Spring 2008 Symposia Series on Mechanisms of Behavior Change-February 27, 2008

The first symposium of the three-part series is entitled:

GETTING AT WHY PEOPLE CHANGE

Getting Back to Basics:

Using Basic Behavioral Research to

Study Mechanisms of Clinical Change

Matthew K. Nock, Ph.D.

Associate Professor

Department of Psychology

Harvard University

Translation Science Framework:

Using Basic Behavioral Research to Identify

Clinically Significant Mechanisms of Behavioral Change

Marsha E. Bates, Ph.D.

Research Professor

Center for Alcohol Studies

Rutgers University

Wednesday, February 27, 2008

1:00 PM– 3:00 PM

Neuroscience Center Building

6001 Executive Boulevard

Room C

Webcast at: http://videocast.nih.gov/

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Dissociation and alexithymia among men with alcoholism
Psychiatry and Clinical Neurosciences 62 (1) , 40–47

The aim of the present study was to evaluate the relationship between alexithymia and dissociation among men with alcoholism.

Fifty-three patients were considered as having alexithymia. The alexithymic group had a significantly higher rate of dissociative taxon members (patients with pathological dissociation; 62.3%) according to Bayesian probability.

Trait anxiety, overall psychiatric symptom severity, and pathological dissociation predicted alexithymia on covariance analysis. A multivariate analysis of covariance demonstrated that these predictors were related only to difficulty of identifying feelings, whereas trait anxiety was a significant covariant for difficulty of expressing feelings as well.

Alexithymic phenomena are interrelated with dissociation and chronic anxiety among men with alcoholism. The relevance of this triad for prevention and treatment of alcoholism deserves interest in further research.

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Level of Response to Alcohol Within the Context of Alcohol-Related Domains: An Examination of Longitudinal Approaches Assessing Changes Over Time
Alcoholism: Clinical and Experimental Research 32 (3) , 472–480

The manner in which a low level of response (LR) to alcohol relates to domains that enhance the risk for heavy drinking has traditionally been studied through cross-sectional models. However, many of the relevant domains, such as the maximum number of drinks consumed in 24 hours (MAXDRINK) and drinking among peers (PEER) typically decrease across adulthood.

This study evaluated whether a person’s LR to alcohol predicted alcohol-related domains at multiple time-points and examined longitudinal relations among these domains in a sample of probands from the San Diego Prospective Study.

A low LR to alcohol at T1 predicted higher levels of MAXDRINK and COPE at T15, consistent with prior studies. Using latent growth curve models, higher levels of T15 MAXDRINK predicted less decreases in PEER drinking over time. Additional analyses found a time-specific effect of T20 COPE on T25 MAXDRINK even after accounting for the growth factors of both domains.

These evaluations illustrate that LR prospectively predicted relevant outcomes, and clarify how alcohol-related domains related to each other as the probands progressed through middle adulthood. Treatment implications are discussed and drinking to cope may be an important intervention target for problematic alcohol use.

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Brain Activation, Response Inhibition, and Increased Risk for Substance Use Disorder
Alcoholism: Clinical and Experimental Research 32 (3) , 405–4

Youth at high risk for developing substance use disorders (SUDs) often exhibit differences which suggest inhibitory impairments when compared to average risk youth.

To examine the underlying neural activity related to these impairments, functional MRI (fMRI) was employed in adolescents during an antisaccade task requiring inhibition of an eye movement response. Each subject’s level of neurobehavioral disinhibition (ND) was assessed using a multi-informant, multi-method approach, which has been shown to be highly predictive of SUD onset. The fMRI data was categorized into neural regions of interest according to total frontal, parietal, occipital, and temporal lobe activation.

Results demonstrated that ND score was negatively correlated with total amount of frontal activation, but was not significantly correlated with total activation in any other neural region.

These results indicate deficits in frontal activation in youth with high amounts of ND, suggesting a possible developmental delay of executive processes in high-risk youth.

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Differences in Frontostriatal Responses Between Vulnerable and Resilient Children of Alcoholic Parents
Alcoholism: Clinical and Experimental Research 32 (3) , 414–426

Children of alcoholics (COAs) are at elevated risk for alcohol use disorders (AUD), yet not all COAs will develop AUD. The 2 primary aims of this study were to identify neural activation mechanisms that may mark protection or vulnerability to AUD in COAs and to map the same activation patterns in relation to risk behavior (externalizing or internalizing behavior).

Twenty-two adolescent COAs were recruited from an ongoing community longitudinal study of alcoholic and matched control families. They were categorized as either vulnerable (n = 11) or resilient (n = 11) based on the level of problem drinking over the course of adolescence. Six other adolescents with no parental history of alcoholism, and no evidence of their own problem drinking were recruited from the same study and labeled as low-risk controls. Valenced words were presented to the participants in a passive viewing task during functional magnetic resonance imaging. Activation to negative versus neutral words and positive versus neutral words were compared between groups. Behavior problems were assessed with the Youth Self-Report (YSR).

The resilient COA group had more activation of the orbital frontal gyrus (OFG), bilaterally, and left insula/putamen than the control and vulnerable groups, in response to emotional stimuli. In contrast, the vulnerable group had more activation of the dorsomedial prefrontal cortex and less activation of the ventral striatum and extended amygdala, bilaterally, to emotional stimuli than the control and resilient groups. The vulnerable group had more externalizing behaviors which correlated with increased dorsomedial prefrontal activation and decreased ventral striatal and extended amygdala activation.

These results are consistent with dissociable patterns of neural activation underlying risk and resiliency in COAs. We propose that the pattern observed in the resilient COAs represents an active emotional monitoring function, which may be a protective factor in this group. On the other hand, the vulnerable group displayed a pattern consistent with active suppression of affective responses, perhaps resulting in the inability to engage adaptively with emotional stimuli.

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Britain should tax "alcohol epidemic"


February 22, 2008

Britain is suffering from an epidemic of alcohol abuse, the country's doctors said, demanding higher taxes and stricter regulation to curb it.

A British Medical Association report said new laws were needed to tackle an affliction which is costing the country's health and law enforcement services billions of pounds a year.

The report comes at a crucial juncture in the national debate about how to tackle Britain's booze culture - one which has lawmakers re-examining everything from super-size glasses at fancy wine bars to super-cheap ciders at supermarkets.
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UK Doctors Urge Higher Taxes on Alcohol

By THE ASSOCIATED PRESS

Published: February 21, 2008

LONDON (AP) -- The British Medical Association lobbied Thursday for higher taxes on alcohol, an end to happy hours, and a steep reduction in the permitted blood alcohol-limit for drivers.

A report by the group said new laws were needed to combat an epidemic of alcohol misuse that is costing health and law enforcement services billions of dollars a year.

It comes at a crucial juncture in the national debate about how to tackle Britain's booze culture -- one which has lawmakers re-examining everything from super-size glasses at fancy wine bars to super-cheap ciders at discount supermarkets.
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Press Release - TESCO WILLING TO DISCUSS ALCOHOL PRICE RESTRICTIONS BUT GOVERNMENT MUST LEAD TO AVOID COMPETITION CONCERNS
21/02/2008

Tesco has today told the Government that it is willing to take an active role in discussions around the introduction of legislation to ensure responsible pricing on alcohol and alcohol promotions.

But Britain’s biggest supermarket warned that Ministers must initiate and lead these discussions to avoid retailers falling foul of competition legislation which prevents discussion of prices between businesses.
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Exploring Pregnancy-Related Changes in Alcohol Consumption Between Black and White Women
Alcoholism: Clinical and Experimental Research 32 (3) , 505–512

Although epidemiological data indicate that White women are more likely to drink and binge drink before pregnancy, fetal alcohol syndrome (FAS) is more common in the Black population than among Whites in the United States. Differences in drinking cessation between Black and White women who become pregnant may help explain the disparity in FAS rates.

Pregnant White women averaged 79.5% fewer drinks per month than non-pregnant White women , and 85.4% fewer binge drinking occasions . Pregnant Black women averaged 58.2% fewer drinks per month than non-pregnant Black women and 64.0% fewer binge occasions .

Compared to Black women, White women appear to make a 38% greater reduction in drinks per month, and a 33% greater reduction in binge occasions.

Non-Hispanic White women appear more likely to reduce drinks per month and binge drinking occasions than non-Hispanic Black women during pregnancy.

These findings may help explain disparities in FAS in the United States, though this cross-sectional sample does not permit claims of causation. To better describe the impact of differential drinking reduction on FAS rates, future studies of longitudinal data should be done.

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Letter - Are the Effects of Gamma-Hydroxybutyrate (GHB) Treatment Partly Physiological in Alcohol Dependence?
The American Journal of Drug and Alcohol Abuse, Volume 34, Issue 2 March 2008 , pages 235 - 236

It has been hypothesized that the therapeutic effects of Gamma-hydroxybutyrate (GHB) in alcohol dependence could be related to ethanol-mimicking action of the drug and that GHB could reduce alcohol craving, intake and withdrawal by acting as a "substitute" of the alcohol in the central nervous system.

Nevertheless, alcohol being the strongest trigger of craving and intake, it is difficult to ascribe reduction of craving and intake to ethanol-mimicking activity of GHB.

I have recently proposed that alcohol/substance dependence could result from a GHB-deficiency-related dysphoric syndrome in which alcohol/substances would be sought to "substitute" for insufficient GHB effect. GHB is the sole identified naturally occurring gamma-aminobutyric acid B (GABA (B)) receptor agonist.

Here, I propose that exogenous GHB might in fact "substitute" for deficient endogeneous GHB and represent true substitutive treatment for GHB-deficiency. And that baclofen and GHB could both compensate for deficient effect of the physiological GABA (B) receptor agonist(s).

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Family History of Alcoholism Does Not Influence Adrenocortical Hyporesponsiveness in Abstinent Alcohol-Dependent Men
The American Journal of Drug and Alcohol Abuse, Volume 34, Issue 2 March 2008 , pages 151 - 160


Early abstinence in alcohol-dependent subjects is marked by adrenocortical hyporesponsivity. However, it is uncertain whether the blunted response is primarily attributable to a genetic vulnerability or to the chronic abuse of alcohol.

In the present study, the authors investigated the influence of a family history (FH) of alcoholism upon suppressed glucocorticoid reactivity.

Neither a parental history or familial loading of alcoholism had a significant effect upon glucocorticoid responsivity in abstinent alcohol-dependent men.

Adrenocorticol responsiveness in recently abstinent alcohol-dependent men does not appear to reflect a preexisting biologic vulnerability to alcoholism.

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Clinical Implications of Tolerance to Alcohol in Nondependent Young Drinkers
The American Journal of Drug and Alcohol Abuse, Volume 34, Issue 2 March 2008 , pages 133 - 149


Ten percent of teenagers and young adults with no alcohol diagnosis and a third of those with alcohol abuse report tolerance to alcohol. However, relatively few data are available on the clinical implications of tolerance in nondependent men and women.

Data were gathered from 649 18-to-22-year-old drinking offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) families. The prevalence and clinical correlates of tolerance were evaluated across subjects with no DSM-IV alcohol abuse and no tolerance, similar individuals with tolerance, subjects with alcohol abuse but no tolerance, and individuals with both alcohol abuse and tolerance.

Tolerance was associated with an almost doubling of the number of drinks needed to feel alcohol's effects, and correlated with additional alcohol-related problems. In regression analyses, the most consistent and robust correlates of tolerance were the maximum number of drinks and alcohol problems, and tolerance remained informative after covarying for drinking quantity.

Tolerance to alcohol may be a useful concept regarding nondependent drinkers that is not just a proxy for alcohol quantity but also reflects the presence of additional problems.

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CHRONIC BINGE-LIKE MODERATE ETHANOL DRINKING IN RATS RESULTS IN WIDESPREAD DECREASES IN BRAIN SEROTONIN, DOPAMINE AND NOREPINEPHRINE TURNOVER RATES REVERSED BY ETHANOL INTAKE.
Journal of Neurochemistry OnlineAccepted Articles 12n February 2008


This research was initiated to assess the turnover rates (TORs) of dopamine (DA), norepinephrine (NA), serotonin (5-HT), aspartate (Asp), glutamate (Glu) and GABA in brain regions during rodent ethanol/sucrose (EtOH) and sucrose (SUC) drinking and in animals with a history of EtOH or SUC drinking to further characterize the neuronal systems that underlie compulsive consumption.

Changes in the TOR of 5-HT, DA and NA were detected specific to EtOH drinking, SUC drinking or a history of EtOH or SUC drinking. An acute EtOH deprivation effect was detected that was mostly reversed with EtOH drinking.

These results suggest that binge-like drinking of moderate amounts of EtOH produces a deficit in neuronal function that could set the stage for the alleviation of anhedonic stimuli with further EtOH intake that strengthen EtOH seeking behaviors which may contribute to increased EtOH use in at risk individuals.

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Exploring daily variations of drinking in the Swiss general population. A growth curve analysis
International Journal of Methods in Psychiatric Research Volume 17, Issue 1 , Pages 1 - 11

This study aims to address the underlying trajectories of weekly individual drinking patterns by growth models and to relate differences in drinking patterns to socio-demographic and drinking characteristics of respondents.

Data came from a two-stage stratified random subsample of 747 persons aged 15 years or more from a Swiss study on alcohol consumption using a within-subject design conducted between March 1999 and July 1999. Beverage specific assessment of daily alcohol consumption was obtained by a weekly drinking diary and other characteristics via telephone interviews. The diary had to be filled out on seven consecutive days.

The growth models accounted for up to 37.6% of the initial error variance and provided evidence for two distinct, negatively correlated underlying trajectories of drinking patterns.

The first trajectory described an increase in consumption from Monday to Sunday.

The second trajectory was about a specific weekend consumption culminating on Saturday with a significantly higher growth rate among young people and heavy episodic drinkers than in other subgroups.

Therefore, young and heavy episodic drinkers may be exposed to sudden adverse consequences of alcohol consumption during the weekend. Prevention efforts which are targeted to this subgroup should take its specific drinking pattern into account.

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Call to halt cheap alcohol offers


Thursday, 21 February 2008,

The government needs to introduce tougher measures to limit the sale of cheap alcohol, doctors warn.

A British Medical Association report said pricing and promotion of drinks was fuelling an "alcohol epidemic".

It called for an end to happy hours in pubs and cut-price supermarket deals as well as improved access to treatment.

The government is due to carry out research into the issue this year, but Tesco has already indicated it is prepared to discuss pricing.

The BMA report is based on placing greater restrictions on the availability and access to alcohol.
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Press Release - Stronger government action needed to tackle the epidemic of alcohol misuse, says new BMA report
(issued Thursday 21 Feb 2008)

A new hard-hitting report¹ ‘Alcohol misuse: tackling the UK epidemic’ launched today (Thursday 21 February 2008) by the BMA calls on the government to show leadership and implement a full range of effective control policies that will reduce the burden of alcohol misuse.

“Recent governments have worked too closely with the alcohol industry and have pursued policies of deregulation and liberalisation regarding alcohol control” said BMA Head of Science and Ethics, Dr Vivienne Nathanson. She added: “As doctors we see first hand how alcohol misuse destroys lives. It causes family breakdowns, is a major factor in domestic violence, ruins job prospects, is often related to crime and disorderly behaviour and it kills. Alcohol misuse is related to over 60 medical conditions including heart and liver disease, diabetes, strokes and mental health problems. The government approach has led to increased consumption levels and alcohol-related problems and demonstrates a failure in the political drive to improve public health and order.

“Alcohol misuse not only costs lives it also costs the country many millions of pounds. The NHS spends millions every year on treating and dealing with alcohol problems and the criminal justice system also spends similarly large amounts dealing with alcohol-related and drink-driving offences. The BMA is very worried about alcohol consumption among young people, particularly young girls. It is shocking that in Europe, the UK’s teenagers are most likely to be heavy drinkers.”

Key recommendations from the report include (a full list can be found on page seven of the report):

• Higher taxes on alcoholic drinks and this increase should be proportionate to the amount of alcohol in the product.
• An end to irresponsible promotional activities like happy hours and two-for-one offers.
• Standard labels should be displayed on all alcoholic products that clearly state alcohol units, recommended guidelines for consumption and a warning message advising that exceeding these guidelines may cause the individual and others harm.
• The legal limit for the level of alcohol permitted while driving should be reduced from 80mg/100ml to 50mg/100ml throughout the UK.

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Alcohol misuse: tackling the UK epidemic
February 2008

Alcohol consumption represents an integral part of modern culture in the UK and internationally. The production of alcoholic beverages such as beer, wine and spirits occurs on a vast scale as part of a multi-billion pound global industry.

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The control of alcohol at a national and international level is therefore essential. This requires the implementation of strategies that are effective at reducing overall alcohol consumption levels in a population, as well as targeted interventions aimed at specific populations such as young people or individuals who are dependant on alcohol. Tackling alcohol misuse also requires greater personal responsibility from individuals who consume alcohol in a manner that is harmful to themselves and those around them

This report considers the problematic levels of alcohol misuse in the UK and is not aimed at those who enjoy consuming alcohol in moderation. It examines the patterns and trends of alcohol consumption and goes on to review the range of adverse effects both on the individual and society that are associated with its misuse.

The report concludes by considering the evidence for effective alcohol control policies and discusses the current approaches in the UK. The recommendations are for action by the UK Government and are evidence-based policies that need to be adopted in order to tackle alcohol misuse and its associated harms


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Govt Crafts Alcohol Policy

Wednesday, 20th of February 2008

By Wezi Tjaronda

WINDHOEK

The Ministry of Health and Social Services and its partners yesterday met to amend and update the draft demand reduction policy on alcohol use and misuse.

The policy is in keeping with the World Health Organisation and the World Bank which have agreed that a comprehensive set of measures to reduce the harmful use of alcohol remains the most effective approach to reduce alcohol use and its related negative effects.

Minister of Health, Dr Richard Kamwi, said the draft policy will serve as a national guiding document for legislative reforms and will inform appropriate national responses to the problem. He said the policy would regulate alcohol consumption to a point of moderation.

The policy arose from concerns that most Namibians believe that drinking 10 units of alcohol at a single occasion is acceptable.

A baseline study in 2002 found that 56 percent of Namibia’s population consumes more than 10 litres of alcohol per session and those that drink did it excessively.
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Mandatory Reporting by Physicians of Patients Potentially Unfit to Drive
Open Medicine, Vol 2, No 1 (2008)

One strategy for the prevention of motor vehicle crashes is physician reporting of medically unfit drivers to vehicle licensing authorities, as mandated by law in Ontario, Canada.

We studied drivers involved in life-threatening crashes who required hospital admission to determine how many had previously been seen and reported by a physician in the community.

A total of 1,605 injured drivers were identified, of whom 37% had a reportable condition (95% confidence interval [CI] 35–39). Those with a reportable condition had made a total of 20,505 previous visits to 2,332 physicians during the five years before the crash. The majority of patients with a reportable condition (85%, 95% CI 82–88) had seen a physician in the year before the crash but few (3%, 95% CI 2–4) had been reported to licensing authorities.

Alcohol abuse was the most common underlying reportable condition (prevalent in 72% of trauma patients with a reportable condition) and the least common reason for a previous report (reported in 2% of those with a reportable condition).

Unsafe drivers often visit physicians and yet are rarely reported to licensing authorities even under mandatory reporting laws for preventive medical reporting.

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Complaints About Sleep in Trauma Patients in An Emergency Department in Respect to Alcohol Use
Alcohol and Alcoholism Advance Access published online on February 16, 2008

Among other lifestyle problems, sleeping problems have been related to alcohol use.

The aim of this study was to evaluate complaints about sleep in trauma patients in an emergency department and its relation to alcohol use disorders (AUD).

An AUDIT score 8 points was found in 24.2% of the males and 8.3% of the females. Complaints about sleep were reported by 28% and 34% of the patients, respectively.

These complaints about sleep were more likely in males at-risk drinkers (AUDIT 8 versus 1–4 points (Adjusted odds ratio: AOR = 1.60, P = 0.001) or abstainers (AUDIT = 0 versus 1–4 points, AOR = 1.55, P = 0.029), and with increasing age (AOR = 1.01, P = 0.010), in patients not feeling "fit" (AOR = 2.15, P <> users of pain (AOR = 2.24, P <> (AOR = 8.03, P < 0.001).

In females, complaints about sleep were more likely with higher age (AOR = 1.04, P = 0.023), higher BMI (AOR = 1.04, P = 0.023), with not-feeling-fit (AOR = 1.87, P < aor =" 5.24,">P <> and less likely in patients with a higher education (AOR = 0.57, P <>

Complaints about sleep were reported frequently by trauma patients. There was an association between AUDs and sleep complaints (mainly problems about sleeping through) in males, but not in females.

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Pathways to Substance-Related Disorder: A Structural Model Approach Exploring the Influence of Temperament, Character, and Childhood Adversity in a National Cohort of Prisoners
Alcohol and Alcoholism Advance Access published online on February 18, 2008

Using Cloninger's model of personality, we aimed to specify the relative influence of the more biologically determined variables, temperament and character and more environmentally driven influence, childhood adversity in the development of addiction; and to compare patterns found among alcoholics with those found among drug addicts.

We studied a group of prisoners, at a high risk of substance abuse and past history of childhood adversity. Using a stratified random strategy we selected (i) 23 prisons among the different types of prison in France, (ii) 998 prisoners. Each prisoner was assessed by two psychiatrists—one junior, using a structured interview (MINI 5 plus), and one senior, completing the procedure with an open clinical interview. At the end of the interview the clinicians met and agreed on a list of diagnoses. Cloninger's Temperament and Character Inventory was used to measure personality. Structural equations models, which have been advocated to disentangle the respective influence of complex risk factors, were used.

The "novelty seeking" temperament was a crucial vulnerability factor, for both alcoholics and drug addicts, in the same proportion. Character and childhood adversity played a significant part only in the development of drug abuse.

In a prison population, a common biological loaded factor, novelty seeking is found both at the core of alcohol- and drug-related disorder whereas environmentally loaded factors play a greater role in drug problems.

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Request Reprint E-Mail:</sup> michael.lukasiewicz@gmail.com
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Associations of Alcohol Drinking and Cigarette Smoking with Serum Lipid Levels in Healthy Middle-Aged Men
Alcohol and Alcoholism Advance Access published online on February 18, 2008

The aim of this study is to determine whether influences of drinking alcohol on serum lipid levels are different in smokers and non-smokers.

In overall subjects, serum HDL, LDL and total cholesterol were significantly lower and triglyceride was significantly higher in heavy smokers than in non-smokers. In the smoker groups, serum total cholesterol was significantly lower in heavy drinkers than in non-drinkers, while no difference in total cholesterol was observed in non- and heavy drinkers of the non-smoker group. Both in the smoker and non-smoker groups, HDL cholesterol was higher and LDL cholesterol was lower in drinkers than in non-drinkers. The difference in LDL cholesterol between non-drinkers and drinkers was more prominent in smokers than in non-smokers. The above associations were not altered after the adjustment for age, body weight and alcohol intake.

The results suggest that smoking increases the lowering effect of alcohol drinking on LDL cholesterol, but does not affect the relationship of alcohol drinking with HDL cholesterol.

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Request E-Mail: wakabaya@hyo-med.ac.jp

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Alcohol Exposure Alters Cell Cycle and Apoptotic Events During Early Neurulation.
Alcohol and Alcoholism Advance Access published online on February 18, 2008


Fetal alcohol exposure causes growth deficits, microencephaly, and neurological abnormalities. Although the effects of alcohol on developmental delay and growth-related deficits have been hypothesized, little is understood about how alcohol alters, in particular, the cyclin pathway within the cell cycle, which is critical to proliferation and apoptotic control.

In this study, we examined cell cycle proteins pertinent to the G1–S phase transition and apoptosis, to determine if cell cycle misregulation can be attributed to apoptotic induction and growth defects.

Alcohol-exposed DRG-NC demonstrated a dose-dependent increase in cells expressing increased cyclin D1 protein, and increased DNA fragmentation. Western blot analysis, using embryos, demonstrated an overexpression of cyclin D1, D2, and E2F1, key G1 to S-phase cell cycle regulatory components, and increases in p53, linking the cell cycle and apoptotic pathways. Bromodeoxyuridine incorporation indicated reduced DNA synthesis and growth in several embryonic regions. Propidium iodide staining demonstrated decreases in DNA content and increases in DNA fragmentation in several embryonic tissues.

This study indicated that retarded growth of DRG-NC and embryos, induced by alcohol, is associated with altered expression of cell cycle and apoptotic proteins and concurrent inhibition of proliferation and increased DNA fragmentation. We suggest that alcohol induces an increase in cyclin D1 expression, premature S-phase entry, and disjointed DNA synthesis with increased apoptosis.

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Correction: Alcohol group lobbying story


February 20, 2008

(AP) - In a Feb. 15 story about lobbying by the Global Alcohol Producers Group, The Associated Press erroneously reported that Akin Gump Strauss Hauer & Feld lobbied the World Health Organization on behalf of the trade group. Akin Gump lobbied U.S. government officials, not WHO officials.

A corrected version of the story appears below.
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HIV-positive patients’ discussion of alcohol use with their HIV primary care providers
Drug and Alcohol Dependence ,Article in Press, Corrected Proof 19 February 2008

We investigated the prevalence of HIV-positive patients discussing alcohol use with their HIV primary care providers and factors associated with these discussions.

Thirty-five percent of participants reported discussion of alcohol use with their primary care providers. The odds of reporting discussion of alcohol were three times greater for problem drinkers than for non-drinkers, but only 52% of problem drinkers reported such a discussion in the prior 12 months.

Sociodemographic factors associated with discussion of alcohol use (after controlling for problem drinking) were being younger than 40, male, being non-white Hispanic (compared with being Hispanic), being in poorer health, and having a better patient–provider relationship.

Efforts are needed to increase the focus on alcohol use in the HIV primary care setting, especially with problem drinkers. Interventions addressing provider training or brief interventions that address alcohol use by HIV-positive patients in the HIV primary care setting should be considered as possible approaches to address this issue.

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Request Reprint E-Mail: Lmetsch@med.miami.edu

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A prospective study of risk drinking: At risk for what?
Drug and Alcohol Dependence Article in Press, Corrected Proof 19 Februry 2008

Data from two waves of a nationally representative U.S. population sample were used to link frequency of risk drinking in the year preceding the Wave 1 interview with the incidence or occurrence of various adverse outcomes in the approximately 3-year-period between the two interviews (n = 22,122 Wave 1 drinkers who were reinterviewed at Wave 2).

Risk drinking was defined as consuming the equivalent of 5+ standard drinks in a day for men and the equivalent of 4+ standard drinks in a day for women. Controls included sociodemographic and health characteristics, mean quantity of drinks consumed on risk drinking days and average volume of intake on non-risk drinking days.

The odds of nonhierarchical alcohol abuse and dependence, initiation of smoking and incidence of nicotine dependence were increased at all frequencies of risk drinking and showed a fairly continuous increase in magnitude with increasing frequency, reaching OR of 3.03–7.23 for daily/near daily risk drinking. The incidence of liver disease was strongly increased among weekly or more frequent risk drinkers (OR = 2.78–4.76). The odds of social harm and drug use were increased among daily/near daily risk drinkers (OR = 1.61–2.54), and the likelihood of drivers license revocation showed near-significant increases at all frequencies of risk drinking.

Frequency of risk drinking interacted with volume of intake on non-risk drinking days in predicting alcohol abuse and illicit drug use and with duration of drinking in predicting alcohol dependence.

Risk drinking poses a threat of many types of harm, both directly and indirectly through its association with smoking initiation and nicotine dependence.

These findings have illustrative value for prevention programs, and they indicate that frequent risk drinking is a strong marker for alcoholism.

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Externalizing disorders in Southwest California Indians: Comorbidity and a genome wide linkage analysis
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Early View 19 February 2008

Alcohol dependence is one of the leading causes of morbidity and mortality in Native Americans. Externalizing disorders such as conduct disorder (CD) and antisocial personality disorder (ASPD) have been demonstrated to have significant comorbidity with alcohol dependence in the general population.

This study's aims were to: assess the comorbidity of DSM-III-R ASPD and CD with alcohol dependence, to map susceptibility loci for ASPD and CD, and to see if there is overlap with loci previously mapped for alcohol dependence phenotypes in 587 Southwest California Mission Indians (SWC).

Alcohol dependence was found to be comorbid with DSM-III-R ASPD but not CD. However, the amount of alcohol dependence in the population attributable to ASPD and/or CD is low. ASPD and the combined phenotype of participants with ASPD or CD were both found to have significant heritability, whereas no significant evidence was found for CD alone.

Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 251 of the participants. Analyses of multipoint variance component LOD scores, for ASPD and ASPD/CD, revealed six locations that had a LOD score of 2.0 or above: on chromosome 13 for ASPD and on chromosomes 1, 3, 4, 14, 17, and 20 for ASPD/CD.

These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies for externalizing diagnoses.

These results also further identify new regions of the genome, that do not overlap with alcohol dependence phenotypes previously identified in this population, that may be unique to either the phenotypes evaluated or this population of SWC Indians.

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Employee Assistance Research Foundation

Our Mission

Employee Assistance comprises of a body of professional knowledge and skills with tremendous practical benefit to individuals and organizations. It need not be a commodity!

The aim of the Foundation is to address this challenge by elevating our general practice and professional stature, through solid research in EA efficacy and the stimulation of graduate level scholarship.

Getting Involved

The first step on this road is for interested parties to make contact. If you have an interest in assisting or just learning more about this mission please Click here to join the mailing list.

The inaugural meeting of the Employee Assistance Research Foundation was held in San Diego on October 24, 2007. This meeting was recorded, and there are a few complimentary CDs remaining which will be distributed on a "first-come, first-serve" basis. Be sure to leave your mailing address here.

For additional background information, please read the Carl Tisone "Call to Action" article. Click here for the article and click here for the latest correspondence on this subject, including a synopsis of the Foundation's development efforts thus far.

Employee Assistance Research Foundation Website

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Chronic cigarette smoking modulates injury and short-term recovery of the medial temporal lobe in alcoholics
Psychiatry Research: Neuroimaging Volume 162, Issue 2, 28 February 2008, Pages 133-145


Memory function is largely mediated by the medial temporal lobe (MTL), and its compromise has been observed in alcohol dependence and chronic cigarette smoking. The effects of heavy alcohol consumption and chronic smoking on hippocampal volumes and MTL metabolites and their recovery during abstinence from alcohol have not been assessed.

Male alcoholics in treatment (ALC) [13 smokers (sALC) and 11 non-smokers (nsALC)] underwent quantitative magnetic resonance imaging and short-echo proton magnetic resonance spectroscopic imaging at 1 week and 1 month of sobriety. Outcome measures were compared with 14 age-matched, non-smoking light-drinkers and were related to visuospatial learning and memory.

Over 1 month of abstinence, N-acetyl-aspartate, a neuronal marker, and membrane-associated choline-containing metabolites normalized in the MTL of nsALC subjects, but remained low in the MTL of sALC subjects. Metabolite concentration changes in both groups were associated with improvements in visuospatial memory.

Hippocampal volumes increased in both groups during abstinence, but increasing volumes correlated with visuospatial memory improvements only in nsALC subjects.

In summary, chronic cigarette smoking in alcohol-dependent men appears to have adverse effects on MTL metabolite recovery during short-term sobriety.

These data may also have implications for other conditions with established MTL involvement and significant smoking co-morbidity, such as schizophrenia-spectrum and mood disorders.


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Moderate doses of alcohol disrupt the functional organization of the human brain
Psychiatry Research: Neuroimaging, Article in Press, Corrected Proof 15 February 2008


Acute alcohol administration decreases overall brain glucose metabolism, which serves as a marker of brain activity. The behavioral effects of alcohol, however, are likely to reflect not only changes in regional brain activity but also the patterns of brain functional organization. Here we assessed the effects of a moderate dose of alcohol on the patterns of brain activity and cerebral differentiation.

We measured brain glucose metabolism in 20 healthy controls with positron emission tomography and fluorodeoxyglucose during baseline and during alcohol intoxication (0.75 g/kg). We used the coefficient of variation (CV) to assess changes in brain metabolic homogeneity, which we used as a marker for cerebral differentiation.

We found that alcohol decreased the CV in the brain and this effect was independent of the decrements in overall glucose metabolism. Our study revealed marked disruption in brain activity during alcohol intoxication including decreases in global and regional brain differentiation, a loss of right versus left brain metabolic laterality and a shift in the predominance of activity from cortical to limbic brain regions.

The widespread nature of the changes induced by a moderate dose of alcohol is likely to contribute to the marked disruption of alcohol on behavior, mood, cognition and motor activity.

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Drink and drugs can damage men's sperm, study suggests

Alok Jha, science correspondent
The Guardian,
Tuesday February 19 2008

Men should not smoke, drink or take unnecessary drugs if they are planning to become fathers to avoid causing health problems for their children, a health expert has warned.

Scientists found that toxic chemicals can damage sperm, which then pass altered genes onto babies. In experiments on rats Matthew Anway of the University of Idaho found that some garden chemicals caused problems such as damaged and overgrown prostates, infertility and kidney problems, all of which were present up to four generations later.

Cynthia Daniels, of Rutgers University in New York, an expert in the relation between a father and child's health, said: "If I was a young man I would not drink beer, I would not be smoking when I'm trying to conceive a child."
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Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women
Molecular Psychiatry (2008) 13, 334–347



Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior.

Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone.

The MAOA-LPR low activity allele was associated with alcoholism , particularly antisocial alcoholism, only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern.

In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women.

The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P=0.008) and antisocial alcoholics. Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism, and to a lesser extent with antisocial alcoholism.

In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone.

A MAOB haplotype was associated with alcoholism independently from ASPD.

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Role of the NO/cGMP/K_ATP pathway in the protective effects of sildenafil against ethanol-induced gastric damage in rats
British Journal of Pharmacology (2008) 153, 721–727

Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K_ATP) is involved in gastric defence.

Our objective was to evaluate the role of the NO/cGMP/K_ATP pathway in the protective effects of sildenafil against ethanol-induced gastric damage.

Sildenafil significantly reduced ethanol-induced gastric damage in rats. L-NAME alone, without L-arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol-induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil.

Sildenafil had a protective effect against ethanol-induced gastric damage through the activation of the NO/cGMP/K_ATP pathway.

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Request Reprint E-Mail: souzamar@ufc.br
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Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABA_A receptors as an opportunity for drug development?
British Journal of Pharmacology advance online publication 18 February 2008;

Alcohol (ethanol, EtOH) has pleiotropic actions and induces a number of acute and long-term effects due to direct actions on alcohol targets, and effects of alcohol metabolites and metabolism.

Many detrimental health consequences are due to EtOH metabolism and metabolites, in particular acetaldehyde, whose high reactivity leads to nonspecific chemical modifications of proteins and nucleic acids. Like acetaldehyde, alcohol has been widely considered a nonspecific drug, despite rather persuasive evidence implicating inhibitory GABA_A receptors (GABA_ARs) in acute alcohol actions, for example, a GABA_AR ligand, the imidazobenzodiazepine Ro15-4513 antagonizes many low-to-moderate dose alcohol actions in mammals.

It was therefore rather surprising that abundant types of synaptic GABA_ARs are generally not responsive to relevant low concentrations of EtOH. In contrast, -subunit-containing GABA_ARs and extrasynaptic tonic GABA currents mediated by these receptors are sensitive to alcohol concentrations that are reached in blood and tissues during low-to-moderate alcohol consumption.

We recently showed that low-dose alcohol enhancement on highly alcohol-sensitive GABA_AR subtypes is antagonized by Ro15-4513 in an apparently competitive manner, providing a molecular explanation for behavioural Ro15-4513 alcohol antagonism.

The identification of a Ro15-4513/EtOH binding site on unique GABA_AR subtypes opens the possibility to characterize this alcohol site(s) and screen for compounds that modulate the function of EtOH/Ro15-4513-sensitive GABA_ARs.

The utility of such drugs might range from novel alcohol antagonists that might be useful in the emergency room, to drugs for the treatment of alcoholism, as well as alcohol-mimetic drugs to harness acute positive effects of alcohol.

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Stock News - Alcoholism drug market: shift in disease perception required for long-term growth

Feb 18, 2008 (Datamonitor via COMTEX) -- ALKS | news | PowerRating | PR Charts -- Estimated to be worth just $86 million in 2006, the alcohol dependence pharmaceutical market is set to grow to $304 million by 2016, driven by the launch of two pipeline opioid antagonists and the continued uptake of Alkermes and Cephalon's opioid antagonist Vivitrol. However, for substantial long-term success in drug treatment for alcohol dependence, a shift in disease perception is required.
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Self Assessment of Warning Symptoms in Upper Gastrointestinal Bleeding

Dtsch Arztebl Int 2008; 105(5):73-7

Alcohol addicted patients are at increased risk of upper gastrointestinal bleeding. Delay to endoscopy is mainly determined by patients´ self assessment.

The authors asked 417 patients with high alcohol consumption from Leipzig (n = 277) and Munich (n = 140) with an average alcohol consumption of 660 g/week about their behaviour when faced with symptoms of acute upper gastrointestinal bleeding.

71% or 51% said they would call the emergency physician if they were to vomit blood or black liquid. Only 32% would call emergentcy medical aid if they were to pass black stools, and only 25% of those surveyed thought urgent medical attention necessary in any of the 3 scenarios. Patients with regular contact with health care providers, and women, were more likely to consider these 3 scenarios as medical emergencies. The authors found no differences by age, educational level, marital status and alcohol consumption.

Knowledge concerning the impact of symptoms of gastrointestinal bleeding was poor, in our study. Patients with high alcohol consumption and infrequent contact with health care providers, in particular, should be informed about symptoms such as melena and hematemesis, as delayed presentation significantly affects prognosis and resource consumption.

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