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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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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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

Current Issue: November–December 2011

Interventions & Assessments

• Buprenorphine-Naloxone Works for Prescription Opioid Dependence As Long As It Is Maintained
• Ongoing Primary and Specialty Care Is Associated with Improved Substance Use Outcomes
• Patients Who Receive Opioids for Chronic Pain Are Inadequately Managed
• Accuracy of “Last Occasion” Self-Reported Drinking in Young Adults
• Does Mailed Feedback Decrease Risky Drinking After an Emergency Department Visit?
  
• Buprenorphine Treatment Is Not Associated with Significant Impairment of Driving Ability

Health Outcomes

• “Moderate” Drinking Is a Risk Factor for Breast Cancer
• Association between Open-Angle Glaucoma and Cocaine Use
• Heavier Alcohol Consumption Linked to Colorectal Cancer
• Heavy Beer Consumption Is a Risk Factor for Gastric Cancer
• Regular Moderate Alcohol Intake Associated with “Successful Aging” in Women
• Unhealthy Alcohol Use Is Associated with Unhealthy Eating Patterns

HIV and HCV

• A Multidisciplinary Approach to Hepatitis-C Treatment Reduced Viral Load and Increased Abstinence in Patients with Co-Occurring Alcohol Dependence
• A New Piece of the Harm Reduction Puzzle? Directly Observed Antiretroviral Therapy for HIV-infected Opioid-Dependent Individuals
• Factors Associated with Substance-Abuse Treatment Utilization among Patients Living with HIV/AIDS Who Use Alcohol and Other Drugs

Slide Presentations

• Update on Alcohol, Other Drugs, and Health
• Journal Club

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Critique 069: Little effect of binge drinking on heart disease or mortality among moderate drinkers in Denmark

Skov-Ettrup LS, Eliasen M, Ekholm O, Grønbaek M, Tolstrup JS. Binge drinking, drinking frequency, and risk of ischaemic heart disease: A population-based cohort study. Scandinavian Journal of Public Health 2011;39:880–887.

Comments on study: This appears to be a well-done population–based study with good follow up and excellent ascertainment of outcomes: IHD and all-cause mortality. This was made possible by the unique civil registry number allocated to each Danish citizen at birth. This number is used in any sort of business with the authorities such as tax, social security, and health, and a social security card with the number must be presented with any contact with the national health system – a failsafe method of securing exact follow-up of all diagnoses or death.

The assessments of alcohol were based on consumption in the week prior to the examination, and binge drinking was defined as more than 5 drinks/occasion. Given that the assessment was from only one week, data were not available to judge whether or not binge-drinking episodes occurred rarely or regularly.

Data were available on the usual covariates related to IHD: smoking, education, physical activity, BMI, and self-reported hypertension and diabetes. There was a strong correlation between binge drinking and the total amount of alcohol consumed, but the authors controlled for total alcohol intake when comparing binge and non-binge drinkers.

When comparing outcomes in binge vs. non-binge drinkers, the analyses were restricted to subjects in the “light-to-moderate” categories. Here, there were no significant differences noted between subjects who binged and those who did not. In all comparisons, the relative risk of IHD and all-cause mortality was higher for non-drinkers than for all categories of drinkers.

When relating frequency of drinking (the number of days of the week when subjects consumed alcohol) to IHD and total mortality, all subjects (not just the light-to-moderate drinkers) were included. Here, again, there were no significant differences in outcomes comparing people consuming alcohol on 1-2, 3-4, 5-6, or 7 days/week (although , once again, the highest risk was always among the non-drinkers). These results differ from those of Mukamal et al¹ and Tolstrup et al,² studies showing that frequency of consumption was a key determinant of health outcomes.

Thus, these findings do not show differences in effects of binge vs. non-binge drinking in terms of IHD or mortality. Further, the study does not show a significant effect according to the number of days per week that subjects consumed alcohol. As one reviewer stated: “The present paper suggests that, within the group of persons following sensible drinking limits of weekly amount of alcohol intake, there does not appear to be adverse effects on the heart when not following the recommendation to avoid having more than five drinks on a single occasion.”

Specific comments on the results of the present study: As a Forum reviewer commented: “The sensible drinking limits of up to 21 drinks/week for men or up to 14 drinks/week for women (1 drink = 12 grams of alcohol) proposed by the Danish National Board of Health are well known in Denmark. It is estimated that, overall, 20% of the population over 16 years of age drink in excess of the proposed drinking limits.³ However, by limiting the study of the effect of binge drinking to subjects who follow the weekly drinking limits (83.7% of the male and 90.4% of the female participants), you have restricted the analysis of binge drinking effects to a population of genuine moderate drinkers.” If binge drinking among all drinkers were evaluated, the results may well have been different.

In the present analyses, a very high percentage of the “light-to-moderate drinkers” reported binge drinking: up to 61% of men in the 14-21 drinks/week category and 35% of the women in the 7-14 drinks/week category. The median number of drinks on a binge was 9 for men and 7 for women. Despite reporting binge drinking, the overall average intake of the subjects in these analyses remained in the light-to-moderate category. Hence, although they reported binge drinking on at least one occasion in the preceding week, they were not overall heavy drinkers.

As one reviewer commented, “The combination of moderate drinking with occasional parties with intake of >5 drinks is a normal pattern of drinking in Denmark. It is assumed that many were in the habit of sharing some bottles of wine with friends on a Saturday evening and then drink very little during work days, while others prefer the daily glass of wine or beer with their meals. However, they would be very similar in other choices of lifestyle.” While the type of beverage consumed was not reported in this paper, a reviewer comments: “Based on data from earlier reports from the Danish National Cohort Study. you would expect that most of the female participants are wine drinkers and that many of the moderate male consumers also prefer wine.” Previous studies from Copenhagen have shown better health outcomes for wine drinkers than for consumers of other beverages.⁴ In this study, non-drinkers tended to have lower levels of education than the moderate drinkers, as has been found commonly in other studies. > > > > Read More

Alcohol Use Disorders Identification Test (AUDIT) scores are elevated in antipsychotic-induced hyperprolactinaemia

Hyperprolactinaemia in antipsychotic treated patients with schizophrenia is a consequence of D2 receptor (DRD2) blockade. Alcohol use disorder is commonly comorbid with schizophrenia and low availability of striatal DRD2 may predispose individuals to alcohol use.

In this pilot study we investigated whether hyperprolactinaemia secondary to pharmacological DRD2 blockade was associated with alcohol use disorder in 219 (178 males and 41 females) patients with schizophrenia.

Serum prolactin determinations were made in patients diagnosed with schizophrenia and maintained on antipsychotic agents. Clinical assessment included demographics, family history and administration of the AUDIT (Alcohol Use Disorders Identification Test).

Higher AUDIT scores were associated with prolactin-raising antipsychotic medication (n = 106) compared with prolactin-sparing medication (n = 113). Risperidone (n = 63) treated patients had higher AUDIT scores and prolactin levels than those on other atypical antipsychotics (n = 113). Across the entire sample, patients with a prolactin greater than 800 mIU/L had higher AUDIT scores and were more likely to exceed the cut-off score for harmful and hazardous alcohol use.

These differences were not explained by potential confounds related to clinical features and demographics, comorbidity or medication side-effects. These data suggest that by lowering dosage, or switching to another antipsychotic agent, the risk for alcohol use disorder in those with schizophrenia may be reduced.

This hypothesis requires testing using a prospective methodology.



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Request Reprint E-Mail: bruce_lawford@health.qld.gov.au

Pharmacokinetics and central nervous system effects of the novel dopamine D3 receptor antagonist GSK598809 and intravenous alcohol infusion at pseudo-

GSK598809 is a novel selective dopamine D₃ receptor antagonist, currently in development for the treatment of substance abuse and addiction.

In a blinded, randomized, placebo-controlled study, effects of single oral doses of 175 mg GSK598809 were evaluated in healthy volunteers. Pharmacokinetics, central nervous system (CNS) effects and potential for interactions with alcohol were evaluated, using an alcohol infusion paradigm and analysis of eye movements, adaptive tracking, visual analogue scales, body sway, serum prolactin and verbal visual learning test.

Adverse effects of GSK598809 included headache, dizziness and somnolence. Plasma concentration of GSK598809 was maximal 2–3 hours postdose and decreased with a half-life of roughly 20 hours. CNS effects were limited to prolactin elevation and decreased adaptive tracking. Co-administration of GSK598809 and alcohol did not affect alcohol pharmacokinetics, but caused a 9% decrease of C_max and a 15% increase of AUC of GSK598809. CNS effects of co-administration were mainly additive, except a small supra-additive increase in saccadic reaction time and decrease in delayed word recall.

In conclusion, GSK598809 causes elevation of serum prolactin and a small decrease in adaptive tracking performance. After co-administration with alcohol, effects of GSK598809 are mainly additive and the combination is well tolerated in healthy volunteers.



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Request Reprint E-Mail: etbeek@chdr.nl

Model-based appraisal of alcohol minimum pricing and off-licensed trade discount bans in Scotland using the Sheffield Alcohol Policy Model (v.2)

In 2009, ScHARR developed an adaptation of the Sheffield Alcohol Policy Model for the population of Scotland. The findings of this original modelling work were published in September 2009 (Purshouse et al, 2009b). A first update using more up to date evidence was published in April 2010 (Meng et al, 2010). Since this time, a series of more recent datasets have become available. These include:

• New adult consumption data from the Scottish Health Survey (SHeS) is available for 2010 (the data in the previous model relates to 2008).

• New purchase data from the Living Costs and Food Survey (LCF), previously known as the Expenditure and Food Survey (EFS) is available for 2006 to 2009 (the data in the previous model relates to 2001/2 to 2005/6).

• The Scottish Government has also procured market research data on the 2010 price distribution of off-trade alcohol (in terms of ethanol content) in Scotland from The Nielsen Company.

• New mortality data is available for 2010.

• New person specific hospitalisation data is available for 2009/10.

• Police recorded crime statistics and the Scottish Crime and Justice Survey (SCJS) data is available for 2009/10.

• The Labour Force Survey data is available for 2010.

The requirement of this research project was to update the previous Scotland model with the new data to provide revised estimates of the effects of current proposals for minimum pricing and prohibition of off-trade discounting. The technical details of the methodology have not been changed. Therefore the methods section (Chapter 2) of the original published report has not been reproduced in full. > > > > Read More

The effects of TPA023, a GABAAα2,3 subtype-selective partial agonist, on essential tremor in comparison to alcohol

Essential tremor (ET) is a relatively frequent neurological disorder that responds in some patients to gamma-aminobutyric acid A (GABA_A) agonists such as the benzodiazepines. Partial subtype-selective GABA_A agonists may have an improved side effect profile compared to non-selective GABA_A agonists. However, it is unknown which GABA_A subtypes are involved in the therapeutic effects of benzodiazepines in ET.

The effects of 2 mg TPA023, a GABA_A α2,3 subtype-selective partial agonist, on ET were compared to the effects of a stable alcohol level (0.6 g/L) and placebo in nine patients with ET. Tremor evaluation included laboratory accelerometry and a performance-based scale. Additional measurements were performed to evaluate other effects on the central nervous system (CNS).

Alcohol significantly diminished tremor symptoms in the postural and kinetic condition, as assessed by laboratory accelerometry, but the performance-based rating scale was unaffected.

Tremor was also reduced after TPA023 treatment in the kinetic condition, albeit not significantly. Additionally, TPA023 decreased saccadic peak velocity, while alcohol decreased subjective feelings of alertness.

This study showed that alcohol reduced maximum tremor power, as assessed by laboratory accelerometry, unlike TPA023, which decreased tremor symptoms to some extent but not significantly.

This study showed that treatment with an α2,3 subunit-selective GABA_A partial agonist was less effective than a stable level of alcohol in reducing ET symptoms.

These results provide no support for a therapeutic role of TPA023 in the suppression of ET symptoms.


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Request Reprint E-Mail: rzoethout@chdr.nl

A [11C]Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced α5 benzodiazepine receptors in limbic regions

Preclinical evidence suggests the α5 subtype of the GABA-benzodiazepine receptor is involved in some of the actions of alcohol and in memory. The positron emission tomography (PET) tracer, [¹¹C]Ro15 4513 shows relative selectivity in labelling the α5 subtype over the other GABA-benzodiazepine receptor subtypes in limbic regions of the brain.

We used this tracer to investigate the distribution of α5 subtype availability in human alcohol dependence and its relationship to clinical variables. Abstinent (>6 weeks) alcohol-dependent men and healthy male controls underwent an [¹¹C]Ro15 4513 PET scan. We report [¹¹C]Ro15 4513 brain uptake for 8 alcohol-dependent men and 11 healthy controls.

We found a significant reduction in [¹¹C]Ro15 4513 binding in the nucleus accumbens, parahippocampal gyri, right hippocampus and amygdala in the alcohol-dependent compared with the healthy control group.

Levels of [¹¹C]Ro15 4513 binding in both hippocampi were significantly and positively associated with performance on a delayed verbal memory task in the alcohol-dependent but not the control group. We speculate that the reduced limbic [¹¹C]Ro15 4513 binding seen here results from the effects of alcohol, though we cannot currently distinguish whether they are compensatory in nature or evidence of brain toxicity.


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Request Reprint E-Mail: anne.lingford-hughes@ic.ac.uk

Effects of acute alcohol intoxication on automated processing: evidence from the double-step paradigm

Reflexive and voluntary levels of processing have been studied extensively with respect to possible impairments due to alcohol intoxication.

This study examined alcohol effects at the ‘automated’ level of processing essential to many complex visual processing tasks (e.g., reading, visual search) that involve ongoing modifications or reprogramming of well-practiced routines.

Data from 30 participants (16 male) were collected in two counterbalanced sessions (alcohol vs. no-alcohol control; mean breath alcohol concentration = 68 mg/dL vs. 0 mg/dL). Eye movements were recorded during a double-step task where 75% of trials involved two target stimuli in rapid succession (inter-stimulus interval [ISI] = 40, 70, or 100 ms) so that they could elicit two distinct saccades or eye movements (double steps). On 25% of trials a single target appeared.

Results indicated that saccade latencies were longer under alcohol. In addition, the proportion of single-step responses and the mean saccade amplitude (length) of primary saccades decreased significantly with increasing ISI.

The key novel finding, however, was that the reprogramming time needed to cancel the first saccade and adjust saccade amplitude was extended significantly by alcohol. The additional time made available by prolonged latencies due to alcohol was not utilized by the saccade programming system to decrease the number of two-step responses.

These results represent the first demonstration of specific alcohol-induced programming deficits at the automated level of oculomotor processing.



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Request Reprint E-Mail: vorstius@psy.fsu.edu

Effects of acute alcohol consumption on the perception of eye gaze direction

Alcohol consumption is associated with increases in aggressive behaviour, but the mechanisms underlying this relationship are poorly understood. One mechanism by which alcohol consumption may influence behaviour is via alterations in the processing of social cues such as gaze.

We investigated the effects of acute alcohol consumption on the perception of gaze, using a task in which participants determined whether a stimulus face was looking towards or away from them. Gaze direction varied across trials, allowing calculation of a threshold at which participants considered gaze to switch from direct to averted. Target faces varied in both sex and attractiveness. Thirty social drinkers attended three randomized experimental sessions. At each session, participants consumed 0.0, 0.2 or 0.4 g/kg alcohol, and completed the gaze perception task.

A significant three-way interaction involving target sex, participant sex and alcohol dose indicated that alcohol increased the cone of gaze for females viewing male targets (i.e. females were biased towards making a direct gaze judgement), but decreased the cone of gaze for males viewing male targets.

Our data indicate that alcohol consumption influences gaze perception, but that these effects vary across sex of both stimulus and rater. These effects may have important implications for alcohol-related violence.

Effects of acute alcohol consumption on alcohol-related cognitive biases in light and heavy drinkers are task-dependent

We investigated (1) the effects of alcohol on cognitive biases for alcohol-related cues, (2) the effects of drinking status on alcohol-related cognitive biases and (3) the similarity of any effects of alcohol across two measures of alcohol cognitive bias.

Healthy, heavy and light social alcohol users (n = 72) were examined in a single-blind placebo-controlled design. Participants received 0.00 g/kg, 0.13 g/kg or 0.40 g/kg of alcohol in a between-subjects design and then completed both a modified Stroop task and a visual probe task.

Modified Stroop data indicated a main effect of cue type, which was qualified by drinking status, with heavier drinkers slower to respond to alcohol-related cues. Visual probe data, in contrast, indicated a significant interaction effect between validity (valid: alcohol-related, invalid: neutral) and drink condition.

Participants receiving a moderate dose of alcohol (0.40 g/kg) were faster to respond to alcohol-related stimuli compared with participants receiving a low dose of alcohol or placebo.

These data indicate that the cognitive processes assayed by the visual probe and Stroop tasks may not be mediated by a common underlying mechanism.



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Request Reprint E-Mail: sally.adams@bristol.ac.uk

Alcohol stress response dampening: selective reduction of anxiety in the face of uncertain threat

Problematic alcohol use and stress response dampening (SRD) are intimately interconnected. Recent evidence suggests that alcohol produces selective SRD during uncertain but not certain threat.

We systematically varied shock probability in a novel task assessing alcohol SRD during low probable/uncertain threat, while holding temporal precision of threat constant. Intoxicated (0.08% target blood alcohol concentration) and placebo participants completed a cued shock threat task in which probability of shock administration at the offset of brief visual cues varied parametrically. High probability (100%) shock cues represented certain threat as used in earlier research, while lower probability (20% and 60%) shock cues provided novel uncertain threat conditions. Startle potentiation during cues and inter-trial intervals (ITIs) served as the measure of affective response.

General linear model analysis indicated that alcohol SRD magnitude increased monotonically as threat uncertainty increased. Alcohol SRD was significantly greater during 20% and 60% shock threat relative to 100% shock threat. Alcohol also significantly reduced startle potentiation during distal threat in shock-free ITIs. Alcohol SRD magnitude during distal/uncertain threat was meaningfully moderated by individual differences in negative affectivity and weekly alcohol consumption.

This work advances understanding of which properties of uncertainty are relevant to anxiety and anxiolytic effects of alcohol.



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Request Reprint E-Mail: jjcurtin@wisc.edu

Acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of exposure to stress and modulation by me

Nicotinic acetylcholine receptors mediate some of the rewarding and motivational effects of ethanol, including relapses. Relapses are common in drug addicts during abstinence when exposure to any stressor ensues. However, the role of nicotinic acetylcholine receptors in the ethanol- and stress-induced reinstatement of ethanol-induced conditioned place preference has not yet been explored.

Therefore, the present study investigated the influence of mecamylamine, a nicotinic acetylcholine receptors antagonist on acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in adult male Swiss mice.

The results revealed that mecamylamine (0.1–10 µg/mouse, intracerebroventricularly) dose dependently prevented the development, expression, and reinstatement of ethanol-induced conditioned place preference. Further, acute treatment with mecamylamine blocked the restraint stress and forced swim stress-induced reinstatement of ethanol-induced conditioned place preference. All of these treatments had no influence on the locomotor activity.

Therefore, it is concluded that mecamylamine blocks the acquisition, expression and reinstatement of conditioned reinforcing effects of ethanol without per se reinforcing or aversive influence. This ability of mecamylamine might be a potential advantage in the treatment of alcoholism.



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Request Reprint E-Mail: psbhutada@live.com

Alcohol selectively impairs negative self-relevant associations in young drinkers

The stress-dampening effects of alcohol have been attributed to ‘appraisal disruption’− decreased ability of stimuli to evoke threatening associations in memory. Appraisal disruption could apply to oneself as well as situational stimuli.

This question was investigated in undergraduate drinkers (n = 90/Gender) with low or high anxiety sensitivity (AS; n = 90/AS Group), a trait linked with hyper-vigilance to threat. Subjects received alcohol (0.7 g/kg males; 0.63 g/kg females), placebo or soft drink and performed a speech about their appearance. Sequence of drink administration and speech advisory (threat) was manipulated between subjects: Threat before Drink, Threat after Drink, No-Threat Control. The Implicit Association Test measured self-relevant associations based upon time to classify positive and negative attribute words (e.g. Cute, Ugly) paired with self-relevant or non-self-relevant object words (e.g. Me, Them).

Alcohol selectively slowed negative self-relevant decisions, regardless of other factors. Relative fluency of negative versus positive decisions (D) correlated inversely with state anxiety and systolic blood pressure immediately before speech performance, and correlated directly with severity of alcohol problems.

These findings are consistent with the Appraisal Disruption hypothesis. Preferential impairment of negative self-relevant associations may decrease perceived vulnerability under alcohol and increase risk for alcohol problems in young drinkers.



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Request Reprint E-Mail: martin_zack@camh.net

Popular intoxicants: what lessons can be learned from the last 40 years of alcohol and cannabis regulation

In this paper we discuss the relative physical, psychological and social harms of the two most frequently used intoxicant drugs in the UK, namely cannabis and alcohol.

Over the past 40 years, the use of both drugs has risen significantly with differential consequences.

It is argued that increased policing of cannabis use under the current drug classification system will lead to increased criminalization of young people, but is unlikely to significantly reduce the rates of schizophrenia and psychosis.

In comparison, increases in alcohol drinking are related to significant increases in liver cirrhosis hospital admissions and mortality, at a time when mortality rates from other major causes are on the decline.

A recent expert-led comparison of the health and social harms to the user and to others caused by the most commonly used drugs in the UK showed alcohol to be more than twice as harmful as cannabis to users, and five times as harmful as cannabis to others.

The findings underline the need for a coherent, evidence-based drugs policy that enables individuals to make informed decisions about the consequences of their drug use.

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Request Reprint E-Mail: D.Nutt@imperial.ac.uk

Effects of 0.4g/kg alcohol on attentional bias and alcohol-seeking behaviour in heavy and moderate social drinkers

Alcohol intoxication is known to influence attentional biases for alcohol-related cues and alcohol-seeking behaviour. It is unknown if heavier drinkers are more or less sensitive to these effects of alcohol, or whether the effects of alcohol on attentional bias are associated with subsequent alcohol-seeking behaviour.

In the present study, 55 social drinkers were administered either 0.4 g/kg alcohol or placebo in a repeated measures, double-blind experimental design. Participants completed a visual probe task with eye movement monitoring (to measure attentional bias) and a bogus taste test (to measure alcohol-seeking) in both alcohol and placebo sessions.

Heavy drinkers showed an attentional bias for alcohol cues that was unaffected by alcohol, whereas in moderate drinkers attentional bias was present after alcohol administration, but was absent after placebo.

All participants voluntarily consumed more beer during the taste test after administration of alcohol compared with placebo.

The effects of alcohol on attentional bias were unrelated to the effects of alcohol on beer consumption.

Results are consistent with the development of tolerance, rather than sensitization, to the acute effects of alcohol on attentional biases in heavy drinkers.

However, alcohol-induced increases in attentional bias were not related to the effects of alcohol on the motivation to drink.



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Request Reprint E-Mail: mfield@liverpool.ac.uk