Alcoholism and Cellular Vulnerability in Different Brain Regions

Alcohol-induced damage causes dysfunction of selected brain regions. Multidisciplinary studies have provided an extensive description of changes observed in neurons and glia following alcohol consumption.

In this study the authors have elucidated preferential cellular vulnerability in three different brain regions.

Autopsy material of the prefrontal cortex, striatum, and substantia nigra obtained from the brain tissue of alcoholic subjects was used in this study.

We found that dendritic tree and astroglial damage is irreversible, while neuronal somata and most axons do not display irreversible changes.


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sandra.skuja@gmail.com

Gene Coexpression Networks in Human Brain Identify Epigenetic Modifications in Alcohol Dependence

Alcohol abuse causes widespread changes in gene expression in human brain, some of which contribute to alcohol dependence. Previous microarray studies identified individual genes as candidates for alcohol phenotypes, but efforts to generate an integrated view of molecular and cellular changes underlying alcohol addiction are lacking.

Here, we applied a novel systems approach to transcriptome profiling in postmortem human brains and generated a systemic view of brain alterations associated with alcohol abuse.

We identified critical cellular components and previously unrecognized epigenetic determinants of gene coexpression relationships and discovered novel markers of chromatin modifications in alcoholic brain.

Higher expression levels of endogenous retroviruses and genes with high GC content in alcoholics were associated with DNA hypomethylation and increased histone H3K4 trimethylation, suggesting a critical role of epigenetic mechanisms in alcohol addiction.

Analysis of cell-type-specific transcriptomes revealed remarkable consistency between molecular profiles and cellular abnormalities in alcoholic brain.

Based on evidence from this study and others, we generated a systems hypothesis for the central role of chromatin modifications in alcohol dependence that integrates epigenetic regulation of gene expression with pathophysiological and neuroadaptive changes in alcoholic brain.

Our results offer implications for epigenetic therapeutics in alcohol and drug addiction.



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

Veteran Status and Alcohol Use in Men in the United States

This study sought to compare patterns of alcohol use between male veterans and nonveterans.

Data came from the 2004 Behavioral Risk Factor Surveillance System, a U.S. national telephone survey using stratified random sampling. Outcomes were 30-day alcohol use, binge drinking (5+ drinks on one occasion), and heavy drinking (2+ drinks per day). Age-stratified weighted regression analyses compared men who were veterans (n = 36,874) to those who were not (n = 77,056), and veterans who used Veterans Health Administration (VHA) services in the past year (n = 7,606) to veterans who did not, adjusting for potential confounders.

Veterans aged 41 to 60 were less likely to binge drink (adjusted odds ratio [AOR] = 0.8) and veterans aged 61 to 70 were more likely to drink heavily compared to same-age men without military experience (AOR = 1.7). There were no significant differences in binge or heavy drinking for other age groups. Among veterans aged 51 to 60, those who used VHA services were more likely to report binge drinking than those who did not (AOR = 1.4).

Male veterans generally have similar patterns of alcohol use as men without a history of military service, but the elevated alcohol use of specific groups of veterans merits concern.


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Request Reprint E-Mail: Amy.Bohnert@va.gov

The effect of job stress on smoking and alcohol consumption

This paper examines the effect of job stress on two key health risk-behaviors: smoking and alcohol consumption, using data from the Canadian National Population Health Survey. Findings in the extant literature are inconclusive and are mainly based on standard models which can model differential responses to job stress only by observed characteristics.

However, the effect of job stress on smoking and drinking may largely depend on unobserved characteristics such as: self control, stress-coping ability, personality traits and health preferences.
Accordingly, we use a latent class model to capture heterogeneous responses to job stress.

Our results suggest that the effects of job stress on smoking and alcohol consumption differ substantially for at least two "types" of individuals, light and heavy users.

In particular, we find that job stress has a positive and statistically significant impact on smoking intensity, but only for light smokers, while it has a positive and significant impact on alcohol consumption mainly for heavy drinkers.

These results provide suggestive evidence that the mixed findings in previous studies may partly be due to unobserved individual heterogeneity which is not captured by standard models.


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Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk

Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent.

We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk.

We analyzed data from a nested case–control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array.

We observed a statistically significant association between a common 3′-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)_{A v T} = 1.30, 95% confidence interval (CI) = 1.07–1.59].

Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (OR_{T v C} = 0.59; 95% CI = 0.38–0.91 and OR_{T v C} = 1.34; 95% CI = 1.00–1.79, respectively).

Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (OR_A+T = 2.0; 95% CI = 1.25–3.20) as those not carrying variant alleles.

The association between rs1230025 and GC was modified by alcohol intake (<5 g/day: OR_A = 0.89, 95% CI = 0.57–1.39; ≥5 g/day: OR_A = 1.45, 95% CI = 1.08–1.94, P-value = 0.05). The association was also modified by ethanol intake from beer.

A known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P-value = 0.04) but not GC risk.

Variants in ADH7 were not associated with alcohol intake or GC risk.

In conclusion, genetic variants at ADH1 and ALDH2 loci may influence GC risk, and alcohol intake may further modify the effect of ADH1 rs1230025.

Additional population-based studies are needed to confirm our results.


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Request Reprint E-Mail: eduell@iconcologia.net

Alcohol-induced memory blackouts as an indicator of injury risk among college drinkers

An alcohol-induced memory blackout represents an amnesia to recall events but does not involve a loss of consciousness. Memory blackouts are a common occurrence among college drinkers, but it is not clear if a history of memory blackouts is predictive of future alcohol-related injury above and beyond the risk associated with heavy drinking episodes.

To determine whether baseline memory blackouts can prospectively identify college students with alcohol-related injury in the next 24 months after controlling for heavy drinking days.

Data were analysed from the College Health Intervention Project Study (CHIPS), a randomised controlled trial of screening and brief physician intervention for problem alcohol use among 796 undergraduate and 158 graduate students at four university sites in the USA and one in Canada, conducted from 2004 to 2009. Multivariate analyses used generalised estimating equations with the logit link.

The overall 24-month alcohol-related injury rate was 25.6%, with no significant difference between men and women (p=0.51). Alcohol-induced memory blackouts at baseline exhibited a significant dose–response on odds of alcohol-related injury during follow-up, increasing from 1.57 (95% CI 1.13 to 2.19) for subjects reporting 1–2 memory blackouts at baseline to 2.64 (95% CI 1.65 to 4.21) for students acknowledging 6+ memory blackouts at baseline. The link between memory blackouts and injury was mediated by younger age, prior alcohol-related injury, heavy drinking, and sensation-seeking disposition.

Memory blackouts are a significant predictor of future alcohol-related injury among college drinkers after adjusting for heavy drinking episodes.

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Request Reprint E-Mail: marlon.mundt@fammed.wisc.edu

Sibling influences on adolescent substance use: The role of modeling, collusion, and conflict

The longitudinal associations of older sibling substance use as well as dyadic sibling conflict and collusion to younger sibling substance use were examined in a community-based sample of 244 same-sex sibling pairs.

Indirect effects of older siblings on younger sibling substance use were hypothesized via younger sibling deviant peer affiliation and conflict with friends.

Adolescents, parents, friends, and teachers completed measures of substance use, conflict, and deviant peer involvement. Observational data were used for both measures of collusion and conflict.

Findings suggest that older sibling substance use has a direct effect on younger sibling use, but relationship dynamics and reinforcement played a significant role as well. Specifically, collusion and conflict in the sibling relationship both had indirect effects through younger siblings’ deviant peer affiliation

Findings validate the powerful socializing role of both siblings and peers, and elucidate the complex mechanisms through which socialization occurs. Furthermore, data underscore the importance of considering how multiple dimensions of socialization operate in the elaboration of antisocial behavior.


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Request Reprint E-Mail: Sabina.low@wichita.edu

Welsh alcohol campaigners criticise Cardiff's Carnage student event

Wales' alcohol watchdog has called for a change in the cultural that glorifies notorious student pub crawl events like Cardiff's controversial Carnage UK event.

A spokesman for Alcohol Concern Cymru said that the student event – which descended on Cardiff a week ago – encouraged people to into an unhealthy relationship with alcohol. > > > > Read More

Government alcohol ad 'scaremongering'

New UK government guidelines warning that drinking two large glasses of wine a day triples the risk of mouth cancer are 'scaremongering’' an influential alcohol lobby group claims.

A TV advert launched yesterday claims that regularly drinking around two large glasses of wine or two strong pints of beer a day triple the risk of developing mouth cancer and double the risk of developing high blood pressure.

In the advert cartoon figures (pictured) swig wine and beer while a voiceover warns, ‘apparently two large glasses of wine or more a day could make me three times more likely to get mouth cancer.’ > > > > Read More

Through a glass darkly: can we improve clarity about mechanism and aims of medications in drug and alcohol treatments?

The treatment of addiction and dependence on, and misuse of, alcohol and other drugs is one of the largest unmet needs in medicine today, so the development of new treatments is a pressing need. However, we have seen the development and use of different terminologies for different drug addictions, which confuses prescribers, users and regulators alike. Here we try to clarify terminology of treatment models based on the pharmacology of treatment agents. This editorial covers all drugs that are used for their pleasurable effects and which therefore can lead to harmful/hazardous use, dependence and addiction. These include nicotine, alcohol and abused prescription drugs such as benzodiazepines, as well as opioids and stimulants.


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Evaluation of Moderate Alcohol Use and Cognitive Function Among Men Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study

Observational studies usually show that moderate alcohol use is associated with better cognitive function. Such studies are vulnerable to residual confounding arising from systematic differences between moderate alcohol users and others.

A Mendelian randomization study carried out in a suitable population, such as southern Chinese men, in which alcohol use is low to moderate and is influenced by genotype, offers an alternative and superior approach for clarifying the causal effect of moderate alcohol use on cognitive function.

The authors used aldehyde dehydrogenase 2 (ALDH2) genotype (AA, GA, or GG) as an instrumental variable in 2-stage least squares analysis to obtain unbiased estimates of the relation of alcohol consumption (measured in alcohol units (10 g ethanol) per day) with cognitive function, assessed from delayed 10-word recall score (n = 4,707) and Mini-Mental State Examination (MMSE) score (n = 2,284), among men from the Guangzhou Biobank Cohort Study (2003–2008).

ALHD2 genotype was strongly associated with alcohol consumption, with an F statistic of 71.0 in 2-stage least squares analysis. Alcohol consumption was not associated with delayed 10-word recall score (−0.03 words per alcohol unit, 95% confidence interval: −0.18, 0.13) or MMSE score (0.06 points per alcohol unit, 95% confidence interval: −0.22, 0.34).

Moderate alcohol use is unlikely to be cognitively protective.



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Request Reprint E-Mail: commed@hkucc.hku.hk

Beer à No-Go: Learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inh

Previous research showed that consistently not responding to alcohol-related stimuli in a Go/No-Go training reduces drinking behavior. This study aimed to further examine the mechanisms underlying this Go/No-Go training effect.

Fifty-seven heavy drinkers were randomly assigned to two training conditions: In the beer/no-go condition, alcohol-related stimuli were always paired with a stopping response, while in the beer/go condition, participants always responded to alcohol-related stimuli. Participants were individually tested in a laboratory at Maastricht University.

Weekly alcohol intake, implicit attitudes toward beer, approach-avoidance action tendencies toward beer, and response inhibition were measured before and after the training.

Results showed a significant reduction in both implicit attitudes (p= .03) and alcohol intake (p= .02) in the beer/no-go condition, but not in the beer/go condition. There were no significant training effects on action tendencies or response inhibition.

Repeatedly stopping prepotent responses toward alcohol-related stimuli effectively reduces excessive alcohol use via a devaluation of alcohol-related stimuli rather than via increased inhibitory control over alcohol-related responses.


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Request Reprint E-Mail: K.Houben@maastrichtuniversity.nl

Prevalence And Correlates Of Alcohol Use Disorders In The Singapore Mental Health Survey

To establish the prevalence, correlates, comorbidity, and treatment gap of alcohol use disorders in the Singapore resident population.

The Singapore Mental Health Study is a cross-sectional epidemiological survey.

A nationally representative survey of the resident (citizens and permanent residents) population in Singapore.

6616 Singaporean adults aged 18 years and older.

The diagnoses were established using the World Mental Health Composite International Diagnostic Interview (WMH-CIDI) diagnostic modules for lifetime and 12-month prevalence of select mental illnesses including alcohol use disorders.

The lifetime prevalence of alcohol abuse and alcohol dependence was 3.1% and 0.5%, while the 12-month prevalence of alcohol abuse and alcohol dependence was 0.5% and 0.3%, respectively. The lifetime and 12-month prevalence of alcohol use disorders was 3.6% and 0.8%, respectively. Those with alcohol use disorder had significantly higher odds of having major depressive disorder (OR 3.1) and nicotine dependence (OR 4.5). Compared to the rest of the population, those with an alcohol use disorder had significantly higher odds of having gastric ulcers (OR 3.0), respiratory conditions OR (2.1) and chronic pain (OR 2.1). Only 1 in 5 of those with alcohol use disorder had ever sought treatment.

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Request Reprint E-Mail: Mythily@imh.com.sg.

Bulimic Behaviors and Alcohol Use: Shared Genetic Influences

Bulimic behaviors are frequently associated with alcohol use disorders. However, extant family and twin study findings have been inconsistent with regard to whether these behaviors share etiologic influences.

A sample of 292 young adult, female twins was used to examine genetic and environmental factors underlying the association between binge eating and compensatory behaviors (e.g., vomiting) and alcohol use. Binge eating and compensatory behaviors were assessed using the Minnesota Eating Behavior Survey. Alcohol use was measured using the Alcohol Use Disorders Identification Test.

Univariate models indicated that the heritability of binge eating, compensatory behaviors, and alcohol use was 41, 28, and 78%, respectively, with the remaining variance due to nonshared environmental effects.

Bivariate models indicated that there was a moderate-to-large degree of overlap (genetic correlation = 0.31–0.61) in additive genetic factors between alcohol use and binge eating and compensatory behaviors, and no overlap in environmental effects.

Findings suggest that these phenotypes co-aggregate in families and that similar genes or heritable traits may be contributing to their co-occurrence.


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Request Reprint E-Mail: slane@msu.edu.

'Don't let drink sneak up on you' - new Change4Life alcohol campaign launched

A new Change 4 Life alcohol campaign, 'Don't let the drinks sneak up on you', has been launched - see the press release, TV advert and Change4Life alcohol pages including a new tool to check your drinking.

The campaign warns against drinking above lower risk guidelines, highlighting the potential impacts on long term health. A TV advert warns that regularly drinking just 2 large glasses of wine or 2 strong pints of lager a day can triple the risk of developing mouth cancer and double the risk of getting high blood pressure. A supporting leaflet [pdf] is also available to order. > > > > Read More

Impact of Different Reference Period Definitions in the Quantification of Alcohol Consumption: Results from a Nationwide STEPS Survey in Mozambique

To compare the estimates of alcohol consumption in Mozambique obtained with different reference period definitions. This is a critical methodological aspect when measuring alcohol consumption and its impact is likely to vary across settings.

A nationally representative sample of 3264 Mozambicans aged 25–64 years was evaluated in a community-based cross-sectional study conducted between September and November 2005. Face-to-face interviews were conducted following the World Health Organization-Stepwise approach to Surveillance methodology. The amount of alcohol consumed was estimated among current drinkers, using the previous week (1W) and the 12 months (12M) prior to the data collection as the reference.

Among drinkers, the prevalence of consumption of >14 drinks/week was higher in men (12M: 18.6 vs. 7.8%; 1W: 16.3 vs. 6.1%), although the prevalence of excessive weekly intake (>7 drinks for women and >14 drinks for men) was higher among women (12M: 25.9 vs. 18.6%; 1W: 18.1 vs. 16.3%). The concordance between the reported intakes according to the reference period was low (κ = 0.25).

In this setting where alcohol consumption is a male-dominated behaviour, among drinkers the prevalence of gender-defined excessive amounts was higher in women. The concordance between different recall periods was low and this needs to be taken into account when comparing results from different studies.



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Request Reprint E-Mail: nlunet@med.up.pt

Gene-Selective Histone H3 Acetylation in the Absence of Increase in Global Histone Acetylation in Liver of Rats Chronically Fed Alcohol

The aim of this study was to determine the effect of chronic ethanol feeding on acetylation of histone H3 at lysine 9 (H3-Lys9) at promoter and coding regions of genes for class I alcohol dehydrogenase (ADH I), inducible nitric oxide synthase (iNOS), Bax, p21, c-met and hepatocyte growth factor in the rat liver.

Rats were fed ethanol-containing liquid diet (5%, w/v) for 1–4 weeks. The global level of acetylation of H3-Lys9 in the liver was examined by western blot analysis. The levels of mRNA for various genes were measured by real-time reverse transcriptase-polymerase chain reaction. The association of acetylated histone H3-Lys9 with the different regions of genes was monitored by chromatin immunoprecipitation assay.

Chronic ethanol treatment increased mRNA expression of genes for iNOS, c-jun and ADH 1. Chronic ethanol treatment did not cause increase in global acetylation of H3-Lys9, but significantly increased the association of acetylated histone H3-Lys9 in the ADH I gene, both in promoter and in coding regions. In contrast, chronic ethanol treatment did not significantly increase the association of acetylated histone H3-Lys9 with iNOS and c-jun genes.

Chronic ethanol exposure increased the gene-selective association of acetylated H3-Lys9 in the absence of global histone acetylation. Thus, not all genes expressed by ethanol are linked to transcription via histone H3 acetylation at Lys9.



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Request Reprint E-Mail: shuklasd@missouri.edu

Breath Alcohol Elimination Rate and Widmark Factor Derived from Breath Alcohol Concentration in Chinese and Indians in Singapore

To determine the breath alcohol elimination rate (AER) and Widmark factor derived from the maximum breath alcohol concentration (r_{peak BrAC}) in Chinese and Indians in Singapore, and to evaluate the contribution of genetic and non-genetic factors to variability of AER and r_{peak BrAC}.

A total of 180 subjects ingested a Vodka–orange juice mixture, together with a standardized meal and underwent a series of BrAC measurements.

Significant inter-ethnic differences in AER and r_{peak BrAC} were observed in females and males, respectively. Alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase (ALDH2) genotypes were identified as significant predictors for AER among males, accounting for 8.5% (P = 0.048) and 23.4% (P < 0.001) of the variance, respectively. ADH1B genotype was identified as a significant predictor for r_{peak BrAC} among males, accounting for 17.1% of the variance (P = 0.001). In females, however, none of the genotypes were found to be significant predictors for breath AER, and r_{peak BrAC}.

ALDH2 and/or ADH1B genotypes in males, but not in females, appear to contribute, albeit modestly, to variability in AER and r_{peak BrAC}. The median AER in Chinese males, Indian males, Chinese females and Indian females is 6.6 μg dl⁻¹ h⁻¹ [99% confidence interval (CI), 5.6–7.5 μg dl⁻¹ h⁻¹], 6.2 μg dl⁻¹ h⁻¹ (99% CI, 5.5–7.0 μg dl⁻¹ h⁻¹), 8.6 μg dl⁻¹ h⁻¹ (99% CI, 7.4–9.7 μg dl⁻¹ h⁻¹) and 7.4 μg dl⁻¹ h⁻¹ (99% CI, 6.2–8.4 μg dl⁻¹ h⁻¹), respectively. The median r_{peak BrAC} in Chinese males, Indian males, Chinese females and Indian females is 0.0229 (99% CI, 0.0216–0.0268), 0.0209 (99% CI, 0.0190–0.0237), 0.0214 (99% CI, 0.0185–0.0254) and 0.0199 (99% CI, 0.0187–0.0227), respectively.



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Request Reprint E-Mail: edmund_jd_lee@nuhs.edu.sg

'Tackling alcohol misuse: Should abstinence be our preferred approach?' British Liver Trust call for public health action on alcohol

The British Liver Trust have released a new report outlining the need for a comprehensive approach to tackling alcohol misuse. It warns against a "one size fits all approach for treatment" for a range of problem drinkers "each of whom will need tailored approach with the interventions and appropriate treatment goals."

Download 'Reducing alcohol harm: recovery and informed choice for those with alcohol related health problems'

A supporting commentary piece by Andrew Langford, Chief Executive of the British Liver Trust also appeared in the Guardian. > > > > Read More

News Release - NIH study uncovers probable mechanism underlying resveratrol activity

Findings may settle scientific debate surrounding this chemical found in red wine and other foods

National Institutes of Health researchers and their colleagues have identified how resveratrol, a naturally occurring chemical found in red wine and other plant products, may confer its health benefits. The authors present evidence that resveratrol does not directly activate sirtuin 1, a protein associated with aging. Rather, the authors found that resveratrol inhibits certain types of proteins known as phosphodiesterases (PDEs), enzymes that help regulate cell energy.

These findings may help settle the debate regarding resveratrol's biochemistry and pave the way for resveratrol-based medicines. The chemical has received significant interest from pharmaceutical companies for its potential to combat diabetes, inflammation, and cancer. The study appears in the Feb. 3 issue of Cell. > > > > Read More