To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, June 22, 2013

Patients with early arthritis consume less alcohol than controls, regardless of the type of arthritis

There are conflicting reports concerning the association between alcohol consumption and RA. We performed a case–control study to investigate the association of alcohol consumption with RA as well as with other forms of arthritis. To assess whether alcohol consumption affects long-term disease outcome, we also investigated its association with radiographic progression and sustained drug-free remission in RA.

Patients with arthritis and various diagnoses including RA, OA, ReA, SpA and PsA were compared with 5868 controls from the general population. The association of disease with alcohol consumption was analysed by logistic regression analysis.
Alcohol consumption was inversely associated with not only RA [odds ratio (OR) 0.28, 95% CI 0.23, 0.35] but also OA (OR 0.31, 95% CI 0.16, 0.62) and other forms of arthritis (OR 0.34, 95% CI 0.24, 0.48). A higher degree of systemic inflammation, reflected by the ESR and CRP level, was associated with a smaller proportion of patients consuming alcohol. There was no dose–response relationship between the amount of alcohol consumed and the presence of arthritis. The extent of joint destruction and the rate of sustained drug-free remission were not affected by alcohol consumption.

Arthritis patients report less alcohol consumption than controls, regardless of the type of arthritis. This suggests that alcohol may either protect against different kinds of arthritis or that the inverse association between alcohol and arthritis may be secondary to disease development, with arthritis patients being less inclined to consume alcohol due to their decreased general well-being.

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Friday, June 21, 2013

Obstacles to alcohol and drug care Are Medicare Locals the answer?

Harms related to alcohol and drug use have an enormous cost on the community, yet most patients with substance use disorders do not receive care from primary healthcare providers. The establishment of a system of large primary healthcare organisations (Medicare Locals) across Australia provides an opportunity to address this service gap.

This article considers barriers to delivering alcohol and drug interventions from primary healthcare settings, strategies for their resolution, and the ensuing benefits for patients.

Help seeking for alcohol and drug problems is low. Stigmatisation can be countered by policy development,
training and support to increase staff awareness and skills, and building relationships with specialist services. Co-location, outreach clinics, and collaborative models simplify access, tailor intensity of interventions, and improve patient satisfaction and health outcomes. Screening and brief intervention at intake, with appropriate training and support for nursing staff, can advance the delivery of timely and effective care.

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Associations of Alcohol Use with Radiographic Disease Progression in African Americans with Recent-onset Rheumatoid Arthritis

To investigate the associations of alcohol consumption and radiographic disease progression in African Americans with recently diagnosed rheumatoid arthritis (RA).

Patients with RA included in the study were participants in the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) registry. Patients were categorized based on self-reported alcohol consumption; those consuming < 15 beverages per month versus those with ≥ 15 per month. Association of radiographic disease progression over a 1-year to 3-year period of observation with alcohol consumption was evaluated using multivariate generalized estimating equations. 
Of 166 patients included in the study, 39% reported that they had never consumed alcohol. Of the 61% who had consumed alcohol, 73% reported that they consumed on average < 15 alcoholic beverages per month and 27% reported consuming ≥ 15 per month. In multivariate analysis, consumption of ≥ 15 alcoholic beverages per month was associated with an increased risk of radiographic disease progression (p = 0.017). There was no evidence of a relationship in those consuming < 15 beverages per month (p = 0.802). 
There appears to be a dose-dependent relationship between alcohol use and radiographic disease progression in RA. Individuals who consume 15 or more alcoholic beverages per month may have faster rates of radiographic joint damage than those with lower levels of consumption.

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The protective effect of alcohol on developing rheumatoid arthritis: a systematic review and meta-analysis


Our aim was to establish whether alcohol protects against RA development and to determine whether this effect is influenced by alcohol dose, duration and serological status through systematically reviewing the literature and undertaking a meta-analysis. 
We searched Medline/EMBASE (1946 to July 2012) using the terms rheumatoid or arthritis, rheumatoid/ and or ethanol/. Manuscript bibliographies were reviewed. Observational studies were included that were case–control/cohort, examined the relationship between alcohol and RA risk and reported or allowed the calculation of effect size data [odds ratios (ORs)/relative risks (RRs) with 95% CIs] in drinkers vs non-drinkers. A random-effects model was used to estimate pooled ORs/RRs. Dose–risk relationships were evaluated by trend tests.
Nine studies (from 893 articles) met our inclusion criteria, comprising six case–control (3564 cases; 8477 controls) and three cohort studies (444 RA cases; 84 421 individuals). A significant protective effect of alcohol on RA risk was observed—summary OR for RA in drinkers vs non-drinkers 0.78 (95% CI 0.63, 0.96). This effect was confined to ACPA-positive RA—summary OR 0.52 (95% CI 0.36, 0.76), with no significant risk reduction seen for ACPA-negative RA—summary OR 0.74 (95% CI 0.53, 1.05). Subgroup analysis by study design identified a significant relationship in case–control but not cohort studies. 
Alcohol intake is inversely associated with ACPA-positive RA, suggesting a protective effect. As this finding is confined to case–control studies further research is required with prospective cohort studies incorporating ACPA status to confirm this relationship.

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Parental Monitoring and Alcohol Use among Mexican Students

Parental monitoring has been described as a protective factor and useful strategy to prevent substance misuse among youths.

The aims of this study were to examine whether perceived parental monitoring influences frequency of alcohol use, age of drinking onset and risky drinking among entering public high school and university students in Mexico City.

The study is a cross-sectional survey of entering first year students in the high school and university school system of a large public university in Mexico City conducted during registration at the beginning of the school year. In 2008, of 34,840 students accepted to the affiliated high schools, 28,996 students (51.8% female) completed the alcohol survey and of 37,683 students accepted into university 30,084 students (51.5% female) completed the alcohol survey.

The findings suggest that compared to students with higher perceived parental monitoring those reporting lower perceived parental monitoring were more likely to report risky behavior. They were more likely to be ever drinkers, frequent drinkers, have earlier age of onset and high AUDIT scores.

Overall, higher parental monitoring was strongly associated with being female and lower parental monitoring with being male.

Our findings suggest that more research on parental monitoring as a protective strategy against alcohol misuse is needed. Research focusing on cultural factors including gender and age-related norms and familismo would increase knowledge of the association of parental monitoring and alcohol use among Mexican youths, Mexican American youths and potentially youths from other Hispanic backgrounds.

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Co-occurring Mental Health and Alcohol Misuse: Dual Disorder Symptoms in Combat Injured Veterans


Service members face difficulties during military deployment potentially resulting in morbidities such as posttraumatic stress disorder (PTSD), depression, and alcohol misuse. The co-occurrence of alcohol misuse and mental health disorders is termed dual disorder and has been associated with adverse outcomes.

The study included 812 high-risk (i.e., endorsing combat exposure with documented combat injury) male U.S. veterans of Operation Iraqi Freedom, injured between October 2004 and November 2007, identified from the Expeditionary Medical Encounter Database.

PTSD and depression symptoms were significant correlates of alcohol misuse. Veterans with dual disorder symptoms reported a significantly higher mean number of health complaints on the Post-Deployment Health Reassessment compared with those endorsing only mental health symptoms.

These results highlight how mental health disorders among injured service members increases the odds of problem drinking and those with dual disorder have elevated health complaints

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Experimental model of alcohol-related peripheral neuropathy

The aim of this work was to determine the effect of chronic alcohol exposure on peripheral nerves in a nutritionally balanced rat model of alcoholism.
Three different strains of adult male rats were pair-fed for 8 weeks with isocaloric liquid diets containing 0% or 37% ethanol. Nerve conduction studies (NCS) were performed. Peripheral nerve and muscle were examined histologically with morphometrics.
Ethanol exposure significantly slowed velocity in tibial and fibular nerves, but not in the plantar nerve in all 3 strains. Studies of the sciatic nerve revealed decreased fiber diameters and increased regenerative sprouts in peripheral nerves. There was muscle denervation of ethanol-exposed rats in all 3 strains.
Chronic ethanol exposure caused a polyneuropathy characterized by axonal degeneration despite adequate nutrition. These results suggest that ethanol exposure has direct neurotoxic effects on peripheral nerves. This model may be useful in understanding the underlying mechanism(s) of alcohol-related peripheral neuropathy.

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Alcohol and NMDA receptor: current research and future direction

The brain is one of the major targets of alcohol actions. Most of the excitatory synaptic transmission in the central nervous system is mediated by N-methyl-D-aspartate (NMDA) receptors.

However, one of the most devastating effects of alcohol leads to brain shrinkage, loss of nerve cells at specific regions through a mechanism involving excitotoxicity, oxidative stress.

Earlier studies have indicated that chronic exposure to ethanol both in vivo and in vitro, increases NR1 and NR2B gene expression and their polypeptide levels. The effect of alcohol and molecular changes on the regulatory process, which modulates NMDAR functions including factors altering transcription, translation, post-translational modifications, and protein expression, as well as those influencing their interactions with different regulatory proteins (downstream effectors) are incessantly increasing at the cellular level.

Further, I discuss the various genetically altered mice approaches that have been used to study NMDA receptor subunits and their functional implication.

In a recent countable review, epigenetic dimension (i.e., histone modification-induced chromatin remodeling and DNA methylation, in the process of alcohol related neuroadaptation) is one of the key molecular mechanisms in alcohol mediated NMDAR alteration.

Here, I provide a recount on what has already been achieved, current trends and how the future research/studies of the NMDA receptor might lead to even greater engagement with many possible new insights into the neurobiology and treatment of alcoholism.

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The relationship between group size, intoxication and continuing to drink after bar attendance



The present study was undertaken to explore multilevel determinants of planning to continue to drink alcohol after leaving public drinking events. We assessed whether individual-level factors, group-related factors, or event-level bar characteristics were associated with post-bar drinki

We recruited a total of 642 participants from 30 participating bars in urban Southern California. Groups who arrived to patron a bar were interviewed upon their entrance and exit. Given data nesting, we employed a multilevel modeling approach to data analysis.

More than one-third (40%) of our sample reported the intention to continue drinking as they exited the bar. Results of our multilevel model indicated eight individual-level variables significantly associated with intending to continue to drink. Time of night moderated the relationship between BrAC change and intentions to continue to drink. Although none of the group factors were significant in our model, a significant cross-level interaction between BrAC change and number of group members indicated the effect of intoxication on planning to continue to drink increases as group members increase. At the bar level, the presence of temporary bars and server offers of non-alcoholic drinks significantly decreased intentions to continue to drink.

Given the large percentage of participants who reported the intention to continue drinking after exiting a bar, this study draws attention to the fact that field studies of drinking behavior may assess drinking mid-event rather than at the end of a drinking event.

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Alcohol misuse and relationship breakdown: Findings from a longitudinal birth cohort


This study examined the associations between measures of alcohol abuse/dependence (AAD) and relationship dissolution from ages 19 to 30 in a New Zealand birth cohort.

The outcome measure was self-reported breakdown of a marital/cohabiting relationship during each year from age 20–21 to age 29–30. The study also used contemporaneous and one-year lagged measures of AAD symptoms; and time-dynamic covariate factors including life stress, other substance use, mental health status, peer and partner substance use and offending, unemployment, exposure to intimate partner violence, and prior relationship breakdown. Data were analysed using conditional fixed effects regression modelling augmented by time-dynamic covariate factors to control for confounding.

Those with three or more AAD symptoms had unadjusted odds of relationship breakdown that were 2.17–2.23 times higher than those with no symptoms, but these associations did not differ by gender. Adjustment of the associations for both unobserved fixed effects and time-dynamic covariate factors reduced the magnitude of the associations, with those with three or more AAD symptoms having rates of relationship breakdown that were 1.57–1.66 times higher than those with no symptoms.

The results suggest a causal association between alcohol misuse and relationship breakdown, with estimates suggesting that alcohol use disorder accounted for 4.5–4.6% of marital/cohabiting relationship dissolution in the cohort.

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Thursday, June 20, 2013

A review of patients who died with alcohol-related liver disease: report calls for improved prevention and treatment

A review of patients who died with alcohol-related liver disease has been released by the National Confidential Enquiry into Patient Outcomes and Death (NCEPOD). The report calls for improvements in alcohol brief intervention (IBA), access to treatment, alcohol care teams and improved pathways across hospitals.

Download the full report Alcohol Related Liver Disease: Measuring the Units (2013) here or the Executive Summary.    > > > >   Read More

Kenya: Nyanza Drug and Alcohol Abuse Worries NACADA

Young people in Nyanza have been told to desist from drug abuse and engage in productive activities that will change their lives.

National Authority for the Campaign against Alcohol and Drug chief executive officer, William Okedi said there is high rate of drug abuse in the region with Nyanza recording a big increase of bhang use from 1.4 to 1.7 percent in 2012, according to the 2012 NACADA report.

The report says there was a national decline in the abuse of bhang in 2012. The report indicates that 13.6% of Kenyans aged 15-65 years are current consumers of alcohol, 5.8% are abusers and 5.5 per cent are dependent on alcohol.   > > > >  Read More

Global Actions: Commitments to Reduce Harmful Drinking. June 20, 2013


Global Actions in Focus
Pernod Ricard: responsib’all day 2013
The Global Actions newsletter will periodically feature best practices shared by our readers, including companies that are signatories of the Beer, Wine and Spirits Producers’ Commitments to Reduce Harmful Drinking. In this issue, we focus on Pernod Ricard and its work in one of the five key areas addressed by the Commitments: providing consumer information. We look forward to highlighting more examples from Commitments stakeholders over the course of 2013 and beyond.
In 2011, Pernod Ricard launched Responsib’All Day, a one-day event that promotes the sharing of good practices by utilizing company employees as ambassadors. Responsib’All Day focuses on highlighting yearlong Pernod Ricard initiatives and raises awareness about responsible drinking. Before Responsib’All Day was launched, Pernod Ricard conducted internal training seminars on specific issues, such as drink driving and consumption by youth. Since the start of this influential campaign, employees spread key messages about responsible drinking to communities by engaging local populations in schools, bars, and other public places.
Responsib’All Day 2013 took place on June 5, 2013, where 18,800 employees rallied to promote responsible drinking and informed consumers about the possible consequences of excessive alcohol consumption. This year, Pernod Ricard Argentina celebrated its third Responsib’All Day by tailoring their message to beverage alcohol retailers. Pernod Ricard employees trained 100 client representatives on how to prevent the sale of alcohol to underage youth. In its first Responsib’All Day, Pernod Ricard Nigeria discussed the consequences of drink driving with public transport drivers and passengers in Lagos. Employees also handed out flyers on responsible consumption of alcohol beverages to locals at a nearby mall.
During the worldwide event, Vice-Chairman of the Board of Directors and Chief Executive Officer Pierre Pringuet announced that Pernod Ricard will add a logo to the back label of all bottles produced by Pernod Ricard that recommends pregnant women abstain from consuming beverage alcohol. In 2006, Pernod Ricard became the first wine and spirits group to apply the logo to bottles distributed throughout Europe, yet Pernod Ricard’s goal is to expand this program to unambiguously inform pregnant women worldwide to abstain from consuming alcohol throughout their pregnancy.
Key Recent Milestones
· Colombia: On May 29, 2013, Yumbo Mayor Fernando Murgueitio and Global Actions signed an agreement to begin the Project Patrullero initiative in the city. The signing took place ahead of seminars held May 30 and 31, 2013, where 163 participants, which included municipal officials, police officers, and owners of licensed alcohol venues, received training on alcohol basics, Colombian drink driving laws, road traffic crash statistics, and sobriety checkpoint best practices.
What's Happening Next
· Mexico: ICAP Senior Vice President Brett Bivans will be meeting with Signatory Companies in Mexico from June 24 to 26, 2013 to discuss drink driving initiatives. Companies will also evaluate the programs currently in place and indentify how these programs can be sustained by local communities

αCaMKII autophosphorylation controls the establishment of alcohol-induced conditioned place preference in mice

The autophosphorylation of alpha Ca2+/calmodulin dependent protein kinase II (αCaMKII) is important for memory formation and is becoming increasingly implicated in the development of drug addiction. Previous work suggests that αCaMKII acts via the monoaminergic systems to facilitate the establishment of alcohol drinking behaviour.

The present study aims to investigate whether αCaMKII autophosphorylation deficient αCaMKIIT286A mice show a difference in the rewarding properties of alcohol (2 g/kg, i.p.), as measured by conditioned place preference (CPP).

We found that alcohol-induced CPP could be established at an accelerated rate in αCaMKIIT286A compared to wild type (WT) mice. Hyperactivity/hyper-arousal induced by the test environment was normalised by alcohol in the αCaMKIIT286A, but not WT mice.

This effect could be conditioned to the test environment and may suggest enhanced negative reinforcing action of alcohol in αCaMKII autophosphorylation deficient mice.

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The cyclic nature of serious mental illness (SMI) and substance-use disorders (SUD) suggests that persons with these conditions may experience high rates of transitions among employment states (full-time, part-time, and no employment).

This study uses longitudinal data from two waves of the National Epidemiologic Survey of Alcoholism and Related Conditions to examine employment transitions for persons with SMI/SUD relative to a no-disorder control group. Conditional on employment status in Wave I, we estimate conditional odds ratios and marginal effects of each diagnosis on the probabilities of part-time or full-time employment in Wave II, holding constant other characteristics that influence employment decisions.

The results show transitions across employment states are common for all groups but more frequent for persons with SMI/SUD than the controls.

Persons with SMI are less likely, and persons with SUDs more likely, to transition out of no employment than the controls. Part-time employment is a relatively transitory state, particularly for persons with SMI/SUD, but full-time employment brings a measure of job stability to all groups.
After controlling for differences in observable characteristics, the marginal effects of SMI and alcohol disorders on employment transitions are largely significant, but the effects of drug disorders are not.

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Genetic Variants in the Fat Mass- and Obesity-Associated (FTO) Gene are Associated with Alcohol Dependence

Variants (such as rs9939609) in the fat mass- and obesity-associated (FTO) gene have been associated with obesity, type 2 diabetes, some cancers, and alcohol consumption.
This study tested the associations of 167 single-nucleotide polymorphisms (SNPs) within FTO gene with alcohol dependence (AD) using two Caucasian samples: the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis of AD as a binary trait was performed using the PLINK software.
For the SAGE sample, the top three SNPs showing associations with AD were rs8062891, rs1108086, and rs1420318 (p = 0.00088, 0.00086 and 0.00086, respectively). Two SNPs (rs12597786 and rs7204609) associated with AD in the SAGE sample (p = 0.017 and 0.034, respectively) were replicated in the COGA sample (p = 0.017 and 0.014, respectively).
Through meta-analysis of two samples using PLINK, the top three SNPs associated with AD were rs8062891, rs12597786, and rs7204609 (p = 0.00064, 0.00076 and 0.0011, respectively). Haplotype analysis in the SAGE sample further supported the associations with AD in single-marker analysis.
In addition, we found association of rs17817449 (which has a strong linkage disequilibrium with rs9939609) with AD in the SAGE sample (p = 0.00339).

The findings provide evidence of joint intervention and prevention of AD and obesity.

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Acute Use of Alcohol and Methods of Suicide in a US National Sample

We explored age, gender, and racial/ethnic differences with alcohol use and firearms, hanging or asphyxiation, and poisoning methods of suicide.
We analyzed data for 37 993 suicide decedents aged 18 years and older from the 2005–2010 National Violent Death Reporting System database. Multinomial logistic regressions examined associations of method with alcohol use defined by blood alcohol content. Two-way interactions tested the effects of age, gender, and race/ethnicity on the associations between alcohol use and method of suicide.

Alcohol was present among decedents who used the 3 leading methods of suicide: firearm (35.0%), hanging (36.8%), and poisoning (32.7%). Two-way interaction tests suggested that in young and middle adulthood, individuals were more likely to drink alcohol when they used a firearm or hanging (compared with poisoning), but in older adulthood, the reverse was true, with alcohol use more likely with poisoning. Interaction tests also suggested that Asians and Pacific Islanders were most likely to use alcohol in poisonings and that Blacks were least likely to use alcohol in hangings.
The results suggested that alcohol use before suicide was influenced by several factors, including age, race/ethnicity, and suicide method.

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Wednesday, June 19, 2013

14-Deoxyandrographolide targets adenylate cyclase and prevents ethanol-induced liver injury through constitutive NOS dependent reduced redox signaling in rats

Chronic alcoholism is one of the most common causes of liver diseases worldwide. Nitric oxide (NO) has been proposed to have potential for clinical application against chronic hepatocellular injuries. However, mechanisms underlying hepatoprotective functions of NO in ethanol-induced apoptosis are largely unknown.

Sprauge–Dawley rats were exposed to ethanol for 8 weeks. Half of the ethanol-fed animals received 14-deoxyandrographolide (14-DAG) treatment for the last 4 weeks of study. Preventive effect of 14-DAG against ethanol-induced hepatotoxicity involved constitutive nitric oxide synthase (cNOS) activation followed by up-regulation of γ-glutamylcysteine synthetase activity and reduced oxidative stress.

Enhanced interaction of cNOS with caveolin-1 caused down-regulation of enzyme activity and led to depletion of NO in the hepatocytes of ethanol-fed animals. 14-DAG acted as activator of adenylate cyclase and modulated cyclic AMP (cAMP) mediated expression of caveolin-1 and calmodulin. This eventually favored activation of cNOS through inhibition of cNOS-caveolin-1 interaction.

Our results suggest that, protective effect of 14-DAG against ethanol-induced hepatic injury is based on its ability to reduce oxidative stress through cNOS dependent improvement of redox status.

14-DAG mediated activation of adenylate cyclase-cAMP signaling leading to up-regulation of cNOS may provide a promising approach in the prevention of liver diseases during chronic alcoholism.

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Alcohol-use disorders during and within one year of pregnancy: a population-based cohort study 1985–2006

To examine alcohol-use disorders in pregnant women and the extent of under-reporting.
Population-based cohort study.
Western Australia.
Women with a birth recorded on the Western Australian Midwives Notification System (1985–2006).
Mothers with an International Classification of Diseases 9/10 alcohol-related diagnosis, indicating heavy alcohol consumption, recorded on population-based health datasets (non-Aboriginal n = 5839; Aboriginal n = 2583) were identified through the Western Australian data-linkage system. This ‘exposed’ cohort was frequency matched (on maternal age, year of birth of offspring, Aboriginal status) with comparison mothers without an alcohol-related diagnosis (non-Aboriginal n = 33 979; Aboriginal n = 8005).
Trends in maternal alcohol diagnoses in relation to pregnancy for non-Aboriginal and Aboriginal women. The proportion of children diagnosed with fetal alcohol syndrome (FAS) who had a mother with an alcohol diagnosis recorded during pregnancy.
The proportion of Aboriginal mothers in Western Australia with an alcohol diagnosis (23.1%) is ten times greater than for non-Aboriginal mothers (2.3%). There has been a six-fold increase in the percentage of non-Aboriginal births with a maternal alcohol diagnosis recorded during pregnancy and a 100-fold increase for Aboriginal births. Around 70% of the mothers of children diagnosed with FAS did not have an alcohol diagnosis recorded during pregnancy and 18% of the mothers had no record of an alcohol diagnosis.
Maternal alcohol exposure during pregnancy is significantly under-ascertained. Given the severe risks to the fetus from heavy prenatal alcohol exposure, assessment and recording of alcohol use should be routinely undertaken in maternity and other health settings.

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Californians drinking less beer, more wine, spirits

California adults now drink, on average, less than a gallon of ethanol from beer each year. They're making up for it by drinking more wine and distilled spirits.

California beer consumption per adult fell 12 percent from 1998 to 2010, according to the latest federal statistics.

Over that same period California wine consumption per adult grew by 22 percent, while distilled spirits consumption grew by 16 percent. 

Beer remains the most popular alcoholic beverage, with California adults drinking an average of 0.97 gallons of ethanol from beer a year, compared to three-quarters of a gallon of spirits and half a gallon of wine. Beer is about 4.4% ethanol, so California adults drink, on average, about 22 gallons a year.

California alcohol consumption decreased slightly during the recession but has trended upward slightly overall in the last decade. Consumption remains well below levels from the 1980s and 1990s. (About 40 percent of California adults rarely or never drink alcohol.)   > > > >    Read More

Maternal Factors Predicting Cognitive and Behavioral Characteristics of Children with Fetal Alcohol Spectrum Disorders

To provide an analysis of multiple predictors of cognitive and behavioral traits for children with fetal alcohol spectrum disorders (FASDs).

Multivariate correlation techniques were used with maternal and child data from epidemiologic studies in a community in South Africa. Data on 561 first-grade children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and not FASD and their mothers were analyzed by grouping 19 maternal variables into categories (physical, demographic, childbearing, and drinking) and used in structural equation models (SEMs) to assess correlates of child intelligence (verbal and nonverbal) and behavior.

 A first SEM using only 7 maternal alcohol use variables to predict cognitive/behavioral traits was statistically significant (B = 3.10, p < .05) but explained only 17.3% of the variance. The second model incorporated multiple maternal variables and was statistically significant explaining 55.3% of the variance. Significantly correlated with low intelligence and problem behavior were demographic (B = 3.83, p < .05) (low maternal education, low socioeconomic status [SES], and rural residence) and maternal physical characteristics (B = 2.70, p < .05) (short stature, small head circumference, and low weight). Childbearing history and alcohol use composites were not statistically significant in the final complex model and were overpowered by SES and maternal physical traits.

Although other analytic techniques have amply demonstrated the negative effects of maternal drinking on intelligence and behavior, this highly controlled analysis of multiple maternal influences reveals that maternal demographics and physical traits make a significant enabling or disabling contribution to child functioning in FASD.

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The Association of DRD2 −141C and ANKK1 TaqIA Polymorphisms with Alcohol Dependence in Korean Population Classified by the Lesch Typology

Dopamine receptors are associated with reward and dependence towards alcohol. The polymorphisms of dopamine D2 receptor (DRD2) genes have been reported to be involved in susceptibility to alcoholism. Therefore, we investigated the association of three single-nucleotide polymorphisms (SNPs) in DRD2 and ankyrin repeat and kinase domain containing one (ANKK1) genes with alcohol dependence in Korean subjects, who were classified by the criteria of the Lesch typology.

The DRD2 −141C (Insertion (Ins)/Deletion (Del)), exon8 (A/G) and the ANKK1 TaqIA (A1/A2) polymorphisms were genotyped in a case–control sample consisting of 245 alcohol-dependent (AD) patients and 110 healthy controls. AD patients were classified into four subtypes by the Lesch typology. The majority of them (77.1%) were Lesch type 1. Differences in genotype and allele frequencies were examined between the AD patients and the controls. Also those analyses were done between the Lesch type 1 group and the controls.

There were significant differences in the genotype and allele frequencies of −141C Ins/Del and TaqIA A1/A2 between the AD patients and the controls. However, there were no significant differences in genotype or allele frequencies of exon8 A/G between the AD patients and the controls. The −141C Ins/Ins and TaqIA A1+ variants were associated with Lesch type 1 AD patients. When analysing haplotypes of three SNPs, the odds ratio of −141C Ins-A-A1 was 2.286, while the odds ratio of −141C Del-G-A2 was 0.323.

The present study showed a significant difference in DRD2 −141C and ANKK1 TaqIA polymorphisms between the AD patients and the controls. Our findings suggest that −141C Ins and TaqIA A1 alleles can be a predisposing factor for alcohol dependence in the Korean population.

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Characterization of Functional Polymorphisms and Glucocorticoid-Responsive Elements in the Promoter of TDO2, a Candidate Gene for Ethanol-Induced Behavioural Disorders

In response to acute ethanol consumption, tryptophan 2,3-dioxygenase (TDO) induces the kynurenine pathway (KP) through a glucocorticoid-mediated mechanism, which could lead to a dramatic accumulation of neurotoxic metabolites in association with serotonin depletion. As a result, interindividual variability in ethanol-induced behavioural disorders, such as black-outs and violent impulsive behaviours (BOVIBs) following binge drinking, could be partly explained by genetic polymorphisms affecting the KP.

The aim of this study was to identify polymorphisms on the promoter of the TDO2 gene that could affect expression and/or activity of TDO through glucocorticoid induction.

Polymorphisms were screened using a PCR-sequencing strategy applied to 31 alcohol-dependent patients and 49 unrelated healthy volunteers, and functionally analysed with bioinformatic prediction tools and gene reporter assays in HepG2 and A549 cell lines.

We identified 12 polymorphisms in the human TDO2 promoter region, 2 of them corresponding to previously unknown single-nucleotide polymorphisms (SNPs) and 3 of them located in putative glucocorticoid-responsive elements (GREs). Gene reporter assays using HepG2 and A549 cell lines confirmed the presence of several functional GREs in the promoter region of TDO2 and revealed that some of the identified polymorphisms affect the promoter activity under glucocorticoid receptor over-expression and dexamethasone exposure conditions.

Correlational studies in larger samples could help to determine whether these polymorphisms are responsible for variations of expression and/or activity of TDO, in particular under conditions where release of glucocorticoids is increased, such as acute ethanol intake. If confirmed, such results would be of major interest in explaining part of the interindividual variability observed in behavioural responses to acute ethanol consumption.

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First Sips of Alcohol Start in Second Grade

The age at which many children in the U.S. take their first sip of alcohol is surprisingly young, finds a new study in the Journal of Adolescent Health.

Researchers from the University of Pittsburgh collected data from 452 children in one Pennsylvania county each year from ages 8 and a half through 18. The children were asked how old they were when they first sipped or tasted alcohol, had a drink, had three or more drinks in a row, or were drunk.

By age 8, 37 percent had sipped alcohol. That number jumped to 66 percent by age 12. By age 18.5, nearly all (96 percent) had sipped or tasted alcohol. Also, 16 percent of 16-year-olds reported binge drinking (three or more drinks).  > > > >   Read More