To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, January 15, 2011

Acceptance of Private Health Insurance in Substance Abuse Treatment Facilities

  • In 2008, nearly two thirds (65 percent) of substance abuse treatment facilities accepted some private health insurance as a form of client payment

  • Facilities with a primary focus of providing mental health services (85 percent), general health care (82 percent), or a mix of mental health services and substance abuse treatment (78 percent) were more likely than facilities with a substance abuse treatment focus (56 percent) or other focus (37 percent) to accept private health insurance

  • Facilities that accepted private health insurance were more likely than those that did not to accept adolescents into treatment (58 vs. 33 percent)

  •  Facilities in urban areas were less likely than facilities in non-urban areas to accept private health insurance

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New Course in Psychopathology and Behavioral Evaluation

Vatsalya Vatsalya M.D., M.S., P.G.D., of the Section on Human Psychopharmacology, will be the principal instructor for a new course developed by NIAAA to be offered at the Foundation for Advanced Education in the Sciences (FAES) Graduate School at NIH. The course, MEDI 505: Psychopathology and Behavioral Evaluation, is aimed at students preparing for careers in clinical work, academics, and research related to psychology, mental health, nursing, and other health care fields. 

The course will familiarize students with the Diagnostic and Statistical Manual of Mental Disorders (DSM–IV–TR) standards of classification, psychological pathologies, neuroimaging concepts, and methods for evaluating patients using advanced statistical techniques.

This course will familiarize students with clinical cases and assist them in learning how to correlate and apply basic and clinical scientific concepts related to behavioral measures. 

The course also will provide a foundation for understanding and applying the factual and conceptual information gained from research in areas such as etiology and epidemiology. There will be an emphasis on occurrence, symptoms, and criteria for differential diagnoses of various disorders, with an evidence-based review of relevant scientific literature. 

The 3-credit course will take place at FAES, One Cloister Court, Bethesda, MD, from January 24, 2011, through May 13, 2011. Registration begins January 10, 2011. For more information, contact the FAES Graduate School at 301–496–7976.

Evaluation of chronic alcohol self-administration by a 3- bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory

Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. 

In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3- bottle choice paradigm with water, 10% ethanol solution, and white wine (10% v/v), along a four-week period.

The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated.

Our results indicate that: i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. 

In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicate that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility.

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Using daily drinking data to characterize the effects of a brief alcohol intervention in an emergency room

Clinical trials often aggregate daily alcohol consumption data across long-term follow-up intervals (e.g., 6 or 12 months). Although important in understanding general treatment outcomes, these analyses tell us little about when treatment effects emerge or decline. 

We previously demonstrated that motivational interviewing (MI) reduced heavy drinking (vs. personalized feedback only; FO) among young adult drinkers (N = 198; ages 18–24) recruited in a hospital emergency room (ER) using aggregated drinking data from a 6-month follow up.

In the current study, we used daily alcohol consumption data from a calendar-assisted interview (Timeline Followback) to examine the timing and course of these treatment effects. Participants in both conditions received brief telephone booster sessions at 1 and 3 months. 

There were no treatment effects in the time between the initial intervention session and the 3-month booster session. 

Significant effects emerged after the 3-month booster and were driven by an increase in heavy drinking within the FO group. 

This suggests that the effects of brief interventions may not emerge immediately following an initial session. Aggregated data would be unable to detect this time trend. 

This research underscores the potential value added by examining the day-to-day timing of effects following treatments for alcohol use.

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Early life exposure to violence and substance misuse in adulthood—The first Brazilian national survey

Substance misuse has been a major source of health and social problems in developing societies as it has been elsewhere. There is a growing body of evidence from developed nations linking early exposure to violence in childhood with substance misuse in adulthood. The role of depression on this association is not clear. 

This study estimates the association between early life exposure to violence, alcohol disorders and illegal substance use in adulthood and the role of depression on these associations using a national Brazilian sample.

The first Brazilian National Alcohol Survey gathered information on early exposure to violence and use of psychoactive substances in 1880 participants aged 20 to 60 years old selected at random from the Brazilian household population. We used weighted logistic regression to calculate adjusted odds ratios for the associations between early exposure to violence and substance misuse. To assess the mediating effect of depression on these associations we used the Sobel–Goodman Mediation Test.

Witnessing violence during childhood or adolescence was reported by nearly 20% of the participants whilst over 8% reported having been victims of at least one form of violence. There was a statistically significant association between early exposure to violence and alcohol abuse and/or dependence and use of illegal substances in adulthood with a dose–response relationship. Depression partially explained the association between early exposure to violence with alcohol dependence (18.77% p < 0.001) and did not have a statistically significant mediating effect on the association with illegal substance use (5.83% p = 0.220).

Adverse early life events may affect individual's susceptibility to substance misuse which can be partially mediated by depression. Prevalence of substance misuse in adulthood may be in part attributed to the prevalence of adverse childhood experience. While prevention is the ideal goal, detection and intervention with children exposed to violence must be prioritised.

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Friday, January 14, 2011

What Can Alcohol Researchers Learn from Research about the Relationship Between Macro-Level Gender Equality and Violence against Women?

This systematic review focuses on research about macro-level gender equality and violence against women (VAW) and identifies conceptually and theoretically driven hypotheses as well as lessons relevant for alcohol research. 

Hypotheses include: amelioration—increased equality decreases VAW; backlash—increased equality increases VAW; and convergence—increased equality reduces the gender gap; and hypotheses that distinguish between relative and absolute status, with relative status comparing men's and women's status and absolute status measuring women's status without regard to men. 

Systematic review of studies published through June 2009 identified through PubMed and Web of Science, as well as citing and cited articles. 

A total of 30 studies are included. Of 85 findings examining amelioration/backlash, 25% support amelioration, 22% backlash; and 53% are null. Of 13 findings examining convergence, 31% support and 23% are inconsistent with convergence; 46% are null. 

Neither the existence nor the direction of the equality and VAW relationship can be assumed. This suggests that the relationship between macro-level gender equality and alcohol should also not be assumed, but rather investigated through research. 

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Perception of Sleep and Dreams in Alcohol-Dependent Patients during Detoxication and Abstinence

This study aims to investigate sleep quality and the subjective dream experience in alcohol-dependent patients during withdrawal and abstinence compared with healthy controls. 

Thirty-seven patients with alcohol dependency and 35 healthy control subjects were asked to fill in several questionnaires and to give information about their subjective sleep and dream experiences. Twelve patients participated in a follow-up interview 4 weeks later. 

Sleep quality is impaired in alcohol-dependent patients during detoxication, and the subjective dream experience is more negatively toned compared with healthy controls. Both sleep quality and dream experience improves slightly after 4 weeks of abstinence. Patients with alcohol dependency during withdrawal and abstinence dream significantly more often about alcohol. However, none of the abstinent alcohol-dependent patients dreamt about alcohol during withdrawal. 

This study shows that the subjective sleep and dream quality is strongly impaired in patients with alcohol dependency. Differences in the dream experience between alcohol-dependent patients and healthy controls are in accordance with the continuity hypotheses of dreaming. 

The hypothesis of dreaming about alcohol as a compensatory effect, however, could not be confirmed. 

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Thursday, January 13, 2011

Only 2 in 5 adults correctly identify unit content, finds Drinkaware survey

Only two in five adults (42%) recognise how many alcohol units are in common drinks, according to research by Drinkaware. The survey also found that less than a third of adults (29% of women and 32% of men) can correctly state the recommended daily unit guidelines for their respective gender.

The survey of over 4,000 UK adults found whilst 85% of adults had heard of 'alcohol units', only 30% of women and 46% of men could correctly identify which drinks roughly equate to one unit of alcohol when given a list of drinks. See the press release here.  > > > > Read More

Ethanol Feeding Potentiates the Pro-Inflammatory Response of Kupffer Cells to Cellular Fibronectin

Excessive alcohol consumption leads to the increased extracellular matrix deposition of cellular fibronectin (cFn) in the liver, which is also implicated as an initiating event in the fibrogenic process. 

We propose that cFn directly stimulates Kupffer cells (KCs), which are involved in the early response to tissue damage, to produce factors that enhance the progression of alcohol-induced liver injury toward inflammation and fibrosis.
KCs were isolated from rats fed a control or ethanol liquid diet for 4 to 6 weeks. The effect of exogenous cFn on KC viability and the secretion of the cytokines, TNF-α and IL-6, as well as of matrix remodeling factors, MMP-2 and TIMP-2, was determined after 20 hours of cell culture.
For KCs from both control- and ethanol-fed rats, viability remained unaffected by treatment with cFn. TNF-α and IL-6 production were increased in KCs exposed to cFn, with cells treated with 1, 2.5, and 5 μg/ml cFn secreting significantly higher levels of both cytokines compared with untreated cells (p < 0.05). 

Chronic ethanol administration resulted in a significantly enhanced secretion of IL-6 by KCs regardless of treatment with cFn. When MMP-2 protein and activity levels were measured by western blot analysis and gelatin zymography, respectively, we found that cFn stimulated a dramatic increase in both cells from ethanol- and control-fed rats, with the KCs from ethanol animals being more responsive to cFn at higher concentrations (p < 0.05). 

Significantly higher levels of TIMP-2, which inhibits both the activation and activity of MMP-2, were secreted by KCs treated with 5 μg/ml cFn. Correspondingly, more pro-MMP-2 than active-MMP-2 was detected.
Altogether, these results show that cFn stimulates KCs to produce factors that may enhance the promotion of tissue damage and that ethanol administration increases these responses.

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Development and Pilot Testing of an Internet-Based Survey Instrument to Measure the Alcohol Brand Preferences of U.S. Youth

Although we know a great deal about the percentage of youth who drink alcohol, we know very little about the specific brands they choose to drink. This information gap needs to be addressed if public health officials are to develop more effective interventions. Unfortunately, there are no national youth surveys that collect data on alcohol brand consumption. 

In this paper, we describe the development and pilot testing of what we believe to be the first comprehensive, Internet-based youth survey of brand-specific alcohol use.
We used online advertising in 3 U.S. cities to recruit a convenience sample of 241 respondents, ages 16 to 18 years. We used Craigslist, a network of online communities that features local classified advertisements, to recruit the sample. We used SurveyGizmo, an online software program for designing Internet surveys, collecting data, and performing basic analysis, to survey these respondents about their brand-specific alcohol consumption patterns. The survey instrument assessed each respondent’s 30-day drinking history, including the frequency of consumption for each alcohol brand.
Using Internet survey technology, we were able to collect information on 366 brands and still have respondents complete the instrument quickly and easily. 

The total number of brands consumed in the past 30 days ranged from 1 to 18, with a median of 4 brands. The top 5 brands consumed were beer brands, as were eleven of the top 15 brands. The remaining 4 brands in the top 15 included 3 brands of flavored alcoholic beverages and 1 brand of mixed drink. Among the top 15 alcohol brands consumed during heavy drinking episodes were 8 brands of beer, 4 brands of flavored alcoholic beverages, 2 brands of wine, and 1 brand of mixed drink.

This pilot study helps establish the feasibility of including brand-specific questions on federal or other national youth alcohol surveys.

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Implication of the Purinergic System in Alcohol Use Disorders

In the central nervous system, adenosine and adenosine 5′-triphosphate (ATP) play an important role in regulating neuronal activity as well as controlling other neurotransmitter systems, such as, GABA, glutamate, and dopamine. 

Ethanol increases extracellular adenosine levels that regulate the ataxic and hypnotic/sedative effects of ethanol. Interestingly, ethanol is known to increase adenosine levels by inhibiting an ethanol-sensitive adenosine transporter, equilibrative nucleoside transporter type 1 (ENT1). 

Ethanol is also known to inhibit ATP-specific P2X receptors, which might result in such similar effects as those caused by an increase in adenosine. 

Adenosine and ATP exert their functions through P1 (metabotropic) and P2 (P2X-ionotropic and P2Y-metabotropic) receptors, respectively. 

Purinergic signaling in cortex-striatum-ventral tegmental area (VTA) has been implicated in regulating cortical glutamate signaling as well as VTA dopaminergic signaling, which regulates the motivational effect of ethanol. 

Moreover, several nucleoside transporters and receptors have been identified in astrocytes, which regulate not only adenosine-ATP neurotransmission, but also homeostasis of major inhibitory-excitatory neurotransmission (i.e., GABA or glutamate) through neuron–glial interactions. 

This review will present novel findings on the implications of adenosine and ATP neurotransmission in alcohol use disorders.

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The Limbic–Hypothalamic–Pituitary–Adrenal Axis and the Development of Alcohol Use Disorders in Youth

As the initiation and acceleration of alcohol use commonly occurs during adolescence, the etiological basis for this phenomenon is of critical importance. 

Using the diathesis-stress model as a framework, this review will evaluate the emerging evidence implicating the limbic–hypothalamic–pituitary–adrenal (LHPA) axis in the development of alcohol use disorder (AUD).
Searches were conducted of the PubMed/Medline, PsycInfo, PsycBooks, Cochrane and ISI Web of Science databases, using a specified set of search terms.
Genetic liabilities, antenatal stress/anxiety or exposure to addictive substances, exposure to maltreatment or other traumatic events in childhood and psychiatric illness in childhood/adolescence can all increase the risk, or diathesis, for AUD. 

Greater LHPA dysfunction may serve as a marker for higher diathesis levels in youth. When exposed to stressors in adolescence, high-risk youth (or those with greater LHPA dysfunction) may use alcohol and/or other substances to cope with stressors and, in turn, become more vulnerable to AUD.
Evidence suggests that LHPA dysfunction and stress play an important role in the development of AUD. Genetic liabilities, antenatal insults, maltreatment, and psychiatric illness appear to increase LHPA dysfunction, raising risk for AUD. 

Further research is needed to clarify the complex interplay among adverse developmental experiences, LHPA dysfunction, and the development of AUD in 

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Alcohol's harm to others: reduced wellbeing and health status for those with heavy drinkers in their lives

The impact of alcohol on those other than the drinker is an under- researched area with important policy implications. 

This study is a first step in investigating relationships between exposure to heavy drinkers in respondent's lives with measures of health status and wellbeing.
A cross-sectional general population survey was carried out among 3068 New Zealand residents aged 12 to 80 years (response rate - 64%) using an in house Computer Assisted Telephone Interviewing system.
Respondents’ estimates of health status (EQ5 – D) and subjective wellbeing (Personal Wellbeing Index) were measured along with self reports of heavy drinkers in their lives, demographic variables and own drinking.
More than one in four of the sample had experienced someone they considered to be a heavy drinker in their environment in the past 12 months. An index of exposure to heavy drinkers, reflecting numbers of heavy drinkers and co-habitation, predicted lower health status and personal wellbeing while controlling for demographic variables and respondent's own drinking.
There is a relationship between exposure to heavy drinkers and reduced personal wellbeing and poorer health status in this cross-sectional general population sample. Exposure to heavy drinkers may have negative impacts for others.

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Partial Agonists of the α3β4* Neuronal Nicotinic Acetylcholine Receptor Reduce Ethanol Consumption and Seeking in Rats

Alcohol use disorders (AUDs) impact millions of individuals and there remain few effective treatment strategies. 

Despite evidence that neuronal nicotinic acetylcholine receptors (nAChRs) have a role in AUDs, it has not been established which subtypes of the nAChR are involved. Recent human genetic association studies have implicated the gene cluster CHRNA3–CHRNA5–CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools. 

To determine the role of the α3, and β4 subunits of the nAChR in ethanol self-administration, we developed and characterized high-affinity partial agonists at α3β4 nAChRs, CP-601932, and PF-4575180. 

Both CP-601932 and PF-4575180 selectively decrease ethanol but not sucrose consumption and operant self-administration following long-term exposure. 

We show that the functional potencies of CP-601932 and PF-4575180 at α3β4 nAChRs correlate with their unbound rat brain concentrations, suggesting that the effects on ethanol self-administration are mediated via interaction with α3β4 nAChRs.

Also varenicline, an approved smoking cessation aid previously shown to decrease ethanol consumption and seeking in rats and mice, reduces ethanol intake at unbound brain concentrations that allow functional interactions with α3β4 nAChRs. 

Furthermore, the selective α4β2* nAChR antagonist, DHβE, did not reduce ethanol intake. 

Together, these data provide further support for the human genetic association studies, implicating CHRNA3 and CHRNB4 genes in ethanol-mediated behaviors. 

CP-601932 has been shown to be safe in humans and may represent a potential novel treatment for AUDs.

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Brief Insight-enhancement Intervention among Patients with Alcohol Dependence

Patients' insight has a critical role in the recovery from problematic behavior. 

The aim of this study was to evaluate the effects of a brief intervention to promote insight among alcohol-dependent patients. 

A total of 41 alcohol-dependent patients (30 males, 11 females) in an insight-deficient state who had been admitted to a community-based alcohol treatment center, were randomized into two groups based on their admission order: an intervention group (IG) (n = 20) and a control group (CG) (n = 21). Patients in both the IG and CG participated in an identical treatment program with one exception: patients in the IG were required to undergo five sessions of brief individual intervention focusing on insight enhancement. Changes in insight state were assessed after the intervention. 

The IG exhibited significant (P < 0.05) changes in the distribution of insight level, while the CG did not exhibit any significant changes in the distribution of insight level. The insight score after intervention was significantly (P < 0.05) greater for the IG than the CG with adjustment for the baseline characteristics. 

The results suggest that a brief individual intervention focused on insight enhancement may be an effective tool to improve insight among alcohol-dependent patients.

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Wednesday, January 12, 2011

Perceptions of alcohol risk among individuals living with HIV

The documented prevalence of alcohol use among individuals with HIV is higher than reported among the general public. Little is known about how populations with HIV perceive the risks of alcohol use and what they consider to be safe levels of consumption. 

This qualitative study was conducted to increase understanding of the situations and environments in which alcohol is consumed and to explore the perceptions of risks among individuals with HIV, who were engaged in medical care and using alcohol regularly. 

Nineteen qualitative semi-structured individual interviews were conducted. 

The major themes that arose from these analyses were patterns of alcohol use, perceptions of risk based on the type of alcohol used, and the impact alcohol had on health. 

Findings suggest that alcohol is used regularly with little perception of risk; alcohol is perceived to have little effect on health and HIV progression; and providers rarely discuss alcohol use with patients. 

Future research includes assessment of alcohol use and the delivery of brief interventions to improve general health and HIV-related outcomes.

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Identifying Factors That Increase the Likelihood for Alcohol-Induced Blackouts in the Prepartying Context

The present study examined risk factors related to “blacking out” (e.g., temporary periods of memory loss during drinking) during preparty drinking events (i.e., pregaming, predrinking). 

Participants were students from two universities on the West Coast who reported past month prepartying (N = 2,546) in online surveys administered in the fall of 2008. Among these students, 25% (n = 636) reported blacking out during at least one occasion in which they prepartied in the past month.

A logistic regression model underscored that Greek student affiliation, family history of alcohol abuse, frequency of prepartying, and both playing drinking games and consuming shots of liquor while prepartying increased the likelihood of blacking out. 

Limitations and implications for future research and collegiate prevention strategies are discussed.

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Personality Moderates the Longitudinal Relationship Between Psychological Symptoms and Alcohol Use in Adolescents

A great deal of research has emerged on the comorbidity between alcohol misuse and psychological symptoms (e.g., depression, anxiety, and antisocial behavior or conduct disorder) in adolescence. Research has also shown that personality traits underlie vulnerability to alcohol use and psychological symptoms, but how personality moderates this association has not been comprehensively examined. 

The goals of this study are to clarify (i) whether early alcohol use effects the rate of change of psychological symptoms and vice versa, (ii) whether initial levels and rate of change in both domains vary according to individual differences in personality traits, and (iii) whether personality moderates the relationship between alcohol use and psychological symptoms.
Self-reported alcohol use, depression, anxiety, and antisocial behavior were collected from 393 adolescents at four separate time points across an 18-month period. Parallel growth models were used to assess the main objectives of the study. Personality traits [anxiety sensitivity (AS), hopelessness (H), impulsivity (IMP), and sensation seeking (SS)] were included as time-invariant predictors of initial levels and rates of change of each construct.
The results indicated that elevated levels of depression predicted faster rates of increase in alcohol use. Personality-specific relationships were demonstrated across all models. 

IMP was shown to moderate the relationship between alcohol use and depression, suggesting that adolescents who showed a susceptibility to elevated levels of IMP, and heavier drinking were less likely to demonstrate a normative decline in depression. 

Adolescents with higher levels of AS and anxiety were more likely to show a faster rate of increase in alcohol use.
These results highlight the importance of examining personality traits in studying the associations between alcohol use and psychological symptoms.

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How Psychosocial Alcohol Interventions Work: A Preliminary Look at What fMRI Can Tell Us

Current work in motivational interviewing (MI) has supported the role of in-session client and therapist language in predicting postintervention substance use outcomes. In particular, a relationship has been found between specific therapist language (e.g., MI-consistent behaviors), specific types of client speech (e.g., change talk; CT and counterchange talk; CCT), and subsequent drinking outcomes. 

One hypothesis to explain this phenomenon is that CT is an indication of a neurocognitive shift that happens during the course of a psychosocial intervention. And, it is possible that this shift is responsible for catalyzing and maintaining changes in drinking behaviors following MI interventions. 

To investigate this question, the effect of CT on blood oxygen level–dependent (BOLD) response during the presentation of alcohol cues was evaluated using functional magnetic resonance imaging.

To examine changes in neural response to alcohol cues following client language, 10 adults with alcohol dependence (50% men; 40% Caucasian; 40% Hispanic; M age = 42.6; M years of education = 13.3) were presented with CT and CCT derived from their prescan MI session during the presentation of alcohol cues.

Following CCT, there was significant neural response to alcohol cues in several key reward areas (cluster-corrected p < 0.05, z > 2.3; orbitofrontal cortex, nucleus accumbens, anterior insula, posterior insula, caudate, and putamen). On the contrary, there were no areas of significant reward activation following CT.

These results indicate that CT may be effectively inhibiting activation in brain regions that respond to the salience of alcohol cues. 

These findings provide preliminary biological support of the psychosocial literature findings, highlighting the critical importance of change talk during psychosocial interventions.

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Intermittent (Every-Other-Day) Drinking Induces Rapid Escalation of Ethanol Intake and Preference in Adolescent and Adult C57BL/6J Mice

Using adult C57BL/6J (B6) mice, we previously developed a procedure that causes a progressive increase in ethanol intake and preference (i.e., alcohol escalation effect) following weekly (intermittent) access to ethanol (Melendez et al., 2006). A limitation of this procedure is that it requires many weeks of testing, which limits its use to study ethanol escalation (i.e., binge-like drinking) during adolescence. Previous studies have shown that intermittent every-other-day (EOD) access to ethanol is sufficient to induce ethanol escalation in rats. 

The objective of this study was to verify whether EOD access is sufficient to induce escalated levels of ethanol intake and preference in adult and adolescent B6 mice.
Male B6 mice received free-choice 24-hour access to 15% ethanol and water on an EOD or daily basis for 2 weeks. Food and water were available at all times. Using adult mice, Experiment 1 characterized the induction of ethanol escalation following EOD access at 6 (i.e., drinking in the dark) and 24-hour intervals, whereas Experiment 2 determined whether daily drinking reverses escalation induced by EOD drinking. Experiment 3 compared ethanol-drinking capacity following daily versus EOD drinking in adolescent (P30-45) and adult (P70-85) mice.
Experiment 1 revealed that EOD drinking leads to a significant (nearly 2-fold) increase in ethanol intake and preference over mice given daily access. Experiment 2 demonstrated that EOD-elicited escalation is blocked and subsequently reversed following daily drinking. Experiment 3 revealed that ethanol drinking was greater in adolescent mice compared with adults following daily drinking and EOD (escalated) drinking. Although the escalated levels of ethanol intake were greater in adolescent mice, the rate or onset of escalation was comparable between both age-groups.
This study is the first to demonstrate that EOD drinking leads to escalation of ethanol intake and preference in adolescent and adult mice. Moreover, our results indicate that daily ethanol reverses ethanol escalation induced by intermittent drinking. 

The study also revealed that adolescent mice have a greater capacity to drink ethanol under both daily (controlled) and EOD (escalated) conditions, which further supports the notion of adolescent’s susceptibility to heavy drinking.

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Adolescent Binge Drinking Alters Adult Brain Neurotransmitter Gene Expression, Behavior, Brain Regional Volumes, and Neurochemistry in Mice

Binge drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. 

Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol-use disorders.
To determine whether adolescent ethanol (AE) binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5 g/kg/d, i.g., postnatal days P28 to P37) and assessed during adulthood (P60 to P88). An array of neurotransmitter-specific genes, behavioral tests (i.e., reversal learning, prepulse inhibition, and open field), and postmortem brain structure using magnetic resonance imaging (MRI) and immunohistochemistry, were employed to assess persistent alterations in adult brain.
At P38, 24 hours after AE binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. 

Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38 to P88) resulted in decreased neurotransmitter mRNA, e.g., an average decrease of 56%. 

Following AE treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by AE treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following AE. 

Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons.
Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal forebrain acetylcholine neurons. Loss of cholinergic neurons and forebrain structure could underlie adult reversal learning deficits following adolescent binge drinking.

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Can We Assess Blood Alcohol Levels of Attendees Leaving Professional Sporting Events?

We measured blood alcohol content (BAC) levels of attendees at professional sporting events and assessed the factors associated with higher BACs.
We conducted BAC tests of 362 adult attendees following 13 baseball games and three football games. We ran multivariate analyses to obtain factors associated with the risk of having a higher BAC.
In this assessment, 40% of the participants had a positive BAC, ranging from 0.005 to 0.217. Those who reported tailgating before the event had 14 times the odds of having a BAC > 0.08 and those under age 35 had nearly 8 times the odds of having a BAC > 0.08 (both compared to a zero BAC). Attendees of Monday night football games were more likely to have positive BACs compared to attendees at all other games.

We found that it is feasible to assess BAC levels of attendees at professional sporting events. 

Our findings suggest that a significant number of attendees at professional sporting events may have elevated BAC levels, particularly young adults and those who participated in tailgating activities. Further research using a representative sample is warranted to confirm the findings from this preliminary study.

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Tuesday, January 11, 2011

Molecular Profiles of Drinking Alcohol to Intoxication in C57BL/6J Mice

Alcohol addiction develops through a series of stages, and mechanistic studies are needed to understand the transition from initial drug use to sustained controlled alcohol consumption followed by abuse and physical dependence. The focus of this study was to examine the effects of voluntary alcohol consumption on brain gene expression profiles using a mouse model of binge drinking. 

The main goal was to identify alcohol-responsive genes and functional categories after a single episode of drinking to intoxication.
We used a modification of a “Drinking In the Dark” (DID) procedure (Rhodes et al., 2005) that allows mice to experience physiologically relevant amounts of alcohol in a non-stressful environment and also allows for detection of alcohol-sensitive molecular changes in a dose-dependent manner. C57BL/6J male mice were exposed to either 20% ethanol solution or water (single bottle) starting 3 hours after lights off for 4 hours and brains were harvested immediately after the drinking session. cDNA microarrays were used to assess the effects of voluntary drinking on global gene expression in 6 brain regions. We employed three statistical approaches to analyze microarray data.
A commonly used approach that applies a strict statistical threshold identified the eight top statistically significant genes whose expression was significantly correlated with blood ethanol concentration (BEC) in one of the brain regions. 

We then used a systems network approach to examine brain region-specific transcriptomes and identify modules of co-expressed (correlated) genes. In each brain region, we identified alcohol-responsive modules, i.e., modules significantly enriched for genes whose expression was correlated with BEC. 

A functional over-representation analysis was then applied to examine the organizing principles of alcohol-responsive modules. Genes were clustered into modules according to their roles in different physiological processes, functional groups, and cell types, including blood circulation, signal transduction, cell–cell communication, and striatal neurons. 

Finally, a meta-analysis across all brain regions suggested a global role of increasing alcohol dose in coordination of brain blood circulation and reaction of astrocytes.
This study showed that acute drinking resulted in small but consistent changes in brain gene expression which occurred in a dose-dependent manner. We identified both general and region-specific changes, some of which represent adaptive changes in response to increasing alcohol dose, which may play a role in alcohol-related behaviours, such as tolerance and consumption. Our systems approach allowed us to estimate the functional values of individual genes in the context of their genetic networks and formulate new refined hypotheses. 

An integrative analysis including other alcohol studies suggested several top candidates for functional validation, including Mt2, Gstm1, Scn4b, Prkcz, and Park7.

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Subdiagnostic Alcohol Use by Depressed Men and Women Seeking Outpatient Psychiatric Services: Consumption Patterns and Motivation to Reduce Drinking

This study examined alcohol use patterns among men and women with depression seeking outpatient psychiatric treatment, including factors associated with recent heavy episodic drinking and motivation to reduce alcohol consumption.
The sample consisted of 1,183 patients aged 18 and over who completed a self-administered, computerized intake questionnaire and who scored ≥10 on the Beck Depression Inventory-II (BDI-II). Additional measures included current and past alcohol questions based on the Addiction Severity Index, heavy episodic drinking (≥5 drinks on 1 or more occasions in the past year), alcohol-related problems on the Short Michigan Alcoholism Screening Test (SMAST), and motivation to reduce drinking using the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES).

Among those who consumed any alcohol in the past year (73.9% of the sample), heavy episodic drinking in the past year was reported by 47.5% of men and 32.5% of women. 

In logistic regression, prior-year heavy episodic drinking was associated with younger age (= 0.011), male gender (= 0.001), and cigarette smoking (= 0.002). 

Among patients reporting heavy episodic drinking, motivation to reduce alcohol consumption was associated with older age (= 0.008), greater usual quantity of alcohol consumed (< 0.001), and higher SMAST score (< 0.001).
In contrast to prior clinical studies, we examined subdiagnostic alcohol use and related problems among psychiatric outpatients with depression. 

Patients reporting greater drinking quantities and alcohol-related problems also express more motivation to reduce drinking, providing intervention opportunities for mental health providers that should not be overlooked.

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Alcohol Alters DNA Methylation Patterns and Inhibits Neural Stem Cell Differentiation

Potential epigenetic mechanisms underlying fetal alcohol syndrome (FAS) include alcohol-induced alterations of methyl metabolism, resulting in aberrant patterns of DNA methylation and gene expression during development. 

Having previously demonstrated an essential role for epigenetics in neural stem cell (NSC) development and that inhibiting DNA methylation prevents NSC differentiation, here we investigated the effect of alcohol exposure on genome-wide DNA methylation patterns and NSC differentiation.
Neural stem cells in culture were treated with or without a 6-hour 88 mM (“binge-like”) alcohol exposure and examined at 48 hours, for migration, growth, and genome-wide DNA methylation. 

The DNA methylation was examined using DNA-methylation immunoprecipitation followed by microarray analysis. Further validation was performed using Independent Sequenom analysis.
Neural stem cell differentiated in 24 to 48 hours with migration, neuronal expression, and morphological transformation. Alcohol exposure retarded the migration, neuronal formation, and growth processes of NSC, similar to treatment with the methylation inhibitor 5-aza-cytidine. 

When NSC departed from the quiescent state, a genome-wide diversification of DNA methylation was observed—that is, many moderately methylated genes altered methylation levels and became hyper- and hypomethylated. 

Alcohol prevented many genes from such diversification, including genes related to neural development, neuronal receptors, and olfaction, while retarding differentiation. 

Validation of specific genes by Sequenom analysis demonstrated that alcohol exposure prevented methylation of specific genes associated with neural development [cut-like 2 (cutl2), insulin-like growth factor 1 (Igf1), epidermal growth factor–containing fibulin-like extracellular matrix protein 1 (Efemp1), and SRY-box-containing gene 7 (Sox 7)]; eye development, lens intrinsic membrane protein 2 (Lim 2); the epigenetic mark Smarca2Dgcr2)]. 

Specific sites altered by DNA methylation also correlated with transcription factor binding sites known to be critical for regulating neural development.
The data indicate that alcohol prevents normal DNA methylation programming of key neural stem cell genes and retards NSC differentiation. Thus, the role of DNA methylation in FAS warrants further investigation.

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Activation of Brain NOP Receptors Attenuates Acute and Protracted Alcohol Withdrawal Symptoms in the Rat

Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. 

In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. 

In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats.
For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat).
Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals.
These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms.

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2009 National Survey on Drug Use and Health (NSDUH) Data and Reports Released With Improved Access

NSDUH is the primary source of information on the use of illegal drugs, alcohol, and tobacco by the civilian, noninstitutionalized population of the United States age 12 or older. The survey is also a source of national estimates on mental health measures such as serious mental illness, other mental illness, depression, and treatment.

The 2009 NSDUH data and documentation files are available for download and online analysis. Also, custom analytic tables can be produced with NSDUH data using Quick Tables—choose from preselected core variables by pointing and clicking from dropdown menus. Results from online analysis or Quick Tables can be copied easily and inserted into documents.  

Two reports from the 2009 NSDUH are now available:

National Findings Report—Presents national estimates of rates of use, numbers of users, and other measures related to illicit drugs, alcohol, and tobacco products. The report focuses on trends between 2008 and 2009 and from 2002 to 2009, as well as differences across population subgroups in 2009.

Mental Health Findings   —Presents national estimates of the prevalence of past-year mental health disorders and past-year mental health service utilization for youth age 12 to 17 and adults age 18 or older.