The Crhr1 Gene, Trauma Exposure, And Alcoholism Risk: A Test Of G × E Effects

The corticotropin-releasing hormone type I receptor (CRHR1) gene has been implicated in the liability for neuropsychiatric disorders, particularly under conditions of stress. Based on the hypothesized effects of CRHR1 variation on stress reactivity, measures of adulthood traumatic stress exposure were analyzed for their interaction with CRHR1 haplotypes and SNPs in predicting the risk for alcoholism.

Phenotypic data on 2,533 non-related Caucasian individuals (1167 alcoholics and 1366 controls) were culled from the publically available Study of Addiction: Genetics and Environment (SAGE) genome-wide association study (GWAS). Genotypes were available for 19 tag SNPs. Logistic regression models examined the interaction between CRHR1 haplotypes / SNPs and adulthood traumatic stress exposure in predicting alcoholism risk.

Two haplotype blocks spanned CRHR1. Haplotype analyses identified one haplotype in the proximal block 1 (p = 0.029) and two haplotypes in the distal block 2 (p = 0.026, 0.042) that showed nominally significant (corrected p < .025) genotype × traumatic stress interactive effects on the likelihood of developing alcoholism. The block 1 haplotype effect was driven by SNPs rs110402 (p = 0.019) and rs242924 (p = 0.019). In block 2, rs17689966 (p = 0.018) showed significant, and rs173365 (p = 0.026) showed nominally significant, gene × environment (G x E) effects on alcoholism status.

This study extends the literature on the interplay between CRHR1 variation and alcoholism, in the context of exposure to traumatic stress. These findings are consistent with the hypothesized role of the extra hypothalamic CRF system dysregulation in the initiation and maintenance of alcoholism. Molecular and experimental studies are needed to more fully understand the mechanisms of risk and protection conferred by genetic variation at the identified loci.


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Request Reprint E-Mail:  lararay@psych.ucla.edu

Increased brain uptake and oxidation of acetate in heavy drinkers

When a person consumes ethanol, the body quickly begins to convert it to acetic acid, which circulates in the blood and can serve as a source of energy for the brain and other organs. 

This study used ¹³C magnetic resonance spectroscopy to test whether chronic heavy drinking is associated with greater brain uptake and oxidation of acetic acid, providing a potential metabolic reward or adenosinergic effect as a consequence of drinking. Seven heavy drinkers, who regularly consumed at least 8 drinks per week and at least 4 drinks per day at least once per week, and 7 light drinkers, who consumed fewer than 2 drinks per week were recruited. The subjects were administered [2-¹³C]acetate for 2 hours and scanned throughout that time with magnetic resonance spectroscopy of the brain to observe natural ¹³C abundance of N-acetylaspartate (NAA) and the appearance of ¹³C-labeled glutamate, glutamine, and acetate. 

Heavy drinkers had approximately 2-fold more brain acetate relative to blood and twice as much labeled glutamate and glutamine. The results show that acetate transport and oxidation are faster in heavy drinkers compared with that in light drinkers. 

Our finding suggests that a new therapeutic approach to supply acetate during alcohol detoxification may be beneficial. 


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Chapter 2 - Drinking (General Lifestyle Survey Overview - a report on the 2011 General Lifestyle Survey)

 

The General Household Survey (GHS) and the General Lifestyle Survey (GLF) have, between them, been measuring drinking behaviour for over 30 years. This chapter presents information on recent trends over time in drinking behaviour and detailed data for the 2011 survey year.

The Department of Health estimates that the harmful use of alcohol costs the National Health Service around £2.7bn a year and 7% of all hospital admissions are alcohol related. Drinking can lead to over 40 medical conditions, including cancer, stroke, hypertension, liver disease and heart disease. Reducing the harm caused by alcohol is therefore a priority for the Government and the devolved administrations. Excessive consumption of alcohol is a major preventable cause of premature mortality with alcohol-related deaths accounting for almost 1.5% of all deaths in England and Wales in 2011. The GHS/GLF is an important source for monitoring trends in alcohol consumption.
The GHS/GLF drinking data are widely used by universities and health organisations. The School of Health and Related Research (ScHARR) at the University of Sheffield has used GHS/GLF data to carry out alcohol-related public health research. The Public Health Observatories (PHOs) also use GLF data on drinking to produce model-based estimates of alcohol consumption at local authority level to inform local decision making.

The survey is one of the main sources for GB statistics on health determinants and is therefore often used for international comparison. For example, GHS/GLF drinking data were used in the Organisation for Economic Co-operation and Development’s (OECD) Health at a Glance publication. This publication looks at the factors that affect the health of EU populations and the performance of health systems in these countries.  > > > >  Read More

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Letter to the Editori - Msleading UK alcohol industry criticism of Canadian research on minimum pricing

We would like to respond to criticism of our research by the UK Wine and Spirit Trade Association (1), a UK alcohol industry trade magazine (2) and the Scotch Whisky Association (3). 

Our study, recently published in Addiction (4), reported a significant negative association between minimum alcohol prices and rates of wholly alcohol caused deaths. We are accused of misleading the public by reporting false estimates of the effects of minimum price changes on rates of death “hypothetically” estimated to be caused by alcohol and not “real deaths” such as those we report on our own website (5,6,7).

We are also charged with publishing results which contradict official trends in alcohol-related deaths in British Columbia, the Canadian province on which our research has focused. 

Finally, it is claimed that minimum pricing in Canada bears no relation to what is being proposed for the United Kingdom.


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Population drinking and drink driving in Norway and Sweden: an analysis of historical data 1957–89

Research suggests an association between population drinking and a large number of outcomes. However, driving while under the influence of alcohol (DWI) is conspicuously absent from this list of outcomes. The aim of this study was to estimate the relation between DWI and total consumption of alcohol on annual time–series data for Norway and Sweden.

For Norway, we used data on convictions for DWI per 100 000 inhabitants (aged 15–69 years). The DWI proxy for Sweden comprised the proportion (%) of all police-reported traffic accidents with personal injuries where the driver was under the influence of alcohol. Data on total alcohol sales in litres of pure alcohol per inhabitant (aged 15 years and older) were used as proxy for total alcohol consumption. We focused on the period 1957–89, during which the legislation concerning DWI remained unchanged in Norway as well as in Sweden. The statistical analyses were based on co-integrated models.

The estimates of the association between DWI and per capita alcohol consumption were strongly significant in Norway as well as in Sweden. For Norway, the estimated elasticity equalled 2 (P < 0.001) and for Sweden 1.5 (P < 0.001).

In Norway and Sweden, as total population level of alcohol consumption increases or decreases so does the incidence of driving while intoxicated.


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Request Reprint E-Mail:   totto@sofi.su.se

“A Different Atmosphere of Love”: A Qualitative Study of the Experiences of Participants in Evangelical Substance User Rehabilitation Programs in the Russian Federation

This article explores the lived experiences of individuals who have participated in faith-based substance user rehabilitation programs in the Russian Federation. The Russian Federation has high rates of alcohol and opioid dependence and a dearth of professional treatment options. In the post-Soviet period, Evangelical Christian groups have developed substance user rehabilitation programs to attempt to address substance use and its related problems. 

Data were collected during 2010 via focus group interviews with participants in three Evangelical rehabilitation programs in the Volga region of the Russian Federation. 

Themes emerging from the qualitative data analysis process were classified into three broad categories: Typical Day, Personal Background/Decision to Enter Rehabilitation, and Helpful Aspects of Rehabilitation Process.

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Request Reprint E-Mail:  kstoltzfus@lcc.lt

Gray matter volume correlates of global positive alcohol expectancy in non-dependent adult drinkers

Alcohol use and misuse is known to involve structural brain changes. Numerous imaging studies have examined changes in gray matter (GM) volumes in dependent drinkers, but there is little information on whether non-dependent drinking is associated with structural changes and whether these changes are related to psychological factors—such as alcohol expectancy—that influence drinking behavior. 

We used voxel-based morphometry (VBM) to examine whether the global positive scale of alcohol expectancy, as measured by the Alcohol Expectancy Questionnaire-3, is associated with specific structural markers and whether such markers are associated with drinking behavior in 113 adult non-dependent drinkers (66 women). 

Alcohol expectancy is positively correlated with GM volume of left precentral gyrus (PCG) in men and women combined and bilateral superior frontal gyri (SFG) in women, and negatively correlated with GM volume of the right ventral putamen in men. 

Furthermore, mediation analyses showed that the GM volume of PCG mediate the correlation of alcohol expectancy and the average number of drinks consumed per occasion and monthly total number of drinks in the past year. When recent drinking was directly accounted for in multiple regressions, GM volume of bilateral dorsolateral prefrontal cortices correlated positively with alcohol expectancy in the combined sample. 

To our knowledge, these results are the first to identify the structural brain correlates of alcohol expectancy and its mediation of drinking behaviors. These findings suggest that more studies are needed to investigate increased GM volume in the frontal cortices as a neural correlate of alcohol expectancy.


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Request Reprint E-Mail:   chiang-shan.li@yale.edu

Neural activation during processing of aversive faces predicts treatment outcome in alcoholism

Neuropsychological studies reported decoding deficits of emotional facial expressions in alcohol-dependent patients, and imaging studies revealed reduced prefrontal and limbic activation during emotional face processing. However, it remains unclear whether this reduced neural activation is mediated by alcohol-associated volume reductions and whether it interacts with treatment outcome. 

We combined analyses of neural activation during an aversive face-cue-comparison task and local gray matter volumes (GM) using Biological Parametric Mapping in 33 detoxified alcohol-dependent patients and 33 matched healthy controls. 

Alcoholics displayed reduced activation toward aversive faces–neutral shapes in bilateral fusiform gyrus [FG; Brodmann areas (BA) 18/19], right middle frontal gyrus (BA46/47), right inferior parietal gyrus (BA7) and left cerebellum compared with controls, which were explained by GM differences (except for cerebellum). 

Enhanced functional activation in patients versus controls was found in left rostral anterior cingulate cortex (ACC) and medial frontal gyrus (BA10/11), even after GM reduction control. 

Increased ACC activation correlated significantly with less (previous) lifetime alcohol intake [Lifetime Drinking History (LDH)], longer abstinence and less subsequent binge drinking in patients. 

High LDH appear to impair treatment outcome via its neurotoxicity on ACC integrity. Thus, high activation of the rostral ACC elicited by affective faces appears to be a resilience factor predicting better treatment outcome. 

Although no group differences were found, increased FG activation correlated with patients' higher LDH. Because high LDH correlated with worse task performance for facial stimuli in patients, elevated activation in the fusiform ‘face’ area may reflect inefficient compensatory activation. 

Therapeutic interventions (e.g. emotion evaluation training) may enable patients to cope with social stress and to decrease relapses after detoxification.


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Request Reprint E-Mail:    andreas.heinz@charite.de

Examination of Rare Missense Variants in the CHRNA5-A3-B4 Gene Cluster to Level of Response to Alcohol in the San Diego Sibling Pair Study

Common variants in the CHRNA5-A3-B4 gene cluster have been shown to be associated with nicotine dependence and alcohol use disorders (AUDs) and related traits, including the level of response (LR) to alcohol. Recently, rare variants (MAF < 0.05) in CHRNB4 have been reported to be associated with a decreased risk of developing nicotine dependence. However, the role of rare variants in the CHRNA5-A3-B4 gene cluster to the LR to alcohol has not yet been established.

To determine whether rare variants in the CHRNA5-A3-B4 gene cluster contribute to the LR to alcohol, the coding regions of these 3 genes were sequenced in 538 subjects from the San Diego Sibling Pair study.

The analyses identified 16 rare missense variants, 9 of which were predicted to be damaging using in silico analysis tools. Carriers of these variants were compared to noncarriers using a family-based design for each gene and for the gene cluster as a whole. In these analyses, a CHRNA5 carrier status was significantly associated with the phenotype related to the feeling of intoxication experienced during the alcohol challenge (p = 0.039).

These results indicate that rare genetic variation in the CHRNA5-A3-B4 gene cluster contributes modestly to the LR to alcohol in the San Diego Sibling Pair study and may protect against AUDs. However, replication studies are needed to confirm our findings.  


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Request Reprint E-Mail:    ChoquetH@anesthesia.ucsf.edu   

ONS alcohol-related deaths bulletin (2011) indicate rates remain steady

Earlier this year the ONS released the latest Statistical bulletin for alcohol-related deaths in the UK (2011). In 2011 there were 8,748 alcohol-related deaths in the UK, a small decrease of 42 fewer than 2010.

The trend remains relatively stable over the last 10 years, though with some fluctuations amongst males and significant regional variations. However overall rates are still significantly higher than 20 years ago following rising rates during the 1990s, and a Lancet piece last year predicted a longer term rise. Alcohol-related hospital admissions are also continuing to rise despite a fall in consumption since 2004.    > > >  Read More

Lifetime Drinking Trajectories Among Veterans in Treatment for HIV+

Previous work on the course of drinking across the life course identified 4 distinct patterns of problem drinking: severe chronic (SC), severe nonchronic (SNC), late onset (LO), and young adult (YA). The purpose of the current study was to determine the generalizability of these findings to a sample of midlife veterans with quite different characteristics from those previously assessed; specifically, veterans in treatment for HIV and veterans in treatment for non-HIV medical issues.

Participants were drawn from the Veterans Aging Cohort Study that included HIV-positive and matched non-HIV participants. As in our earlier studies, the lifetime drinking history was used to assess drinking phases, and latent growth mixture models were used for analyses.

Similar to previous findings, both the HIV+ and non-HIV groups exhibited 4 patterns of drinking (SC, SNC, LO, and YA). SC drinkers had younger ages of onset for drinking and longer duration of smoking. SC drinkers also had the highest rates of cocaine use. Within the HIV+ subsample, SC and LO drinkers increased their drinking after their HIV diagnosis.

This study is the first to examine lifetime drinking patterns among those treated for HIV and provides an excellent starting point for examining finer-grained relationships involving drinking, onset of HIV, and treatment outcomes. Absent from the current study and of particular importance to future work in this area is the need for precise information regarding the temporal relationship between date of HIV diagnosis, onset of treatment, and changes in drinking behavior over the life course.


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Request Reprint E-Mail:    ttjbocaj@aol.com

Predictors of Initial and Sustained Remission from Alcohol Use Disorders: Findings from the 30-Year Follow-Up of the San Diego Prospective Study

Individuals who report problematic drinking early in life often recover from alcohol-related disorders, with or without formal treatment. While risk factors associated with developing alcohol use disorders (AUDs), such as a family history of alcoholism and the genetically influenced low level of response (LR) to alcohol, have been identified, less is known about characteristics that relate to remission from AUDs.

The male subjects (98% Caucasian) for this study were 129 probands from the San Diego Prospective Study who were first evaluated at age 20 as drinking but not alcohol-dependent young men, most of whom were college graduates by follow-up. The individuals evaluated here met criteria for an AUD at their first follow-up at ages 28 to 33 and were followed every 5 years for the next 2 decades. Discrete-time survival analysis was used to examine rates of initial and sustained AUD remission and to evaluate the relationships of premorbid characteristics and other risk factors to these outcomes.

Sixty percent of the sample met criteria for an initial AUD remission of 5 or more years, including 45% with sustained remission (i.e., no subsequent AUD diagnosis). Higher education, lower drinking frequency, and having a diagnosis of alcohol abuse (rather than dependence) were associated with higher rates of initial AUD remission. A lower LR to alcohol at age 20, as well as lower drinking frequency, having received formal alcohol treatment, and older age at the first follow-up all predicted a greater likelihood of sustained AUD remission.

This study identified key factors associated with initial and sustained AUD remission in subjects diagnosed with AUD in young adulthood. Characteristics associated with better outcomes early in the life span, such as lower drinking frequency and early treatment, appear to have a lasting impact on remission from AUD across adulthood.


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Request Reprint E-Mail:  mschuckit@ucsd.edu

The Relationship Between Parent and Student Religious Coping and College Alcohol Use

The present study examined social support and alcohol norms as mediators of the relationship between religious coping and college drinking (e.g., frequency and heavy drinking).

The sample consisted of college students (n = 129) and their parents (n = 113). Religious coping (parent and student) was associated with less frequent alcohol use and less heavy drinking. Using a path model to test direct and indirect effects, the mediators were entered simultaneously and allowed to correlate with each other.

 Alcohol norms mediated the relationship between religious coping and drinking outcomes. Social support was not a significant mediator. Broader protective implications of religious coping are discussed.

           

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Request Reprint E-Mail:  harrellz@msu.edu

What is the burden of alcohol-related injuries in an inner city emergency department?

The annual cost to the NHS of alcohol-related injury and illness is estimated to be £2.7 billion. Alcohol-related violence has become a concerning public health issue. This study set out to establish the burden of alcohol-related violence in an inner city UK emergency department (ED). 
                               

This single centre study was undertaken in the ED of the Bristol Royal Infirmary. This department serves an inner city population. An independent researcher administered a questionnaire to every patient who attended during the study period. A questionnaire was also administered to the treating clinician to ascertain the diagnosis, and whether the patient's attendance was related to alcohol use.

 

14% (n=111) of participants felt that their attendance at the ED was related to alcohol. 11% of all injured patients felt it was due to alcohol consumption. 3% of patients attended with an alcohol-related illness. The treating clinicians reported that 21% of all patients in this study attended with a problem either directly or indirectly attributable to alcohol. 

                               

The number of attendances attributable to alcohol-related injury and illness was at least 14% of all patients. One third of patients presenting with an alcohol-related illness or injury required admission to hospital. If these figures are extrapolated, the number of patients presenting with alcohol-related injury is in excess of 7000 attendances to the Bristol Royal Infirmary annually, or nearly 2 million ED patients every year in England and Wales, resulting in 640 000 admissions.

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Request Reprint E-Mail:    rebecca.hoskins@uhbristol.nhs.uk

News Release - Unhealthy drinking widespread around the world, CAMH study shows

 

A new study by the Centre for Addiction and Mental Health (CAMH) shows that alcohol is now the third leading cause of the global burden of disease and injury, despite the fact most adults worldwide abstain from drinking.

 

This research, part of the 2010 Global Burden of Disease study, was published in this month’s issue of the journal Addiction. It also found that Canadians drink more than 50 per cent above the global average.

 

“Alcohol consumption has been found to cause more than 200 different diseases and injuries,” said Kevin Shield, the lead author of the study. “These include not only well-known outcomes of drinking such as liver cirrhosis or traffic accidents, but also several types of cancer, such as female breast cancer.”

The study reports the amount and patterns of alcohol consumption by country for 2005, and calculates estimates for these figures for 2010. It reveals vast differences by geographical region in the numbers of people who consume alcohol, the amount they drink, and general patterns of drinking. Some other findings:

• Drinkers in Europe and parts of Sub-Saharan Africa are the world’s heaviest consumers of alcohol, on average.
• People in Eastern Europe and Southern Sub-Saharan Africa consumed alcohol in the unhealthiest manner, as they frequently consumed large quantities, drank to intoxication, engaged in prolonged binges, and consumed alcohol mainly outside of meals.
• People in North Africa, the Middle East and South Asia consumed the least amount of alcohol.
• North Americans in general, and Canadians in particular drink more than 50 per cent above the global average, and show a more detrimental drinking pattern than most EU countries, with more bingeing. > > > >  Read More

Longitudinal associations between attitudes towards binge drinking and alcohol-free drinks, and binge drinking behavior in adolescence

Alcohol attitudes are often considered an important predecessor of drinking behavior, although the literature is equivocal. Lately, attention has turned to enhancing positive cognitions on alcoholic-free drinks to discourage heavy drinking. 

The current study was the first to longitudinally examine associations between attitudes towards binge drinking and alcohol-free drinks and binge drinking behavior in a cross-lagged path model in Mplus. 

Participants were 293 adolescents (131 boys, M_age = 16.1 years) who filled in two online questionnaires with a six-month interval. Binge drinking behavior and attitudes towards binge drinking and alcohol-free drinks were all significantly correlated at both waves. The multivariate model, however, showed that only higher levels of binge drinking at T1 were prospectively related to more positive binge drinking attitudes at T2, and not vice versa. Analyses were controlled for sex, educational level, and age. 

Findings discard the Theory of Planned Behavior, but rather seem consistent with the Theory of Cognitive Dissonance, i.e., adolescents may adapt their cognitions to their behavior. 

More longitudinal research with several time points and over a longer period of time is needed to further examine the development of attitudes and drinking behavior.


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Request Reprint E-Mail:  m.kleinjan@pwo.ru.nl

Alcohol- or drug-use disorders and motor vehicle accident mortality: A retrospective cohort study

 

A large body of research has linked alcohol consumption and motor vehicle accidents (MVAs), but far fewer studies have estimated the risk of MVA fatality among drug users.

Our study addresses this gap. We identified cohorts of individuals hospitalized in California from 1990 to 2005 with ICD-9 diagnoses of methamphetamine- (n = 74,170), alcohol- (n = 592,406), opioids- (n = 68,066), cannabis- (n = 47,048), cocaine- (n = 48,949), or polydrug-related disorders (n = 411,175), and these groups were followed for up to 16 years. Age-, sex-, and race-adjusted standardized mortality rates (SMRs) for deaths due to MVAs were generated in relation to the California general population.

Standardized MVA mortality ratios were elevated across all drug cohorts: alcohol (4.5, 95% CI, 4.1–4.9), cocaine (3.8, 95% CI, 2.3–5.3), opioids (2.8, 95% CI, 2.1–3.5), methamphetamine (2.6, 95% CI, 2–3.1), cannabis (2.3, 95% CI, 1.5–3.2) and polydrug (2.6, 95% CI, 2.4–2.9).

Males and females had similar MVA SMRs.

Our large, population-based study found elevated risk of MVA mortality across all cohorts of individuals with alcohol- or drug-use disorders.

Given that illicit drug users are often unaware of or misperceive the impacts of drug use on safe driving, it may be important for health-service or public-health interventions to address such biases and improve road safety


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Request Reprint E-Mail:    Russ.Callaghan@UNBC.ca

Effects of admission and treatment strategies of DWI courts on offender outcomes

 

The purpose of this study is to classify DWI courts on the basis of the mix of difficult cases participating in the court (casemix severity) and the amount of involvement between the court and participant (service intensity). Using our classification typology, we assessed how casemix severity and service intensity are  associated with program outcomes. We expected that holding other factors constant, greater service intensity would improve program outcomes while a relatively severe casemix would result in worse program outcomes.

The study used data from 8 DWI courts, 7 from Michigan and 1 from North Carolina. Using a 2-way classification system based on court casemix severity and program intensity, we selected participants in 1 of the courts, and alternatively 2 courts as reference groups. Reference group courts had relatively severe casemixes and high service intensity. We used propensity score matching to match participants in the other courts to participants in the reference group court programs. Program outcome measures were the probabilities of participants’: failing to complete the court's program; increasing educational attainment; participants improving employment from time of program enrollment; and re-arrest.

For most outcomes, our main finding was that higher service intensity is associated with better outcomes for court participants, as anticipated, but a court's casemix severity was unrelated to study outcomes.

Our results imply that devoting more resources to increasing duration of treatment is productive in terms of better outcomes, irrespective of the mix of participants in the court's program.

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Request Reprnt E-Mail:  fsloan@duke.edu

Validation of the Drinking Motives Questionnaire (DMQ) in older adults

 

Drinking motives have been established as an important construct in the prediction of alcohol use and drinking problems among younger adults, but there is little understanding about the drinking motivations of older adults. Although emerging evidence shows the importance of studying older adults' own reasoning for their alcohol consumption, measures that have been used to assess such reasons lack psychometric assessment.

This study aims to validate the three-dimensional structure of the Drinking Motives Questionnaire (DMQ) in older adults and to investigate the relationships between drinking motives and alcohol use.

A sample of community dwelling older adults (N = 370) completed self-report measures assessing drinking behavior and motives for drinking. Using confirmatory factor analysis, the results supported a three-factor model of drinking motives. Multi-group analysis of invariance showed support for configural and metric invariance, and partial support was met for scalar invariance.

Social motivations for drinking were the most frequently endorsed, followed by enhancement, and coping motives. Males reported more frequent drinking for each of the three motives. Social motives were consistently related to drinking behaviors and coping had a direct relationship to drinking problems.

Overall, the study shows that the DMQ has promise as a measure for use with older adults.


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Request Reprint E-Mail:  kim.gilson@gmail.com

Global alcohol exposure estimates by country, territory and region for 2005—a contribution to the Comparative Risk Assessment for the 2010 Global Burden of Disease Study

This study aimed to estimate the prevalence of life-time abstainers, former drinkers and current drinkers, adult per-capita consumption of alcohol and pattern of drinking scores, by country and Global Burden of Disease region for 2005, and to forecast these indicators for 2010.

Statistical modelling based on survey data and routine statistics.

A total of 241 countries and territories.

Per-capita consumption data were obtained with the help of the World Health Organization's Global Information System on Alcohol and Health. Drinking status data were obtained from Gender, Alcohol and Culture: An International Study, the STEPwise approach to Surveillance study, the World Health Survey/Multi-Country Study and other surveys. Consumption and drinking status data were triangulated to estimate alcohol consumption across multiple categories.

In 2005 adult per-capita annual consumption of alcohol was 6.1 litres, with 1.7 litres stemming from unrecorded consumption; 17.1 litres of alcohol were consumed per drinker, 45.8% of all adults were life-time abstainers, 13.6% were former drinkers and 40.6% were current drinkers. Life-time abstention was most prevalent in North Africa/Middle East and South Asia. Eastern Europe and Southern sub-Saharan Africa had the most detrimental pattern of drinking scores, while drinkers in Europe (Eastern and Central) and sub-Saharan Africa (Southern and West) consumed the most alcohol.

Just over 40% of the world's adult population consumes alcohol and the average consumption per drinker is 17.1 litres per year. However, the prevalence of abstention, level of alcohol consumption and patterns of drinking vary widely across regions of the world.


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Request Reprint E-Mail:    Kevin.Shield@utoronto.ca

Depressive symptoms are a vulnerability factor for heavy episodic drinking: A short-term, four-wave longitudinal study of undergraduate women

Heavy episodic drinking is increasingly common among undergraduate women. Cross-sectional research suggests that depressive symptoms and heavy episodic drinking are related. Nonetheless, surprisingly little is known about whether depressive symptoms are an antecedent of heavy episodic drinking, a consequence of heavy episodic drinking, or both. Such knowledge is essential to the accurate conceptualization of heavy episodic drinking, depressive symptoms, and their interrelations. 

In the present short-term longitudinal study, depressive symptoms and heavy episodic drinking were proposed to reciprocally influence each other over time, with depressive symptoms predicting changes in heavy episodic drinking over 1 week and vice versa. This reciprocal relations model was tested in 200 undergraduate women using a 4-wave, 4-week longitudinal design. Structural equation modeling was used to conduct cross-lagged analyses testing reciprocal relations between depressive symptoms and heavy episodic drinking.

Consistent with hypotheses, both depressive symptoms and heavy episodic drinking were temporally stable, and depressive symptoms predicted changes in heavy episodic drinking over 1 week.

Contrary to hypotheses, heavy episodic drinking did not predict changes in depressive symptoms over 1 week. 

Results are consistent with a vulnerability model suggesting depressive symptoms leave undergraduate women vulnerable to heavy episodic drinking. For undergraduate women who are struggling with feelings of sadness, worthlessness, and hopelessness, heavy episodic drinking may provide a temporary yet maladaptive means of avoiding or alleviating depressive symptoms.


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Request Reprint E-Mail:      sherry.stewart@dal.ca    

NKAIN1–SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent

We aimed to identify novel, functional, replicable and genome-wide significant risk regions specific for alcohol dependence using genome-wide association studies (GWASs).

A discovery sample (1409 European-American cases with alcohol dependence and 1518 European-American controls) and a replication sample (6438 European-Australian family subjects with 1645 alcohol dependent probands) underwent association analysis. Nineteen other cohorts with 11 different neuropsychiatric disorders served as contrast groups. Additional eight samples underwent expression quantitative locus (eQTL) analysis.

A genome-wide significant risk gene region (NKAIN1–SERINC2) was identified in a meta-analysis of the discovery and replication samples. This region was enriched with 74 risk SNPs (unimputed); half of them had significant cis-acting regulatory effects. The distributions of −log(p) values for the SNP-disease associations or SNP-expression associations in this region were consistent throughout eight independent samples. Furthermore, imputing across the NKAIN1–SERINC2 region, we found that among all 795 SNPs in the discovery sample, 471 SNPs were nominally associated with alcohol dependence (1.7 × 10⁻⁷ ≤ p ≤ 0.047); 53 survived region- and cohort-wide correction for multiple testing; 92 SNPs were replicated in the replication sample (0.002 ≤ p ≤ 0.050). This region was neither significantly associated with alcohol dependence in African-Americans, nor with other non-alcoholism diseases. Finally, transcript expression of genes in NKAIN1–SERINC2 was significantly (p < 3.4 × 10⁻⁷) associated with expression of numerous genes in the neurotransmitter systems or metabolic pathways previously associated with alcohol dependence.

NKAIN1–SERINC2 may harbor a causal variant(s) for alcohol dependence. It may contribute to the disease risk by way of neurotransmitter systems or metabolic pathways.

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Request Reprint E-Mail:  Lingjun.Zuo@yale.edu

Prevalence and Patterns of Polysubstance Use in a Nationally Representative Sample of 10th Graders in the United States

The current study examines the prevalence and demographic correlates of self-reported substance use and identifies subgroups of polysubstance users among a cohort of United States 10th-grade students.

A nationally representative school-based cohort of United States 10th-grade students completed the NEXT Generation Health Study baseline survey in spring 2010 (N = 2,524).

Past-year use of marijuana was most common among illicit drugs (26%), followed by misuse of medication (9%) and use of other illicit drugs (8%). During the past month, alcohol use was reported by more than one third (35%), binge drinking by 27%, and cigarette smoking by 19%. Results further show that substance use varied somewhat by demographic characteristics. Results from the latent class analysis of polysubstance use indicated a four-class solution as the best-fitting model; class 1 (59%) included the nonuser group; class 2 (23%) comprised the predominant alcohol user group; class 3 (11%) formed the predominant marijuana user group; and class 4 (8%) was characterized as the predominant polysubstance user group. Somatic and depressive symptoms varied significantly by class membership, with predominant polysubstance users reporting elevated levels of somatic and depressive symptoms.

The findings from this national study of 10th-grade students indicate high rates of substance and polysubstance use. The high level of depressive and somatic symptoms among polysubstance users indicates the need for mental health screening and referral.


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Request Reprint E-Mail:   kconway@nida.nih.gov

Ethanol and dietary unsaturated fat (corn oil/linoleic acid enriched) cause intestinal inflammation and impaired intestinal barrier defense in mice chronically fed alcohol

Alcohol and dietary fat both play an important role in alcohol-mediated multi-organ pathology, including gut and liver. In the present study we hypothesized that the combination of alcohol and dietary unsaturated fat (USF) would result in intestinal inflammatory stress and mucus layer alterations, thus contributing to disruption of intestinal barrier integrity. 

C57BL/6N mice were fed Lieber-DeCarli liquid diets containing EtOH and enriched in USF (corn oil/linoleic acid) or SF (medium chain triglycerides: beef tallow) for 8 weeks. Intestinal histology, morphometry, markers of inflammation, as well as levels of mucus protective factors were evaluated. 

Alcohol and dietary USF triggered an intestinal pro-inflammatory response, characterized by increase in Tnf-α, MCP1, and MPO activity. Further, alcohol and dietary USF, but not SF, resulted in alterations of the intestinal mucus layer, characterized by decreased expression of Muc2 in the ileum. 

A strong correlation was observed between down-regulation of the antimicrobial factor Cramp and increased Tnf-α mRNA. Therefore, dietary unsaturated fat (corn oil/LA enriched) is a significant contributing factor to EtOH-mediated intestinal inflammatory response and mucus layer alterations in rodents.


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Evaluating the Effects of the Introduction of Off-Sale Alcohol Outlets on Violent Crime

To examine the effects on violence of a policy change that ended prohibition of off-sale alcohol outlets in Lubbock, Texas. \

Time-series analysis of violent crime data from police records comparing the periods before and after the policy change. 

The effect of the policy change on both total violent crime and aggregated assault was small and did not approach statistical significance. 

Increased availability of alcohol through off-sale premises may not influence the type of violence reported to the police in Lubbock, Texas.                


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Mouse model of chronic and binge ethanol feeding (the NIAAA model)

Chronic alcohol consumption is a leading cause of chronic liver disease worldwide, leading to cirrhosis and hepatocellular carcinoma. Currently, the most widely used model for alcoholic liver injury is ad libitum feeding with the Lieber-DeCarli liquid diet containing ethanol for 4–6 weeks; however, this model, without the addition of a secondary insult, only induces mild steatosis, slight elevation of serum alanine transaminase (ALT) and little or no inflammation.

Here we describe a simple mouse model of alcoholic liver injury by chronic ethanol feeding (10-d ad libitum oral feeding with the Lieber-DeCarli ethanol liquid diet) plus a single binge ethanol feeding. 

This protocol for chronic-plus-single-binge ethanol feeding synergistically induces liver injury, inflammation and fatty liver, which mimics acute-on-chronic alcoholic liver injury in patients. This feeding protocol can also be extended to chronic feeding for longer periods of time up to 8 weeks plus single or multiple binges. 

Chronic-binge ethanol feeding leads to high blood alcohol levels; thus, this simple model will be very useful for the study of alcoholic liver disease (ALD) and of other organs damaged by alcohol consumption.


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Use of record-linkage to handle non-response and improve alcohol consumption estimates in health survey data: a study protocol

Reliable estimates of health-related behaviours, such as levels of alcohol consumption in the population, are required to formulate and evaluate policies. National surveys provide such data; validity depends on generalisability, but this is threatened by declining response levels. Attempts to address bias arising from non-response are typically limited to survey weights based on sociodemographic characteristics, which do not capture differential health and related behaviours within categories. This project aims to explore and address non-response bias in health surveys with a focus on alcohol consumption.

 

The Scottish Health Surveys (SHeS) aim to provide estimates representative of the Scottish population living in private households. Survey data of consenting participants (92% of the achieved sample) have been record-linked to routine hospital admission (Scottish Morbidity Records (SMR)) and mortality (from National Records of Scotland (NRS)) data for surveys conducted in 1995, 1998, 2003, 2008, 2009 and 2010 (total adult sample size around 40 000), with maximum follow-up of 16 years. Also available are census information and SMR/NRS data for the general population. Comparisons of alcohol-related mortality and hospital admission rates in the linked SHeS-SMR/NRS with those in the general population will be made. Survey data will be augmented by quantification of differences to refine alcohol consumption estimates through the application of multiple imputation or inverse probability weighting. The resulting corrected estimates of population alcohol consumption will enable superior policy evaluation. An advanced weighting procedure will be developed for wider use.

Ethics approval for SHeS has been given by the National Health Service (NHS) Multi-Centre Research Ethics Committee and use of linked data has been approved by the Privacy Advisory Committee to the Board of NHS National Services Scotland and Registrar General. Funding has been granted by the MRC. The outputs will include four or five public health and statistical methodological international journal and conference paper.

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