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1.  Transitions In and Out of Alcohol Use Disorders: Their Associations with Conditional Changes in Quality of Life Over a 3-Year Follow-Up Interval† 
Aims: The aim of this study was to investigate longitudinal changes in quality of life (QOL) as a function of transitions in alcohol use disorders (AUD) over a 3-year follow-up of a general US population sample. Methods: The analysis is based on individuals who drank alcohol in the year preceding the Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions and were reinterviewed at Wave 2 (n = 22,245). Using multiple linear regression models, changes in SF-12 QOL were estimated as a function of DSM-IV AUD transitions, controlling for baseline QOL and multiple potential confounders. Results: Onset and offset of AUD were strongly associated with changes in mental/psychological functioning, with significant decreases in mental component summary (NBMCS) scores among individuals who developed dependence and significant increases among those who achieved full and partial remission from dependence. The increases in overall NBMCS and its social functioning, role emotional and mental health components were equally great for abstinent and nonabstinent remission from dependence, but improvements in bodily pain and general health were associated with nonabstinent remission only. Onset of abuse was unrelated to changes in QOL, and the increase in NBMCS associated with nonabstinent remission from abuse only was slight. Individuals with abuse only or no AUD who stopped drinking had significant declines in QOL. Conclusions: These results suggest the possible importance of preventing and treating AUD for maintaining and/or improving QOL. They are also consistent with the sick quitter hypothesis and suggest that abuse is less a mental disorder than a maladaptive pattern of behavior.
PMCID: PMC2605522  PMID: 19042925
2.  Transitions In and Out of Alcohol Use Disorders: Their Associations with Conditional Changes in Quality of Life Over a 3-Year Follow-Up Interval 
To investigate longitudinal changes in quality of life (QOL) as a function of transitions in alcohol use disorders (AUD) over a 3-year follow-up of a general U.S. population sample.
The analysis is based on individuals who drank alcohol in the year preceding the Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions and were reinterviewed at Wave 2 (n=22,245). Using multiple linear regression models, changes in SF-12 QOL were estimated as a function of DSM-IV AUD transitions, controlling for baseline QOL and multiple potential confounders.
Onset and offset of AUD were strongly associated with changes in mental/psychological functioning, with significant decreases in mental component summary (NBMCS) scores among individuals who developed dependence and significant increases among those who achieved full and partial remission from dependence. The increases in overall NBMCS and its social functioning, role emotional and mental health components were equally great for abstinent and nonabstinent remission from dependence, but improvements in bodily pain and general health were associated with nonabstinent remission only. Onset of abuse was unrelated to changes in QOL, and the increase in NBMCS associated with nonabstinent remission from abuse only was slight. Individuals with abuse only or no AUD who stopped drinking had significant declines in QOL.
These results suggest the possible importance of preventing and treating AUD for maintaining and/or improving QOL. They are also consistent with the sick quitter hypothesis and suggest that abuse is less a mental disorder than a maladaptive pattern of behavior.
PMCID: PMC2605522  PMID: 19042925
quality of life; QOL; HRQOL; alcohol use disorders; remission; transitions
3.  Corrigendum 
PMCID: PMC4351356  PMID: 25512658
4.  Exogenous Activation of Wnt/β-Catenin Signaling Attenuates Binge Alcohol-Induced Deficient Bone Fracture Healing 
Aims: Excessive alcohol consumption is associated with fracture non-union. Canonical Wnt pathway signaling activity regulates normal fracture healing. We previously demonstrated that binge alcohol exposure modulates β-catenin levels in the fracture callus of mice. Here, we sought to determine whether exogenous enhancement β-catenin signaling activity could restore normal fracture healing to binge-exposed mice. Methods: C57BL/6 male mice were exposed to episodic alcohol or saline for 6 total days of alcohol exposure over a 2-week period. Following alcohol exposure, mice were subjected to a stabilized mid-shaft tibia fracture. Beginning 4 days post-injury, mice received daily injections of either lithium chloride or saline subcutaneously. Protein levels of activated, inactivated, and total β-catenin and GSK-3β in fracture calluses were measured at post-injury day 9. Biomechanical strength testing and histology of callus tissue was assessed at post fracture day 14. Results: Binge alcohol was associated with decreased callus biomechanical strength, and reduced cartilaginous callus formation. Alcohol decreased levels of callus-associated activated β-catenin while concomitantly increasing the levels of inactive β-catenin at post-injury day 9. Alcohol also increased callus associated activated GSK-3β at post-injury day 9. Lithium chloride (an inhibitor of GSK-3β) treatment increased activated β-catenin protein levels, significantly decreased activated GSK-3β and restored cartilaginous callus formation and endochondral ossification. Conclusion: These data link alcohol-impaired fracture healing with deregulation of Canonical Wnt signaling activity in the fracture callus. Exogenous activation of the Wnt pathway using LiCl attenuated the damaging effects of binge alcohol exposure on the fracture healing process by modulating canonical Wnt signaling activity.
PMCID: PMC4060733  PMID: 24627571
5.  Exploring Structural Relationships Between Blood Alcohol Concentration and Signs and Clinical Assessment of Intoxication in Alcohol-Involved Injury Cases 
Aims: Although the relationship between the Y90 (blood alcohol concentration, BAC) and Y91 (clinician intoxication assessment) ICD-10 codes has received attention recently, the role of 10 signs of intoxication in the Y91–Y90 relationship has not been studied yet. This work examines these signs in the estimation of alcohol intoxication levels of patients in medical settings. Methods: Collected and analyzed were data on 1997 injured emergency room patients from 17 countries worldwide reporting drinking prior to injury or presenting with a non-zero BAC from 17 countries worldwide. A model is estimated describing how the 10 signs inform the Y91, Y90 prediction with the goal of the use of observations on patients in place of a biological measure. Results: Signs were consistent with a single underlying construct that strongly predicted Y91. Smell of alcohol on breath predicted Y91 above its contribution through the construct and was stronger for those with tolerance to alcohol than for those without. Controlling for Y91, no sign further contributed to prediction of Y90 indicating that Y91 incorporated all intoxication sign information in predicting Y90. Variance explained was high for Y91 (R2 = 0.84) and intoxication signs (above 0.72 for all but smell on the breath, 0.57) and lower for Y90 (0.38). Conclusion: Intoxication assessments are well predicted by overall intoxication severity, which itself is well represented by intoxication signs along with differential emphasis on smell of alcohol on breath, especially for those with alcohol tolerance. However, BAC levels remain largely unexplained by intoxication signs with a clinician's assessment serving as the primary predictive measure.
PMCID: PMC4060734  PMID: 24705784
6.  How Accurate Are Blood (or Breath) Tests for Identifying Self-Reported Heavy Drinking Among People with Alcohol Dependence? 
Managing patients with alcohol dependence includes assessment for heavy drinking, typically by asking patients. Some recommend biomarkers to detect heavy drinking but evidence of accuracy is limited.
Among people with dependence, we assessed the performance of disialo-carbohydrate-deficient transferrin (%dCDT, ≥1.7%), gamma-glutamyltransferase (GGT, ≥66 U/l), either %dCDT or GGT positive, and breath alcohol (> 0) for identifying 3 self-reported heavy drinking levels: any heavy drinking (≥4 drinks/day or >7 drinks/week for women, ≥5 drinks/day or >14 drinks/week for men), recurrent (≥5 drinks/day on ≥5 days) and persistent heavy drinking (≥5 drinks/day on ≥7 consecutive days). Subjects (n = 402) with dependence and current heavy drinking were referred to primary care and assessed 6 months later with biomarkers and validated self-reported calendar method assessment of past 30-day alcohol use.
The self-reported prevalence of any, recurrent and persistent heavy drinking was 54, 34 and 17%. Sensitivity of %dCDT for detecting any, recurrent and persistent self-reported heavy drinking was 41, 53 and 66%. Specificity was 96, 90 and 84%, respectively. %dCDT had higher sensitivity than GGT and breath test for each alcohol use level but was not adequately sensitive to detect heavy drinking (missing 34–59% of the cases). Either %dCDT or GGT positive improved sensitivity but not to satisfactory levels, and specificity decreased. Neither a breath test nor GGT was sufficiently sensitive (both tests missed 70–80% of cases).
Although biomarkers may provide some useful information, their sensitivity is low the incremental value over self-report in clinical settings is questionable.
PMCID: PMC4060735  PMID: 24740846
7.  Chronic Ethanol Consumption Increases Myocardial Mitochondrial DNA Mutations: A Potential Contribution by Mitochondrial Topoisomerases 
Aims: Alcoholic cardiomyopathy (ACM) presents as decreased myocardial contractility, arrhythmias and secondary non-ischemic dilated cardiomyopathy leading to heart failure. Mitochondrial dysfunction is known to have a significant role in the development and complications of ACM. This study investigated if chronic ethanol feeding promoted myocardial mitochondrial topoisomerase dysfunction as one underlying cause of mitochondrial DNA (mtDNA) damage and mitochondrial dysfunction in ACM. Methods: The impact of chronic ethanol exposure on the myocardial mitochondria was examined in both neonatal cardiomyocytes using 50 mM ethanol for 6 days and in rats assigned to control or ethanol feeding groups for 4 months. Results: Chronic ethanol feeding led to significant (P < 0.05) decreases in M-mode Fractional Shortening, ejection fraction, and the cardiac output index as well as increases in Tau. Ethanol feeding promoted mitochondrial dysfunction as evidenced by significantly decreased left ventricle cytochrome oxidase activity and decreases in mitochondrial protein content. Both in rats and in cultured cardiomyocytes, chronic ethanol presentation significantly increased mtDNA damage. Using isolated myocardial mitochondria, both mitochondrial topoisomerase-dependent DNA cleavage and DNA relaxation were significantly altered by ethanol feeding. Conclusion: Chronic ethanol feeding compromised cardiovascular and mitochondrial function as a result of a decline in mtDNA integrity that was in part the consequence of mitochondrial topoisomerase dysfunction. Understanding the regulation of the mitochondrial topoisomerases is critical for protection of mtDNA, not only for the management of alcoholic cardiomyopathy, but also for the many other clinical treatments that targets the topoisomerases in the alcoholic patient.
PMCID: PMC4060737  PMID: 24852753
8.  Effectiveness of Nurse-Practitioner-Delivered Brief Motivational Intervention for Young Adult Alcohol and Drug Use in Primary Care in South Africa: A Randomized Clinical Trial 
Aims: To assess the effectiveness of brief motivational intervention for alcohol and drug use in young adult primary care patients in a low-income population and country. Methods: A randomized controlled trial in a public-sector clinic in Delft, a township in the Western Cape, South Africa recruited 403 patients who were randomized to either single-session, nurse practitioner-delivered Brief Motivational Intervention plus referral list or usual care plus referral list, and followed up at 3 months. Results: Although rates of at-risk alcohol use and drug use did not differ by treatment arm at follow-up, patients assigned to the Brief Motivational Intervention had significantly reduced scores on ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) for alcohol—the most prevalent substance. Conclusion: Brief Motivational Intervention may be effective at reducing at-risk alcohol use in the short term among low-income young adult primary care patients; additional research is needed to examine long-term outcomes.
PMCID: PMC4060738  PMID: 24899076
9.  Alcoholic Liver Disease: A Synopsis of the Charles Lieber's Memorial Symposia 2009–2012 
This paper is based upon the ‘Charles Lieber Satellite Symposia’ organized by Manuela G. Neuman at each of the 2009–2012 Research Society on Alcoholism (RSA) Annual Meetings. The presentations represent a broad spectrum dealing with alcoholic liver disease (ALD). In addition, a literature search (2008–2013) in the discussed area was performed in order to obtain updated data. The presentations are focused on genetic polymorphisms of ethanol metabolizing enzymes and the role of cytochrome P4502E1 (CYP2E1) in ALD. In addition, alcohol-mediated hepatocarcinogenesis, immune response to alcohol and fibrogenesis in alcoholic hepatitis as well as its co-morbidities with chronic viral hepatitis infections in the presence or absence of human deficiency virus are discussed. Finally, emphasis was led on alcohol and drug interactions as well as liver transplantation for end-stage ALD.
PMCID: PMC4072899  PMID: 24816574
10.  Effects of Ceftriaxone on Systemic and Central Expression of Anti- and Pro-inflammatory Cytokines in Alcohol-Preferring (P) Rats Exposed to Ethanol 
Aims: Determine the effect of reduction in ethanol consumption by alcohol-preferring (P) rats, following ceftriaxone treatment, on the cytokines levels in prefrontal cortex (PFC) and plasma. Methods: Following 5 weeks of free access to ethanol (15 and 30%), P rats were treated daily with ceftriaxone or saline vehicle for either 2 or 5 consecutive days. Plasma and PFC were collected from ceftriaxone- and saline vehicle-treated groups, and assayed for the levels of pro- and anti-inflammatory cytokines. Results: A significant increase in the plasma level of anti-inflammatory cytokine IL-10 was observed in the ceftriaxone-treated group when compared with the saline-treated group in both the 2-day and 5-day treatments. Furthermore, ceftriaxone treatment for 2 days induced reduction in TNFα level in both plasma and PFC. Additionally, ceftriaxone treatment for 2 days significantly reduced the IFNγ level in PFC. Conclusion: These findings show the ability of ceftriaxone to reduce alcohol consumption and induce modulation of the anti-inflammatory and pro-inflammatory cytokines levels in P rats.
PMCID: PMC4133570  PMID: 24743029
11.  Can Cannabis be Considered a Substitute Medication for Alcohol? 
Aims: Substituting cannabis for alcohol may reduce drinking and related problems among alcohol-dependent individuals. Some even recommend prescribing medical cannabis to individuals attempting to reduce drinking. The primary aim of this review is to assess whether cannabis satisfies the seven previously published criteria for substitute medications for alcohol [e.g. ‘reduces alcohol-related harms’; ‘is safer in overdose than alcohol’; ‘should offer significant health economic benefits’; see Chick and Nutt ((2012) Substitution therapy for alcoholism: time for a reappraisal? J Psychopharmacol 26:205–12)]. Methods: Literature review. Results: All criteria appear either satisfied or partially satisfied, though studies relying on medical cannabis patients may be limited by selection bias and/or retrospective designs. Individual-level factors, such as severity of alcohol problems, may also moderate substitution. Conclusions: There is no clear pattern of outcomes related to cannabis substitution. Most importantly, the recommendation to prescribe alcohol-dependent individuals cannabis to help reduce drinking is premature. Future studies should use longitudinal data to better understand the consequences of cannabis substitution.
PMCID: PMC3992908  PMID: 24402247
12.  Interactive Effects of OPRM1 and DAT1 Genetic Variation on Subjective Responses to Alcohol 
Aims: Subjective response to alcohol represents a marker of alcoholism risk. The A118G single-nucleotide polymorphism (SNP) of the mu opioid receptor (OPRM1) gene has been associated with subjective response to alcohol. Recently, the dopamine transporter (DAT1) variable number of tandem repeat (VNTR; SLC6A3) has been found to interact with the OPRM1 A118G SNP in predicting neural and behavioral responses to naltrexone and to alcohol. This exploratory study examines the OPRM1 × DAT1 interaction on subjective responses to alcohol. Methods: Non-treatment-seeking problem drinkers (n = 295) were assessed in the laboratory for alcohol dependence. Following prospective genotyping for the OPRM1 gene, 43 alcohol-dependent individuals were randomized to two intravenous infusion sessions, one of alcohol (target BrAC = 0.06 g/dl) and one of saline. Measures of subjective responses to alcohol were administered in both infusion sessions. Results: Analyses revealed significant Alcohol × OPRM1 × DAT1 interactions for alcohol-induced stimulation, vigor and positive mood as well as significant Alcohol × OPRM1 × DAT1 × Time interactions for stimulation and positive mood. These effects were such that, compared with other genotype groups, OPRM1 G-allele carriers + DAT1 A10 homozygotes reported steeper increases in stimulation and positive mood across rising BrAC, when compared with placebo. All Alcohol × OPRM1 × DAT1 interactions remained significant when analyses were restricted to a subsample of Caucasian participants (n = 34); however, 4-way interactions did not reach statistical significance in this subsample. Conclusions: This study suggests that the contribution of OPRM1 genotype to alcohol-induced stimulation, vigor and positive mood is moderated by DAT1 genotype. These findings are consistent with the purported interaction between opioidergic and dopaminergic systems in determining the reinforcing properties of alcohol.
PMCID: PMC3992909  PMID: 24421289
13.  Risky Alcohol Use Among Migrant Women in Entertainment Venues in China 
Aims: The aims of this study are to describe the prevalence of hazardous drinking among migrant women working in entertainment venues in an urban setting in China and to identify specific risk factors and locations where hazardous drinking occurs. Methods: From March to July 2012, we conducted a cross-sectional survey of 358 young migrant women working in entertainment venues in the capital city of Hefei, Anhui Province, China. Participants were asked about information regarding their demographic characteristics, sexual behavior, mental health, alcohol use and drug use. Results: Overall, 203 (57%) participants had an AUDIT score ≥8 (risky drinking) and 95 (27%) women had an AUDIT ≥16 (probable dependence). Greater likelihood of probable alcohol dependence was associated with being younger (OR = 0.85, 95% CI: 0.76–0.95), working at an affluent venue (OR = 2.46, 95% CI: 1.13–5.36) and depressive symptoms during the past week (OR = 2.74, 95% CI = 1.10–6.83). Conclusion: Our study documents risky drinking practices among female migrants, irrespective of whether or not women reported engaging in commercial sex, working in entertainment venues. Our data suggest that entertainment venues, particularly those that are higher end (i.e. affluent) venues, should be targeted for public health interventions aimed to reduce harmful drinking practices.
PMCID: PMC3992910  PMID: 24452724
14.  Alcohol Consumption and Liver Disease in Australia: A Time Series Analysis of the Period 1935–2006 
Aims: The aim of the study was to examine for Australia whether the link between population alcohol consumption and liver disease mortality varies over time, using 71 years of data. Methods: Overall and gender-specific rates of liver disease mortality were analysed in relation to total alcohol consumption as well as for different beverage types by using autoregressive integrated moving average (ARIMA) time series methods. Separate models were developed for the entire time period and for two sub-periods (1935–1975, 1976–2006). Results: A 1-l increase in adult per capita consumption of pure alcohol led to a rise of ∼10% in overall liver disease mortality rates and a 11 and 9% increase in female and male liver disease mortality, respectively. The strength of the relationship between per capita consumption and liver disease mortality diminished over time. Spirits consumption was found to be the main driving factor in liver mortality rates between 1935 and 1975, while beer consumption was found to be the most significant predictor in liver diseases in the last three decades. In a comparative perspective, the effect of per capita alcohol consumption on liver disease in Australia is similar to the USA, Southern and Eastern Europe countries, but weaker than in Canada and western European countries. Conclusion: An increase in per capita alcohol consumption in Australia is likely to lead to an increase in liver disease. Changes in the most important beverage over the study period suggest substantial shifts in drinking patterns and preferences among the heaviest Australian drinkers.
PMCID: PMC4007106  PMID: 24052533
15.  RCT of Effectiveness of Motivational Enhancement Therapy Delivered by Nurses for Hazardous Drinkers in Primary Care Units in Thailand 
To determine the effectiveness of Motivational Enhancement Therapy (MET) for hazardous drinkers in Primary Care Unit (PCU) settings in rural Thailand.
A randomized controlled trial was conducted in eight PCUs in Ubonratchatanee and Chachoengsao provinces in Thailand. Hazardous drinkers were identified using the World Health Organization-recommended Alcohol Use Disorder Identification Test. Of 117 eligible participants (91% male), 59 were randomized to the intervention group to receive MET in three individual appointments with a trained nurse and 58 to an assessment-only control group. Outcome evaluations were carried out after 6 weeks, 3 months and 6 months.
Follow-up data were available on 84, 94 and 91% of subjects, respectively, at the three intervals. Self-reported drinks per drinking day, frequency of hazardous drinking assessed either on a daily or weekly basis, and of binge drinking sessions were reduced in the intervention group more than in the control group (P < 0.05) after both 3 and 6 months. The groups did not generally differ at 6 weeks. However, although self-reported consumption in both groups fell from baseline to 6-month follow-up, serum gamma-glutamyl transferase increased in both groups, which raises doubts about the validity of this marker in this sample and/or the validity of the self-reported data in this study.
MET delivered by nurses in PCUs in Thailand appears to be an effective intervention for male hazardous drinkers. Uncertainties about the validity of self-reported data jeopardize the safety of this conclusion.
PMCID: PMC4394355  PMID: 20236990
16.  Navigating the Alcohol Treatment Pathway: A Qualitative Study from the Service Users' Perspective 
Provision of effective treatment for dependent drinkers has been identified as a priority in England yet evidence suggests that access is problematic and there are low levels of retention. This qualitative study explores how the alcohol treatment system is experienced by service users, identifying barriers and facilitators that influence treatment outcomes.
A total of 20 semi-structured face-to-face interviews were conducted with patients from community alcohol treatment services in three London boroughs in 2012. Interviews were undertaken one year after initially entering treatment. A thematic analysis was conducted, with the results further abstracted to relate them to specific aspects of the treatment journey.
Patients journeys were characterized by a perceived lack of control leading to help-seeking, with treatment outcomes influenced by an individuals' self-efficacy and the capabilities and skills of staff in actively engaging and supporting patients on the journey. A focus of services on the detoxification process and fragmented care pathways impacted negatively on engagement.
Current alcohol care pathways require significant levels of motivation and self-efficacy to navigate that few patients possess. Pathways need to better reflect the capacity and capabilities of patients to be successful in supporting recovery.
PMCID: PMC4474003  PMID: 25825267
17.  Increased Facial Attractiveness Following Moderate, but not High, Alcohol Consumption 
Aims: Alcohol consumption is known to be associated with risky sexual behaviours, but this relationship may be complex and bidirectional. We explored whether alcohol consumption leads to the consumer being rated as more attractive than sober individuals.
Methods: Heterosexual social alcohol consumers completed an attractiveness-rating task, in which they were presented with pairs of photographs depicting the same individual, photographed while sober and after having consumed alcohol (either 0.4 or 0.8 g/kg), and required to decide which image was more attractive.
Results: Photographs of individuals who had consumed a low dose of alcohol (equivalent to 250 ml of wine at 14% alcohol by volume for a 70 kg individual) were rated as more attractive than photographs of sober individuals. This was not observed for photographs of individuals who had consumed a high dose of alcohol.
Conclusion: In addition to perceiving others as more attractive, a mildly intoxicated alcohol consumer may also be perceived as more attractive by others. This in turn may play a role in the relationship between alcohol consumption and risky sexual behaviour.
PMCID: PMC4398990  PMID: 25716115
18.  Prevalence of Major Depressive Disorder Among Spouses of Men Who Use Alcohol in a Rural Community in Central Sri Lanka 
Aims: To estimate the prevalence of major depressive disorder (MDD) among spouses of men who use alcohol in two rural areas in Sri Lanka, and to examine whether the severity of alcohol-related problems (ARPs) in men and presence of alcohol-related domestic violence are associated with MDD among these women.
Method: In a cross-sectional study, ARPs among men were assessed using Alcohol Use Disorders Identification Test (AUDIT) questionnaire filled in by men, and domestic violence and husbands' drinking pattern data obtained from the women. MDD among the women was ascertained using the Structured Clinical Interview for DSM–IV Disorders for major depression. Using logistic regression we examined whether age, past history of depression, different indices of ARPs and domestic violence were associated with current MDD among the women.
Results: Point prevalence of MDD in the sample was 33.3% (95% CI: 25.93, 40.73%). Once adjusted for other factors, morning drinking of the spouse (odds ratio = 4.11, 95% CI: 1.25, 13.47; P = 0.019) and increasing age (odds ratio = 1.05, 95% CI: 1.01, 1.09; P = 0.003) significantly increased the odds of MDD. Being subjected to domestic violence/arguments also had a trend to be associated with MDD among women, but was not significant (odds ratio = 2.29, 95% CI: 0.95, 5.48; P = 0.062).
Conclusion: The prevalence of MDD among spouses of men who use alcohol is markedly higher than that has been observed among Sri Lankan women in previous studies. The prevalence of MDD in women seems to increase when their husbands are morning drinkers, and with increasing age.
PMCID: PMC4398988  PMID: 25589089
19.  Alcohol, Moods and Male–Female Differences: Daily Interactive Voice Response over 6 Months 
Aims: The goal of this study was to better understand the predictive relationship in both directions between negative (anger, sadness) and positive (happiness) moods and alcohol consumption using daily process data among heavy drinkers. Methods: Longitudinal daily reports of moods, alcohol use and other covariates such as level of stress were assessed over 180 days using interactive voice response telephone technology. Participants were heavy drinkers (majority meeting criteria for alcohol dependence at baseline) recruited through their primary care provider. The sample included 246 (166 men, 80 women) mostly Caucasian adults. Longitudinal statistical models were used to explore the varying associations between number of alcoholic drinks and mood scores the next day and vice versa with gender as a moderator. Results: Increased alcohol use significantly predicted decreased happiness the next day (P < 0.005), more strongly for females than males. Increased anger predicted higher average alcohol use the next day for males only (P < 0.005). Conclusion: This daily process study challenges the notion that alcohol use enhances positive mood for both males and females. Our findings also suggest a strong association between anger and alcohol use that is specific to males. Thus, discussions about the effects of drinking on one's feeling of happiness may be beneficial for males and females as well as anger interventions may be especially beneficial for heavy-drinking males.
PMCID: PMC3865813  PMID: 23847021
20.  The Relationship Between Midlife and Late Life Alcohol Consumption, APOE e4 and the Decline in Learning and Memory Among Older Adults 
Aims: The aim of the study was to determine whether the trajectory of learning and memory is modified according to an interaction between midlife or late life alcohol consumption status and the presence of one or more APOE e4 alleles. Methods: This was a secondary analysis of cognitive, genetic and alcohol consumption data collected from members of the Framingham Heart Study Offspring Cohort. Results: Light and moderate alcohol consumption during late life was associated with greater decline in learning and memory among APOE e4 carriers, whereas light and moderate alcohol consumption was associated with an increase in learning and memory among non-APOE e4 carriers. There was not a significant interaction between midlife alcohol consumption status and APOE e4 on the trajectory of learning and memory. Conclusion: Light to moderate alcohol consumption during late life may protect against a decline in learning and memory for non-APOE e4 allele carriers, but not for older adults who carry one or more APOE e4 alleles.
PMCID: PMC3865814  PMID: 24049153
21.  A GABRA2 Variant Is Associated with Increased Stimulation and ‘High’ Following Alcohol Administration 
Aims: Variation in genes encoding GABAA receptor subunits has been implicated in the risk of alcohol dependence (AD). We sought to replicate and extend previous findings of a moderating effect of single nucleotide polymorphisms (SNPs) in GABRA2 (which encodes the GABAA α-2 subunit) on the subjective effects of alcohol by examining SNPs in this and the adjacent GABRG1 gene on chromosome 4. Methods: Fifty-two European-Americans (22 males, 28 light drinkers and 24 heavy drinkers) completed 3 laboratory sessions, during which they drank low-dose, high-dose, or placebo alcohol prior to undergoing periodic assessments of stimulation, sedation and drug enjoyment. We genotyped subjects for three SNPs previously associated with AD: rs279858 in GABRA2, and rs7654165 and rs6447493 in GABRG1. Results: Two SNPs were associated with altered stimulatory effects of alcohol as measured on the Biphasic Alcohol Effects Scale, (rs279858: P = 0.0046; rs6447493: P = 0.0023); both effects were in the opposite direction of previous findings. Carriers of the rs279858 C allele experienced greater stimulation from alcohol. Further inspection of the rs6447493 interaction did not support a pharmacogenetic effect. The effects of rs279858 (but not the other two SNPs) on items from a secondary outcome measure, the Drug Effects Questionnaire (DEQ), were significant. Higher ratings by individuals with the C allele were observed on the DEQ items ‘feel the alcohol effect’ (P < 0.001), ‘like the alcohol effect’ (P < 0.001) and feel ‘high’ (P < 0.001). Conclusion: We did not find that the GABRG1 SNPs rs7654165 and rs6447493 moderated the effects of alcohol. Greater stimulatory and euphoric effects of alcohol in carriers of the rs279858 C allele may, in part, explain the previously reported association of this allele with AD.
PMCID: PMC3865816  PMID: 24166645
This paper describes adolescents’ exposure to alcohol advertising in stores and to alcohol-branded promotional items and their association with self-reported drinking.
A cross-sectional survey was administered in non-tracked required courses to sixth, seventh, and eighth graders (n = 2125) in three California middle schools. Logistic regressions compared the odds of ever (vs. never) drinking and current (vs. ever) drinking after controlling for psychosocial and other risk factors for adolescent alcohol use.
Two-thirds of middle school students reported at least weekly visits to liquor, convenience, or small grocery stores where alcohol advertising is widespread. Such exposure was associated with higher odds of ever drinking, but was not associated with current drinking. One-fifth of students reported owning at least one alcohol promotional item. These students were three times more likely to have ever tried drinking and 1.5 times more likely to report current drinking than students without such items.
This study provides clear evidence of an association of adolescent drinking with weekly exposure to alcohol advertising in stores and with ownership of alcohol promotional items. Given their potential influence on adolescent drinking behaviour, retail ads, and promotional items for alcohol deserve further study.
PMCID: PMC4238906  PMID: 17218364
23.  Time Course of SERCA 2b and Calreticulin Expression in Purkinje Neurons of Ethanol-Fed Rats with Behavioral Correlates 
Chronic ethanol consumption for 40 weeks in adult rats results in dilation of the extensive smooth endoplasmic reticulum (SER), a major component of the calcium homeostatic system within Purkinje neuron (PN) dendrites. Aims: The aim of the present study was to determine whether chronic ethanol consumption results in alterations of the sarco/endoplasmic reticulum Ca2+ ATPase pump (SERCA) on the SER membrane of PN dendrites. The density of calreticulin, a calcium chaperone, was also investigated in the PN along with balancing ability. Methods: Ninety 8-month-old rats were exposed to rat chow, the AIN-93 M liquid control or ethanol diets (30/diet) for a duration of 10, 20 or 40 weeks (30/duration). Age changes relative to the rat chow controls were assessed with 3-month-old control rats (n = 10). Balance was assessed prior to euthanasia. Quantitative immunocytochemistry was used to determine the density of SERCA 2b + dendrites and calreticulin + PN soma and nuclei. Molecular layer volumes were also determined. Results: Following 40 weeks of ethanol treatment, there were ethanol-induced decreases in SERCA 2b densities within the dendritic arbor and decreased balancing ability on the more difficult round rod balance test. There were no ethanol-induced changes in calreticulin densities. Conclusion: It can be concluded that ethanol-induced decreases in the SERCA pump accompany SER dilation and contribute to previously reported ethanol-induced dendritic regression in PN. Ethanol-induced changes in balance also occurred. Chronic ethanol consumption does not alter calreticulin expression in PN.
PMCID: PMC3799558  PMID: 23884168
24.  A Cross-Sectional Study of Attitudes About the Use of Genetic Testing for Clinical Care Among Patients with an Alcohol Use Disorder 
Aim: Modification and individualization of medical treatments due to genetic testing has the potential to revolutionize healthcare delivery. As evidence mounts that genetic testing may improve treatment decisions for patients with alcohol use disorder (AUD), we explored patient concerns and attitudes toward genetic testing. Methods: Subjects of two USA cross-sectional AUD studies were surveyed regarding their attitudes regarding the use of genetic testing for AUD treatment. Results: Four hundred and fifty-seven participants were surveyed. Overall, subjects showed a high degree of willingness to provide DNA for clinical use and recognized genetics as important to the pathophysiology of a number of disorders including AUD. There were, however, significant concerns expressed related to insurance denial or employment problems. Conclusion: We found that patients enrolled in AUD studies had some concerns about use of genetic testing. The patients in these two samples were, however, willing and knowledgeable about providing DNA samples.
PMCID: PMC3799560  PMID: 23926212
25.  Use of Novel Technology-Based Techniques to Improve Alcohol-Related Outcomes in Clinical Trials 
With a better understanding of the biologic basis of alcohol dependence and the considerable financial burden of alcohol abuse and dependence, the number of alcohol-related clinical pharmacotherapy trials has been on the rise. Subsequently, the potential to find efficacious treatments is more promising. Unfortunately, alcohol-related trials face a number of challenges, as a result of the difficulties that arise from traditional and outdated methods to collect data and ensure medication adherence. Novel technology-based assessments, such as ecological momentary assessment, interactive voice response, transdermal sensor and medication-event monitoring system provide a prospective solution—albeit not without possible concerns—to the difficulties faced in alcohol-related clinical trials. Clinical trials are meant to define the efficacy of the treatment and to determine an effective and safe dosage. However, due to lack of adherence a drug could inappropriately or mistakenly be judged as ineffective for treating a specific disorder. The described technologies may be important tools to prevent false negatives in validating drug efficacy, to provide consistency in clinical trials and to improve available data regarding the study of pharmacotherapies for alcohol dependence.
PMCID: PMC3816323  PMID: 23955872

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