Differential Effects of Single Versus Repeated Alcohol Withdrawal on the Expression of Endocannabinoid System-Related Genes in the Rat Amygdala

Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity, and affective control.

The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol (EtOH)-exposed rats were generated by maintenance on an EtOH liquid diet (10%): the first group received continuous access to EtOH for 15 days, whereas the second group was given intermittent access to the EtOH diet (5 d/wk for 3 weeks). Control subjects were maintained on an isocaloric EtOH-free liquid diet. To provide an initial profile of acute withdrawal, amygdala tissue was harvested following either 6 or 24 hours of EtOH withdrawal.

Acute EtOH withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL], respectively) were evident, as were reductions in mRNA expression for CB₁, CB₂, and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent EtOH exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g., CB₁, CB₂, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in 2-AG biosynthesis (e.g., diacylglicerol lipase-α/β) were found in any condition.

These findings suggest that EtOH dependence and withdrawal are associated with dysregulated endocannabinoid signaling in the amygdala. These alterations may contribute to withdrawal-related dysregulation of amygdalar neurotransmission.

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Request Reprint E-Mail: lparsons@scripps.edu

A Longitudinal Analysis of Circulating Stress-Related Proteins and Chronic Ethanol Self-Administration in Cynomolgus Macaques

Alcoholics have alterations in endocrine and immune functions and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates.

Plasma proteins (n = 60; Luminex) and hormones (adrenocorticotropic hormone [ACTH]; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4 months, and after 12 months of 22-hour daily concurrent access to ethanol and water.

Significant changes were observed in ACTH, cortisol, and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, 8 proteins were elevated, and 9 showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates.

Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity.

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Request Reprint E-Mail: helmsc@ohsu.edu

Early Growth Response-1 Contributes to Steatosis Development After Acute Ethanol Administration

Previous work demonstrated that the transcription factor, early growth response-1 (Egr-1), participates in the development of steatosis (fatty liver) after chronic ethanol (EtOH) administration. Here, we determined the extent to which Egr-1 is involved in fatty liver development in mice subjected to acute EtOH administration.

In acute studies, we treated both wild-type and Egr-1 null mice with either EtOH or phosphate-buffered saline (PBS) by gastric intubation. At various times after treatment, we harvested sera and livers and quantified endotoxin, indices of liver injury, steatosis, and hepatic Egr-1 content. In chronic studies, groups of mice were fed liquid diets containing either EtOH or isocaloric maltose-dextrin for 7 to 8 weeks.

Compared with controls, acute EtOH-treated mice showed a rapid, transient elevation in serum endotoxin beginning 30 minutes after treatment. One hour postgavage, livers from EtOH-treated mice exhibited a robust elevation of both Egr-1 mRNA and protein. By 3 hours postgavage, liver triglyceride increased in EtOH-treated mice as did lipid peroxidation. Acute EtOH treatment of Egr-1-null mice showed no Egr-1 expression, but these animals still developed elevated triglycerides, although significantly lower than EtOH-fed wild-type littermates. Despite showing decreased fatty liver, EtOH-treated Egr-1 null mice exhibited greater liver injury. After chronic EtOH feeding, steatosis and liver enlargement were clearly evident, but there was no indication of elevated endotoxin. Egr-1 levels in EtOH-fed mice were equal to those of pair-fed controls.

Acute EtOH administration induced the synthesis of Egr-1 in mouse liver. However, despite its robust increase, the transcription factor had a smaller, albeit significant, function in steatosis development after acute EtOH treatment. We propose that the rise in Egr-1 after acute EtOH is an hepatoprotective adaptation to acute liver injury from binge drinking that is triggered by EtOH metabolism and elevated levels of endotoxin.

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Request Reprint E-Mail: tdonohue@unmc.edu

Nociceptin/Orphanin FQ Blockade of Corticotropin-Releasing Factor-Induced Gamma-Aminobutyric Acid Release in Central Amygdala Is Enhanced After Chroni

The central nucleus of the amygdala (CeA) mediates stress- and addiction-related processes. Corticotropin-releasing factor (CRF) and nociceptin/orphanin FQ (nociceptin) regulate ethanol intake and anxiety-like behavior. In the rat, CRF and ethanol significantly augment CeA gamma-aminobutyric acid (GABA) release, whereas nociceptin diminishes it.

Using electrophysiologic techniques in an in vitro slice preparation, we investigated the interaction of nociceptin and CRF on evoked and spontaneous GABAergic transmission in CeA slices of naive and ethanol-dependent rats and the mechanistic role of protein kinase A.

In neurons from naive animals, nociceptin dose-dependently diminished basal-evoked GABA_A receptor-mediated inhibitory postsynaptic potentials (IPSPs) by decreasing GABA release and prevented, as well as reversed, CRF-induced augmentation of IPSPs, actions that required PKA signaling. In neurons from ethanol-dependent animals, nociceptin decreased basal GABAergic transmission and blocked the CRF-induced increase in GABA release to a greater extent than in naive controls.

These data provide new evidence for an interaction between the nociceptin and CRF systems in the CeA. Nociceptin opposes CRF effects on CeA GABAergic transmission with sensitization of this effect in dependent animals. These properties of nociceptin may underlie its anti-alcohol and anxiolytic properties and identify the nociceptin receptor as a useful therapeutic target for alcoholism.

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Request Reprint E-Mail: mroberto@scripps.edu

Synchrony of Corticostriatal-Midbrain Activation Enables Normal Inhibitory Control and Conflict Processing in Recovering Alcoholic Men

Alcohol dependence is associated with inhibitory control deficits, possibly related to abnormalities in frontoparietal cortical and midbrain function and connectivity.

We examined functional connectivity and microstructural fiber integrity between frontoparietal and midbrain structures using a Stroop Match-to-Sample task with functional magnetic resonance imaging and diffusion tensor imaging in 18 alcoholic and 17 control subjects. Manipulation of color cues and response repetition sequences modulated cognitive demands during Stroop conflict.

Despite similar lateral frontoparietal activity and functional connectivity in alcoholic and control subjects when processing conflict, control subjects deactivated the posterior cingulate cortex (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity predicted the degree of PCC deactivation in control but not alcoholic subjects. Also, PCC activity was modulated by executive control demands: activated during response switching and deactivated during response repetition. Alcoholics showed the opposite pattern: activation during repetition and deactivation during switching. Here, in alcoholic subjects, greater deviations from the normal PCC activity correlated with higher amounts of lifetime alcohol consumption. A functional dissociation of brain network connectivity between the groups further showed that control subjects exhibited greater corticocortical connectivity among middle cingulate, posterior cingulate, and medial prefrontal cortices than alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain-orbitofrontal cortical network connectivity than control subjects. Degree of microstructural fiber integrity predicted robustness of functional connectivity.

Thus, even subtle compromise of microstructural connectivity in alcoholism can influence modulation of functional connectivity and underlie alcohol-related cognitive impairment.

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Request Reprint E-Mail: tilman.schulte@sri.com

Early age alcohol use and later alcohol problems in adolescents: Individual and peer mediators in a bi-national study.

This paper examines whether there is cross-national similarity in the longitudinal relationship between early age alcohol use and adolescent alcohol problems. Potential mechanisms underlying this relationship also are examined, testing adolescent alcohol use, low self-regulation, and peer deviance as possible mediators.

Students (N = 1,945) participating in the International Youth Development Study, a longitudinal panel survey study, responded to questions on alcohol use and influencing factors, and were followed annually over a 3-year period from 2002 to 2004 (98% retention rate). State-representative, community student samples were recruited in grade 7 in Washington State, United States (US, n = 961, 78% of those eligible; Mage = 13.09, SD = .44) and Victoria, Australia (n = 984, 76% of those eligible; Mage = 12.93, SD = .41). Analyses were conducted using multiple-group structural equation modeling.

In both states, early age alcohol use (age 13) had a small but statistically significant association with subsequent alcohol problems (age 15).

Overall, there was little evidence for mediation of early alcohol effects. Low self-regulation prospectively predicted peer deviance, alcohol use, and alcohol problems in both states.

Peer deviance was more positively related to alcohol use and low self-regulation among students in Victoria compared to students in Washington State.

The small but persistent association of early age alcohol use with alcohol problems across both samples is consistent with efforts to delay alcohol initiation to help prevent problematic alcohol use.

Self-regulation was an important influence, supporting the need to further investigate the developmental contribution of neurobehavioral disinhibition.



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Request Reprint E-Mail: wamason@u.washington.edu

Preventing Alcohol Abuse and Alcoholism—An Update

133 In This Issue

135 The Risks Associated With Alcohol Use and Alcoholism
Jürgen Rehm, Ph.D.

144 Defining Risk Drinking
Deborah A. Dawson, Ph.D.

157 School-Based Programs to Prevent and Reduce Alcohol Use Among Youth
Melissa H. Stigler, Ph.D., M.P.H.; Emily Neusel, M.P.H.; and Cheryl L. Perry, Ph.D.

163 A Review of Environmental-Based Community Interventions
Traci L. Toomey, Ph.D., and Kathleen M. Lenk, M.P.H.

167 Engaging Communities to Prevent Underage Drinking
Abigail A. Fagan, Ph.D.; J. David Hawkins, Ph.D.; and Richard F. Catalano, Ph.D.

175 Prevention Interventions of Alcohol Problems in the Workplace: A Review and Guiding Framework
Genevieve M. Ames, Ph.D., and Joel B. Bennett, Ph.D.

180 Prevention in the Military: Early Results of an Environmental Strategy
Genevieve M. Ames, Ph.D., and Christopher Spera, Ph.D.

188 Translating Family-Focused Prevention Science Into Public Health Impact: Illustrations From Partnership-Based Research
Richard L. Spoth, Ph.D.; Lisa M. Schainker, Ph.D., M.P.H.; and Susanne Hiller-Sturmhöefel, Ph.D.

204 Environmental Approaches to Prevention in College Settings
Robert F. Saltz, Ph.D.

210 Individual-Focused Approaches to the Prevention of College Student Drinkin]
Jessica M. Cronce, Ph.D., and Mary E. Larimer, Ph.D.

222 College Prevention: A View of Present (and Future) Web-Based Approaches
Scott T. Walters, Ph.D., and Clayton Neighbors, Ph.D.

225 Preventing Impaired Driving: Opportunities and Problems
Robert B. Voas, Ph.D., and James C. Fell, M.S.

236 The Effects of Prices on Alcohol Use and Its Consequences
Xin Xu, Ph.D., and Frank J. Chaloupka, Ph.D.

246 The Alcohol Policy Information System (APIS) and Policy Research At NIAAA
Gregory Bloss, M.A.

248 Regulating Availability: How Access to Alcohol Affects Drinking and Problems in Youth and Adults
Paul J. Gruenewald, Ph.D.

257 The Road to a World Health Organization Global Strategy for Reducing the Harmful Use of Alcohol
Maristela G. Monteiro, M.D., Ph.D.

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The Fraction of Cancer Attributable to Lifestyle and Environmental Factors in the UK in 2010

This supplement provides up-to-date estimates of the numbers (and percentages) of new cancer cases in the UK that are attributable to factors that have been established by international consensus as potentially avoidable causes of the disease. It therefore offers a useful guide to the relative importance of different preventive interventions.

Excluded from consideration are factors that, although known to be effective in reducing the risk of numerically important cancers, do not offer acceptable or practical preventive strategies at present. Early and multiple childbearing (to prevent breast cancer) and the widespread use of anti-androgen drugs (to prevent prostate cancer) come under this category. What remains is a limited number of important factors that can, at least to some extent, be affected by personal or political choices. The most important among these is continuation of the significant reduction in tobacco exposure. Next in importance are reductions in obesity and in heavy alcohol consumption, and certain other dietary changes. Each of these four main strategies for cancer control would also substantially reduce the burden of other non-communicable diseases, particularly cardiovascular, diabetic, renal and hepatic disease.

Whether, and to what extent, changes in these major causes of cancer can be achieved is another consideration. Thus, for example, although substantial progress has been made in reducing the number of young people who start smoking, and in helping those who smoke to escape their addiction in time to avoid most of the risk of premature death, tobacco still remains the most important avoidable cause of cancer, responsible for almost 20% of all cases of cancer (and, although this supplement does not quantify cancer mortality, for about 25% of all deaths from cancer, plus similar numbers of deaths from other diseases).

Taken together, the causative factors reviewed in this supplement account for an estimated 43% of all new cases of cancer in the UK (approximately 134 000 new cases in 2010), and about 50% of all cancer deaths. Most of these cases of cancer (excluding a few thousand due to the natural background of ionising radiation, or due to certain infections that are currently neither preventable nor treatable) could have been prevented by methods that would also prevent many premature deaths from other non-communicable disease. Over the past 40 years in the UK, the probability of death before the age of 70 years has been halved, and over the next few decades it could be halved again by continued improvements in the treatment of disease and by paying appropriate attention to the few major avoidable causes of disease. This supplement will help focus the attention of researchers, individuals and policy makers on the relative importance of the currently known causes of cancer.


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Adolescents Living with a Parent Who Drives Under the Influence Are at Increased Risk for Driving Under the Influence Themselves

According to the National Survey on Drug Use and Health, an annual average1 of 932,000 16 to 17 year olds (11.5 percent) drove under the influence of alcohol or illicit drugs in the 12 months prior to the interview. Youths in this age group were more likely to drive under the influence if they lived with a mother or father who also had driven under the influence in the past year. These data suggest the importance of parents as role models in promoting children’s healthy behavior.


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'Alcohol pricing and taxation policies': IFS still favours taxation over minimum pricing

The economics think-tank the Institute for Fiscal Studies (IFS) have published a new report on Alcohol pricing and taxation policies. It echoes many of the findings from a report last year in which it suggested minimum pricing would transfer further profits to industry and retailers, therefore favouring increased taxation.

The new report however suggests the current alcohol taxation system is not optimal and a "sensible starting point would be to tax all alcohols at an equivalent rate per unit. Such a change would require policy action at the EU level which the Government should pursue." > > > > Read More

African women are non-drinkers

In the latest round of the WHO World Health Surveys 40.739 women from 20 African countries were interviewed also about their alcohol drinking habits. Close to 34.000 reported lifetime abstinence from alcohol. This is 81 % of the respondents in the survey. The proportion of current alcohol drinkers ranged from 1% in Malawi to 20% in Burkina Faso. > > > > Read More

A Sobering Look at Alcohol: 10-Year Study Finds High Death Rate

A number of studies in the past few years have suggested health benefits from drinking small or moderate amounts of alcohol. This can encourage people to look at alcohol almost as if it's medicine. A recent study of alcohol use in Italy paints a much more sobering picture. > > > > Read More

Alcoholism expert Dora Goldstein dies at 89

Pharmacologist Dora B. “Dody” Goldstein, MD, one of the world’s leading experts on alcoholism and a pioneer of women in medicine, died Oct. 2 at Stanford Hospital after suffering a fall in her Palo Alto home. She was 89.

A professor emerita of molecular pharmacology at the Stanford University School of Medicine, Goldstein was widely recognized for her research on the effects of alcohol on the body. Her work established some of the basic biological principles underlying alcoholism, including the mechanisms of alcohol dependence and tolerance. One of the first women to graduate from Harvard Medical School, she also became a champion for women in medicine and served in leadership positions in the civil rights and gay rights movements. > > > > Read More

Ethanol Exposure During Pregnancy Persistently Attenuates Cranially Directed Blood Flow in the Developing Fetus: Evidence from Ultrasound Imaging in a

Ethanol (EtOH) consumption during pregnancy can lead to fetal growth retardation, mental retardation, and neurodevelopmental delay. The fetal brain initiates neurogenesis and vasculogenesis during the second trimester, and depends on maternal-fetal circulation for nutrition and growth signals. We used high-resolution in vivo ultrasound imaging to test the hypothesis that EtOH interferes with fetal brain-directed blood flow during this critical developmental period.

Pregnant mice were lightly anesthetized on gestational day 12 with an isoflurane/oxygen mixture. We assessed the effect of single and repeated binge-like maternal EtOH exposures at 3 g/kg, administered by intragastric gavage or intraperitoneal injection, on maternal circulation and fetal umbilical, aortic, internal carotid, and middle cerebral arterial circulation.

Binge maternal EtOH exposure, regardless of exposure route, significantly reduced fetal arterial blood acceleration and velocity time integral (VTI), from umbilical to cerebral arteries, without a change in fetal heart rate and resistivity indices. Importantly a single maternal binge EtOH exposure induced persistent suppression of fetal arterial VTI for at least 24 hours. Repeated binge episodes resulted in a continuing and persistent suppression of fetal VTI. Qualitative assessments showed that maternal EtOH exposure induced oscillatory, nondirectional blood flow in fetal cerebral arteries. Maternal cardiac and other physiological parameters remained unaltered.

These data show that binge-type maternal EtOH exposure results in rapid and persistent loss of blood flow from the umbilical artery to the fetal brain, potentially compromising nutrition and the maternal/fetal endocrine environment during a critical period for neuron formation and angiogenesis in the maturing brain.

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Request Reprint E-Mail: miranda@medicine.tamhsc.edu

Early Growth Response-1 Contributes to Steatosis Development After Acute Ethanol Administration

Previous work demonstrated that the transcription factor, early growth response-1 (Egr-1), participates in the development of steatosis (fatty liver) after chronic ethanol (EtOH) administration. Here, we determined the extent to which Egr-1 is involved in fatty liver development in mice subjected to acute EtOH administration.

In acute studies, we treated both wild-type and Egr-1 null mice with either EtOH or phosphate-buffered saline (PBS) by gastric intubation. At various times after treatment, we harvested sera and livers and quantified endotoxin, indices of liver injury, steatosis, and hepatic Egr-1 content. In chronic studies, groups of mice were fed liquid diets containing either EtOH or isocaloric maltose-dextrin for 7 to 8 weeks.

Compared with controls, acute EtOH-treated mice showed a rapid, transient elevation in serum endotoxin beginning 30 minutes after treatment. One hour postgavage, livers from EtOH-treated mice exhibited a robust elevation of both Egr-1 mRNA and protein. By 3 hours postgavage, liver triglyceride increased in EtOH-treated mice as did lipid peroxidation. Acute EtOH treatment of Egr-1-null mice showed no Egr-1 expression, but these animals still developed elevated triglycerides, although significantly lower than EtOH-fed wild-type littermates. Despite showing decreased fatty liver, EtOH-treated Egr-1 null mice exhibited greater liver injury. After chronic EtOH feeding, steatosis and liver enlargement were clearly evident, but there was no indication of elevated endotoxin. Egr-1 levels in EtOH-fed mice were equal to those of pair-fed controls.

Acute EtOH administration induced the synthesis of Egr-1 in mouse liver. However, despite its robust increase, the transcription factor had a smaller, albeit significant, function in steatosis development after acute EtOH treatment. We propose that the rise in Egr-1 after acute EtOH is an hepatoprotective adaptation to acute liver injury from binge drinking that is triggered by EtOH metabolism and elevated levels of endotoxin.

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Request Reprint E-Mail: tdonohue@unmc.edu

A Longitudinal Analysis of Circulating Stress-Related Proteins and Chronic Ethanol Self-Administration in Cynomolgus Macaques

Alcoholics have alterations in endocrine and immune functions and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates.

Plasma proteins (n = 60; Luminex) and hormones (adrenocorticotropic hormone [ACTH]; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4 months, and after 12 months of 22-hour daily concurrent access to ethanol and water.

Significant changes were observed in ACTH, cortisol, and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, 8 proteins were elevated, and 9 showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates.

Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity.

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Request Reprint E-Mail: helmsc@ohsu.edu

Chronic Intermittent Ethanol Exposure and Its Removal Induce a Different miRNA Expression Pattern in Primary Cortical Neuronal Cultures

Increasing evidence indicates that repeated exposure to and withdrawal from alcohol can result in persistent molecular and cellular adaptations. One molecular adaptation that occurs is the regulation of gene expression, which is thought to lead to the functional alterations that characterize addiction: tolerance, dependence, withdrawal, craving, and relapse. MicroRNAs (miRNAs) have been recently identified as master regulators of gene expression through post-transcriptional regulation. However, the role of miRNAs in the neuroadaptations after alcohol removal has not yet been directly addressed.

We employed a chronic intermittent ethanol (CIE) model in primary cortical neuronal cultures to examine the global extent of differential miRNA expression using a TaqMan real-time PCR miRNA array.

Sixty-two miRNAs were differentially expressed after 10 days of CIE (CIE10) treatment (n = 42 with false discovery rate [FDR] < 0.05 and fold change > 2) and 5 days post-CIE (P5) treatment (n = 26) compared with untreated control values. Compared to CIE10, ethanol (EtOH) removal experience in P5 induced a distinct expression pattern, including 20 differentially expressed miRNAs, which did not exhibit a significant change at CIE10. The predicted target molecules of EtOH removal-induced miRNAs function mainly in the regulation of gene transcription, but also function in neuron differentiation, embryonic development, protein phosphorylation, and synaptic plasticity. Interestingly, some of the miRNAs differentially expressed 5 days after CIE treatment were found to cluster on chromosomes near CpG islands, suggesting that they share functional similarity by targeting alcohol-related genes.

Taken together, these results suggest a potential role of differentially expressed miRNAs in mediating EtOH removal-related phenotypes.

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Request Reprint E-Mail:

qiang@uthscsa.edu

Prediction of the Risk of Comorbid Alcoholism in Schizophrenia by Interaction of Common Genetic Variants in the Corticotropin-Releasing Factor System

Stress plays a major role in the development of comorbid alcohol use disorder (AUD). In turn, AUD worsens the outcome of psychiatric patients with respect to global disease severity, social situation, and socioeconomic burden. Prediction of persons at risk for AUD is crucial for future preventive and therapeutic strategies.

To investigate whether genetic variants of the corticotropin-releasing factor system or their interaction influence the risk of developing AUD in chronic disease populations.

Genotype analysis comprising selected single-nucleotide polymorphisms within the CRHR1 and CRHBP genes in patients with schizophrenia and in a nonschizophrenic psychiatric disease control sample should allow the extraction of predictors of comorbid AUD. Gene expression (messenger RNA) analysis in peripheral blood mononuclear cells was performed to gain the first mechanistic insight.

An ideal setup for this study was the Göttingen Research Association for Schizophrenia Data Collection of schizophrenic patients, specifically intended to enable association of genetic information with quantifiable phenotypes in a phenotype-based genetic association study.

Patients A total of 1037 schizophrenic patients (Göttingen Research Association for Schizophrenia sample), 80 nonschizophrenic psychiatric disease controls as a small replicate sample, and a case-control study including 1141 healthy subjects.

Main Outcome Measures Association of CRHR1 and CRHBP genotypes with the following: (1) AUD; (2) a newly developed alcoholism severity score comprising 5 AUD-relevant variables; and (3) quantitative CRHR1 and CRHBP messenger .RNA expression.

An interaction of CRHR1 rs110402 and CRHBP rs3811939 predicts high risk of comorbid AUD in schizophrenic patients (odds ratio = 2.27; 95% confidence interval, 1.56-3.30; P < .001) as well as psychiatric disease controls (odds ratio = 4.02; 95% confidence interval, 0.95-17.05; P = .06) and leads to the highest CRHR1/CRHBP messenger RNA ratio (P = .02; dysbalanced stress axis).

The high predictive value of a genetic interaction within the stress axis for the risk of comorbid AUD may be used for novel preventive and individualized therapeutic approaches.

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Request Reprint E-Mail: ehrenreich@em.mpg.de

Inebriation, Drinking Motivations and Sexual Risk Taking Among Sexually Transmitted Disease Clinic Patients in St. Petersburg, Russia

We investigated whether inebriation was associated with having non-main partners and unprotected sex with non-main partners and whether drinking motivations were associated with sexual risk behaviors among patients attending an STD clinic in St Petersburg, Russia.

A cross-sectional behavior survey was applied to 362 participants between 2008 and 2009. Multivariate logistic regression was used for analysis.

At-risk drinking per Alcohol Use Disorders Identification Test (AUDIT-C) criteria (OR 2.5, 95% CI 1.4–4.4) was independently associated with having non-main sexual partners. Inebriation (OR 3.2, 95% CI 1.3–8.1) but not at-risk drinking or drinking prior to sex was associated with unprotected sex with non-main partners.

Among drinkers, the consumption of alcohol to facilitate sexual encounters (OR 2.7, 95% CI 1.6–4.5) was associated with having non-main sexual partners.

HIV prevention programs in Russia must address inebriation in addition to conventional patterns of problem drinking such as those measured by AUDIT-C and consider individuals’ motivations to drink that lead to sexual risk taking.



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Request Reprint E-Mail: nadia.abdala@yale.edu

Alcohol News - 49/2011

Medscape (Sweden) - Alcohol Abuse More Detrimental to the Female Brain

Alcohol abuse appears to be much more detrimental to the female brain than to the male brain, new research suggests. Investigators from the multidisciplinary Gothenburg Alcohol Research Project in Sweden found that after 4 years of excessive drinking, women experienced the same loss of serotonergic function that occurred in men who had been abusing alcohol for 12 years.

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The Local.se (Sweden) - Half of Swedes 'unsure' if they have driven drunk

Some 46 percent of Swedes are uncertain whether they have drunk too much when they get behind the wheel, according to a new survey carried out by a major insurance company.

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Stockholm News (Sweden) - Police: We can’t get rid of pub violence

The police can not reduce pub violence more than marginally. This because of Swedish drinking culture and the availability of alcohol. Efforts are now concentrated on keeping such crime at a "reasonable" level.

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Baltic Business News (Estonia) - Researcher: Estonia should triple alcohol excise duty

Indrek Saar writes in his doctor’s thesis that the alcohol taxation rate that was introduced in 2009 is notably below the optimum level.

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The Guardian (UK) - Alcohol-induced liver problems soar among young adults

There has been a huge increase in the number of young adults treated in hospital for serious liver problems brought on by drinking too much, NHS figures show.

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American Medical News - Avoiding alcohol in adolescence may reduce breast cancer risk

Drinking alcohol during adolescence has been linked to an increased risk of breast cancer, especially for girls with a family history of the disease, a study says.

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RTE.ie (Ireland) - Alcohol tops drug-related deaths

Alcohol accounted for the greatest number of drug-related deaths in Ireland between 2004 and 2009.

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The Atlantic (Italy) - A Sobering Look at Alcohol: 10-Year Study Finds High Death Rate

A number of studies in the past few years have suggested health benefits from drinking small or moderate amounts of alcohol. This can encourage people to look at alcohol almost as if it's medicine. A recent study of alcohol use in Italy paints a much more sobering picture.

Read more

CBC.ca (Canada) - B.C. drunk-driving law could be overturned

The B.C. Supreme Court is expected to rule Wednesday on whether the province's tough new drunk-driving law violates constitutional rights. Described as the strictest impaired driving law in Canada, the B.C. Motor Vehicle Act's automatic roadside driving prohibition clause allows police to issue roadside suspensions, impound cars and levy fines in the hundreds of dollars for drivers with a blood alcohol level of 0.05 or higher.

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The Economist (Scotland) - The battle of the bottle

SATURDAY nights in most British cities are high-spirited, but in Glasgow they are the stuff of legend. Some 75,000 people stream through its streets, crowding into pubs and clubs. After the bouncers push their last all-but-senseless clients out of the door, and the last punch-up outside a chippy is dispersed by the Strathclyde police, pavements lie deserted under a dense coating of fag ends and glass shards. Over a thousand people will have been admitted to accident and emergency units.

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Fin24 (South Africa) - Minister calls for alcohol ban at functions

Social Development Minister Bathabile Dlamini has called on her government colleagues to lead by example and ban alcohol at all state functions, City Press reported on Sunday.

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New Zealand Herald (Australia/New Zealand) - Fetal harm warnings likely for alcohol labels

Alcoholic drinks in New Zealand and Australia could soon carry health warnings aimed at pregnant women and their unborn babies. The Australian Government indicated this week that it will aim for compulsory warnings in two years as part of a transtasman agreement on food labelling standards.

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RIA Novosti (Ingushetia) - Ingushetia MPs seek alcohol ban on Thursdays, Fridays

Lawmakers of Ingushetia’s outgoing parliament voted for the first reading of a bill to ban alcohol sales in the predominantly Moslem Russian republic on Friday, the local government’s spokeswoman said.

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Irish Independent (Ireland) - Alcohol locks and tracking devices planned for drivers who flout law

DRIVERS who repeatedly flout road-traffic laws face the prospect of having tracking devices and alcolocks installed in their vehicles.

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ABC Online (Australia) - Declaring homes alcohol free could reduce violence

For some, it's an everyday reality - the walls are smashed as a fist goes through or there are holes or marks where a chair has been thrown.

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The Independent (UK) - Editor-At-Large: Let's sober up – and stand up to booze industry bullies

It's that time of year again – pubs and pizzerias full of gurning office workers wearing paper hats and pulling crackers, downing house plonk by the bucket load, all in the name of seasonal good cheer. Later there'll be puke in the gutters and piss on the back walls of buildings up and down the land.

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Engagement with alcohol marketing and early brand allegiance in relation to early years of drinking

This study aimed to examine the relationship between measures of awareness to marketing and drinking among a sample of young people in New Zealand.

The sample consisted of 1302 males and 1236 females predominantly aged between 13 and 14 years and drawn from a number of schools in a metropolitan city. They were surveyed using a computer assisted telephone interview.

Regression analyses examined relationships between marketing (awareness of and engagement with a range of alcohol marketing channels) and reports of brand allegiance and drinking status, drinking frequency and quantity and future drinking intentions.

The results showed that awareness of each alcohol marketing channel increased the odds of being a drinker by 8%. Engagement with web-based marketing increased the odds of being a drinker by 98% while engagement with traditional marketing increased the odds by 51%. Brand allegiance increased the odds of being a drinker by 356% and increased the likelihood of non-drinkers reporting future drinking intentions (by 73%). Brand allegiance was also associated with more frequent alcohol consumption (1.65 times more drinking occasions per year) and 86% more alcohol consumed on a typical occasion.

The results suggest that, while exposure to all forms of marketing are associated with drinking by young people, measures of more active engagement, such as owning merchandise and downloading screensavers are stronger predictors of drinking. Having established a brand allegiance, at this early age, was related to not only drinking and future intentions to drink but also drinking patterns including consuming larger quantities.

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Alcohol and Student Performance: Estimating the Effect of Legal Access

We consider the effect of legal access to alcohol on student achievement. We first estimate the effect using an RD design but argue that this approach is not well suited to the research question in our setting.

Our preferred approach instead exploits the longitudinal nature of the data, identifying the effect by measuring the extent to which a student’s performance changes after he gains legal access to alcohol, controlling flexibly for the expected evolution of grades as students make progress towards their degrees.

We find that students’ grades fall below their expected levels upon being able to drink legally, but by less than previously documented.

We also show that there are effects on women and that the effects are persistent.


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Request Reprint E-Mail: jlindo @ uoregon. edu

Hello Sunday Morning is a movement towards a better drinking culture.

Our purpose is to provide a platform for individuals to create meaningful change in their lives through a period of sobriety. By sharing their story, each persons' stand is a unique and essential contribution to a better drinking culture. > > > > Read More

The Future of AA, NA, and Other Recovery Mutual Aid Organizations

Addiction recovery mutual aid societies have played a significant role in the resolution of severe alcohol and other drug problems throughout the world and have exerted a particularly profound influence on the professional treatment of addiction (Humphreys, 2004; White, 2004). The purpose of this article is to discuss five current contextual influences that will influence the future of Alcoholics Anonymous (AA), Narcotics Anonymous (NA), and other addiction recovery mutual aid groups. First, we will place that future within its historical context.


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National Survey of Substance Abuse Treatment Services (N-SSATS): 2010

This report presents results from the 2010 National Survey of Substance Abuse Treatment
Services (N-SSATS), an annual census of facilities providing substance abuse treatment.

Conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA), N-SSATS is designed to collect data on the location, characteristics, and use of alcohol and drug abuse treatment facilities and services throughout the 50 States, the District of Columbia, and other U.S. jurisdictions.


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Social Norm Influences on Evaluations of the Risks Associated with Alcohol Consumption: Applying the Rank-Based Decision by Sampling Model to Health J

The research first tested whether perceptions of other people's alcohol consumption influenced drinkers' perceptions of the riskiness of their own consumption. Second, the research tested how such comparisons are made—whether, for example, people compare their drinking to the ‘average’ drinker's or ‘rank’ their consumption amongst other people's. The latter untested possibility, suggested by the recent Decision by Sampling Model of judgment, would imply different cognitive mechanisms and suggest that information should be presented differently to people in social norm interventions.

Study 1 surveyed students who provided information on (a) their own drinking, (b) their perceptions of the distribution of drinking in the UK and (c) their perceived risk of various alcohol-related disorders. Study 2 experimentally manipulated the rank of ‘target’ units of alcohol within the context of units viewed simultaneously.

In both studies, the rank of an individual's drinking in a context of other drinkers predicted perceptions of developing alcohol-related disorders. There was no evidence for the alternative hypothesis that people compared with the average of other drinkers' consumptions. The position that subjects believed they occupied in the ranking of other drinkers predicted their perceived risk, and did so as strongly as how much they actually drank.

Drinking comparisons are rank-based, which is consistent with other judgments in social, emotional and psychophysical domains. Interventions should be designed to work with people's natural ways of information processing, through providing clients with information on their drinking rank rather than how their drinking differs from the average.


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Request Reprint E-Mail: alex.wood@manchester.ac.uk

Council conclusions on closing health gaps within the EU through concerted action to promote healthy lifestyle behaviours

The Council adopted the following conclusions:
"THE COUNCIL OF THE EUROPEAN UNION RECALLS
that under Article 168 of the Treaty on the Functioning of the European Union, a high level of human health protection shall be ensured in the definition and implementation of all Union policies and activities. Union action, which shall complement national policies, shall be directed towards improving public health, preventing illness and disease, and obviating sources of danger to physical and mental health. The Union and Member States shall foster cooperation with third countries and the competent international organisations in the sphere of public health. > > > > Read More

Light drinking during pregnancy: still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age?

This study examines the relationship between light drinking during pregnancy and the risk of socioemotional problems and cognitive deficits at age 5 years.

Data from the nationally representative prospective UK Millennium Cohort Study (N=11 513) were used. Participants were grouped according to mothers' reported alcohol consumption during pregnancy: never drinker; not in pregnancy; light; moderate; heavy/binge. At age 5 years the strengths and difficulties questionnaire (SDQ) and British ability scales (BAS) tests were administered during home interviews. Defined clinically relevant cut-offs on the SDQ and standardised scores for the BAS subscales were used.

Boys and girls born to light drinkers were less likely to have high total difficulties (for boys 6.6% vs 9.6%, OR=0.67, for girls 4.3% vs 6.2%, OR=0.69) and hyperactivity (for boys 10.1% vs 13.4%, OR=0.73, for girls 5.5% vs 7.6%, OR=0.71) scores compared with those born to mothers in the not-in-pregnancy group. These differences were attenuated on adjustment for confounding and mediating factors. Boys and girls born to light drinkers had higher mean cognitive test scores compared with those born to mothers in the not-in-pregnancy group: for boys, naming vocabulary (58 vs 55), picture similarities (56 vs 55) and pattern construction (52 vs 50), for girls naming vocabulary (58 vs 56) and pattern construction (53 vs 52). Differences remained statistically significant for boys in naming vocabulary and picture similarities.

At age 5 years cohort members born to mothers who drank up to 1–2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of mothers in the not-in-pregnancy group.

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Request Rerprint E-Mail: y.kelly@ucl.ac.uk

Correlating the Blood Alcohol Concentration with Outcome after Traumatic Brain Injury: Too Much Is Not a Bad Thing

Although recent evidence suggests a beneficial effect of alcohol for patients with traumatic brain injury (TBI), the level of alcohol that confers the protective effect is unknown.

Our objective was to investigate the relationship between admission blood alcohol concentration (BAC) and outcomes in patients with isolated moderate to severe TBI.

From 2005 to 2009, the Los Angeles County Trauma Database was queried for all patients ≥14 years of age with isolated moderate to severe TBI and admission serum alcohol levels. Patients were then stratified into four levels based on admission BAC: None (0 mg/dL), low (0-100 mg/dL), moderate (100-230 mg/dL), and high (≥230 mg/dL). Demographics, patient characteristics, and outcomes were compared across levels.

In evaluating 3794 patients, the mortality rate decreased with increasing BAC levels (linear trend P < 0.0001).

In determining the relationship between BAC and mortality, multivariable logistic regression analysis demonstrated a high BAC level was significantly protective (adjusted odds ratio 0.55; 95% confidence interval: 0.38-0.8; P = 0.002).

In the largest study to date, a high (≥230 mg/dL) admission BAC was independently associated with improved survival in patients with isolated moderate to severe TBI.

Additional research is warranted to investigate the potential therapeutic implications.



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Request Reprint E-Mail: ali.salim@cshs.org

Global Actions: December 1, 2011

Key Recent Milestones:

· In Nairobi, ICAP’s Ken Williams and Guillermo Cantor recently concluded their participation in Working Towards a Better Understanding of the Informal Alcohol Markets in Five Countries. The meeting explored the extent of the unrecorded alcohol market in Kenya, Uganda, Tanzania, Botswana, and Rwanda.

Global Actions Spotlight:

Mexico Summit Global Actions recently held a landmark summit in Mexico City. A joint effort of the Mexico Council for Injury Prevention (CONAPRA), the Police Department of Mexico City, the Mexico Global Road Safety Partnership (GRSP), and the International Center for Alcohol Policies (ICAP), Toward Zero Alcohol Deaths centered on traffic safety issues, with emphasis on drink driving prevention.

Attendees included law enforcement, traffic safety, and health professionals from across Mexico. Dr. Othon Sanchez Cruz of the Mexico City Police, Jalisco Legislative Deputy Director Jesus Casillas, ICAP’s Bill Georges, and John Sullivan of the New York State STOP-DWI Association presented on topics ranging from legislative issues, criminal activity and traffic safety, and developing comprehensive programs to reduce drink driving. Participants reviewed current trends, examined best practices, and will use information from the summit to assist them in planning efforts to combat drink driving.

“The summit was a significant launch of our efforts with representatives from jurisdictions across Mexico,” said ICAP Vice President Brett Bivans. “We have a shared commitment to work with all interested parties toward the goal of zero drink driving deaths.” Global Actions and our Mexico partners continue to work under the leadership of CONAPRA Secretary Dr. Arturo Cervantes Trejo to develop comprehensive programs that demonstrate long-term positive impact to reduce harmful drinking and can be replicated across the country.

What’s Happening Next:

· Miami: ICAP’s Industry Workshop for Latin America is taking place December 1-2, as part of our efforts to support industry engagement around the WHO Global Strategy. The meeting will bring together industry members from across Latin America

Does the Alcohol Make Them Do It? Dating Violence Perpetration and Drinking Among Youth

Strong evidence links alcohol use to partner violence perpetration among adults, but the relation between youth alcohol use and dating violence perpetration (DVP) is not as well studied.

The authors used meta-analytic procedures to evaluate current knowledge on the association between alcohol use and DVP among youth. The authors reviewed 28 studies published in 1985–2010; most (82%) were cross-sectional. Alcohol use was measured in 3 main ways: 1) frequency or quantity of use, 2) frequency of heavy episodic drinking, or 3) problem use.

Collectively, results support the conclusion that higher levels of alcohol use are positively associated with youth DVP. With fixed-effects models, the combined odds ratios for DVP for frequency/quantity, heavy episodic drinking, and problem use were 1.23 (95% confidence interval (CI): 1.16, 1.31), 1.47 (95% CI: 1.17, 1.85), and 2.33 (95% CI: 1.94, 2.80), respectively. This association persisted even after accounting for heterogeneity and publication bias.

No studies were designed to assess the immediate temporal association between drinking and DVP. Future research should assess whether there are acute or pharmacologic effects of alcohol use on youth DVP.

Furthermore, few studies have been hypothesis driven, controlled for potential confounding, or examined potential effect measure modification.

Studies designed to investigate the youth alcohol–DVP link specifically, and whether results vary by individuals’ gender, dev


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Media Release - RESEARCH SHOWS INDUSTRY REGULATED ALCOHOL LABELS WON’T WORK

Market research has overwhelmingly rejected the alcohol health warning labels recently launched by the Australian alcohol industry in favour of informative, clear and specific labels produced by the Foundation for Alcohol Research & Education (FARE).

Across all categories, the alcohol industry’s labels were dismissed in preference for the FARE labels:

• 95% selected the FARE health warning labels as being more noticeable.

• 89% believed the FARE health warning labels are more likely to raise awareness of alcohol‐related harms.

• 88% felt the FARE health warning labels would be more likely to prompt conversations about alcoholrelated harms.

• 88% believed the FARE warning labels would be more likely to result in people drinking less alcohol.

• 60% selected the FARE labels as telling them something they did not already know while only 10% selected the DrinkWise labels. > > > > Read More

2ND International SAFFrance Colloquium, 15- 16 December 2011, Strasbourg, France

The second international conference of SAFFrance to be organised on the 15th and 16th of December in Strasbourg is linked to the first conference organised in the Senate in September 2009 to which the higher head of state participated.

Its aim will be to facilitate the professionals’ awareness on the link between prenatal alcohol, brain damage, difficulties to learn and social maladjustment and hence, on the way to prevent these issues.

With the help of the Ministries of Health, Social Cohesion and Education this international conference’s aim is to focus on :

- The short and long term effects of prenatal alcohol on the developing brain (clinical, neuro-imaging, biomedical)

The aims of the conference:

- on the diagnostic tools and the on the diagnostic tools and the assessment from the antenatal period to school age

- on the methods of coaching, compensation and on the diagnostic tools and the assessment from the antenatal period to school age

-on the methods of coaching, compensation and taking care of Neurodevelopmental Disorders linked to alcohol (through a support network, rehabilitations, adapted teaching, psychological support…)

- on the prevention of FASD with the help of a cross-wise network support based on a real national plan for the next ten years.

It has the ambition to bring together the best specialists worldwide and all french professionals involved, from near or far in this issue through a crosswise approach : Medico - psycho - educational - social.

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