Genome Wide Association for Addiction: Replicated Results and Comparisons of Two Analytic Approaches

Vulnerabilities to dependence on addictive substances are substantially heritable complex disorders whose underlying genetic architecture is likely to be polygenic, with modest contributions from variants in many individual genes. “Nontemplate” genome wide association (GWA) approaches can identity groups of chromosomal regions and genes that, taken together, are much more likely to contain allelic variants that alter vulnerability to substance dependence than expected by chance.

We report pooled “nontemplate” genome-wide association studies of two independent samples of substance dependent vs control research volunteers (n=1620), one European-American and the other African-American using 1 million SNP (single nucleotide polymorphism) Affymetrix genotyping arrays. We assess convergence between results from these two samples using two related methods that seek clustering of nominally-positive results and assess significance levels with Monte Carlo and permutation approaches. Both “converge then cluster” and “cluster then converge” analyses document convergence between the results obtained from these two independent datasets in ways that are virtually never found by chance. The genes identified in this fashion are also identified by individually-genotyped dbGAP data that compare allele frequencies in cocaine dependent vs control individuals.

These overlapping results identify small chromosomal regions that are also identified by genome wide data from studies of other relevant samples to extents much greater than chance. These chromosomal regions contain more genes related to “cell adhesion” processes than expected by chance. They also contain a number of genes that encode potential targets for anti-addiction pharmacotherapeutics. “Nontemplate” GWA approaches that seek chromosomal regions in which nominally-positive associations are found in multiple independent samples are likely to complement classical, “template” GWA approaches in which “genome wide” levels of significance are sought for SNP data from single case vs control comparisons.

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News Release - Alaska’s fetal alcohol syndrome rate fell 32 percent between 1996-2002

Alaska Native babies were born with fetal alcohol syndrome (FAS) half as often around the year 2000 as they were five to seven years earlier, Department of Health and Social Services researchers found in an analysis of Alaska Birth Defects Registry data. That change brought the state’s overall rate from 1996 to 2002 down by a third, researchers reported in the State of Alaska Epidemiology Bulletin released yesterday.

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Decline in the Birth Prevalence of Fetal Alcohol Syndrome in Alaska

Population-based estimates of fetal alcohol syndrome (FAS) birth prevalence are higher for Alaska than other states using similar and consistent surveillance methodology. Trend analysis is critical to evaluating FAS prevention programs but is problematic because diagnostic and surveillance factors that affect FAS case determination are often inconsistent. The objective of this study was to evaluate overall and population specific FAS birth prevalence trends in Alaska.

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Recovery-Oriented System of Care: A Recovery Community Perspective

The Recovery Oriented Systems of Care (ROSC) Subcommittee was formed as part of the Drug and Alcohol Coalition with the specific charge to develop this White Paper.

The overarching goal of the subcommittee is to improve the system of care offered in Pennsylvania by expanding to a chronic care model of care. This attached White Paper was developed in order to inform the larger Coalition and future efforts in Pennsylvania on this historic endeavor to expand services using a Recovery Oriented System of Care model.

This paper then fits into a larger process to inform and influence service development through the Department of Health, the Department of Public Welfare and beyond.

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Alcohol/Drug/Substance “Abuse”: The History and (Hopeful) Demise of a Pernicious Label

The language used to label alcohol and other drug (AOD) problems exerts a significant influence on people experiencing such problems and on how professional helpers, policy makers, and the public view such people. Whether AOD-related problems are viewed primarily in terms of medicine (illnesses), psychology (habits), sociology (norms), morality (vices), religion (sins), or law (crimes) rests on a choice of concepts and words. America’s enduring and ambivalent relationship with psychoactive drugs is replete with cycles of stigmatization/de-stigmatization/re-stigmatization, criminalization/decriminalization/recriminalization, and medicalization/de-medicalization/re-medicalization. Put simply, we can’t seem to make up our collective minds about these substances and the people who use them to excess. As a result, we have not achieved any enduring consensus on the language that best depicts AOD-related problems (White, 2004).

This brief commentary is about two such word choices—abuse/abuser—whose origins and shortcomings we will explore. We join a growing list of addiction professionals who have advocated the immediate and permanent removal of abuse/abuser from the lexicon of the addictions field and discouragement of their use in broader cultural discussions of AOD problems. Five arguments support this recommendation. . . . . .

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Use of an Electronic Clinical Reminder for Brief Alcohol Counseling is Associated with Resolution of Unhealthy Alcohol Use at Follow-Up Screening

Brief alcohol counseling is a foremost US prevention priority, but no health-care system has implemented it into routine care.

This study evaluated the effectiveness of an electronic clinical reminder for brief alcohol counseling (“reminder”).

The specific aims were to (1) determine the prevalence of use of the reminder and (2) evaluate whether use of the reminder was associated with resolution of unhealthy alcohol use at follow-up screening.

Among 4,198 participants who screened positive for unhealthy alcohol use, 71% had use of the alcohol counseling clinical reminder documented in their medical records. Adjusted proportions of patients who resolved unhealthy alcohol use were 31% (95% CI 30–33%) and 28% (95% CI 25–30%), respectively, for patients with and without reminder use (p-value = 0.031).

The brief alcohol counseling clinical reminder was used for a majority of patients with unhealthy alcohol use and associated with a moderate decrease in drinking at follow-up.

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Request Reprint E-Mail: emily.williams3@va.gov

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The Effects of Current Subsyndromal Psychiatric Symptoms or Past Psychopathology on Alcohol Dependence Treatment Outcomes and Acamprosate Efficacy

This secondary analysis of the first U.S. acamprosate trial (N = 601) for alcohol dependence examines the effects of subsyndromal psychiatric symptoms or history of severe psychopathology on alcoholism treatment outcomes and any mitigating effects of acamprosate.

Psychiatric antecedents were documented using a protocol-specific interview. Current psychiatric symptoms were assessed using Hamilton Anxiety and Depression (HAM-A, HAM-D) rating scales. Predictors of good response, defined as abstinence for ≥90% of trial duration, were identified using logistic regression.

Subsyndromal anxiety (as determined by HAM-A "Anxious Mood" item) and the presence of ≥1 psychiatric antecedent were significant negative predictors of good response. Lower pretreatment drinking intensity, baseline motivation to have abstinence as a goal, and treatment with acamprosate were significant positive predictors of good response.

No significant interactions among predictors were detected, indicating that they are independent, additive factors.

Thus, the beneficial effects of acamprosate treatment in combination with motivational therapy may offset the liabilities for alcoholism recovery that are associated with current anxiety symptoms and/or a significant past psychiatric history.

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Request Reprint E-Mail: mason@scripps.edu
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Age at Regular Drinking, Clinical Course, and Heritability of Alcohol Dependence in the San Francisco Family Study: A Gender Analysis

We examined gender differences in age of onset, clinical course, and heritability of alcohol dependence in 2,524 adults participating in the University of California San Francisco (UCSF) family study of alcoholism.

Men were significantly more likely than women to have initiated regular drinking during adolescence. Onset of regular drinking was not found to be heritable but was found to be significantly associated with a shorter time to onset of alcohol dependence.

A high degree of similarity in the sequence of alcohol-related life events was found between men and women, however, men experienced alcohol dependence symptoms at a younger age and women had a more rapid clinical course. Women were found to have a higher heritability estimate for alcohol dependence (h²= .46) than men (h²= .32).

These findings suggest that environmental factors influencing the initiation of regular drinking rather than genetic factors associated with dependence may in part underlie some of the gender differences seen in the prevalence of alcohol dependence in this population.

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Request Reprint E-Mail: cindye@scripps.edu
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Studentship Grant Scheme 2010

Taught Course Prospectus

The purpose of the scheme is to encourage research in the alcohol field and to improve the quality of service provided for those with drinking problems. These objectives are very much within the aims of the Council.

A small number of Studentships are available for people working in the alcohol field, who wish to acquire appropriate professional qualifications by following a taught course. The Council will make a one-off payment of £1,200 towards the fees for 2010/11 for successful students.

Applications should normally be for studies or courses beginning in the academic year 2010/11. In exceptional circumstances the Council will accept applications to finance existing courses. In such cases the applicant will need to provide a satisfactory progress report from the course tutor or supervisor. The AERC will not fund retrospectively. . . . . .

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Gamma-hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of relapses

Excessive long term alcohol consumption can lead to dependence on alcohol. This means that when a person stops drinking suddenly he or she experiences withdrawal symptoms. The main goals for clinical management of alcohol withdrawal are to minimize the severity of symptoms and facilitate entry into a treatment program so that the person can achieve and maintain abstinence from alcohol.

Symptoms of withdrawal range from tremor, nausea, anxiety, restlessness and insomnia to a more severe form with seizures, hallucinations, agitation and delirium. Progression to coma and cardiac arrest is possible.

Medications include benzodiazepines, anticonvulsants and gamma-hydroxybutyrate, which was first available as a health food and body-building supplement. Reports of adverse events led to its withdrawal for that purpose.

Thirteen randomised controlled trials involving 648 participants were included in this review. Eleven were conducted in Italy. Six trials with a total of 286 participants evaluated the effectiveness of gamma-hydroxybutyric acid (GHB) in reducing withdrawal syndrome. Single studies showed that GHB could reduce withdrawal symptoms when compared to a placebo and Chlormethiazole but with more side effects. No strong differences were observed between GHB and benzodiazepines. In the other comparisons the differences were not statistically significant.

Seven trials involving 362 participants tested the use of GHB to treat alcohol dependence or prevent relapses if a person was already detoxified (mid-term outcomes). GHB was better than naltrexone and Disulfiram in maintaining abstinence and had a better effect on craving than placebo and Disulfiram. Sample sizes in individual trials were generally small (range 17 to 98 participants). The most consistently reported side effect of GHB was dizziness and vertigo, which was clearly dose dependent.

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The NSDUH Report - -Substance Use among Black Adults

Among black adults aged 18 or older, rates of past month alcohol use and binge alcohol use were lower than the national average for adults (44.3 vs. 55.2 percent and 21.7 vs. 24.5 percent, respectively); the rate of past month illicit drug use, however, was higher than the national average (9.5 vs. 7.9 percent).

The rate of need for treatment for an alcohol use problem in the past year among black adults was similar to that of the national average among adults (7.7 and 8.1 percent); however, the rate of need for treatment for an illicit drug use problem was higher among blacks than the national average (4.4 vs. 2.9 percent).

One in seven (14.2 percent) black adults in need of alcohol treatment in the past year and 24.2 percent of those in need of illicit drug treatment received treatment at a specialty facility; both of these rates were higher than the national averages for adults.

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A survey of general practitioners’ knowledge, attitudes and practices regarding the prevention and management of alcohol-related problems: an update o

Alcohol related problems are one of the leading causes of morbidity and premature death. Primary care is ideal for early detection and secondary prevention of alcohol-related problems and brief interventions have been shown to reduce excessive consumption in primary care patients.

However, General Practitioners (GPs) exhibit low levels of formal identification, treatment and referral of patients with alcohol related problems. In a survey carried out in 1999, GPs reported receiving more alcohol-related education than in previous studies, that they were prepared to counsel patients about reducing consumption and that a perceived lack of effectiveness in helping patients change alcohol consumption could be ameliorated by more information, training and support.

However, GPs were little involved in, and poorly motivated to work with, alcohol issues and identification of alcohol problems was hampered by a focus on physical symptoms. Compared to other areas of lifestyle counselling (e.g. smoking cessation, diet and physical activity), GPs reported that the largest gap between their preparedness to intervene and their sense of being a success at changing behaviour was for alcohol issues.

Given that alcohol has risen higher up the public policy agenda, it is timely to assess if personal, organisational and structural factors have altered over time to promote alcohol intervention work.

The aim of this study was therefore to assess the current knowledge, attitudes and practices of GPs concerning brief alcohol intervention and to examine whether these had changed over the last ten years and in light of recent health policy initiatives.

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DRAFT GLOBAL STRATEGY TO REDUCE THE HARMFUL USE OF ALCOHOL

The harmful use of alcohol has a serious effect on public health and is considered to be one of the main risk factors for poor health globally.

In the context of this draft strategy, the concept of the harmful use of alcohol is broad and encompasses the drinking that causes detrimental health and social consequences for the drinker, the people around the drinker and society at large, as well as the patterns of drinking that are associated with increased risk of adverse health outcomes.

The harmful use of alcohol compromises both individual and social development. It can ruin the lives of individuals, devastate families, and damage the fabric of communities.

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The impact of relative residence times on the distribution of heavy drinkers in highly distinct environments

Alcohol consumption is a function of social dynamics, environmental contexts, individuals' preferences and family history.

Empirical surveys have focused primarily on identification of risk factors for high-level drinking but have done little to clarify the underlying mechanisms at work. Also, there have been few attempts to apply nonlinear dynamics to the study of these mechanisms and processes at the population level.

A simple framework where drinking is modeled as a socially contagious process in low- and high-risk connected environments is introduced. Individuals are classified as light, moderate (assumed mobile), and heavy drinkers. Moderate drinkers provide the link between both environments, that is, they are assumed to be the only individuals drinking in both settings.

The focus here is on the effect of moderate drinkers, measured by the proportion of their time spent in “low-” versus “high-” risk drinking environments, on the distribution of drinkers.

A simple model within our contact framework predicts that if the relative residence times of moderate drinkers are distributed randomly between low- and high-risk environments then the proportion of heavy drinkers is likely to be higher than expected.

However, the full story even in a highly simplified setting is not so simple because “strong” local social mixing tends to increase high-risk drinking on its own.

High levels of social interaction between light and moderate drinkers in low-risk environments can diminish the importance of the distribution of relative drinking times on the prevalence of heavy drinking.

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How intelligence and education contribute to substance use: Hints from the Minnesota Twin family study

In old and even middle age, there are associations between physical health and both intelligence and education. This may occur because intelligence and/or education exert effects on lifestyle choices that, in turn, affect later health.

Substance use is one aspect of lifestyle choice in young adulthood that could play such a role. The effects of intelligence and/or education on substance use could be direct and environmental, or indirect due to the presence of confounding genetic and shared family influences.

We used the Minnesota Twin Family Study to distinguish these effects in males and females at age 24.

In contrast to prevailing expectations, there were moderately negative direct nonshared environmental effects of both IQ and education on both smoking and drinking in both males and females.

That is, controlling for family background effects in the form of both genetic and shared environmental influences, both higher IQ and greater education were associated with greater alcohol and nicotine use. These effects were accounted for by alcohol and nicotine use at age 17.

Our results suggest that genetic and family-culture variables confound the associations between intelligence and education and substance use in young adults, rendering them indirect.

Further research is needed to understand the roles of IQ and education in alcohol and nicotine use and their relative impacts on physical health throughout the lifespan.

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Request Reprint E-Mail: wendy.Johnson@ed.ac.uk
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In vivo wireless ethanol vapor detection in the Wistar rat

Traditional alcohol studies measure blood alcohol concentration to elucidate the biomedical factors that contribute to alcohol abuse and alcoholism. These measurements require large and expensive equipment, are labor intensive, and are disruptive to the subject.

To alleviate these problems, we have developed an implantable, wireless biosensor that is capable of measuring alcohol levels for up to 6 weeks.

Ethanol levels were measured in vivo in the interstitial fluid of a Wistar rat after administering 1 and 2 g/kg ethanol by intraperitoneal (IP) injection. The data were transmitted wirelessly using a biosensor selective for alcohol detection. A low-power piezoresistive microcantilever sensor array was used with a polymer coating suitable for measuring ethanol concentrations at 100 % humidity over several hours.

A hydrophobic, vapor permeable nanopore membrane was used to screen liquid and ions while allowing vapor to pass to the sensor from the subcutaneous interstitial fluid.

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Request Reprint E-Mail: ccheney@utk.edu

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A randomised controlled feasibility trial of alcohol consumption and the ability to appropriately use a firearm

To show the feasibility of using a controlled trial to investigate the effect of alcohol on firearm use.

12 subjects enrolled in the trial, completing 160 training scenarios. All subjects in the alcohol arm reached target alcohol level. 33% of placebo subjects reported alcohol consumption. Mechanical malfunction of the simulator occurred in 9 of 160 (5.6%) scenarios. Intoxicated subjects were less accurate, slower to fire in reaction time scenarios, and quicker to fire in scenarios requiring judgement relative to controls.

The feasibility of a randomised, controlled trial exploring the relationship between alcohol consumption and firearm use was shown. The hypothesis that alcohol consumption worsens accuracy and retards judgement about when to use a gun should be tested. Larger trials could inform policies regarding firearm use while intoxicated.

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Request Reprint E-Mail: carrb@upenn.edu

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Don’t lose your snooze - cut back on the booze

Drinkers across England are losing valuable sleep and disrupting vital brain functions without knowing that their boozing is the cause, new research for the Government’s Know Your Limits campaign has today revealed.

More than half (58%) of nearly 2,000 drinkers surveyed by YouGov did not realise that drinking above the recommended daily limits can cause sleep problems, with more men (63%) than women (53%) unaware of the link.

Almost half (45%) of those surveyed admit to experiencing tiredness the day after drinking over the recommended daily limits, but it seems many people don’t realise this could be due to alcohol interfering with their normal, restful sleep. . . . .

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Alcohol Consumption before and after a Significant Reduction of Alcohol Prices in 2004 in Finland: Were the Effects Different across Population Subgro

To examine trends in adult alcohol consumption by age, gender and education from 1982 to 2008 and evaluate the effects that a significant reduction in alcohol prices in 2004 had on alcohol consumption in different population subgroups.

Following the reduction of alcohol prices in 2004, drinking increased among men and women aged 45–64. Among men, both moderate to heavy drinking and heavy episodic drinking increased in the lowest educational group. Among women, moderate to heavy drinking increased mostly in the lowest and intermediate educational groups, while the highest increases for heavy episodic drinking were in the intermediate and highest female educational groups.

Alcohol consumption increased especially among those aged 45–64 and among lower educated people following the reduction in alcohol prices in 2004 in Finland.

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Request Reprint E-Mail: satu.helakorpi@thl.fi
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Social inequalities in alcohol consumption in the Czech Republic: A multilevel analysis

Czech Republic traditionally ranks among the countries with the highest alcohol, consumption.

This paper examines both risk and protective factors for frequent of alcohol, consumption in the Czech population using multilevel analysis.

Risk factors were measured at the, individual level and at the area level. The individual-level data were obtained from a survey for a, sample of 3526 respondents aged 18–64 years. The area-level data were obtained from the Czech, Statistical Office.

The group most inclinable to risk alcohol consumption and binge drinking are mainly, men, who live as single, with low education and also unemployed.

Only the variable for divorce rate, showed statistical significance at both levels, thus the individual and the aggregated one.

No cross-level interactions were found to be statistically significant.

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Request Reprint E-Mail: dzurova@natur.cuni.cz

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A Review of Alcoholics Anonymous/ Narcotics Anonymous Programs for Teens

The investigation of the applicability of Alcoholics Anonymous/Narcotics Anonymous (AA/NA) for teens has only been a subject of empirical research investigation since the early 1990s.

In the present review, the author describes teen involvement in AA/NA programming, provides an exhaustive review of the outcomes of 19 studies that used an AA/NA model as part of their formal teen substance abuse treatment programs, and provides data on the effects of AA/NA attendance on abstinence at follow-up, on which youth tend to become involved in AA/NA, and on mediation of the benefits of AA/NA participation.

In addition, the author suggests the reasons for somewhat limited participation by teens in more informal, community-based 12-step meetings, and makes suggestions for maximizing participation at meetings in the community.

The author concludes that AA/ NA participation is a valuable modality of substance abuse treatment for teens and that much can be done to increase teen participation, though more research is needed.

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Request Reprint E-Mail: ssussma@usc.edu
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Effects of Adolescent Ethanol Exposure on Event-Related Oscillations (EROs) in the Hippocampus of Adult Rats

Electrophysiological studies have shown that adolescent ethanol (EtOH) exposure can produce long-term changes in hippocampal EEG and ERP activity.

Recently, evidence has emerged suggesting that event-related oscillations (EROs) may be good indices of alcoholism risk in humans, however, have not been evaluated for their ability to index the effects of EtOH exposure.

The objective of the present study was to characterize EROs generated in hippocampus in adult rats exposed to EtOH during adolescence.

Adolescent male Sprague-Dawley rats were exposed to EtOH vapor for 12 h/d for 10 days. A time-frequency representation method was used to determine delta, theta, alpha and beta ERO energy and the degree of phase variation in the hippocampus of adult rats exposed to EtOH and age-matched controls.

The present results suggest that the decrease in P3 amplitudes, previously observed in adult rats exposed to EtOH during adolescence, is associated with increases in evoked theta ERO energy.

These studies suggest that EROs are suitable for characterizing the long-term effects of adolescent EtOH exposure.

Further studies are needed to determine the relationship between the mechanisms that regulate these neurophysiological endophenotypes and the consequences of adolescent EtOH exposure.

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Request Reprint E-Mail: cindye@scripps.edu

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Associations Between ADH Gene Variants and Alcohol Phenotypes in Dutch Adults

Recently, Macgregor et al. (2009) demonstrated significant associations of ADH polymorphisms with reactions to alcohol and alcohol consumption measures in an Australian sample.

The aim of the present study was to replicate these findings in a Dutch sample.

Survey data on alcohol phenotypes came from 1,754 unrelated individuals registered with the Netherlands Twin Register. SNPs in the ADH gene cluster located on chromosome 4q (n = 491) were subdivided in seven gene sets: ADH5, ADH4, ADH6, ADH1A, ADH1B, ADH1C and ADH7. Within these sets associations of SNPs with alcohol consumption measures, age at onset variables, reactions to alcohol and problem drinking liability were examined.

Of the original 38 SNPs studied by Macgregor et al. (2009), six SNPs were not available in our dataset, because one of them had a minor allele frequency < .01 (rs1229984) and five could not be imputed.

The remaining SNP associations with alcohol phenotypes as identified by Macgregor et al. (2009) were not replicated in the Dutch sample, after correcting for multiple genotype and phenotype testing.

Significant associations were found however, for reactions to alcohol with a SNP in ADH5 (rs6827292, p = .001) and a SNP just upstream of ADH5 (rs6819724, p = .0007) that is in strong LD with rs6827292.

Furthermore, an association between age at onset of regular alcohol use and a SNP just upstream of ADH7 (rs2654849, p = .003) was observed.

No significant associations were found for alcohol consumption and problem drinking liability.

Although these findings do not replicate the earlier findings at the SNP level, the results confirm the role of the ADH gene cluster in alcohol phenotypes.

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Request Reprint E-Mail: JHDA.van.Beek@psy.vu.nl
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A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity.

To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls.

Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND.

Thirdly, we performed a meta-analysis of the 10,000 most significant AD- and ND-related SNPs from the Australian and Dutch samples.

In the Australian GWAS, one SNP achieved genomewide significance (p <>⁻⁸) for ND (rs964170 in ARHGAP10 on chromosome 4, p = 4.43 × 10⁻⁸) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 × 10⁻⁹), rs1784300 near DDX6 on chromosome 11 (p = 2.60 × 10⁻⁹) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 × 10⁻⁸)).

None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepresentation of genes coding for ion-channels and cell adhesion molecules.

Further studies will be required before the detailed causes of comorbidity between AD and ND are understood.

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Request Reprint E-Mail: penelope.lind@qimr.edu.au
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Overexpression of Serum Response Factor Restores Ocular Dominance Plasticity in a Model of Fetal Alcohol Spectrum Disorders

Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in fetal alcohol spectrum disorders (FASD).

Recently, we showed that third trimester alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. For instance, a few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol.

This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors such as the cAMP response element binding protein (CREB) and the serum response factor (SRF). SRF is important for many plasticity processes such as LTP, LTD, spine motility, and axonal pathfinding.

Here we attempt to rescue OD plasticity in alcohol-treated ferrets using a Sindbis viral vector to express a constitutively active form of SRF during the period of monocular deprivation.

Using optical imaging of intrinsic signals and single-unit recordings, we observed that overexpression of a constitutively active form of SRF, but neither its dominant-negative nor GFP, restored OD plasticity in alcohol-treated animals. Surprisingly, this restoration was observed throughout the extent of the primary visual cortex and most cells infected by the virus were positive for GFAP rather than NeuN.

This finding suggests that overexpression of SRF in astrocytes may reduce the deficits in neuronal plasticity seen in models of FASD.

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Request Reprint E-Mail: amedina@vcu.edu

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A pharmacogenetic model of naltrexone-induced attenuation of alcohol consumption in rhesus monkeys

Variation at the human μ-opioid receptor has been associated with alcohol abuse. The A118G (N40D) polymorphism in humans is functionally mimicked by the C77G (P26R) polymorphism in rhesus monkeys; both show similar in vitro influences on ligand binding and in vivo correlations with physiological measures as well as behavioral measures including predilection towards alcohol consumption. Naltrexone, an antagonist at the receptor, has been used to treat alcoholism in humans and has been reported to show differences in effectiveness depending on genotype.

Here we describe a study in which we a priori selected rhesus monkeys based on genotype at the OPRM1 C77G single nucleotide polymorphism, trained them to self-administer alcohol, and assessed naltrexone responsiveness.

Alcohol intake in rhesus monkeys varied with genotype across a range of alcohol concentrations (0.5–4%, w/v) such that animals with the G/G genotype drank consistently more alcohol than those animals with the C/C genotype. Additionally, naltrexone attenuated alcohol drinking in a dose- and genotype-dependent manner. Animals harboring the G/G genotype were more sensitive to the effects of naltrexone and showed greater reductions in alcohol consumption at lower naltrexone doses compared to animals with a C/G or C/C genotype.

This preliminary study demonstrates a pharmacogenomic response to naltrexone in rhesus monkeys that parallels that seen in humans. This finding provides a basis for developing a pharmacogenetic animal model for naltrexone effect that can expand further our understanding of the causes and treatments of alcohol use disorders.

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Request Reprint E-Mail: gmiller@hms.harvard.edu

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The epidemiological profile of alcohol and other drug use in metropolitan China

There is evidence that alcohol, tobacco, and other drug use may be rising in China, but epidemiological studies that examine several drugs simultaneously and the transition from initial try to current use are limited.

The present study provides an epidemiological profile of drug use in contemporary metropolitan China.

An estimated 70–76% had used any type of drug: alcohol and tobacco were the most commonly used drugs (alcohol, 67%; tobacco, 39%). Regarding extra-medical use of internationally regulated drugs, sedatives and analgesics were most common and illegal drug use was rare. The majority of tobacco users used it recently (82.5%), especially young adults. Male–female differences were observed in lifetime tobacco use, but not for recent use. Concurrent use of alcohol and tobacco was very common.

Psychoactive drug use is common in metropolitan China. Public health policies and prevention initiatives may be needed to address associated problems that may increase following the country’s rapid socioeconomic change.

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Request Reprint E-Mail: chenghu2@msu.edu

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Controlled Drinking Programs Is One of Our Programs for You?

The Controlled Drinking by Correspondence Program and Control Your Drinking Online Program are beneficial for:

• People who wish to reduce their drinking
• People who wish to remain anonymous during their involvement in a treatment program
• People who do not wish to attend any alcohol treatment clinic
• People who cannot attend an alcohol treatment clinic due to other reasons (e.g. live to far away, do not have time etc.)
• People who wish to take part in a program that is FREE and requires very LITTLE TIME involvement

For more information on these programs click on the following links:
Controlled Drinking by Correspondence Program
more information

Control Your Drinking Online
more information

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DRUGS AND SOCIETY IN AFRICA Ninth Biennial International Conference

Announcement & Call for Papers

The African Centre for Research and Information on Substance Abuse (CRISA) is pleased to announce its Ninth Biennial International Conference on “Drugs and Society in Africa” scheduled to take place in Abuja, Nigeria, in August 2010. The organizers invite you to this very important conference that will focus on the role of alcohol and other drug use in the HIV/AIDS epidemics in different African societies. Interested researchers in various disciplines, policy experts, practitioners, representatives of NGOs and students are encouraged to submit abstracts of papers for presentation at the conference.

Major Theme:

Alcohol, Drugs and HIV/AIDS in Africa

Research, Prevention and Treatment Issues

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News Release - APA Announces Draft Diagnostic Criteria for DSM-5 New Proposed Changes Posted for Leading Manual of Mental Disorders

The American Psychiatric Association today released the proposed draft diagnostic criteria for the fifth edition of Diagnostic and Statistical Manual of Mentaln Disorders (DSM). The draft criteria represent content changes under consideration for DSM, which is the standard classification of mental disorders used by mental health and other health professionals, and is used for diagnostic and research purposes.

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Alcohol Consumption, Serum Gamma-Glutamyltransferase, and Helicobacter Pylori Infection in a Population-Based Study Among 9733 Older Adults

Moderate alcohol consumption has been suggested to facilitate the elimination of Helicobacter pylori infection as the result of its antibacterial effect.

We aimed to assess the associations of current and lifetime alcohol consumption as well as serum gamma-glutamyltransferase (GGT), an established biomarker of alcohol consumption, with H. pylori infection in a large population-based study.

A significant inverse association, in dose-response manner, was observed between both current and lifetime alcohol consumption and H. pylori seropositivity. The estimates based on lifetime consumption were more pronounced than the results for current consumption, and such inverse associations were found both for men and women. Stronger relations were observed for those who only drank wine or mixed drinkers compare with those who only drank beer. Furthermore, there was a significant inverse dose-response relationship between serum GGT levels and H. pylori seropositivity, which was selectively observed among alcohol drinkers.

In conclusion, our results support the hypothesis that moderate alcohol consumption may facilitate elimination of H. pylori.

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Request Reprint E-Mail: gaolei615@sohu.com

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NIAAA Spectrum
Volume 2, Issue 1, February 2010


In This Issue Features
Playing Matchmaker:Finding Personalized
Approaches To Solve
Alcohol Problems

Alcohol and Cancer News

Photo essay
Input, Output, Throughput:
How Is High-Throughput
Technology Advancing
Alcohol Research Problems

Charticle
Drinking Too Much Can
Kill You Quickly...or Slowly

News From the Field
Molecule Repairs Alcohol
Metabolism Enzyme

The Vine That Ate the
South May Help Alcoholics
Curb Cravings

Can Drinking During
Pregnancy Affect Kids’
Behavior?

Can Drinking Policies Keep
Risks at Bay?

Looking To Sober Up?
Caffeine Is Not the Answer

Marriage and Parenthood
May Protect Against Stress-
Induced Harmful Drinking

Questions with...
David Goldman, M.D.

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Consultation on options for improving information on the labels of alcoholic drinks to support consumers to make healthier choices in the UK

Next Steps on Alcohol Labelling

In May 2007 the Government announced its voluntary agreement with the alcohol industry to introduce, by the end of 2008, labels on the majority of alcoholic drinks containers showing unit and other health information, including advice to women on alcohol and pregnancy. A report was published, following the first stage of an independent market survey conducted by CCFRA (Campden & Chorleywood Food Research Association) in March 2008, which showed the extent to which the elements of the labelling regime had been implemented.

In April 2009 a second stage monitoring survey was conducted. This survey found that the Government’s expectation that a majority of labels should be covered by the end of 2008 was a long way from being achieved. The latest report (2009) is available below.

The Government is launching a UK wide consultation on 15 February 2009 to consider how best to improve unit and health information for consumers on alcohol labels, whether through a renewed and strengthened voluntary agreement or a mandatory requirement through legislation under the Food Safety Act. The consultation is being launched jointly by the Department of Health, the Scottish Government, the Welsh Assembly Government, and the Northern Ireland Department of Health, Social Services and Public Safety.

The views of alcohol producers and other stakeholders for improving the labelling of alcoholic drinks is being sought.

• Download Consultation on options for improving information on the labels of alcoholic drinks to support consumers to make ealthier choices in the UK (PDF, 1340K)
• Download Monitoring Implementation of Alcohol Labelling Regime Stage 2 (including advice to women on alcohol and pregnancy) (PDF, 5642K)

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Too much of the hard stuff: what alcohol costs the NHS

Consumption of alcohol in the UK has increased by 19 per cent over the last three decades. Recent reports indicate that 10.5 million adults in England drink above sensible limits and around 1.1 million have a level of alcohol addiction. Alcohol is the third leading cause of disease burden in developed countries and, as a result, the cost of providing alcohol-related services is escalating. The burden on the NHS will be unsustainable if this continues.

This Briefing, produced with the Royal College of Physicians, outlines the extent of the problem and gives examples of where the NHS is managing problem drinkers effectively and efficiently. The NHS Confederation visited hospitals between August and November 2009 and gathered evidence from members to gain an understanding of the extent of the burden and the ways in which hospitals can improve their services.

Read Full Briefing (PDF)

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Changing network support for drinking: Network Support Project 2-year follow-up.

The Network Support Project was designed to determine whether a treatment could lead patients to change their social network from one that supports drinking to one that supports sobriety.

This study reports 2-year posttreatment outcomes. Alcohol-dependent men and women (N = 210) were randomly assigned to 1 of 3 outpatient treatment conditions: network support (NS), network support + contingency management (NS + CM), or case management (CaseM, a control condition).

Analysis of drinking rates indicated that the NS condition yielded up to 20% more days abstinent than the other conditions at 2 years posttreatment. NS treatment also resulted in greater increases at 15 months in social network support for abstinence, as well as in AA attendance and AA involvement than did the other conditions.

Latent growth modeling suggested that social network changes were accompanied by increases in self-efficacy and coping that were strongly predictive of long-term drinking outcomes.

The findings indicate that a network support treatment can effect long-term adaptive changes in drinkers' social networks and that these changes contribute to improved drinking outcomes in the long term.

Read Full Abstract

Request Reprint E-Mail: Litt@nso.uchc.edu ________________________

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

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

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

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

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