

First, microdialysis was used to characterize the pharmacokinetics of acute intraperitoneal (i.p.) injections of 3 doses of ethanol (0.5, 1.0, and 2.0 g/kg) in the mouse SCN circadian clock. Second, the effects of acute i.p. ethanol administration on photic phase delays and serotonergic ([+]8-OH-DPAT-induced) phase advances of the circadian activity rhythm were assessed. Third, the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized.

Peak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20 to 40 minutes postinjection with half-lives for clearance ranging from 0.6 to 1.8 hours. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase delays.

These results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and nonphotic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral, physiological, and endocrine rhythms associated with alcoholism.


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Request Reprint E-Mail:   jglass@kent.edu  

A Time-Series Analysis of Alcohol Tax Policy in Relation to Mortality from Alcohol Attributed Causes in Taiwan

It is known that taxation on alcohol products may effectively reduce the alcohol consumption. However, whether alcohol taxation may lead to a decrease in alcohol attributed disease mortality (ADM) has been inclusively. 

 

We conducted this time-series analysis to assess the effect of alcohol tax policy intervention in 2002 on rate of ADM in Taiwan. 

 

Mortality data were retrieved from Taiwan’s Death Registry. We employed the autoregression integrated moving average technique to examine secular patterns of quarterly rate of ADM in residents aged 15 or above between 1991 and 2007, and to determine whether alcohol tax policy intervention, imposed in January 2002, had affected the time trend in rate of ADM in subsequent years. 

 

We observed a statistically significant reduction in the rate of ADM following the implementation of alcohol tax policy for all sex- and age-specific segments of population. 

 

Further analyses revealed that the effect was most obvious in men aged 15–64 years, who showed an abrupt decline in AMD rate (10.9%) in the first quarter of 2002. 

 

For elderly men and women, the tax intervention was followed by a gradually declining trend of ADM, with a magnitude ranging from 0.53% per season (elderly women) to 0.63% per season (elderly men). 

 

This study demonstrated that alcohol taxation policy may pose favorite influences on the time trend of ADM rate in Taiwan, and such influence was most noteworthy in young and middle aged men. 

 

 

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Request Reprint E-Mail:   cyli99@mail.ncku.edu.tw

News Release - Scientists find gene linked to alcohol consumption

The researchers say that finding a common genetic variation influencing levels of alcohol consumption may lead to a better understanding of mechanisms underlying alcohol drinking behaviour in the general population.

The gene, called “autism susceptibility candidate 2”, or AUTS2, has previously been linked to autism and attention deficit hyperactivity disorder, but its function is not known.

Today’s study, by an international consortium led by scientists at Imperial College London and King’s College London, found that there are two versions of the AUTS2 gene, one three times more common than the other. People with the less common version drink on average five per cent less alcohol than people with the more common version.  > > > >  Read More

Previous Ethanol Experience Enhances Synaptic Plasticity of NMDA Receptors in the Ventral Tegmental Area

Alcohol addiction (alcoholism) is one of the most prevalent substance abuse disorders worldwide. Addiction is thought to arise, in part, from a maladaptive learning process in which enduring memories of drug experiences are formed. 

However, alcohol (ethanol) generally interferes with synaptic plasticity mechanisms in the CNS and thus impairs various types of learning and memory. Therefore, it is unclear how powerful memories associated with alcohol experience are formed during the development of alcoholism. 

Here, using brain slice electrophysiology in mice, we show that repeated in vivo ethanol exposure (2 g/kg, i.p., three times daily for 7 d) causes increased susceptibility to the induction of long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated transmission in mesolimbic dopamine neurons, a form of synaptic plasticity that may drive the learning of stimuli associated with rewards, including drugs of abuse. 

Enhancement of NMDAR plasticity results from an increase in the potency of inositol 1,4,5-trisphosphate (IP₃) in producing facilitation of action potential-evoked Ca²⁺ signals, which is critical for LTP induction. This increase in IP₃ effect, which lasts for a week but not a month after ethanol withdrawal, occurs through a protein kinase A (PKA)-dependent mechanism. 

Corticotropin-releasing factor, a stress-related neuropeptide implicated in alcoholism and other addictions, further amplifies the PKA-mediated increase in IP₃ effect in ethanol-treated mice. 

Finally, we found that ethanol-treated mice display enhanced place conditioning induced by the psychostimulant cocaine. 

These data suggest that repeated ethanol experience may promote the formation of drug-associated memories by enhancing synaptic plasticity of NMDARs in dopamine neurons. 

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Request Reprint E-Mail:  morikawa@mail.utexas.edu  

Alcohol involvement as a function of co-occurring alcohol use disorders and major depressive episode: Evidence from the National Epidemiologic Survey on Alcohol and Related Conditions

Co-occurring alcohol use disorder and major depression (C-ALDP) is a major public health problem. Yet, the available evidence is mixed regarding the implications of C-ALDP for alcohol involvement. The purpose of this research was to examine the associations between past 12-month co-occurring AUDs (abuse and dependence) and major depressive episode (MDE) and alcohol involvement in a representative community sample.
 
The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is a national household survey of 43,093 adults ages 18 and older. For the NESARC, the target population is the civilian noninstitutionalized population, 18 years of age and older, living in the United States and the District of Columbia.
 
All NESARC interviews were conducted with the Alcohol Use Disorder and Associated Disabilities Interview Schedule – DSM IV Version (AUDADIS-IV; Grant et al., 2003a).

Prevalence of past 12-month co-occurring AUD (abuse or dependence) and MDE was 1.2%, corresponding to about 2.4 million adults ages 18 and older. Among males with alcohol dependence, comorbid MDE was associated with a greater number of days drinking at home alone. Among females and males with alcohol abuse and dependence, comorbid MDE was associated with higher prevalence of drinking to enhance depressed mood. Comorbid MDE was also associated with lower levels of some drinking behaviors among those with alcohol abuse.

Co-occurring AUDs and MDE are associated with specific dimensions of alcohol involvement, and this association is more consistent for alcohol dependence than abuse.


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Request Reprint E-Mail:  jcranfor@med.umich.edu   

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumptio

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. 

We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. 

SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10⁻⁸ to P = 4 × 10⁻⁹). 

We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. 

Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001).

Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior. 

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Request Reprint  E-Mail:  gunter.schumann@kcl.ac.uk, m.jarvelin@imperial.ac.uk, or p.elliott@imperial.ac.uk.    


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Empowerment. Advocacy. NGO´s. Vilnius, Lithuania 21. – 23. October 2011.

How to make efficient alcohol and drug policy?
What kind of important things NGOs must know before reaching this aim? It is important to get policymakers interested and involved in public health policy. How? With better advocacy?  Mobilizing people? Training and education?   > > > >    Read More

2010 Partnership Attitude Tracking Study, sponsored by MetLife Foundation

The 22nd annual Partnership Attitude Tracking Study (PATS), sponsored by MetLife Foundation, shows that teen drug and alcohol use is headed in the wrong direction, with marked increases in teen use of marijuana and Ecstasy over the past three years. The study confirms a disturbing trend that has emerged among American teens since 2008 and highlights that underage drinking has become more normalized among adolescents.

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Press Release - State disburses $6.3 million to reduce alcohol abuse

Community coalitions statewide are invited to apply for six grants to develop comprehensive prevention programs targeting youth alcohol use, ages 12–20, and adult heavy and binge drinking, ages 21–44. The two age and behavior targets were chosen as those causing Alaskans the most harm, via accidents, homicides, suicides, crime, domestic violence and other categories.
 
The state grants are funded by a $10.7 million federal Strategic Prevention Framework State Incentive Grant program awarded in 2009. Some funding will go to building state infrastructure, such as trainers and prevention resources, and evaluation of grantee performance. The Department of Health and Social Services, Division of Behavioral Health, is now accepting proposals from coalitions in both urban and rural areas of Alaska to provide services from July 1, 2011 to June 30, 2014.
 
The funding agent, the federal Substance Abuse and Mental Health Services Administration, requires that grantees 1) be part of a community coalition; 2) provide a comprehensive array of promotion, prevention and early intervention strategies; 3) use data-focused, community-designed strategies that have proven effective; and 4) have clearly defined and measurable outcomes.  > > > >  Read More

News Release - Three in Ten Americans Drink Alcohol at Least Once a Week

Maybe it’s a glass of wine. For some, it might be a beer or a gin and tonic. But whatever the choice is, three in ten Americans, 21 and older (29%) say they drink alcohol at least once a week, including 5% who drink daily and 10% who drink several times a week. One in five Americans 21 or older (20%) say they drink alcohol at least once a month and 15% drink it several times a year. One in five Americans (22%) say they never drink alcohol. Men are more frequent drinkers than women are as almost two in five men (38%) say they drink at least once a week compared to 21% of women.  > > > >  Read More

Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol

The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. 

Using whole genome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. 

However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases.

Cocaine- and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. 

There was no direct correlation, however, between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications. 

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Request Reprint E-Mail:   davidgoldman@mail.nih.gov.

 

Pathway based analysis of genotypes in relation to alcohol dependence

We introduce a method for detecting variants in several genes of related function with small effect on a phenotype of interest. 

Our method uses logistic regression to test whether multiple alleles within a functional set have significantly higher than expected predictive value, even though none individually may have strong individual effects. 

We illustrate this method by testing seven gene sets (including 48 genes), from a study with1350 single nucleotide polymorphisms in 130 addiction candidate genes studied in a sample of 575 alcohol dependence (AD) cases and 530 controls. 

We conclude that AD is related to variation in genes participating in Glutamate and γ-amino butyric acid signaling, as has been reported elsewhere, and in stress response pathways, but not with genes in several other systems implicated in other drugs of abuse.

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Request Reprint E-Mail:   mreimers@vcu.edu
 

The Chinese Translations of Alcohol Use Disorders Identification Test (AUDIT) in China: A Systematic Review

To systematically review the literature on the Chinese translations of the Alcohol Use Disorders Identification Test (AUDIT) and their cross-cultural applicability in Chinese language populations.

We identified peer-reviewed articles published in English (n = 10) and in Chinese (n = 11) from 1980 to September 2009, with key words China, Chinese and AUDIT among PubMed, EBSCO, PsycInfo, FirstSearch electronic databases and two Chinese databases.

Five teams from Beijing, Tibet, Taiwan and Hong Kong reported their region-specific translation procedures, cultural adaptations, validity (0.93–0.95 in two versions) and reliability (0.63–0.99).

These Chinese translations and short versions demonstrated relatively high sensitivity (0.880–0.997) and moderate specificity (0.709–0.934) for hazardous/harmful drinking and alcohol dependence, but low specificity for alcohol dependence among Min-Nan Taiwanese (0.58).

The AUDIT and its adaptations were most utilized in workplace- and hospital-settings for screening and brief intervention. However, they were under-utilized in population-based surveys, primary care settings, and among women, adolescents, rural-to-urban migrants, the elderly and minorities.
 

Among 12 studies from mainland China, four included both women and men, and only one in Tibet was published in English.  

There is a growing amount of psychometric, epidemiologic and treatment research using Chinese translations of the AUDIT, much of it still unavailable in the English-language literature.

Given the increase in burden of disease and injury attributable to alcohol use in the Western Pacific region, the use of an internationally comparable instrument (such as the AUDIT) in research with Chinese populations presents a unique opportunity to expand clinical and epidemiologic knowledge about alcohol problem epidemics. 

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Request Reprint E-Mail:   youliqing@hotmail.com

 

Surrogate Alcohol Drinking in Estonia

Surrogate, nonbeverage alcohols, provide a cheap and concentrated source of ethanol for drinking that has been associated with premature mortality.

The aim of this study was to provide the first estimate of the prevalence of surrogate alcohol consumption in a national population sample of Estonia.

The Estonian Health Interview Survey conducted in 2006 to 2007 was a nationally representative sample of the population aged 15 to 84 years (N = 6,370). The age-standardized percentage prevalences of ever having drunk surrogates were estimated. The association of age, ethnicity, and education with the prevalence of surrogate drinking was estimated using logistic regression.

Of all respondents who reported drinking at least once in their lifetime (N = 5,423), 65% had consumed alcohol during the previous 4 weeks. In this group (N = 3,525), the age-standardized prevalence rate of surrogate drinking was 1.4% (2.3% men, 0.3% women). Among men, surrogate drinking was rare under the age of 35 years (0.3%). Ethnicity and education were both related to surrogate drinking: relative to Estonian men, non-Estonians (mainly Russians) had an odds ratio (OR) for surrogate drinking (adjusted for age and education) of 2.58 (95% CI 1.41, 4.72), while relative to those with higher education those with secondary education had an OR (adjusted for age and ethnicity) of 2.28 (0.78, 6.67) and those with basic education an OR of 3.91 (1.29, 11.84).

Surrogate alcohols are drunk in Estonia, particularly among men. This behavior shows pronounced variation in prevalence by ethnicity and education. Reducing consumption of these substances needs to be part of any strategy to reduce the burden of alcohol-related problems in Estonia today.


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Request Reprint E-Mail:  kersti.parna@ut.ee  

Ethanol Inhibits Lipid Raft-Mediated TCR Signaling and IL-2 Expression: Potential Mechanism of Alcohol-Induced Immune Suppression

Alcohol abuse has long-term deleterious effects on the immune system, and results in a depletion and loss of function of CD4⁺ T lymphocytes, which regulate both innate and adaptive immunity. T-lymphocyte activation via T-cell receptor (TCR) involves the lipid raft colocalization and aggregation of proteins into the immunological signalosome, which triggers a signaling cascade resulting in the production of interleukin-2 (IL-2). IL-2 regulates the proliferation and clonal expansion of activated T cells and is essential for an effective immune response. 


The present work examines the mechanisms underlying ethanol-induced dysfunction of CD4⁺ T lymphocytes based on the hypothesis that ethanol downregulates lipid raft-mediated TCR signal transduction and resultant IL-2 production.

Primary or cultured human T lymphocytes were exposed to ethanol for 24 hours prior to stimulation with anti-CD3/anti-CD28 antibodies or phytohemagglutinin. Effects of ethanol exposure on TCR-signaling (including activation of Lck, ZAP70, LAT, and PLCγ1) and IL-2 gene expression were examined.

Exposure of both primary and cultured human CD4⁺ T lymphocytes to physiologically relevant concentrations of ethanol leads to down-regulation of IL-2 mRNA and protein via inhibition of DNA-binding activity of NFAT, the essential transcription factor for IL-2. Ethanol decreases tyrosine phosphorylation and activation of upstream signaling proteins PLCγ1, LAT, ZAP70, and Lck. These effects are prevented by inhibition of metabolism of ethanol. Sucrose density gradient fractionation and confocal microscopy revealed that ethanol inhibited essential upstream lipid raft-mediated TCR-dependent signaling events, namely colocalization of Lck, ZAP70, LAT, and PLCγ1 with plasma membrane lipid rafts.

Overall, our data demonstrate that ethanol inhibits lipid raft-mediated TCR-signaling in CD4⁺ T lymphocytes, resulting in suppression of IL-2 production. These findings may represent a novel mechanism underlying alcohol abuse-associated immune suppression and may be particularly relevant in diseases such as HIV/AIDS and hepatitis C virus infection where alcohol abuse is a known comorbidity.


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Request Reprint E-Mail:  s0josh01@louisville.edu  

A New Model of Interactive Effects of Alcohol and High-Fat Diet on Hepatic Fibrosis

Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are the most frequent conditions leading to elevated liver enzymes and liver cirrhosis, respectively, in the Western world. However, despite strong epidemiological evidence for combined effects on the progression of liver injury, the mutual interaction of the pathophysiological mechanisms is incompletely understood.

The aim of this study was to establish and analyze an experimental murine model, where we combined chronic alcohol administration with a NASH-inducing high-fat (HF) diet.

Balb/c mice were randomly allocated into 4 experimental groups receiving (i) standard chow, (ii) an HF diet, (iii) alcohol in drinking water (increasing concentrations up to 5%), or (iv) an HF diet and alcohol ad libitum for 6 weeks.

An HF diet significantly induced hepatic triglyceride accumulation and expression of proinflammatory genes (p47^phox and tumor necrosis factor), while the effects of alcohol alone were less pronounced. However, in combination with HF diet, alcohol significantly enhanced proinflammatory gene expression compared to the HF diet alone. Furthermore, alcohol as well as HF diet led to a marked increase in profibrogenic genes (collagen type I and transforming growth factor-β), activation of hepatic stellate cells, and extracellular matrix deposition in the liver tissue, and noteworthy, the combination of both alcohol and HF diet led to a further marked induction of hepatic fibrosis. Moreover, endotoxin levels in the portal circulation were significantly elevated in mice that received alcohol or HF diet and were further significantly increased in those receiving both. Furthermore and surprisingly, HF diet alone and in combination with alcohol led to a markedly increased hepatic expression of the endotoxin receptor Toll-like receptor 4 (TLR4), which is known to play a crucial role in hepatic fibrosis.

In summary, this new model allows the investigation of isolated or joint effects of alcohol and HF diet on hepatic injury, where alcohol and HF diet appear to act synergistically on the development of hepatic fibrosis, potentially via enhanced TLR4 signaling.


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Request Reprint E-Mail:   claus.hellerbrand@klinik.uni-regensburg.de

A Longitudinal Twin Study of Effects of Adolescent Alcohol Abuse on the Neurophysiology of Attention and Orienting

Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure.

We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism.

Twin pairs (N = 177; 150 selected for intrapair concordance/discordance for alcohol-related problems at age 18½) were recruited from ongoing studies of twins born 1975–1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ∼25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent “standards” and to ignore occasional “novel” sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intra-pair differences in alcohol variables.

Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between- and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins’ similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors.

Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors.


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Request Reprint E-Mail:   sini.koskinen@helsinki.fi

Role of Intestinal Circadian Genes in Alcohol-Induced Gut Leakiness

Several studies have indicated that endotoxemia is the required co-factor for alcoholic steatohepatitis (ASH) that is seen in only about 30% of alcoholics. Recent studies have shown that gut leakiness that occurs in a subset of alcoholics is the primary cause of endotoxemia in ASH. The reasons for this differential susceptibility are not known. Since disruption of circadian rhythms occurs in some alcoholics and circadian genes control the expression of several genes that are involved in regulation of intestinal permeability, we hypothesized that alcohol induces intestinal hyperpermeability by stimulating expression of circadian clock gene proteins in the intestinal epithelial cells.

We used Caco-2 monolayers grown on culture inserts as an in vitro model of intestinal permeability and performed Western blotting, permeability, and siRNA inhibition studies to examine the role of Clock and Per2 circadian genes in alcohol-induced hyperpermeability. We also measured PER2 protein levels in intestinal mucosa of alcohol-fed rats with intestinal hyperpermeability.

Alcohol, as low as 0.2%, induced time dependent increases in both Caco-2 cell monolayer permeability and in CLOCK and PER2 proteins. SiRNA specific inhibition of either Clock or Per2 significantly inhibited alcohol-induced monolayer hyperpermeability. Alcohol-fed rats with increased total gut permeability, assessed by urinary sucralose, also had significantly higher levels of PER2 protein in their duodenum and proximal colon than control rats.

Our studies: (i) demonstrate a novel mechanism for alcohol-induced intestinal hyperpermeability through stimulation of intestinal circadian clock gene expression, and (ii) provide direct evidence for a central role of circadian genes in regulation of intestinal permeability.


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Request Reprint E-Mail:   ali_keshavarzian@rush.edu 

Geographic and Maternal Characteristics Associated with Alcohol Use in Pregnancy

To date, no studies have used population-level data to investigate whether maternal location of residence (metropolitan vs. regional/remote populations) is associated with alcohol use in pregnancy. This information has important implications for appropriate service provision.

Information on all live births in New South Wales Australia was linked to records of alcohol-related admissions for mothers of these births over a 6-year period (2000 to 2006). Cases were women who had at least 1 alcohol-related hospital admission during pregnancy or at birth. Controls were women who had at least 1 live birth over that same time period but no alcohol-related hospital admissions during that time. Admissions were considered to be alcohol-related based on the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) code. Demographic, obstetric, and neonatal variables were compared.

A total of 417,464 singleton birth records were analyzed, 488 of which were coded positive for at least 1 alcohol-related ICD-10-AM diagnosis. 


Characteristics associated with alcohol-related admissions in pregnancy were residence in a remote/very remote area, being Australian-born, having had a previous pregnancy, smoking in the current pregnancy, and presenting late to antenatal care. 


Alcohol-exposed pregnancies were associated with a range of poor obstetric and neonatal outcomes, with no geographic differences noted. However, women in regional/remote areas were less likely to attend specialist obstetric hospitals.

This study shows the need for standardized screening programs for alcohol use in pregnancy and where problematic use is detected, for clear clinical guidelines on management and referral.



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Increased Myostatin Activity and Decreased Myocyte Proliferation in Chronic Alcoholic Cardiomyopathy

Apoptosis mediates in alcohol-induced heart damage leading to cardiomyopathy (CMP). Myocyte proliferation may compensate for myocyte loss. Myostatin is upregulated after cardiac damage and by alcohol consumption thereby decreasing myocyte renewal. 

We assess the potential role of alcohol in inducing myocyte apoptosis as well as in inhibiting myocyte proliferation.

Heart samples were obtained from organ donors, including 22 high alcohol consumers, 22 with hypertension, 8 with other causes of CMP, and 10 healthy donors. Evaluation included medical record with data on daily, recent and lifetime ethanol consumption, chest X-ray, left ventricular (LV) function assessed by two-dimensional echocardiography, and LV histology and immunohistochemistry. Apoptosis was evaluated by TUNEL, BAX, and BCL-2 assays. Myocyte proliferation was evaluated with Ki-67 assay. Myostatin activity was measured with a specific immunohistochemical assay. CMP was assessed by functional and histological criteria.

Alcoholic and hypertensive donors with CMP showed higher apoptotic indices than did their partners without CMP. Myostatin activity was higher in alcoholics than in controls, mainly in those with CMP. The increase in myostatin expression in alcoholic CMP was higher than in other groups. The Ki-67 proliferation index increased in all groups with CMP compared to those without CMP, with alcoholics showing a lower increase in this proliferation response.

Alcohol produces cardiac myocyte loss through apoptosis but also partially inhibits myocyte proliferation through myostatin up-regulation.


The final result may suppose an imbalance in myocyte homeostasis, with a net loss in total ventricular myocyte mass and progressive ventricular dysfunction.




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The Ghrelin Signalling System Is Involved in the Consumption of Sweets

The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. 

Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. 

It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. 

In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. 

Moreover, the effects of GHS-R1A antagonism on voluntary sucrose- intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined.

Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. 

The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats.

Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours.


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Rewarding, Stimulant, and Sedative Alcohol Responses and Relationship to Future Binge Drinking

Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse.

To prospectively assess the relationship of acute alcohol responses to future binge drinking.

Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses.

Participants recruited from the community.

High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n = 104) and light drinker controls (n = 86).

We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520).

Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Timeline Follow-Back, Drinker Inventory of Consequences–Recent, and DSM-IV alcohol abuse and dependence.

Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse 

and dependence.

The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems.


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Request Reprint E-Mail:  aking@yoda.bsd.uchicago.edu.    

Alcohol News - 14/2011

Life through my Lens (Denmark) - Portrait Series: Adolescent Drinking

No one in Denmark knows what the drinking age is. I’ve asked multiple people. At first, I heard 18 to buy beer and get into clubs. Then, someone said at 15 they can buy beer and at 18 they can buy liquor and get into clubs. And then someone else told me they thought it was 16 to buy, but there was no law against consuming alcohol at any age.

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Stockholm News (Sweden) - Expect more licensed premises in Stockholm

Since the Swedish alcohol law was changed at the new year, the number of applications for a liquor license has increased substantially in Stockholm. The Permit Unit usually receives around 100 applications for a full year, but after barely three months has received more than 50.

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Baltic News Network (Latvia) - Government approves excise tax rise to cigarettes, gasoline and alcohol

Today, March 29, the government of Latvia approved increasing excise tax rate to cigarettes, strong spirits and gasoline.

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Herald Sun (Australia) - Welfare linked to Northern Territory alcoholism

THE severe beating of a woman in Alice Springs is a poignant but all too common symbol of a town in crisis. For months local business owners and residents have been speaking out against the sharp increase in alcohol-fuelled violence and crime in the Red Centre.

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BCM (Russia) - Vladimir Putin speaks out against sharp rise in prices on alcohol in Russia

Speaking at the meeting of the Government Presidium on Thursday, Russian Prime Minister Vladimir Putin said that a sharp hike in excise duties and, accordingly, the price of alcohol would be unacceptable. He criticized the initiative of the Ministry of Finance to raise excise taxes on alcohol and said that a surge of prices on alcohol products will not resolve the problem of alcoholism, but will only promote using substitutes, increase the demand for counterfeit products and lead to the resurgence and growth of moonshine making.

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WalesOnline (Wales) - Obesity and alcohol cost Welsh NHS £150m a year

The true cost of Wales’ problem has been laid out in an academic study commissioned by the Assembly Government.Around £73m is spent treating and combating obesity each year while between £69.9m and £73.3m is spent dealing with excessive alcohol consumption.

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New Zealand Herald (New Zealand) - Experts' breakfast beer worry

It's nicknamed the "breakfast beer" but alcohol watchdogs are hoping a new Kiwi brew to be launched early on a weekday morning is nothing but a fizzer.

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Irish Independent (Ireland) - Forces of nature cannot break free of alcohol's tight marking

I met a woman a few months ago who was employed in the addiction industry in America. She wasn't of addictive tendency herself but she had read all the studies, seen all the reports and had a lot of ideas on how the world could be a better place and how we all could be better people.

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Huffington Post (USA) - Heavy Drinking Remains A Constant On College Campuses

Times may change, but some things stay the same -- and on college campuses, it's the presence of alcohol. New findings have emerged, however, in how alcohol consumption effects students.

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The Independent (UK) - TV alcohol advertising ban proposed

A bid to impose a total ban on alcohol advertising on television has been launched in Parliament. The legislation, proposed by GP and Tory MP Sarah Wollaston, would also prevent alcohol brands being used to sponsor sporting and cultural events.

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EurekAlert - Bad mix: Heavy beer drinking and a gene variant increases gastric cancer risk

Heavy beer drinkers who have a specific genetic variant in the cluster of three genes that metabolize alcohol are at significantly higher risk of developing non-cardia gastric cancer, according to research presented at the AACR 102nd Annual Meeting 2011, held here April 2-6.

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Mail & Guardian Online (South Africa) - Govt eyes overhaul of alcohol industry

If the government gets its way, the alcohol industry could be in for a massive overhaul. But whether the strict new regulations being proposed will be implemented effectively and result in less harmful drinking remains to be seen.

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swissinfo.ch (Switzerland) - Alcohol and tobacco still part of growing up

Swiss schoolchildren’s consumption of alcohol, tobacco and cannabis has remained stable in the past four years, despite prevention measures, nationwide figures reveal.

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Eureka! Science News - Underage binge drinking can create lasting brain changes

Adolescents represent the majority of people who binge drink. This may come as a surprise to some, but recent surveys indicate that episodes of heavy alcohol drinking within the previous two weeks are reported by 12 percent of 8th graders, 22 percent of 10th graders, 28 percent of 12th grade seniors and 44 percent of college students.

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The Portugal News (Portugal) - Two million youths at risk of liver disease

Portugal’s Society of Hepatology has announced that up to “two million” Portuguese adolescents are at risk of contracting liver disease because of their drinking habits.

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