Magnetic Resonance-Based Imaging in Animal Models of Fetal Alcohol Spectrum Disorder

Magnetic resonance imaging (MRI) techniques, such as magnetic resonance microscopy (MRM), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS), have recently been applied to the study of both normal and abnormal structure and neurochemistry in small animals. 

Herein, findings from studies in which these methods have been used for the examination of animal models of Fetal Alcohol Spectrum Disorder (FASD) are discussed. 

Emphasis is placed on results of imaging studies in fetal and postnatal mice that have highlighted the developmental stage dependency of prenatal ethanol exposure-induced CNS defects. 

Consideration is also given to the promise of methodological advances to allow in vivo studies of aberrant brain and behavior relationships in model animals and to the translational nature of this work. 

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

What Does Diffusion Tensor Imaging Reveal About the Brain and Cognition in Fetal Alcohol Spectrum Disorders?

Over the past 5 years, Diffusion Tensor Imaging (DTI) has begun to provide new evidence about the effects of prenatal alcohol exposure on white matter development. DTI, which examines microstructural tissue integrity, is sensitive to more subtle white matter abnormalities than traditional volumetric MRI methods. 

Thus far, the available DTI data suggest that white matter microstructural abnormalities fall on a continuum of severity in Fetal Alcohol Spectrum Disorder (FASD).

Abnormalities are prominent in the corpus callosum, but also evident in major anterior-posterior fiber bundles, corticospinal tracts, and cerebellum. These subtle abnormalities are correlated with neurocognitive deficits, especially in processing speed, non-verbal ability, and executive functioning. 

Future studies using larger samples, increasingly sophisticated DTI methods, and additional functional MRI connectivity measures will better characterize the full range of abnormalities in FASD. 

Ultimately, these measures may serve as indices of change in future longitudinal studies and in studies of interventions for FASD. 

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Request Reprint E-Mail:   jwozniak@umn.edu

Imaging the Impact of Prenatal Alcohol Exposure on the Structure of the Developing Human Brain

Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. 

We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. 

The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. 

More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. 

Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions. 

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Insights Into the Development of Alcoholic Chronic Pancreatitis at Soweto, South Africa: A Controlled Cross-Sectional Study

We asked why so few working-class Africans of Soweto have chronic pancreatitis (CP) when alcoholism is the norm.

Twenty-one alcoholics with acute psychosis but normal pancreas were investigated for lifestyle, micronutrient status, electrophilic stress, and iron overload.

Alcoholics consumed more ethanol daily than did 14 previously studied patients with CP (P = 0.003); cigarette usage was similar; both groups had even poorer vitamin C status than 14 healthy controls, and no participant had iron overload. The CP group had higher scores for exposure to occupational xenobiotics than did alcoholics (P < 0.05), with lower plasma glutathione (P = 0.047) and urinary inorganic sulfate (P = 0.009). Further analysis identified hyperhomocysteinemia in the alcoholic set, with lower vitamin B₁₂ (P < 0.001), higher folic acid (P = 0.003), and similar vitamin B₆ levels compared with controls.

The transition from alcoholism to CP in Soweto is associated with occupational exposure to xenobiotics. Among detoxification systems that are strained thereby, glutathione and inorganic sulfate depend on methionine intake, which is ample in Sowetans, whereas vitamin C, which exerts a glutathione-sparing effect, is deficient. Hence, a daily tablet of vitamin C may enable community prophylaxis against the disease-but homocysteine status would need monitoring.

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Request Reprint E-Mail:  aidd@netdial.co.za 

Tobacco and Alcohol: Learning From Each Other International Conference

12th and 13th October 2011
Parc Thistle Hotel, Cardiff, Wales

Cigarette smoking is highly prevalent among people with alcohol use disorders. People who are dependent on alcohol are three times more likely than those in the general population to be smokers, and people who are dependent on tobacco are four times more likely than the general population to be dependent on alcohol. Alcohol use problems are associated with higher levels of nicotine dependence and a lower likelihood -of smoking cessation.
 
The link between alcohol and tobacco has important implications for those in the alcohol and smoking cessation treatment and policy fields. More alcoholics die of tobacco-related illness than die of alcohol-related problems.
Although the health threats of smoking are clear, many unanswered questions remain about how to best approach smoking cessation in alcohol dependent populations. Effective treatment hinges on a better understanding of how these substances—and their addictions—interact.
 
The conference will enable alcohol and tobacco treatment providers and policy makers the opportunity to learn from each other. In addition to co-use issues, the conference will offer alcohol and tobacco specific sessions for practitioners.
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Substance Use Comorbidity among Veterans with Posttraumatic Stress Disorder and Other Psychiatric Illness

There is considerable concern about the emergence of significant substance abuse among younger veterans of war in the Middle East, especially among those with Posttraumatic Stress Disorder (PTSD), but little information exists on the magnitude of this problem. 

Using national administrative data from the Department of Veterans Affairs (VA) (n = 1,001,996), we examined rates of diagnosed substance use disorders in Veterans who served in Iraq and Afghanistan diagnosed with PTSD compared to other psychiatric disorders; and compared rates among veterans of other service eras. 

Of VA patients with a selected mental disorder, 21.0% had a comorbid substance diagnosis. Veterans who served in the post-Vietnam era (VET) (1973–1991) had the highest rates of comorbidity. 

Logistic regression models indicated that veterans with each selected psychiatric diagnosis were significantly more likely to be dually diagnosed in comparison to veterans with PTSD; post-Vietnam veterans were significantly more likely to be dually diagnosed than veterans from other eras. 

Bipolar disorder and schizophrenia are most strongly associated with dual diagnosis in OEF/OIF (Operation Enduring Freedom/Operation Iraqi Freedom) veterans. 

There are high rates of substance use disorders among veterans with mental illness. The highest rates of comorbidity occur among those with bipolar disorder and schizophrenia; and in post-VET veterans.


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Request Reprint E-Mail:    ismene.petrakis@yale.edu 

Outcomes of Patients with Alcohol Use Disorders Experiencing Healthcare-Associated Infections

Healthcare-associated infections (HAI) affect 1.7 million patients annually in the United States, and patients with alcohol use disorders (AUD) are at increased risk of developing HAI. HAI have been shown to substantially increase the hospital length of stay, mortality, and cost. In a cohort of patients with HAI, we sought to determine mortality, cost, and hospital length of stay attributable to AUD.

Using the Nationwide Inpatient Sample for the year 2007, the largest all-payer database of hospitalized patients comprising approximately 1,000 hospitals, we performed a retrospective cohort study of all patients who developed healthcare-associated pneumonia or sepsis. We excluded patients who were transferred from another healthcare facility, who were diagnosed with community-acquired infections, immunosuppression, or cancer. Logistic regression was computed to calculate attributable mortality. Linear regression analyses were computed to determine cost and hospital length of stay α = 10⁻¹⁰.

A total of 149,892 patients developed HAI, and 8,830 (5.9%) had a codiagnosis of AUD. Patients with AUD were younger, more likely to be men, less likely to be Asian, and more likely to be Hispanic. Patients with AUD were more likely to have tobacco dependence, less likely to be electively admitted to the hospital, and less likely to undergo surgery. They also had lower severity of illness, lower income, and were more likely to be in academic medical centers. 

Logistic regression revealed that AUD was an independent predictor of increased mortality: Odds ratio = 1.71, 95% confidence interval (CI) [1.626; 1.799], p < 10⁻¹⁰. Linear regression demonstrated that AUD independently predicted increased hospital length of stay by 2 days: Patients with AUD had a length of stay of 13 days, 95% CI [12.4; 13.6] compared with 11 days, 95% CI [11.1; 11.4] for patients without AUD, p < 10⁻¹⁰. Linear regression also revealed that patients with AUD had a higher hospital cost: $34,826, 95% CI [32,415.71; 37,416.52] for patients with AUD compared with $27,167, 95% CI [25,703.18; 28,714.05] for patients without AUD, p < 10⁻¹⁰.

Patients with AUD who experience HAI have worse outcomes compared with patients without AUD. Patients with AUD have higher mortality, longer hospital length of stay, and higher costs. Studies aimed at decreasing the morbidity and mortality of HAI in patients with AUD are warranted.


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Request Reprint E-Mail:  mdewit@mcvh-vcu.edu 

The Contribution of Parental Alcohol Use Disorders and Other Psychiatric Illness to the Risk of Alcohol Use Disorders in the Offspring

Few population-based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD).

Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status.

Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members.

Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.



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Request Reprint E-Mail:   elme@sund.ku.dk  

Effects of Energy Drinks Mixed with Alcohol on Behavioral Control: Risks for College Students Consuming Trendy Cocktails

There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmED) in young people. AmED have been implicated in risky drinking practices and greater accidents and injuries have been associated with their consumption. Despite the increased popularity of these beverages (e.g., Red Bull and vodka), there is little laboratory research examining how the effects of AmED differ from alcohol alone. This experiment was designed to investigate if the consumption of AmED alters neurocognitive and subjective measures of intoxication compared with the consumption of alcohol alone.

Participants (n = 56) attended 1 session where they were randomly assigned to receive one of 4 doses (0.65 g/kg alcohol, 3.57 ml/kg energy drink, AmED, or a placebo beverage). Performance on a cued go/no-go task was used to measure the response of inhibitory and activational mechanisms of behavioral control following dose administration. Subjective ratings of stimulation, sedation, impairment, and level of intoxication were recorded.

Alcohol alone impaired both inhibitory and activational mechanisms of behavioral control, as evidenced by increased inhibitory failures and increased response times compared to baseline performance. Coadministration of the energy drink with alcohol counteracted some of the alcohol-induced impairment of response activation, but not response inhibition. For subjective effects, alcohol increased ratings of stimulation, feeling the drink, liking the drink, impairment, and level of intoxication, and alcohol decreased the rating of ability to drive. Coadministration of the energy drink with alcohol increased self-reported stimulation, but resulted in similar ratings of the other subjective effects as when alcohol was administered alone.

An energy drink appears to alter some of the objective and subjective impairing effects of alcohol, but not others. Thus, AmED may contribute to a high-risk scenario for the drinker. The mix of impaired behavioral inhibition and enhanced stimulation is a combination that may make AmED consumption riskier than alcohol consumption alone.


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Request Reprint E-Mail:   marczinskc1@nku.edu 

Neural and Behavioral Mechanisms of Impulsive Choice in Alcohol Use Disorder

Alcohol dependence has repeatedly been associated with impulsive choice, or the inability to choose large delayed rewards over smaller, but more immediate rewards. However, the neural basis of impulsive choice in alcohol use disorders (AUDs) is not well understood.

One hundred fifty-one individuals with a range of alcohol use from social drinking to severe alcohol dependence completed a delay discounting task while undergoing functional magnetic resonance imaging. Participants received customized trials designed to ensure an approximately equivalent number of immediate responses.

Delaying gratification recruited regions involved in cognitive control, conflict monitoring, and the interpretation of somatic states. Individuals with more severe alcohol use problems showed increased discounting of delayed rewards and greater activation in several regions including supplementary motor area, insula/orbitofrontal cortex, inferior frontal gyrus, and the precuneus.

These results suggest that impulsive choice in alcohol dependence is the result of functional anomolies in widely distributed, but interconnected brain regions involved in cognitive and emotional control. Furthermore, our results suggest that the neural mechanisms of impulsive choice in AUD both overlaps with that observed in previous studies, and shows that individuals with AUD recruit additional mechanisms when making intertemporal choices.



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Request Reprint E-Mail:   eclaus@mrn.org

Persistent Next-Day Effects of Excessive Alcohol Consumption on Laparoscopic Surgical Performance

To examine the effect of previous-day excessive alcohol consumption on laparoscopic surgical performance.

Study 1 was a randomized controlled trial. Study 2 was a cohort study.

Sixteen science students (laparoscopic novices) participated in study 1. Eight laparoscopic experts participated in study 2.

  

All participants were trained on the Minimally Invasive Surgical Trainer Virtual Reality (MIST-VR). The participants in study 1 were randomized to either abstain from alcohol or consume alcohol until intoxicated. All study 2 subjects freely consumed alcohol until intoxicated. Subjects were assessed the following day at 9 AM, 1 PM, and 4 PM on MIST-VR tasks.

Assessment measures included time, economy of diathermy use, and error scores.

In study 1, both groups performed similarly at baseline, but the alcohol group showed deterioration on all performance measures after alcohol consumption. Overall, although the time score differences between the 2 groups were not statistically significant (P = .29), there was a significant difference between the 2 groups' diathermy (P < .03) and error (P < .003) scores. There was also a significant effect for time of testing (P < .003), diathermy (P < .001), and errors (P < .001). In study 2, experts demonstrated a similar postalcohol performance decrement for time (P < .02), diathermy (P < .001), and error scores (P < .001).

Excessive consumption of alcohol appeared to degrade surgical performance the following day even at 4 PM, suggesting the need to define recommendations regarding alcohol consumption the night before assuming clinical surgical responsibilities.

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^{Request Reprint E-Mail:   aggallagher@comcast.net.}  

Mechanisms of Neurodegeneration and Regeneration in Alcoholism

This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies

The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration. 

Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain.
 
Degeneration is associated with increased NF-κB proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-κB transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. 

Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans. 

Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. 

Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans.


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Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: Effects on cell cycle kinetics

Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. 

Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. 

Cell cycle distribution was measured using a combination of markers (Ki-67, bromo-deoxy-uridine incorporation, and phospho-histone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromo-deoxy-uridine injection protocol to determine the effect of alcohol on cell cycle length and S-phase duration. 

Binge alcohol exposure reduced the proportion of NPCs in S-phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S-phase of the cell cycle. 

Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S-phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle. 

This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox-2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure. 

These studies suggest the mechanism of alcohol inhibition of neurogenesis but also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure.


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Request Reprint E-Mail:  kim-nixon@uky.edu  

Clinical and pathological features of alcohol-related brain damage

One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B₁) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). 

When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. 

Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. 

Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. 

This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. 

An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD.



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Request Reprint E-Mail:   clive.harper@sydney.edu.au 

Prevalence and Predictors of Carotid Wall Triple Line Pattern in a General Population Sample

Carotid intima-media thickness (IMT) and plaques are markers of atherosclerosis and predict cardiovascular events. A specific triple line pattern (TLP) in the sonograph of the carotid wall has been identified in different conditions, but its origin and clinical significance are unclear. 

We examined the prevalence and predictors of TLP in a general population.

The study was conducted in random sample of the general population of Novosibirsk, Russia, within the international Health, Alcohol and Psychosocial Factors in Eastern Europe project. 

In a subsample of 418 men (aged 45 to 69), carotid IMT, the presence of atherosclerotic plaques, and the presence of TLP were assessed by ultrasound.  

The prevalence of TLP was 21%. It was associated with IMT (odds ratio=9.53 per 1 SD, P<0.001) and the presence of plaques (odds ratio=2.42, P=0.002). Other predictors of TLP in multivariate models included age, systolic blood pressure, total cholesterol, and smoking.

In addition, infrequent consumption of high amounts of alcohol approximately doubled the risk of triple pattern.

Our findings showed high prevalence of TLP of carotid wall in a general male population sample from a typical Russian city. This sonographic pattern was strongly associated with cardiovascular risk factors and diseases, bioimaging indicators of atherosclerosis, and episodic heavy drinking.



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Request Reprint E-Mail: andrew_ryabikov@mail.ru   

Can Ireland's Increased Rates of Alcoholic Liver Disease Morbidity and Mortality be Explained by Per Capita Alcohol Consumption?

Analysis of data from Ireland's Hospital In-Patient Enquiry (HIPE) scheme has revealed a considerable increase in alcohol liver disease (ALD) morbidity and mortality between 1995 and 2007. The rate/100,000 adults (aged ≥15) increased by 190% from 28.3 in 1995 to 82.2 in 2007. 

Over two-fifths (43%) of all discharges were aged 50–64 years; 6% were 15–34 years old, 35% were 35–49 years old and 16% were aged ≥65 years. There were considerable increases in age-specific rates especially among younger age groups, albeit from a low base; the rate of ALD discharges increased by 247% for 15–34 year olds and by 224% for 35–49 year olds. This is a worrying trend but is not surprising as survey data have shown that 18–29-year-old drinkers have the highest …

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Request Reprint E-Mail:  dmongan@hrb.ie  

Alcohol News - 16/2011

The Nordic Page (Norway) - Youth Want Alcohol Limit

Young people would actually like parents to set limits for alcohol consumption. This comes from a new survey done for the Health Directorate.

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Drugs.com (Denmark) - Alcoholic Parents May Predispose Kids to Drinking Problem

Children of parents with an alcohol use disorder (AUD) are at increased risk for the same type of problem, says a new study from Denmark.

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TIME - A Bad Mix: Why Alcohol and Energy Drinks Are Dangerous

Mixing alcohol with other substances is never really a good idea, and pairing it with energy drinks may be especially hazardous.

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BusinessWeek - Problem Drinking May Make Hospital Infections More Deadly

Hospital patients with alcohol use disorders who develop health care-associated infections are more likely to die from the infections, have longer hospital stays and higher hospital costs than those without alcohol disorders, a new study finds.

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Daily News & Analysis - Certain Genes Could Add to Alcoholism Risk

People with certain variations in a gene called GABRA2 have an increased risk for alcoholism, a new study has found.

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EurekAlert - Researchers link alcohol-dependence impulsivity to brain anomalies

Researchers already know that alcohol dependence (AD) is strongly associated with impaired impulse control or, more precisely, the inability to choose large, delayed rewards rather than smaller but more immediate rewards. Findings from a study using functional magnetic resonance imaging (fMRI) to investigate the neural basis of impulsive choice among individuals with alcohol use disorders (AUDs) suggest that impulsive choice in AD may be the result of functional anomalies in widely distributed but interconnected brain regions that are involved in cognitive and emotional control.

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ThirdAge (Russia) - Alcohol Deaths in Russia Rise After Program Abandoned, Study Finds

Alcohol deaths in Russia increased when the anti-alcohol campaign started in 1985 was abandoned in 1988, which U.S. researchers say accounts for almost half the mortality rate from 1990 to 1994.

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ABC Online (Australia) - Doctors attack Government over alcohol policies

Some of the Northern Territory's most senior doctors have attacked the NT Government over the way it is dealing with alcohol problems.

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International Federation of Gynecology and Obstetrics - Premature birth risk 'linked to drinking during pregnancy'

Women who drink alcohol during pregnancy are more likely to give birth prematurely or have a miscarriage, a new study has revealed.

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AngolaPress (Angola) - Youth Ministry warns on alcohol use

The Angola Ministry of Youth and Sports will promote at the end of the current month throughout the country, an awareness campaign on the use and abuse of alcohol and drugs.

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Park Rapids Enterprise (USA) - An Issue of Influence: Alcohol, drugs can lead to domestic abuse

Native American elders teach that children are gifts from the Creator and it is the family, community, school, and tribe’s responsibility to nurture, protect and guide them.

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Medscape - Gastric Cancer Linked to Gene Variant, Heavy Beer Drinking

A genetic variant might predispose heavy beer drinkers to a higher risk for gastric cancer, according to the results of a new study.

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New York Times (Russia) - Moscow’s Drinking Problem

IN an effort to reduce both its sky-high alcoholism rate and its budget gap, Russia recently announced plans to quadruple the tax on the country’s eternal vice, vodka, over the next three years.

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Royal Gazette (Bermuda) - Alcohol is a $100m 'un-policed' industry: CADA

Alcohol is a $100 million dollar industry “largely un-policed” in Bermuda, according to the anti-drinking and driving organisation CADA.

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The Guardian (UK) - White cider is becoming like heroin among alcoholics, says report

Super-strength ciders are becoming popular among heavy drinkers as tax breaks to protect the industry make them a cheaper fix.

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Morning Advertiser (EU) - Serve Legal to address Euro conference on underage drinking

Test purchasing company Serve Legal is to address a major European conference on tackling underage drinking today.

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NEWS.com.au (Australia) - Four million drink to get drunk: study

MORE than four million Australians say they drink alcohol with the aim of getting drunk, a new study has found. And about half of those people try to get drunk at least once a week.

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A human laboratory study of the effects of quetiapine on subjective intoxication and alcohol craving

The available treatments for alcoholism are only modestly effective, and patients vary widely in their treatment response. Quetiapine, an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT_1A and 5-HT_2A, H₁, and α1 and α2 receptors was shown to promote abstinence, reduce drinking days, and reduce heavy drinking days in a 12-week double-blind placebo-controlled trial.

 

Although quetiapine represents one of the promising pharmacotherapies for the treatment of alcoholism, its mechanisms of action are poorly understood. The objective of this study is to elucidate the biobehavioral mechanisms of action of quetiapine for alcoholism, by examining its effects on subjective intoxication and craving.

 

A total of 20 non-treatment-seeking alcohol-dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants were on the target medication dose (or matched placebo) for 4 weeks during which they completed weekly assessments of drinking, sleep, mood, and anxiety. Participants completed two counterbalanced intravenous placebo-alcohol administration sessions as well as cue-reactivity assessments.

 

Analyses revealed a significant effect of quetiapine in reducing craving during the alcohol administration, the alcohol cue-exposure, and the weekly reports of alcohol craving. Quetiapine was also found to reduce subjective intoxication and alcohol-induced sedation during the alcohol administration paradigm.

 

This study contributes critical new information about mechanisms of response to quetiapine for alcoholism, which, in turn, can inform larger-scale studies and ultimately, clinical practice. 

 

 

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Request Reprint E-Mail:  lararay@psych.ucla.edu 

Validation of the French Version of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)

The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was developed to detect substance use disorders.  

The objective of the present study was to evaluate the psychometric properties of the French version of ASSIST in various clinical groups with different levels of substance use.  

150 subjects were recruited from clients attending primary health care, psychiatric and addiction treatment facilities. Measures included ASSIST, Addiction Severity Index (ASI), Mini-International Neuropsychiatric Interview (MINI-Plus), Alcohol Use Disorders Identification Test (AUDIT) and Revised Fagerstrom Tolerance Questionnaire-Smoking (RTQ). 


Concurrent validity was demonstrated by significant correlations between ASSIST scores and scores from ASI, AUDIT and RTQ, as well as significantly greater ASSIST scores for patients with a MINI-Plus diagnosis of abuse or dependence. The ASSIST questionnaire was found to have high internal consistency for the total substance involvement as well as for specific substance involvement as assessed with Cronbach’s α, ranging from 0.74 to 0.93. When possibly computed, ASSIST cutoff scores have interesting sensitivity and specificity for discrimination between use and abuse and between abuse and dependence. 

The findings demonstrated that the French version of ASSIST is a valid screening test for identifying substance use disorders in various health care settings, including psychiatric settings.

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Request Reprint E-Mail: riaz.khan@hcuge.ch   

Handedness and drinking behaviour

A number of papers have investigated whether there is an association between handedness and alcohol consumption hypothesizing that alcoholism may be a consequence of atypical cerebral lateralization or a response to the stress involved in being a minority in a right-handed world. Research to date has mostly used small clinical samples, some without a comparison group.
 
This paper exams this issue using a large population-based random sample.

A large multi-country data set of nationally representative samples of the non-institutional population aged 50 years and older from 12 European countries was used (N= 27,428).

Logistic regression was used to model the frequency with which individuals self-report the frequency of alcohol consumption. A series of models with differing numbers of potential confounders are estimated. The predictors of frequent and infrequent drinking are investigated separately.

After controlling for a number of confounders it is shown that left-handers do drink more often. However, this is due to them being less likely to drink rarely (less than once a month) or not at all.

The evidence suggests that while there is an association between left-handedness and frequency of alcohol consumption there is no reason to believe that it is associated with excessive alcohol consumption or risky drinking.



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Request Reprint E-Mail:   kevin.denny@ucd.ie 

Genetic Analysis of the Neurosteroid Deoxycorticosterone and Its Relation to Alcohol Phenotypes: Identification of QTLs and Downstream Gene Regulation

Deoxycorticosterone (DOC) is an endogenous neurosteroid found in brain and serum, precursor of the GABAergic neuroactive steroid (3α,5α)-3,21-dihydroxypregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) and the glucocorticoid corticosterone. These steroids are elevated following stress or ethanol administration, contribute to ethanol sensitivity, and their elevation is blunted in ethanol dependence.

To systematically define the genetic basis, regulation, and behavioral significance of DOC levels in plasma and cerebral cortex we examined such levels across 47 young adult males from C57BL/6J (B6)×DBA/2J (D2) (BXD) mouse strains for quantitative trait loci (QTL) and bioinformatics analyses of behavior and gene regulation. Mice were injected with saline or 0.075 mg/kg dexamethasone sodium salt at 8:00 am and were sacrificed 6 hours later. DOC levels were measured by radioimmunoassay. Basal cerebral cortical DOC levels ranged between 1.4 and 12.2 ng/g (8.7-fold variation, p<0.0001) with a heritability of ~0.37. Basal plasma DOC levels ranged between 2.8 and 12.1 ng/ml (4.3-fold variation, p<0.0001) with heritability of ~0.32. QTLs for basal DOC levels were identified on chromosomes 4 (cerebral cortex) and 14 (plasma). Dexamethasone-induced changes in DOC levels showed a 4.4-fold variation in cerebral cortex and a 4.1-fold variation in plasma, but no QTLs were identified. DOC levels across BXD strains were further shown to be co-regulated with networks of genes linked to neuronal, immune, and endocrine function. DOC levels and its responses to dexamethasone were associated with several behavioral measures of ethanol sensitivity previously determined across the BXD strains by multiple laboratories.

Both basal and dexamethasone-suppressed DOC levels are positively correlated with ethanol sensitivity suggesting that the neurosteroid DOC may be a putative biomarker of alcohol phenotypes. DOC levels were also strongly correlated with networks of genes associated with neuronal function, innate immune pathways, and steroid metabolism, likely linked to behavioral phenotypes.

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Preliminary Evidence for Associations of CHRM2 with Substance Use and Disinhibition in Adolescence

Evidence for shared heritable influences across domains of substance use suggests that some genetic variants influence broad risk for externalizing behaviors. 

Theories of externalizing psychopathology also suggest that genetic liability for substance use manifests as temperamental risk factors, particularly those related to behavioral disinhibition, during adolescence. The cholinergic muscarinic receptor 2 gene (CHRM2) is a promising candidate for studying genetic influences on broad-based risk for externalizing traits. 

This study examined a candidate CHRM2 polymorphism (rs1455858) in relation to substance use and personality measures of disinhibition in a sample of high-risk adolescents (n = 124). Bivariate analyses and structural equation modeling (SEM) evaluated associations of rs1455858 with measures of drug involvement (alcohol, tobacco and marijuana) and disinhibition (indexed by impulsivity and sensation seeking scores).

Bivariate analyses showed significant associations of CHRM2 with several behavioral phenotypes. In SEM analyses CHRM2 related significantly to latent measures of substance use and disinhibition; additionally, disinhibition mediated the association of CHRM2 with substance use. 

These results suggest that CHRM2 variants are potentially relevant for adolescent substance use and that temperamental risk factors could contribute to these associations. 

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