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Friday, August 24, 2012
The burden and cost of disorders of the brain in Europe with the inclusion of harmful alcohol use and nicotine addiction
Interactions Between the Apolipoprotein A1/C3/A5 Haplotypes and Alcohol Consumption on Serum Lipid Levels
The interactions between apolipoprotein (Apo) A1/C3/A5 haplotypes and alcohol consumption on serum lipid profiles have not been previously explored. The present study was undertaken to detect the polymorphisms of ApoA1 −75 bp G>A (rs1799837), ApoC3 3238C>G (rs5128), ApoA5 −1131T>C (rs662799), ApoA5 c.553G>T (rs2075291), and ApoA5 c.457G>A (rs3135507) and the interactions between their haplotypes and alcohol consumption on serum lipid levels.
Genotyping was performed in 1,030 unrelated subjects (516 nondrinkers and 514 drinkers) aged 15 to 89. The interactions between ApoA1/C3/A5 haplotypes and alcohol consumption on serum lipid levels were detected by factorial regression analysis after controlling for potential confounders.
The frequencies of ApoC3 3238 CG/GG genotypes and ApoA1 −75 bp A allele in nondrinkers were higher in females than in males (p < 0.05). The frequencies of ApoC3 3238 CG/GG genotypes and G allele in drinkers were higher in females than in males (p < 0.05). The frequencies of ApoA1 −75 bp GA/AA genotypes and A allele in males were higher, and those of ApoC3 3238 CG/GG genotypes were lower in drinkers than in nondrinkers (p < 0.05 to 0.01). The frequency of ApoC3 3238 GG genotype in male drinkers was also higher in ≥25 g/d than in <25 g/d subgroups (p < 0.05). There were 11 haplotypes with a frequency >1% in our study population. The haplotypes of G–G–T–C–G (in the order of c.553G>T, c.457G>A, −1131T>C, 3238C>G, and −75 bp G>A), G–G–T–C–A, and G–G–C–G–G were shown consistent interactions with alcohol consumption to increase serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), and ApoA1 levels (p < 0.05 to 0.001). The interactions between G–G–T–G–G (HDL-C and ApoA1), G–G–C–C–A (ApoA1), G–A–T–C–G (triglyceride), G–G–T–C–G (ApoA1/ApoB ratio), and G–G–C–G–G (ApoB) haplotypes and alcohol consumption on serum lipid levels were also detected (p < 0.05 to 0.001); the levels of these serum lipid parameters were significantly higher in drinkers than in nondrinkers.
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Adolescent Rearing Conditions Influence the Relationship Between Initial Anxiety-Like Behavior and Ethanol Drinking in Male Long Evans Rats
Rodent studies have demonstrated that adolescent social isolation results in many behavioral perturbations, including increases in anxiety-like behaviors. Socially isolated (SI) rats have also been shown to self-administer greater amounts ethanol (EtOH) in some, but not all, studies. Here, we tested whether juvenile social isolation increases EtOH drinking using an intermittent procedure that engenders relatively high intake in normally reared animals. We also compared the behavioral phenotype of rats reared under social isolation or group-housed conditions with adult rats housed under conditions commonly used in EtOH-drinking studies.
Male Long Evans rats were procured immediately postweaning and were group housed for 1 week. Subjects were then randomly divided into 2 groups: SI rats, housed individually for 6 weeks and group-housed (GH) rats (4/cage). A third group was procured as young adults and was housed individually upon arrival for 1 week (standard housing condition). Rats were then tested in a plus-maze and novelty assay, and then, all subjects were singly housed and EtOH drinking was assessed.
SI rats displayed increased anxiety-like behaviors on the plus-maze, a greater locomotor response to a novel environment, and increased EtOH intake, relative to GH rats. Age-matched standard housed (STD) rats exhibited an anxiety-like behavioral profile on the plus-maze that was similar to SI, and not GH rats, and also drank EtOH at levels comparable with SI subjects. In addition, anxiety-like behavior on the plus-maze correlated with intermittent EtOH intake in SI and GH rats.
These data further support the validity of the rodent juvenile social isolation model for studies directed at elucidating behavioral and neurobiological mechanisms linking anxiety and EtOH drinking. These findings further suggest that housing conditions commonly employed in rodent drinking studies may recapitulate the anxiety-like and EtOH-drinking phenotype engendered by a juvenile social isolation procedure.
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Epigenetic regulation through DNA methylation may influence vulnerability to numerous disorders, including alcohol dependence (AD).
Peripheral blood DNA methylation levels of 384 CpGs in the promoter regions of 82 candidate genes were examined in 285 African Americans (AAs; 141 AD cases and 144 controls) and 249 European Americans (EAs; 144 AD cases and 105 controls) using Illumina GoldenGate Methylation Array assays. Association of AD and DNA methylation changes was analyzed using multivariate analyses of covariance with frequency of intoxication, sex, age, and ancestry proportion as covariates. CpGs showing significant methylation alterations in AD cases were further examined in a replication sample (49 EA cases and 32 EA controls) using Sequenom's MassARRAY EpiTYPER technology.
In AAs, 2 CpGs in 2 genes (GABRB3 and POMC) were hypermethylated in AD cases compared with controls (p ≤ 0.001). In EAs, 6 CpGs in 6 genes (HTR3A, NCAM1, DRD4, MBD3, HTR2B, and GRIN1) were hypermethylated in AD cases compared with controls (p ≤ 0.001); CpG cg08989585 in the HTR3A promoter region showed a significantly higher methylation level in EA cases than in EA controls after Bonferroni correction (p = 0.00007). Additionally, methylation levels of 6 CpGs (including cg08989585) in the HTR3A promoter region were analyzed in the replication sample. Although the 6 HTR3A promoter CpGs did not show significant methylation differences between EA cases and EA controls (p = 0.067 to 0.877), the methylation level of CpG cg08989585 was nonsignificantly higher in EA cases (26.9%) than in EA controls (18.6%; p = 0.139).
The findings from this study suggest that DNA methylation profile appears to be associated with AD in a population-specific way and the predisposition to AD may result from a complex interplay of genetic variation and epigenetic modifications.
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This study explores the lives of young people, aged 15-24, in two study areas located in regions of England where the harm caused by alcohol is markedly different. The aim of the research was to explore whether living in these places influenced young people’s drinking.
- Significant differences in alcohol-related harms have been observed between English regions. The north has a higher degree of reported indicators of harms than the south-east and the south-west.
- Despite these variations, young people’s drinking behaviour in the two areas studied followed similar patterns with regard to their choice of drink, where they drank, and the days of the week and times at which they drank.
- The differences between young people’s behaviour in the case study areas was subtle and related to how those places had developed over long periods of time.
- The pri.mary motivation for drinking at all ages was sociability, having a good time and avoiding trouble. On a ‘good night out’, laughter and fun were important. In the case of the north-eastern city, this was a significant part of local culture. Young people rarely drank on their own.
- Young people actively sought out ‘clusters’ of youth-orientated bars. A concentration of ‘clusters’ in the north east formed part of the impetus for young people to drink more than they originally intended.
- In the south east, young people below the legal age of drinking engaged in a wider range of leisure activities, sports and hobbies.
- In the north east, adult drinking was more visible both in the city centre and in streets and parks. There were more spaces where young people drank alongside adults.
- Despite a wish to limit the number of licensed premises in the north east, planning authorities had been unable to resist commercial pressures to allow clubs and bars to fill units that would otherwise be vacant
This study examines the lives and choices of young people (aged 16-25) who drink little or no alcohol. It explores the influences that shape their decisions and how their choices and patterns of consumption affect their lives.
- Drinking and getting drunk is not an automatic rite of passage for young people in the UK. The findings of this study reflect that it is commonplace for young people to choose to drink little or no alcohol.
- Choosing to drink little or no alcohol is a positive choice made for many reasons. For some young people the decision not to drink is central to their identity, for others it is ‘no big deal’, just one of many life choices.
- Major influences stem from observing people around them. Good parental role models play a part, as does witnessing the negative effects of alcohol on others.
- Young people who choose to drink little or no alcohol do not fall into easy stereotypes; their lives are busy and varied. As alcohol does not feature in their lives they tend to prefer activities where drinking alcohol rarely plays a role.
- Young people develop responses and strategies to help them manage not drinking alcohol. While some avoid drinking environments, many are content to socialise with those who drink.
- The immediate effects of drinking alcohol (i.e. hangovers, loss of control) concern young people more than longer-term health effects.
- Young people feel that alcohol education and alcohol messages are based on the assumption that young people will drink. They emphasise the importance of presenting not drinking as a legitimate option to young people, parents and society more broadly.
Thursday, August 23, 2012
Previous Use of Alcohol, Cigarettes, and Marijuana and Subsequent Abuse of Prescription Opioids in Young Adult
There has been an increase in the abuse of prescription opioids, especially in younger individuals. The current study explores the association between alcohol, cigarette, and/or marijuana use during adolescence and subsequent abuse of prescription opioids during young adulthood.
We used demographic/clinical data from community-dwelling individuals in the 2006–2008 National Survey on Drug Use and Health. We used logistic regression analyses, adjusted for these characteristics, to test whether having previous alcohol, cigarette, or marijuana use was associated with an increased likelihood of subsequently abusing prescription opioids.
Twelve percent of the survey population of 18–25 year olds (n = 6,496) reported current abuse of prescription opioids. For this population, prevalence of previous substance use was 57% for alcohol, 56% for cigarettes, and 34% for marijuana. We found previous alcohol use was associated with the subsequent abuse of prescription opioids in young men but not young women. Among both men and women, previous marijuana use was 2.5 times more likely than no previous marijuana to be associated with subsequent abuse of prescription opioids. We found that among young boys, all previous substance use (alcohol, cigarettes, and marijuana), but only previous marijuana use in young girls, was associated with an increased likelihood of subsequent abuse of prescription opioids during young adulthood.
Previous alcohol, cigarette, and marijuana use were each associated with current abuse of prescription opioids in 18–25-year-old men, but only marijuana use was associated with subsequent abuse of prescription opioids in young women. Prevention efforts targeting early substance abuse may help to curb the abuse of prescription opioids.
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The goal of this study is to better understand the longitudinal cross-lagged associations between popularity, assessed through self-rating and peer nominations, and alcohol use among middle school students.
The analytical sample comprises 1,835 sixth- to eighth-grade students who were initially recruited from three California middle schools and surveyed in the fall and spring semesters of 2 academic years. Students reported on their background characteristics, past-month alcohol use, and perceived popularity. Additionally, students provided school-based friendship nominations, which were used to calculate peer-nominated popularity. A cross-lagged regression approach within a structural equation modeling framework was used to examine the longitudinal relationship between popularity (self-rated and peer-nominated) and alcohol use.
There was a statistically significant (p = .024) association between peer-nominated popularity and the probability of alcohol consumption at the subsequent survey, but not vice versa. Our results suggest that in a scenario where 8% of students are past-month drinkers, each increase of five friendship nominations is associated with a 30% greater risk of being a current drinker at the next wave. We found no evidence of longitudinal associations between past-month alcohol consumption and self-rated popularity.
Popularity is a risk factor for drinking during the middle school years, with peer-nominated popularity being more predictive of use than self-perceptions of popularity. To inform alcohol prevention efforts for middle school students, additional research is needed to better understand why adolescents with a larger number of school-based friendship ties are more inclined to drink.
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Effects of a Natural Community Intervention Intensifying Alcohol Law Enforcement Combined With a Restrictive Alcohol Policy on Adolescent Alcohol Use
Determining whether intensified inspections on alcohol retailers, combined with a policy withdrawing liquor licenses if retailers are fined twice per annum, is effective in reducing adolescents' odds to initiate weekly drinking and drunkenness. Causal pathways by which the intervention was assumed to work were tested.
A longitudinal (2008, 2009, and 2010) quasi-experimental comparison group design including two Dutch communities, one intervention and one comparison, was used. Outcomes were assessed by following a cohort of 1,327 adolescents (aged 13–15 years at baseline).
The intervention resulted in increased retail inspections but only seven sanctions and no repeated sanctions in 1 year. The intervention did not reduce adolescents' odds to initiate weekly drinking. Weekly drinking adolescents in the intervention community were at reduced risk to initiate drunkenness. This effect was not mediated by smaller increases in the frequency of adolescents' alcohol purchases or their perceived ease of purchasing alcohol.
Intensified enforcement was effective in preventing adolescent drunkenness. No mediating causal pathways were detected. Effectiveness of enforcement could be increased by adopting enforcement methods with a high likelihood of apprehension, increasing social support for restrictive measures, and mobilizing the community to be more outspoken against adolescent (heavy) drinking.
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By demonstrating that early prenatal ethanol exposure can cause more than one temporally-specific pattern of defects, these findings illustrate the need for an expansion of current diagnostic criteria to better capture the full range of facial and brain dysmorphology in fetal alcohol spectrum disorders.
Effects of Heavy Prenatal Alcohol Exposure and Iron Deficiency Anemia on Child Growth and Body Composition through Age 9 Years
Prenatal alcohol exposure has been associated with pre- and postnatal growth restriction, but little is known about the natural history of this restriction throughout childhood or the effects of prenatal alcohol on body composition. The objective of this study was to examine the effects of heavy prenatal alcohol exposure on longitudinal growth and body composition.
Eighty-five heavy drinking pregnant women (≥2 drinks/d or ≥4 drinks/occasion) and 63 abstaining and light-drinking controls (<1 drink/d, no binging) were recruited at initiation of prenatal care in an urban obstetrical clinic in Cape Town, South Africa and prospectively interviewed during pregnancy about alcohol, smoking, drug use, and demographics. Among their children, length/height, weight, and head circumference were measured at 6.5 and 12 months and at 5 and 9 years. Percent body fat (BF) was estimated at age 9 years using bioelectric impedance analysis.
In multiple regression models with repeated measures (adjusted for confounders), heavy alcohol exposure was associated with reductions in weight (0.6 SD), length/height (0.5 SD), and head circumference (0.9 cm) from 6.5 months to 9 years that were largely determined at birth. These effects were exacerbated by iron deficiency in infancy but were not modified by iron deficiency or measures of food security at 5 years. An alcohol-related postnatal delay in weight gain was seen at 12 months. Effects on head circumference were greater at age 9 than at other age points. Although heavy alcohol exposure was not associated with changes in body composition, children with fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) had lower percent BF than heavy exposed nonsyndromal and control children.
Heavy prenatal alcohol exposure is related to prenatal growth restriction that persists through age 9 years and an additional delay in weight gain during infancy. FAS and PFAS diagnoses are associated with leaner body composition in later childhood.
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Ethanol-Induced Mast Cell-Mediated Inflammation Leads to Increased Susceptibility of Intestinal Tumorigenesis in the APCΔ468 Min Mouse Model of Colon
Chronic and frequent alcohol (ethanol [EtOH]) intake has been associated with an increased incidence of several types of cancers including breast, mouth, throat, esophageal, stomach, and colorectal (CRC). The underlying mechanism of this deleterious carcinogenic effect of alcohol has not been clearly established but inflammation may be 1 unifying feature of these cancers. We have recently shown that intestinal mast cells play a central role in intestinal carcinogenesis. In this study, we tested our hypothesis that mast cell-mediated inflammation is 1 underlying mechanism by which chronic alcohol promotes intestinal tumorigenesis.
APCΔ468 mice were fed either an alcohol-containing Nanji liquid diet or isocaloric dextrose-containing Nanji diet for 10 weeks and then sacrificed to collect small and large intestine samples. Assessments of tumor number and size as well as mast cell number and mast cell activity and histology score for invasion were compared between Control (dextrose-fed) and alcohol-fed APC∆468 mice. The effect of alcohol on mast cell-mediated tumor migration was also assessed using an in vitro migration assay.
Alcohol feeding increased both polyp number and size within both the small and the large intestines of APC∆468 mice. Only alcohol-fed mice showed evidence of tumor invasion. Chronic alcohol feeding also resulted in an increased mast cell number and activity in tumor stroma and invading borders. In vitro migration assay showed that alcohol significantly increases mast cell-mediated tumor migration in vitro.
Our data show that chronic alcohol intake promotes: (i) intestinal tumorigenesis and tumor invasion in genetically susceptible mice; (ii) increases in polyp-associated mast cells; and (iii) mast cell-mediated tumor migration in vitro. Both our in vivo and in vitro studies suggest that mast cell-mediated inflammation could be 1 mechanism by which alcohol promotes carcinogenesis.
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A Role of Genomic Copy Number Variation in the Complex Behavioral Phenotype of Alcohol Dependence: A Commentary
Male and female adult Sprague-Dawley rats were provided free access to a liquid replacement diet that was supplemented with either 4% ethanol or Maltodextrin for a period of two weeks. Proliferating cells were labeled with 5-bromo-2-deoxyuridine (BrdU) and the number of BrdU-positive cells in the hippocampus was assessed after the final day of drinking. A subset of rats was also exposed to a motor skill or associative learning task to examine the functional effects of alcoholconsumption.
The drinking regime resulted in an average blood alcohol concentration of approximately 0.08%;which is comparable to the human legal driving limit in many countries. This level of intoxication did not impair motor skill learning or function in either sex;nor did the alcoholconsumption disrupt associative learning two days after drinking.
Therefore; moderate alcohol consumption did not disrupt basic sensory;motor or learning processes. However;the number of cells produced in the dentate gyrus of the hippocampus was reduced by nearly 40%.
Wednesday, August 22, 2012
Alcohol use was not associated with prior HIV testing among men. HIV testing strategies may thus need to specifically target women who drink alcohol.
We examined whether distance from home to the nearest bar, i.e. alcohol outlet permitting consumption on the premises, is associated with risky alcohol behaviours.
Cross-sectional and longitudinal study.
The cross-sectional data consisted of 78 858 and the longitudinal data of 54 778 Finnish Public Sector Study participants in between 2000 and 2009 [mean follow-up 6.8 years (SD=2.0)].
Distances from home to the nearest bar were calculated using Global Positioning System-coordinates. The outcome variables were heavy alcohol use (drinking above the weekly guidelines) and extreme drinking occasions (passing out due to alcohol use). We used binomial logistic regression in cross-sectional analyses and in longitudinal mixed effects (between-individual) analyses. Conditional logistic regression was used in longitudinal fixed effects (within-individual) analyses.
Cross-sectionally, the likelihood of an extreme drinking occasion and heavy use was higher among those who resided <1 vs. ≥1 km from a bar. Longitudinally, between individuals, a decrease from >1 km to ≤1 km in distance was weakly associated with an extreme drin
king occasion (1.18, 95% CI 0.98–1.41), and heavy use (1.12, 95% CI 0.97–1.29). Within-individual, the odds ratio for becoming a heavy user was 1.17 (95% CI, 1.02–1.34), per 1 km decrease in log-transformed continuous distance, the corresponding odds ratio for an extreme drinking occasion was 1.03 (95% CI, 0.89–1.18).
Moving place of residence close to or far from a bar appears to be associated with a small corresponding increase or decrease in risky alcohol behaviour.
Almost 30 years after discovery of a link between alcohol consumption and certain forms of cancer, scientists are reporting the first evidence from research on people explaining how the popular beverage may be carcinogenic. The results, which have special implications for hundreds of millions of people of Asian descent, were reported here today at the 244th National Meeting & Exposition of the American Chemical Society.
Silvia Balbo, Ph.D., who led the study, explained that the human body breaks down, or metabolizes, the alcohol in beer,
The 5-item Alcohol Use Disorders Identification Test (AUDIT-5): An Effective Brief Screening Test for Problem Drinking, Alcohol Use Disorders and Alco
To identify an optimal brief version of the Alcohol Use Disorders Identification Test (AUDIT) and to evaluate its effectiveness as a screening test for problem drinking (PD), alcohol use disorders (AUD) and alcohol dependence (AD).