Midbrain-driven Emotion and Reward Processing in Alcoholism

Alcohol dependence is associated with impaired control over emotionally motivated actions, possibly associated with abnormalities in the frontoparietal executive control network and midbrain nodes of the reward network associated with automatic attention.
To identify differences in the neural response to alcohol-related word stimuli, 26 chronic alcoholics (ALC) and 26 healthy controls (CTL) performed an alcohol-emotion Stroop Match-to-Sample task during functional MR imaging. Stroop contrasts were modeled for color-word incongruency (eg, word RED printed in green), and for alcohol (eg, BEER), positive (eg, HAPPY), and negative emotional (eg, MAD) word content relative to congruent word conditions (eg, word RED printed in red).

During color-Stroop processing, ALC and CTL showed similar left dorsolateral prefrontal activation, and CTL, but not ALC, deactivated posterior cingulate cortex/cuneus. An interaction revealed a dissociation between alcohol-word and color-word Stroop processing: ALC activated midbrain and parahippocampal regions more than CTL when processing alcohol-word relative to color-word conditions.

In ALC, the midbrain region was also invoked by negative emotional Stroop words thereby showing significant overlap of this midbrain activation for alcohol-related and negative emotional processing.

Enhanced midbrain activation to alcohol-related words suggests neuroadaptation of dopaminergic midbrain systems. We speculate that such tuning is normally associated with behavioral conditioning to optimize responses but here contributed to automatic bias to alcohol-related stimuli.


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Request Reprint E-Mail:    evamoe@stanford.edu

Gut Peptide GLP-1 and Its Analogue, Exendin-4, Decrease Alcohol Intake and Reward

Glucagon-like-peptide-1 (GLP-1) is a gut- and neuro-peptide with an important role in the regulation of food intake and glucose metabolism. Interestingly, GLP-1 receptors (GLP-1R) are expressed in key mesolimbic reward areas (including the ventral tegmental area, VTA), innervated by hindbrain GLP-1 neurons.

Recently GLP-1 has emerged as a potential regulator of food reward behavior, an effect driven by the mesolimbic GLP-1Rs. Its role in other reward behaviors remains largely unexplored.

Since a considerable overlap has been suggested for circuitry controlling reward behavior derived from food and alcohol we hypothesized that GLP-1 and GLP-1Rs could regulate alcohol intake and alcohol reward. We sought to determine whether GLP-1 or its clinically safe stable analogue, Exendin-4, reduce alcohol intake and reward. To determine the potential role of the endogenous GLP-1 in alcohol intake we evaluated whether GLP-1R antagonist, Exendin 9-39, can increase alcohol intake. Furthermore, we set out to evaluate whether VTA GLP-1R activation is sufficient to reduce alcohol intake.

Male Wistar rats injected peripherally with GLP-1 or Exendin-4 reduced their alcohol intake in an intermittent access two bottle free choice drinking model. Importantly, a contribution of endogenously released GLP-1 is highlighted by our observation that blockade of GLP-1 receptors alone resulted in an increased alcohol intake. Furthermore, GLP-1 injection reduced alcohol reward in the alcohol conditioned place preference test in mice.

To evaluate the neuroanatomical substrate linking GLP-1 with alcohol intake/reward, we selectively microinjected GLP-1 or Exendin 4 into the VTA. This direct stimulation of the VTA GLP-1 receptors potently reduced alcohol intake.

Our findings implicate GLP-1R signaling as a novel modulator of alcohol intake and reward. We show for the first time that VTA GLP-1R stimulation leads to reduced alcohol intake. Considering that GLP-1 analogues are already approved for clinical use, this places the GLP system as an exciting new potential therapeutic target for alcohol use disorders.


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The One-Two Punch of Alcoholism: Role of Central Amygdala Dynorphins/Kappa-Opioid Receptors

The dynorphin (DYN)/kappa-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacologic manipulations.

Male Wistar rats were trained to self-administer alcohol using operant behavioral strategies and subjected to intermittent alcohol vapor or air exposure. Changes in self-administration were assessed by pharmacologic challenges during acute withdrawal. In addition, 22-kHz ultrasonic vocalizations were utilized to measure negative affective-like states. Immunohistochemical techniques assessed DYN A peptide expression and [³⁵S]GTPγS coupling assays were performed to assess KOR function.

 

Alcohol-dependent rats displayed increased alcohol self-administration, negative affective-like behavior, DYN A-like immunoreactivity, and KOR signaling in the amygdala compared with nondependent control rats. Site-specific infusions of a KOR antagonist selectively attenuated self-administration in dependent rats, whereas a mu-opioid receptor/delta-opioid receptor antagonist cocktail selectively reduced self-administration in nondependent rats. A mu-opioid receptor antagonist/partial KOR agonist attenuated self-administration in both cohorts.

Increased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Importantly, intracentral nucleus of the amygdala pharmacologic challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive alcohol consumption during withdrawal.


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Request Reprint E-Mail:   brendan.walker@wsu.edu

Housing and harm reduction: What is the role of harm reduction in addressing homelessness?

Homelessness and drug use often overlap and the harms of substance use are exacerbated by homelessness. Responding to the twin problems of homelessness and substance use is an important aspect of strategies to end homelessness.

The introduction and development of ten year plans to end homelessness in North America heralds a new era of systemic responses to homelessness. Central to many of these plans is the adoption of ‘Housing First’ as a policy response.

Housing First focuses directly on housing people regardless of current patterns of substance use. As such, harm reduction is a key principle of Housing First.

In this paper, we examine Housing First as an example of the integration of housing and harm reduction and then put forth a community level policy framework to further promote the integration of harm reduction as part of a response to homelessness.

Drawing on Rhodes’ risk environment framework and current evidence of Housing First and harm reduction, we describe four key policy areas for action: (1) social inclusion policies; (2) adequate and appropriate supply of housing; (3) on demand harm reduction services and supports and (4) systemic and organizational infrastructure.

We conclude by identifying areas for future research.


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Request Reprint E-Mail:      bpauly@uvic.ca

Ethanol Modulates Spontaneous Calcium Waves in Axonal Growth Cones in Vitro

 
In developing neurons the frequency of long duration, spontaneous, transient calcium (Ca²⁺) elevations localized to the growth cone, is inversely related to the rate of axon elongation and increases several fold when axons pause.

Here we report that these spontaneous Ca²⁺ transients with slow kinetics, called Ca²⁺ waves, are modulated by conditions of ethanol exposure that alter axonal growth dynamics.

Using time-series fluorescence calcium imaging we found that acute treatment of fetal rat hippocampal neurons with 43 or 87 mM ethanol at an early stage of development in culture decreased the percent of axon growth cones showing at least one Ca²⁺ wave during 10 min of recording, from 18% in controls to 5% in cultures exposed to ethanol.

Chronic exposure to 43 mM ethanol also reduced the incidence of Ca²⁺ waves to 8%, but exposure to 87 mM ethanol increased their incidence to 31%.

Neither chronic nor acute ethanol affected the peak amplitude, time to peak or total duration of Ca²⁺ waves.

In some experiments, we determined the temporal correlation between Ca²⁺ waves and growth and non-growth phases of axonal growth dynamics. As expected, waves were most prevalent in stationary or retracting growth cones in all treatment groups, except in cultures exposed chronically to 87 mM ethanol.

Thus, the relationship between growth cone Ca²⁺ waves and axon growth dynamics is disrupted by ethanol.


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The NASOROSSO (Rednose) Project: An Italian Study on Alcohol Consumption in Recreational Places

The Nasorosso project of the Italian Youth Department and the National Institute of Health, aimed to raise awareness about drinking and driving under the influence of alcohol among club goers with a series of initiatives.

Within the framework of the project, blood alcohol concentration (BAC) was measured on 106,406 individuals before and after clubbing in 66 different recreational sites from 11 Italian provinces, over 16 months. Participating individuals were interviewed regarding sociodemographic and environmental characteristics and alcohol intoxicated people were offered to be taken home

The BAC median at the club entry was 0.26 g/L with 65.3% subjects showing a BAC value under the driving legal limit of 0.5g/L. At the exit from clubs, BAC median value rose to 0.44 g/L and subjects with BAC value under the legal limit decreased to 54.9%.

Being male, aged between 18 and 34 years with a diploma, being a drinker and entering the disco with a BAC already beyond the legal limit predicted a BAC value beyond 0.5 g/L at exit from the recreational place.

Conversely, being a driver, being a student and exiting from the disco before 4 a.m. reduced the probability of having a BAC higher than 0.5 g/L at the end of the night. 

Health policies to prevent harmful use of alcohol in young people should continue to offer targeted information/ prevention; in order to steadily increase the awareness of the dangers and the damages of excessive use of alcohol.


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Beta prime regression with application to risky behavior frequency screening

Our aim is to model the frequency of certain behavioral acts, especially those that are likely to transmit communicable diseases between persons.

We develop a generalized linear model on the basis of the beta prime distribution to model the responses to a survey question of the form, ‘When was the last time that you engaged in this behavior?’ Intuitively, individuals reporting more recent events are more likely to have greater frequency of the risky behavior. The beta prime distribution is especially suited to this application because of its long tail. We adjust for length-biased sampling. We show how to use this distribution as the basis of a linear regression model that accounts for differences in demographic and psychological characteristics of the respondents. We discuss estimation of parameters, residuals, tests for heterogeneity of these parameters, and jackknife measures of influence.

We apply the methods to a survey of alcohol abuse use among individuals who are at high risk for spreading HIV and other communicable diseases in a study conducted in Saint Petersburg, Russia.



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Request Reprint E-Mail:     daniel.zelterman@yale.edu

In the fight against alcohol misuse, pricing policies are the way to go

Today Members of the European Parliament from various political groups, along with representatives of governments, leading academics and public health organisations, have renewed their support for strong measures to bring down the current high rate of alcohol misuse in Europe.

“If policy-makers are serious about tackling the danger that heavy alcohol use poses to the health of European citizens, they should take care that weak economic arguments do not override public health concerns,” Rebecca Taylor MEP (UK, ALDE).  > > > >  Read More

NQO1 609C > T polymorphism interaction with tobacco smoking and alcohol drinking increases colorectal cancer risk in a Chinese population

 

NAD (P)H:quinone oxidoreductase (NQO1) catalyzes the activation of some environmental procarcinogens present in tobacco smoke or the diet. We conducted a hospital-based case–control study to evaluate the potential association between NQO1 609C > T polymorphisms and colorectal cancer risk in a Chinese population.

The study population comprised 672 histologically confirmed colorectal cancer patients and 672 frequency-matched control subjects without cancer or systemic illness. We used PCR restriction fragment length polymorphism-based methods for genotyping analyses and unconditional logistic regression model for statistical evaluations.

The risk of colorectal cancer increased with the level of smoking and decreased with the consumption of tea, fresh fruits, and vegetables. In addition, we found that the NQO1 609 CT and TT genotypes were associated with an increased risk of colorectal cancer (CT: adjusted OR = 2.02, 95% CI = 1.55–2.57; TT: adjusted OR = 2.51, 95% CI = 1.82–3.47), compared with the CC genotype. Moreover, NQO1 609C > T appeared to have a multiplicative joint effect with both tobacco smoking and alcoholic drinking (P for multiplicative interactions were 0.0001 and 0.013, respectively) on colorectal cancer risk.

Our findings suggest that the NQO1 609C > T polymorphism plays an important role in the development of colorectal cancer in the Chinese population, which is strengthened by alcohol drinking or tobacco smoking.

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Request Reprint E-Mail:   fmuxe@163.com

Fatal Connections Socioeconomic Determinants of Road Accident Risk and Drunk Driving in Sweden

This paper uses both regional data and aggregated time series data to determine what factors influence the number of accidents and the accident outcome.

Using time series data, it is found that the number of traffic fatalities increases for both per capita and per person kilometer travelled during economic booms. This indicates that the death risk rises not only because of increased mileage or motorization during booms.

Using panel data, it is found that traffic fatalities decrease with unemployment.

The paper also examines whether drunk-driving is correlated with unemployment.


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Request Reprint E-Mail:  niclas.kruger@vti.se

New Studies Prove Lethal Link between Alcohol, Weight and Liver Disease in Women

Research announced today at the International Liver CongressTM 2013 has revealed the deadly impact that alcohol and body weight have on liver disease.

Women should forgo the wine and doughnuts after a new study found the harmful combination of high alcohol intake and high body mass index (BMI) causes an increased risk of chronic liver disease. The study analysed a cohort of over 107,000 women to investigate how a female’s weight and alcohol consumption affected their chances of suffering and dying from chronic liver disease.[1]   > > > >   Read More

Life in Recovery Survey

The results from the first nationwide survey of persons in recovery from addiction to alcohol and other drugs released today by Faces & Voices of Recovery documents the heavy costs of addiction to the individual and the nation and for the first time, measures and quantifies the effects of recovery over time. During their active addiction, 50 percent of respondents had been fired or suspended once or more from jobs, 50 percent had been arrested at least once and a third had been incarcerated at least once, contributing to a total societal cost of $343 billion to our nation annually.


ADDICTION RECOVERY IS ASSOCIATED WITH DRAMATIC IMPROVEMENTS IN ALL AREAS OF LIFE

• Involvement in illegal acts and involvement with the criminal justice system (e.g., arrests, incarceration, DWIs) decreases by about ten-fold
• Steady employment in addiction recovery increases by over 50% greater relative to active addiction
• Frequent use of costly Emergency Room departments decreases ten-fold
• Paying bills on time and paying back personal debt doubles
• Planning for the future (e.g., saving for retirement) increases nearly three-fold
• Involvement in domestic violence (as victim or perpetrator) decreases dramatically
• Participation in family activities increases by 50%
• Volunteering in the community increases nearly three-fold compared to in active addiction
• Voting increases significantly
• Reports of untreated emotional/mental health problems decrease over four-fold
• Twice as many participants further their education or training than in active addiction

THE BENEFITS OF ADDICTION RECOVERY OVER TIME

• The percentage of people owing back taxes decreases as recovery gets longer while a greater number of people in longer recovery report paying taxes, having good credit, making financial plans for the future and paying back debts
• Civic involvement increases dramatically as recovery progresses in such areas as voting and volunteering in the community
• People increasingly engage in healthy behaviors such as taking care of their health, having a healthy diet, getting regular exercise and dental checkups, as recovery progresses
• As recovery duration increases, a greater number of people go back to school or get additional job training
• Rates of steady employment increase gradually as recovery duration increases
• More and more people start their own business as recovery duration increases
• Participation in family activities increases from 68% to 95%

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Light drinking versus abstinence in pregnancy – behavioural and cognitive outcomes in 7-year-old children: a longitudinal cohort study

To assess whether light drinking in pregnancy is linked to unfavourable developmental outcomes in children.

 

Prospective population-based cohort.

 

UK.

 

Ten thousand five hundred and thirty-four 7-year-olds.

 

Quasi-experimental using propensity score matching (PSM) to compare children born to light (up to 2 units per week) and non-drinkers.

 

Behavioural difficulties rated by parents and teachers; cognitive test scores for reading, maths and spatial skills.

 

Ordinary least squares (OLS) regression and PSM analyses are presented. For behavioural difficulties, unadjusted estimates for percentage standard deviation (SD) score differences ranged from 2 to 14%. On adjustment for potential confounders, differences were attenuated, with a loss of statistical significance, except for teacher-rated boys' difficulties. For boys, parent-rated behavioural difficulties: unadjusted, −11.5; OLS, −4.3; PSM, −6.8; teacher-rated behavioural difficulties: unadjusted, −13.9; OLS, −9.6; PSM, −10.8. For girls, parent-rated behavioural difficulties: unadjusted, −9.6; OLS, −2.9; PSM, −4.5; teacher-rated behavioural difficulties: unadjusted, −2.4; OLS, 4.9; PSM, 3.9. For cognitive test scores, unadjusted estimates for differences ranged between 12 and 21% of an SD score for reading, maths and spatial skills. After adjustment for potential confounders, estimates were reduced, but remained statistically significantly different for reading and for spatial skills in boys. For boys, reading: unadjusted, 20.9; OLS, 8.3; PSM, 7.3; maths: unadjusted, 14.7; OLS, 5.0; PSM, 6.5; spatial skills: unadjusted, 16.2; OLS, 7.6; PSM, 8.1. For girls, reading: unadjusted, 11.6; OLS, −0.3; PSM, −0.5; maths: unadjusted, 12.9; OLS, 4.3; PSM, 3.9; spatial skills: unadjusted, 16.2; OLS, 7.7; PSM, 6.4.

 

The findings suggest that light drinking during pregnancy is not linked to developmental problems in mid-childhood. These findings support current UK Department of Health guidelines on drinking during pregnancy.


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Request Reprint E-Mail:   y.kelly@ucl.ac.uk

AUDIT-C Scores as a Scaled Marker of Mean Daily Drinking, Alcohol Use Disorder Severity, and Probability of Alcohol Dependence in a U.S. General Population Sample of Drinkers

Brief alcohol screening questionnaires are increasingly used to identify alcohol misuse in routine care, but clinicians also need to assess the level of consumption and the severity of misuse so that appropriate intervention can be offered. Information provided by a patient's alcohol screening score might provide a practical tool for assessing the level of consumption and severity of misuse.

 

This post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U.S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test—Consumption questionnaire (AUDIT-C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria (“AUD severity”), and the probability of alcohol dependence associated with each individual AUDIT-C score (1 to 12), after testing for effect modification by gender and age.

 

Among eligible past-year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT-C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT-C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT-C scores among younger versus older age group.
 

Results of this study could be used to estimate patient-specific consumption and severity based on age, gender, and alcohol screening score. This information could be integrated into electronic decision support systems to help providers estimate and provide feedback about patient-specific risks and identify those patients most likely to benefit from further diagnostic assessment.


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Request Reprint E-Mail:   anna.rubinsky@va.gov
 

Effects of Caffeine on Alcohol Consumption and Nicotine Self-Administration in Rats

Caffeine, alcohol, and nicotine are 3 of the most widespread self-administered psychoactive substances, which are known to be extensively co-administered. However, little is known about the degree to which they may mutually potentiate each other's consumption.

 

In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring (P) rats, caffeine (5, 10, and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of PO caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute PO administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute PO caffeine administration on nicotine self-administration in Sprague–Dawley rats were also determined.

 

Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute PO caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague–Dawley rats trained to self-administer i.v. nicotine, acute PO administration of caffeine significantly increased self-administration of nicotine in a dose-related manner.

 

These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions.


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Request Reprint E-Mail:   azadi@duke.edu

Microheterogeneity of Serum β-Hexosaminidase in Chronic Alcohol Abusers in a Driver's License Regranting Program

 

Carbohydrate-deficient transferrin (CDT) is one of the best indicators for chronic alcohol abuse and detection of relapse. In this study, we explore the microheterogeneity of β-hexosaminidase (β-HEX) in chronic alcohol abusers in the framework of a driver's license regranting program. Studies have shown that increased serum activity of β-HEX B (isoforms P, I, and B) may be a sensitive marker for chronic alcohol abuse. Here, we describe methodology, limitations, and correlation of β-HEX isoforms with CDT.

 

CDT was assayed at the central laboratory of the Ghent University Hospital by capillary zone electrophoresis, measured on the Capillarys 2™ system and was expressed as a percentage of total serum transferrin (%CDT). Serum of chronic alcohol abusers was compared to nonheavy drinkers using agarose gel isoelectric focusing (IEF). Total β-HEX activity was assayed fluorimetrically following preparative IEF in 81 subjects. β-HEX isoforms were investigated and compared between nonheavy drinkers and heavy drinkers.

 

Agarose gel IEF shows additional cathodal bands in serum of chronic alcohol abusers. Mean total β-HEX activity between pH 6.8 and 7.7, designated as HEX-7, showed the highest correlation with %CDT (r = 0.70, p < 0.0001, n = 68). In a selected subgroup, where CDT could not be quantified (n = 13) because of an atypical electropherogram, HEX-7 was in concordance with either estimated %CDT value or liver enzyme activities.

 

In this proof-of-concept study, we introduce a novel approach to quantify β-HEX isoforms using preparative IEF and fluorimetry. A highly significant correlation of HEX-7 and %CDT has been found. Because of exclusion of the P isoform, HEX-7 could be a useful supplementary marker for detecting chronic alcohol abuse.


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Request Reprint E-Mail:  joris.delanghe@ugent.be

Associations Between Multivitamin Supplement Use and Alcohol Consumption Before Pregnancy: Pregnancy Risk Assessment Monitoring System, 2004 to 2008

Approximately 50 to 70% of childbearing-aged women consume alcohol and up to 23% of pregnancies have some level of prenatal alcohol exposure.

Using data from the Pregnancy Risk Assessment Monitoring System from 2004 to 2008, 111,644 women who completed questions relating to periconceptional alcohol use and multivitamin supplement use were included in the study. This study explored associations between periconceptional alcohol use and multivitamin supplementation use. Weighted multivariable logistic regression was used to explore associations, adjusting for maternal education, maternal ethnicity, maternal age, household income, and parity.

 

During the periconceptional period, a dose-dependent association was found where women who consumed alcohol (≤3 drinks/wk, odds ratio [OR] = 0.76; 4 to 6 drinks/wk, OR = 0.60; 7 to 13 drinks/wk, OR = 0.49; ≥14 drinks/wk, OR = 0.39) and binged on alcohol (1 time, OR = 0.76; 2 to 3 times, OR = 0.66; 4 to 5 times, OR = 0.56; ≥6 times, OR = 0.50) were significantly less likely to take a multivitamin supplement compared with those that did not consume alcohol.

 

These findings emphasize the importance of periconceptional multivitamin supplement use, especially among alcohol-consuming women of childbearing age.


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Request Reprint E-Mail:     lbweiss@ucsd.edu:   

Minimum Alcohol Prices and Outlet Densities in British Columbia, Canada: Estimated Impacts on Alcohol-Attributable Hospital Admissions

 

We investigated whether periodic increases in minimum alcohol prices were associated with reduced alcohol-attributable hospital admissions in British Columbia.

The longitudinal panel study (2002–2009) incorporated minimum alcohol prices, density of alcohol outlets, and age- and gender-standardized rates of acute, chronic, and 100% alcohol-attributable admissions. We applied mixed-method regression models to data from 89 geographic areas of British Columbia across 32 time periods, adjusting for spatial and temporal autocorrelation, moving average effects, season, and a range of economic and social variables.

A 10% increase in the average minimum price of all alcoholic beverages was associated with an 8.95% decrease in acute alcohol-attributable admissions and a 9.22% reduction in chronic alcohol-attributable admissions 2 years later. A Can$ 0.10 increase in average minimum price would prevent 166 acute admissions in the 1st year and 275 chronic admissions 2 years later. We also estimated significant, though smaller, adverse impacts of increased private liquor store density on hospital admission rates for all types of alcohol-attributable admissions.

 

Significant health benefits were observed when minimum alcohol prices in British Columbia were increased. By contrast, adverse health outcomes were associated with an expansion of private liquor stores.

 

 

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Request Reprint E-Mail:   timstock@uvic.ca

Drinking Patterns of Older Adults with Chronic Medical Conditions

 

 

Understanding alcohol consumption patterns of older adults with chronic illness is important given the aging baby boomer generation, the increase in prevalence of chronic conditions and associated medication use, and the potential consequences of excessive drinking in this population.

 

To estimate the prevalence of alcohol consumption patterns, including at-risk drinking, in older adults with at least one of seven common chronic conditions.

This descriptive study used the nationally representative 2005 Medicare Current Beneficiary Survey linked with Medicare claims. The sample included community-dwelling, fee-for-service beneficiaries 65 years and older with one or more of seven chronic conditions (Alzheimer’s disease and other senile dementia, chronic obstructive pulmonary disease, depression, diabetes, heart failure, hypertension, and stroke; n = 7,422). Based on self-reported alcohol consumption, individuals were categorized as nondrinkers, within-guidelines drinkers, or at-risk drinkers (exceeds guidelines).

 

Overall, 30.9 % (CI 28.0–34.1 %) of older adults with at least one of seven chronic conditions reported alcohol consumption in a typical month in the past year, and 6.9 % (CI 6.0–7.8 %) reported at-risk drinking. Older adults with higher chronic disease burdens were less likely to report alcohol consumption and at-risk drinking.

 

Nearly one-third of older adults with selected chronic illnesses report drinking alcohol and almost 7 % drink in excess of National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines. It is important for physicians and patients to discuss alcohol consumption as a component of chronic illness management. In cases of at-risk drinking, providers have an opportunity to provide brief intervention or to offer referrals if needed.

 

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Request  Reprint E-Mail:   mryan@brandeis.edu.

 

 

Binge Drinking Found to Impair Vascular Function in Healthy Young Adults

History of repeated binge drinking in healthy young adults caused alterations in macro- and microvascular function similar to those seen in individuals with recognized cardiovascular risk factors, according to a study published April 23 in the Journal of the American College of Cardiology (JACC).  > > > >   Read More

Binge Drinking Impairs Vascular Function in Young Adults

The study aimed to assess whether young binge drinkers have impaired macrovascular and microvascular function and cardiovascular (CV) disease risk factors compared to age-matched alcohol abstainers.

Binge drinking rates are highest on college campuses and among 18- to 25-year-olds; however, macrovascular and microvascular endothelial function in young adults with a history of repeated binge drinking (≥5 standard drinks in 2 hrs. in men; ≥4 standard drinks in 2 hrs. in women) has not been investigated

We evaluated the cardiovascular profile, brachial artery endothelial-dependent flow mediated vasodilation (FMD), and flow independent nitroglycerin (NTG)-mediated dilation and vasoreactivity of resistance arteries (isolated from gluteal fat biopsies) in abstainers and binge drinkers.

Men and women (18-25 years of age, abstainers [A] n = 17, binge drinkers [BD] n = 19) were enrolled. Among the BD group, past-month average number of binge episodes was 6 ± 1, and average duration of binge drinking behavior was 4 ± 0.6 years. FMD and NTG-mediated dilations were significantly lower in the BD (FMD: 8.4% ± 0.7, P = 0.022; NTG: 19.6% ± 2, P = 0.009) than the A group (FMD: 11 ± 0.7%; NTG: 28.6 ± 2%). ACh- and SNP-induced dilation in resistance arteries was not significantly different between the A and BD groups. However, ET-1-induced constriction was significantly enhanced in the BD group compared to the A group (P = 0.032). No differences between groups were found in blood pressure, lipoproteins, and C-reactive protein.

Alterations in the macrocirculation and microcirculation may represent early clinical manifestations of CV risk in otherwise healthy young binge drinkers. This study has important clinical implications for screening young adults for a repeated history of binge drinking.

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Request Reprint E-Mail:  shanep@uic.edu

Ethanol- and/or Taurine-Induced Oxidative Stress in Chick Embryos

Because taurine alleviates ethanol- (EtOH-) induced lipid peroxidation and liver damage in rats, we asked whether exogenous taurine could alleviate EtOH-induced oxidative stress in chick embryos.

Exogenous EtOH (1.5 mmol/Kg egg or 3 mmol/Kg egg), taurine (4 mol/Kg egg), or EtOH and taurine (1.5 mmol EtOH and 4 mol taurine/Kg egg or 3 mmol EtOH and 4 mol taurine/Kg egg) were injected into fertile chicken eggs during the first three days of embryonic development (E_0–2). At 11 days of development (midembryogenesis), serum taurine levels and brain caspase-3 activities, homocysteine (HoCys) levels, reduced glutathione (GSH) levels, membrane fatty acid composition, and lipid hydroperoxide (LPO) levels were measured.

Early embryonic EtOH exposure caused increased brain apoptosis rates (caspase-3 activities); increased brain HoCys levels; increased oxidative-stress, as measured by decreased brain GSH levels; decreased brain long-chain polyunsaturated levels; and increased brain LPO levels.

Although taurine is reported to be an antioxidant, exogenous taurine was embryopathic and caused increased apoptosis rates (caspase-3 activities); increased brain HoCys levels; increased oxidative-stress (decreased brain GSH levels); decreased brain long-chain polyunsaturated levels; and increased brain LPO levels.

Combined EtOH and taurine treatments also caused increased apoptosis rates and oxidative stress.


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mTOR activation is required for the anti-alcohol effect of ketamine, but not memantine, in alcohol-preferring rats

 

Glutamate NMDA receptors mediate many molecular and behavioral effects of alcohol, and they play a key role in the development of excessive drinking. Uncompetitive NMDA receptor antagonists may, therefore, have therapeutic potential for alcoholism.

The first aim was to compare the effects of the NMDA antagonists memantine and ketamine on ethanol and saccharin drinking in alcohol-preferring rats. The second aim was to determine whether the effects of the two NMDA receptor antagonists were mediated by the mammalian target of rapamycin (mTOR).

TSRI Sardinian alcohol-preferring rats were allowed to self-administer either 10% w/v ethanol or 0.08% w/v saccharin, and water. Operant responding and motor activity were assessed following administration of either memantine (0–10 mg/kg) or ketamine (0–20 mg/kg). Finally, ethanol self-administration was assessed in rats administered with either memantine or ketamine but pretreated with the mTOR inhibitor rapamycin (2.5 mg/kg).

The uncompetitive NMDA receptor antagonists memantine and ketamine dose-dependently reduced ethanol drinking in alcohol-preferring rats; while memantine had a preferential effect on alcohol over saccharin, ketamine reduced responding for both solutions. Neither antagonist induced malaise, as shown by the lack of effect on water intake and motor activity. The mTOR inhibitor rapamycin blocked the effects of ketamine, but not those of memantine.

Memantine and ketamine both reduce alcohol drinking in alcohol-preferring rats, but only memantine is selective for alcohol. The effects of ketamine, but not memantine, are mediated by mTOR. The results support the therapeutic potential of uncompetitive NMDA receptor antagonists, especially memantine, in alcohol addiction.

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Alcohol hangover: Type and time-extension of motor function impairments

Alcohol hangover is defined as the unpleasant next-day state following an evening of excessive alcohol consumption. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. During hangover cognitive functions and subjective capacities are affected along with inefficiency, reduced productivity, absenteeism, driving impairments, poor academic achievement and reductions in motor coordination.

The aim of this work was to study the type and length of motor and exploratory functions from the beginning to the end of the alcohol hangover.

Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance, walking deficiency, motor strength, locomotion and exploratory activity were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset).

Motor performance was 80% decreased at the onset of hangover (p < 0.001). Hangover mice exhibited a reduced motor performance during the next 16 h (p < 0.01). Motor function was recovered 20 h after hangover onset. Hangover mice displayed walking deficiencies from the beginning to 16 h after hangover onset (p < 0.05).

Moreover, mice suffering from a hangover, exhibited a significant decrease in neuromuscular strength during 16 h (p < 0.001). Averaged speed and total distance traveled in the open field test and the exploratory activity on T-maze and hole board tests were reduced during 16 h after hangover onset (p < 0.05).

Our findings demonstrate a time-extension between 16 to 20 h for hangover motor and exploratory impairments. As a whole, this study shows the long lasting effects of alcohol hangover.


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Report to Congress on the Nation's Substance Abuse and Mental Health Workforce Issues

Provides an overview of the facts and issues affecting the substance abuse and mental health workforce in America. Presents demographic data on the workforce, major factors that impact the workforce, and efforts to address workforce challenges.


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Industry Use of Evidence to Influence Alcohol Policy: A Case Study of Submissions to the 2008 Scottish Government Consultation

 

Summary Points

• We examine how research evidence is used in alcohol industry submissions made to a Scottish Government consultation in 2008 to advocate policies in line with their commercial interests.
• Industry actors consistently oppose the approaches found in research to be most likely to be effective at a population level without actually engaging with the research literature in any depth.
• Strong evidence is misrepresented and weak evidence is promoted. Unsubstantiated claims are made about the adverse effects of unfavoured policy proposals and advocacy of policies favoured by industry is not supported by the presentation of evidence.
• The potential for corporations with vested interests to interfere with the evaluation of scientific evidence by policy makers needs to be restricted for effective policies to be designed.
• Studies of the nature of alcohol industry and other corporate influences on public policies can be informed by work already conducted on the tobacco industry.

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Briefing warns of sharp rise in admissions of older people with alcohol-related mental health problems

An Alcohol Concern briefing has warned of a 150% rise in hospital admissions for over 60’s with alcohol related mental health problems in the last decade. The briefing 'Trends in alcohol related admissions for older people with mental health problems: 2002 to 2012' finds a disproportionate rise amongst older adults, despite an overall rise in all adults and accounting for a growing older population.   > > > >  Read More

World Health Authorities meet in Istanbul to discuss alcohol policy

The Turkish Green Crescent Society will hold the first symposium on alcohol policies in Turkey with the World Health Organization. Margaret Chan, will be a guest speaker.

The Turkish Prime Minister, Recep Tayyip Erdogan, will attend the opening part of the symposium.

The “Global Alcohol Policy Symposium” will take place on April 26-27 and will bring together more than 1200 leading experts from 53 countries.   > > > >  Read More

Multi-cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

 

 

A number of studies have reported associations between the serotonin transporter gene (SLC6A4) and alcohol, heroin, cocaine, or methamphetamine abuse. Other studies have yielded contrary results. There are a number of reasons for non-replication, including inadequate statistical power, population stratification, and poor phenotype definition.

 

This study was to test the association using a meta-analytic approach across a variety of racial and ethnic populations. Using the genotype data of 55 studies (7999 cases, 8264 controls, and 676 families or parent-offspring trios) published in the past 15 years, we have conducted comprehensive meta-analyses to examine the associations of the 5-HTTLPR and STin2 polymorphisms with substance use disorder.

 

The meta-analyses support the associations of 5-HTTLPR with alcohol, heroin, cocaine, and methamphetamine dependence and abuse (eg, the smallest P-values were 0.0058 with odds ratio (OR)=0.54 (0.35, 0.84); 0.0024 with OR=0.77 (0.66, 0.91); 0.018 with OR=1.38 (1.06, 1.81); and 0.028 with OR=0.46 (0.23, 0.92) for alcohol, heroin, cocaine, and methamphetamine dependence/abuse, respectively).

 

When all the phenotypes are combined, the P-value was 0.0006 with OR=0.86 (0.78, 0.94) in the combined European, Asian, and Mexican populations and P-value was 0.0028 with OR=1.41 (1.13, 1.78) in the African populations.

Evidence of significant associations was also identified in other subgroup analyses regarding differently combined substance and populations. The effect sizes of 5-HTTLPR were comparable among the European, Asian, and Mexican populations, however, the risk allele was more frequent in Asians than in Europeans and Mexicans. The opposite directions of risk allele in African population might be driven by the opposite directions of risk allele in cocaine dependence.

 

This meta-analysis supports that the association of the SLC6A4 gene with substance use disorder varies depending on substances with different risk allele frequencies in the multi-cultural populations. Further studies using larger sample size are warranted.

 

 

 

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