For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.
Saturday, April 21, 2012
Alcohol use and abuse play a major role in both crime and negative health outcomes in Scotland.
This paper provides a description and ethical and legal analyses of a novel remote alcohol monitoring scheme for offenders which seeks to reduce alcohol-related harm to both the criminal and the public.
It emerges that the prospective benefits of this scheme to health and public order vastly outweigh any potential harms.
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"I THINK WE'LL BEGIN. WE'LL VERY FORTUNATE TO HAVE TWO GLOBAL LEADERS IN THE FIELD OF ADDICTION. I'LL TELL YOU JUST A LITTLE BIT ABOUT THEM IN A MOMENT. BUT IN THINKING ABOUT TODAY'S SESSION AND TALKING ABOUT IT WITH SEVERAL POST DOCS AND FELLOWS, SOME OF THESE QUESTIONS POPPED UP AS THE THINGS THAT CROSSED OUR MINDS. AND I SUSPECT FOR THOSE OF YOU WHO ARE NOT DEEPLY FAMILIAR WITH ALL OF THIS, VERY SIMILAR THINGS. SO THIS ISN'T REALLY A QUIZ BUT IT'S SOMETHING YOU MIGHT THINK ABOUT.
THESE ARE WHAT WE WERE TALKING ABOUT, IS ADDICTION A PSYCHOLOGICAL OR AN ORGANIC BRAIN DISEASE? OR IS IT BOTH? CAN YOU PREDICT VULNERABILITY? WHO IS ON GOING TO BECOME ADDICTED. ISN'T THERE ANY WAY IT'S POSSIBLE TO DETERMINE OR GET SOME CLUES ABOUT THAT. SO IF THERE IS SOME VULNERABILITY, IS THERE A GENETIC BASIS AND IF SO HOW IMPORTANT IS THAT. IN A WAY, A SUBTITLE OF TODAY'S SESSION COULD BE ADDICTION IN THE GENOMIC ERA, BECAUSE THIS IS A POWERFUL TOOL FOR PROBING BEYOND THE CLASSICAL EPIDEMIOLOGY TYPE STUDIES OF ADDICTION AND FAMILIES OR DIFFERENT TIMES AND GENDERS AND SUCH. A VERY IMPORTANT QUESTION THAT ONE OF MY POST DOCS ASKED ME WAS IS ADDICTION A DEVELOPMENTAL DISEASE. MEANING IS IT SOMETHING THAT OCCURS ESSENTIALLY, IS THE STAGE SET EARLY IN LIFE. OR IS IT SOMETHING YOU CAN SORT OF ACQUIRE ANYWHERE. . . . . "
Human epidemiological and animal experimental data indicate that the risk of developing adult onset diseases and neurological disorders is influenced by persistent adaptations to prenatal and early postnatal environmental exposures.
One group of epigenetically regulated genes that potentially links environmental exposures early in development to adult diseases are those with metastable epialleles. These genes have highly variable expression because of stochastic allelic changes in the epigenome rather than mutations in the genome. The viable yellow agouti (Avy) mouse harbors a metastable Agouti gene because of an upstream insertion of a transposable element.
We have used the Avy mouse to investigate the importance of epigenetic alterations in determining adult disease risk in response to early developmental exposure to both chemical and physical agents.
The importance these studies with regards to human health and disease will be discussed.
Advances in the fields of genomics and genetics in the last decade have identified a large number of genes that can potentially influence alcohol-drinking behavior in humans as well as animal models. Consequently, the task of identifying efficient molecular targets that could be used to develop effective therapeutics against the disease has become increasingly daunting.
One of the reasons for this is the fact that each of the many alcohol-responsive genes only contributes a small effect to the overall mechanism and disease phenotype, as is characteristic of complex traits.
Current research trends are hence shifting toward the analysis of gene networks rather than emphasizing individual genes. The discovery of microRNAs and their mechanisms of action on regulation of transcript level and protein translation have made evident the utility of these small non-coding RNA molecules that act as central coordinators of multiple cross-communicating cellular pathways.
Cells exploit the fact that a single microRNA can target hundreds of mRNA transcripts and that a single mRNA transcript can be simultaneously targeted by distinct microRNAs, to ensure fine-tuned and/or redundant control over a large number of cellular functions. By the same token, we can use these properties of microRNAs to develop novel, targeted strategies to combat complex disorders.
In this review, we will focus on recent discoveries of microRNA signatures in brain of human alcoholics supporting the hypothesis that changes in gene expression and regulation by microRNAs are responsible for long-term neuroadaptations occurring during development of alcoholism.
We also discuss insights into the potential modulation of epigenetic regulators by a subset of microRNAs. Taken together, microRNA activity may be controlling many of the cellular mechanisms already known to be involved in the development of alcoholism, and suggests potential targets for the development of novel therapeutic interventions.
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The present study evaluated the heritability of personality traits and psychopathology symptoms assessed by the Minnesota Multiphasic Personality Interview 2nd edition (MMPI-2) in a family-based sample selected for alcohol dependence.
Participants included 950 probands and 1204 first-degree relatives recruited for the UCSF Family Alcoholism Study.
Heritability estimates (h2) for MMPI-2 scales ranged from .25–.49. When alcohol dependence was used as a covariate, heritability estimates remained significant but generally declined.
However, when the MMPI-2 scales were used as covariates to estimate the heritability of alcohol dependence, scales measuring antisocial behavior (ASP), depressive symptoms (DEP), and addictive behavior (MAC-R) led to moderate increases in the heritability of alcohol dependence.
This suggests that the ASP, DEP, and MAC-R scales may explain some of the non-genetic variance in the alcohol dependence diagnosis in this population when utilized as covariates, and thus may serve to produce a more homogeneous and heritable alcohol dependence phenotype.
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Friday, April 20, 2012
GABAB receptors do not internalize after baclofen treatment, possibly due to a lack of β-arrestin association: Study with a real-time visualizing assa
The mechanism of agonist-induced GABAB receptor (GABABR) internalization is not well understood. To investigate this process, we focused on the interaction of GABABR with β-arrestins, which are key proteins in the internalization of most of the G protein-coupled receptors (GPCRs), and the agonist-induced GABABR internalization and the interaction of GABABR with β-arrestin1 and β-arrestin2 were investigated in real time using GABABR and β-arrestins both of which were fluorescent protein-tagged.
We then compared these profiles with those of μ-opioid receptors (μOR), well-studied receptors that associate and co-internalize with β-arrestins.
When stimulated by the specific GABABR agonist baclofen, GABABR composed of GABAB1aR (GB1aR) and fluorescent protein-tagged GABAB2R-Venus (GB2R-V) formed functional GABABR; they elicited G protein-activated inwardly rectifying potassium channels as well as non-tagged GABABR.
In cells coexpressing GB1aR, GB2R-V, and β-arrestin1-Cerulean (βarr1-C) or β-arrestin2-Cerulean (βarr2-C), real-time imaging studies showed that baclofen treatment neither internalized GB2R-V nor mobilized βarr1-C or βarr2-C to the cell surface.
This happened regardless of the presence of G protein-coupled receptor kinase 4 (GRK4), which forms a complex with GABABR and causes GABABR desensitization. On the other hand, in cells coexpressing μOR-Venus, GRK2, and βarr1-C or βarr2-C, the μOR molecule formed μOR/βarr1 or μOR/βarr2 complexes on the cell surface, which were then internalized into the cytoplasm in a time-dependent manner.
Fluorescence resonance energy transfer (FRET) assay also indicated scarce association of GB2R-V and β-arrestins-C with or without the stimulation of baclofen, while robust association of μOR-V with β-arrestins-C was detected after μOR activation.
These findings suggest that GABABR's failure to undergo agonist-induced internalization results in part from its failure to interact with β-arrestins.
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Dopamine and serotonin (5-HT) in the nucleus accumbens (ACC) and ventral tegmental area of the mesoaccumbens reward pathways have been implicated in the mechanisms underlying development of alcohol dependence.
We used a C57BL/6J mouse model with increased voluntary alcohol-drinking behavior by exposing the mice to alcohol vapor for 20 consecutive days. In the alcohol-exposed mice, the expression of 5-HT2C receptor mRNA increased in the ACC, caudate nucleus and putamen, dorsal raphe nucleus (DRN), hippocampus and lateral hypothalamus, while the protein level of 5-HT2C receptor significantly increased in the ACC.
The expression of 5-HT7 receptor mRNA increased in the ACC and DRN. Contents of 5-HT decreased in the ACC shell (ACCS) and DRN of the alcohol-exposed mice. The basal extracellular releases of dopamine (DA) and 5-HT in the ACCS increased more in the alcohol-exposed mice than in alcohol-naïve mice.
The magnitude of the alcohol-induced ACCS DA and 5-HT release in the alcohol-exposed mice was increased compared with the control mice. Intraperitoneal (i.p.) administration or local injection into ACCS of the 5-HT2C receptor antagonist, SB-242084, suppressed voluntary alcohol-drinking behavior in the alcohol-exposed mice. But the i.p. administration of the 5-HT7 receptor antagonist, SB-258719, did not have significant effects on alcohol-drinking behavior in the alcohol-exposed mice. The effects of the
5-HT2C receptor antagonist were not observed in the air-exposed control mice.
These results suggest that adaptations of the 5-HT system, especially the upregulation of 5-HT2C receptors in the ACCS, are involved in the development of enhanced voluntary alcohol-drinking behavior.
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Drowsy driving and drink driving are two of the major causes of serious traffic accidents, which arouse an area of great socioeconomic concern. Continuous monitoring of drivers’ state thus is of great importance to reduce drowsy and drunken caused accidents.
An early warning system was proposed for real-time driver state monitoring. The system not only eliminates drink driving by sensor technique, but also uses a computer vision system to track the eyes for drowsiness detection of drivers.
The experimental results of this system showed exceed 88.3% eye detection rate which verified the practicability of the system.
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Association of µ-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in alcohol dependence: a systematic review and meta-analysis
Previous studies have suggested that the effect of naltrexone in patients with alcohol dependence may be moderated by genetic factors. In particular, the possession of the G allele of the A118G polymorphism of the µ-opioid receptor gene (OPRM1) has been associated with a better response to naltrexone, although controversial results have been reported.
The aim of this paper is to combine previous findings by means of a systematic review and a meta-analysis. We retrieved studies on the relationship between A118G polymorphism in OPRM1 gene and response to treatment with naltrexone in patients with alcohol dependence by means of electronic database search.
A meta-analysis was conducted using a random-effects model. Calculations of odds ratio (OR) and their confidence intervals (CI) and tests for heterogeneity of the results have been performed. Six previous studies have analyzed the role of A118G polymorphism in response to naltrexone for alcohol dependence.
After meta-analysis, we found that naltrexone-treated patients carrying the G allele had lower relapse rates than those who were homozygous for the A allele (OR: 2.02, 95% CI 1.26–3.22; P = 0.003). There were no differences in abstinence rates.
Our results support the fact that the G allele of A118G polymorphism of OPRM1 moderates the effect of naltrexone in patients with alcohol dependence. This genetic marker may therefore identify a subgroup of individuals more likely to respond to this treatment.
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Webinars - Supporting Recovery from Alcohol or Drug Addiction on Campus Recovery High Schools & Collegiate Recovery Programs
NCSL Webinars allow attendees to participate in meetings taking place around the world from the comfort of their desk. They are collaborative, interactive and easy to use. Most webinars will be recorded for those who are unable to attend the live meeting.
Supporting Recovery from Alcohol or Drug Addiction on Campus Recovery High Schools & Collegiate Recovery Programs
Monday, April 23, 2012
1 p.m. ET/ Noon CT/ 11 a.m. MT/10 a.m. PT
Online Registration* available now!
You are invited to a free* webinar specifically for state policy makers, including past graduates of the Addiction Studies Program for the States; legislators and their staffs, and members of state Executive Branches.
This webinar will provide participants information about the latest advances in recovery high schools and collegiate recovery programs at publicly funded colleges and universities.
This must-attend, policy-oriented webinar will feature presentations by:
- Peter Gaumond, MA; Chief, Recovery Branch at Office of National Drug Control Policy. Mr. Gaumond will speak about the importance of recovery and recovery support services, including educational support programs to achieving key goals of the National Drug Control Strategy (NDCS).
- David Friedman, Ph.D.; Wake Forest University and co-Director of the Addiction Studies Program (ASP) for the States. Dr. Friedman’s presentation will be on the neurobiology of drug/alcohol addiction among adolescents and young adults.
- Andrew Finch, Ph.D.; Vanderbilt University who will present initial findings from a NIDA-funded evaluation of recovery high schools.
- Kitty Harris, Ph.D.; expert on collegiate programs and Director of the Texas Tech University Center for Studies on Addiction and Recovery and of the Texas Tech collegiate recovery program, will explain the various forms that collegiate recovery programs have taken and present what is currently known about their effectiveness.
Recovery/Remission from Substance Use Disorders: An Analysis of Reported Outcomes in 415 Scientific Reports, 1868-2011
The emergence of recovery as an organizing paradigm for addiction treatment and the larger arena of behavioral health care underscores the need to measure both early recovery initiation and stabilization and the prevalence of long-term recovery maintenance. Such measurement is critical in evaluating addiction treatment as a system of care and monitoring broader dimensions of community health.
Efforts to measure recovery are challenged by the lack of professional and cultural consensus on the definition and measurement of key constructs (recovery, remission, abstinence, and subclinical/asymptomatic/controlled/moderate use) and by conflicting rates of recovery—rates reported across clinically and culturally diverse populations in studies marked by widely varying methodologies, follow-up periods, and follow-up rates. Of particular import is the wide divergence between portrayals of the natural course of alcohol and other drug (AOD) problems in community populations and portrayals of such problems in clinical populations following specialized addiction treatment. These divergent portrayals constitute the ultimate “apples and oranges” of the AOD problems arena.
The question of recovery stability and prevalence is more than an academic one. The constant media onslaught of celebrities heading back to “rehab” after their latest falls from grace has produced a public unsure of exactly what “recovery” means and whether it is really
attainable for all, or for only a few “morally enlightened” exceptions to the rule. The failure of a celebrity to achieve stable recovery garners great cultural attention, while the masses of those
in long-term recovery pass invisibly through our culture each day. Recovery surrounds us in our
neighborhoods, our businesses, our schools, and our houses of worship, but we do not see it. We see instead the highly visible fruits of the problem. The pessimism flowing from such selective attention feeds misunderstanding and fuels stigma and its far-reaching consequences.
This paper reviews 415 scientific studies of recovery outcomes (79 community studies,
276 adult clinical studies, and 60 adolescent clinical studies) conducted with clinically and
culturally diverse populations in multiple countries over the past century. This review provides preliminary answers to five of the most important questions about recovery from alcohol and
other drug problems.
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Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with nonalcoholic fatty liver disease (NAFLD)
Nonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor. Although modest alcohol consumption may reduce the risk for cardiovascular mortality, whether patients with NAFLD should be allowed modest alcohol consumption remains an important unaddressed issue. We aimed to evaluate the association between modest alcohol drinking and nonalcoholic steatohepatitis(NASH), among subjects with NAFLD.
In a Cross-sectional analysis of adult participants in the NIH NASH Clinical Research Network, only modest or non-drinkers were included: participants identified as 1) drinking > 20gm/day, 2) binge drinkers, or 3) non-drinkers with previous alcohol consumption were excluded. The odds of having a histological diagnosis of NASH and other histological features of NAFLD were analyzed using multiple ordinal logistic regression.
The analysis included 251 lifetime non-drinkers and 331 modest drinkers. Modest drinkers compared to nondrinkers had lower odds of having a diagnosis of NASH (Summary odds ratio 0.56, 95%CI 0.39-0.84, p=0.002). The odds of NASH decreased as the frequency of alcohol consumption increased within the range of modest consumption. Modest drinkers also had significantly lower odds for fibrosis (OR 0.56 95%CI 0.41–0.77) and ballooning hepatocellular injury (OR 0.66 95%CI 0.48–0.92) than lifetime non-drinkers.
In a large, well-characterized population with biopsy-proven NAFLD, modest alcohol consumption was associated with lesser degree of severity as determined by lower odds of the key features that comprise a diagnosis of steatohepatitis, as well as fibrosis. These findings demonstrate the need for prospective studies and a coordinated consensus on alcohol consumption recommendations in NAFLD.
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Thursday, April 19, 2012
The role of kappa-opioid receptors (KOR) in the regulation of alcohol-related behaviors is not completely understood. For example, alcohol consumption has been reported to increase following treatment with KOR antagonists in rats, but was decreased in mice with genetic deletion of KOR. Recent studies have further suggested that KOR antagonists may selectively decrease alcohol self-administration in rats following a history of dependence.
We assessed the effects of the KOR antagonist JDTic on alcohol self-administration, reinstatement of alcohol seeking induced by alcohol-associated cues or stress, and acute alcohol withdrawal-induced anxiety (‘hangover anxiety’).
JDTic dose-dependently reversed hangover anxiety when given 48 hours prior to testing, a time interval corresponding to the previously demonstrated anxiolytic efficacy of this drug. In contrast, JDTic decreased alcohol self-administration and cue-induced reinstatement of alcohol seeking when administered 2 hours prior to testing, but not at longer pre-treatment times. For comparison, we determined that the prototypical KOR antagonist nor-binaltorphimine can suppress self-administration of alcohol at 2 hours pre-treatment time, mimicking our observations with JDTic.
The effects of JDTic were behaviorally specific, as it had no effect on stress-induced reinstatement of alcohol seeking, self-administration of sucrose, or locomotor activity. Further, we demonstrate that at a 2 hours pre-treatment time JDTic antagonized the antinociceptive effects of the KOR agonist U50,488H but had no effect on morphine-induced behaviors.
Our results provide additional evidence for the involvement of KOR in regulation of alcohol-related behaviors and provide support for KOR antagonists, including JDTic, to be evaluated as medications for alcoholism.
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It highlights the connection between evidence and policy and practice is relatively recent – a connection which has risen with some force since the 1970s. The post explores:
- temperance investigation and how it became science
- interest in the action of alcohol on the body
- the particular impact of the First World War
- drink driving and science
- new influences coming from the US and WHO
- new directions in Britain after the Second World War
- the rise of ‘evidence’
- international networks
- the former AERC, now run as Alcohol Research UK
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Genetic Dissection of Acute Ethanol Responsive Gene Networks in Prefrontal Cortex: Functional and Mechanistic Implications
Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol.
Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity.
Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2.
The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol response of gene networks could have important implications for future studies regarding the mechanisms and treatment of alcohol use disorders.
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Key Recent Milestones:
· China: Global Actions began training police on conducting roadside breath alcohol surveys on April 16 for the drink driving initiative in Nanjing.
Global Actions in Focus: October 2012 Conference
ICAP has announced that registration is now available for the international conference Global Actions: Initiatives to Reduce Harmful Drinking in Washington, D.C. on October 8 and 9, 2012.
The event will feature presentations of industry-sponsored initiatives from around the world in support of the World Health Organization (WHO) Global Strategy to Reduce the Harmful Use of Alcohol.
A provisional agenda is now available on the conference website. Speakers will be announced closer to the date.
“This conference is the first of its kind globally,” said ICAP President Marcus Grant. “Since WHO adopted the Global Strategy in 2010, there hasn’t been an opportunity to take stock of what has been done by governments, industry, civil society, and other key stakeholders. This conference will be the first chance for the international community to assess what has been achieved, particularly when it comes to industry actions.”
Agenda highlights include participation from CEOs of major alcohol producers in sessions dedicated to topics such as: conflicts of interest; evaluation of initiatives; the roles of developers, producers, distributers, and sellers; and multi-stakeholder cooperation.
What’s Happening Next:
· Worldwide: With United Nations Economic and Social Council (UN ECOSOC) special consultative status, ICAP staff will be attending the United Nations Commission on Population and Development session from April 23 to 27 in New York.
· Vietnam: The Global Actions workshop “Production, Consumption, and Use of Noncommercial Alcohol” is scheduled for April 27 in Hanoi.
Critique 079: Moderate alcohol consumption both prior to, and following, a myocardial infarction is associated with lower risk of mortality — 17 April
Pai JK, Mukamal KJ, Rimm EB. Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study. European Heart Journal 2012; doi:10.1093/eurheartj
The present paper is based on data from a very well-done prospective follow-up study of male health professionals, initially recruited in 1986. Among the cohort, 1,818 men had a confirmed myocardial infarction (MI) during follow up. The alcohol intake of the subjects had been recorded prior to, and at intervals following, the MI.
There are a number of informative and interesting results described from this study. First, there was little change in reported alcohol prior to and following the MI: drinkers tended to remain drinkers of similar amounts. Few non-drinkers began to drink after their MI; among heavier drinkers, there was a tendency to decrease the amount somewhat (but very few stopped drinking completely). There were no significant differences in outcome according to type of beverage consumed although, interestingly, lower hazard ratios were seen for consumers of beer and liquor than of wine.
The associations of alcohol consumption with mortality were almost the same for alcohol intake reported prior to the MI as that reported after the MI: for 10-29.9 g/day, the adjusted hazard ratio for mortality was 0.70 for both. While the authors state that the effects of alcohol were stronger for the association with non-anterior MIs, the HRs for all-cause mortality were little different: among the moderately drinking men the HRs were 0.58 for anterior MI and 0.51 for other types of MI when compared with abstainers.
The overall results show that, in comparison with no alcohol consumption, the intake of light (0.1-9.9 g/day) and moderate (10.0-29.9 g/d) amounts of alcohol was associated with lower risk of all-cause mortality and cardiovascular morality. The significant reductions in all-cause mortality risk (22% lower for 0.1-9.9 g/day and 34% lower for 10.0 – 29.9 g/day, in comparison with non-drinkers) were no longer present for consumers of ≥ 30 g/day; for this
highest consumer group, the adjusted hazard ratio was 0.87 with 95% CI of 0.61-1.25.
As stated by the authors: “Our findings are consistent with the recent European Society of Cardiology (ESC) recommended guidelines for long-term management of acute coronary syndromes that moderate alcohol consumption of 10–30 g per day in men should not be discouraged and may be beneficial for long-term prognosis after MI.1-3” > > > > Read More
Alcohol is a commonly used drug worldwide. Epidemiological studies have identified alcohol consumption as a factor that may either positively or negatively influence many diseases including cardiovascular disease, certain cancers and dementia.
Often there seems to be a differential effect of various drinking patterns, with frequent moderate consumption of alcohol being salutary and binge drinking or chronic abuse being deleterious to one’s health.
A better understanding of the cellular and molecular mechanisms mediating the many effects of alcohol consumption is beginning to emerge, as well as a clearer picture as to whether these effects are due to the direct actions of alcohol itself, or caused in part by its metabolites, e.g., acetaldehyde, or by incidental components present in the alcoholic beverage (e.g., polyphenols in red wine).
This review will discuss evidence to date as to how alcohol (ethanol) might affect atherosclerosis that underlies cardiovascular and cerebrovascular disease, and the putative mechanisms involved, focusing on vascular endothelial and smooth muscle cell effects.
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Studies have found that higher levels of cardiorespiratory fitness and light to moderate alcohol intake reduce the risk for premature death. Scant evidence, however, exists assessing the joint effects of both measures on all-cause and cardiovascular disease (CVD) mortality.
This study aims to examine the independent and joint effects of alcohol consumption and cardiorespiratory fitness on all-cause and cardiovascular-related mortality in a large cohort of men.
This prospective study included 29,402 men who came to the Cooper Clinic (Dallas, TX) for a preventive medicine visit from 1973 to 2006. Data were analyzed in 2011. The primary exposure variables were tertiles of cardiorespiratory fitness and four categories of alcohol consumption, and the outcomes were all-cause and CVD mortality. Cox proportional hazards regression was used to model the association between alcohol intake, cardiorespiratory fitness, and all-cause and CVD mortality, controlling for potential confounders.
A total of 1830 (all-cause) and 523 (CVD) deaths occurred in men over an average follow-up period of 17.4 years (SD=9.1). A linear relationship was observed (p<0.001) between increased fitness and reduced all-cause and CVD mortality. Specifically, moderate and high levels of fitness reduced the risk for all-cause mortality (HR=0.67, 95% CI=0.60, 0.74, and HR=0.57, 95% CI=0.49, 0.67, respectively) and CVD mortality in comparison to the low-fitness reference group (HR=0.70, 95% CI=0.57, 0.85; HR=0.54, 95% CI=0.40, 0.75, respectively), while controlling for alcohol intake and other covariates. A significant curvilinear relationship was found (p=0.01) between alcohol intake and all-cause mortality (but not CVD mortality), while controlling for fitness and other covariates. In a categoric examination of alcohol intake and mortality, adjusting for fitness and other confounders, there was no statistically significant effect of light drinking compared to heavy drinking on all-cause mortality or CVD mortality. An examination of the joint effects of fitness and alcohol on all-cause mortality showed that moderate and high fitness levels were protective against mortality irrespective of alcohol consumption levels. Few significant combined effects for CVD mortality reduction were found.
Alcohol consumption did not significantly modify the association between fitness and mortality in this large cohort of men.
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Emotional Intelligence: An Untapped Resource for Alcohol and Other Drug Related Prevention among Adolescents and Adults
Alcohol and Other Drug abuse in adolescents and adults continues to be a major public health problem in the United States. Care in intervention programs aimed at high risk populations identified occurs after the maladaptive behavioral delinquency has occurred, and only then is an individual afforded the opportunity to join an intervention program.
The focus of this paper is to illustrate and highlight the value of prevention programs which emphasize altering maladaptive behavior before the behavior becomes problematic. Emotional Intelligence is not only an indicator of alcohol and other drug abuse, but is linked to emotional competence, social and emotional learning, the development of healthy and life promoting behavior, and has been proven to reduce some of the risk factors associated with alcohol and other drug abuse in adolescents and adults.
This paper seeks to recognize the significance of Emotional Intelligence as a desirable health promoting attribute and to establish the importance of its conceptual use in a prevention based model for reducing associated high risk behaviors.
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Alcohol-related Social Problems among Mexican Americans Living in U.S.-Mexico Border and Non-border Areas
This paper examines alcohol-related social problems among Mexican Americans living along the U.S.-Mexico border and in non-border areas.
Interviews were conducted among Mexican Americans in the border regions of California, Arizona, New Mexico, and Texas (N = 1,307). Non-border respondents were interviewed primarily in Houston and Los Angeles (N = 1,288) as part of the Hispanic Americans Baseline Alcohol Survey (HABLAS).
Both the border and HABLAS surveys employed multistage cluster sample designs (response rates were 67% and 76%, respectively).
In the bivariate analysis, there were no significant differences between border and non-border areas in the proportion of those with one or more social problem. In non-border areas, the prevalence of alcohol problems did not differ significantly by age.
However, along the border the prevalence of alcohol problems was significantly different across age groups, with 18 to 29 year old men and women having the highest prevalence.
The final models showed no residence effect on problem likelihood. Drinking was strongly associated with problems.
Although young border residents had higher problem prevalence rates than older residents, the logistic regression models showed no effect of border residence on the likelihood of problems, indicating that problems are due to alcohol consumption, not the border environment. The border, however, did appear to influence more drinking among young people.
Regardless of residence, alcohol treatment and preventive interventions tailored to Mexican Americans are essential and special attention should be focused on younger individuals near the border.
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Measuring College Students’ Motives behind Prepartying Drinking: Development and Validation of the Prepartying Motivations Inventory
Drinking motives are vital in identifying risk factors and better understanding alcohol-related outcomes. However, context-specific motivations could provide greater motivational perspective on high-risk context-specific alcohol use behaviors such as prepartying (consuming alcohol prior to attending one's intended destination) than general alcohol motivations.
In the current study, students’ open-ended responses to reasons for prepartying were collected from a large diverse sample (n = 2497), and the most commonly offered reasons were used to create a prepartying motivations inventory (PMI) that was then administered to a different sample (n = 1085).
A split-half validation procedure was used for the purpose of evaluating the PMI's factor structure. Exploratory and confirmatory factor analyses yielded a final 12-item measure consisting of four distinct, but inter-related, factors: Interpersonal Enhancement, Situational Control, Intimate Pursuit, and Barriers to Consumption. Internal consistency reliability, discriminant validity, and criterion-related validity were empirically demonstrated.
Results support the notion that individuals preparty for a variety of reasons that are distinct from general motives. Researchers are encouraged to use the PMI in future research with young adults to provide further understanding of prepartying behavior and its psychosocial
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Maternal substance use during pregnancy is a common modifiable risk factor for poor birth outcomes, and is associated with long term psychological risks to offspring. As self concept is known to affect substance use behaviors in non-pregnant women, we hypothesized that self concept as a provider may be particularly salient to cessation of use during pregnancy. To isolate psychological processes specific to pregnancy from those associated with the transition to parenthood, we examined birth mothers who made adoption placements participating in the Early Growth and Development Study.
We obtained lifetime and pregnancy substance use history and psychological measures at 3 to 4 months postpartum from 693 women recruited from the Northwest, Southwest, and Mid-Atlantic regions of the United States. Life history calendar and computer-assisted personal interviewing methods were used to minimize reporting bias. Using logistic regression, we assessed the association of self concept as an adequate provider with cessation of substance use during pregnancy, controlling for sociodemographic variables, depressive symptoms experienced during pregnancy, past year antisocial behaviors, family history of substance abuse, timing of pregnancy recognition, timing of initiation of prenatal care, and emotional adjustment to the adoption decision.
More positive self-concept as an adequate provider was independently associated with cessation of substance use and earlier initiation of prenatal care during pregnancy [OR = 1.223; 95% C.I. (1.005 - 1.489); B(SE) = .201(.100)]. Familial substance abuse, depressive symptoms, and antisocial behaviors during pregnancy, were also independent predictors, and more strongly associated with cessation [OR = .531; 95% C.I. (.375 - .751); B(SE) = −.634 (.178)], [OR. 940; 95% C.I. (.906 - .975); B(SE) = −.062(.019)], [OR = .961; 95% C.I. (.927 - .996); B(SE) = −.040(.018)].
Enhancing maternal identity as a provider for the fetus during pregnancy, along with treatment of depression, may improve motivation to stop substance use.
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Wednesday, April 18, 2012
Rising unemployment, austerity, shrinking growth: it’s enough to drive you to drink.
Legislators and activists appear determined, however, to divert Europeans from seeking refuge from hard times in the bottle.
But differences have emerged over the role of taxation and pricing in curbing a perceived booze scourge in the continent, and doubts remain about the ability of the alcoholic beverage industry to police its own behavior.
As European Union officials prepare to review a common alcohol strategy for the entire 27-nation alliance, the region’s major beer, wine and spirits producers agreed this week to a tougher self-regulatory regime to govern alcohol advertising.
The main target of the measure is to prevent young people being lured into drinking by unsuitable advertising, including on social media sites. Ads would only be able to be placed in media where at least 70 percent of the audience is “reasonably expected to be above legal purchase age,” according to the agreement. > > > > Read More
To identify independent risk factors of the recurrence of alcohol dependence (AD) in people with a remitted disorder at baseline and persistence of AD in people with a current disorder at baseline.
Prospective cohort study with assessments at baseline and 2-year follow-up.
Recruitment from the general population, primary care and out-patient mental health-care services.
People with remitted AD (n = 253) and current AD (n = 135).
Recurrence and persistence of AD during 2-year follow-up were established using the Composite International Diagnostic Interview (CIDI) interview based on DSM-IV. Logistic regression analyses were performed to explore the role of potential risk factors (i.e. baseline severity of alcohol problems, measures for depression and anxiety, socio-demographics, vulnerability factors and addiction-related factors) as independent predictors of a negative course.
Overall recurrence and persistence rates of AD were 14.6 and 40.7%, respectively, and were highly conditional on the severity of alcohol problems [adjusted odds ratio (OR) per standard deviation (SD) increase: OR = 3.64, 95% confidence interval (CI): 2.21–6.01 and OR = 2.12, 95% CI: 1.32–3.40, respectively). Severity of depressive/anxiety symptoms was an additional independent predictor of the recurrence of AD, whereas male gender and high education were significant independent risk factors of the persistence of AD.
Alcohol dependence has a dynamic course, with only moderate levels of diagnostic stability. Both recurrence and persistence of alcohol dependence are highly dependent on severity of baseline alcohol problems, whereas severity of depressive/anxiety symptoms predicts only the recurrence of alcohol dependence. Both measures may be useful in identifying people at an increased risk of a negative course and who could be targeted by prevention strategies.
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Alcohol-dependence is associated with cognitive and biological alterations, and also with interpersonal impairments. Although overwhelming in clinical settings and involved in relapse, these social impairments have received little attention from researchers. Particularly, brain alterations related to social exclusion have not been explored in alcohol-dependence.
Our primary purpose was to determine the neural correlates of social exclusion feelings in this population.
In all, 44 participants (22 abstinent alcohol-dependent patients and 22 paired controls) played a virtual game (‘cyberball’) during fMRI recording. They were first included by other players, then excluded, and finally re-included. Brain areas involved in social exclusion were identified and the functional connectivity between these areas was explored using psycho-physiological interactions (PPI).
Results showed that while both groups presented dorsal anterior cingulate cortex (dACC) activations during social exclusion, alcohol-dependent participants exhibited increased insula and reduced frontal activations (in ventrolateral prefrontal cortex) as compared with controls.
Alcohol-dependence was also associated with persistent dACC and parahippocampal gyrus activations in re-inclusion. PPI analyses showed reduced frontocingulate connectivity during social exclusion in alcohol-dependence.
Alcohol-dependence is thus linked with increased activation in areas eliciting social exclusion feelings (dACC–insula), and with impaired ability to inhibit these feelings (indexed by reduced frontal activations).
Altered frontal regulation thus appears implied in the interpersonal alterations observed in alcohol-dependence, which seem reinforced by impaired frontocingulate connectivity.
This first exploration of the neural correlates of interpersonal problems in alcohol-dependence could initiate the development of a social neuroscience of addictive states.
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In alcoholics, the activation of Kupffer cells by gram negative bacteriae leads to an inflammatory response and cytokine secretion, which in turn activate T-lymphocytes. Possibly, Th-1 lymphocytes are activated first, followed by a Th-2 response. Th-2 cytokines, especially interleukin (IL)-13 (scarcely studied in alcoholics), may be involved in the progression to chronic stages.
The aim of the study was to analyze the relationship of Th-1 and Th-2 cytokines with liver function, alcohol consumption, nutritional status and survival.
Serum Th-1 [interferon-γ (IFN-γ)] and Th-2 cytokines (IL-4, IL-13), IL-10, IL-6 and tumor necrosis factor (TNF-α), were determined for 18 controls and 47 stable alcoholics with variable liver function impairment, who were followed-up during a median time of 90 months, a period during which 14 patients died.
IL-4 was lower among patients; no differences were observed regarding IL-6, but the remaining ILs were higher among alcoholics. IL-10 and IL-13 were even higher in cirrhotics (Z = 2.88, P = 0.004, and Z = 2.09, P = 0.037, respectively). A significant, direct, correlation was observed between IL-13 and IL-10 (ρ = 0.49, P = 0.001), and non-significant, inverse ones were observed between IFN-γ and IL-13 (ρ = −0.23), IL-4 (ρ = −0.14) and IL-10 (ρ = −0.09). IL-13 and IL-10 were inversely related with liver function and, directly with immunoglobulin A levels, but not with survival.
Serum IFN-γ values were increased in alcoholics, who also showed raised IL-13 and IL-10, but lower IL-4 levels. Given the immunomodulatory roles of IL-10 and IL-13, this increase may be interpreted as a compensatory rise of anti-inflammatory cytokines. We failed to find any relation with mortality.
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Acoustic Startle Responses and Prepulse Inhibition of Acoustic Startle Responses in Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Prefer
An assessment of the acoustic startle response (ASR) and prepulse inhibition (PPI) of ASR in laboratory animals is used to model human anxiety and psychotic states, respectively.
The aim of the study was to evaluate ASR and PPI in alcohol-naive male and female Warsaw alcohol high-preferring (WHP) and Warsaw alcohol low-preferring (WLP) rats.
ASR and PPI were assessed in two separate experiments by using the SR-LAB apparatus (San Diego Instruments, San Diego, CA, USA). In the ASR session, animals (n = 13–16 rats per group) were exposed to startling stimuli of different intensities (72, 84, 98, 112 and 124 dB) in a random order. In the PPI session, prepulse stimuli (78, 81, 84 and 90 dB) preceded a pulse startling stimulus (120 dB) in a random order. The background white noise was set at 70 dB. PPI was calculated according to the formula: [(startle amplitude in pulse alone trials—startle amplitude in prepulse-and-pulse trials)/startle amplitude in pulse alone trials] × 100%.
The WHP males exhibited higher startle amplitudes in response to 112 dB stimuli when compared with their WLP counterparts. The WHP females showed higher startle reactivity to 112 and 124 dB stimuli when compared with the WLP females. There were no differences between the WHPs and WLPs in PPI of ASR.
The results of the present study suggest that exaggerated startle responses can be a physiological/behavioral marker of a propensity to abuse alcohol.
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Ethanol, Glutamate, and the Ventral Tegmental Area—A Commentary on: Ding, Engleman, Rodd, and McBride, “Ethanol Increases Glutamate Neurotransmission
The recent study by Ding and colleagues (2012) utilized in vivo microdialysis to demonstrate that acute and repeated alcohol administration produces dose-dependent effects on extracellular levels of the glutamate in the posterior ventral tegmental area.
These findings have important implications for interactions between glutamatergic and dopaminergic mediation of alcohol reinforcement in the ventral midbrain.
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Choline Supplementation and DNA Methylation in the Hippocampus and Prefrontal Cortex of Rats Exposed to Alcohol During Development
Some of the most frequent deficits seen in children with fetal alcohol spectrum disorders (FASD) and in animal models of FASD are spatial memory impairments and impaired executive functioning, which are likely related to alcohol-induced alterations of the hippocampus and prefrontal cortex (PFC), respectively. Choline, a nutrient supplement, has been shown in a rat model to ameliorate some of alcohol's teratogenic effects, and this effect may be mediated through choline's effects on DNA methylation.
Alcohol was given by intragastric intubation to rat pups during the neonatal period (postnatal days 2 to 10) (ET group), which is equivalent to the third trimester in humans and a period of heightened vulnerability of the brain to alcohol exposure. Control groups included an intubated control group given the intubation procedure without alcohol (IC) and a nontreated control group (NC). Choline or saline was administered subcutaneously to each subject from postnatal days 2 to 20. On postnatal day 21, the brains of the subjects were removed and assayed for global DNA methylation patterning as measured by chemiluminescence using the cpGlobal assay in both the hippocampal region and PFC.
Alcohol exposure caused hypermethylation in the hippocampus and PFC, which was significantly reduced after choline supplementation. In contrast, control animals showed increases in DNA methylation in both regions after choline supplementation, suggesting that choline supplementation has different effects depending upon the initial state of the brain.
This study is the first to show changes in global DNA methylation of the hippocampal region and PFC after neonatal alcohol exposure. Choline supplementation impacts global DNA methylation in these 2 brain regions in alcohol-exposed and control animals in a differential manner. The current findings suggest that both alcohol and choline have substantial impact on the epigenome in the PFC and hippocampus, and future studies will be needed to describe which gene families are impacted in such a way that function of the nervous system is changed.
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