The relationship of comorbidity of mental and substance use disorders with suicidal behaviors in the Nigerian Survey of Mental Health and Wellbeing

Mental and substance use disorders are often associated with an elevated risk for suicidal behaviors. The role of the co-occurrence of multiple disorders in this association is still unclear.

Persons with lifetime suicide attempt were more likely than those without attempt to have experienced lifetime DSM-IV disorders. Lifetime attempters were also more likely to have comorbid conditions. Compared with only 0.4% of persons with no history of lifetime attempts, over 11% of persons with lifetime attempt had three or more co-occurring disorders.

Multivariate analysis controlling for the effects of comorbid conditions suggests that while mood disorder is independently associated with suicidal outcomes, comorbidity partly explains the association of anxiety disorders and almost fully accounts for the association of substance use disorders with suicidal outcomes.

Comorbidity is an important factor in the association of mental and substance use disorders with suicidal behavior.

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Request Reprint E-Mail: ogureje@comui.edu.ng
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Ethanol alters endosomal recycling of human dopamine transporters

Dynamic membrane trafficking of the monoamine dopamine transporter (DAT) regulates dopaminergic signaling. Various intrinsic and pharmacological modulators can alter this trafficking. Previously we have shown ethanol potentiates in vitro DAT function and increases surface expression. However, the mechanism underlying these changes is unclear.

In the present study, we found ethanol directly regulates DAT function by altering endosomal recycling of the transporter.

We defined ethanol's action on transporter regulation by [3H]DA uptake functional analysis combined with biochemical and immunological assays in stably expressing DAT HEK-293 cells.

Short-term ethanol exposure potentiated DAT function in a concentration-, but not time-dependent manner. This potentiation was accompanied by a parallel increase in DAT surface expression.

Ethanol had no effect on function or surface localization of the ethanol-insensitive mutant (G130T DAT), suggesting a trafficking-dependent mechanism in mediating the ethanol sensitivity of the transporter.

The ethanol-induced increase in DAT surface expression occurred without altering the overall size of DAT endosomal recycling pools.

We found ethanol increased the DAT membrane insertion rate while having no effect on internalization of the transporter.

Ethanol had no effect on the surface expression or trafficking of the endogenously expressing transferrin receptor, suggesting ethanol does not have a non-specific effect on endosomal recycling.

These results define a novel trafficking mechanism by which ethanol regulates DAT function.

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Request Reprint E-Mail: dayne.mayfield@mail.utexas.edu
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Prevention of cardiovascular risk by moderate alcohol consumption: epidemiologic evidence and plausible mechanisms

An inverse association between moderate alcohol intake and cardiovascular risk, in particular coronary disease and ischemic stroke, has been shown in many epidemiologic studies.

In addition, several other diseases are also known to occur less frequently in moderate drinkers than in non-drinkers, whereas excess of drinking is invariably harmful.

However, some concern has been recently raised about the possibility that at all dosages the harm of alcohol could overcome its beneficial effects.

We present here the epidemiologic and mechanistic evidence to support the protective effect of moderate alcohol intake against cardiovascular disease and all-cause mortality.

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Request Reprint E-Mail: dicastel@ngi.it
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Alcohol-Induced Neurodegeneration, Suppression of Transforming Growth Factor-β, and Cognitive Impairment in Rats: Prevention by Group II Metabotropic

Glutamatergic neurotransmission has been implicated in mechanisms of alcohol-induced neurodegeneration and cognitive impairment, but the underlying mechanism remains unknown.

Here, we examined whether the group II metabotropic glutamate receptor agonist LY379268 prevents neuronal death and learning deficits in a rat model of binge-like exposure to alcohol.

Our data support a neuroprotective role for group II metabotropic glutamate receptor agonists and TGF-β in alcohol-induced neurodegeneration.

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

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Community Norms, Enforcement of Minimum Legal Drinking Age Laws, Personal Beliefs and Underage Drinking: An Explanatory Model

Strategies to enforce underage drinking laws are aimed at reducing youth access to alcohol from commercial and social sources and deterring its possession and use. However, little is known about the processes through which enforcement strategies may affect underage drinking.

The purpose of the current study is to present and test a conceptual model that specifies possible direct and indirect relationships among adolescents’ perception of community alcohol norms, enforcement of underage drinking laws, personal beliefs (perceived parental disapproval of alcohol use, perceived alcohol availability, perceived drinking by peers, perceived harm and personal disapproval of alcohol use), and their past-30-day alcohol use.

This study used data from 17,830 middle and high school students who participated in the 2007 Oregon Health Teens Survey.

Structural equations modeling indicated that perceived community disapproval of adolescents’ alcohol use was directly and positively related to perceived local police enforcement of underage drinking laws. In addition, adolescents’ personal beliefs appeared to mediate the relationship between perceived enforcement of underage drinking laws and past-30-day alcohol use.

Enforcement of underage drinking laws appeared to partially mediate the relationship between perceived community disapproval and personal beliefs related to alcohol use.

Results of this study suggests that environmental prevention efforts to reduce underage drinking should target adults’ attitudes and community norms about underage drinking as well as the beliefs of youth themselves.

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Request Reprint E-Mail: skreda@prev.org
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Empirically defined subtypes of alcohol dependence in an Irish family sample

Alcohol dependence (AD) is clinically and etiologically heterogeneous.

The goal of this study was to explore AD subtypes among a sample of 1221 participants in the Irish Affected Sib Pair Study of Alcohol Dependence, all of whom met DSM-IV criteria for AD.

Variables used to identify the subtypes included major depressive disorder, antisocial personality disorder, illicit drug dependence (cannabis, sedatives, stimulants, cocaine, opioids, and hallucinogens), nicotine dependence, the personality traits of neuroticism and novelty seeking, and early alcohol use.

Using latent class analysis, a 3-class solution was identified as the most parsimonious description of the data. Individuals in a Mild class were least likely to have comorbid psychopathology, whereas a severe class had highest probabilities of all comorbid psychopathology. The third class was characterized by high probabilities of major depression and higher neuroticism scores, but lower likelihood of other comorbid disorders than seen in the severe class.

Overall, sibling pair resemblance for class was stronger within than between classes, and was greatest for siblings within the severe class, suggesting a stronger familial etiology for this class.

These findings are consistent with the affective regulation and behavioral disinhibition subtypes of alcoholism, and are in line with prior work suggesting familial influences on subtype etiology.

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Request Reprint E-Mail: cprescot@usc.edu
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Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study

COMBINE is the largest study of pharmacotherapy for alcoholism in the United States to date, designed to answer questions about the benefits of combining behavioral and pharmacological interventions.

Trajectory-based analyses of daily drinking data allowed identification of distinct drinking trajectories in smaller studies and demonstrated significant naltrexone effects even when primary analyses on summary drinking measures were unsuccessful.

The objective of this study was to replicate and refine trajectory estimation and to assess effects of naltrexone, acamprosate and therapy on the probabilities of following particular trajectories in COMBINE.

It was hypothesized that different treatments may affect different trajectories of drinking.

We replicated the trajectories (“abstainer”, “sporadic drinker”, “consistent drinker”) established previously in smaller studies. However, greater numbers of trajectories better described the heterogeneity of drinking over time.

Naltrexone reduced the chance to follow a “nearly daily” trajectory and Combined Behavioral Intervention (CBI) reduced the chance to be in an “increasing to nearly daily” trajectory of any drinking. The combination of naltrexone and CBI increased the probability of membership in a trajectory in which the frequency of any drinking declined over time. Trajectory membership was associated with different patterns of treatment compliance.

The trajectory-analyses identified specific patterns of drinking that were differentially influenced by each treatment and provided support for hypotheses about the mechanisms by which these treatments work.

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Request Reprint E-Mail: ralitza.gueorguieva@yale.edu

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Predicting drinking onset with discrete-time survival analysis in offspring from the San Diego prospective study

Previous research has shown that an early onset of drinking is associated with a range of problematic drinking outcomes in adulthood.

However, earlier drinking is also linked to additional characteristics that themselves predict alcohol problems including male gender, a family history (FH) of alcoholism, age, race, parental alcoholism, depression symptoms, prior drug use, and conduct problems.

This study tested the relationship between the age of first drink (AFD) and a range of risk factors that predict the onset of alcohol use. Participants were offspring from the San Diego Prospective Study (SDPS) who were at least 15 years old at the time of their most recent interview (n=147). Discrete-time survival analysis (DTSA) was used to relate multiple characteristics to the hazard function of alcohol onset across a relevant age range.

The results demonstrated the predicted relationships to AFD for conduct problems, male gender, prior marijuana use, and a FH of alcoholism, even when these characteristics were estimated together.

Furthermore, an interaction occurred such that offspring with both conduct problems and marijuana use were at substantially higher risk for alcohol use onset during this time period than would be predicted from the effect of these two risk factors alone.

However, age at interview, ethnicity, parent education, and depressive symptoms did not predict the pattern of onset of drinking.

Implications for future research and prevention efforts are discussed.

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Request Reprint E-Mail: mschuckit@ucsd.edu
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Alcohol and drug involvement after adolescent treatment and functioning during emerging adulthood

This study identified patterns of alcohol and other drug (AOD) involvement during the decade following adolescent AOD treatment and developmental outcomes in emerging adulthood.

AOD and psychosocial variables were assessed at eight time points from adolescence into adulthood (n=153; 41.2% women) in an inpatient treatment sample of alcohol and other drug dependent teens.

Latent class growth analysis identified six trajectories based on alcohol and substance use frequency which were consistent with developmental transitions and validated by measures of dependency symptoms.

While few differences were evident at intake, the educational, occupational and interpersonal attainments were differentially associated with the alcohol/drug trajectories as youth transitioned into adulthood.

High rates of high school graduation (71.1%), professional occupations (45.2%), marriage/cohabitation (48.5%), and financial responsibility for children (F[5,27]=2.75, p=.02) were evident for those with the least alcohol and drug involvement.

More severe drug use trajectories were associated with higher rates of dependence, incarceration and more treatment at the final period of assessment.

Outcomes of the trajectory of frequent alcohol involvement were distinct from combined alcohol and drug use.

These findings highlight the long-term diversity of substance use outcomes following adolescent treatment and suggest that identification of these patterns of use following treatment can help clarify the developmental impact of youth alcohol and drug use on outcomes in young adulthood.

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Request Reprint E-Mail: sanbrown@ucsd.edu
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Beliefs about the empirical support of drug abuse treatment interventions: A survey of outpatient treatment providers

This study assessed substance abuse treatment providers’ beliefs about empirically supported treatments (ESTs) to determine if providing information about empirical support for interventions would change beliefs.

Treatment providers (N=136) completed an interview regarding five interventions with varied empirical support: contingency management (CM), motivational interviewing (MI), relapse prevention (RP), 12-step approaches (TSA), and verbal confrontation (VC). Participants then read primers describing empirical support for each intervention prior to completing a repeat interview.

Overall, providers reported positive beliefs about ESTs. Baseline beliefs about empirical support for each intervention were inflated relative to that of expert raters except for CM. After reading the primers, beliefs about efficacy changed in the direction of the experts for all interventions except MI, but continued to be inflated except for CM.

Willingness to utilize interventions increased for RP, MI, and CM and decreased for TSA and VC, but remained higher than warranted by empirical support.

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Request Reprint E-Mail: lbenishek@tresearch.org

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Regulation of GABAA Receptor Subunit Expression by Pharmacological Agents

The γ-aminobutyric acid (GABA) type A receptor system, the main fast-acting inhibitory neurotransmitter system in the brain, is the pharmacological target for many drugs used clinically to treat, for example, anxiety disorders and epilepsy, and to induce and maintain sedation, sleep, and anesthesia.

These drugs facilitate the function of pentameric GABA_A receptors that exhibit widespread expression in all brain regions and large structural and pharmacological heterogeneity as a result of composition from a repertoire of 19 subunit variants.

One of the main problems in clinical use of GABA_A receptor agonists is the development of tolerance. Most drugs, in long-term use and during withdrawal, have been associated with important modulations of the receptor subunit expression in brain-region-specific manner, participating in the mechanisms of tolerance and dependence.

In most cases, the molecular mechanisms of regulation of subunit expression are poorly known, partly as a result of neurobiological adaptation to altered neuronal function. More knowledge has been obtained on the mechanisms of GABA_A receptor trafficking and cell surface expression and the processes that may contribute to tolerance, although their possible pharmacological regulation is not known.

Drug development for neuropsychiatric disorders, including epilepsy, alcoholism, schizophrenia, and anxiety, has been ongoing for several years.

One key step to extend drug development related to GABA_A receptors is likely to require deeper understanding of the adaptational mechanisms of neurons, receptors themselves with interacting proteins, and finally receptor subunits during drug action and in neuropsychiatric disease processes.

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Request Reprint E-Mail: mikko.uusi-oukari@utu.fi
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Seminar - Drinking spaces and places: Examining who drinks alcohol, where and why?

The impact of drinking alcohol in excess is seen both in terms of individual health and disorder in public spaces. This seminar focuses on why policy levers need to recognise the importance of where and how people drink.

• Wednesday 10 February 2010 10.00am to 4.00pm

• RGS-IBG, London

9.30 Registration

10.00 Introduction

Rita Gardner, Director RGS-IBG & Morning Chair (Professor Graham Moon, Geography, Southampton)

10.05 Session 1: Policy Context

Binge drinking in England, a regional view: Dr Nicola Shelton, Department of Epidemiology and Public Health University College London
Learning to drink: 11 to 15 year olds and alcohol: Elizabeth Fuller, National Centre for Social Research (NATCEN)
Developments in Scotland: Dr Emilia Crighton, Scottish Convenor, Faculty for Public Health (FPH)
Just Added Working to put Home Office alcohol policy into practice: Eric Stark, Regional Alcohol Lead, Government Office of London

11.30 Coffee Break

11.45 Session 2: Private Drinking Places: Home and Away

The Historical culture of drinking: Historical/cultural reasons for drinking – how the ‘current crisis’ has built over thirty years, focusing on ‘public spaces’ Dr James Kneale, Geography, University College London
Where people drink - assessing the shift in emphasis from city-centre to the home, and the role of relationships at home (Joseph Rowntree Funded work): Professor Gill Valentine, Geography, Leeds; Dr Mark Jayne, Geography, Manchester; and Dr Sarah Holloway, Geography, Loughborough

12.45 Lunch Break

13.45 Session 3: Public Drinking Spaces

Just Added Night time economies: Alistair Turnham, MAKE Associates
Designing drinking spaces: From Park to Club: youth, alcohol and place Professor Marion Roberts, School of Architecture and the Built Environment, University of Westminster
Local spaces: licensing and managing public disorder John Thornhill, Chairman of the Magistrates Association

15.00 Coffee Break

15.15 Session 4: Panel Discussion

including: Dr Mark Jayne, Geography, Manchester; Don Shenker, Chief Executive, Alcohol Concern and Alistair Turnham, MAKE Associates

16.00 Conclusions and closing statement

Afternoon Chair

Environment & Society Forum Read More

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Substance Use Treatment Need among Uninsured Workers

More than 18.4 million full-time employees aged 18 to 64 (15.5 percent of the full-time adult workers in that age range) had no health insurance coverage and represented the majority (54.5 percent) of adults under age 65 without health insurance coverage.

An estimated 3.0 million uninsured full-time workers (16.3 percent) needed substance use treatment in the past year; specifically, 13.3 percent needed alcohol use treatment, 5.6 percent needed illicit drug use treatment, and 2.7 percent needed both alcohol and illicit drug use treatment.

Of the uninsured workers who needed substance use treatment in the past year, 12.6 percent (378,000 persons) received treatment at a specialty facility.

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Alcohol Consumption in Young Adults and Incident Hypertension: 20-Year Follow-up From the Coronary Artery Risk Development in Young Adults Study

The relation between alcohol consumption and incident hypertension is unclear, and most observational studies have not accounted for socioeconomic factors.

This study examined the association between alcohol consumption in a diverse group of young adults and incident hypertension over 20 years.

The 20-year incidence of hypertension for never, former, light, moderate, and at-risk drinkers was 25.1%, 31.8%, 20.9%, 22.2%, and 18.8%, respectively (P 0.001). Race, gender, age, family history of hypertension, body mass index, income, education, and difficulty paying for basics and medical care were associated with hypertension.

Adjustment using Cox proportional hazard models revealed no association between baseline alcohol consumption and incident hypertension, except among European-American women in whom any current alcohol consumption was associated with lower risk of incident hypertension.

The lack of association between alcohol and hypertension in the majority of this socioeconomically diverse cohort is not definitive.

Future studies should include social factors, such as income and education, and consider additional characteristics that may modify or confound associations between alcohol and blood pressure.

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Request Reprint E-Mail: jhalanych@uab.edu
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How Scandinavian Publications Portray Self-Help Groups in Relation to Health and Welfare Systems

The aim of this article is to review the relationships of self-help groups to health and welfare services and professionals/service representatives in a Scandinavian research context.

Eight Swedish, Norwegian, and Danish publications written by researchers within an academic research context are discussed; understanding self-help groups in a national context is stressed. The analysis was based on a conflict/consensus model proposed by the author.

Results indicate that Scandinavian researchers often view the relationship between health and welfare services and professionals/service representatives and self-help groups as more consensus-oriented than groups described in early American self-help group literature where there is a higher degree of distrust.

The high level of trust toward governmental organizations in Scandinavian countries is suggested as one explanation for this difference.

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Request Reprint E-Mail: magnus.karlsson(at)esh.se

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Telephone Hotlines for Men in Japan

The purposes of this study were to identify telephone hotline programs specifically for men in Japan and to describe their structure, characteristics, and practices.

Using the internet and snowball sampling, we identified 17 telephone hotlines. The hotlines were established within approximately the past 10 years. Callers learn about the hotlines from a variety of sources, including government and private websites, newspapers, doctors, and callers' family members.

Programs are largely staffed by volunteer and paid male staff with either non-professional or professional backgrounds. The hotlines are typically open about 6 hours per month. They provide free support resources, including psychological counseling, information, and referral to relevant legal and other organizations.

These findings are discussed in the context of traditional Japanese cultural values about gender and helping. By considering how belief and value systems are accommodated and assimilated by culturally diverse individuals and groups, telephone hotlines and self-help/mutual-aid groups can be more effective.

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Request Reprint E-Mail: mikam@pdx.edu
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An Initial View of Self-Help Groups for Japanese Alcoholics: Danshukai in its Historical, Social, and Cultural Contexts

Danshukai is Japan's largest self-help/mutual-aid group for alcoholics, with approximately 10,000 members nationwide.

This article aims to examine Danshukai in the Tokyo area. While leaders of Danshukai in the 1950s were inspired by Alcoholics Anonymous (AA), it was AA's general structure and not its therapeutic content that was translated into the Japanese context.

For therapeutic content Danshukai turned to existing cultural understandings within Japanese society, and made the "meeting" pivotal to recovery.

In Danshukai, alcoholics manage their dependence by changing their social routines by "belonging" to Danshukai and attending meetings, paying membership fees, and sharing stories about the damaging effects of alcohol among members. Recovery is not an individual journey, but is inclusive of the family in the therapeutic process.

Danshukai also provides service to help alcoholics in need who are outside their membership. At the individual level, service is more local, being linked to supporting the family through recovery.

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Request Request E-Mail: t-oka@sophia.ac.jp

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Surveillance of Certain Health Behaviors and Conditions Among States and Selected Local Areas — Behavioral Risk Factor Surveillance System, United Sta

Heart disease, stroke, cancer, and diabetes are among of the leading causes of death in the United States. Controlling health-risk behaviors and using preventive health-care services can reduce or prevent morbidity and premature mortality from such diseases.

The Behavioral Risk Surveillance System (BRFSS) is an ongoing telephone survey of U.S. adults on health-risk behaviors and the use of preventative health-care services related to the leading causes of death and disability in the United States.

This report summarizes the results from the 2007 BRFSS.

Alcohol Consumption

Binge Drinking

Binge drinking was defined as adult males having five or more drinks, and adult females having four or more drinks on at least one occasion during the last 30 days. In 2007, among adults aged ≥18 years, the estimated prevalence of binge drinking ranged from 8.2% in Kentucky to 23.4% in Wisconsin (median: 15.7%) (Table 31). Among selected MMSAs, the estimated prevalence of binge drinking ranged from 4.3% in Provo-Orem, Utah, to 21.4% in Milwaukee-Waukesha-West Allis, Wisconsin (median: 15.7%) (Table 32). Among selected counties, the estimated prevalence ranged from 4.3% in Utah County, Utah, to 25.6% in Arlington County, Virginia (median: 15.6%) (Table 33).

Heavy Drinking

Heavy drinking was defined as adult males having more than two drinks, and adult females having more than one drink per day during the last 30 days. In 2007, among adults aged ≥18 years, the estimated prevalence of heavy drinking ranged from 2.5% in Utah to 7.7% in Hawaii (median: 5.2%) (Table 34). Among selected MMSAs, the estimated prevalence of heavy drinking ranged from 2.1% in Idaho Falls, Idaho and Wauchula, Florida, to 11.0% in Key West-Marathon, Florida (median: 5.3%) (Table 35). Among selected counties, the estimated prevalence ranged from 1.2% in Davis County, Utah, to 11.6% in St. Johns County, Florida (median: 5.5%) (Table 36).

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Initial Preference for Drinking Goal in the Treatment of Alcohol Problems: II. Treatment Outcomes

To compare treatment outcomes between clients preferring abstinence and those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (the United Kingdom Alcohol Treatment Trial) and to interpret any differential outcome in light of baseline differences between goal preference groups outlined in an accompanying paper.

Clients initially stating a preference for abstinence showed a better outcome than those stating a preference for non-abstinence. This superior outcome was clearer at 3 months’ follow-up but still evident at 12 months’ follow-up. The better outcome consisted almost entirely in a greater frequency of abstinent days, with only a modest benefit in drinking intensity for goal abstainers that disappeared when baseline covariates of goal preference were controlled for. Type of successful outcome (abstinence/non-problem drinking) was related to initial goal preference, with clients preferring abstinence more likely to obtain an abstinent outcome and those preferring non-abstinence a non-problem drinking outcom

The client’s personal drinking goals should be discussed in assessment at treatment entry and as a basis for negotiation. Clinicians should be prepared to identify and support goal change as an unexceptional part of the treatment process that need not jeopardize good outcome.

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Request Reprint E-Mail: nick.heather@northumbria.ac.uk

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Initial Preference for Drinking Goal in the Treatment of Alcohol Problems: I. Baseline Differences Between Abstinence and Non-Abstinence Groups

To compare baseline characteristics of clients initially preferring abstinence with those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (UKATT) and to identify predictors of goal preference from client characteristics present before the preference was stated.

Across all UKATT sites, 54.3% of clients expressed a preference for abstinence and 45.7% for non-abstinence. In univariate comparisons, clients preferring abstinence were significantly (P <> (iii) report drinking more heavily but less frequently, (iv) have been detoxified in the 2 weeks prior to assessment, (v) report more alcohol problems, (vi) be in the action stage of change, (vii) report greater negative expectancies of drinking, (viii) report greater mental and physical ill-health, (ix) report less social support for drinking and (x) be more confident of their ability to resist heavy drinking in tempting situations. In the logistic regression model, the strongest predictors of goal preference were gender, drinking pattern, recent detoxification and social support for drinking.

The implications of these findings for service delivery are best considered in conjunction with findings from a companion paper reporting treatment outcomes associated with each goal preference.

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Request Reprint E-Mail: nick.heather@northumbria.ac.uk

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Interactive Voice Response Technology Can Deliver Alcohol Screening and Brief Intervention in Primary Care

Alcohol screening and brief intervention (BI) is an effective primary care preventive service, but implementation rates are low. Automating BI using interactive voice response (IVR) may be an efficient way to expand patient access to needed information and advice.

Call duration ranged from 3–7 minutes. Subjective reactions were generally positive or neutral. About 40% of subjects indicated IVR-BI had motivated them to change. About half of the patients had discussed drinking with their provider at the visit. These tended to be heavier drinkers with greater concerns about drinking. Patients who reported a provider-delivered BI and called the IVR-BI endorsed greater comfort and honesty with the IVR-BI. On average, a 25% reduction in alcohol use was reported two weeks after the clinic visit.

Using IVR technology to deliver BI in a primary care setting is feasible and data suggest potential for efficacy in a larger trial.

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Request Reprint E-Mail: Gail.Rose@vtmednet.org
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Candidate genes for alcohol preference identified by expression profiling in alcohol-preferring and -nonpreferring reciprocal congenic rats

Selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats differ greatly in alcohol preference, in part due to a highly significant quantitative trait locus (QTL) on chromosome 4. Alcohol consumption scores of reciprocal chromosome 4 congenic strains NP.P and P.NP correlated with the introgressed interval.

The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-naive inbred alcohol preferring and P.NP congenic rats: amygdala, nucleus accumbens, hippocampus, caudate putamen, and frontal cortex.

Within the QTL region, 104 cis-regulated probe sets were differentially expressed in more than one region, and an additional 53 were differentially expressed in a single region. Fewer trans-regulated probe sets were detected, and most differed in only one region. Analysis of the average expression values across the 5 brain regions yielded 141 differentially expressed cis-regulated probe sets and 206 trans-regulated probe sets. Comparing the present results from inbred alcohol-preferring vs. congenic P.NP rats to earlier results from the reciprocal congenic NP.P vs. inbred alcohol-nonpreferring rats demonstrated that 74 cis-regulated probe sets were differentially expressed in the same direction and with a consistent magnitude of difference in at least one brain region.

Cis-regulated candidate genes for alcohol consumption that lie within the chromosome 4 QTL were identified and confirmed by consistent results in two independent experiments with reciprocal congenic rats. These genes are strong candidates for affecting alcohol preference in the inbred alcohol-preferring and inbred alcohol nonpreferring rats.

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New NHS Campaign Reveals Unseen Alcohol Damage

A new campaign backed by major health charities will warn drinkers of the unseen health damage caused by regularly drinking more than the NHS advises. The £6 million Government funded campaign shows the damage that is being done to drinkers’ organs while they are drinking in a pub or at home.

This is being launched by Public Health Minister, Gillian Merron today and is part of the cross-Government strategy to tackle the harms that alcohol causes.

The Department of Health has developed the campaign in association with Cancer Research UK, the British Heart Foundation and the Stroke Association to create the series of stark TV, press and outdoor adverts showing the harm that regularly drinking more than two drinks a day can cause.

A new YouGov poll launched to coincide with the campaign shows that more than half (55%) of English drinkers misguidedly believe that alcohol only damages your health if you regularly get drunk or binge drink. . . .

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Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant

In approximately one billion people, a point mutation inactivates a key detoxifying enzyme, aldehyde dehydrogenase (ALDH2).

This mitochondrial enzyme metabolizes toxic biogenic and environmental aldehydes, including the endogenously produced 4-hydroxynonenal (4HNE) and the environmental pollutant acrolein, and also bioactivates nitroglycerin.

ALDH2 is best known, however, for its role in ethanol metabolism. The accumulation of acetaldehyde following the consumption of even a single alcoholic beverage leads to the Asian alcohol-induced flushing syndrome in ALDH2*2 homozygotes. The ALDH2*2 allele is semidominant, and heterozygotic individuals show a similar but less severe phenotype.

We recently identified a small molecule, Alda-1, that activates wild-type ALDH2 and restores near-wild-type activity to ALDH2*2.

The structures of Alda-1 bound to ALDH2 and ALDH2*2 reveal how Alda-1 activates the wild-type enzyme and how it restores the activity of ALDH2*2 by acting as a structural chaperone.

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Request Reprint E-Mail: thurley@iupui.edu.
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Supervised Disulfiram in Relapse Prevention in Alcohol-Dependent Patients Suffering From Comorbid Borderline Personality Disorder—A Case Series

Disulfiram is widely used to prevent alcoholic relapse. However, due to the intended adverse reaction with ethanol, some believe that its use is dangerous for patients with personality disorders or psychiatric comorbidities because of their increased risk of impulsivity or suicidal behaviour.

We examined the safety and efficacy in relapse prevention of a series of alcoholics with borderline personality disorder (BPD).

Two out of eight patients remained completely abstinent during the supervised disulfiram therapy over a mean period of 9.25 months. Adherence to treatment was 18.44 ± 21.78 months. The first relapse occurred after 1.38 ± 1.41 months. The cumulated time of abstinence was 16.88 ± 20.48 months. The overall tolerability was considered to be high; dizziness and fatigue appeared in all patients at the beginning of the therapy but did not persist. No serious adverse events or ethanol–disulfiram interactions were observed. No suicidal behaviour was reported.

Although case observations should be interpreted with caution, supervised disulfiram seems to deserve further investigation in patients with comorbid BPD, for whom it appears to help prevent alcoholic relapse.

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Request Reprint E-Mail: jochen.mutschler@puk.zh.ch :

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Use of Carbohydrate-Deficient Transferrin (CDT) and a Combination of GGT and CDT (GGT–CDT) to Assess Heavy Alcohol Consumption in Traffic Medicine

Carbohydrate-deficient transferrin (CDT) has become widely used in traffic medicine to detect chronic alcohol abuse among subjects applying for driving-license renewal or regranting. By defining cut-off values in a large population of abstainers and moderate drinkers, we report on CDT, GGT–CDT (a combination of gamma-glutamylaminotransferase (GGT) and CDT) and the association between blood alcohol concentration (BAC) and CDT among Italian drivers.

A common CDT cut-off (1.8%) and gender-specific GGT–CDT cut-off (4.15% for males, 3.56% for females) were calculated as 99.9th percentiles of the control population. Also, 3% and 27% of subjects were classified as CDT positive respectively among drivers applying for license regranting and drivers involved in car accidents. A significant association between BAC and both CDT values and CDT positivity was found, with a frequency up to 49% of CDT samples, suggesting chronic alcohol abuse, among drivers with BAC >2.5g/l. Concordance between CDT and GGT–CDT was only moderate (kappa = 0.44), with CDT performing better than GGT–CDT.

A relevant proportion of drivers with high BAC are chronic abusers. GGT–CDT, previously validated with CDT immunoassays, should not be applied to traffic medicine in its current form and its performances re-evaluated with CDT measured by HPLC.

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Request Reprint E-Mail: vidali@med.unipmn.it
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H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence

Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function.

An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype.

Here, we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (CRHR1n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project.

Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from four indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence.

A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA (P <>

Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence.

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