Interaction between dopamine D2 receptor genotype and parental rule-setting in adolescent alcohol use: evidence for a gene-parenting interaction

Molecular Psychiatry advance online publication 24 February 2009

Association studies investigating the link between the dopamine D2 receptor gene (DRD2) and alcohol (mis)use have shown inconsistent results. This may be due to lack of attention for environmental factors. High levels of parental rule-setting are associated with lower levels of adolescent alcohol use and delay of initiation of drinking.

We tested whether DRD2 TaqI A (rs1800497) genotype interacts with alcohol-specific parenting practices in predicting the uptake of regular adolescent alcohol use.

Parental rule-setting was directly and inversely related to adolescent alcohol use over time.

For DRD2 genotype no significant main effect was found. DRD2 genotype interacted with parental rule-setting on adolescent alcohol use over time: adolescents, with parents highly permissive toward alcohol consumption and carrying a genotype with the DRD2 A1 (rs1800497T) allele, used significantly more alcohol over time than adolescents without these characteristics.

The DRD2 genotype may pose an increased risk for alcohol use and abuse, depending on the presence of environmental risk factors, such as alcohol-specific parenting.

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Request Reprint E-Mail: C.vanderZwaluw@bsi.ru.nl_

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Finland's u-turn on alcohol tax



Health ministers are describing drinking as the new smoking amid rising concern about the price of alcohol in the UK.

The Scottish government has suggested a range of radical measures, including a minimum price per unit of alcohol.

After a public consultation they are due to respond with more detailed proposals for legislation later this month.

The idea of minimum pricing is supported by medical organisations and charities, but opposed by retailers who say moderate drinkers would be unfairly penalised.

The Scottish government says the connection between price and consumption is backed by international evidence, including the recent experience of Finland.

Tax cut
In 2004 tax on alcohol in Finland was dramatically reduced, leading to price reductions of up to a third, depending on the type of alcohol.

Health campaigners say alcohol related harm visibly increased within the space of two or three years.
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Moderate Alcohol Intake and Cancer Incidence in Women

Journal of the National Cancer Institute Advance Access published online on February 24, 2009

With the exception of breast cancer, little is known about the effect of moderate intakes of alcohol, or of particular types of alcohol, on cancer risk in women.

A quarter of the cohort reported drinking no alcohol; 98% of drinkers consumed fewer than 21 drinks per week, with drinkers consuming an average of 10 g alcohol (1 drink) per day. During an average 7.2 years of follow-up per woman 68 775 invasive cancers occurred. Increasing alcohol consumption was associated with increased risks of cancers of the oral cavity and pharynx (increase per 10 g/d = 29%, 95% CI = 14% to 45%, Ptrend < .001), esophagus (22%, 95% CI = 8% to 38%, Ptrend = .002), larynx (44%, 95% CI = 10% to 88%, Ptrend = .008), rectum (10%, 95% CI = 2% to 18%, Ptrend = .02), liver (24%, 95% CI = 2% to 51%, Ptrend = .03), breast (12%, 95% CI = 9% to 14%, Ptrend < .001), and total cancer (6%, 95% CI = 4% to 7%, Ptrend < .001). The trends were similar in women who drank wine exclusively and other consumers of alcohol. For cancers of the upper aerodigestive tract, the alcohol-associated risk was confined to current smokers, with little or no effect of alcohol among never and past smokers (Pheterogeneity < .001). Increasing levels of alcohol consumption were associated with a decreased risk of thyroid cancer (Ptrend = .005), non–Hodgkin lymphoma (Ptrend = .001), and renal cell carcinoma (Ptrend = .03).

Low to moderate alcohol consumption in women increases the risk of certain cancers. For every additional drink regularly consumed per day, the increase in incidence up to age 75 years per 1000 for women in developed countries is estimated to be about 11 for breast cancer, 1 for cancers of the oral cavity and pharynx, 1 for cancer of the rectum, and 0.7 each for cancers of the esophagus, larynx and liver, giving a total excess of about 15 cancers per 1000 women up to age 75.

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Request Reprint E-Mail: naomi.allen@ceu.ox.ac.uk

Alcohol Intake and Cigarette Smoking and Risk of a Contralateral Breast Cancer

American Journal of Epidemiology Advance Access published online on February 11, 2009

Women with primary breast cancer are at increased risk of developing second primary breast cancer. Few studies have evaluated risk factors for the development of asynchronous contralateral breast cancer in women with breast cancer.

In the Women's Environmental Cancer and Radiation Epidemiology Study (1985–2001), the roles of alcohol and smoking were examined in 708 women with asynchronous contralateral breast cancer (cases) compared with 1,399 women with unilateral breast cancer (controls).

Ever regular drinking was associated with an increased risk of asynchronous contralateral breast cancer (rate ratio = 1.3, 95% confidence interval: 1.0, 1.6), and the risk increased with increasing duration (P = 0.03). Smoking was not related to asynchronous contralateral breast cancer.

In this, the largest study of asynchronous contralateral breast cancer to date, alcohol is a risk factor for the disease, as it is for a first primary breast cancer.

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Request Reprint E-Mail: knight@lunenfeld.ca

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Sequence Variations of the Human MPDZ Gene and Association With Alcoholism in Subjects With European Ancestry

Alcoholism: Clinical and Experimental Research Published Online: 28 Jan 2009

Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice.

Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019).

Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS.

Further functional genomic analysis of MPDZ variants and investigation of their association with a broader array of alcoholism-related phenotypes could reveal additional genetic markers of alcoholism.

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Request Reprint E-Mail: karpyak.victor@mayo.edu

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Media coverage of celebrity DUIs: teachable moments or problematic social modeling?
Alcohol and Alcoholism Advance Access published online on0 on February 16, 2009

Alcohol in the media influences norms around use, particularly for young people. A recent spate of celebrity arrests for drinking and driving (DUI) has received considerable media attention. We asked whether these newsworthy events serve as teachable moments or problematic social modeling for young women. .

Stories were brief, episodic and focused around glamorous celebrity images. They included routine discussion of the consequences of the DUI for the individual celebrities without much evidence of a consideration of the public health dimensions of drinking and driving or possible prevention measures.

Our analysis found little material in the media coverage that dealt with preventing injury or promoting individual and collective responsibility for ensuring such protection. Media attention to such newsworthy events is a missed opportunity that can and should be addressed through media advocacy efforts.

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Request Reprint E-Mail: kasmith@jhsph.edu
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Alcohol, Gestation and Breastfeeding: Selenium as an Antioxidant Therapy
Alcohol and Alcoholism Advance Access published online on February 12, 2009

The aim of this paper is to study the relationship between alcohol, selenium and oxidative stress in breastfeeding rat pups exposed to ethanol during gestation and lactation. We have also studied how a Se-supplemented diet among mothers could prevent different oxidative liver disorders in the pups.

In the liver of pups, exposure to ethanol provoked a decrease in selenium and GPx activity and an increase in GR and CAT activity, as well as in carbonyl groups in protein. A pups had higher Se levels and GPx activity in serum than C pups. Administering Se with alcohol balances the activities of scavenging enzymes and reduces peroxidation protein products.

These results suggest that selenium could be effective in neutralizing the damage of ethanol consumption during gestation and lactation in pups since it repairs selenium levels in liver as well as the activity of scavenging enzymes and peroxidation protein products. In serum, Se also recovers GPx activity and increases the levels of Se that are available to other organs.

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Request Reprint E-Mail: olimpia@us.es
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The TEDS Report: Treatment Outcomes among Clients Discharged from Residential Substance Abuse Treatment:

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  SAMHSA's annual Treatment Episode Data Set (TEDS) provides data on completion rates by race, gender, primary substance of abuse, and type of residential treatment for those with discharge information provided by the States for their specialty substance abuse treatment facilities.


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  In 2005, clients discharged from short-term residential treatment (30 days or less) were more likely to complete treatment than those discharged from long-term residential treatment (57% vs. 38%).


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  Among short-term residential treatment discharges, a higher proportion of American Indian/Alaska Natives (63%) and Asian/Pacific Islanders (60%) completed treatment than Whites (57%), Blacks (55%), or Hispanics (52%).


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  Clients who reported alcohol as their primary drug of abuse were more likely to complete treatment among residential short-term discharges (66%) and long-term discharges (46%) than those with other primary drugs of abuse.


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  Discharged clients who reported stimulants as their primary drug of abuse were the least likely to complete short-term residential treatment (46%) and were almost as likely (19%) as those reporting opiates (21%) as their primary drug to drop out of short-term residential treatment.


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  Treatment completion among clients discharged from long-term residential treatment was lowest among those reporting cocaine abuse (33%) or opiate abuse (35%) as their primary drug of abuse.

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Health Disadvantage in US Adults Aged 50 to 74 Years: A Comparison of the Health of Rich and Poor Americans With That of Europeans

American Journal of Public Health March 2009, Vol 99, No. 3, 540-548

We compared the health of older US, English, and other European adults, stratified by wealth.

American adults reported worse health than did English or European adults. Eighteen percent of Americans reported heart disease, compared with 12% of English and 11% of Europeans. At all wealth levels, Americans were less healthy than were Europeans, but differences were more marked among the poor. Health disparities by wealth were significantly smaller in Europe than in the United States and England. Odds ratios of heart disease in a comparison of the top and bottom wealth tertiles were 1.94 (95% confidence interval [CI] = 1.69, 2.24) in the United States, 2.13 (95% CI = 1.73, 2.62) in England, and 1.38 (95% CI = 1.23, 1.56) in Europe. Smoking, obesity, physical activity levels, and alcohol consumption explained a fraction of health variations.

American adults are less healthy than Europeans at all wealth levels. The poorest Americans experience the greatest disadvantage relative to Europeans.

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Request Reprint E-Mail: m.avendanopabon@erasmusmc.nl

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Curbing Problem Drinking with Personalized-Feedback Interventions: A Meta-Analysis

American Journal of Preventive MedicineVolume 36, Issue 3, March 2009, Pages 247-255

The effectiveness of personalized-feedback interventions to reduce problem drinking has been evaluated in several RCTs and systematic reviews.

A meta-analysis was performed to examine the overall effectiveness of brief, single-session personalized-feedback interventions without therapeutic guidance.

The selection and analyses of studies were conducted in 2008. Fourteen RCTs of single-session personalized-feedback interventions without therapeutic guidance were identified, and their combined effectiveness on the reduction of problematic alcohol consumption was evaluated in a meta-analysis. Alcohol consumption was the primary outcome measure.

The use of single-session personalized-feedback interventions without therapeutic guidance appears to be a viable and probably cost-effective option for reducing problem drinking in student and general populations. The Internet offers ample opportunities to deliver personalized-feedback interventions on a broad scale, and problem drinkers are known to be amenable to Internet-based interventions. More research is needed on the long-term effectiveness of personalized-feedback interventions for problem drinking, on its potential as a first step in a stepped-care approach, and on its effectiveness with other groups (such as youth obliged to use judicial service programs because of violations of minimum-age drinking laws) and in other settings (such as primary care).

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Request Reprint E-Mail: hriper@trimbos.nl

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State Alcohol-Use Estimates Among Youth and Adults, 1993–2005

American Journal of Preventive MedicineVolume 36, Issue 3, March 2009, Pages 218-224

Underage drinking, particularly binge drinking, is an important public health problem that results in substantial premature mortality and morbidity. Little is known about the potential influence of the alcohol-use behaviors of adults on youth alcohol use at a population level.

The purpose of this study was to examine the correlation of alcohol-use behaviors among youth with those of adults at a population level.

Overall and subgroup-specific state youth estimates of current drinking and binge drinking were generally moderately to strongly correlated with adult alcohol use (range of r -values for pooled estimates across all years: 0.35–0.68 for current drinking

Most state youth alcohol-use estimates were correlated with state adult estimates. These findings have implications for underage-drinking control strategies and suggest that efforts to address this problem need to be targeted on a broader societal level.

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Request Reprint E-Mail: den2@cdc.gov

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Binge Drinking Among U.S. Active-Duty Military Personnel

American Journal of Preventive MedicineVolume 36, Issue 3, March 2009, Pages 208-217

Binge drinking (drinking on a single occasion ≥5 drinks for men or ≥4 drinks for women) is a common risk behavior among U.S. adults that is associated with many adverse health and social consequences. However, little is known about binge drinking among active-duty military personnel (ADMP). The objectives of this study were to quantify episodes of binge drinking, to characterize ADMP who binge-drink, and to examine the relationship between binge drinking and related harms.

In 2005, a total of 43.2% of ADMP reported past-month binge drinking, resulting in 29.7 episodes per person per year. In all, 67.1% of binge episodes were reported by personnel aged 17–25 years (46.7% of ADMP), and 25.1% of these episodes were reported by underage youth (aged 17–20 years). Heavy drinkers (19.8% of ADMP) were responsible for 71.5% of the binge-drinking episodes and had the highest number of annual per-capita episodes of binge drinking (112.6 episodes). Compared to nonbinge drinkers, binge drinkers were more likely to report alcohol-related harms, including job performance problems (AOR=6.5; 95% CI=4.65, 9.15); alcohol-impaired driving (AOR=4.9; 95% CI=3.68, 6.49); and criminal justice problems (AOR=6.2; 95% CI=4.00, 9.72).

Binge drinking is common among ADMP and is strongly associated with adverse health and social consequences. Effective interventions (e.g., the enforcement and retainment of the minimum legal drinking age) to prevent binge drinking should be implemented across the military and in conjunction with military communities to discourage binge drinking.

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Request Reprint E-Mail: mstahre@cdc.gov

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New Resource Available on Detoxification


The Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) Center for Substance Abuse Treatment (CSAT) is pleased to announce the availability of the Detoxification and Substance Abuse Treatment Training Manual.

This new curriculum, based on Treatment Improvement Protocol (TIP) 45, is for use by clinical supervisors for training staff members about detoxification services for individuals with substance use disorders.

The manual includes information on the physiology of withdrawal, pharmacological management of withdrawal, patient placement, and incorporating detoxification services into comprehensive systems of care. It includes step-by-step instructions for providing inservice training.

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Low alcohol alternatives: A promising strategy for reducing alcohol related harm

International J Drug Policy Volume 20, Issue 2, Pages 183-187 (March 2009)

Less than 1% of the beer market in British Columbia comprises beers with an alcohol content below 4%, despite the success of low alcohol beers in other countries, e.g. Australia.

A small experimental study is described in which male students were given either unmarked low alcohol beer (3.8%) or regular strength beer (5.3%) to investigate their enjoyment and subjective intoxication..

We conclude beer drinkers cannot readily distinguish low and regular strength beers and can enjoy socializing equally with either. We recommend taxation strategies to create incentives for the manufacture, marketing and consumption of low alcohol alternatives.

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Request Reprint E-Mail: dsegal@uvic.ca

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ADH SNP ASSOCIATIONS WITH ALCOHOL METABOLISM IN VIVO

Human Molecular Genetics Advance Access published online on February 4, 2009

We have previously found that variation in alcohol metabolism in Europeans is linked to the chromosome 4q region containing the ADH gene family.

We have now typed 103 SNPs across this region to test for allelic associations with variation in blood and breath alcohol concentrations after an alcohol challenge.

In vivo alcohol metabolism was modelled with three parameters that identified the absorption and rise of alcohol concentration following ingestion, and the rate of elimination. Alleles of ADH7 SNPs were associated with the early stages of alcohol metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions.

Rate of elimination was associated with SNPs in the intragenic region between ADH7 and ADH1C, and across ADH1C and ADH1B.

SNPs affecting alcohol metabolism did not correspond to those reported to affect alcohol dependence or alcohol-related disease.

The combined SNP associations with early and late stage metabolism only account for about 20% of the total genetic variance linked to the ADH region, and most of the variance for in vivo alcohol metabolism linked to this region has yet to be explained.

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Request Reprint E-Mail: John.Whitfield@qimr.edu.au

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4-Containing GABAA Receptors in the Nucleus Accumbens Mediate Moderate Intake of Alcohol

The Journal of Neuroscience, January 14, 2009, 29(2):543-549;

Alcohol has subjective and behavioral effects at the pharmacological levels typically reached during the consumption of one or two alcoholic drinks.

Here we provide evidence that an 4-subunit-containing GABAA receptor contributes to the consumption of low-to-moderate levels of alcohol.

Using viral-mediated RNA interference (RNAi), we found that reduced expression of the 4 subunit in the nucleus accumbens (NAc) shell of rats decreased their free consumption of and preference for alcohol. The time course for the reduced alcohol intake paralleled the time course of 4 mRNA reductions achieved after viral-mediated RNAi for 4.

Furthermore, the reduction in drinking was region- and alcohol-specific: there was no effect of reductions in 4 expression in the NAc core on alcohol intake, and reductions in 4 expression in the NAc shell did not alter sucrose or water intake.

These results indicate that the GABAA receptor 4 subunit in the NAc shell mediates alcohol intake.

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Request Reprint E-Mail: pjanak@gallo.ucsf.edu

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Review: Should ethanol be scheduled as a drug of high risk to public health?

Journal of Psychopharmacology, Vol. 23, No. 1, 94-100 (2009)

Six criteria described in the New Zealand Misuse of Drugs Act and used by the Expert Advisory Committee on Drugs (EACD) for determining the risk of a drug to public health were examined in relation to ethanol, using -hydroxybutyric acid (GHB) as a comparator drug.

GHB is an ideal candidate for use as a comparator because it is a sedative substance very similar to ethanol and has been previously investigated by the EACD using these six criteria. GHB was subsequently classified as a Class B1 drug under the Misuse of Drugs Act, that is, as a prohibited drug of high risk to public health.

The dangerousness level of ethanol was found to be at least similar to that of GHB in this analysis. This highlights a major discrepancy in public policy.

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Request Reprint E-Mail: doug.sellman@otago.ac.nz
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Effects of acute alcohol consumption on processing of perceptual cues of emotional expression

Journal of Psychopharmacology, Vol. 23, No. 1, 23-30 (2009)

Alcohol consumption has been associated with increases in aggressive behaviour. However, experimental evidence of a direct association is equivocal, and mechanisms that may underlie this relationship are poorly understood. One mechanism by which alcohol consumption may increase aggressive behaviour is via alterations in processing of emotional facial cues.

We investigated the effects of acute alcohol consumption on sensitivity to facial expressions of emotion. Participants attended three experimental sessions where they consumed an alcoholic drink (0.0, 0.2 or 0.4 g/kg), and completed a psychophysical task to distinguish expressive from neutral faces.

The level of emotion in the expressive face varied across trials the threshold at which the expressive face was reliably identified and measured. We observed a significant three-way interaction involving emotion, participant sex and alcohol dose. Male participants showed significantly higher perceptual thresholds for sad facial expressions compared with female participants following consumption of the highest dose of alcohol.

Our data indicate sex differences in the processing of facial cues of emotional expression following alcohol consumption. There was no evidence that alcohol altered the processing of angry facial expressions.

Future studies should examine effects of alcohol expectancy and investigate the effects of alcohol on the miscategorisation of emotional expressions.

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Request Reprint E-Mail: Angela.Attwood@bris.ac.uk

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Alcohol Consumption Behaviours and Social Mobility in Men and Women of the Midspan Family Study
Alcohol and Alcoholism Advance Access published online on January 23, 2009

The aim of this study was to investigate relationships between alcohol consumption and social mobility in a cohort study in Scotland.

More downwardly mobile men exceeded the weekly limit, the daily limit, were defined as binge drinkers and drank the most units per week of the four social mobility groups. Stable non-manual women were more likely to consume alcohol on 5+ days a week but very few were binge drinkers. Stable non-manual and upwardly mobile men and women were more likely to drink wine, and downwardly mobile men to drink beer.

Downward mobility was associated with less favourable alcohol behaviours, especially in men. Wine consumption was more closely related to the social mobility groups than beer and spirits consumption. Drinking patterns could both influence and be influenced by social mobility.

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Psychiatrist Directed Army, VA Programs For Substance Abuse

By Patricia Sullivan Washington Post Staff Writer February 6, 2009; Page B06

Stewart L. Baker, 88, a psychiatrist who developed comprehensive drug abuse and alcoholism treatment programs for the Army in 1971 and later directed similar programs for the Veterans Administration, died Jan. 13 at the Riderwood Village retirement community in Silver Spring after a stroke.

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