A Variable-Number-of-Tandem-Repeats Polymorphism in the Dopamine D4 Receptor Gene Affects Social Adaptation of Alcohol Use

Research suggests that people adapt their own drinking behavior to that of other people.

According to a genetic-differences approach, some individuals may be more inclined than others to adapt their alcohol consumption level to that of other people.

Using a 3 (drinking condition) × 2 (genotype) experimental design (N = 113), we tested whether susceptibility to alcohol-related cues (i.e., seeing someone drink) was related to the variable number of tandem repeats in exon 3 of the D4 dopamine receptor gene.

A strong gene-environment interaction showed that participants carrying at least one copy of the 7-repeat allele consumed substantially more alcohol in the presence of a heavy-drinking individual than did participants without this allele.

This study highlights that individual variability in sensitivity to other people’s drinking behavior may be attributable to genetic differences.

Carrying the 7-repeat allele may increase the risk for heavy alcohol use or abuse in the company of heavy-drinking peers.


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Smoking, drinking and drug use among young people in England in 2008 full report

More than half (52%) of pupils aged between 11 and 15 have had at least one alcoholic drink in their lifetimes. This increases with age from 16% of 11 year olds to 81% of 15 year olds.

The proportion of pupils who have never drunk alcohol has risen in recent years, from 39% in 2003 to 48%in 2008.

The proportion of pupils who drank alcohol in the last week has fallen from a peak of 26% in 2001 to 18%in 2008. Similar proportions of boys and girls drank alcohol in the last seven days, and older pupils are more likely to have done so than younger pupils (from 3%of 11 year olds to 38%of 15 year olds). White pupils are more likely to have drunk alcohol recently than Black or Asian pupils.


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Disability Associated With Alcohol Abuse and Dependence

Alcohol use disorders (AUD), i.e., alcohol dependence and abuse, are major contributors to burden of disease. A large part of this burden is because of disability. However, there is still controversy about the best disability weighting for AUD.

The objective of this study was to provide an overview of alcohol-related disabilities.

Systematic literature review and expert interviews.

There is heterogeneity in experts' descriptions of disabilities related to AUD. The major core attributes of disability related to AUD are changes of emotional state, social relationships, memory and thinking. The most important supplementary attributes are anxiety, impairments of speech and hearing.

This review identified the main patterns of disability associated with AUD. However, there was considerable variability, and data on less prominent patterns were fragmented. Further and systematic research is required for increasing the knowledge on disability related to AUD and for application of interventions for reducing the associated burden.

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Request Request E-Mail: avsamokhvalov@yahoo.ca

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Measurement of Serum, Liver, and Brain Cytokine Induction, Thiamine Levels, and Hepatopathology in Rats Exposed to a 4-Day Alcohol Binge Protocol

In rodent and human studies, ethanol (EtOH) exposure is associated with elevated brain levels of the magnetic resonance spectroscopy (MRS) signal representing choline-containing compounds (Cho). One interpretation of elevated brain Cho is that it is a marker of neuroinflammation, and some evidence suggests that EtOH exposure promotes neuroinflammation.

This study aimed to determine whether binge EtOH exposure (intragastric 3 g/kg 25% EtOH every 8 hours for 4 days) would induce the expression of certain cytokines in blood, liver, or brain, thereby supporting the neuroinflammation hypothesis of elevated Cho.

Ten of 18 wild-type male Wistar rats (∼322 g at baseline) were exposed to EtOH and attained average blood alcohol levels of ∼315 mg/dl across 4 days. Blood for cytokine immunoassays was collected at baseline, after 5 doses of EtOH (binge), and immediately preceding euthanasia either 4 or 24 hours after the last dose of EtOH. Blood was additionally assayed for the levels of thiamine and liver enzymes; liver histopathology was performed postmortem; and tissue from liver and 6 brain regions was assayed for the potential induction of 7 cytokines.

There were no group effects on the levels of thiamine or its phosphate derivatives, thiamine monophosphate or thiamine diphosphate. ANOVAs of liver enzyme levels indicated that only alkaline phosphatase (ALP) levels were higher in the EtOH group than in control group at binge; ALP elevations, however, are difficult to explain in the absence of changes in the levels of additional liver enzymes. Postmortem liver pathology provided evidence for minimal microvesicular lipidosis and portocentric fibrosis in the EtOH group. Group effects on the levels of the measured cytokines in the blood (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-13, and GRO/CXCL1) were not significant. Similarly, postmortem evaluation of liver cytokines did not reveal group effects. Postmortem evaluation of the 7 cytokines in 6 brain regions (anterior cerebellar vermis, cingulate cortex, frontal cortex, hippocampus, hypothalamus, striatum) also failed to identify group effects.

A single 4-day bout of binge EtOH exposure alone was insufficient to induce the expression of 7 cytokines in blood, liver, or 6 brain regions of wild-type Wistar rats. Alternative interpretations for elevations in brain Cho in response to a 4-day binge EtOH treatment are therefore necessary and may include induction of cytokines not measured herein or other noninflammatory mechanisms.

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Request Reprint E-Mail: nzahr@stanford.edu

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Efficacy and Safety of Baclofen for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

Recent clinical trials and case-reports indicate that baclofen, a GABA_B agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol-dependent individuals in 2 placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited.

The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States.

The study was a double-blind, placebo-controlled, randomized study comparing 30 mg/d of baclofen to placebo over 12 weeks of treatment and utilizing 8 sessions of BRENDA, a low-intensity psychosocial intervention. One hundred and twenty-one subjects were screened to yield 80 randomized subjects (44 men) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined.

Seventy-six percent of subjects completed the study. No difference by drug condition was seen in percentage of heavy drinking days where on-average rates were 25.5% (±23.6%) for placebo and 25.9% (±23.2%) for baclofen during treatment (t₇₃ = 0.59, p = 0.56). Similarly, no differences were seen by drug condition in percentage of days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F_1,73 = 5.39, p = 0.02). Baclofen was well tolerated with only 2 individuals stopping baclofen because of adverse events. There were no serious adverse events.

Baclofen, a GABA_B agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is necessary to establish whether baclofen does or does not have therapeutic efficacy in alcohol dependence and, if it does, what factors are predictive of response.

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Request Reprint E-Mail: jc_garbutt@med.unc.edu

Irreversible Exocrine Pancreatic Insufficiency in Alcoholic Rats Without Chronic Pancreatitis After Alcohol Withdrawal

Long-term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism.

Forty-eight healthy male Wistar rats were divided randomly into 4 groups: 6-month control, 6-month ethanol, 9-month control, and 9-month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK-A receptors was quantitatively analyzed by Western blot.

Alcohol-induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence. The outputs of amylase and lipase, FFA content in intestinal chyme, and the intestinal and the pancreatic CCK levels in rats were reduced after chronic alcohol intake and were still lower than the control after cessation of alcohol use. Chronic ethanol intake or abstinence did not induce any change in the expression of CCK-A receptors.

Exocrine pancreatic insufficiency was irreversible in alcoholic rats without CP after alcohol withdrawal. It may be attributed to reduced pancreatic CCK, long-standing fatty infiltration, ultramicrostructure injuries in pancreatic acinar cells, and aging.

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Request Reprint E-Mail: chengweitang@163.com

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Role of Microglia in Ethanol's Apoptotic Action on Hypothalamic Neuronal Cells in Primary Cultures

Microglia are the major inflammatory cells in the central nervous system and play a role in brain injuries as well as brain diseases.

In this study, we determined the role of microglia in ethanol's apoptotic action on neuronal cells obtained from the mediobasal hypothalamus and maintained in primary cultures. We also tested the effect of cAMP, a signaling molecule critically involved in hypothalamic neuronal survival, on microglia-mediated ethanol's neurotoxic action.

Ethanol's neurotoxic action was determined on enriched fetal mediobasal hypothalamic neuronal cells with or without microglia cells or ethanol-activated microglia-conditioned media. Ethanol's apoptotic action was determined using nucleosome assay. Microglia activation was determined using OX6 histochemistry and by measuring inflammatory cytokines secretion from microglia in cultures using enzyme-linked immunosorbent assay (ELISA). An immunoneutralization study was conducted to identify the role of a cytokine involved in ethanol's apoptotic action.

We show here that ethanol at a dose range of 50 and 100 mM induces neuronal death by an apoptotic process. Ethanol's ability to induce an apoptotic death of neurons is increased by the presence of ethanol-activated microglia-conditioned media. In the presence of ethanol, microglia showed elevated secretion of various inflammatory cytokines, of which TNF-α shows significant apoptotic action on mediobasal hypothalamic neuronal cells. Ethanol's neurotoxic action was completely prevented by cAMP. The cell-signaling molecule also prevented ethanol-activated microglial production of TNF-α. Immunoneutralization of TNF-α prevented the microglia-derived media's ability to induce neuronal death.

These results suggest that ethanol's apoptotic action on hypothalamic neuronal cells might be mediated via microglia, possibly via increased production of TNF-α. Furthermore, cAMP reduces TNF-α production from microglia to prevent ethanol's neurotoxic action.

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Request Reprint E-Mail: sarkar@aesop.rutgers.edu

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Priorities for policy research on treatments for alcohol and drug use disorders

The Robert Wood Johnson Foundation's Substance Abuse Policy Research Program (SAPRP) supported 368 awards for nearly $60 million to complete policy research related to alcohol, tobacco, and illicit drug use and abuse.

As part of its closure in 2009, SAPRP commissioned four papers that articulated policy research priorities for tobacco cessation and control, alcohol prevention, drug prevention, and addiction treatment.

The papers were released at a Congressional Briefing on October 2, 2009 and are available on the SAPRP Web site (http://www.saprp.org/Research_Agenda.cfm).

An abridged version of the treatment policy paper summarizes what we know, what we need to know, and research recommendations.

The paper examines five categories of policy concerns that are likely to affect addiction treatment services over the next 5 years: (a) organization and delivery of care, (b) quality of care, (c) evidence-based practices, (d) access to care, and (e) financing, costs, and value of care.

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Request Reprint E-Mail: mccartyd@ohsu.edu

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The 10-year course of remission, abstinence, and recovery in dual diagnosis

This study examined the frequency, stability, predictors, and long-term outcomes of 6-month remissions of alcohol use disorders among 116 adults with co-occurring severe mental illnesses followed up prospectively for 10 years.

Remission was defined as 6 months without meeting syndromal criteria for alcohol abuse or dependence.

Most participants (86%) experienced at least one 6-month remission, and these remissions were relatively durable. One third did not relapse during follow-up, and two thirds relapsed on average 3 years after remission.

Six-month remissions were preceded by increased participation in substance abuse treatments, reductions in alcohol and drug use, decreases in psychiatric symptoms, increases in competitive employment, and increases in life satisfaction.

Following remissions, participants improved in multiple domains of adjustment: reductions of psychiatric symptoms, decreases in alcohol and drug use, increases in work and social contacts with nonabusers, decreases in hospitalizations and incarcerations, increases in independent living, and increases in life satisfaction.

Participants with alcohol dependence rather than alcohol abuse were less likely to attain 6-month remissions and more likely to relapse after attaining remissions.


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Request Reprint E-Mail: haiyi.xie@dartmouth.edu


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Ethnicity and alcohol: a review of the UK literature and BME workshop presentations

A literature review of evidence on drinking patterns among minority ethnic groups in the UK over the last 15 years and on service provision for this group has been produced by the Joseph Rowntree Foundation. See the the report and summary page here.

The review:

• describes drinking levels as reported in national surveys and local research;
• considers why drinking rates among ethnic groups may change over time;
• examines help-seeking, support and service provision for minority ethnic groups;
• examines how services are equipped to respond to the needs of minority ethnic groups.

BME national alcohol workshop

A national workshop event covering alcohol issues relating to Black and Minority Ethnic groups in the UK took place in Peterborough on the 6th July. See here for presentations from the event and supporting workshops. > > > >

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Increased Risk for Suicidal Behavior in Comorbid Bipolar Disorder and Alcohol Use Disorders: Results From the National Epidemiologic Survey on Alcohol

Bipolar disorder is associated with a high rate of suicide attempt, and alcohol use disorders have also been associated with elevated risk for suicidal behavior. Whether risk for suicidal behavior is elevated when these conditions are comorbid has not been addressed in epidemiologic studies.

1,643 individuals with a DSM-IV lifetime diagnosis of bipolar disorder were identified from 43,093 general-population respondents who were interviewed in the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions. Assessments were made using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule–DSM-IV Version (AUDADIS-IV). Lifetime prevalence of reported history of suicide attempt and suicidal thoughts among bipolar disorder respondents with and without DSM-IV lifetime alcohol use disorders (abuse or dependence) was assessed using χ2 and adjusted odds ratios with confidence intervals. Logistic regression was used to test the relevance of other comorbid clinical conditions to suicide risk in bipolar respondents with and without comorbid alcohol use disorders.

More than half of the respondents (54%) who met criteria for bipolar disorder also reported alcohol use disorder. Bipolar individuals with comorbid alcohol use disorder were at greater risk for suicide attempt than those individuals without alcohol use disorder (adjusted odds ratio = 2.25; 95% CI, 1.61–3.14) and were more likely to have comorbid nicotine dependence and drug use disorders. Nicotine dependence and drug use disorders did not increase risk for suicidal behavior among those with bipolar disorder, nor did they confer additional risk among bipolar respondents who also reported alcohol use disorder. Despite greater psychopathological burden, individuals with comorbid bipolar disorder and alcohol use disorder did not receive more treatment or more intensive treatment.

Suicidal behavior is more likely to occur in bipolar respondents who also suffer from alcohol use disorder. Interventions to reduce suicide risk in bipolar disorder need to address the common and high-risk comorbidity with alcohol use disorders.

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Request Reprint E-Mail: mao4@columbia.edu

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Alcohol intake and risk of colorectal cancer: Results from the UK Dietary Cohort Consortium

Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent.

We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ).

Compared with individuals in the lightest category of drinkers (>0 – 5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5 – < 15g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15 –  30g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30 – 45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with 45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results.

We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium.

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Request Reprint E-Mail: kk101@medschl.cam.ac.uk

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Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wis

Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction.

We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3–30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats.

Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected.

Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.


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Request Reprint E-Mail: markus.heilig@mail.nih.gov


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Alcohol impairment of saccadic and smooth pursuit eye movements: impact of risk factors for alcohol dependence

While persons at risk for alcohol dependence by virtue of heavy drinking patterns or family history (FH) of alcohol use disorders have exhibited differential alcohol responses on a variety of measures, few studies have examined alcohol's effects on eye movements in these subgroups.

The purpose of this study was to (1) conduct a placebo-controlled, dose-ranging study of alcohol's effects on eye movements and (2) examine the impact of these risk factors on oculomotor response to alcohol.

A within-subject, double-blind laboratory study was conducted in N = 138 heavy (HD; n = 78) and light social drinkers (LD; n = 60) with self-reported positive (FH+) or negative (FH−) family history. Subjects participated in three laboratory sessions in which they consumed a beverage containing a high (0.8 g/kg) or low (0.4 g/kg) dose of alcohol or placebo. Smooth pursuit, pro-saccadic, and anti-saccadic eye movements were recorded before and at two intervals after alcohol consumption.

Alcohol significantly impaired smooth pursuit gain and pro- and anti-saccade latency, velocity, and accuracy in a dose and time specific matter. HD and LD showed similar impairment on smooth pursuit gain and anti-saccade measures, but HD were less impaired in pro-saccade latency, velocity, and accuracy. FH+ and FH− subjects were equally impaired in nearly all pro- and anti-saccade measures, but FH+ were less impaired in smooth pursuit gain.

In sum, alcohol produced systematic impairment on oculomotor functioning, even at a non-intoxicating dose. Furthermore, high- and low-risk drinkers may be vulnerable to select performance deficits relative to eye movement task.



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Request Reprint E-Mail: aking@bsd.uchicago.edu


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Help-seeking for substance use, anxiety and affective disorders among young people: results from the 2007 Australian National Survey of Mental Health

To provide a more detailed analysis of the relationship between type and severity of mental disorders (substance use, anxiety and affective disorders) and help-seeking in those aged 16–24 years compared to those aged 25–44 and 45–85 years.

Data from the National Survey of Mental Health and Wellbeing (NSMHWB) which was conducted in 2007. The survey sample comprised residents of private dwellings across Australia aged 16–85 years.

More than one in four Australians aged 16–24 years experienced a mental disorder in the preceding 12 months. This compared to one in five in those aged 16–85 years. Fewer than one in four 16–24-year-olds with a 12-month mental disorder accessed health services in a 12-month period compared with just over one in three of those aged 16–85. The gap in help-seeking was primarily related to higher rates of substance use disorders and low help-seeking associated with these, particularly in young men.

Findings from the 2007 NSMHWB show that the gap in help-seeking in young people with mental health problems is largely due to high rates of substance use disorders and the low rates of help-seeking associated with these.

In order to address this gap there is a need for better coordination and integration of mental health and alcohol and drug services within primary care settings. Population health approaches that tackle erroneous beliefs about alcohol and related harms and improve overall mental health literacy are also needed.

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Request Reprint E-Mail: nreavley@unimelb.edu.au

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Alcohol Withdrawal and Brain Injuries: Beyond Classical Mechanisms

Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol) adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex.

In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW) provokes the intense generation of reactive oxygen species (ROS) and the activation of stress-responding protein kinases, which are the focus of this review article.

EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria.

Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17β-estradiol (E2), interferes with the EW-induced alteration of oxidative signaling pathways and thereby protects neurons, mitochondria, and behaviors.

The current review attempts to provide integrated information at the levels of oxidative signaling mechanisms by which EW provokes brain injuries and E2 protects against it. Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol) adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex.

In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW) provokes the intense generation of reactive oxygen species (ROS) and the activation of stress-responding protein kinases, which are the focus of this review article.

EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria.

Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW.

A major female sex steroid, 17β-estradiol (E2), interferes with the EW-induced alteration of oxidative signaling pathways and thereby protects neurons, mitochondria, and behaviors.

The current review attempts to provide integrated information at the levels of oxidative signaling mechanisms by which EW provokes brain injuries and E2 protects against it.


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Scotland - Alcohol sales 2005-2009

NHS Health Scotland has purchased alcohol sales data from The Nielsen Company to contribute to the monitoring and evaluation of Scotland’s alcohol strategy.

This report describes trends in per capita sales of alcohol in Scotland, England & Wales from 2005 to 2009.

It was originally published in January 2010 and is now updated to include figures for the full calendar year 2009. The accompanying dataset is also available below.


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Alcohol — the good side

As California contemplates legalizing the sale of marijuana, the real war over intoxicants in this country is, as always, over alcohol.

Since Prohibition ended in 1933 with the 21st Amendment to the Constitution — which repealed the 18th Amendment authorizing the ban on alcohol — states, counties and municipalities have see-sawed back and forth over alcohol sales. States are still passing laws on the sale of alcohol on Sundays, and municipalities and counties are still voting on whether to permit local alcohol purchases.

But as an addiction psychologist and alcohol epidemiologist, I am more interested in another debate over alcohol: whether it can be good for you. This issue arises every five years as the United States issues new dietary guidelines, including for alcohol consumption. In 1990, the Dietary Guidelines for Americans firmly declared that alcohol "has no net health benefit, is linked with many health problems, is the cause of many accidents and can lead to addiction. Their consumption is not recommended."

But in 1995, based on the results of studies identifying subjects who drank and did not drink and then following their health outcomes over time, the guidelines modestly declared — amid a sea of information about the dangers of drinking — that "alcoholic beverages have been used to enhance the enjoyment of meals by many societies throughout human history" and that "current evidence suggests that moderate drinking…is associated with a lower risk for coronary heart disease in some individuals."

> > > > > Read More

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Computational modeling study of human nicotinic acetylcholine receptor for developing new drugs in the treatment of alcoholism

Alcohol abuse and alcoholism are serious and costly problem in USA. Thus, the development of anti-alcoholism agents could be very significant.

The understanding of the neurochemical basis underlying the addictive properties of drugs of abuse is imperative for the development of new pharmacological means to reverse the addictive state, prevent relapse or to reduce the intake of addictive compounds. The nicotinic acetylcholine receptors (nAChRs) are important therapeutic targets for various diseases.

Recent studies have revealed that the α3β2, α3β3, and α6 subunits of nAChR protein family might be pharmacological targets for developing new drugs in the treatment of alcoholism.

We have performed computational homology modeling of the α3β2, α3β3, and α6 subunits of human nACHRs based upon the recently determined crystal structure of the extracellular domain (ECD) of the mouse nAChR α1 subunit complexed with α-bungarotoxin at 1.94 Å resolution.

For comparison, we also built the ECD models of α4β2, and α7 subunits of human nACHRs which are neurochemical targets for cessation of smoking. The three-dimensional (3D) models of the ECD of the monomer, and pentamer of these human nAChR were constructed.

The docking of the agonist in the ligand-binding pocket of the human nAChR dimers was also performed.

Since the nAChR ligand-binding site is a useful target for mutagenesis studies and the rational design of drugs against various diseases, these models provide useful information for future investigation.


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Request Reprint E-Mail: huzengjian@yahoo.com


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The Impact of Maternal Age on the Effects of Prenatal Alcohol Exposure on Attention

Prenatal exposure to alcohol has a variety of morphologic and neurobehavioral consequences, yet more than 10% of women continue to drink during pregnancy, placing their offspring at risk for fetal alcohol spectrum disorders (FASD). Identification of at-risk pregnancies has been difficult, in part, because the presence and severity of FASD are influenced by factors beyond the pattern of alcohol consumption.

Establishing maternal characteristics, such as maternal age, that increase the risk of FASD is critical for targeted pregnancy intervention.

We examined the moderating effect of maternal age on measures of attention in 462 children from a longitudinal cohort born to women with known alcohol consumption levels (absolute ounces of alcohol per day at conception) who were recruited during pregnancy. Analyses examined the impact of binge drinking, as average ounces of absolute alcohol per drinking day. Smoking and use of cocaine, marijuana, and opiates were also assessed. At 7 years of age, the children completed the Continuous Performance Test, and their teachers completed the Achenbach Teacher Report Form.

After controlling for covariates, stepwise multiple regression analyses revealed a negative relation between levels of prenatal binge drinking and several measures of attention. The interaction between alcohol consumption and maternal age was also significant, indicating that the impact of maternal binge drinking during pregnancy on attention was greater among children born to older drinking mothers.

These findings are consistent with previous findings that children born to older alcohol-using women have more deleterious effects of prenatal alcohol exposure on other neurobehavioral outcomes.

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Request Reprint E-Mail: lchiodo@med.wayne.edu

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Gender Differences in Alcohol Treatment: An Analysis of Outcome From the COMBINE Study

Relatively few studies have examined gender differences in the effectiveness of specific behavioral or pharmacologic treatment of alcohol dependence.

The aim of this study is to assess whether there were gender differences in treatment outcomes for specific behavioral and medication treatments singly or in combination by conducting a secondary analysis of public access data from the national, multisite NIAAA-sponsored COMBINE study.

The COMBINE study investigated alcohol treatment among 8 groups of patients (378 women, 848 men) who received medical management (MM) with 16 weeks of placebo, naltrexone (100 mg/day), acamprosate (3 g/day), or their combination with or without a specialist-delivered combined behavioral intervention. We examined efficacy measures separately for men and women, followed by an overall analysis that included gender and its interaction with treatment condition in the analyses. These analyses were performed to confirm whether the findings reported in the parent trial were also relevant to women, and to more closely examine secondary outcome variables that were not analyzed previously for gender effects.

Compared to men, women reported a later age of onset of alcohol dependence by approximately 3 years, were significantly less likely to have had previous alcohol treatment, and drank fewer drinks per drinking day. Otherwise, there were no baseline gender differences in drinking measures. Outcome analyses of 2 primary (percent days abstinent and time to first heavy drinking day) and 2 secondary (good clinical response and percent heavy drinking days) drinking measures yielded the same overall pattern in each gender as that observed in the parent COMBINE study report. That is, only the naltrexone by behavioral intervention interaction reached or approached significance in women as well as in men. There was a naltrexone main effect that was significant in both men and women in reduction in alcohol craving scores with naltrexone-treated subjects reporting lower craving than placebo-treated subjects.

This gender-focused analysis found that alcohol-dependent women responded to naltrexone with COMBINE's Medical Management, similar to the alcohol-dependent men, on a wide range of outcome measures. These results suggest that clinicians can feel comfortable prescribing naltrexone for alcohol dependence in both men and women. In this study, it is also notable that fewer women than men reported receiving any alcohol treatment prior to entry into the COMBINE study. Of note, women tend to go to primary health care more frequently than to specialty substance abuse programs for treatment, and so the benefit we confirm for women of the naltrexone and MM combination has practical implications for treating alcohol-dependent women.

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Request Reprint E-Mail: sgreenfield@mclean.harvard.edu


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Sociodemographic Predictors of Pattern and Volume of Alcohol Consumption Across Hispanics, Blacks, and Whites: 10-Year Trend (1992–2002)

There have been limited trend studies examining variations on the patterns of alcohol consumption among Whites, Blacks, and Hispanics in the United States. The current paper reports national trends in drinking patterns, volume of drinking (number of drinks per month), binge drinking, and drinking to intoxication among Blacks, Whites, and Hispanics over a period of 10 years and identifies sociodemographic predictors of these behaviors across the 3 ethnic groups.

Data are from the 1991 to 1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES; n = 42,862) and the 2001 to 2002 National Epidemiologic Study on Alcohol and Related Conditions (NESARC; n = 43,093). Both surveys used multistage cluster sample procedures to select respondents 18 years of age and older from the U.S. household population.

Trends varied across different dimensions of drinking and ethnic groups. There were no statistically significant differences in the mean number of drinks consumed per month among men and women in any of the 3 ethnic groups between 1992 and 2002, but there was a significant rise in the proportion of current drinkers in both genders and in all 3 ethnic groups. Multivariate analysis indicated that, compared to Whites in 1992, Blacks and Hispanics did not increase their volume of drinking, but Whites did. Drinking 5 or more drinks in day at all did not increase between 1992 and 2002, but drinking 5 or more drinks at least once a month was more likely for all groups in 2002 compared to Whites in 1992. Drinking to intoxication at all was more likely among Whites in 2002 than 1992, but drinking to intoxication at least once a month was more likely among Whites and Blacks in 2002 than 1992.

The only common trend between 1992 and 2002 across both genders and 3 ethnic groups was a rise in the proportion of drinkers. There was also a rise in drinking 5 or more drinks in a day (Whites, Blacks, and Hispanics) and drinking to intoxication (Whites and Blacks), but this was limited to those reporting such drinking at least once a month. The reasons for these changes are many and may involve complex sociodemographic changes in the population. It is important for the field to closely monitor these cross-ethnic trends in alcohol consumption.

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Request Reprint E-Mail: raul.caetano@utsouthwestern.edu

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Gender-Related Influences of Parental Alcoholism on the Prevalence of Psychiatric Illnesses: Analysis of the National Epidemiologic Survey on Alcohol

Offspring of individuals with alcoholism are at increased risk for psychiatric illness, but the effects of gender on this risk are not well known. In this study, we tested the hypothesis that the gender of the parent with alcoholism and the gender of offspring affect the association between parental alcoholism and offspring psychiatric illness.

We analyzed the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) data to examine the gender-specific prevalence of axis I and axis II disorders in 23,006 male and 17,368 female respondents with and without a history of paternal or maternal alcoholism. Adjusted odds ratios were calculated for the disorders based on gender and presence of maternal or paternal alcoholism.

Maternal or paternal alcoholism was associated with a higher prevalence of every disorder examined, regardless of the gender of offspring. Gender-related differences in prevalences were present in nearly all examined disorders, and the association between parental alcoholism and offspring psychiatric disorders was significantly different in men and women. These differences included stronger associations in female offspring of men with alcoholism (alcohol abuse without dependence); in female offspring of women with alcoholism (mania, nicotine dependence, alcohol abuse, and schizoid personality disorder); in male offspring of men with alcoholism (mania); and in male offspring of women with alcoholism (panic disorder).

Interactions between gender and parental alcoholism were specific to certain disorders but varied in their effects, and in general female children of women with alcoholism appear at greatest risk for adult psychopathology.

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Request Reprint E-Mail: peter.morgan@yale.edu

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Weekly newsletter of Alcohol News and Articles around the world

Tuesday, July 20, 2010

• New Study Links Alcohol Consumption And Stroke
  

• Alcohol-induced abuse of children is rife, says bishop

• Probe sought into alcohol-energy drinks marketing

• Campaign against drugs, liquor billed a big success

• Moonshine 'tempts new generation'

• Buzz from kombucha health drink is probably the alcohol, say US inspectors

• NSW police seeks more alcohol-free zones in Sydney residential areas

• Binge drinking in teenage years causes osteoporosis and fractures in old age

• 4th European Alcohol Policy Conference : "From capacity to action"

• How Australia decided there is no good to drinking

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Update on Alcoholism

From the 2009 Annual Scientific Meeting of the American Psychiatric Association

Marc A. Schuckit, MD, Distinguished Professor of Psychiatry, University of California, San Diego, School of Medicine

The goal of this program is to improve preventive intervention for alcoholism through the investigation of genetic and envi­ronmental influences on its development. After hearing and assimilating this program, the clinician will be better able to:

1. Discuss the differential risk of developing alcoholism in children of alcoholics vs children of non-alcoholics.

2. Cite current theories on the effect of genetics on alcohol use and dependence.

3. Explain the differences in response to alcohol between people of Asian ancestry and those of other ethnicities.

4. Discuss how level of response to alcohol predicts alcohol outcome.

5. Recognize the role of environment in alcohol outcome.

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Incorporation of covariates in simultaneous localization of two linked loci using affected relative pairs.

Many dichotomous traits for complex diseases are often involved more than one locus and/or associated with quantitative biomarkers or environmental factors. Incorporating these quantitative variables into linkage analysis as well as localizing two linked disease loci simultaneously could therefore improve the efficiency in mapping genes.

We extended the robust multipoint Identity-by-Descent (IBD) approach with incorporation of covariates developed previously to simultaneously estimate two linked loci using different types of affected relative pairs (ARPs).

We showed that the efficiency was enhanced by incorporating a quantitative covariate parametrically or non-parametrically while localizing two disease loci using ARPs. In addition to its help in identifying factors associated with the disease and in improving the efficiency in estimating disease loci, this extension also allows investigators to account for heterogeneity in risk-ratios for different ARPs.

Data released from the collaborative study on the genetics of alcoholism (COGA) for Genetic Analysis Workshop 14 (GAW 14) were used to illustrate the application of this extended method.

The simulation studies and example illustrated that the efficiency in estimating disease loci was demonstratively enhanced by incorporating a quantitative covariate and by using all relative pairs while mapping two linked loci simultaneously.

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Caregiver Burden and Alcohol Use in a Community Sample

Little attention has been paid to the relationship between caregiver burden and alcohol use. It is important to examine the particular aspects of caregiver burden that most influence alcohol use.

A mail survey was conducted using a representative sample of 998 employed Chicago residents who provided informal care for at least one person. Ordinary least squares regression models were computed to examine the relationship between caregiver burden and drinking outcomes.

Findings suggest that caregivers who experience social and emotional burdens related to caregiving are at risk for problematic alcohol use and warrant attention from health care and mental health service professionals.

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Request Reprint E-Mail: Krospenda@psych.uic.edu


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Determinants and relationship of homocysteinemia with cardiometabolic risk factors. A Study in Benin, West Africa

Elevated circulating homocystein (Hcy) is considered as an independent cadiovascular disease risk factor. Hyperhomocysteinaemia (HHcy) is influenced by nutritional, genetic, and environmental factors.

The purpose of the study was to assess HHcy prevalence in Benin, its association with intakes of B-vitamins (B2, B6, B9, B12), alcohol intake, and socio-economic status (SES), and its links with other factors of cardio-metabolic risk.

The cross-sectional study included 541 apparently healthy subjects, aged 25 to 65 years, from three sites: the main city, a small city and a rural area. Hcy was measured with an ELISA test kit. The HHcy cut-off was 12 μmol/L. Dietary intake was assessed with three 24-hour recalls. We used a structured questionnaire to assess alcohol consumption, demographics, and SES according to education and an amenity score as income proxy. Criteria for obesity, hypertension, dyslipidemia and hyperglycemia were primarily those of World Health Organization (WHO) and the International Diabetes Federation.

Mean age was 38.1 ± 10.1 years. The prevalence of HHcy was 52.2% in men and 24.7% in women. In multiple linear regression models, Hcy in men was positively associated with alcohol intake, but only alcohol in beer. In women, Hcy was negatively related to vitamin B12 intake. According to multivariate models of cardio-metabolic risk factors, HHcy was associated in women with more than twice the odds of hypertension and with high TC/HDL-c ratio. In men, Hcy was positively and independently associated with diastolic blood pressure and with LDL-cholesterol and total cholesterol in linear regression models.

The prevalence of HHcy is high in Benin, when compared with other studies, and it was as expected higher in men than in women. Elevated Hcy was associated with inadequate intake of vitamin B12 in women, whereas alcohol consumption and its negative correlation with B12 intake was also involved in men. Although HHcy was independently associated with hypertension (in women) and more adverse cholesterol profile, no inference can be made because of the cross-sectional design of the study.

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Request Reprint E-Mail: helene.delisle@umontreal.ca

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Featured Vacancy: Director, Division of Treatment and Recovery Research (DTRR)

The National Institute on Alcohol Abuse and Alcoholism (NIAAA), a major research component of the National Institutes of Health (NIH) and the Department of Health and Human Services (HHS), is recruiting for a senior executive to serve as the Director of the Division of Treatment and Recovery Research (DTRR).

The Director, DTRR, provides national leadership for research on the treatment of alcohol use disorders, including setting scientific priorities through the development of long-term strategic plans and execution of funding decisions. In this capacity, the Director, DTRR, leads the Division’s efforts on planning, stimulating, developing, and supporting clinical research on cutting-edge therapies for alcoholism. Clinical research at the NIAAA encompasses medications development, behavioral therapies, combined medications and behavioral therapies, recovery research, health services research, and the translation of research into clinical practice. Medications development is one of the NIAAA’s top research priorities. The Director, DTRR, oversees the NIAAA’s work on the full continuum of research included under medications development—from human laboratory studies to clinical trials, which requires close collaboration with internal and external scientists and researchers with other Federal State and Local government agencies, and national and international research organizations. The Director, DTRR, serves as the principal advisor to the Director, NIAAA on alcohol treatment and recovery issues and advises the National Advisory Council on pending grant applications and the status of programs in the federal and private sector.

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Selling addictions

The purpose of this research was to identify, through alcohol industry documents, similarities between tobacco and alcohol companies in approaches to evidence and counter-arguments to public health measures.

A search of the tobacco document archives through the World Wide Web for alcohol industry documents was conducted. Alcohol-related search terms were entered into search fields of the tobacco document archives.

The documents show that alcohol and tobacco companies have worked closely together, have shared information, share similar concerns and have used similar arguments to defend their products and prevent or delay restrictions being placed on their products.

This paper provides evidence that alcohol and tobacco companies are similar in a number of ways and there is scope to use these similarities in developing more effective public health approaches to addressing alcohol consumption and related harms.

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Podcast -- The Truth About Addiction and Recovery

Host Name: Monda Williams
Show Name:	Dr. Stanton Peele- The Truth About Addiction and Recovery

Date / Length:

7/16/2010 8:00 PM - 1 hr 5 min

Stanton Peele is a psychologist who has changed the addiction field. He has pioneered, among other things, the idea that addiction occurs with a range of experiences, and the “harm reduction” approach to addiction; investigating, thinking, and writing about addiction since 1969. His first bombshell book, Love and Addiction, appeared in 1975. Its experiential and environmental approach to addiction revolutionized thinking on the subject by indicating that addiction is not limited to narcotics, or to drugs at all, and that addiction is a pattern of behavior and experience which is best understood by examining an individual's relationship with his/her world. This is a distinctly nonmedical approach. It views addiction as a general pattern of behavior that nearly everyone experiences in varying degrees at one time or another. Viewed in this context, addiction is not unusual, although it can grow to overwhelming and life-defeating dimensions. It is not essentially a medical problem

, but a problem of life.









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