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Sample records for alcohol dependence results

  1. Neurobiology of Alcohol Dependence

    PubMed Central

    Gilpin, Nicholas W.; Koob, George F.

    2008-01-01

    Alcoholism is a debilitating disorder for the individual and very costly for society. A major goal of alcohol research is to understand the neural underpinnings associated with the transition from alcohol use to alcohol dependence. Positive reinforcement is important in the early stages of alcohol use and abuse. Negative reinforcement can be important early in alcohol use by people self-medicating coexisting affective disorders, but its role likely increases following the transition to dependence. Chronic exposure to alcohol induces changes in neural circuits that control motivational processes, including arousal, reward, and stress. These changes affect systems utilizing the signaling molecules dopamine, opioid peptides, γ-aminobutyric acid, glutamate, and serotonin, as well as systems modulating the brain’s stress response. These neuroadaptations produce changes in sensitivity to alcohol’s effects following repeated exposure (i.e., sensitization and tolerance) and a withdrawal state following discontinuation of alcohol use. Chronic alcohol exposure also results in persistent neural deficits, some of which may fully recover following extended periods of abstinence. However, the organism remains susceptible to relapse, even after long periods of abstinence. Recent research focusing on brain arousal, reward, and stress systems is accelerating our understanding of the components of alcohol dependence and contributing to the development of new treatment strategies. PMID:19881886

  2. Sociodemographic Factors and Comorbidities Associated with Remission from Alcohol Dependence: Results from a Nationwide General Population Survey in Korea

    PubMed Central

    Han, Song Yi; Cho, Maeng Je; Won, Seunghee; Hong, Jin Pyo; Bae, Jae Nam; Cho, Seong-Jin; Park, Jong-Ik; Lee, Jun-Young; Jeon, Hong Jin

    2015-01-01

    Objective The lifetime prevalence of alcohol dependence in South Korea remains higher than other countries. The aim of our study is to identify factors associated with remission from alcohol dependence. Methods Data from the Korean Epidemiological Catchment Area-Replication (KECA-R) study were used in our study. The Korean version of the Composite International Diagnostic Interview 2.1 (K-CIDI 2.1) was administered. Remission was defined as having no symptom of alcohol dependence for 12 months or longer at the time of the interview. Demographic and clinical variables putatively associated with remission from alcohol dependence were examined by t-test, chi-square-test and logistic regression analysis. Results The lifetime prevalence rate of alcohol dependence was 7.0%. Among them, 3.2% of the subjects were diagnosed with active alcohol dependence in the previous 12 months, and 3.8% were found to be in remission. Subjects in 35- to 44-year-old group, not living with partner group, and lower level of educational attainment group were more likely to be in the active alcohol dependence state. Of the comorbid mental disorders, dysthymia, anxiety disorder, nicotine use, and nicotine dependence were more common among the actively alcohol-dependent subjects. Conclusion There is considerable level of recovery from alcohol dependence. Attention to factors associated with remission from alcohol dependence may be important in designing more effective treatment and prevention programs in this high-risk population. PMID:26207123

  3. [Prevention of alcohol dependence].

    PubMed

    Trova, A C; Paparrigopoulos, Th; Liappas, I; Ginieri-Coccossis, M

    2015-01-01

    With the exception of cardiovascular diseases, no other medical condition causes more serious dysfunction or premature deaths than alcohol-related problems. Research results indicate that alcohol dependent individuals present an exceptionally poor level of quality of life. This is an outcome that highlights the necessity of planning and implementing preventive interventions on biological, psychological or social level, to be provided to individuals who make alcohol abuse, as well as to their families. Preventive interventions can be considered on three levels of prevention: (a) primary prevention, which is focused on the protection of healthy individuals from alcohol abuse and dependence, and may be provided on a universal, selective or indicated level, (b) secondary prevention, which aims at the prevention of deterioration regarding alcoholic dependence and relapse, in the cases of individuals already diagnosed with the condition and (c) tertiary prevention, which is focused at minimizing deterioration of functioning in chronically sufferers from alcoholic dependence. The term "quaternary prevention" can be used for the prevention of relapse. As for primary prevention, interventions focus on assessing the risk of falling into problematic use, enhancing protective factors and providing information and health education in general. These interventions can be delivered in schools or in places of work and recreation for young people. In this context, various programs have been applied in different countries, including Greece with positive results (Preventure, Alcolocks, LST, SFP, Alcohol Ignition Interlock Device). Secondary prevention includes counseling and structured help with the delivery of programs in schools and in high risk groups for alcohol dependence (SAP, LST). These programs aim at the development of alcohol refusal skills and behaviors, the adoption of models of behaviors resisting alcohol use, as well as reinforcement of general social skills. In the

  4. Awareness and Treatment of Alcohol Dependence in Japan: Results from Internet-Based Surveys in Persons, Family, Physicians and Society

    PubMed Central

    Taguchi, Yurie; Takei, Yoshiyuki; Sasai, Ryoko; Murteira, Susana

    2014-01-01

    Aims: To understand current awareness of, and views on, treatment of alcohol dependence in Japan. Methods: (a) Nationwide internet-based survey of 520 individuals, consisting of 52 diagnosed alcohol-dependent (AD) persons, 154 potentially alcohol-dependent (ADP) persons, 104 family members and 106 friends/colleagues of AD persons, and 104 general individuals, derived from a consumer panel where the response rate was 64.3%. We enquired into awareness about the treatment of alcohol dependence and patient pathways through the healthcare network. (b) Nationwide internet-based survey of physicians (response rate 10.1% (2395/23,695) to ask 200 physicians about their management of alcohol use disorders). Results: We deduced that 10% of alcohol-dependent Japanese persons had ever been diagnosed with alcohol dependence, with only 3% ever treated. Regarding putative treatment goals, 20–25% of the AD and ADP persons would prefer to attempt to abstain, while 60–75% preferred ‘reduced drinking.’ A half of the responding physicians considered abstinence as the primary treatment goal in alcohol dependence, while 76% considered reduced drinking as an acceptable goal. Conclusion: AD and ADP persons in Japan have low ‘disease awareness’ defined as ‘understanding of signs, symptoms and consequences of alcohol use disorders,’ which is in line with the overseas situation. The Japanese drinking culture and stigma toward alcohol dependence may contribute to such low disease awareness and current challenging treatment environment. While abstinence remains the preferred treatment goal among physicians, reduced drinking seems to be an acceptable alternative treatment goal to many persons and physicians in Japan. PMID:24893604

  5. Consumption of Alcohol Surrogates Among Alcohol-Dependent Women.

    PubMed

    Razvodovsky, Yury Evgeny

    2015-01-01

    This is the first in-depth study of alcohol and surrogate drinking patterns, types, reasons, and correlates among alcohol-dependent women in Belarus. The structured interviews were performed in 2013 with 103 alcohol-dependent women admitted to a narcological clinic in Grodno, Belarus. The results suggest that at least 30.3% of alcohol-dependent women regularly consume samogon (moonshine) and 10.8% of women use surrogates, the most popular among which are medications with a high percentage of ethanol and industrial spirits. The belief that samogon exceeds licensed vodka in quality is the main motive for its consumption. The results from the present study confirm that noncommercial alcohol use is common among alcohol-dependent women although its use may be underreported. These findings emphasize that the implementation of a comprehensive alcohol policy must take fully into account the consumption of alcohol from illicit sources. PMID:26549001

  6. Alcoholism, Field Dependency and Organic Impairment.

    ERIC Educational Resources Information Center

    Lafferty, Patricia; Kahn, Marvin W.

    Although research has suggested that field dependency is a relatively stable characteristic of alcoholics, the results have been confounded by the use of different measures and different time intervals. To investigate the degree of organic brain impairment and its association with measured field dependency amongst alcoholics, 41 male alcoholics,…

  7. Mindfulness training modifies cognitive, affective, and physiological mechanisms implicated in alcohol dependence: Results of a randomized controlled pilot trial

    PubMed Central

    Garland, Eric L.; Gaylord, Susan A.; Boettiger, Charlotte A.; Howard, Matthew O.

    2010-01-01

    Mindfulness training may disrupt the risk chain of stress-precipitated alcohol relapse. In 2008, 53 alcohol-dependent adults (mean age = 40.3) recruited from a therapeutic community located in the urban southeastern U.S. were randomized to mindfulness training or a support group. Most participants were male (79.2%), African American (60.4%), and earned < $20,000 annually (52.8%). Self-report measures, psychophysiological cue-reactivity, and alcohol attentional bias were analyzed via repeated measures ANOVA. 37 participants completed the interventions. Mindfulness training significantly reduced stress and thought suppression, increased physiological recovery from alcohol cues, and modulated alcohol attentional bias. Hence, mindfulness training appears to target key mechanisms implicated in alcohol dependence, and therefore may hold promise as an alternative treatment for stress-precipitated relapse among vulnerable members of society. PMID:20648913

  8. Consumption of Noncommercial Alcohol among Alcohol-Dependent Patients.

    PubMed

    Razvodovsky, Y E

    2013-01-01

    This study explores types of alcohol and surrogates consumed, patterns of consumption, and reasons behind noncommercial alcohol consumption among alcohol-dependent patients in Belarus. The study was conducted in the Belarusian city Grodno in 2012 with 223 alcoholics admitted to narcological clinic using structured interviews. The results suggest that at least 20.2% of alcohol dependent patients regularly consume samogon and 11.8% of patients use surrogates, the most popular among which are medications with a high percentage of ethanol and industrial spirits. The belief that, according to quality criteria, samogon exceeds licensed vodka is the main motive for its consumption. The results of this study suggest the existence of the problem of consumption of noncommercial alcohol among alcohol dependent patients in Belarus. PMID:24233448

  9. ▼Nalmefene for alcohol dependence.

    PubMed

    2014-05-01

    The burden of morbidity and mortality resulting from alcohol dependence is high. World Health Organization (WHO) figures suggest that in the UK the prevalence of alcohol use disorders in those aged 15 years and older is around 6.4% for men and 1.5% for women.1 Reduction of harm resulting from alcohol dependence remains a high priority in all four devolved health services in the UK.2-5 Several medicines are licensed for the maintenance of abstinence in alcohol-dependent patients. However, until recently no drug was licensed for the management of alcohol dependence in people who are still drinking. ▼Nalmefene (Selincro, Lundbeck), an opioid modulator licensed for the reduction of alcohol consumption, was launched in the UK in May 2013.6,7 Here we discuss the evidence for its effectiveness and safety and consider its place in therapy. PMID:24809337

  10. Genetic factors influencing alcohol dependence

    PubMed Central

    Mayfield, R D; Harris, R A; Schuckit, M A

    2008-01-01

    Plentiful data from both animal and human studies support the importance of genetic influences in substance abuse and dependence (Bierut et al., 1998; Tsuang et al., 1998; Kendler et al., 2003). This review summarizes the evidence supporting such genetic influences, places them into perspective regarding animal and human studies, discusses the importance of both genes and environment, and highlights some specific genes of interest regarding the vulnerabilities for problems associated with alcohol use disorders. A long history of repetitive heavy use of alcohol exists across generations as well as the high prevalence of alcohol-related problems in Western societies. Moreover, the information offered here addresses the importance of more general issues regarding genetics and gene expression related to alcohol abuse and dependence. PMID:18362899

  11. [Influence of alcohol beverage vending machine on alcohol dependence syndrome].

    PubMed

    Ino, A; Fujita, S

    1994-12-01

    The vending machines which sell alcohol beverages (AVM) can be found quite easily in front of shops or on the roadside in this country. Although it is easily supposed that these vending machines might have badly influenced on developing alcohol dependence syndrome, no scientific study has been reported in this regard so far. In this study, we analyzed the present status of alcoholics (n = 759) and their family members (n = 512) and of ordinary people (n = 334) in terms of their "relation" and "attitudes" to the vending machines by a questionnaire method. The results obtained show as follows: The majority of alcoholics (60%) had used AVM a couple of times or more often in a week, and 18% of alcoholics had not used AVM at all. It was found that the natures of AVM such as "machine," "long time operation," "easy accessibility," are closely related to the development of their alcohol seeking behavior, resulting in forming unfavorable drinking patterns such as concealed drinking, gulping, early morning drinking or binge drinking. Unusual patterns of using AVM were also noticed among them, such as, go to AVM before 5 a.m. and wait until it starts to work, go to a far away AVM deliberately, or, visiting AVM one after another. It was noticed that these drinking habits affected seriously not only the alcoholics but their families also. The number of the family members who insisted that AVM affected badly on the course of alcohol dependence syndrome is larger than that of alcoholics who admit the same thing. As for the future abolition of AVM, 91% of the family members, 70% of alcoholics and 39% of ordinary persons agreed with. The rate of "agreed with abolition" is higher than that of "disagreed with abolition" among ordinary persons. PMID:7695515

  12. Nalmefene. Alcohol dependence: no advance.

    PubMed

    2014-06-01

    Alcohol dependence is a chronic, severe and sometimes fatal disease. Psychological and social support is a crucial element of patient management. Acamprosate and naltrexone are the drugs of choice to help patients remain abstinent, but they are only moderately effective. Nalmefene, an opioid receptor antagonist related to naltrexone, has been authorised in the European Union to help alcohol-dependent patients reduce their alcohol consumption. Nalmefene has not been compared with naltrexone or acamprosate in clinical trials. Clinical evaluation is mainly based on two double-blind, randomised, placebo-controlled trials in which nalmefene was taken "on demand" at a dose of one tablet per day. The trials lasted 6 months and included a total of 1322 patients. During an initial two-week period in which all patients received medical and psychosocial support, about one-third of patients in both trials reduced their alcohol consumption without medication. Depending on the subgroup and the trial, about one-third to one-half of patients discontinued medical treatment before the end of the study period. In both trials, patients taking nalmefene had two fewer "heavy drinking days" per month than patients in the placebo groups. However, at the end of the study, they continued to drink heavily at least one week per month on average. Daily alcohol consumption was 5 to 9 grams lower with nalmefene than with placebo. The most frequent adverse effects observed in clinical trials were insomnia, dizziness, headache and nausea, which were severe in more than 10% of patients. Other serious but less frequent adverse effects included confusion, hallucinations and dissociation, usually at the beginning of treatment. These adverse effects affected about 3% of patients treated with nalmefene, a proportion three times higher than in the placebo groups. The consequences of mixing nalmefene with large amounts of alcohol are not known. In practice, the effects of nalmefene in alcohol-dependent

  13. Salivary lysozyme in smoking alcohol dependent persons.

    PubMed

    Waszkiewicz, Napoleon; Zalewska-Szajda, Beata; Zalewska, Anna; Waszkiewicz, Magdalena; Szajda, Slawomir Dariusz; Repka, Bernadeta; Szulc, Agata; Kepka, Alina; Minarowska, Alina; Ladny, Jerzy Robert; Zwierz, Krzysztof

    2012-01-01

    The purpose of this study was to evaluate the effect of chronic alcohol intoxication and smoking on the concentration and output of salivary lysozyme. Thirty seven men participated in the study, including 17 male smoking alcohol-dependent patients after chronic alcohol intoxication (AS), and 20 control non-smoking male social drinkers (CNS) with no history of alcohol abuse or smoking. The level of lysozyme was assessed by the radial immunodiffusion method. Significantly lower lysozyme output in the AS group compared to the CNS group was found. Moreover, gingival index was significantly higher in AS than in the CNS group. It appeared that the reduced salivary lysozyme output was more likely the result of ethanol action than smoking. In conclusion, persons addicted to alcohol and nicotine have a poorer periodontal status than non-smoking social drinkers, which may partially be due to the diminished protective effects of lysozyme present in the saliva. PMID:23264227

  14. Alcohol dependence in the Naval Service.

    PubMed

    Dickie, A K; Coetzee, R H

    2014-01-01

    Alcohol misuse is a significant occupational health issue in the United Kingdom Armed Forces. Dependence associated with alcohol misuse represents the severe end of the clinical and occupational consequences of sustained alcohol misuse. This article aims to explore the diagnosis, management and occupational considerations of alcohol dependence in the Naval Service environment. PMID:25335312

  15. Alcohol Dependence in Adult Children of Alcoholics: Longitudinal Evidence of Early Risk.

    ERIC Educational Resources Information Center

    Jennison, Karen M.; Johnson, Kenneth A.

    1998-01-01

    Investigates familial alcoholism effects and the comparative probability of risk that adult children of alcoholics have for alcohol dependence. Results, based on a national survey of 12,686 young adults over a five-year period, show that the risk for alcoholism is relatively greater for males than females. (MKA)

  16. Quantitative electroencephalography analysis in university students with hazardous alcohol consumption, but not alcohol dependence.

    PubMed

    Núñez-Jaramillo, Luis; Vega-Perera, Paulo; Ramírez-Lugo, Leticia; Reyes-López, Julián V; Santiago-Rodríguez, Efraín; Herrera-Morales, Wendy V

    2015-07-01

    Hazardous alcohol consumption is a pattern of consumption that leads to a higher risk of harmful consequences either for the user or for others. This pattern of alcohol consumption has been linked to risky behaviors, accidents, and injuries. Individuals with hazardous alcohol consumption do not necessarily present alcohol dependence; thus, a study of particular neurophysiological correlates of this alcohol consumption pattern needs to be carried out in nondependent individuals. Here, we carried out a quantitative electroencephalography analysis in health sciences university students with hazardous alcohol consumption, but not alcohol dependence (HAC), and control participants without hazardous alcohol consumption or alcohol dependence (NHAC). We analyzed Absolute Power (AP), Relative Power (RP), and Mean Frequency (MF) for beta and theta frequency bands under both eyes closed and eyes open conditions. We found that participants in the HAC group presented higher beta AP at centroparietal region, as well as lower beta MF at frontal and centroparietal regions in the eyes closed condition. Interestingly, participants did not present any change in theta activity (AP, RP, or MF), whereas previous reports indicate an increase in theta AP in alcohol-dependent individuals. Our results partially resemble those found in alcohol-dependent individuals, although are not completely identical, suggesting a possible difference in the underlying neuronal mechanism behind alcohol dependence and hazardous alcohol consumption. Similarities could be explained considering that both hazardous alcohol consumption and alcohol dependence are manifestations of behavioral disinhibition. PMID:26035281

  17. National Council on Alcoholism and Drug Dependence

    MedlinePlus

    ... Affiliate of the Month NCADD National Council on Alcoholism and Drug Dependence Addiction is a Disease - Treatment ... For over 70 years, The National Council on Alcoholism and Drug Dependence, Inc. (NCADD) has been a ...

  18. Estimating Risk of Alcohol Dependence Using Alcohol Screening Scores*

    PubMed Central

    Rubinsky, Anna D.; Kivlahan, Daniel R.; Volk, Robert J.; Maynard, Charles; Bradley, Katharine A.

    2010-01-01

    Brief alcohol counseling interventions can reduce alcohol consumption and related morbidity among non-dependent risky drinkers, but more intensive alcohol treatment is recommended for persons with alcohol dependence. This study evaluated whether scores on common alcohol screening tests could identify patients likely to have current alcohol dependence so that more appropriate follow-up assessment and/or intervention could be offered. This cross-sectional study used secondary data from 392 male and 927 female adult family medicine outpatients (1993–1994). Likelihood ratios were used to empirically identify and evaluate ranges of scores of the AUDIT, the AUDIT-C, two single-item questions about frequency of binge drinking, and the CAGE questionnaire for detecting DSM-IV past-year alcohol dependence. Based on the prevalence of past-year alcohol dependence in this sample (men: 12.2%; women: 5.8%), zones of the AUDIT and AUDIT-C identified wide variability in the post-screening risk of alcohol dependence in men and women, even among those who screened positive for alcohol misuse. Among men, AUDIT zones 5–10, 11–14 and 15–40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 18–87%, and AUDIT-C zones 5–6, 7–9 and 10–12 were associated with probabilities ranging from 22–75%. Among women, AUDIT zones 3–4, 5–8, 9–12 and 13–40 were associated with post-screening probabilities of past-year alcohol dependence ranging from 6–94%, and AUDIT-C zones 3, 4–6, 7–9 and 10–12 were associated with probabilities ranging from 9–88%. AUDIT or AUDIT-C scores could be used to estimate the probability of past-year alcohol dependence among patients who screen positive for alcohol misuse and inform clinical decision-making. PMID:20042299

  19. [Dimensions of parental rearing styles in alcohol dependent patients: first results of the questionnaire on parental attitudes and rearing practices (FEPS)].

    PubMed

    Lotzin, Annett; Kriston, Levente; Richter-Appelt, Hertha; Leichsenring, Irina; Ramsauer, Brigitte; Schäfer, Ingo

    2013-07-01

    To date no instrument for the assessment of parenting styles is available in the German -language area that has been validated in patients with addictive disorders. Therefore the aim of this study was the confirmatory evaluation of the factor structure of the Questionnaire on Parental Attitudes and Rearing Practices (FEPS) in 186 alcohol dependent patients. The model as proposed by the test developers with the 4 factors Care, Autonomy, Low Punishment, and Low Material Reinforcement showed acceptable fit when residual correlations were allowed (mother: χ(2)/df=1,92, RMSEA=0,07, TLI=0,79; father: χ(2)/df=1,75, RMSEA=0,07, TLI=0,82). All factors showed sufficient factor reliabilities as well as good to very good internal consistencies. Factor loadings, discriminations and difficulties of the indicators could be regarded as good, with the exception of 2 items. These results indicate the factorial validity of the FEPS in patients with alcohol dependence. PMID:23446826

  20. Acamprosate: a prototypic neuromodulator in the treatment of alcohol dependence.

    PubMed

    Mason, Barbara J; Heyser, Charles J

    2010-03-01

    Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence have identified specific neurotransmitter targets for the development of pharmacological treatments. Acamprosate, marketed under the brand name Campral, is an orally administered drug available by prescription in the U.S. and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in numerous clinical trials worldwide. Here we provide an overview of acamprosate in the context of the neurobiological underpinnings of alcohol dependence. We propose that unlike previously available pharmacotherapies, acamprosate represents a prototypical neuromodulatory approach in the treatment of alcohol dependence. A neuromodulatory approach seeks to restore the disrupted changes in neurobiology resulting from chronic alcohol intake. We believe that a neuromodulatory approach will provide a heuristic framework for developing more effective pharmacotherapies for alcohol dependence. PMID:20201812

  1. National Council on Alcoholism and Drug Dependence

    MedlinePlus

    ... the Month NCADD National Council on Alcoholism and Drug Dependence Addiction is a Disease - Treatment is Available - Recovery Brings ... Research Addiction Get the Facts Alcohol Learn More Drugs Learn More Addiction Update Learn More Underage Issues Learn More FAQ ...

  2. DISABILITY ASSOCIATED WITH ALCOHOL ABUSE AND DEPENDENCE

    PubMed Central

    Samokhvalov, Andriy V.; Popova, Svetlana; Room, Robin; Ramonas, Milita; Rehm, Jürgen

    2010-01-01

    BACKGROUND Alcohol use disorders (AUD), i.e., alcohol dependence and abuse are major contributors to burden of disease. A large part of this burden is due to disability. However, there is still controversy about the best disability weighting for alcohol use disorders. The objective of this study was to provide an overview of alcohol-related disabilities. METHODS Systematic literature review and expert interviews. RESULTS There is heterogeneity in experts’ descriptions of disabilities related to AUD. The major core attributes of disability related to AUD are changes of emotional state, social relationships, memory and thinking. The most important supplementary attributes are anxiety, impairments of speech and hearing. CONCLUSIONS This review identified the main patterns of disability associated with alcohol use disorders. However, there was considerable variability, and data on less prominent patterns were fragmented. Further and systematic research is required for increasing the knowledge on disability related to alcohol use disorders and for application of interventions for reducing the associated burden. OBJECTIVE To provide an overview of disabilities associated with AUD. PMID:20662803

  3. [Drugs, a current problem. Alcohol dependency].

    PubMed

    Amigó Tadín, Montserrat

    2006-01-01

    Alcohol is a socially accepted drug which is commercialized in multiple products including wine, cognac, gin, beer, anisette, vermouth, rum, etc. and which can be consumed in small quantities without producing harmful effects on one's health; nonetheless, women are more susceptible to alcohol's damages and an abusive consumption of alcohol creates dependence and chronic diseases. Ten percent of those people who consume alcohol develop dependency and comprise the leading group of drug addicts in many countries. PMID:16493852

  4. Correlates of Baclofen Effectiveness in Alcohol Dependence

    PubMed Central

    Shukla, Lekhansh; Shukla, Tulika; Bokka, Spandana; Kandasamy, Arun; Benegal, Vivek; Murthy, Pratima; Chand, Prabhat

    2015-01-01

    Alcohol dependence is a global concern. Baclofen has shown promise as an anti-craving agent but its efficiency remains to be settled. We reviewed 549 male cases diagnosed with alcohol dependence who received Acamprosate (201) or Baclofen (348). ‘Time to first drink’ was compared between two groups and multiple regression analysis was done in baclofen group to identify correlates of effectiveness. There was a significant difference in outcome measure between Baclofen (M = 4.44, SD = 3.75) and Acamprosate group (M = 3.73, SD = 2.19); t (547) = 2.45, P = 0.01. Initial regression analysis with six predictor variables (average daily alcohol units, current age, age at onset of dependence, family history, duration of dependence and dose of baclofen in mg/day) showed significant correlation of outcome variable with only two predictor variables — dose of baclofen and average daily intake. Using the hierarchical method it was found that ‘dose of baclofen’ and ‘average alcohol intake’ explain a significant amount of variance in ‘time to first drink’. [F (1, 345) = 182.8, P < 0.001, R2 = 0.52, R2adjusted = 0.51]. This information can be used to select patients in long term longitudinal studies and may explain variable results seen in clinical trials of baclofen done earlier. PMID:26664095

  5. Does Gender Contribute to Heterogeneity in Criteria for Cannabis Abuse and Dependence? Results from the National Epidemiological Survey on Alcohol and Related Conditions

    PubMed Central

    Agrawal, Arpana; Lynskey, Michael T.

    2007-01-01

    Previous research has noted that a unidimensional latent construct underlies criteria for cannabis abuse and dependence. However, no study to date has explored whether gender contributes to heterogeneity in the latent abuse and dependence construct and furthermore, whether after accounting for differences in the mean scores of abuse and dependence across genders, there is any evidence for heterogeneity in the individual abuse and dependence criteria. The present study utilizes data on criteria for cannabis abuse and dependence from a large, nationally representative sample (National Epidemiological Survey on Alcohol and Related Conditions) of 8,172 lifetime cannabis users to investigate whether gender contributes to heterogeneity in the underlying construct of cannabis abuse and dependence, and in each individual criterion as well. Analyses, all of which were conducted in MPlus, included factor analysis, as well as MIMIC and multiple-group models for an examination of dimensionality and gender heterogeneity, respectively. Results favor a uni-dimensional construct for cannabis abuse/dependence, as seen in prior research. We also identify 2 abuse (Legal and Hazard) and 2 dependence (Quit and Problems) criteria, which show significant gender heterogeneity with the abuse criteria exhibiting higher thresholds in women and the dependence criteria in men. We conclude that the criteria that serve as indicators of DSM-IV cannabis abuse and dependence do not function identically in men and women and that certain criteria (e.g. hazardous use) require further refinement. PMID:17084563

  6. GABA receptors, alcohol dependence and criminal behavior.

    PubMed

    Terranova, Claudio; Tucci, Marianna; Sartore, Daniela; Cavarzeran, Fabiano; Di Pietra, Laura; Barzon, Luisa; Palù, Giorgio; Ferrara, Santo D

    2013-09-01

    The aim of this study was to analyze the connection between alcohol dependence and criminal behavior by an integrated genetic-environmental approach. The research, structured as a case-control study, examined 186 alcohol-dependent males; group 1 (N = 47 convicted subjects) was compared with group 2 (N = 139 no previous criminal records). Genetic results were innovative, highlighting differences in genotype distribution (p = 0.0067) in group 1 for single-nucleotide polymorphism rs 3780428, located in the intronic region of subunit 2 of the GABA B receptor gene (GABBR2). Some environmental factors (e.g., grade repetition) were associated with criminal behavior; others (e.g., attendance at Alcoholics Anonymous) were inversely related to convictions. The concomitant presence of the genetic and environmental factors found to be associated with the condition of alcohol-dependent inmate showed a 4-fold increase in the risk of antisocial behavior. The results need to be replicated on a larger population to develop new preventive and therapeutic proposals. PMID:23822588

  7. Alcoholic neurobiology: changes in dependence and recovery.

    PubMed

    Crews, Fulton T; Buckley, Tracey; Dodd, Peter R; Ende, Gabriele; Foley, Nina; Harper, Clive; He, Jun; Innes, David; Loh, El-Wui; Pfefferbaum, Adolph; Zou, Jian; Sullivan, Edith V

    2005-08-01

    This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of

  8. Expression of a heat-stable NADPH-dependent alcohol dehydrogenase in Caldicellulosiruptor bescii results in furan aldehyde detoxification

    SciTech Connect

    Chung, Daehwan; Verbeke, Tobin J.; Cross, Karissa L.; Westpheling, Janet; Elkins, James G.

    2015-07-22

    Compounds such as furfural and 5-hydroxymethylfurfural (5-HMF) are generated through the dehydration of xylose and glucose, respectively, during dilute-acid pretreatment of lignocellulosic biomass and are also potent microbial growth and fermentation inhibitors. The enzymatic reduction of these furan aldehydes to their corresponding, and less toxic, alcohols is an engineering approach that has been successfully implemented in both Saccharomyces cerevisiae and ethanologenicEscherichia coli, but has not yet been investigated in thermophiles relevant to biofuel production through consolidated bioprocessing (CBP). Developing CBP-relevant biocatalysts that are either naturally resistant to such inhibitors, or are amenable to engineered resistance, is therefore, an important component in making biofuels production from lignocellulosic biomass feasible.

  9. Expression of a heat-stable NADPH-dependent alcohol dehydrogenase in Caldicellulosiruptor bescii results in furan aldehyde detoxification

    DOE PAGESBeta

    Chung, Daehwan; Verbeke, Tobin J.; Cross, Karissa L.; Westpheling, Janet; Elkins, James G.

    2015-07-22

    Compounds such as furfural and 5-hydroxymethylfurfural (5-HMF) are generated through the dehydration of xylose and glucose, respectively, during dilute-acid pretreatment of lignocellulosic biomass and are also potent microbial growth and fermentation inhibitors. The enzymatic reduction of these furan aldehydes to their corresponding, and less toxic, alcohols is an engineering approach that has been successfully implemented in both Saccharomyces cerevisiae and ethanologenicEscherichia coli, but has not yet been investigated in thermophiles relevant to biofuel production through consolidated bioprocessing (CBP). Developing CBP-relevant biocatalysts that are either naturally resistant to such inhibitors, or are amenable to engineered resistance, is therefore, an important componentmore » in making biofuels production from lignocellulosic biomass feasible.« less

  10. Psychosocial predictors of impulsivity in alcohol-dependent patients.

    PubMed

    Jakubczyk, Andrzej; Klimkiewicz, Anna; Mika, Katarzyna; Bugaj, Marcin; Konopa, Aleksandra; Podgórska, Anna; Brower, Kirk J; Wojnar, Marcin

    2013-01-01

    Impulsivity is an important risk factor of severe course of alcohol dependence. However, the significance of environmental determinants of impulsivity has been underestimated. The aim of this study was to identify psychosocial factors increasing the level of impulsivity in alcoholics. Levels of impulsivity were measured in 304 alcohol-dependent patients. The stop-signal task was used to assess behavioral impulsivity, and the Barratt Impulsiveness Scale, to measure global and cognitive impulsivity. Correlations between impulsivity and psychosocial variables were examined. A significant association between level of impulsivity and severity of psychopathological symptoms was observed. Patients who reported childhood sexual or physical abuse, lower social support, and more severe course of alcohol dependence were more impulsive, especially in the cognitive domain. When entered into a linear regression analysis model, severity of alcohol dependence, psychopathology, and childhood physical abuse remained significant. These results suggest that psychosocial variables are important factors associated with high levels of impulsivity in alcohol-dependent patients. PMID:23274294

  11. Acamprosate in the treatment of alcohol dependence.

    PubMed

    Mason, Barbara J

    2005-10-01

    Acamprosate is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation in combination with psychosocial support. Acamprosate is a synthetic taurine analogue that seems to act centrally to restore the normal activity of glutamatergic neurotransmission altered by chronic alcohol exposure. Over the past 15 years, the safety and efficacy of acamprosate for alcohol dependence have been well established in multiple double-blind, placebo-controlled trials. Overall, acamprosate has been consistently associated with greater beneficial effects on measures of alcohol abstinence compared with placebo. Specifically, patients treated with acamprosate achieve greater rates of complete abstinence, longer times to first drink and/or increased duration of cumulative abstinence when compared with placebo. Acamprosate received approval by the US FDA for the treatment of alcohol dependence in July 2004 and is currently prescribed in 28 countries. PMID:16197362

  12. Socio-Emotional Factors in Alcohol Dependence

    PubMed Central

    Tikka, Deyashini Lahiri; Ram, Daya; Dubey, Indu; Tikka, Sai Krishna

    2014-01-01

    Background: Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. Aim: To understand the relationships amongst various of the socio-emotional factors. Materials and Methods: Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score <3) were compared on attachment styles (on Relationship Scale Questionnaire), anger domains (on State Trait Anger Expression Inventory), and self-esteem (on Rosenberg Self-esteem Scale). Statistics and Analysis: Comparison using independent samples t test and chi square test; correlation using Pearson's correlation coefficient. Results: Patients had significantly higher anger expression, ‘anger in’ and ‘anger out,’ and lower self-esteem than healthy controls. Severity of alcohol dependence had significant correlation with ‘anger out,’ and self-esteem had significant negative correlation with anger expression. Conclusion: The present study suggests that the socio-emotional factors studied are developmentally linked to each other. PMID:24860216

  13. Family Behavior Therapy for Use in Child Welfare: Results of a Case Study Involving an Abused Woman Formally Diagnosed With Alcohol Dependence, Bipolar Disorder, and Several Anxiety Disorders

    PubMed Central

    Romero, Valerie; Donohue, Brad C.; Hill, Heather H.; Powell, Suzanne; Van Hasselt, Vincent B.; Azrin, Nathan; Allen, Daniel N.

    2012-01-01

    The results of a multiple-baseline case study of family behavior therapy (FBT) is described in a woman formally diagnosed with alcohol dependence, bipolar disorder, generalized anxiety disorder, specific phobia, and panic disorder. She was referred to treatment from the local Department of Family Services for child neglect and domestic violence. After baseline measures were administered, the first phase of treatment involved home safety tours aimed at reducing home hazards and cleanliness. A second phase of treatment additionally targeted family relationships through communication skills training exercises, and a third phase involved administration of the remaining FBT components to assist in comprehensively addressing other problem areas. Results indicated most problem areas were substantially improved, but only after they were comprehensively targeted in therapy. PMID:23136557

  14. Alcohol Dependence and Health Care Utilization in African Americans

    PubMed Central

    Marshall, Vanessa J.; Kalu, Nnenna; Kwagyan, John; Scott, Denise M.; Cain, Gloria E.; Hill, Karen; Hesselbrock, Victor; Ferguson, Clifford L.; Taylor, Robert E.

    2013-01-01

    Objective Ethnic and cultural differences in patterns of alcohol use disorders must be understood in order to address improvement in prevention of such disorders and accessibility to health care services. The purpose of this study was to evaluate factors that influence the utilization of medical and mental health services among alcohol-dependent and non alcohol–dependent African Americans. Method A cohort of 454 African Americans was evaluated. Alcohol-dependent participants were recruited from various inpatient treatment facilities in the Washington, DC, metropolitan area and through advertisement and word of mouth. Non–alcohol-dependent participants were recruited by advertisements. Each participant was administered the Semi-Structured Assessment for the Genetics of Alcoholism to assess alcohol dependency and the Family History Assessment module to access family history of alcoholism. χ2 Test and analysis of variance were used to analyze the data. Results Alcohol dependence was more prevalent among men, those with lower income, those with less education, and they utilized mental health counseling as opposed to medical-based therapy. Increased reports of medical conditions such as migraine (p < .001), loss of consciousness (p = .001), and sexually transmitted diseases (p < .001) were also associated with alcohol dependency. Other factors, including visits to inpatient treatment programs, were directly related to incidence of alcohol dependency regardless of gender status (p < .001). Conclusions This study suggests an association exists among alcohol dependence, medical conditions, health care, and mental care utilization among African Americans. Future research may benefit from investigating if an association exists between alcohol use disorders and health care utilization for other ethnic groups. PMID:23862295

  15. Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats.

    PubMed

    Vendruscolo, Leandro F; Barbier, Estelle; Schlosburg, Joel E; Misra, Kaushik K; Whitfield, Timothy W; Logrip, Marian L; Rivier, Catherine; Repunte-Canonigo, Vez; Zorrilla, Eric P; Sanna, Pietro P; Heilig, Markus; Koob, George F

    2012-05-30

    Alcoholism is characterized by a compulsion to seek and ingest alcohol, loss of control over intake, and the emergence of a negative emotional state during abstinence. We hypothesized that sustained activation of neuroendocrine stress systems (e.g., corticosteroid release via the hypothalamic-pituitary-adrenal axis) by alcohol intoxication and withdrawal and consequent alterations in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation drive compulsive alcohol drinking. Our results showed that rats exposed to alcohol vapor to the point of dependence displayed increased alcohol intake, compulsive drinking measured by progressive-ratio responding, and persistent alcohol consumption despite punishment, assessed by adding quinine to the alcohol solution, compared with control rats that were not exposed to alcohol vapor. No group differences were observed in the self-administration of saccharin-sweetened water. Acute alcohol withdrawal was accompanied by downregulated GR mRNA in various stress/reward-related brain regions [i.e., prefrontal cortex, nucleus accumbens (NAc), and bed nucleus of the stria terminalis (BNST)], whereas protracted alcohol abstinence was accompanied by upregulated GR mRNA in the NAc core, ventral BNST, and central nucleus of the amygdala. No significant alterations in MR mRNA levels were found. Chronic GR antagonism with mifepristone (RU38486) prevented the escalation of alcohol intake and compulsive responding induced by chronic, intermittent alcohol vapor exposure. Chronic treatment with mifepristone also blocked escalated alcohol drinking and compulsive responding during protracted abstinence. Thus, the GR system appears to be involved in the development of alcohol dependence and may represent a potential pharmacological target for the treatment of alcoholism. PMID:22649234

  16. Psychiatric Comorbidity in Alcohol Dependence.

    PubMed

    Fein, George

    2015-12-01

    We review our clinical studies of psychiatric comorbidity in short-term and long-term abstinent and in treatment naïve alcoholics (STAA, LTAA and TNA). TNA ypically have less severe alcoholism than treated abstinent samples and evidence less severe psychiatric disturbance. Lifetime psychiatric diagnoses are the norm for STAA and LTAA but not for TNA. Individuals with alcohol and drug use disorders show greater antisocial personality disturbance, but do not show differences in the mood or anxiety domains or in borderline personality disorder (BPD) symptoms. The studies show that alcoholics can achieve and maintain abstinence in the face of ongoing mood, anxiety, or BPD problems. By contrast, for ASPD, LTAA essentially stop current antisocial behaviors in all seven domains of antisocial behaviors. We believe that ongoing antisocial behavior is not consistent with maintaining abstinence, and that LTAA modify their antisocial behavior despite continued elevated social deviance proneness and antisocial dispositionality. Abstinent individuals without lifetime psychiatric disorders and TNA show more (subdiagnostic threshold) psychiatric symptoms and abnormal psychological measures than non-alcoholic controls in the mood, anxiety, BPD, and antisocial domains. In summary, our studies show that although LTAA have achieved multi-year abstinence, they still report significant psychological distress compared to NAC. We believe this distress may negatively affect their quality of life. This suggests the importance of developing effective care models to address comorbid mental health problems in LTAA. We also show that antisocial personality disorder symptoms decline to the levels seen in normal controls, and that excluding individuals from research with a psychiatric diagnosis does not control for subdiagnostic psychiatric differences between alcoholics and controls. PMID:26590836

  17. ALCOHOL DEPENDENCE--NEUROBIOLOGY AND TREATMENT.

    PubMed

    Michalak, Agnieszka; Biała, Grazyna

    2016-01-01

    The consequences of alcohol dependence concern serious health care, social and economic problems. The scope of many studies is to better understand mechanisms underlying alcohol addiction in order to work out new, more effective treatment strategies. Alcohol affects many neurotransmission systems within the brain. In general, acute alcohol enhances inhibitory transmission, up-regulating the GABAergic system and impairing glutamatergic function, therefore interfering the balance between excitatory and inhibitory synaptic inputs. Chronic alcohol consumption, meanwhile, in order to restore equilibrium leads to neuroadaptive changes caus- ing both decreased GABAergic and increased glutamatergic activity. Also function of other neurotransmitters and modulators is modified by the presence of alcohol, including glycine, adenosine, serotonin and dopamine. Moreover, a significant impact of alcohol on the endogenous opioid system, nicotinic cholinergic transmission and the endocannabinoids system has been also established. At present, only four medications are approved for the treatment of alcohol dependence in Europe, that is naltrexone, acamprosate, disulfiram and the most recent nalmefene. Among other promising strategies the following drugs are mentioned: baclofen, topiramate, ondansetron, aripiprazole, rimonabant and varenicline. Additionally, the role of appetite-regulating hormones, neuroimmune modulators or the body's stress-response system modulators in reducing alcohol consumption is currently of great interest, however, further investigations are needed. PMID:27008795

  18. Brain Pathways to Recovery from Alcohol Dependence

    PubMed Central

    Cui, Changhai; Noronha, Antonio; Warren, Kenneth; Koob, George F.; Sinha, Rajita; Thakkar, Mahesh; Matochik, John; Crews, Fulton T.; Chandler, L. Judson; Pfefferbaum, Adolf; Becker, Howard C.; Lovinger, David; Everitt, Barry; Egli, Mark; Mandyam, Chitra; Fein, George; Potenza, Marc N.; Harris, R. Adron; Grant, Kathleen A.; Roberto, Marisa; Meyerhoff, Dieter J.; Sullivan, Edith V.

    2015-01-01

    This article highlights the research presentations at the satellite symposium on “Brain Pathways to Recovery from Alcohol Dependence” held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed. PMID:26074423

  19. Positive Affect and Stress Reactivity in Alcohol-Dependent Outpatients

    PubMed Central

    McHugh, R. Kathryn; Kaufman, Julia S.; Frost, Katherine H.; Fitzmaurice, Garrett M.; Weiss, Roger D.

    2013-01-01

    Objective: Reactivity to stress is a common feature of alcohol dependence and is associated with poorer treatment outcome among alcohol-dependent patients. Despite the importance of stress reactivity in alcohol dependence, little is known about markers of resilience to stress in this population. The current study examined whether positive affect buffered the effect of stress on negative affect and alcohol craving in an alcohol-dependent sample. Method: Outpatients (N = 1,375) enrolled in a large, randomized controlled trial for alcohol dependence (the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence [COMBINE] Study) completed measures of stress, positive affect, negative affect, and alcohol craving. In this secondary analysis, we hypothesized that positive affect would moderate the association between stress and negative affect and that positive affect would be negatively associated with craving. Results: Results supported these hypotheses, such that patients with higher levels of positive affect exhibited a weaker relationship between stress and negative affect relative to those with low positive affect. Positive affect was negatively associated with craving but did not moderate the association between stress and craving. Conclusions: These results replicate studies suggesting a protective effect of positive affect on stress reactivity and extend this effect to an alcohol-dependent sample. If positive affect can aid in resilience to stress, the utilization of interventions that enhance positive affect may be of particular utility for alcohol-dependent patients. Future experimental studies testing the causality of this association as well as studies examining the effect of interventions to enhance positive affect are needed. PMID:23200161

  20. Cognitive Regulation of Craving in Alcohol Dependent and Social Drinkers

    PubMed Central

    Naqvi, Nasir H.; Ochsner, Kevin N.; Kober, Hedy; Kuerbis, Alexis; Feng, Tianshu; Wall, Melanie; Morgenstern, Jon

    2014-01-01

    Background Helping alcohol dependent individuals to cope with, or regulate, cue-induced craving using cognitive strategies is a therapeutic goal of cognitive behavioral therapy (CBT) for alcohol dependence. An assumption that underlies this approach is that alcohol dependence is associated with deficits in such cognitive regulation abilities. To date, however, the ability to utilize such strategies for regulation of craving has never been tested in a laboratory setting. Methods Here we compared 19 non-treatment-seeking, alcohol dependent drinkers (AD) to 21 social drinkers (SD), using a laboratory task that measured the ability to reduce cue-induced alcohol craving by thinking about long-term negative consequences of drinking, which is a specific cognitive regulation strategy that is taught in CBT. The task also assessed the ability to reduce food craving elicited by high-calorie food cues using a similar strategy. Results The reduction in craving when using this cognitive regulation strategy was approximately double in SD, compared to AD, for both alcohol and food cues. Furthermore, in SD but not AD, the ability to regulate cue-induced alcohol craving was correlated with the ability to regulate food craving. There were no significant correlations found between the ability to regulate cue-induced alcohol craving and a number of self-report measures related to severity of alcohol dependence, baseline craving, impulsivity and general self-regulation ability, for either AD or SD. Conclusions The results suggest that alcohol dependence is associated with deficits in cognitive regulation of cue-induced craving, and that these deficits are not specific to the regulation of alcohol craving, but generalize to the regulation of other appetitive states, such as food craving. Future studies may use similar procedures to address the neural and cognitive processes that underlie such regulation deficits, as well as the effects of treatments such as CBT on these processes. PMID

  1. Person-Environment Interaction in the Prediction of Alcohol Abuse and Alcohol Dependence in Adulthood

    PubMed Central

    Hill, Karl G.; Hawkins, J. David; Bailey, Jennifer A.; Catalano, Richard F.; Abbott, Robert D.; Shapiro, Valerie

    2010-01-01

    Background Behavioral disinhibition (externalizing/impulsivity) and behavioral inhibition (internalizing/anxiety) may contribute to the development of alcohol abuse and dependence. But tests of person-by-environment interactions in predicting alcohol use disorders are needed. This study examined the extent to which interactions between behavioral disinhibition, behavioral inhibition and family management during adolescence predict alcohol abuse and alcohol dependence at age 27. Methods This study used longitudinal data from a community sample of 808 men and women interviewed from age 10 to 27 in the Seattle Social Development Project. Zero-order correlations followed by a series of nested regressions examined the relationships between individual characteristics (behavioral disinhibition and behavioral inhibition/anxiety) and environment (good versus poor family management practices during adolescence) in predicting alcohol abuse and dependence criterion counts at age 27. Results Behavioral disinhibition and poor family management predicted increased likelihood of both alcohol abuse and alcohol dependence at age 27. Behavioral inhibition/anxiety was unrelated to both outcomes. Youths high in behavioral disinhibition were at increased risk for later alcohol abuse and dependence only in consistently poorly managed family environments. In consistently well-managed families, high levels of behavioral disinhibition did not increase risk for later alcohol abuse or dependence. Conclusions Behavioral disinhibition increases risk for alcohol abuse and dependence in early adulthood only for individuals who experience poor family management during adolescence. Interventions seeking to reduce environmental risks by strengthening consistent positive family management practices may prevent later alcohol abuse and dependence among individuals at risk due to behavioral disinhibition. PMID:20299164

  2. The Expected Personality Characteristics of Alcohol-Dependent Individuals.

    ERIC Educational Resources Information Center

    Malouff, John M.; Schutte, Nicola S.

    2002-01-01

    Uses the Big Five personality factors as a framework for examining the expected personality characteristics of individuals who are alcohol-dependent. Results help explain prior findings about the social handicap of problem drinking with regard to making friends, dating, marriage, and working. Findings have potential use in alcohol-problem…

  3. Cannabinoid receptor 1 blocker rimonabant (SR 141716) for treatment of alcohol dependence: results from a placebo-controlled, double-blind trial.

    PubMed

    Soyka, Michael; Koller, Gabriele; Schmidt, Peggy; Lesch, Otto-Michael; Leweke, Markus; Fehr, Christoph; Gann, Horst; Mann, Karl F

    2008-06-01

    Multiple lines of evidence suggest that the endocannabinoid system is implicated in the development of alcohol dependence. In addition, in animal models, the cannabinoid receptor 1 blocker rimonabant was found to decrease alcohol consumption, possibly by indirect modulation of dopaminergic neurotransmission. This was a 12-week double-blind, placebo-controlled, proof-of-concept study to assess the possible efficacy of the cannabinoid receptor 1 antagonist rimonabant 20 mg/d (2 x 10 mg) in the prevention of relapse to alcohol in recently detoxified alcohol-dependent patients. A total of 260 patients were included, 258 were exposed to medication, and 208 (80.6%) were men. Patients had an alcohol history of 15 years on average. More patients in the rimonabant group (94/131 [71.8%]) completed treatment compared with the placebo group (79/127 [62.2%]). Although there was a modest effect of rimonabant with respect to relapse rate, there were no statistically significant differences between treatment groups. Approximately 41.5% of the rimonabant group had relapsed to drinking at the end of the study compared with 47.7% of the placebo group (obtained from Kaplan-Meier-curve). Differences were more marked but not statistically significant in patients who relapsed to heavy drinking: 27.7% versus 35.6%, respectively. Safety and tolerance of the drug were good. Similar rates of adverse events were reported between the 2 groups; less patients experienced serious events or discontinued the treatment with rimonabant compared with placebo. Rates of depression-related events were low (3.8% with rimonabant compared with 1.6% with placebo). Patients on rimonabant lost weight (Mean, -1.7 kg) compared with baseline, whereas there was no such change in the placebo group. Weight loss was more pronounced in patients with a higher body mass index. In addition, there was a significant decrease in leptin levels in the rimonabant group compared with baseline. Lack of efficacy in this study may

  4. [The Amygdala in mechanisms of alcohol dependence].

    PubMed

    Akhmadeev, A V; Kalimullina, L B

    2016-01-01

    In the present review for the first time systematized literature data about reactive changes, of neurons in the basolateral and medial nuclei of the Amygdala which occur in response to acute and chronic exposure of ethanol. Summarized information about the mechanisms of disturbances in glutamatergic-and GABAergic systems of the basolateral nucleus that determining an increased level of anxiety, which is seen as a main motivating factor of desire for alcohol, thus involved to the manifestation of alcohol dependence. Reviewed molecular and genetic aspects of rsearchs involvement of medial nucleus in the mechanisms of alcoholism. PMID:27530042

  5. Applying the new genomics to alcohol dependence.

    PubMed

    Farris, Sean P; Pietrzykowski, Andrzej Z; Miles, Michael F; O'Brien, Megan A; Sanna, Pietro P; Zakhari, Samir; Mayfield, R Dayne; Harris, R Adron

    2015-12-01

    This review summarizes the proceedings of a symposium presented at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference held in Volterra, Italy on May 6-9, 2014. The overall goal of the symposium titled "Applying the New Genomics to Alcohol Dependence", chaired by Dr. Adron Harris, was to highlight recent genomic discoveries and applications for profiling alcohol use disorder (AUD). Dr. Sean Farris discussed the gene expression networks related to lifetime consumption of alcohol within human prefrontal cortex. Dr. Andrzej Pietrzykowski presented the effects of alcohol on microRNAs in humans and animal models. Alcohol-induced alterations in the synaptic transcriptome were discussed by Dr. Michael Miles. Dr. Pietro Sanna examined methods to probe the gene regulatory networks that drive excessive alcohol drinking, and Dr. Samir Zakhari served as a panel discussant and summarized the proceedings. Collectively, the presentations emphasized the power of integrating multiple levels of genetics and transcriptomics with convergent biological processes and phenotypic behaviors to determine causal factors of AUD. The combined use of diverse data types demonstrates how unique approaches and applications can help categorize genetic complexities into relevant biological networks using a systems-level model of disease. PMID:25896098

  6. Nalmefene and its use in alcohol dependence.

    PubMed

    Gual, A; Bruguera, P; López-Pelayo, H

    2014-05-01

    Nalmefene is the first available drug approved in the E.U. to reduce alcohol use in alcohol-dependent patients. Reduction in alcohol use in heavy drinkers diminishes mortality risk and socio-economic burden. Nalmefene has shown efficacy at 6 months in alcohol-dependent patients with high or very high drinking risk levels in reducing total alcohol consumption (-7.6 g/day [95% confidence interval (CI): -11.6 to -3.5]; P = 0.0003), heavy drinking days (-2.00 days/month [95% CI: -3.00 to -1.00]; P ⟨ 0.00001) and other secondary outcome measures such as γ-glutamyl transferase, alanine aminotransferase, drinking risk level and Clinical Global Impression. It is generally well tolerated and has limited contraindications and interactions. As-needed dosage is a novel concept in the addictions field, which may overcome limitations of traditional regimens. In the pivotal trials, nalmefene was taken 52% of the days and compliance with the as-needed treatment regimen was good (above 80% of the days) in 68% of the nalmefene-treated patients. A new pharmacological approach combined with a brief psychosocial intervention for alcoholism is available and appears to be feasible, safe and efficacious. PMID:24918835

  7. PTSD-related alcohol expectancies and impulsivity interact to predict alcohol use severity in a substance dependent sample with PTSD

    PubMed Central

    Schaumberg, Katherine; Vinci, Christine; Raiker, Joseph S.; Mota, Natalie; Jackson, Michelle; Whalen, Diana; Schumacher, Julie A.; Coffey, Scott F.

    2016-01-01

    Introduction Problematic alcohol use is highly comorbid with posttraumatic stress disorder (PTSD), and prior work has demonstrated that individuals with PTSD may self-medicate with alcohol in an effort to reduce their symptoms. The combination of impulsivity and alcohol-related expectancies influences the development of problematic drinking patterns. When examining individuals diagnosed with PTSD, PTSD-related alcohol expectancies may be particularly relevant to the etiology of problematic drinking. To date, no studies have specifically examined PTSD-specific alcohol expectancies as they relate to alcohol use severity in a clinical sample. Methods The current study examined the relationship between impulsivity, PTSD-related alcohol expectancies, and severity of alcohol use in a sample of 63 individuals diagnosed with comorbid PTSD and substance use disorders who were receiving treatment in a residential substance use treatment program. Results Results indicated that PTSD-related alcohol expectancies moderated the relationship between impulsivity and alcohol use severity. Specifically, at low to moderate levels of positive PTSD-related alcohol expectancies, impulsivity significantly predicted alcohol use severity, while impulsivity had no impact on the prediction of alcohol use severity when such expectancies were high. Additionally, the relationship between impulsivity, expectancies, and alcohol use severity was significant for positive, but not negative, PTSD-related alcohol expectancies. Conclusions Overall, these results suggest that impulsivity and PTSD-related alcohol expectancies interact to predict alcohol use severity in a comorbid PTSD and substance dependent sample. PMID:25299460

  8. Emotional Intelligence Components in Alcohol Dependent and Mentally Healthy Individuals

    PubMed Central

    Mohagheghi, Arash; Amiri, Shahrokh; Mousavi Rizi, Seyedreza; Safikhanlou, Salman

    2015-01-01

    Objective. Emotional intelligence might play an important role in the onset and persistence of different psychopathologies. This study investigated the relationship between emotional intelligence and alcohol dependence. Methods. In this case-control study, participants included alcohol dependent individuals and mentally healthy inpatients. Each group consisted of 40 individuals (male/female: 1). The diagnosis was based on the criteria of the DSM-IV-TR using the Structured Clinical Interview for DSM-IV (SCID-IV). All the participants completed Bar-On emotional intelligence test. Results. 20 males and 20 females were included in each group. Mean age of alcohol dependent participants and controls was 31.28 ± 7.82 and 34.93 ± 9.83 years in that order. The analyses showed that the alcohol dependent individuals had a significant difference compared with the control group and received lower scores in empathy, responsibility, impulse control, self-esteem, optimism, emotional consciousness, stress tolerance, autonomy, problem-solving, and total score of emotional intelligence components. Conclusion. Patients with alcohol dependence have deficits in components of emotional intelligence. Identifying and targeted training of the individuals with lower scores in components of emotional intelligence may be effective in prevention of alcohol dependence. PMID:25893214

  9. Alcohol dependence in adult children of alcoholics: longitudinal evidence of early risk.

    PubMed

    Jennison, K M; Johnson, K A

    1998-01-01

    This study investigates familial alcoholism effects and the comparative probability of risk for alcohol dependence in adult children of alcoholics (ACAs) with a control group of non-ACAs. A cohort of 12,686 young adults from the National Longitudinal Survey of Youth (NLSY) is examined over a five-year period and conventional and lineal intergenerational models of alcoholism transmission are assessed. The results of multivariate logistic regression analyses indicate that the risk is relatively greater for male ACAs; sons of alcoholics drink significantly more heavily, experience problems earlier, and develop alcohol dependence more extensively than female ACAs or non-ACAs of either gender. The extent of dependence found in subjects with a lineal history of alcoholism on the father's side of the family, as well as heavy drinking, cigarette smoking and drinking onset in adolescence should be considered as critical predisposing factors of high risk for dependence at later ages. These observations corroborate clinical studies and support a growing body of biopsychosocial research literature. PMID:9567578

  10. Association of VMAT2 gene polymorphisms with alcohol dependence.

    PubMed

    Fehr, Christoph; Sommerlad, Daniel; Sander, Thomas; Anghelescu, Ion; Dahmen, Norbert; Szegedi, Armin; Mueller, Christiana; Zill, Peter; Soyka, Michael; Preuss, Ulrich W

    2013-08-01

    Alcohol-related diseases cause significant harm in the western world. Up to 65 % of the phenotypic variance is genetically determined. Few candidate genes have been identified, comprising ADH4, ALDH2, COMT, CRHR1, DAT (SLC6A3), GABRA2 and MAOA. While abnormalities in the dopaminergic mesolimbic reward system are considered important mediators of alcoholism, studies analyzing variants of dopamine receptors showed conflicting results. Other modulators of the reward system are synaptosomal genes. Among candidate genes, polygenic variants of the Vesicular Monamine Transporter 2 (VMAT2) gene locus associated with alterations of drinking behavior were published. These variants comprise single nucleotide polymorphisms (SNPs) within the promoter region and the open reading frame. In this study, we confirm the association of VMAT2 SNP rs363387 (allelic association: p = 0.015) with alcohol dependence. This SNP defines several haplotypes including up to four SNPs (minimal p = 0.0045). In addition, numeric effects in the subgroups of males and patients with positive family history were found. We suggest that several rs363387 T-allele containing haplotypes increase the risk of alcohol dependence (OR 1.53), whereas G-allele containing haplotypes confer protection against alcohol dependence. Taken together, there is supporting evidence for a contribution of VMAT2 gene variants to phenotypes of alcohol dependence. PMID:23504072

  11. Alcohol dependence and driving: knowledge of DVLA regulations

    PubMed Central

    Collier, Andrew; Watts, Maggie; Ghosh, Sujoy; Rice, Peter; Dewhurst, Neil

    2015-01-01

    Aims and Methods The UK’s Driver Vehicle Licensing Authority (DVLA) requires individuals to report if they have a medical condition such as alcohol dependence. General Medical Council guidance indicates that medical practitioners should ensure patients are aware of their impairment and requirement to notify the DVLA. Results In a survey of 246 people with known alcohol dependence, none were aware of advice on driving given by medical practitioners and none had self-reported. In addition, 362 doctors, either attending a college symposium or visiting a college website, were asked about their knowledge of DVLA regulations regarding alcohol dependence: 73% of those attending the symposium and 63% of those visiting the website answered incorrectly. In Scotland, over 20 000 people have alcohol dependence (over 1 million people with alcohol abuse), yet only 2548 people with alcohol problems self-reported to the DVLA in 2011. Clinical implications If the DVLA regulations were implemented, it could make an enormous difference to the behaviours of the driving public. PMID:26191423

  12. Genetic Moderators and Psychiatric Mediators of the link between Sexual Abuse and Alcohol Dependence

    PubMed Central

    Copeland, William E.; Magnusson, Åsa; Göransson, Mona; Heilig, Markus A.

    2011-01-01

    Background/Objective This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that that might affect treatment planning. Methods A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. Results The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Conclusion Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. PMID:21193270

  13. Nalmefene: a new approach to the treatment of alcohol dependence

    PubMed Central

    Paille, François; Martini, Hervé

    2014-01-01

    Reduction of alcohol consumption is not yet a widely accepted treatment objective for alcohol-dependent patients, as abstinence is often considered to be the only possible objective in this situation. However, various studies have demonstrated the value of proposing these two options to such patients. Firstly, reduction of alcohol consumption very significantly reduces the risk of alcohol-related damage, and also modifies the patient’s and the doctor’s perception of the disease, resulting in improved access to care and better patient adherence with the proposed treatment objective and consequently better clinical results. Recent studies have shown that some medicinal products can help patients reduce their alcohol consumption. One such product, nalmefene, has been granted European marketing authorization and is now being released onto the market in various countries. The ESENSE 1 and 2 studies in alcohol-dependent patients showed that, in combination with BRENDA, a psychosocial intervention focusing on reinforcement of motivation and treatment adherence, nalmefene significantly reduced the number of heavy drinking days and mean daily total alcohol consumption versus placebo. This reduction was more marked in the marketing authorization target population, ie, patients with a high or very high drinking risk level according to World Health Organization criteria. Another original feature of this molecule is that it can be used as needed if the patient perceives a risk of drinking, which is a more flexible approach and more likely to ensure the patient’s active involvement in the treatment of his/her disease. This molecule opens up interesting and original therapeutic prospects in the treatment of alcohol dependence. PMID:25187751

  14. Nalmefene: a new approach to the treatment of alcohol dependence.

    PubMed

    Paille, François; Martini, Hervé

    2014-01-01

    Reduction of alcohol consumption is not yet a widely accepted treatment objective for alcohol-dependent patients, as abstinence is often considered to be the only possible objective in this situation. However, various studies have demonstrated the value of proposing these two options to such patients. Firstly, reduction of alcohol consumption very significantly reduces the risk of alcohol-related damage, and also modifies the patient's and the doctor's perception of the disease, resulting in improved access to care and better patient adherence with the proposed treatment objective and consequently better clinical results. Recent studies have shown that some medicinal products can help patients reduce their alcohol consumption. One such product, nalmefene, has been granted European marketing authorization and is now being released onto the market in various countries. The ESENSE 1 and 2 studies in alcohol-dependent patients showed that, in combination with BRENDA, a psychosocial intervention focusing on reinforcement of motivation and treatment adherence, nalmefene significantly reduced the number of heavy drinking days and mean daily total alcohol consumption versus placebo. This reduction was more marked in the marketing authorization target population, ie, patients with a high or very high drinking risk level according to World Health Organization criteria. Another original feature of this molecule is that it can be used as needed if the patient perceives a risk of drinking, which is a more flexible approach and more likely to ensure the patient's active involvement in the treatment of his/her disease. This molecule opens up interesting and original therapeutic prospects in the treatment of alcohol dependence. PMID:25187751

  15. THE TREATMENT OF ALCOHOL AND OPIOID DEPENDENCE IN PREGNANT WOMEN

    PubMed Central

    Heberlein, Annemarie; Leggio, Lorenzo; Stichtenoth, Dirk; Thomas, Hillemacher

    2016-01-01

    Purpose of the review This article addresses the question of “best treatment options,” which clinicians face when treating pregnant women with alcohol and/or opioid dependence. Recent findings Alcohol Studies show that alcohol consumption is associated with fetal abnormalities and long-term cognitive problems depending on amount consumed, drinking pattern, and time of gestation. Screening and evaluation of specific interventions are important to reduce alcohol consumption during pregnancy and associated problems in infants. Opioids Withdrawal-induced fetal distress and the risk of relapse are the primary reasons why opioid detoxification is only recommended in the second or third trimesters and only in those pregnant women who refuse opioid maintenance therapy (OMT). Methadone is the most established treatment of pregnant opioid-dependent women, but recent investigations suggest that substitution with buprenorphine may have advantages over methadone in terms of neonatal abstinence syndrome (NAS). Promising results have been also reported for slow-release oral methadone and the heroin equivalent diamorphin. Summary Data regarding the pharmacological treatment of alcohol abuse and/or dependence is limited in pregnant women. So far, benzodiazepines seem to be the most recommendable option for managing alcohol withdrawal, and psychosocial interventions succeed in reducing alcohol consumption or in maintaining abstinence in alcohol-dependent pregnant women. Recent data, albeit preliminary, support the use of naltrexone in the treatment of alcohol-dependent pregnant women. Regarding opioid dependence meta-analyses do not clearly support the superiority of one substitute over the other during pregnancy owing to the presence of interfering factors (such as illicit drug use) in the studies conducted. Current results suggest that factors like the health status of the mother, the need for additional medications (e.g. treatment for HIV), comorbid drug dependence, and

  16. Serum Levels of Growth Factors in Alcohol-dependent Patients according to Comorbid Depressive Symptoms

    PubMed Central

    Han, Changwoo; Ahn, Donghyun; Hahm, Woong; Nam, Junghyun; Park, Yongchon; Lim, Seulgi; Kim, Dai-Jin

    2016-01-01

    Objective This study aims to reveal the relationship of depression with growth factors such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and insulin-like growth factor-1 (IGF-1) in inpatients diagnosed with alcohol dependence, and to identify candidate growth factors as biological markers to indicate the comorbid of alcohol dependence and depression. Methods This study examined demographic factors in 45 alcohol-dependent patients. The ADS (Korean version of the Alcohol Dependence Scale) and BDI (Korean version of Beck’s Depression Inventory) were used. BDNF, NGF, and IGF-1 were measured through ELISA. Results The average drinking quantity and the ADS score were significantly more severe in alcohol-dependent patients with depression than in those without depression. Linearly comparing BDNF, NGF, and IGF-1 with BDI values, IGF-1 was the growth factor significantly correlated with BDI scores. BDI scores were significantly correlated with ADS scores. IGF-1 was significantly higher in alcohol-dependent patients with depression. Alcohol-dependent patients with depression had greater alcohol use and more severe ADS scores. BDNF and NGF showed no significant difference between alcohol-dependent patients with and without depression, but IGF-1 was significantly higher in those with than in those without depression. Conclusion IGF-1 was found to be associated with depression in alcohol-dependent patients, suggesting that IGF-1 in alcohol-dependent patients could be an important biomarker to indicate whether alcohol-dependence is accompanied by depression. PMID:26792039

  17. Risk of alcohol dependence: prevalence, related problems and socioeconomic factors.

    PubMed

    Martins-Oliveira, Juliana Gabrielle; Jorge, Kelly Oliva; Ferreira, Raquel Conceição; Ferreira, Efigênia Ferreira E; Vale, Míriam Pimenta; Zarzar, Patrícia Maria

    2016-01-01

    The present study evaluated the possible alcohol dependence and related problems among adolescents and determined possible associations with socioeconomic factors and gender. A cross-sectional study was conducted with a representative sample of 936 adolescents aged 15 to 19 years enrolled at public and private schools in the city of Belo Horizonte, Brazil. Data related to alcohol consumption and associated problems were collected using the Alcohol Use Disorder Identification Test (AUDIT). The Social Vulnerability Index (SVI), mother's schooling and type of school were used to assess socioeconomic factors. Statistical analysis involved the chi-square test (p < 0.05) and Poisson regression. The prevalence of possible dependence was 16.4%, 52.1% reported concern of a family member regarding the adolescent's alcohol consumption. Female adolescents were less likely to exhibit possible dependence in comparison to males. Participants with living in a low vulnerability area were more likely to consume alcohol in comparison to those living in underprivileged areas. The results of the present study demonstrate that possible dependence was significantly associated with the male gender and low social vulnerability. PMID:26816159

  18. Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence.

    PubMed

    Keating, Gillian M

    2014-01-01

    A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients. Sodium oxybate was generally well tolerated. The risk of sodium oxybate abuse is generally low when it is administered to alcohol-dependent patients at its approved dosage, under the supervision of a designated family member and with continuous strict medical surveillance. However, certain patient groups, such as patients with alcohol dependence and borderline personality disorder or who are in remission from heroin or cocaine addiction, may not be suitable candidates for sodium oxybate therapy because of an increased risk of abuse. In conclusion, sodium oxybate is a useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. PMID:24307430

  19. Psychiatric advances in the understanding and treatment of alcohol dependence.

    PubMed

    Madden, J S

    1984-01-01

    Several psychiatric topics have been under recent investigation. Cerebral impairment is now known to occur in over half of alcoholic patients. Its improvement with abstinence and its interference with the considerable intellectual and volitional requirements needed by controlled drinking programmes point to abstinence as the necessary drinking goal when brain damage is suspected. A hereditary element to alcohol dependence has been suggested by several adoption and twin studies, but the many contradictions between research results emphasise that any genetic contribution is overshadowed by socio-cultural factors. Depression and anxiety are frequent accompaniments of alcoholism but are shown by investigations usually as results rather than causes of excessive drinking. The onset of depression with suicidal ideas secondary to alcoholism has been sensitively described, and attention drawn to its identification, potential risk, and prevention. Long-term drug treatments are little used at present, but several developments are feasible. They include an effective long-acting chemical deterrent; drugs to protect against organic damage; sobering agents; immunotherapy; chemical reversal of the neuroadaptive changes responsible for physical dependence; drugs to counteract dysphoria and craving produced by alcohol; pharmacological modification of reflex behaviour; and drugs for the abstinence syndrome and for mood disturbance that are not themselves liable to misuse of dependence. Finally, it is suggested that the syndrome of pathological intoxication is a fictitious state that should be discarded from the descriptive literature. PMID:6398077

  20. Individualised treatment in alcohol-dependent patients.

    PubMed

    Mann, Karl; Hermann, Derik

    2010-11-01

    Long-term relapse prevention is the biggest challenge in treating alcohol-dependent patients. It is equally based on psychotherapy and pharmacotherapy. Psychotherapy includes motivational interviewing, community reinforcement, cognitive behavioural therapy, motivational enhancement, twelve-step facilitation, social network behaviour therapy, cue exposure, etc. For pharmacological treatment, we dispose of disulfiram, acamprosate and naltrexone. Reviews and meta-analyses reveal only modest effect sizes of these approaches probably because they are usually tested in large and heterogeneous samples where "one size does not fit all". However, attempts to form more homogeneous subgroups for which specific psychotherapies should be more effective ("matching") also failed. We suppose that this failure may have to do with the fact that these studies used only psychopathology and behavioural analyses as a basis for subtyping. Things look more promising once biologically defined endophenotypes are used as well in order to form more homogeneous subgroups. For example, naltrexone treatment seems more effective in carriers of a specific variant of the mu-opioid receptor gene. The same could be true for acamprosate if a newly found polymorphism was used to preselect potential responders. Very recently biological differences between patient groups are also being detected using functional imaging. Naltrexone is suggested to work better in a subgroup of patients with higher cue reactivity when shown appetitive alcohol pictures. MR spectroscopy of brain glutamate levels may detect potential acamprosate responders. On such a basis, an individualised approach in the treatment of alcoholism ("personalised medicine") seems to hold promise. PMID:20953618

  1. Effects of naltrexone on neural and subjective response to alcohol in treatment-seeking alcohol dependent patients

    PubMed Central

    Spagnolo, Primavera A.; Ramchandani, Vijay A.; Schwandt, Melanie L.; Zhang, Lishu; Blaine, Sara K.; Usala, Julie M.; Diamond, Kristie A.; Phillips, Monte J.; George, David T.; Momenan, Reza; Heilig, Markus

    2014-01-01

    Rationale Positively reinforcing properties of alcohol are in part mediated by activation of the ventral striatum (VS). Alcohol-induced release of endogenous opioids is thought to contribute to this response. Preclinical studies show that the opioid antagonist naltrexone (NTX) can block this cascade, but its ability to do so in treatment seeking alcoholics has not been examined. Objectives To study the effects of NTX on alcohol-induced VS activation and on amygdala response to affective stimuli in treatment seeking alcohol dependent inpatients. Methods Sixty-three treatment seeking alcoholics were randomized to receive NTX (50 mg) or placebo (PLC) daily. On day 7, participants underwent an alcohol cue reactivity session, and craving was measured using the Penn Alcohol Craving Scale. On day 9, participants received a saline infusion followed by an alcohol infusion and also viewed affective stimuli in an MR scanner. Results Irrespective of medication treatment condition, the alcohol infusion did not activate the VS in the alcohol dependent patients. Unexpectedly, VS activation was greater in NTX treated patients than in the PLC group. NTX treated patients also reported increased craving in response to alcohol cue exposure, and increased subjective response to alcohol (‘high’ and ‘intoxicated’) compared to PLC subjects. No significant effects of alcohol infusion on brain response to affective stimuli were in the NTX or placebo groups. Conclusions Unlike previous findings in social drinkers, a moderate level of intoxication did not activate the VS in treatment seeking alcoholics. This is likely to reflect tolerance to the positively reinforcing properties of alcohol in this clinical population. Our findings may help explain the efficacy of NTX to reduce heavy drinking, but not to maintain abstinence. PMID:25581657

  2. Animal models and their results in gastrointestinal alcohol research.

    PubMed

    Siegmund, Soren V; Haas, Stephan; Singer, Manfred V

    2005-01-01

    Alcohol-induced diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the precise pathophysiological mechanisms are still largely unknown. Alcohol research depends essentially on animal models due to the fact that controlled experimental studies of ethanol-induced diseases in humans are unethical. Animal models have already been successfully applied to disclose and analyze molecular mechanisms in alcohol-induced diseases, partially by using knockout technology. Because of a lack of transferability of some animal models to the human condition, results have to be interpreted cautiously. For some alcohol-related diseases like chronic alcoholic pancreatitis, the ideal animal model does not yet exist. Here we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the findings based on animal models as well as the current concepts of pathophysiological mechanisms involved in acute and chronic alcoholic damage of the esophagus, stomach, small and large intestine, pancreas and liver. PMID:16508282

  3. Genome-wide association discoveries of alcohol dependence

    PubMed Central

    Zuo, Lingjun; Lu, Lingeng; Tan, Yunlong; Pan, Xinghua; Cai, Yiqiang; Wang, Xiaoping; Hong, Jiang; Zhong, Chunlong; Wang, Fei; Zhang, Xiang-yang; Vanderlinden, Lauren A.; Tabakoff, Boris; Luo, Xingguang

    2014-01-01

    Objective To report the genome-wide significant and/or replicable risk variants for alcohol dependence and explore their potential biological functions. Methods We searched in PubMed for all genome-wide association studies (GWASs) of alcohol dependence. The following three types of the results were extracted: (1) genome-wide significant associations in an individual sample, the combined samples, or the meta-analysis (p<5×10−8); (2) top-ranked associations in an individual sample (p<10−5) that were nominally replicated in other samples (p<0.05); and (3) nominally replicable associations across at least three independent GWAS samples (p<0.05). These results were meta-analyzed. cis-eQTLs in human, RNA expression in rat and mouse brain and bioinformatics properties of all of these risk variants were analyzed. Results The variants located within ADH cluster were significantly associated with alcohol dependence at genome-wide level (p<5×10−8) in at least one sample. Some associations with the ADH cluster were replicable across six independent GWAS samples. The variants located within or near SERINC2, KIAA0040, MREG-PECR or PKNOX2 were significantly associated with alcohol dependence at genome-wide level (p<5×10−8) in meta-analysis or combined samples, and these associations were replicable across at least one sample. The associations with the variants within NRD1, GPD1L-CMTM8 or MAP3K9-PCNX were suggestive (5×10−8alcohol dependence. PKNOX2, MREG, PECR, GPD1L, CMTM8, MAP3K9, PCNX and OPA3 might play less

  4. Treatment of alcohol dependence: recent progress and reduction of consumption.

    PubMed

    Testino, G; Leone, S; Borro, P

    2014-12-01

    Alcohol dependence (AD) is a major public health problem. Currently, three drugs for the treatment of AD have been approved by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA): acamprosate, disulfiram, and oral naltrexone. The FDA also approved the use of long-acting injectable naltrexone. In Austria and in Italy sodium oxybate is also approved. The EMA's Committee for Medicinal Products for Human Use has recently granted marketing authorization for nalmefene for the reduction of alcohol consumption. Many patients, while accepting the problem, are unable or unwilling to completely stop consuming alcohol, leading to an inevitable deterioration over time of their psycho-physical state, and social and family relationships. It is appropriate to offer these patients the opportunity to significantly reduce their consumption of alcohol. The reduction may be an opportunity to prepare the individual for achieving complete abstinence. Abstinence should always be the main goal. Currently, nalmefene is the only drug that has been authorized for the reduction of alcohol consumption. Its association with psycho-social support is mandatory; it is taken on an "as-needed" basis, which should preferably be 1-2 hours before the possible intake of alcohol. The trials showed a significant reduction in alcohol consumption, which resulted in a significant reduction in morbidity and mortality. Reducing consumption allows a decrease in the progression of numerous alcohol-induced chronic diseases, as well as a reduction in psycho-physical damage, acts of violence, motor vehicle accidents, and accidents at work, which in turn means fewer healthcare costs. PMID:25392958

  5. Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

    PubMed Central

    Jung, Young-Chul

    2006-01-01

    Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence. These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence. PMID:16642544

  6. Age of Alcohol-Dependence Onset: Associations with Severity of Dependence and Seeking Treatment

    ERIC Educational Resources Information Center

    Hingson, Ralph W.; Heeren, Timothy; Winter, Michael R.

    2007-01-01

    Objective: We explored whether people who become alcohol dependent at younger ages are more likely to seek alcohol-related help or treatment or experience chronic relapsing dependence. Methods: In 2001-2002 the National Institute on Alcohol Abuse and Alcoholism completed a face-to-face interview survey with a multistage probability sample of 43…

  7. The dimensionality of alcohol use disorders: results from Israel

    PubMed Central

    Shmulewitz, Dvora; Keyes, Katherine; Beseler, Cheryl; Aharonovich, Efrat; Aivadyan, Christina; Spivak, Baruch; Hasin, Deborah

    2013-01-01

    Aims To prepare for DSM-V, the structure of DSM-IV alcohol dependence and abuse criteria and a proposed additional criterion, at-risk drinking, require study in countries with low per-capita consumption, and comparison of current and lifetime results within the same sample. We investigated DSM-IV Alcohol Use Disorder (AUD) criteria in Israel, where per-capita alcohol consumption is low. Methods Household residents selected from the Israeli population register (N=1,338) were interviewed with the AUDADIS. Item Response Theory analyses were conducted using MPlus, and diagnostic thresholds examined with the kappa statistic. Results Dependence and abuse criteria fit a unidimensional model interspersed across the severity continuum, for both current and lifetime timeframes. Legal problems were rare and did not improve model fit. Weekly at-risk drinking reflected greater severity than in U.S. samples. When dependence and abuse criteria were combined, a diagnostic threshold of ≥3 criteria produced the best agreement with DSM-IV diagnoses (kappa>0.80). Conclusion Consistent with other studies, alcohol dependence and abuse criteria reflected a latent variable representing a single AUD. Results suggested little effect in removing legal problems and little gained by adding weekly at-risk drinking. Results contribute to knowledge about AUD criteria by examining them in a low-consumption country. PMID:20537809

  8. In silico Models of Alcohol Dependence and Treatment.

    PubMed

    Kovatchev, Boris; Breton, Marc; Johnson, Bankole

    2012-01-01

    In this paper we view alcohol dependence and the response to treatment as a recurrent bio-behavioral process developing in time and propose formal models of this process combining behavior and biology in silico. The behavioral components of alcohol dependence and treatment are formally described by a stochastic process of human behavior, which serves as an event generator challenging the metabolic system. The biological component is driven by the biochemistry of alcohol intoxication described by deterministic models of ethanol pharmacodynamics and pharmacokinetics to enable simulation of drinking addiction in humans. Derived from the known physiology of ethanol and the literature of both ethanol intoxication and ethanol absorption, the different models are distilled into a minimal model (as simple as the complexity of the data allows) that can represent any specific patient. We use these modeling and simulation techniques to explain responses to placebo and ondansetron treatment observed in clinical studies. Specifically, the response to placebo was explained by a reduction of the probability of environmental reinforcement, while the effect of ondansetron was explained by a gradual decline in the degree of ethanol-induced neuromodulation. Further, we use in silico experiments to study critical transitions in blood alcohol levels after specific average number of drinks per day, and propose the existence of two critical thresholds in the human - one at 5 and another at 11 drinks/day - at which the system shifts from stable to critical and to super critical state indicating a state of alcohol addiction. The advantages of such a model-based investigation are that (1) the process of instigation of alcohol dependence and its treatment can be deconstructed into meaningful steps, which allow for individualized treatment tailoring, and (2) physiology and behavior can be quantified in different (animal or human) studies and then the results can be integrated in silico. PMID

  9. Prevalence & correlates of metabolic syndrome in alcohol & opioid dependent inpatients

    PubMed Central

    Mattoo, Surendra K.; Chakraborty, Kaustav; Basu, Debasish; Ghosh, Abhishek; Vijaya, Kumar KG; Kulhara, Parmanand

    2011-01-01

    Background & objectives: The research on the association of metabolic syndrome (MS) and substance abuse is scanty. The present research aimed to study the prevalence and correlates of MS among the inpatients at a Drug De-addiction Centre in north India. Methods: Consecutive male subjects (N=110) admitted to a drug de-addiction centre during July to December 2009 with a primary diagnosis of alcohol or opioid dependence were evaluated for the presence of MS as per the International Diabetes Federation (IDF) criteria. Results: The prevalence of MS was 24.6 and 29.3 per cent in alcohol and opioid dependent groups, respectively. MS showed a significant association with the age and body mass index (BMI) in the opioid dependent group. Co-morbid tobacco use was not associated with MS in either group. Interpretation & conclusions: The prevalence of MS in our sample of alcohol and opioid dependent male inpatients was greater than the prevalence of MS in general population, however it was comparable to that reported in physical and other psychiatric disorder populations. Even though the absence of any comparative study limits the generalizability of our findings, results indicate towards a need for screening of the patients with substance dependence especially for those aged above 30 years and/or having a high BMI for MS. PMID:21985817

  10. Gabapentin Treatment for Alcohol Dependence: A Randomized Controlled Trial

    PubMed Central

    Mason, Barbara J.; Quello, Susan; Goodell, Vivian; Shadan, Farhad; Kyle, Mark; Begovic, Adnan

    2013-01-01

    Importance Approved medications for alcohol dependence are prescribed for fewer than 9% of US alcoholics. Objective To determine if gabapentin, a widely-prescribed generic calcium channel/GABA modulating medication, increases rates of sustained abstinence and no heavy drinking, and decreases alcohol-related insomnia, dysphoria and craving, in a dose-dependent manner. Design, Participants and Setting A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women over 18 years of age with current alcohol dependence, conducted 2004–2010 at a single-site outpatient clinical research facility adjoining a general medical hospital. Interventions Oral gabapentin (0, 900, 1800 mg/d) and concomitant manual-guided counseling. Main Outcome Measures Rates of complete abstinence and no heavy drinking (co-primary) and changes in mood, sleep and craving (secondary) over the 12-week study. Results Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1 to 13.7) in the placebo group, 11.1% (95% CI, 5.2 to 22.2) in the 900 mg group, and 17.0% (95% CI, 8.9 to 30.1) in the 1800 mg group (p = 0.04 for linear dose effect, NNT = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6 to 37.2) in the placebo group, 29.6% (95% CI, 19.1 to 42.8) in the 900 mg group, and 44.7% (95% CI, 31.4 to 58.8) in the 1800 mg group (p = 0.02 for linear dose effect, NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F=7.37, df=2, p=0.001), sleep (F=136, df=2, p<0.001), and craving (F=3.56, df=2, p=0.029). There were no serious drug-related adverse events, and terminations from adverse-events (9 of 150 participants), time on study (9.1 [3.8] weeks) and rate of study completion (85 of 150 participants) did not differ between groups. Conclusions and Relevance Gabapentin (particularly the 1800 mg dosage) was effective in treating alcohol dependence and relapse

  11. Association of gene polymorphisms encoding dopaminergic system components and platelet MAO-B activity with alcohol dependence and alcohol dependence-related phenotypes.

    PubMed

    Nedic Erjavec, Gordana; Nenadic Sviglin, Korona; Nikolac Perkovic, Matea; Muck-Seler, Dorotea; Jovanovic, Tanja; Pivac, Nela

    2014-10-01

    The present study aimed to evaluate the association of alcohol dependence and alcohol dependence-related phenotypes with platelet monoamine oxidase type B (MAO-B) activity, Val108/158Met of catechol-o-methyltransferase (COMT), variable number of tandem repeats (VNTR) in the third exon of dopamine receptor D4 (DRD4) gene, VNTR in the 3'-untranslated region of dopamine transporter (DAT) gene, -1021C/T of dopamine beta-hydroxylase (DBH) and MAO-B intron 13 polymorphisms. The study included 1270 Caucasian men and women of Croatian origin: 690 patients with alcohol dependence and 580 healthy controls. Patients with alcohol dependence were subdivided according to the presence or absence of withdrawal symptoms, aggressive behavior, severity of alcohol dependence, delirium tremens, comorbid depression, suicidal behavior, lifetime suicide attempt and early/late onset of alcohol abuse. The results, corrected for multiple testing, revealed increased platelet MAO-B activity in patients with alcohol dependence, subdivided into those with or without alcohol-related liver diseases, compared to control subjects (P<0.001). In addition, we found an increased frequency of the COMT Met/Met genotype among suicidal (P=0.002) and patients who attempted suicide (P<0.001) and an increased frequency of COMT Val/Val genotype in patients with an early onset of alcohol dependence (P=0.004). This study provides data from a sample of ethnically homogeneous unrelated Caucasian subjects for future meta-analyses and suggests that the increased platelet MAO-B activity might be used as independent peripheral indicator of alcohol dependence, while COMT Val108/158Met polymorphism is associated with increased suicidality and early onset of alcohol dependence. PMID:25035107

  12. Reduced Glial and Neuronal Packing Density in the Orbitofrontal Cortex in Alcohol Dependence and Its Relationship with Suicide and Duration of Alcohol Dependence

    PubMed Central

    Miguel-Hidalgo, Jose J.; Overholser, James C.; Meltzer, Herbert Y.; Stockmeier, Craig A.; Rajkowska, Grazyna

    2010-01-01

    Background Reduced metabolism, blood flow, and tissue volume have been detected in the dorsolateral prefrontal cortex (dlPFC) of neurologically intact alcoholic subjects and these deficits are accompanied by lower density of neurons and glial cells. Another prefrontal region, the orbitofrontal cortex (ORB), functionally and structurally differentiated from the dlPFC, and heavily involved in decision-making processes, also shows functional alterations in alcoholic subjects. However, it is unknown whether changes in the packing density of neurons or glial cells also occur in the ORB and whether that density may be related to the increased suicide probability of alcoholic subjects or to the duration of alcohol dependence. Methods The present study used a 3-dimensional cell-counting method in postmortem brain tissue to determine the packing density of neurons and glial cells in the ORB (area 47) of 15 subjects with alcohol dependence (8 suicides, 7 nonsuicides) and 8 normal controls and to determine whether cell density is correlated with suicide and duration of alcohol dependence. Results There was a significantly lower density of both neurons (by 27%) and glial cells (by 25%) in the ORB of alcoholic subjects compared with controls. Packing density of either neurons or glial cells was not significantly different in alcoholic suicides compared with alcoholic nonsuicides. Age was not correlated with neuronal or glial density in either group. However, the duration of alcohol dependence and the ratio of that duration to the length of life span were significantly and negatively correlated to the overall density of neurons. Conclusion The present results indicate that alcohol dependence is associated with a decrease in the packing density of neurons and glia in the ORB and that the reduction in neuronal but not glial density progresses with the duration of alcohol dependence. PMID:17067348

  13. Management of Alcohol Dependence in Patients with Liver Disease

    PubMed Central

    Addolorato, Giovanni; Mirijello, Antonio; Leggio, Lorenzo; Ferrulli, Anna; Landolfi, Raffaele

    2016-01-01

    Alcohol dependence represents a chronic and relapsing disease affecting nearly 10% of the general population both in the United States and in Europe, with a widespread burden of morbidity and mortality. Alcohol dependence represents the most common cause of liver damage in the Western Countries. Although alcoholic liver disease is associated primarily with heavy drinking, continued alcohol consumption, even in low doses after the onset of liver disease, increases the risk of severe consequences, including mortality. Consequently the ideal treatment of patients affected by alcohol dependence and alcoholic liver disease should aim at achieving long-term total alcohol abstinence and preventing relapse. The aim of the present review is to provide an update on the management of alcohol dependence in patients with alcoholic liver disease. Increasing evidences suggests the usefulness of psychosocial interventions and medications combined in order to reduce alcohol intake, promote abstinence and prevent relapse in alcohol dependent patients. Disulfiram, naltrexone and acamprosate have been approved for this indication; gamma-hydroxybutyric acid (GHB) is approved in Italy and Austria. However, these drugs have not been tested in patients with advanced liver disease. Amongst other emerging pharmacotherapies for alcoholism, topiramate, ondansetron, and baclofen seem the most promising ones. Both topiramate and ondansetron hold a safe profile in alcoholic patients; however, none of them has been tested in alcoholic patients with advanced liver disease. To date, baclofen represents the only anti-craving medication formally tested in a randomized clinical trial in alcoholic patients affected by liver cirrhosis, although additional confirmatory studies are warranted. PMID:23456576

  14. Acamprosate: A Review of Its Use in Alcohol Dependence.

    PubMed

    Plosker, Greg L

    2015-07-01

    Acamprosate (Campral(®), Aotal(®), Regtect(®)) is one of a limited number of pharmacological treatment options approved as an adjunct to psychosocial interventions to facilitate the maintenance of abstinence in alcohol-dependent patients. It has been used in Europe, the USA and other countries for many years and was recently approved for this indication in Japan. In several randomized, double-blind, placebo-controlled trials (without active comparators), acamprosate in conjunction with psychosocial therapy for 3-12 months was generally significantly better than placebo plus psychosocial interventions in improving various key outcomes, including the proportion of patients who maintained complete abstinence from alcohol (complete abstinence rate), the mean cumulative abstinence duration, the percentage of alcohol-free days and the median time to first drink. Acamprosate as an adjunct to psychosocial interventions also demonstrated efficacy in some randomized, active-comparator trials of similar duration. Although results were not always consistent across individual trials, overall findings were generally favourable for acamprosate in a recent meta-analysis, which showed that alcohol-consumption outcomes were similarly improved with acamprosate or naltrexone. Acamprosate is generally well tolerated, has a low propensity for drug interactions and may be used without dosage adjustment in patients with mild to moderate hepatic impairment, although dosage adjustments or contraindications are recommended in patients with renal impairment. Thus, the use of acamprosate as an adjunct to psychosocial interventions in alcohol-dependent patients provides modest but potentially valuable improvements in alcohol-consumption outcomes and is generally well tolerated. PMID:26084940

  15. Molecular Genetics of Alcohol Dependence and Related Endophenotypes

    PubMed Central

    Le Strat, Yann; Ramoz, Nicolas; Schumann, Gunter; Gorwood, Philip

    2008-01-01

    Alcohol dependence is a worldwide public health problem, and involves both environmental and genetic vulnerability factors. The heritability of alcohol dependence is rather high, ranging between 50% and 60%, although alcohol dependence is a polygenic, complex disorder. Genome-wide scans on large cohorts of multiplex families, including the collaborative study on genetics of alcoholism (COGA), emphasized the role of many chromosome regions and some candidate genes. The genes encoding the alcohol-metabolizing enzymes, or those involved in brain reward pathways, have been involved. Since dopamine is the main neurotransmitter in the reward circuit, genes involved in the dopaminergic pathway represent candidates of interest. Furthermore, gamma-amino-butyric acid (GABA) neurotransmitter mediates the acute actions of alcohol and is involved in withdrawal symptomatology. Numerous studies showed an association between variants within GABA receptors genes and the risk of alcohol dependence. In accordance with the complexity of the “alcohol dependence” phenotype, another field of research, related to the concept of endophenotypes, received more recent attention. The role of vulnerability genes in alcohol dependence is therefore re-assessed focusing on different phenotypes and endophenotypes. The latter include brain oscillations, EEG alpha and beta variants and alpha power, and amplitude of P300 amplitude elicited from a visual oddball task. Recent enhancement on global characterizations of the genome by high-throughput approach for genotyping of polymorphisms and studies of transcriptomics and proteomics in alcohol dependence is also reviewed. PMID:19506733

  16. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 CFR part 40 (at § 40.25 and appendix H to part 40), not later than March 15 of each year for the... 49 Transportation 3 2011-10-01 2011-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a)...

  17. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 CFR part 40 (at § 40.25 and appendix H to part 40), not later than March 15 of each year for the... 49 Transportation 3 2010-10-01 2010-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a)...

  18. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 CFR part 40 (at § 40.25 and appendix H to part 40), not later than March 15 of each year for the... 49 Transportation 3 2012-10-01 2012-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a)...

  19. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 CFR part 40 (at § 40.25 and appendix H to part 40), not later than March 15 of each year for the... 49 Transportation 3 2014-10-01 2014-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a)...

  20. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 CFR part 40 (at § 40.25 and appendix H to part 40), not later than March 15 of each year for the... 49 Transportation 3 2013-10-01 2013-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a)...

  1. Estimates of US children exposed to alcohol abuse and dependence in the family.

    PubMed Central

    Grant, B F

    2000-01-01

    OBJECTIVES: This study sought to provide direct estimates of the number of US children younger than 18 years who are exposed to alcohol abuse or alcohol dependence in the family. METHODS: Data were derived from the National Longitudinal Alcohol Epidemiologic Survey. RESULTS: Approximately 1 in 4 children younger than 18 years in the United States is exposed to alcohol abuse or alcohol dependence in the family. CONCLUSIONS: There is a need for approaches that integrate systems of services to enhance the lives of these children. PMID:10630147

  2. [Cognitive impairments in alcohol dependence: From screening to treatment improvements].

    PubMed

    Cabé, N; Laniepce, A; Ritz, L; Lannuzel, C; Boudehent, C; Vabret, F; Eustache, F; Beaunieux, H; Pitel, A-L

    2016-02-01

    Alcohol-related cognitive impairments are largely underestimated in clinical practice, even though they could limit the benefit of alcohol treatment and hamper the patient's ability to remain abstinent or to respect his/her therapeutic contract. These neuropsychological deficits can impact the management of patients well before the development of the well-known Korsakoff's syndrome. Indeed, even in the absence of ostensible neurological complications, excessive and chronic alcohol consumption results in damage of brain structure and function. The frontocerebellar circuit and the circuit of Papez, respectively involved in motor and executive abilities and episodic memory, are mainly affected. Those brain dysfunctions are associated with neuropsychological deficits, including deficits of executive functions, episodic memory, social cognition, as well as visuospatial and motor abilities. Such cognitive disorders can interfere with the motivation process to abandon maladjusted drinking behavior in favor of a healthier lifestyle (such as abstinence or controlled alcohol consumption). They can also limit the patient's capacity to fully benefit from treatment (notably psychoeducation and cognitive-behavioural treatments) currently widely proposed in French Addiction departments. In addition, they may contribute to relapse which is multi-determinated. A neuropsychological assessment appears therefore crucial to take relevant clinical decisions. However, very few addiction departments have the human and financial resources to conduct an extensive neuropsychological examination of all patients with alcohol dependence. Some brief screening tools can be used, notably the MOntreal Cognitive Assessment and the Brief Evaluation of Alcohol-Related Neuropsychological Impairments, which has been especially designed to assess cognitive and motor deficits in alcoholism. These tools can be used by non-psychologist clinicians to detect alcohol-related cognitive deficits, which require

  3. Relationships of impulsiveness and depressive symptoms in alcohol dependence

    PubMed Central

    Jakubczyk, Andrzej; Klimkiewicz, Anna; Topolewska-Wochowska, Aleksandra; Serafin, Piotr; Sadowska-Mazuryk, Joanna; Pupek-Pyzioł, Julia; Brower, Kirk J.; Wojnar, Marcin

    2011-01-01

    Background Depressive symptoms as well as high levels of impulsivity are subjects of special interest in alcohol dependence, as these factors are considered to influence the course of this disorder. However, until now mutual relationships between impulsivity and depression have not been investigated thoroughly in alcohol-dependent patients. Methods By means of the Barratt Impulsiveness Scale (BIS-11) and stop-signal task, levels of impulsivity among 304 alcohol-dependent patients were measured. The stop-signal task was used as a manipulation-free method of estimating the level of behavioral impulsiveness, and the BIS-11 is a self report measure of global as well as cognitive impulsivity. Patients were also asked to complete the Beck Depression Inventory (BDI) and Hopelessness Scale (BHS). The results were analyzed in order to examine relationships between impulsiveness and depressive symptoms. Results Statistical analyses revealed significant associations between impulsiveness and severity of depressive symptoms. Individuals with higher scores on the BDI were more impulsive on the BIS-11, whereas patients with higher scores on the BHS were more impulsive on both the stop-signal task and BIS-11. The strongest correlations were found with the attention impulsivity subscale of BIS-11. Adjusting for other variables, a linear regression analysis revealed that cognitive impulsivity was the strongest predictor of depression severity. Limitations The main limitation of the study is a not fully representative sample, with exclusion of patients with active mood disorders Conclusions The results indicate a strong association between depressive symptoms and impulsivity in alcohol-dependent patients, and suggest an important distinction between hopelessness and other depressive symptoms. PMID:22030134

  4. Industrialization Stresses, Alcohol Abuse & Substance Dependence: Differential Gender Effects in a Kenyan Rural Farming Community

    PubMed Central

    Walt, Lisa C.; Kinoti, Elias; Jason, Leonard A.

    2014-01-01

    Developing countries’ industrialization and urbanization attempts have been linked to psychological distress and alcohol abuse. We used Hobfoll’s COR theory to examine the relationship between gender, perceived resource loss (an indicator of industrialization stress), and alcohol abuse and dependence in a sample of Kenyan rural village men and women (N = 186). Regression analyses indicated that both gender and COR loss predicted alcohol abuse and dependence. Additionally, results suggested that gender moderated the relationship between COR loss and alcohol dependence; such that higher COR loss scores predicted higher alcohol dependence for men, but COR loss scores did not predict alcohol dependence for women. Thus, we suggest that gender differences in substance abuse may be due less to actual differences in resource loss, but rather to gender differences in the response to resource loss. Limitations and opportunities for future research are discussed. PMID:24489525

  5. Alcohol and Memory: Storage and State Dependency

    ERIC Educational Resources Information Center

    Parker, Elizabeth S.; And Others

    1976-01-01

    Effects of acute alcohol intoxication on the storage phase of memory were evaluated with two tasks that minimized response retrieval: unpaced paired-associate learning with highly available responses and forced-choice picture recognition. It was concluded that storage processes are sensitive to disruption by alcohol. (CHK)

  6. Dihydrocodeine/Agonists for Alcohol Dependents

    PubMed Central

    Ulmer, Albrecht; Müller, Markus; Frietsch, Bernhard

    2012-01-01

    Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients. Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC) to 102 heavily alcohol addicted patients, later, also Buprenorphine, Clomethiazole (>6 weeks), Baclofen, and in one case Amphetamine, each on individual indication. This paper focuses on the data with DHC, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-steps scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details. Conclusion: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around 1/4 of the patients already. Many further

  7. Methods for inducing alcohol craving in individuals with comorbid alcohol dependence and posttraumatic stress disorder: Behavioral and physiological outcomes

    PubMed Central

    Kwako, L. E.; Schwandt, M. L.; Sells, J. R.; Ramchandani, V. A.; George, D. T.; Sinha, R.; Heilig, M.

    2014-01-01

    Rationale Alcohol addiction is a chronic relapsing disorder that presents a substantial public health problem, and is frequently comorbid with posttraumatic stress disorder (PTSD). Craving for alcohol is a predictor of relapse to alcohol use, and is triggered by cues associated with alcohol and trauma. Identification of reliable and valid laboratory methods for craving induction is an important objective for alcoholism and PTSD research. Objectives The present study compares two methods for induction of craving via stress and alcohol cues in individuals with comorbid alcohol dependence (AD) and PTSD: the combined Trier Social Stress Test and cue reactivity paradigm (Trier/CR), and a guided imagery (Scripts) paradigm. Outcomes include self-reported measures of craving, stress, and anxiety as well as endocrine measures. Methods Subjects were 52 individuals diagnosed with comorbid AD and PTSD seeking treatment at the NIAAA inpatient research facility. They participated in a four week inpatient study of the efficacy of a NK1 antagonist to treat comorbid AD and PTSD, and which included the two challenge procedures. Results Both the Trier/CR and Scripts induced craving for alcohol, as well as elevated levels of subjective distress and anxiety. The Trier/CR yielded significant increases in ACTH and cortisol, while the Scripts did not. Conclusions Both paradigms are effective laboratory means of inducing craving for alcohol. Further research is warranted to better understand the mechanisms behind craving induced by stress vs. alcohol cues, as well as to understand the impact of comorbid PTSD and AD on craving. PMID:24806358

  8. [Treatment of alcohol dependence: rational and arguable approaches.

    PubMed

    Sivolap, Iu P

    2014-01-01

    Treatment of alcohol dependence consist of alcohol detoxification with withdrawal alleviation and relapse prevention or maintenance therapy. Drugs of choice for alcohol withdrawal cure are benzodiazepines and anticonvulsants are an alternative for them. Relapse prevention and alcohol abuse alleviation are carried out using disulfiram, acamprosate, naltrexone and nalmefene. Moreover, therapeutic possibilities of memantine, gabapentine, pregabalin, baclofen, modafinil, ondansetron D-cycloserine and aripiprazole are studying nowadays. Use of selective serotonin reuptake inhibitors including fluvoxamine for alcohol patients is of great importance due to frequent comorbidity of alcoholism, depression and anxiety. There are some doubtful methods of alcoholism treatment accepted in Russian addictive medicine such as clearance detoxification and use of antipsychotics for craving elimination. PMID:24988976

  9. General Practitioners Recognizing Alcohol Dependence: A Large Cross-Sectional Study in 6 European Countries

    PubMed Central

    Rehm, Jürgen; Allamani, Allaman; Vedova, Roberto Della; Elekes, Zsuzsanna; Jakubczyk, Andrzej; Landsmane, Inga; Manthey, Jakob; Moreno-España, José; Pieper, Lars; Probst, Charlotte; Snikere, Sigita; Struzzo, Pierluigi; Voller, Fabio; Wittchen, Hans-Ulrich; Gual, Antoni; Wojnar, Marcin

    2015-01-01

    PURPOSE Although alcohol dependence causes marked mortality and disease burden in Europe, the treatment rate is low. Primary care could play a key role in reducing alcohol-attributable harm by screening, brief interventions, and initiating or referral to treatment. This study investigates identification of alcohol dependence in European primary care settings. METHODS Assessments from 13,003 general practitioners, and 9,098 interviews (8,476 joint number of interviewed patients with a physician’s assessment) were collected in 6 European countries. Alcohol dependence, comorbidities, and health service utilization were assessed by the general practitioner and independently using the Composite International Diagnostic Interview (CIDI) and other structured interviews. Weighted regression analyses were used to compare the impact of influencing variables on both types of diagnoses. RESULTS The rate of patients being identified as alcohol dependent by the CIDI or a general practitioner was about equally high, but there was not a lot of overlap between cases identified. Alcohol-dependent patients identified by a physician were older, had higher rates of physicial comorbidity (liver disease, hypertension), and were socially more marginalized, whereas average consumption of alcohol and mental comorbidity were equally high in both groups. CONCLUSION General practitioners were able to identify alcohol dependence, but the cases they identified differed from cases identified using the CIDI. The role of the CIDI as the reference standard should be reexamined, as older alcohol-dependent patients with severe comorbidities seemed to be missed in this assessment. PMID:25583889

  10. New developments in the pharmacotherapy of alcohol dependence.

    PubMed

    Myrick, H; Brady, K T; Malcolm, R

    2001-01-01

    Neuroscientific underpinnings and pharmacotherapeutic treatments of substance use disorders are rapidly developing areas of study. In particular, there have been exciting new developments in our understanding of the involvement of excitatory amino acid neurotransmitter systems and the opiate and serotonin systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in subtypes of individuals with alcoholism. In this article, new developments in the pharmacotherapy of alcohol dependence will be reviewed. In particular, the use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes will be discussed. New data on opiate antagonists and acamprosate, an agent that exerts actions through excitatory amino acid systems in relapse prevention, will be reviewed. Finally, there will be a review of new data concerning the use of serotonin reuptake inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy. PMID:11268820

  11. Combined alcohol and energy drink use: hedonistic motives, adenosine, and alcohol dependence.

    PubMed

    Marczinski, Cecile A

    2014-07-01

    Consumption of alcohol mixed with energy drinks (AmED) has been associated with both short- and long-term risks beyond those observed with alcohol alone. AmED use has been associated with heavy episodic (binge) drinking, risky behaviors, and risk of alcohol dependence. Laboratory research has demonstrated that AmED beverages lead to greater motivation to drink versus the same amount of alcohol consumed alone. However, the reason consumers find AmED beverages particularly appealing has been unclear. A recent report by Droste and colleagues (Alcohol Clin Exp Res 2014; 38:2087-2095) is the first study to investigate motivations related to AmED consumption and to determine which motives predict AmED consumption patterns, experience of drinking-related harms, and risk of alcohol dependence. The findings of this study significantly enhance our understanding of why AmED consumption is related to the risk of alcohol dependence and change our understanding of why consumers choose AmED beverages. The authors report that hedonistic motives strongly predicted AmED use and the harms associated with use. While intoxication-reduction motives predicted self-reported accidents and injuries, these motives did not predict AmED consumption patterns and risk of dependence. The risk of alcohol dependence may arise from repeated experiences when drinking alcohol is more pleasurable when energy drinks are consumed with the alcohol. This commentary will focus on why energy drinks might increase the rewarding properties of alcohol in social drinkers. In addition, discussion is provided explaining why more research on the neurotransmitter, adenosine, may actually inform us about the mechanisms contributing to the development of alcohol dependence. PMID:25040590

  12. Heart rate variability during sleep in detoxified alcohol-dependent males: A comparison with healthy controls

    PubMed Central

    Ganesha, Suhas; Thirthalli, Jagadisha; Muralidharan, Kesavan; Benegal, Vivek; Gangadhar, Bangalore N.

    2013-01-01

    Context: Alcohol dependence can lead to autonomic neuropathy resulting in increased cardiac morbidity and mortality. This has previously been evaluated using heart-rate variability. Aims: We compared sleep heart-rate variability of alcohol-dependent patients with that of healthy controls in this study. Settings and Design: This study was conducted at NIMHANS, Bangalore. A case control study design was adopted. Materials and Methods: Sleep heart-rate variability of 20 male alcohol-dependent inpatients was recorded on the 5th day after detoxification. Sleep heart-rate variability was also recorded in 18 age- and gender-matched healthy controls. Statistical Analysis: The groups were compared using t-test for continuous variables and Chi-squared test for discrete variables. Results: Both time and frequency domain measures were significantly lower in the patients as compared to the controls, indicating decreased HRV in alcohol-dependent individuals. Conclusions: Decreased HRV in alcohol dependence indicates potential autonomic neuropathy. PMID:23825854

  13. Gene-based and pathway-based genome-wide association study of alcohol dependence

    PubMed Central

    ZUO, Lingjun; ZHANG, Clarence K.; SAYWARD, Frederick G.; CHEUNG, Kei-Hoi; WANG, Kesheng; KRYSTAL, John H.; ZHAO, Hongyu; LUO, Xingguang

    2015-01-01

    Background The organization of risk genes within signaling pathways may provide clues about the converging neurobiological effects of risk genes for alcohol dependence. Aim Identify risk genes and risk gene pathways for alcohol dependence. Methods We conducted a pathway-based genome-wide association study (GWAS) of alcohol dependence using a gene-set-rich analytic approach. Approximately one million genetic markers were tested in the discovery sample which included 1409 European-American (EA) alcohol dependent individuals and 1518 EA healthy comparison subjects. An additional 681 African-American (AA) cases and 508 AA healthy subjects served as the replication sample. Results We identified several genome-wide replicable risk genes and risk pathways that were significantly associated with alcohol dependence. After applying the Bonferroni correction for multiple testing, the ‘cellextracellular matrix interactions’ pathway (p<2.0E-4 in EAs) and the PXN gene (which encodes paxillin) (p=3.9E-7 in EAs) within this pathway were the most promising risk factors for alcohol dependence. There were also two nominally replicable pathways enriched in alcohol dependence-related genes in both EAs (0.015≤p≤0.035) and AAs (0.025≤p≤0.050): the ‘Na+/Cl- dependent neurotransmitter transporters’ pathway and the ‘other glycan degradation’ pathway. Conclusion These findings provide new evidence highlighting several genes and biological signaling processes that may be related to the risk for alcohol dependence. PMID:26120261

  14. Drinking Trajectories From Adolescence to the Fifties Among Alcohol-Dependent Men*

    PubMed Central

    Jacob, Theodore; Koenig, Laura B.; Howell, Donelle N.; Wood, Phillip K.; Haber, Jon Randolph

    2009-01-01

    Objective: Although it has been recognized that the course of alcoholism may differ across individuals, little work has characterized drinking trajectories from drinking onset to midlife. Method: The current study examined trajectories of alcohol dependence from adolescence to the mid-50s in a sample of 420 men with a lifetime diagnosis of alcohol dependence. Men from the Vietnam Era Twin Registry were given the Lifetime Drinking History, which assesses the patterns of alcohol consumption and diagnostic symptoms for self-defined drinking phases. Phase data were converted into person-year data, with alcohol-dependence diagnosis coded as present or absent for each of 13 age groupings, starting with up to age 20 and ending with ages 54-56. Results: Latent growth mixture modeling was used to define four drinking trajectories: young-adult, late-onset, severe-nonchronic, and severe-chronic alcoholics. Further analyses with other diagnostic variables, other drinking variables, alcohol expectancies, personality scales, and religiousness scores were completed to differentiate men best categorized by each trajectory. Conclusions: Extension of Latent Growth Mixture Modeling (LGMM) into the mid-50s revealed that, although some individuals remain chronic alcohol users, others decline in alcohol problem use. Differences seen among these groups may help in the treatment of alcohol dependence, such that more energy can be spent treating those likely to be in the more severe trajectories. PMID:19895762

  15. Cladistic association analysis of Y chromosome effects on alcohol dependence and related personality traits.

    PubMed

    Kittles, R A; Long, J C; Bergen, A W; Eggert, M; Virkkunen, M; Linnoila, M; Goldman, D

    1999-03-30

    Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism-antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism. PMID:10097188

  16. [Cognitive impairment of alcohol-dependent subjects].

    PubMed

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-04-01

    Chronic excessive alcohol consumption induces multiple brain damages. Secondary cognitive disorders include executive functions, episodic memory and visuospatial capacities. The severity of these alcohol induced disorders may vary between sub-clinical manifestations (that may, nevertheless, interfere with medical management) and more important ones like Korsakoff syndrome or dementia. The latter are usually irreversible but many of these manifestations are potentially reversible with persistent abstinence. It therefore appears of particular importance to clearly define neuropsychological management in order to identify and evaluate the type and severity of alcohol-related cognitive disorders. The patients may then be offered rehabilitation for these cognitive impairments. This is the first step of a complete addiction program based especially on cognitive behavioral therapies. PMID:24855773

  17. Quantifying alcohol-related emergency admissions in a UK tertiary referral hospital: a cross-sectional study of chronic alcohol dependency and acute alcohol intoxication

    PubMed Central

    Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R

    2016-01-01

    Objectives Alcohol is responsible for a proportion of emergency admissions to hospital, with acute alcohol intoxication and chronic alcohol dependency (CAD) implicated. This study aims to quantify the proportion of hospital admissions through our emergency department (ED) which were thought by the admitting doctor to be (largely or partially) a result of alcohol consumption. Setting ED of a UK tertiary referral hospital. Participants All ED admissions occurring over 14 weeks from 1 September to 8 December 2012. Data obtained for 5497 of 5746 admissions (95.67%). Primary outcome measures Proportion of emergency admissions related to alcohol as defined by the admitting ED clinician. Secondary outcome measures Proportion of emergency admissions due to alcohol diagnosed with acute alcohol intoxication or CAD according to ICD-10 criteria. Results 1152 (21.0%, 95% CI 19.9% to 22.0%) of emergency admissions were thought to be due to alcohol. 74.6% of patients admitted due to alcohol had CAD, and significantly greater than the 26.4% with ‘Severe’ or ‘Very Severe’ acute alcohol intoxication (p<0.001). Admissions due to alcohol differed to admissions not due to alcohol being on average younger (45 vs 56 years, p<0.001) more often male (73.4% vs 45.1% males, p<0.001) and more likely to have a diagnosis synonymous with alcohol or related to recreational drug use, pancreatitis, deliberate self-harm, head injury, gastritis, suicidal ideation, upper gastrointestinal bleeds or seizures (p<0.001). An increase in admissions due to alcohol on Saturdays reflects a surge in admissions with acute alcohol intoxication above the weekly average (p=0.003). Conclusions Alcohol was thought to be implicated in 21% of emergency admissions in this cohort. CAD is responsible for a significantly greater proportion of admissions due to alcohol than acute intoxication. Interventions designed to reduce alcohol-related admissions must incorporate measures to tackle CAD. PMID:27324707

  18. Association between Socio-Demographics and Alcohol Dependence among Individuals Living in an Indian Setting

    PubMed Central

    Vignesh, B. T.; Singh, Awnish K.; Mohan, S. K.; Murthy, Shruti; Joshi, Ashish

    2014-01-01

    Background: Alcohol use is on the rise worldwide and urgent steps are required to curb this growing burden of alcohol consumption. Alcohol drinking leads to serious social, physical and mental consequences. Objective: The objective of this pilot study is to examine association between socio-demographics and severity of alcohol dependence among individuals obtaining treatment at alcohol de-addiction center. Methods: This pilot cross sectional study was conducted in September 2013 in South India. A convenient sample of 100 participants was enrolled. Individuals aged 30 years and above, receiving treatment from de-addiction center and providing written informed consent were eligible for the study. A modified version of previously validated questionnaires was used for gathering information on socio-demographic characteristics, severity of alcohol dependence (using Alcohol Dependent Scale [ADS] and Short Alcohol Dependence Data questionnaire [SADD]), motivational incentives for alcohol quitting and challenges faced while quitting alcohol. Results: All participants were males with mean age of 43 years (SD = 6.5 years). Significant association was seen between ADS and annual income (p = 0.001), education (p = 0.001), occupation (p < 0.0001) and work timing (p < 0.0001). Similar results were seen with SADD scores. Family support (100%) and health (60%) were reported to be the most important motivating factors for quitting alcohol. Discussion: Results showed an urgent need of interventions that are family centered and focus on unskilled, less educated individuals having high work stress. Public health interventions should not only be home based, but should also include worksite awareness initiatives. A national policy is needed to promote alcohol quitting and to bring awareness regarding the consequences of alcohol consumption on individual’s life. PMID:24762342

  19. Nicotine Dependence and Alcohol Problems from Adolescence to Young Adulthood

    PubMed Central

    Dierker, Lisa; Selya, Arielle; Rose, Jennifer; Hedeker, Donald; Mermelstein, Robin

    2016-01-01

    Background Despite the highly replicated relationship between symptoms associated with both alcohol and nicotine, little is known about this association across time and exposure to both drinking and smoking. In the present study, we evaluate if problems associated with alcohol use are related to emerging nicotine dependence symptoms and whether this relationship varies from adolescence to young adulthood, after accounting for both alcohol and nicotine exposure. Methods The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking Patterns Study which measured smoking, nicotine dependence, alcohol use and alcohol related problems over 6 assessment waves spanning 6 years. Analyses were based on repeated assessment of 864 participants reporting some smoking and drinking 30 days prior to individual assessment waves. Mixed-effects regression models were estimated to examine potential time, smoking and/or alcohol varying effects in the association between alcohol problems and nicotine dependence. Findings Inter-individual differences in mean levels of alcohol problems and within subject changes in alcohol problems from adolescence to young adulthood were each significantly associated with nicotine dependence symptoms over and above levels of smoking and drinking behaviour. This association was consistent across both time and increasing levels of smoking and drinking. Conclusions Alcohol related problems are a consistent risk factor for nicotine dependence over and above measures of drinking and smoking and this association can be demonstrated from the earliest experiences with smoking in adolescents, through the establishment of more regular smoking patterns across the transition to young adulthood. These findings add to accumulating evidence suggesting that smoking and drinking may be related through a mechanism that cannot be wholly accounted for by exposure to either substance. PMID:27610424

  20. Alcohol Use Biomarkers Predicting Cognitive Performance: A Secondary Analysis in Veterans With Alcohol Dependence and Posttraumatic Stress Disorder

    PubMed Central

    Kalapatapu, Raj K.; Delucchi, Kevin L.; Lasher, Brooke A.; Vinogradov, Sophia; Batki, Steven L.

    2013-01-01

    Objective We conducted a secondary analysis of baseline data from a recently completed pharmacological pilot clinical trial among 30 veterans with alcohol dependence and posttraumatic stress disorder (PTSD). This trial included baseline measures of alcohol use biomarkers, both indirect (carbohydrate-deficient transferrin, GGT [γ-glutamyltransferase], mean corpuscular volume, AST [aspartate aminotransferase], alanine aminotransferase) and direct (ethyl glucuronide, ethyl sulfate), as well as neurocognitive measures (Trail Making Test parts A and B, Hopkins Verbal Learning Test—Revised, Balloon Analogue Risk Task, Delay Discounting Task). Methods Two regression models were estimated and tested for each neurocognitive measure (dependent measure). The first model included the alcohol use biomarker alone as the predictor. The second model included the alcohol use biomarker along with the following 3 additional predictors: Beck Depression Inventory, Clinician-Administered PTSD Scale, and receiving medications. Results In both models, the indirect biomarkers, such as GGT and AST, significantly predicted performance on the Hopkins Verbal Learning Test—Revised %Retention. GGT alone significantly predicted performance on the Trail Making Test part A. Conclusions Indirect alcohol use biomarkers may have a specific role in identifying those veterans with alcohol dependence and PTSD who have impaired cognitive performance. However, direct alcohol use biomarkers may not share such a role. PMID:24005546

  1. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity

    PubMed Central

    Leclercq, Sophie; Matamoros, Sébastien; Cani, Patrice D.; Neyrinck, Audrey M.; Jamar, François; Stärkel, Peter; Windey, Karen; Tremaroli, Valentina; Bäckhed, Fredrik; Verbeke, Kristin; de Timary, Philippe; Delzenne, Nathalie M.

    2014-01-01

    Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut–brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence. PMID:25288760

  2. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity.

    PubMed

    Leclercq, Sophie; Matamoros, Sébastien; Cani, Patrice D; Neyrinck, Audrey M; Jamar, François; Stärkel, Peter; Windey, Karen; Tremaroli, Valentina; Bäckhed, Fredrik; Verbeke, Kristin; de Timary, Philippe; Delzenne, Nathalie M

    2014-10-21

    Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence. PMID:25288760

  3. NEURAL PLASTICITY, HUMAN GENETICS, AND RISK FOR ALCOHOL DEPENDENCE

    PubMed Central

    Hill, Shirley Y.

    2013-01-01

    Opportunities for advances in the neurobiology of alcohol dependence have been facilitated by the development of sophisticated neurophysiological and neuroimaging techniques that allow us to have a window on developmental changes in brain structure and function. The search for genes that may increase susceptibility to alcohol dependence has been greatly facilitated by the recognition that intermediate phenotypes, sometimes referred to as endophenotypes. may be closer to the genetic variation than is the more complex alcohol dependence phenotype. This chapter will review the evidence that the brain is highly plastic, exhibiting major postnatal changes, especially during adolescence, in neural circuits that appear to influence addiction susceptibility. This chapter will suggest that heritable aspects of brain structure and function that are seen developmentally may be an important endophenotypic characteristic associated with familial risk for developing alcohol dependence. Finally, a review of studies showing associations between brain structural and functional characteristics and specific genes will be offered. PMID:20813240

  4. Translating the Semi-Structured Assessment for Drug Dependence and Alcoholism in the Western Pacific: Rationale, Study Design and Reliability of Alcohol Dependence

    PubMed Central

    Quinn, Amity E.; Rosen, Rochelle K.; McGeary, John E.; Amoa, Francine; Kranzler, Henry R.; Francazio, Sarah; McGarvey, Stephen T.; Swift, Robert M.

    2014-01-01

    Aims: The aims of this study were to develop a bilingual version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) in English and Samoan and determine the reliability of assessments of alcohol dependence in American Samoa. Methods: The study consisted of development and reliability-testing phases. In the development phase, the SSADDA alcohol module was translated and the translation was evaluated through cognitive interviews. In the reliability-testing phase, the bilingual SSADDA was administered to 40 ethnic Samoans, including a sub-sample of 26 individuals who were retested. Results: Cognitive interviews indicated the initial translation was culturally and linguistically appropriate except items pertaining to alcohol tolerance, which were modified to reflect Samoan concepts. SSADDA reliability testing indicated diagnoses of DSM-III-R and DSM-IV alcohol dependence were reliable. Reliability varied by language of administration. Conclusion: The English/Samoan version of the SSADDA is appropriate for the diagnosis of DSM-III-R alcohol dependence, which may be useful in advancing research and public health efforts to address alcohol problems in American Samoa and the Western Pacific. The translation methods may inform researchers translating diagnostic and assessment tools into different languages and cultures. PMID:24936588

  5. DOUBLE-BLIND, RANDOMIZED PLACEBO-CONTROLLED CLINICAL TRIAL OF BENFOTIAMINE FOR SEVERE ALCOHOL DEPENDENCE

    PubMed Central

    Manzardo, Ann M.; He, Jianghua; Poje, Albert; Penick, Elizabeth C.; Campbell, Jan; Butler, Merlin G.

    2013-01-01

    Background Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analogue, benfotiamine (BF), and BF’s effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. Methods A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Results Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, −611±380 Std Dev; PL: N=11, −159±562 Std Dev, p-value=0.02). Conclusions BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism. PMID:23992649

  6. Results of the "In Control: No Alcohol!" Pilot Study

    ERIC Educational Resources Information Center

    Mares, Suzanne H. W.; van der Vorst, Haske; Vermeulen-Smit, Evelien; Lichtwarck-Aschoff, Anna; Verdurmen, Jacqueline E. E.; Engels, Rutger C. M. E.

    2012-01-01

    More than 50% of Dutch 12-year olds already started drinking. Since it is known that delaying the onset of alcohol use results in a lower risk of alcohol-related problems, the recently developed "In control: No alcohol!" prevention program is targeted at elementary school children and their mothers. In this pilot study, the success of program…

  7. Long-term drug treatment of patients with alcohol dependence.

    PubMed

    Crowley, Philip

    2015-04-01

    Drug therapy for alcohol dependence should only be used in conjunction with a comprehensive treatment plan. Naltrexone and acamprosate have well established efficacy and are first-line treatments. Naltrexone is recommended for patients aiming to cut down their alcohol intake who do not have severe liver disease or an ongoing need for opioids. Acamprosate is recommended for those who have achieved and wish to maintain abstinence. Disulfiram is no longer considered first-line treatment due to difficulties with compliance and toxicity. Although baclofen and topiramate have evidence of benefit, they are not registered for alcohol dependence and should only be considered in specialist practice. PMID:26648614

  8. Subgroup-dependent effects of voluntary alcohol intake on behavioral profiles in outbred Wistar rats.

    PubMed

    Momeni, Shima; Roman, Erika

    2014-12-15

    Experimental animal models are critical for understanding the genetic, environmental and neurobiological underpinnings of alcohol use disorders. Limited studies investigate alcohol-induced effects on behavior using free-choice paradigms. The aims of the present experiment were to study voluntary alcohol intake using a modified intermittent access paradigm, investigate the effects of voluntary alcohol intake on behavioral profiles in water- and alcohol-drinking rats, and select extreme low- and high-drinking animals for a more detailed behavioral characterization. Sixty outbred male Wistar rats were randomized into water and alcohol groups. Behavioral profiles in the multivariate concentric square field™ (MCSF) test were assessed prior to and after voluntary alcohol intake. The animals had intermittent access to 20% alcohol and water for three consecutive days per week for seven weeks. The results revealed increased alcohol intake over time. No major alcohol-induced differences on behavior profiles were found when comparing water- and alcohol-drinking animals. The high-drinking animals displayed an alcohol deprivation effect, which was not found in the low-drinking animals. High-drinking rats had lower risk-taking behavior prior to alcohol access and lower anxiety-like behavior after voluntary alcohol intake compared to low-drinking rats. In conclusion, the modified intermittent access paradigm may be useful for pharmacological manipulation of alcohol intake. With regard to behavior, the present findings highlights the importance of studying subgroup-dependent differences and add to the complexity of individual differences in behavioral traits of relevance to the vulnerability for excessive alcohol intake. PMID:25200519

  9. Cognitive impairments in alcohol-dependent subjects.

    PubMed

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-01-01

    Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units. PMID:25076914

  10. Cognitive Impairments in Alcohol-Dependent Subjects

    PubMed Central

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-01-01

    Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units. PMID:25076914

  11. Revictimization of Violence Suffered by Those Diagnosed with Alcohol Dependence in the General Population

    PubMed Central

    Quintana, M. I.; Bressan, R. A.; Mello, M. F.; Andreoli, S. B.

    2015-01-01

    Objective. To verify the association between violence and alcohol dependence syndrome in sample populations. Method. Population-wide survey with multistage probabilistic sample. 3,744 individuals of both genders, aged from 15 to 75 years, were interviewed from the cities of São Paulo and Rio de Janeiro using the Composite International Diagnostic Interview (CIDI 2.1). Results. In both cities, alcohol dependence was associated with the male gender, having suffered violence related to criminality, and having suffered familial violence. In both cities, urban violence, in more than 50% of cases, and familial violence, in more than 90% of cases, preceded alcohol dependence. The reoccurrence of traumatic events occurred in more than half of individuals dependent on alcohol. In São Paulo, having been diagnosed with PTSD is associated with violence revictimization (P = 0.014; Odds = 3.33). Conclusion. Alcohol dependence syndrome is complexly related to urban and familial violence in the general population. Violence frequently precedes alcoholism, but this relationship is dependent on residence and traumatic events. This vicious cycle contributes to perpetuating the high rates of alcoholism and violence in the cities. Politicians ordering the reduction of violence in the large metropolises can, potentially, reduce alcoholism and contribute to the break of this cycle. PMID:26000304

  12. The psychiatric management of patients with alcohol dependence.

    PubMed

    Ritvo, Jonathan I; Park, Charles

    2007-09-01

    Alcohol dependence is a chronic, relapsing biobehavioral disease mediated by various parts of the brain, including reward systems, memory circuits, and the prefrontal cortex. It is characterized by loss of the ability to drink alcohol in moderation and continued drinking despite negative consequences. The alcohol withdrawal syndrome is a common but not universal diagnostic feature of alcohol dependence. Benzodiazepine detoxification of the alcohol withdrawal syndrome prevents the development of withdrawal seizures and delirium tremens, and makes patients more comfortable, which promotes engagement in treatment. Symptom-triggered dosing, based on a withdrawal rating scale such as the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised, is optimal for minimizing the total benzodiazepine dosage. Use of a long-acting benzodiazepine (eg, chlordiazepoxide) is preferred in uncomplicated patients. Thiamine should be administered routinely before the administration of intravenous fluids to prevent the development of Wernicke's encephalopathy and Wernicke-Korsakoff syndrome. In combination with psychosocial treatment, disulfiram, naltrexone, and acamprosate can reduce the frequency of relapse. Naltrexone may be more effective for reduction of loss of control with the first drink and cue-related craving, and acamprosate may be more effective for stabilizing the physiology of post-acute withdrawal. Disulfiram, an aversive deterrent, can be useful if administration can be monitored and tied to meaningful contingencies or when used prophylactically for situations anticipated to carry high risk of relapse. Psychiatric comorbidity, especially depression, is common and is best addressed concurrently, although definitive diagnosis may have to await a period of prolonged sobriety. Prescription of addictive substances, including benzodiazepines beyond the period of acute detoxification, should be avoided, and if necessary should be closely monitored (eg, by frequent

  13. The Brazilian alcohol program; Foundations, results, and perspectives

    SciTech Connect

    Borges, J.M.M. )

    1990-01-01

    The Brazilian alcohol program, Proalcool, is discussed. It was developed as a strategic answer to the high dependence on imported oil and sharp increases in oil prices that adversely affected the Brazilian balance of payments. The program is intended to replace part of the gasoline consumption with ethanol. The availability of resources, including fertile land and unskilled labor, made possible its implementation. As a result of these measures, there were changes in the Brazilian energy matrix. The most important were the substitution between gasoline and fuel alcohol and also between fuel oil and electricity. Other benefits with Proalcool include environmental gains, employment creation, increase in rural area income, and technological improvements in the sugarcane sector. These have allowed an ethanol cost reduction from US$70/bbl at the beginning the program (1976) to US$45/bbl in 1989.

  14. Cladistic association analysis of Y chromosome effects on alcohol dependence and related personality traits

    PubMed Central

    Kittles, Rick A.; Long, Jeffrey C.; Bergen, Andrew W.; Eggert, Monica; Virkkunen, Matti; Linnoila, Markku; Goldman, David

    1999-01-01

    Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism—antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism. PMID:10097188

  15. Which alcohol use disorder criteria contribute to the association of ADH1B with alcohol dependence?

    PubMed

    Hart, Amy B; Lynch, Kevin G; Farrer, Lindsay; Gelernter, Joel; Kranzler, Henry R

    2016-07-01

    Although alcohol dependence (AD) is approximately 50% heritable, little is known about how specific genetic loci affect AD risk. In a genome-wide association study (GWAS), we identified highly significant associations between two population-specific functional variants in the alcohol dehydrogenase 1B gene (ADH1B) and AD in African-Americans (AAs; rs2066702) and European-Americans (EAs; rs1229984). In the current study, we determined which specific diagnostic criteria contributed to the observed associations of ADH1B SNPs with AD. Our analysis included both the DSM-IV and DSM-5 diagnostic systems. We also investigated the relationship of ADH1B variants to the maximum number of drinks consumed in a 24-hour period (MaxDrinks), a presumed intermediate phenotype of AD. We found that, although all criteria made strong individual contributions to the associations, the largest contributions came from those reflecting neuroadaptation: tolerance (rs2066702) and withdrawal (rs1229984). Overall, evidence for association with DSM-5 criteria was slightly stronger than for DSM-IV criteria. For rs2066702, results were similar for DSM-IV and DSM-5 criteria. However, the most significant DSM-5 criterion associated with rs1229984 was alcohol-related social/interpersonal problems. Both ADH1B variants were associated with MaxDrinks, a measure of innate tolerance, and MaxDrinks mediated the associations between ADH1B and alcohol outcomes. We replicated the findings for rs2066702 and tolerance in an independent sample of AAs. Taken together, these results suggest that variation in ADH1B affects the adaptation to heavy drinking, highlighting population-specific differences in genetic risk for AUD. They also suggest that the revisions reflected in DSM-5 AUD may enhance the utility of that diagnosis for gene finding. PMID:25828809

  16. Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.

    PubMed

    Alaux-Cantin, Stéphanie; Buttolo, Romain; Houchi, Hakim; Jeanblanc, Jérôme; Naassila, Mickaël

    2015-09-01

    Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. PMID:25138717

  17. Genetic variability in tryptophan hydroxylase 2 gene in alcohol dependence and alcohol-related psychopathological symptoms.

    PubMed

    Plemenitaš, Anja; Kores Plesničar, Blanka; Kastelic, Matej; Porcelli, Stefano; Serretti, Alessandro; Dolžan, Vita

    2015-09-14

    Heritability plays an important role in the development and expression of alcohol dependence. The present genetic association study explored the role of TPH2 polymorphisms and their haplotypes to investigate its role in alcohol dependence and comorbid psychopathological symptoms. The sample included 101 subjects currently diagnosed as alcohol abusers, 100 abstinent alcohol-dependent subjects and 97 healthy controls. Subjects were genotyped for TPH2 rs4570625, rs1843809, rs7305115, rs4290270. TPH2 genotypes were not associated with alcohol dependence, but GGAA haplotype was less common (p=0.038) and GTAA and GGGT were more common (p=0.011 and p=0.021, respectively), in currently dependent patients compared to controls. Exploratory analysis of genotypes in currently dependent patients showed that rs1843809 was associated with depressive and aggressive traits (p=0.045 and p=0.001, respectively), rs4290270 with depressive and anxiety traits (p=0.040 and p=0.025, respectively) and rs4570625 with aggressive traits (p=0.011). In abstinent subjects rs1843809 genotype was associated with traits of social anxiety (p=0.003). Only association between rs1843809 and the BDHI score (p=0.001) and associations between GTAA haplotype and Zung Anxiety Scale and BDHI score (p=0.001 and p<0.001, respectively), in currently dependent patients remained significant after applying the Bonferroni's correction. Our findings support a potential role of TPH2 in alcohol dependence. TPH2 genetic variability may be also associated with anxiety and aggression traits in alcohol dependent subjects. PMID:26232682

  18. Greater Monoamine Oxidase A Binding in Alcohol Dependence

    PubMed Central

    Matthews, Brittany A.; Kish, Stephen J.; Xu, Xin; Boileau, Isabelle; Rusjan, Pablo M.; Wilson, Alan A.; DiGiacomo, Dan; Houle, Sylvain; Meyer, Jeffrey H.

    2016-01-01

    Background Alcohol dependence (AD) is a multiorgan disease in which excessive oxidative stress and apoptosis are implicated. Monoamine oxidase A (MAO-A) is an important enzyme on the outer mitochondrial membrane that participates in the cellular response to oxidative stress and mitochondrial toxicity. It is unknown whether MAO-A levels are abnormal in AD. We hypothesized that MAO-A VT, an index of MAO-A level, is elevated in the prefrontal cortex (PFC) during AD, because markers of greater oxidative stress and apoptosis are reported in the brain in AD and a microarray analysis reported greater MAO-A messenger RNA in the PFC of rodents exposed to alcohol vapor. Methods Sixteen participants with alcohol dependence and 16 healthy control subjects underwent [11C]-harmine positron emission tomography. All were nonsmoking, medication- and drug-free, and had no other past or present psychiatric or medical illnesses. Results MAO-A VT was significantly greater in the PFC (37%, independent samples t test, t30 = 3.93, p < .001), and all brain regions analyzed (mean 32%, multivariate analysis of variance, F7,24 = 3.67, p = .008). Greater duration of heavy drinking correlated positively with greater MAO-A VT in the PFC (r = .67, p = .005) and all brain regions analyzed (r = .73 to .57, p = .001–.02). Conclusions This finding represents a new pathological marker present in AD that is therapeutically targetable through direct inhibition or by novel treatments toward oxidative/pro-apoptotic processes implicated by MAO-A overexpression. PMID:24269057

  19. Safety and tolerability of gamma-hydroxybutyric acid in the treatment of alcohol-dependent patients.

    PubMed

    Beghè, F; Carpanini, M T

    2000-04-01

    Gamma-hydroxybutyric acid (GHB) has been in clinical use in Italy since 1991 for treatment of alcohol dependence. Results of phase III and phase IV studies have shown that the drug is effective and well tolerated in the treatment of alcohol withdrawal syndrome and in reducing alcohol consumption and alcohol craving. Pharmacosurveillance indicates that abuse of gamma-hydroxybutyric acid is a limited phenomenon in clinical settings when the drug is dispensed under strict medical surveillance and entrusted to a referring familiar member of the patient. PMID:10869863

  20. Dose Specific Effects of Olanzapine in the Treatment of Alcohol Dependence

    PubMed Central

    Littlewood, Rae A.; Claus, Eric D.; Arenella, Pamela; Bogenschutz, Michael; Karoly, Hollis; Feldstein Ewing, Sarah W.; Bryan, Angela D.; Hutchison, Kent E.

    2014-01-01

    Rationale It is well-established that the rewarding effects of alcohol are modulated by the mesolimbic dopaminergic system. Olanzapine, a D2 dopamine antagonist, has been shown to reduce alcohol craving and consumption. Objective To clarify whether olanzapine has clinical utility in the treatment of alcohol dependence, a 12-week, double-blind, randomized clinical trial was conducted. Methods One-hundred twenty-nine treatment-seeking alcohol dependent adults were randomly assigned to 12-weeks of olanzapine (5mg vs. 2.5mg) or placebo. Outcomes examined were average drinks per drinking day (DDD), proportion of drinking days to total days in treatment (PDD), alcohol craving, and impaired control over alcohol use. Mixed models were used to examine medication effects during the course of treatment on specified outcomes. Results All of the analyses indicated a main effect for time, such that there were reductions in alcohol use and craving and an increase in control over alcohol use across treatment conditions. Dose-response analyses indicated that, in comparison to placebo, participants in the 5mg group experienced reduced craving for alcohol and participants in the 2.5mg group decreased in PDD and increased in their control over alcohol use. Better control over alcohol use remained significant 6 months post-treatment for the 2.5mg group. Subjective experiences of the medication suggest that 2.5mg and 5mg were equally well-tolerated. Conclusions Results provide some support for the notion that dosage is an important consideration in relation to effectiveness; however, the cost-benefit balance does not support the clinical utility of olanzapine in treating alcohol dependence. PMID:25304864

  1. Medicaid coverage of medications to treat alcohol and opioid dependence.

    PubMed

    Mark, Tami L; Lubran, Robert; McCance-Katz, Elinore F; Chalk, Mady; Richardson, John

    2015-08-01

    Substance use disorders affect 12% of Medicaid beneficiaries. The prescription drug epidemic and growing need for treatment of alcohol and opioid dependence have refocused states' attention on their provision of substance use disorder treatment services, including medications. This study characterized how Medicaid programs cover these treatment medications. Data were from 2013 Medicaid pharmacy documents, 2011 and 2012 Medicaid state drug utilization records, and a 2013 American Society of Addiction Medicine survey. Results showed that only 13 state Medicaid programs included all medications approved for alcohol and opioid dependence on their preferred drug lists. The most commonly excluded were extended-release naltrexone (19 programs), acamprosate (19 programs), and methadone (20 programs). For combined buprenorphine-naloxone, 48 Medicaid programs required prior authorization, and 11 programs used 1- to 3-year lifetime treatment limits. Given the chronic nature of substance use disorders and the overwhelming evidence supporting ongoing coverage for many of these medications, states may want to reexamine substance use disorder benefits. PMID:25921475

  2. Disrupted Regulation of Social Exclusion in Alcohol-Dependence: An fMRI Study

    PubMed Central

    Maurage, Pierre; Joassin, Frédéric; Philippot, Pierre; Heeren, Alexandre; Vermeulen, Nicolas; Mahau, Pierre; Delperdange, Christel; Corneille, Olivier; Luminet, Olivier; de Timary, Philippe

    2012-01-01

    Alcohol-dependence is associated with cognitive and biological alterations, and also with interpersonal impairments. Although overwhelming in clinical settings and involved in relapse, these social impairments have received little attention from researchers. Particularly, brain alterations related to social exclusion have not been explored in alcohol-dependence. Our primary purpose was to determine the neural correlates of social exclusion feelings in this population. In all, 44 participants (22 abstinent alcohol-dependent patients and 22 paired controls) played a virtual game (‘cyberball') during fMRI recording. They were first included by other players, then excluded, and finally re-included. Brain areas involved in social exclusion were identified and the functional connectivity between these areas was explored using psycho-physiological interactions (PPI). Results showed that while both groups presented dorsal anterior cingulate cortex (dACC) activations during social exclusion, alcohol-dependent participants exhibited increased insula and reduced frontal activations (in ventrolateral prefrontal cortex) as compared with controls. Alcohol-dependence was also associated with persistent dACC and parahippocampal gyrus activations in re-inclusion. PPI analyses showed reduced frontocingulate connectivity during social exclusion in alcohol-dependence. Alcohol-dependence is thus linked with increased activation in areas eliciting social exclusion feelings (dACC–insula), and with impaired ability to inhibit these feelings (indexed by reduced frontal activations). Altered frontal regulation thus appears implied in the interpersonal alterations observed in alcohol-dependence, which seem reinforced by impaired frontocingulate connectivity. This first exploration of the neural correlates of interpersonal problems in alcohol-dependence could initiate the development of a social neuroscience of addictive states. PMID:22510722

  3. Physiopathological and therapeutical correlations in alcohol dependence.

    PubMed

    Szalontay, Andreea Silvana

    2014-01-01

    No doubt, alcoholism represents nowadays the toxicomany with the highest expansion rate among all population groups, being recognized by the specialists from the medical, social, economic and legal field as a true "toxic pandemy". Researchers consider ethanol, this small but highly aggressive molecule, to have supremacy if we were to consider the number of pages dedicated to it worldwide on daily bases, in the medical or any other specialty literature. Nonetheless, the large volume of data regarding ethanol toxicity does not seen to simplify things, on the contrary it points out new information about the its negative effects on human body. Ethanol represents a toxic that is rapidly and completely absorbed in the intestinal tract being distributed to most tissues and organs; ethanol is recognized as an enzymatic inductor of its own metabolization but also of the metabolization of numerous therapeutic agents. PMID:25341287

  4. Greek Alcohol Survey: Results and Analysis.

    ERIC Educational Resources Information Center

    Jensen, Wesley; And Others

    Alcohol use among 458 members of Greek fraternities and sororities at the University of North Dakota was surveyed. The survey instrument, which was an adaptation of a questionnaire developed by Michael A. Looney, was directed to frequency of use, amounts consumed, type of beverage, attitudes, and demographic information. It was found that…

  5. Impact of Exposure to Childhood Maltreatment on Transitions to Alcohol Dependence in Women and Men

    PubMed Central

    Oberleitner, Lindsay M.; Smith, Philip H.; Weinberger, Andrea H; Mazure, Carolyn M.; McKee, Sherry A.

    2016-01-01

    Background Childhood maltreatment decreases age of first use and speeds the transition from first use to dependence (i.e., telescoping) for alcohol use, however, it is currently unknown whether this influence is the same for men and women. Method Analyses were conducted with the National Epidemiologic Survey on Alcohol and Related Conditions (n=34,653). Outcome variables included: age of alcohol initiation and time to onset of DSM-IV alcohol dependence. Predictor variables included: gender and childhood maltreatment. Linear and Poisson regression analyses were conducted. Results Results demonstrated that in regards to age of drinking initiation, individuals who experienced childhood maltreatment initiated 1 year earlier than those without maltreatment, however, there was no interaction of this relationship with gender. Regarding the time to dependence, it was found that women who experienced childhood maltreatment demonstrated telescoping (shorter time between onset and dependence) compared to women without maltreatment and men (both with and without maltreatment). Conclusion Women with a history of childhood maltreatment are particularly vulnerable to an accelerated time from initiation of alcohol use until dependence, a pattern indicative of increased negative alcohol related outcomes. Findings highlight the need for development of gender-specific prevention efforts and behavioral treatments to aid in early intervention of problematic alcohol use in women. PMID:26130105

  6. Cue reactivity and its relation to craving and relapse in alcohol dependence: a combined laboratory and field study.

    PubMed

    Witteman, Jurriaan; Post, Hans; Tarvainen, Mika; de Bruijn, Avalon; Perna, Elizabeth De Sousa Fernandes; Ramaekers, Johannes G; Wiers, Reinout W

    2015-10-01

    The present study investigated the nature of physiological cue reactivity and craving in response to alcohol cues among alcohol-dependent patients (N = 80) who were enrolled in detoxification treatment. Further, the predictive value with regard to future drinking of both the magnitude of the physiological and craving response to alcohol cues while in treatment and the degree of alcohol-cue exposure in patients' natural environment was assessed. Physiological reactivity and craving in response to experimental exposure to alcohol and soft drink advertisements were measured during detoxification treatment using heart rate variability and subjective rating of craving. Following discharge, patients monitored exposure to alcohol advertisements for five consecutive weeks with a diary and were followed up with an assessment of relapse at 5 weeks and 3 months post-discharge. The results indicated that the presence of alcohol cues such as the portrayal of the drug and drinking behaviour induced physiological cue reactivity and craving. Additionally, cue reactivity and craving were positively correlated, and cue reactivity was larger for patients with shorter histories of alcohol dependence. Further, patients reported a substantial daily exposure to alcohol cues. The magnitude of cue reactivity and the craving response to alcohol cues at baseline and degree of exposure to alcohol cues in patients' natural environment did not predict relapse. It is concluded that the presence of alcohol cues such as portrayal of alcoholic beverages and drinking behaviour induces cue reactivity and craving in alcohol dependence through a conditioned appetitive response. PMID:26257163

  7. Relationship Between Emotional Processing, Drinking Severity and Relapse in Adults Treated for Alcohol Dependence in Poland

    PubMed Central

    Kopera, Maciej; Jakubczyk, Andrzej; Suszek, Hubert; Glass, Jennifer M.; Klimkiewicz, Anna; Wnorowska, Anna; Brower, Kirk J.; Wojnar, Marcin

    2015-01-01

    Aims: Growing data reveals deficits in perception, understanding and regulation of emotions in alcohol dependence (AD). The study objective was to explore the relationships between emotional processing, drinking history and relapse in a clinical sample of alcohol-dependent patients. Methods: A group of 80 inpatients entering an alcohol treatment program in Warsaw, Poland was recruited and assessed at baseline and follow-up after 12 months. Baseline information about demographics, psychopathological symptoms, personality and severity of alcohol problems was obtained. The Schutte Self-Report Emotional Intelligence (EI) Test and Toronto Alexithymia Scale (TAS) were utilized for emotional processing assessment. Follow-up information contained data on drinking alcohol during the last month. Results: At baseline assessment, the duration of alcohol drinking was associated with lower ability to utilize emotions. Patients reporting more difficulties with describing feelings drank more during their last episode of heavy drinking, and had a longer duration of intensive alcohol use. A longer duration of the last episode of heavy drinking was associated with more problems identifying and regulating emotions. Poor utilization of emotions and high severity of depressive symptoms contributed to higher rates of drinking at follow-up. Conclusions: These results underline the importance of systematic identification of discrete emotional problems and dynamics related to AD. This knowledge has implications for treatment. Psychotherapeutic interventions to improve emotional skills could be utilized in treatment of alcohol-dependent patients. PMID:25543129

  8. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection

    PubMed Central

    Leggio, L.; Ferrulli, A.; Zambon, A.; Caputo, F.; Kenna, G.A.; Swift, R.M.; Addolorato, G.

    2016-01-01

    Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABAB receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some LFTs (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients. PMID:22244707

  9. Nicotinic receptor modulation to treat alcohol and drug dependence

    PubMed Central

    Rahman, Shafiqur; Engleman, Eric A.; Bell, Richard L.

    2015-01-01

    Alcohol and drug dependence are serious public health problems worldwide. The prevalence of alcohol and drug dependence in the United States and other parts of the world is significant. Given the limitations in the efficacy of current pharmacotherapies to treat these disorders, research in developing alternative pharmacotherapies continues. Preclinical and clinical evidence thus far has indicated that brain nicotinic acetylcholine receptors (nAChRs) are important pharmacological targets for the development of medications to treat alcohol and drug dependence. The nAChRs are a super family of ligand gated ion channels, and are expressed throughout the brain with twelve neuronal nAChR subunits (α2–α10 and β2–β4) identified. Here, we review preclinical and clinical evidence involving a number of nAChR ligands that target different nAChR subtypes in alcohol and nicotine addiction. The important ligands include cytisine, lobeline, mecamylamine, varenicline, sazetidine A and others that target α4β2* nAChR subtypes as small molecule modulators of the brain nicotinic cholinergic system are also discussed. Taken together, both preclinical and clinical data exist that support nAChR–based ligands as promising therapeutic agents for the treatment of alcohol and drug dependence. PMID:25642160

  10. Alcohol-Induced Changes in Opioid Peptide Levels in Adolescent Rats Are Dependent on Housing Conditions

    PubMed Central

    Palm, Sara; Nylander, Ingrid

    2014-01-01

    Background Endogenous opioids are implicated in the mechanism of action of alcohol and alcohol affects opioids in a number of brain areas, although little is known about alcohol's effects on opioids in the adolescent brain. One concern, in particular when studying young animals, is that alcohol intake models often are based on single housing that may result in alcohol effects confounded by the lack of social interactions. The aim of this study was to investigate short- and long-term alcohol effects on opioids and the influence of housing conditions on these effects. Methods In the first part, opioid peptide levels were measured after one 24-hour session of single housing and 2-hour voluntary alcohol intake in adolescent and adult rats. In the second part, a model with a cage divider inserted during 2-hour drinking sessions was tested and the effects on opioids were examined after 6 weeks of adolescent voluntary intake in single-and pair-housed rats, respectively. Results The effects of single housing were age specific and affected Met-enkephalin-Arg6Phe7 (MEAP) in particular. In adolescent rats, it was difficult to distinguish between effects induced by alcohol and single housing, whereas alcohol-specific effects were seen in dynorphin B (DYNB), beta-endorphin (BEND), and MEAP levels in adults. Voluntary drinking affected several brain areas and the majority of alcohol-induced effects were not dependent on housing. However, alcohol effects on DYNB and BEND in the amygdala were dependent on housing. Housing alone affected MEAP in the cingulate cortex. Conclusions Age-specific housing- and alcohol-induced effects on opioids were found. In addition, prolonged voluntary alcohol intake under different housing conditions produced several alcohol-induced effects independent of housing. However, housing-dependent effects were found in areas implicated in stress, emotionality, and alcohol use disorder. Housing condition and age may therefore affect the reasons and

  11. Neural mechanisms of high-risk decisions-to-drink in alcohol-dependent women.

    PubMed

    Arcurio, Lindsay R; Finn, Peter R; James, Thomas W

    2015-03-01

    A hallmark of alcohol dependence (AD) is continually drinking despite the risk of negative consequences. Currently, it is not known if the pattern of disordered activation in AD is more compatible with an over-sensitive reward system, a deficit in control systems or a combination of both to produce the high risk-taking behavior observed in alcohol dependents (ADs). Here, alcohol cues were used in an ecological decisions-to-drink task that involved high- and low-risk scenarios where the chance of serious negative imagined consequences was varied. Non-alcohol cues were included as control stimuli. Functional magnetic resonance imaging (fMRI) was used to measure blood oxygen level-dependent (BOLD) signal change in 15 alcohol-dependent and 16 control women. This design allowed us to address two major questions concerning AD: first, is there a specific pattern of disordered activation that drives the heightened endorsement of high-risk decisions-to-drink in ADs? And, second, is that pattern specific to decisions-to-drink or does it generalize to other appetitive and/or neutral cues? The results showed that, during high-risk decisions-to-drink, alcohol-dependent women activated reward circuits, cognitive control circuits and regions of the default-mode network (DMN), while control women deactivated approach circuits and showed enhanced activation in regions of the DMN. Group differences were found only for decisions-to-drink, suggesting that they are specific to alcohol cues. Simultaneous activation of reward networks, cognitive control networks and the DMN in alcohol-dependent women suggests that over-endorsement of high-risk drinking decisions by alcohol-dependent women may be due to a problem with switching between different neural networks. PMID:24373127

  12. Structural brain differences in alcohol-dependent individuals with and without comorbid substance dependence

    PubMed Central

    Mon, Anderson; Durazzo, Timothy C.; Abe, Christoph; Gazdzinski, Stefan; Pennington, David; Schmidt, Thomas; Meyerhoff, Dieter J.

    2014-01-01

    Background Over 50% of individuals with alcohol use disorders (AUD) also use other substances. Therefore, brain structural abnormalities observed in alcohol dependent individuals may not be entirely related to alcohol consumption. This MRI study assessed differences in brain regional tissue volumes between short-term abstinent alcohol dependent individuals without (ALC) and with current substance use dependence (polysubstance users, PSU). Methods Nineteen, one-month-abstinent PSU and 40 ALC as well as 27 light-drinkers (LD) were studied on a 1.5 Tesla MR system. Whole brain T1-weighted images were segmented automatically into regional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes. MANOVA assessed group differences of intracranial volume-normalized tissue volumes of the frontal, parietal, occipital, and temporal lobes as well as regional subcortical GM volumes. The volumetric measures were correlated with neurocognitive measures to assess their functional relevance. Results Despite similar lifetime drinking and smoking histories, PSU had significantly larger normalized WM volumes than ALC in all lobes. PSU also had larger frontal and parietal WM volumes than LD, but smaller temporal GM volumes as well as smaller lenticular and thalamic nuclei than LD. By contrast, ALC had smaller frontal, parietal, and temporal GM, thalamic GM and cerebellar volumes than LD. ALC also had more sulcal CSF volumes than both PSU and LD. Conclusion One-month-abstinent ALC and PSU exhibited different patterns of gross brain structural abnormalities. The larger lobar WM volumes in PSU in the absence of widespread GM volume loss contrast with widespread GM atrophy in ALC. These structural differences between ALC and PSU may demand different treatment approaches to mitigate specific functionally relevant brain abnormalities. PMID:25263262

  13. Central pontine myelinolysis in a case of alcohol dependence syndrome

    PubMed Central

    Chatterjee, Kaushik; Fernandes, Austin B.; Goyal, Sunil; Shanker, Sunitha

    2015-01-01

    Osmotic Demyelination Syndrome includes Central Pontine Myelinolysis and Extrapontine Myelinolysis. This condition has been described in cases of chronic Alcohol Dependence Syndrome and in rapid correction of hyponatremia. Though we frequently see patients with Alcohol Dependence Syndrome presenting with complicated withdrawal, Central Pontine Myelinolysis remains largely undetected and under-reported in literature. We present here a case of protracted Delirium Tremens where MRI brain revealed Central Pontine Myelinolysis. Subsequently cognitive assessment revealed significant dysfunction and brain SPECT showed hypo-perfusion of the frontal lobes. Osmotic Demyelination Syndrome should be suspected in protracted Delirium Tremens.

  14. Central pontine myelinolysis in a case of alcohol dependence syndrome.

    PubMed

    Chatterjee, Kaushik; Fernandes, Austin B; Goyal, Sunil; Shanker, Sunitha

    2015-01-01

    Osmotic Demyelination Syndrome includes Central Pontine Myelinolysis and Extrapontine Myelinolysis. This condition has been described in cases of chronic Alcohol Dependence Syndrome and in rapid correction of hyponatremia. Though we frequently see patients with Alcohol Dependence Syndrome presenting with complicated withdrawal, Central Pontine Myelinolysis remains largely undetected and under-reported in literature. We present here a case of protracted Delirium Tremens where MRI brain revealed Central Pontine Myelinolysis. Subsequently cognitive assessment revealed significant dysfunction and brain SPECT showed hypo-perfusion of the frontal lobes. Osmotic Demyelination Syndrome should be suspected in protracted Delirium Tremens. PMID:27212829

  15. Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures.

    PubMed

    Kapoor, M; Chou, Y-L; Edenberg, H J; Foroud, T; Martin, N G; Madden, P A F; Wang, J C; Bertelsen, S; Wetherill, L; Brooks, A; Chan, G; Hesselbrock, V; Kuperman, S; Medland, S E; Montgomery, G; Tischfield, J; Whitfield, J B; Bierut, L J; Heath, A C; Bucholz, K K; Goate, A M; Agrawal, A

    2016-01-01

    Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement. PMID:27003187

  16. Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures

    PubMed Central

    Kapoor, M; Chou, Y-L; Edenberg, H J; Foroud, T; Martin, N G; Madden, P A F; Wang, J C; Bertelsen, S; Wetherill, L; Brooks, A; Chan, G; Hesselbrock, V; Kuperman, S; Medland, S E; Montgomery, G; Tischfield, J; Whitfield, J B; Bierut, L J; Heath, A C; Bucholz, K K; Goate, A M; Agrawal, A

    2016-01-01

    Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement. PMID:27003187

  17. µ-Opioid Receptor Gene (OPRM1) Polymorphism A118G: Lack of Association in Finnish Populations with Alcohol Dependence or Alcohol Consumption

    PubMed Central

    Rouvinen-Lagerström, Noora; Lahti, Jari; Alho, Hannu; Kovanen, Leena; Aalto, Mauri; Partonen, Timo; Silander, Kaisa; Sinclair, David; Räikkönen, Katri; Eriksson, Johan G.; Palotie, Aarno; Koskinen, Seppo; Saarikoski, Sirkku T.

    2013-01-01

    Aims: The molecular epidemiological studies on the association of the opioid receptor µ-1 (OPRM1) polymorphism A118G (Asn40Asp, rs1799971) and alcohol use disorders have given conflicting results. The aim of this study was to test the possible association of A118G polymorphism and alcohol use disorders and alcohol consumption in three large cohort-based study samples. Methods: The association between the OPRM1 A118G (Asn40Asp, rs1799971) polymorphism and alcohol use disorders and alcohol consumption was analyzed using three different population-based samples: (a) a Finnish cohort study, Health 2000, with 503 participants having a DSM-IV diagnosis for alcohol dependence and/or alcohol abuse and 506 age- and sex-matched controls; (b) a Finnish cohort study, FINRISK (n = 2360) and (c) the Helsinki Birth Cohort Study (n = 1384). The latter two populations lacked diagnosis-based phenotypes, but included detailed information on alcohol consumption. Results: We found no statistically significant differences in genotypic or allelic distribution between controls and subjects with alcohol dependence or abuse diagnoses. Likewise no significant effects were observed between the A118G genotype and alcohol consumption. Conclusion: These results suggest that A118G (Asn40Asp) polymorphism may not have a major effect on the development of alcohol use disorders at least in the Finnish population. PMID:23729673

  18. Sub-populations of alcohol-dependent patients: differences in psychological functioning between high- and low-frequency alcohol consumers.

    PubMed

    Hiltunen, A J; Koechling, U M; Voltaire-Carlsson, A; Borg, S

    1996-07-01

    The purpose of the present study was to examine the processes underlying relapse to drinking using objective biological validation of self-reported recent alcohol consumption, using the ratio of 5-hydroxytryptophol to 5-hydroxyindol-3-ylacetic acid (5-HTOL/5-HIAA), a new biological marker to detect single episodes of drinking, in a sample of 38 male alcohol-dependent patients (DSM-III-R) who were assessed prospectively in terms of their clinical symptomatology over a 6-month treatment period. Results showed that nearly all patients obtained positive 5-HTOL/5-HIAA samples during the course of treatment. However, upon closer inspection, results revealed a bimodal distribution for alcohol intake with high and low frequency of consumption episodes. Results showed that high frequency consumers obtained higher ratings of clinical symptoms as measured by the Comprehensive Psychopathological Rating Scale (CPRS) and by the St Göran's Semi-structured Interview (SGSI) compared to low frequency alcohol consumers on symptoms of inner tension, lack of initiative, risk of relapse (as rated by therapists and as rated by patients themselves), dysphoria, negative craving for alcohol, and positive craving for alcohol. The present results provided evidence for the existence of two sub-populations of alcoholics, those who have frequent lapses and those who have low frequency of sporadic lapses. Further, these two sub-populations were shown to differ with respect to overall psychological functioning, and craving for alcohol. In conclusion, the present findings have important treatment implications in that reliable identification of patients' consumption patterns using biological markers would allow for the design of individually tailored treatment needs. PMID:8879293

  19. Personality traits and psychiatric comorbidities in alcohol dependence.

    PubMed

    Donadon, M F; Osório, F L

    2016-01-01

    Non-adaptive personality traits may constitute risk factors for development of psychiatric disorders such as depression and anxiety. We aim to evaluate associations and the predictive value of personality traits among alcohol-dependent individuals, with or without psychiatric comorbidities. The convenience sample comprised two groups of males over 18 years of age: one with subjects who had an alcohol dependence diagnosis (AG, n=110), and a control group without abuse and/or alcohol dependence diagnosis (CG, n=110). The groups were assessed by means of the Structured Clinical Interview DSM-IV (SCID-IV). AG participants were recruited among outpatients from the university hospital, whereas CG participants were recruited from a primary healthcare program. Data collection was done individually with self-assessment instruments. Parametric statistics were performed, and a significance level of P=0.05 was adopted. A positive correlation was observed between openness and the length of time that alcohol has been consumed, as were significant and negative correlations between conscientiousness and both the length of time alcohol has been consumed and the number of doses. For alcoholics, extraversion emerged as a protective factor against depression development (P=0.008) and tobacco abuse (P=0.007), whereas openness worked as a protective factor against anxiety (P=0.02). The findings point to specific deficits presented by alcoholics in relation to personality traits with or without psychiatric comorbidities and to the understanding that therapeutic approaches should favor procedures and/or preventive measures that allow more refined awareness about the disorder. PMID:26628399

  20. Personality traits and psychiatric comorbidities in alcohol dependence

    PubMed Central

    Donadon, M.F.; Osório, F.L.

    2015-01-01

    Non-adaptive personality traits may constitute risk factors for development of psychiatric disorders such as depression and anxiety. We aim to evaluate associations and the predictive value of personality traits among alcohol-dependent individuals, with or without psychiatric comorbidities. The convenience sample comprised two groups of males over 18 years of age: one with subjects who had an alcohol dependence diagnosis (AG, n=110), and a control group without abuse and/or alcohol dependence diagnosis (CG, n=110). The groups were assessed by means of the Structured Clinical Interview DSM-IV (SCID-IV). AG participants were recruited among outpatients from the university hospital, whereas CG participants were recruited from a primary healthcare program. Data collection was done individually with self-assessment instruments. Parametric statistics were performed, and a significance level of P=0.05 was adopted. A positive correlation was observed between openness and the length of time that alcohol has been consumed, as were significant and negative correlations between conscientiousness and both the length of time alcohol has been consumed and the number of doses. For alcoholics, extraversion emerged as a protective factor against depression development (P=0.008) and tobacco abuse (P=0.007), whereas openness worked as a protective factor against anxiety (P=0.02). The findings point to specific deficits presented by alcoholics in relation to personality traits with or without psychiatric comorbidities and to the understanding that therapeutic approaches should favor procedures and/or preventive measures that allow more refined awareness about the disorder. PMID:26628399

  1. Pharmacoprophylaxis of alcohol dependence: Review and update Part I: Pharmacology

    PubMed Central

    Grover, Sandeep; Bhateja, Gaurav; Basu, Debasish

    2007-01-01

    Alcohol dependence is a major problem in India. The pharmacological armamentarium for relapse prevention of alcohol has widened with the addition of new drugs. In this article, we review the pharmacology and efficacy of the four most important such drugs: disulfiram, naltrexone, acamprosate and topiramate. The first part of this two-part review series concerns the comparative pharmacology and the second part concerns the efficacy studies. Overall, all four of these drugs have modest but clinically significant usefulness as pharmacoprophylactic agents for relapse prevention or minimization of alcohol dependence. Combinations might be helpful, especially for naltrexone and acamprosate. The issue of supervision and compliance remains important, especially for such drugs as disulfiram and naltrexone. Topiramate is a promising new agent and requires further study. Disulfiram, while very effective in compliant patients, presents challenges in terms of patient selection and side effects. For patients with hepatic impairment, acamprosate is a good choice. PMID:20640061

  2. A descriptive study of alcohol-dependent women attending Alcoholics Anonymous, a regional council on alcoholism and an alcohol treatment unit.

    PubMed

    Smith, L N

    1992-11-01

    A total of 86 women, attending three different agencies, were interviewed on their help-seeking behaviours for problem drinking. Each agency represented a different type of help available in the community. Self-help was represented by Alcoholics Anonymous; the non-statutory sector by a regional council on alcoholism's offices; and the statutory sector by an alcohol treatment unit's out-patient department. Differences between the groups in terms of demography and drinking history are explored in this paper. It was found that the regional council group resembled the female problem drinkers in other alcohol treatment agencies in terms of alcohol dependency, pattern of alcohol consumption and drinking styles, but differed in age and abstinence behaviour. PMID:1292440

  3. The effects of alcoholism pharmacotherapy on immune responses in alcohol-dependent patients.

    PubMed

    Franchi, S; Sacerdote, P; Moretti, S; Gerra, G; Leccese, V; Tallone, M V; Panerai, A E; Somaini, L

    2010-01-01

    Chronic alcohol use has profound modulatory effects on the immune system. Both the innate and the acquired immunity are compromised. The use of pharmacotherapy is increasingly applied to enhance the percentage of success in maintaining alcoholic patients in remission. Disulfiram, naltrexone and gamma hydroxybutiric acid are the drugs used for this purpose in Italian Addiction Services. In this study we analyze the effect of pharmacotherapy of alcohol dependence on immune responses in alcoholics. Six groups were studied. Group A included 10 patients who were still using alcohol. Group B consisted of 10 patients abstinent from alcohol in treatment only with group therapy. Groups C, D and E were composed of 10 patients each, treated for at least 6 months with oral doses of gamma hydroxybutiric acid, naltrexone or disulfiram respectively. Ten age- and sex-matched healthy volunteers who never misused alcohol were included as a control group. Lymphoproliferation and peripheral mononuclear cell production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokines IL-1 and TNF-alpha were evaluated in all the patients and controls. The level of activity of the hypothalamus pituitary adrenal axis was assessed. Both ACTH and cortisol levels in plasma were elevated in alcoholic patients with no treatment. In this group a significant alteration of cytokine production was observed. TNF and IFN-gamma were lower than controls, while the Th2 cytokine IL-4 was increased. These altered levels state for a Th1/Th2 unbalance characterized by decreased Th1 response in the presence of Th2 predominance. In patients undergoing pharmacological treatment, none of the immune parameters were different from those observed in healthy controls, independently of the type of drug administered. These data indicate that pharmacotherapy more than group therapy treatment is able to ameliorate the immune system functioning in alcoholic patients. PMID:20943056

  4. Trauma exposure, posttraumatic stress disorder and risk for alcohol, nicotine, and marijuana dependence in Israel

    PubMed Central

    Walsh, Kate; Elliott, Jennifer C.; Shmulewitz, Dvora; Aharonovich, Efrat; Strous, Rael; Frisch, Amos; Weizman, Abraham; Spivak, Baruch; Grant, Bridget F.; Hasin, Deborah

    2014-01-01

    Background Substance dependence is more common among trauma-exposed individuals; however, most studies suggest that Posttraumatic Stress Disorder (PTSD) accounts for the link between trauma exposure (TE) and substance dependence. Objectives This study examined associations between TE and substance dependence (alcohol, nicotine, and marijuana), and whether PTSD accounted for this association. Method 1,317 Jewish Israeli household residents completed in-person structured interviews assessing TE, PTSD, and substance (alcohol, nicotine, marijuana) dependence between 2007–2009. Regression analyses examined associations among TE, PTSD, and substance dependence. Results In the full sample, mean number of traumatic events was 2.7 (sd=2.2), with 83.7% experiencing at least one event. In the full sample, mean number of PTSD symptoms was 2.5 (sd=3.4), with 13.5% meeting PTSD diagnostic criteria. Prevalence of alcohol dependence was 13.4%; nicotine dependence 52.8%; and marijuana dependence 12.1%. Number of traumatic events was associated with increased odds of alcohol (OR=1.3; 95% CI=1.2–1.4) and nicotine (OR=1.2; 95% CI=1.1–1.3) dependence. Similarly, any traumatic event exposure was associated with increased odds of alcohol (OR= 3.1; 95% CI= 1.6–6.0) and nicotine (OR=1.9; 95% CI=1.2–2.9) dependence. PTSD symptoms were associated with increased odds of alcohol (OR=1.2; 95% CI=1.1–1.3), nicotine (OR=1.1; 95% CI=1.1–1.2), and marijuana (OR=1.1; 95% CI=1.04–1.2) dependence; similarly, a PTSD diagnosis was associated with increased odds of alcohol (OR=3.4; 95% CI=2.1–5.5), nicotine (OR=2.2; 95% CI = 1.4–3.4), and marijuana (OR=2.6; 95% CI=1.2–5.9) dependence. PTSD symptoms accounted for a sizeable proportion of the TE effect on alcohol (46%) and nicotine dependence (31%). Conclusion Individuals with more traumatic events had heightened risk for alcohol and nicotine dependence, and PTSD symptoms partially accounted for this risk. However, marijuana

  5. Encoding-Imagery Specificity in Alcohol State-Dependent Learning

    ERIC Educational Resources Information Center

    Weingartner, Herbert; And Others

    1976-01-01

    A free-recall procedure demonstrated state-dependent learning using alcohol. Information encoded and stored while intoxicated was more effectively retrieved when later tests of recall were performed while intoxicated, as compared to recall accomplished in the sober state. (Editor/RK)

  6. Alcohol abuse or dependence in the military aviator: guidance for the non-flight surgeon.

    PubMed

    Franzos, M Alaric; Franzos, Tracy L; Woolford, Jeffrey S; McDonald, William A

    2012-10-01

    Alcohol is tightly interwoven with the image and culture of aviation. When alcohol is combined with aviation, the result can be fatal to aircrew, passengers, and bystanders. Alcohol has been implicated in 8 to 12% of fatal general aviation accidents. With approximately 10% of the general population estimated to have alcohol abuse or dependence, alcohol issues are similarly common among aviators. Clear and concise guidelines exist to address alcohol disorders in both civilian and military aviation. However, few health care providers outside the aviation community are aware of these guidelines. When an aviator presents with an alcohol disorder, the well-intentioned provider may be reluctant to address the issue because of poor understanding of the occupational implications or a misplaced effort to preserve the aviator's career. However, proper therapy often permits the aviator to continue flying duties without adverse career impact. This review will discuss the implications, guidelines, and prognosis for the alcohol-dependent aviator and provide resources to enable the responsible health care provider to return the pilot to flight status as soon as practicable. Knowledge of these civilian and military guidelines will help close the treatment and communication gaps between aeromedical specialists and other medical professionals. PMID:23113446

  7. The Ratio of 2nd to 4th Digit Length in Korean Alcohol-dependent Patients

    PubMed Central

    Han, Changwoo; Bae, Hwallip; Lee, Yu-Sang; Won, Sung-Doo; Kim, Dai Jin

    2016-01-01

    Objective The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. Methods In this study, we recruited 87 male patients with alcohol dependence from the alcohol center of one psychiatric hospital and 52 healthy male volunteers who were all employees in the same hospital as controls. We captured images of the right and left hands of patients and controls using a scanner and extracted data with a graphics program. We measured the 2D:4D of each hand and compared the alcohol dependence group with the control group. We analyzed these ratios using an independent-samples t-test. Results The mean 2D:4D of patients was 0.934 (right hand) and 0.942 (left hand), while the mean 2D:4D of controls was 0.956 (right hand) and 0.958 (left hand). Values for both hands were significantly lower for patients than controls (p<0.001, right hand; p=0.004, left hand). Conclusion Patients who are alcohol dependent have a significantly lower 2D:4D than controls, similar to the results of previous studies, which suggest that a higher prenatal testosterone level in the gonadal period is related to alcoholism. Furthermore, 2D:4D is a possible predictive marker of alcohol dependence. PMID:27121425

  8. Efficacy of As-Needed Nalmefene in Alcohol-Dependent Patients with at Least a High Drinking Risk Level: Results from a Subgroup Analysis of Two Randomized Controlled 6-Month Studies

    PubMed Central

    van den Brink, Wim; Aubin, Henri-Jean; Bladström, Anna; Torup, Lars; Gual, Antoni; Mann, Karl

    2013-01-01

    Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461). Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study. Results: The pooled population consisted of 667 patients: placebo n = 332; nalmefene n = 335. There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [treatment difference: −3.2 days (95% CI: −4.8; −1.6); P < 0.0001] and total alcohol consumption [treatment difference: −14.3 g/day (−20.8; −7.8); P < 0.0001] at Month 6. Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group. Adverse events and adverse events leading to dropout were more common with nalmefene than placebo. Conclusion: As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and randomization, and the effect in this subgroup was larger than in the total population. PMID:23873853

  9. Children of men with alcohol dependence: Psychopathology, neurodevelopment and family environment

    PubMed Central

    Raman, Vijaya; Prasad, Suveera; Appaya, M. Prakash

    2010-01-01

    Background: Children of people with alcohol dependence (COAs) are at high risk for behavioral and cognitive problems. Aim: Aim of this study was to compare the nature and extent of these problems in children of men with and without alcohol dependence. Materials and Methods: 32 children (17 in study group and 15 controls) were evaluated for psychopathology, neurodevelopment, cognitive functioning and family environment. Tools used were: Socio-demographic data sheet, Malin’s Intelligence Scale for Indian Children (MISIC), Child Behavior Checklist, Trail Making Test, Neurodevelopment Scale and the Family Environment Scale. Results: Children of men with alcohol dependence had higher externalizing than internalizing scores. Children of alcohol-dependent fathers had higher scores on the neurodevelopment scale and lower scores on the performance scale of the MISIC than the children in control group. These children also made more errors on the Trail Making Test. The family environment of COAs was characterized by lack of independence for its members, greater perceived control and lack of adequate cultural and intellectual activities. Conclusion: Our findings suggest that children of men with alcohol dependence have difficulties with frontal lobe functions and neurodevelopmental tasks. There are also difficulties in the family, which are related to alcohol consumption by the father. PMID:21267372

  10. PROOF-OF-CONCEPT HUMAN LABORATORY STUDY FOR PROTRACTED ABSTINENCE IN ALCOHOL DEPENDENCE: EFFECTS OF GABAPENTIN

    PubMed Central

    Mason, Barbara J.; Light, John M.; Williams, Lauren D.; Drobes, David J.

    2009-01-01

    There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence in alcoholics that may precipitate relapse e.g., craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current DSM-IV alcohol dependence and a strength of craving rating 1σ or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1-week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral, and unpleasant visual stimuli followed by alcohol or water cues. We found a significant attenuating effect of gabapentin (vs. placebo) on several measures of subjective craving for alcohol as well as for affectively-evoked craving. Gabapentin was also found to significantly improve several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and, hence, that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue reactivity studies as proof-of-concept screens for potential anti relapse drugs. PMID:18855801

  11. White matter microstructure, alcohol exposure, and familial risk for alcohol dependence

    PubMed Central

    Hill, Shirley Y.; Terwilliger, Robert; McDermott, Michael

    2013-01-01

    Offspring from families with alcohol dependence (AD) have been shown to exhibit brain morphological alterations that appear to be related to their familial/genetic risk for AD. Greater susceptibility for developing AD may be related to structural underpinnings of behavioral traits that predispose to AD. We examined white matter (WM) integrity in 81 individuals with either a high density of AD in their families (N=44) or without a family history for either alcohol or drug dependence (N=37). Magnetic resonance images were acquired on a Siemens 3 T scanner with fractional anistropy (FA) and the apparent diffusion coefficient (ADC), along with radial diffusivity (RD) and longitudinal (axial) diffusivity calculated for major white matter tracts in both hemispheres. Extensive personal histories of alcohol and drug use were available from longitudinal collection of data allowing for reliable estimates of alcohol and drug exposure. We found that the interaction of personal exposure to alcohol and familial risk for AD predicts reduction in WM integrity for the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF) in the left hemisphere and the forceps major tract. Only one tract showed a significant difference for exposure alone, the anterior thalamic radiation. PMID:23473988

  12. Oxidoreductive homeostasis in alcohol-dependent male patients and the risk of alcohol drinking relapse in a 6-month follow-up.

    PubMed

    Budzyński, Jacek; Ziółkowski, Marcin; Kłopocka, Maria; Czarnecki, Damian

    2016-02-01

    Disturbances in the central signaling of reactive oxygen species (ROS) in response to energy intake are recognized as taking part in appetitive and consummative phases of eating disorders. This study aimed to verify the hypothesis that blood oxidoreductive balance can also affect demand for energy substances, such as alcoholic beverages in alcohol-dependent individuals, as well as the severity of their alcohol dependence and risk of drinking relapse. The following values were determined in the blood of 54 alcohol-dependent male patients after alcohol withdrawal, again after 4 weeks and after 6 months: the aldehyde products of lipid peroxidation (malonyl dialdehyde [MDA] and 4-hydroxynonenal [4-HNE]), nitric oxide (NO) metabolites, total antioxidant status (TAS), the blood activities of glutathione peroxidase (GSHpx), superoxide dismutase (SOD), glutathione reductase (GSHred), blood glucose, and lipids. Alcoholics who relapsed during 6 months of observation (n = 31, 57%) compared with patients who maintained alcohol abstinence for 6 months (n = 23, 43%) differed only in relation to initial and final NO metabolite serum concentrations. The risk of alcohol drinking relapse was lower in patients with an above-median initial blood concentration of NO metabolites and TAS. The oxidative stress parameters correlated with alcohol-dependence severity markers. No significant correlations between the studied antioxidant balance parameters and markers of nutritional status, including blood glucose and lipids, were found. Although the results of our study have some limitations and require further investigation, they suggest the role of oxidoreductive balance in the pathomechanisms of alcohol dependence and drinking relapse. In addition, due to a lack of association found between blood oxidative stress parameters and BMI, blood glucose, and lipid concentrations, they show the presence of disturbances in systemic ROS signaling in response to energy availability in alcoholics after

  13. Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity

    PubMed Central

    Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

    2016-01-01

    Background Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Methods Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Results Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. Conclusions These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity. PMID:27575491

  14. Baclofen and severe alcohol dependence: an uncertain harm-benefit balance as of early 2013.

    PubMed

    2013-09-01

    Alcohol dependence is a severe, chronic illness. Even the best-assessed drugs used to maintain abstinence are poorly effective. Some patients remain dependent after several treatment attempts. Baclofen has been tested for its capacity to reduce craving for alcohol. We reviewed the data available as of early 2013, using the standard Prescrire methodology, in order to assess the harm-benefit balance of baclofen in maintaining abstinence or moderation in alcohol-dependent patients. Two double-blind, randomised, placebo-controlled trials conducted by the same team tested baclofen 30 mg/day in 123 alcohol-dependent patients referred to alcohol treatment centres. After 1 or 3 months of followup, more patients remained abstinent in the baclofen group than in the placebo group. In another double-blind, randomised trial, baclofen 30 mg/day was not more effective than placebo in 80 alcohol-dependent patients recruited through advertisements, many of whom were seeking treatment for the first time. Three uncontrolled retrospective series reported the results obtained in 300 alcohol-dependent patients, most of whom were in treatment failure. They were treated with high, escalating doses of baclofen (on average about 150 mg per day, up to 400 mg per day) with the intention of reducing their craving for alcohol. After 3 to 24 months of follow-up, about half of the patients reported moderate or zero alcohol consumption. At moderate doses, baclofen has been used since the 1970s in the treatment of certain forms of muscle spasticity. The main adverse effects reported in this setting were drowsiness (especially early during treatment) and various neuropsychiatric disorders such as dizziness, euphoria, depression, headache, paraesthesias, speech disorders, ataxia and insomnia. The adverse effects of high-dose baclofen are mainly based on monitoring of hundreds of alcohol-dependent patients, 69 reports to French pharmacovigilance centres in 2011, and cases of overdose or accidental

  15. Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence.

    PubMed

    Gomez, Juan L; Cunningham, Christopher L; Finn, Deborah A; Young, Emily A; Helpenstell, Lily K; Schuette, Lindsey M; Fidler, Tara L; Kosten, Therese A; Ryabinin, Andrey E

    2015-10-01

    An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies. PMID:26051399

  16. Preventive Effects of Forced Exercise against Alcohol-induced Physical Dependency and Reduction of Pain Perception Threshold

    PubMed Central

    Motaghinejad, Majid; Ghaleni, Majid Asadi; Motaghinejad, Ozra

    2014-01-01

    Background: Treatment of postabstinence syndrome of alcohol is one of the major strategies of alcoholism treatment. Exercise can be modulated major brain pathways such as a reward system and pain perception centers. The aim of this study was to evaluation the effects of forced exercise in the management of alcohol dependence and pain perception alteration which induced by alcoholism. Methods: 72 adult male rats were divided into 2 major groups: (1) 40 of them was divided into groups of positive control (alcohol dependent) negative control and alcohol dependent groups under treatment by forced exercise, diazepam (0.4 mg/kg) and forced exercise in combination with diazepam and alcohol withdrawal signs, and blood cortisols, were measured in this groups. (2) 32 rats were divided into control, alcohol dependent (without treatment), and alcohol-dependent groups under treatment by forced exercise or indometacin (5 mg/kg) and then pain perception was assessed by using writhing test, tail-flick and hot plate test. Results: Forced exercise, diazepam, and their combinations significantly attenuates withdrawal syndrome to 20 ± 2, 22 ± 1.3 and 16 ± 2 and blood cortisol level to 6.8 ± 1.3,7.9 ± 1.2 and 5.8 ± 1.1, respectively, in comparison with the positive control group (P < 0.05 and P < 0.001). In alcohol dependent animal under treatment by forced exercise, pain response significantly inhibited with 37%, 57% and 38% decreases in writhing test, hot plate, and tail-flick test, respectively, in comparison with alcohol dependent (without treatment) group (P < 0.05). Conclusions: This study suggested that forced exercise can be useful as adjunct therapy in alcoholism patient and also can be effective in modulation of pain threshold reduction that was induced by alcohol dependency. PMID:25400889

  17. Impaired decision-making under risk in individuals with alcohol dependence

    PubMed Central

    Brevers, Damien; Bechara, Antoine; Cleeremans, Axel; Kornreich, Charles; Verbanck, Paul; Noël, Xavier

    2014-01-01

    Background Alcohol dependence is associated with poor decision-making under ambiguity, that is, when decisions are to be made in the absence of known probabilities of reward and loss. However, little is known regarding decisions made by individuals with alcohol dependence in the context of known probabilities (decision under risk). In this study, we investigated the relative contribution of these distinct aspects of decision making to alcohol dependence. Methods Thirty recently detoxified and sober asymptomatic alcohol-dependent individuals, and thirty healthy control participants were tested for decision-making under ambiguity (using the Iowa Gambling Task), and decision-making under-risk (using the Cups Task and Coin Flipping Task). We also tested their capacities for working memory storage (Digit-span Forward), and dual-tasking (Operation-span Task). Results Compared to healthy control participants, alcohol-dependent individuals made disadvantageous decisions on the Iowa Gambling Task, reflecting poor decisions under ambiguity. They also made more risky choices on the Cups and Coin Flipping Tasks reflecting poor decision-making under risk. In addition, alcohol-dependent participants showed some working memory impairments, as measured by the dual tasking, and the degree of this impairment correlated with high-risk decision-making, thus suggesting a relationship between processes sub-serving working memory and risky decisions. Conclusion These results suggest that alcohol dependent individuals are impaired in their ability to decide optimally in multiple facets of uncertainty (i.e., both risk and ambiguity), and that at least some aspects of these deficits are linked to poor working memory processes. PMID:24948198

  18. Subtypes of Alcohol Dependence in a Nationally Representative Sample

    PubMed Central

    Moss, Howard B.; Chen, Chiung M.; Yi, Hsiao-ye

    2007-01-01

    Objective The authors sought to empirically derive Alcohol Dependence (AD) subtypes based on clinical characteristics using data from a nationally representative epidemiological survey. Method A sample of 1,484 respondents to the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) with past-year AD was subjected to latent class analysis in order to identify homogeneous subtypes. Results The best fitting model was a five-cluster solution. The largest cluster (Cluster 1: ~31%) was comprised of young adults, who rarely sought help for drinking, had moderately high levels of periodic heavy drinking, relatively low rates of comorbidity, and the lowest rate of multigenerational AD (~ 22%). In contrast, Clusters 4 and 5 (~21% and 9%, respectively) had substantial rates of multigenerational AD (53% and 77%, respectively), had the most severe AD criteria profile, were associated with both comorbid psychiatric and other drug use disorders, lower levels of psychosocial functioning, and had engaged in significant help-seeking. Clusters 2 and 3 (~19% each) had the latest onset, the lowest rates of periodic heavy drinking, medium/low levels of comorbidity, moderate levels of help-seeking, and higher psychosocial functioning. Conclusion Five distinct subtypes of AD were derived, distinguishable on the basis of family history, age of AD onset, endorsement of DSM-IV AUD criteria, and the presence of comorbid psychiatric and substance use disorders. These clinically relevant subtypes, derived from the general population, may enhance our understanding of the etiology, treatment, natural history, and prevention of AD and inform the DSM-V research agenda. PMID:17597309

  19. Alcohol and drug misuse, abuse, and dependence in women veterans.

    PubMed

    Hoggatt, Katherine J; Jamison, Andrea L; Lehavot, Keren; Cucciare, Michael A; Timko, Christine; Simpson, Tracy L

    2015-01-01

    We conducted a systematic literature review on substance misuse, abuse, and dependence in women veterans, including National Guard/reserve members. We identified 837 articles published between 1980 and 2013. Of 56 included studies, 32 reported rates of alcohol misuse, binge drinking, or other unhealthy alcohol use not meeting diagnostic criteria for abuse or dependence, and 33 reported rates of drug misuse or diagnosed alcohol or drug use disorders. Rates ranged from 4% to 37% for alcohol misuse and from 7% to 25% for binge drinking; among Veterans Health Administration (VA) health-care system outpatients, rates ranged from 3% to 16% for substance use disorder. Studies comparing women veterans and civilians reported no clear differences in binge or heavy drinking. Substance misuse rates were generally lower among women veterans than men veterans. Substance misuse was associated with higher rates of trauma, psychiatric and medical conditions, and increased mortality and suicide rates. Most studies included only VA patients, and many used only VA medical record data; therefore, the reported substance misuse rates likely do not reflect true prevalence. Rates also varied by assessment method, source of data, and the subgroups studied. Further efforts to develop epidemiologically valid prevalence estimates are needed to capture the true health burden of substance misuse in women veterans, particularly those not using VA care. PMID:25608962

  20. General and Religious Coping Predict Drinking Outcomes for Alcohol Dependent Adults in Treatment

    PubMed Central

    Martin, Rosemarie A.; Ellingsen, Victor J.; Tzilos, Golfo K.; Rohsenow, Damaris J.

    2015-01-01

    Background Religiosity is associated with improved treatment outcomes among adults with alcohol dependence; however, it is unknown whether religious coping predicts drinking outcomes above and beyond the effects of coping in general, and whether gender differences exist. Methods We assessed 116 alcohol-dependent adults (53% women; mean age = 37, SD = 8.6) for use of religious coping, general coping and alcohol use within two weeks of entering outpatient treatment, and again 6 months after treatment. Results Religious coping at 6 months predicted fewer heavy alcohol use days and fewer drinks per day. This relationship was no longer significant after controlling for general coping at 6 months. Conclusion The relationship between the use of religious coping strategies and drinking outcomes is not independent of general coping. Coping skills training that includes religious coping skills, as one of several coping methods, may be useful for a subset of adults early in recovery. PMID:25662479

  1. ADH and ALDH polymorphisms and alcohol dependence in Mexican and Native Americans

    PubMed Central

    Ehlers, Cindy L.; Liang, Tiebing; Gizer, Ian R.

    2012-01-01

    Background Ethanol is primarily metabolized in the liver by 2 rate-limiting reactions: conversion of ethanol to acetaldehyde by alcohol dehydrogenase (ADH) and subsequent conversion of acetaldehyde to acetate by aldehyde dehydrogenase (ALDH). ADH and ALDH exist in multiple isozymes that differ in their kinetic properties. Notably, polymorphisms within the genes that encode for these isozymes vary in their allele frequencies between ethnic groups, and thus, they have been considered as candidate genes that may differentially influence risk for the development of alcohol dependence across ethnic groups. Objectives and Methods Associations between alcohol dependence and polymorphisms in ADH1B, ADH1C, and ALDH2, were compared in a community sample of Native Americans living on reservations (n=791) and Mexican Americans (n=391) living within the same county. Results Two Mexican Americans and no Native Americans possessed one ALDH2*2 allele. Presence of at least one ADH1B*2 allele was found in 7% of the Native Americans and 13% of the Mexican Americans, but was only associated with protection against alcohol dependence in the Mexican Americans. Presence of at least one ADH1B*3 allele was found in 4% if the Native Americans and 2% of the Mexican Americans, but was associated with protection against alcohol dependence only in the Native Americans. No associations between alcohol dependence and polymorphisms in ADH1C were found. Conclusions and Scientific Significance Polymorphisms in ADH1B are protective against alcoholism in these two populations; however, these findings do not explain the high prevalence of alcoholism in these populations. PMID:22931071

  2. Social Support and Treatment Outcome in Alcohol Dependence Syndrome in Armed Forces

    PubMed Central

    Chauhan, Vinay Singh; Azad, Sudip

    2015-01-01

    Introduction Social factors play vital role in unfolding of alcohol use disorders in any given population. Several factors beyond the confines of treatment settings influence treatment outcome in alcohol dependence syndrome. Social support has positive effect in treatment outcome of alcohol dependence syndrome. This has not been much studied in India in past. Therefore we decided to study the perception of social support in cases of alcohol dependence syndrome admitted in a busy hospital in armed forces. Aim The aim was to study the perception of social support across relapsed and abstinent group and see if it reached any statistical proportion and also to see if any socio-demographic variables also affected perception of social support. Materials and Methods Fifty five consecutive male patients of alcohol dependent syndrome without a co-morbid neurological/psychiatric diagnosis were assessed for their perception of social support after taking informed consent. They were explained the procedure and their alcoholic milestones were recorded in specially designed pro-forma. Subjects were then divided in abstinent and relapsed group. Subsequently they were assessed for their perception of social support by administering Social provision scale and Social support questionnaire. Statistical Analysis Data were tabulated and statistically analysed by using chi square test, Mann Whitney U-Test and Rank ANOVA test where applicable p-value <.05 was taken as significant. Results Results indicated that perception of social support across abstinent (n=18) and relapsed (n= 37) group reached significant statistical proportion as measured by social provision scale and social support questionnaire. Duration of use, dependence and family history of alcoholism did not influence perception of social support across patient population. There was inverse relationship between patients with alcohol related problem and their perception of social support. Professional and qualified soldiers

  3. Criminal Justice and Alcohol Treatment: Results from a National Sample

    PubMed Central

    Booth, Brenda M.; Curran, Geoffrey M.; Han, Xiaotong; Edlund, Mark J.

    2012-01-01

    This study investigates the associations of recent criminal justice involvement with perceived need for alcohol treatment and alcohol treatment utilization, adjusting for demographic and clinical characteristics. We examined a national sample of adults with alcohol use disorders (AUD, N=4,390) from the 2006 National Survey on Drug Use and Health (NSDUH). Almost 15% reported criminal justice involvement in the past year. Generalized logit models regressed perceived need for alcohol or drug treatment and past year treatment utilization (versus neither) on past year legal involvement, demographic, and clinical information. In general, results found stronger associations between frequency of criminal justice involvement for treatment utilization compared to perceived need for treatment alone. Treatment utilization was also associated with being on probation, arrests for drug possession/sale and DUI but perceived need was not. Study results suggest opportunities for interventions to increase treatment rates or treatment need, a major correlate of treatment utilization. PMID:22954511

  4. [Geographic Altitude of Residence and Alcohol Dependence in a Peruvian Population].

    PubMed

    Quiñones-Laveriano, Dante Manuel; Espinoza-Chiong, César; Scarsi-Mejia, Ottavia; Rojas-Camayo, José; Mejia, Christian Richard

    2016-01-01

    The aim of this study was to determine the association between alcohol dependence and altitude of residence in 11 villages in two high altitude areas of Peru. An analytical cross-sectional study was performed using a survey conducted by physicians in primary health care in 11 villages until 2013, that were divided into low altitude (≤2500m asl (above sea level)), and high altitude (>2500m asl) areas. The CAGE test for alcoholism (cut point, ≥2) was applied to those who responded positively when asked if they consumed alcohol. Statistical associations were obtained with generalised linear models Of the 737 participants, 51% were women and the median age was 36 years [interquartile range, 25-50], 334 (45%) lived at low altitude, and 113 (15%) had alcohol dependence. The highest frequency of alcoholism was positively associated with being a village considered extremely poor (Likelihood Ratio (LP)=2.42; 95%CI, 1.40-4.19), while being female (LP=0.44; 95%CI, 0.23-0.89) and residing at high altitude (LP=0.15; 95%CI, 0.07-0.31) were negatively associated. These were adjusted for nine socio-occupational and pathological variables. According to these data, there is a higher frequency of alcohol dependence in being, male, extremely poor, and residing at low altitude. These results should be taken into account by professionals who work in primary care and those involved in mental health care, because of their implications in society. PMID:27569012

  5. Divergent regulation of distinct glucocorticoid systems in alcohol dependence.

    PubMed

    Edwards, Scott; Little, Hilary J; Richardson, Heather N; Vendruscolo, Leandro F

    2015-12-01

    Chronic alcohol consumption disrupts glucocorticoid signaling at multiple physiological levels to interact with several disease-related processes associated with neuroendocrine and psychiatric disorders. Excessive alcohol use produces stress-related neuroadaptations at the level of the hypothalamic-pituitary-adrenal (HPA) axis as well as within central (extra-hypothalamic) neural circuitry, including the central amygdala (CeA) and prefrontal cortex (PFC). Altered glucocorticoid receptor (GR) signaling in these areas following excessive alcohol exposure is postulated to mediate the transition from recreational drinking to dependence, as well as the manifestation of a host of cognitive and neurological deficits. Specifically, a bidirectional regulation of stress systems by glucocorticoids leads to the development of an HPA axis tolerance and a concomitant sensitization of cortical and subcortical circuitries. A greater understanding of how hypothalamic and extra-hypothalamic glucocorticoid systems interact to mediate excessive drinking and related pathologies will lead to more effective therapeutic strategies for alcohol use disorder (AUD) and closely related comorbidities. PMID:26003866

  6. Using the SF-6D to measure the impact of alcohol dependence on health-related quality of life.

    PubMed

    Nogueira, Jacinto Mosquera; Rodríguez-Míguez, Eva

    2015-05-01

    Alcohol dependence not only reduces life expectancy, but also causes considerable loss of quality of life of the dependents of and persons around those with alcohol dependence. This article presents new evidence on the impact of alcohol dependence on health-related quality of life in Spain. Three samples were recruited: 150 alcoholics and 64 family members of alcoholics, with both samples taken from an alcoholism treatment unit, and 600 persons from the general population. We used the short form 6D, a preference-based generic instrument, applying the utility scores estimated for Spain. It was found that the annual mean loss of quality-adjusted life years associated with alcohol dependence was 0.144 and 0.083 for the alcoholics and their close family members, respectively. This impact becomes more notable after controlling for socio economic variables and was higher than that estimated in similar studies. Possible explanations for these differences are discussed. The results from this work can be applied to economic evaluation studies measuring benefits from policies targeted at reducing the prevalence of alcohol dependence. PMID:25193526

  7. Alcohol Use and Transactional Sex among Women in South Africa: Results from a Nationally Representative Survey

    PubMed Central

    Magni, Sarah; Christofides, Nicola; Johnson, Saul; Weiner, Renay

    2015-01-01

    Background Transactional sex is a risk factor for HIV infection. Alcohol use may increase the risk of transactional sex. No nationally-representative studies have examined the relationship between multiple dimensions of alcohol use and transactional sex in women in South Africa. The aim of the study was to examine the relationship between alcohol dependence, binge drinking and frequency of drinking in the past month and transactional sex in adult women in South Africa. Methods A cross-sectional study using multi-stage, cluster sampling collected data from a nationally representative sample of 5,969 women aged 16–55 years in 2012. The analysis conducted for this paper was restricted to women reporting sexual activity in the past 12 months (n = 3,594). Transactional sex was defined as having received money/gifts in exchange for sex with any sex partner in the past year. Alcohol use measures included: alcohol dependence (≥2 positive responses to the CAGE questionnaire); binge drinking (≥4 drinks for women on one occasion); and drinking frequency in the previous month. Logistic regression models were built to test the hypotheses that each dimension of alcohol use was associated with transactional sex. Results About 6.3% (n = 225) of sexually active women reported transactional sex. Almost a third (30.6%) of sexually active women had ever drunk alcohol, and 19.2% were current (past month) drinkers. Among lifetime drinkers, 28.0% were alcohol dependent and 56.6% were binge drinkers. Alcohol dependent women were twice as likely to report transactional sex (AOR 2.0, 95% CI 1.1–4.3, p<0.05) than those not alcohol dependent. Binge drinkers were 3.1 times more likely to have had transactional sex (95% CI 1.5–6.6, p<0.01) than non-binge drinkers. There was no significant relationship between frequency of drinking in the past month and transactional sex. Conclusion Alcohol dependency and binge drinking are significantly associated with transactional sex in South

  8. Markers of apoptosis induction and proliferation in the orbitofrontal cortex in alcohol dependence

    PubMed Central

    Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Owusu-Duku, Beverly; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A.; Miguel-Hidalgo, Jose J.

    2014-01-01

    Background Alcohol-dependent (ALC) subjects exhibit glial and neuronal pathology in the prefrontal cortex (PFC). However, in many patients, neurophysiological disturbances are not associated with catastrophic cell depletion despite prolonged alcohol abuse. It is still unclear how some relevant markers of a cell’s propensity to degenerate or proliferate are changed in the PFC of ALC subjects without major neurological disorders. Methods Levels of pro-apoptotic caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 non-psychiatric comparison subjects. Results ALC subjects had significantly higher levels of the 14kDa C8 fragment (C8-14), an indicator of C8 activation. However, there was no change in the levels of DIABLO, XIAP or in the DIABLO/XIAP ratio. PCNA protein level and density of Ki-67-IR cells were not significantly changed in alcoholics, although PCNA levels were increased in older ALC subjects as compared to controls. Conclusions Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in XIAP level, DIABLO/XIAP ratio, or Ki-67 labeling. These results would help to explain the absence of catastrophic cell loss in the PFC of many alcohol dependent subjects, while still being consistent with an alcoholism-related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics. PMID:25421516

  9. Commitment Strength, Alcohol Dependence and HealthCall Participation: Effects on Drinking Reduction in HIV Patients

    PubMed Central

    Aharonovich, Efrat; Stohl, Malka; Ellis, James; Amrhein, Paul; Hasin, Deborah

    2014-01-01

    BACKGROUND The role of three factors in drinking outcome after brief intervention among heavily drinking HIV patients were investigated: strength of commitment to change drinking, alcohol dependence, and treatment type: brief Motivational Interview (MI) only, or MI plus HealthCall, a technological extension of brief intervention. METHODS HIV primary care patients (N=139) who drank ≥4 drinks at least once in the 30 days before study entry participated in MI-only or MI+HealthCall in a randomized trial to reduce drinking. Patients were 95.0% minority; 23.0% female; 46.8% alcohol dependent; mean age 46.3. Outcome at end of treatment (60 days) was drinks per drinking day (Timeline Follow-Back). Commitment strength (CS) was rated from MI session recordings. RESULTS Overall, stronger CS predicted end-of-treatment drinking (p<.001). After finding an interaction of treatment, CS and alcohol dependence (p=.01), we examined treatment × CS interactions in alcohol dependent and non-dependent patients. In alcohol dependent patients, the treatment × commitment strength interaction was significant (p=.006); patients with low commitment strength had better outcomes in MI+HealthCall than in MI-only (lower mean drinks per drinking day; 3.5 and 4.6 drinks, respectively). In non-dependent patients, neither treatment nor CS predicted outcome. CONCLUSIONS Among alcohol dependent HIV patients, HealthCall was most beneficial in drinking reduction when MI ended with low commitment strength. HealthCall may not merely extend MI effects, but add effects of its own that compensate for low commitment strength. Thus, HealthCall may also be effective when paired with briefer interventions requiring less skill, training and supervision than MI. Replication is warranted. PMID:24332577

  10. Positive Selection on Loci Associated with Drug and Alcohol Dependence

    PubMed Central

    Sadler, Brooke; Haller, Gabe; Edenberg, Howard; Tischfield, Jay; Brooks, Andy; Kramer, John; Schuckit, Marc; Nurnberger, John; Goate, Alison

    2015-01-01

    Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima’s D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies. PMID:26270548

  11. Positive Selection on Loci Associated with Drug and Alcohol Dependence.

    PubMed

    Sadler, Brooke; Haller, Gabe; Edenberg, Howard; Tischfield, Jay; Brooks, Andy; Kramer, John; Schuckit, Marc; Nurnberger, John; Goate, Alison

    2015-01-01

    Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies. PMID:26270548

  12. Serotonin 1B Receptor Imaging in Alcohol Dependence

    PubMed Central

    Hu, Jian; Henry, Shannan; Gallezot, Jean-Dominique; Ropchan, Jim; Neumaier, John F.; Potenza, Marc N.; Sinha, Rajita; Krystal, John H.; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E.; Neumeister, Alexander

    2010-01-01

    Background Although animal models suggest that alcohol dependence (AD) is associated with elevations in the number of serotonin-1B receptors (5HT1BR), 5HT1BR levels have not been investigated in people with AD. The selective 5HT1BR antagonist radioligand, [11C]P943, permits in vivo assessment of central 5HT1BR binding potential (BPND) using positron emission tomography (PET). Because of its central role in AD, we were particularly interested in ventral striatal 5HT1BR BPND values. Methods Twelve medication-free, recently abstinent (at least 4 weeks) patients with AD (mean age 35.2±10.1 years, 5 women) and 12 healthy control subjects (HC) (mean age 30.6±9.2 years, 5 women) completed [11C]P943 PET on a high resolution research tomograph (HRRT). Individual MRI scans were collected to exclude individuals with anatomical abnormalities and for co-registration. Imaging data were analyzed using a multilinear reference tissue model. Results Ventral striatal 5-HT1BR BPND values (2.01±0.57 and 1.55±0.09, 29% between-group difference, p=.006) were increased in AD compared to HC subjects. No influence of demographic or clinical variables or amount of injected radiotracer was observed. Conclusions This study provides the first evidence that AD in humans, like in rodent models, is associated with increased levels of ventral striatal 5HT1BRs. PMID:20172504

  13. Development of Screening Questionnaire for Detection of Alcohol Dependence

    PubMed Central

    Bhalla, Ashish; Giri, Om Prakash; Sarkar, Siddharth

    2015-01-01

    Introduction Alcohol dependence (AD) is a major reason for morbidity and visits to emergency medical settings. However, the detection of AD is often difficult or overlooked. This study aimed to develop a brief screening questionnaire in Hindi language for detection of AD in an emergency medical setting. Materials and Methods The authors in consultation devised a set of questions related to AD in the Hindi language requiring binary yes/no type of response. These questions were guided by clinical experience, nosological criteria and previously published screening questionnaires. After initial piloting, these questions were administered by the treating doctors to 100 consenting adult patients presenting with possible AD in the emergency medical services of a tertiary care hospital in North India. A diagnosis of AD was arrived at by administering Mini-International Neuropsychiatric Interview separately. Identification of the most discriminant combinations of items for the detection of AD were based on the chi-square test and binary logistic regression analyses. The final version of the questionnaire was then externally validated on another cohort of patients. Results Based on the analyses, we retained 5 items in the final version of the questionnaire. Sensitivity and specificity values for cut-off scores were calculated. Subsequent external validation revealed satisfactory psychometric properties of the questionnaire. Conclusion The questionnaire represents a simple and brief clinician-administered instrument for screening of AD in an emergency medical setting. PMID:26500989

  14. Alcohol Dependence and Domestic Violence as Sequelae of Abuse and Conduct Disorder in Childhood.

    ERIC Educational Resources Information Center

    Kunitz, Stephen J.; Levy, Jerrold E.; McCloskey, Joanne; Gabriel, K. Ruben

    1998-01-01

    This study compared 204 Navajo men and women for alcohol dependence and domestic violence as sequelae of abuse and conduct disorders in childhood. Both physical and sexual abuse were risk factors for conduct disorder. Physical abuse and conduct disorder were risk factors for alcohol dependence. Alcohol dependence and physical abuse were…

  15. Genome-wide association study of comorbid depressive syndrome and alcohol dependence

    PubMed Central

    Edwards, Alexis C.; Aliev, Fazil; Bierut, Laura J.; Bucholz, Kathleen K.; Edenberg, Howard; Hesselbrock, Victor; Kramer, John; Kuperman, Samuel; Nurnberger, John I.; Schuckit, Marc A.; Porjesz, Bernice; Dick, Danielle M.

    2011-01-01

    Objective Depression and alcohol dependence are common psychiatric disorders that often co-occur. Both disorders are genetically influenced, with heritability estimates in the range of 35–60%. In addition, evidence from twin studies suggests that alcohol dependence and depression are genetically correlated. Here we report results from a genome-wide association study (GWAS) of a comorbid phenotype in which cases meet the DSM-IV symptom threshold for major depressive symptomatology and DSM-IV criteria for alcohol dependence. Methods Samples (N=467 cases and N=407 controls) were of European-American descent, and were genotyped using the Illumina Human 1M BeadChip array. Results Although no SNP meets genome-wide significance criteria, we identify ten markers with p-values < 1 × 10−5, seven of which are located in known genes, which have not been previously implicated in either disorder. Genes harboring SNPs yielding p<1 × 10−3 are functionally enriched for a number of gene ontology categories, notably several related to glutamatergic function. Investigation of expression localization using online resources suggests that these genes are expressed across a variety of tissues, including behaviorally relevant brain regions. Genes that have been previously associated with depression, alcohol dependence, or other addiction-related phenotypes – such as CDH13, CSMD2, GRID1, and HTR1B – were implicated by nominally significant SNPs. Finally, the degree of overlap of significant SNPs between a comorbid phenotype and an alcohol dependence-only phenotype is modest. Conclusions These results underscore the complex genomic influences on psychiatric phenotypes, and suggest that a comorbid phenotype is partially influenced by genetic variants that do not affect alcohol dependence alone. PMID:22064162

  16. Acamprosate in the treatment of alcohol dependence: clinical and economic considerations.

    PubMed

    Mason, Barbara J; Crean, Rebecca

    2007-11-01

    Acamprosate has been commercially available in the USA since 2004 to treat alcohol dependence. Its safety and efficacy have been demonstrated in a number of clinical trials worldwide, which overall have shown significant improvements in abstinence compared with placebo. As with all alcoholism pharmacotherapies, acamprosate is used in conjunction with psychosocial interventions. One frequently described mechanism stipulates that acamprosate supports abstinence by normalizing the often protracted dysregulation of NMDA-mediated glutamatergic neurotransmission that follows chronic heavy alcohol use and withdrawal. This article reviews the clinical safety and efficacy of acamprosate, as well as results from recent pharmacoeconomic and human laboratory studies. These data elucidate the economic benefits of acamprosate, as well as its effects on cognition and alcohol-related sleep disturbances. PMID:17997696

  17. Baclofen for the Treatment of Alcohol Dependence and Possible Role of Comorbid Anxiety

    PubMed Central

    Morley, K.C.; Baillie, A.; Leung, S.; Addolorato, G.; Leggio, L.; Haber, P.S.

    2014-01-01

    Aim: To conduct a double-blind, placebo-controlled randomized clinical trial of baclofen in the treatment of alcohol dependence. Methods: Out of 69 participants consecutively screened, 42 alcohol-dependent patients were randomized to receive placebo, baclofen 30 mg/day or baclofen 60 mg/day for 12 weeks. All subjects were offered BRENDA, a structured psychosocial therapy for alcohol dependence that seeks to improve motivation for change, enhance strategies to prevent relapse and encourage compliance with treatment. Results: Intention-to-treat analyses revealed that alcohol consumption (heavy drinking days, drinks per drinking day) significantly reduced across all three groups during the treatment period. There were no statistically significant advantages to treatment on time to first heavy drinking day (relapse) (P = 0.08), nor time to first drink (lapse) (P = 0.18). A post hoc analysis stratifying according to whether there had been a comorbid anxiety disorder, revealed a beneficial effect of baclofen 30 mg/day versus placebo on time to lapse and relapse (P < 0.05). There was also a beneficial effect for baclofen 60 mg/day relative to placebo on time to relapse in this comorbid group (P < 0.05). Both doses of baclofen were well tolerated. There were no serious adverse events. Conclusions: In spite of the small sample for a 3-arm clinical trial, this study suggests a specific role of baclofen in alcohol-dependent individuals with comorbid anxiety. Replication in larger, fully-powered studies is required. PMID:25246489

  18. Impulsive and non-impulsive suicide attempts in patients treated for alcohol dependence

    PubMed Central

    Wojnar, Marcin; Ilgen, Mark A.; Czyz, Ewa; Strobbe, Stephen; Klimkiewicz, Anna; Jakubczyk, Andrzej; Glass, Jennifer; Brower, Kirk J.

    2009-01-01

    Background Suicidal behavior has been recognized as an increasing problem among alcohol-dependent subjects. The aim of the study was to identify correlates of impulsive and non-impulsive suicide attempts among a treated population of alcohol-dependent patients. Methods A total of 154 patients with alcohol dependence consecutively admitted for addiction treatment participated in the study. Suicidal behavior was assessed together with severity of alcohol dependence, childhood abuse, impulsivity, and family history. A stop-signal procedure was used as a behavioral measure of impulsivity. Results and conclusions Lifetime suicide attempts were reported by 43% of patients in alcohol treatment; of which 62% were impulsive. Compared to patients without a suicide attempt, those with a non-impulsive attempt were more likely to have a history of sexual abuse (OR = 7.17), a family history of suicide (OR = 4.09), and higher scores on a personality measure of impulsiveness (OR = 2.27). The only significant factor that distinguished patients with impulsive suicide attempts from patients without a suicide attempt and from patients with a non-impulsive suicide attempt was a higher level of behavioral impulsivity (OR = 1.84 – 2.42). Limitations Retrospective self-report of suicide attempts and family history. Lack of diagnostic measure. PMID:18835498

  19. Nondaily drinkers score higher on the Alcohol Dependence Scale than daily drinkers.

    PubMed

    Wood, Linda D; Sobell, Linda C; Sobell, Mark B; Dornheim, Liane; Agrawal, Sangeeta

    2003-03-01

    To evaluate the relationship between drinking pattern and alcohol dependence severity, 209 individuals voluntarily seeking treatment for alcohol problems were administered the Alcohol Dependence Scale (ADS), the Short Alcohol Dependence Data (SADD) questionnaire, and a 12-month Timeline Follow-Back (TLFB) drinking assessment as part of their pretreatment assessment. Based on their TLFB data, participants were divided into two groups: daily (DD, n=84) and nondaily (NDD, n=125) drinkers. The two groups were compared on several demographic and drinking variables. It was hypothesized that DD would have higher scores on measures of alcohol dependence than NDD. However, the reverse pattern was found. The NDD had significantly higher ADS scores than the DD. An analysis of ADS subscale scores indicated that the primary difference between the two groups was in the domain of loss of behavior control. It is suggested that NDD may perceive intoxication as more impairing, perhaps because they have acquired less tolerance than DD. These results suggest that treatment focused on restoring a sense of behavior control would be beneficial for NDD. PMID:12573684

  20. The Cannabinoid Receptor 2 Protects Against Alcoholic Liver Disease Via a Macrophage Autophagy-Dependent Pathway.

    PubMed

    Denaës, Timothé; Lodder, Jasper; Chobert, Marie-Noële; Ruiz, Isaac; Pawlotsky, Jean-Michel; Lotersztajn, Sophie; Teixeira-Clerc, Fatima

    2016-01-01

    Kupffer cells, the resident macrophages of the liver, play a major role in the pathogenesis of alcoholic liver disease. We have previously demonstrated that CB2 receptor protects against alcoholic liver disease by inhibiting alcohol-induced inflammation and steatosis via the regulation of Kupffer cell activation. Here, we explored the mechanism underlying these effects and hypothesized that the anti-inflammatory properties of CB2 receptor in Kupffer cells rely on activation of autophagy. For this purpose, mice invalidated for CB2 receptor (CB2(Mye-/-) mice) or for the autophagy gene ATG5 (ATG5(Mye-/-) mice) in the myeloid lineage, and their littermate wild-type mice were subjected to chronic-plus-binge ethanol feeding. CB2(Mye-/-) mice showed exacerbated alcohol-induced pro-inflammatory gene expression and steatosis. Studies in cultured macrophages demonstrated that CB2 receptor activation by JWH-133 stimulated autophagy via a heme oxygenase-1 dependent pathway. Moreover, JWH-133 reduced the induction of inflammatory genes by lipopolysaccharide in wild-type macrophages, but not in ATG5-deficient cells. The CB2 agonist also protected from alcohol-induced liver inflammation and steatosis in wild-type mice, but not in ATG5(Mye-/-) mice demonstrating that macrophage autophagy mediates the anti-inflammatory and anti-steatogenic effects of CB2 receptor. Altogether these results demonstrate that CB2 receptor activation in macrophages protects from alcohol-induced steatosis by inhibiting hepatic inflammation through an autophagy-dependent pathway. PMID:27346657

  1. Alcohol and breast cancer: results from The Netherlands Cohort Study.

    PubMed

    van den Brandt, P A; Goldbohm, R A; van 't Veer, P

    1995-05-15

    Although the results of cohort studies on the association between alcohol and breast cancer are rather consistent, the current evidence is based solely on North American cohorts. Therefore, this association was evaluated in the Netherlands Cohort Study on diet and cancer, conducted since 1986 among 62,573 women aged 55-69 years. After 3.3 years of follow-up (1986-1989), 422 incident breast cancer cases for which there were complete alcohol consumption data were available for analysis. In multivariate case-cohort analyses, the rate ratio for breast cancer in drinkers versus nondrinkers was 1.31 (95 percent confidence interval 1.00-1.71). When separate alcohol intake categories were compared with nondrinking, the rate ratios were 1.30, 1.29, 1.28, and 1.72 for women who consumed < 5, 5-14, 15-29, and > or = 30 g of alcohol per day, respectively (trend p = 0.047). Whereas beer consumption was not associated with breast cancer risk, increased risks were found at higher levels of both wine and liquor consumption. The alcohol-breast cancer association was found to be stronger among women with a history of benign breast disease, women with a history of breast cancer among sister(s), and women with an early menopause, and it varied considerably according to age at first birth. These results support a positive association between alcohol and breast cancer among postmenopausal women. The increased risk was particularly found among women who consumed 30 g or more of alcohol daily. PMID:7741120

  2. Alcohol abuse and dependence among U.S.-Mexico border and non-border Mexican Americans

    PubMed Central

    Caetano, Raul; Caetano Vaeth, Patrice A.; Mills, Britain A.; Rodriguez, Lori A.

    2012-01-01

    BACKGROUND This paper examines the prevalence, the symptom profile, and the drinking and sociodemographic predictors of current (past 12 month) DSM-IV alcohol abuse and dependence among Mexican Americans living along the U.S.-Mexico border and those living in metropolitan areas away from the border. METHODS Respondents in the non-border areas (primarily Houston and Los Angeles) constitute a multistage probability sample (N=1,288) of these areas, interviewed as part of the 2006 Hispanic Americans Baseline Alcohol Survey (HABLAS). Respondents in the border area (N=1,307) constitute a household probability sample of Mexican Americans living on the border. In both surveys, data were collected during computer assisted interviews conducted in respondents’ homes. The HABLAS and the border sample response rates were 76% and 67%, respectively. RESULTS Although bivariate analyses revealed no overall differences between border and non-border locations, (negative) age trends were more pronounced on the border for male abuse and for dependence among both genders. Among females aged 18–29, border residence was linked to significantly higher rates of dependence. In multivariable analyses, the prevalence of male abuse declined more rapidly with age on the border than off the border. Other unique predictors of male abuse were Jewish/other religion and weekly volume of alcohol consumption. Being married or out of the workforce, attaining a higher education, no religious preference, and weekly volume uniquely predicted female dependence. Age and weekly volume uniquely predicted male dependence. CONCLUSIONS The prevalence of alcohol use disorders among Mexican Americans on and off the U.S.-Mexico border largely mirrors previously documented patterns of alcohol consumption in these areas. For young Mexican-American women in particular, border residence is linked to heightened vulnerability to alcohol dependence. PMID:23278433

  3. Ghrelin system in alcohol-dependent subjects: role of plasma ghrelin levels in alcohol drinking and craving

    PubMed Central

    Leggio, Lorenzo; Ferrulli, Anna; Cardone, Silvia; Nesci, Antonio; Miceli, Antonio; Malandrino, Noemi; Capristo, Esmeralda; Canestrelli, Benedetta; Monteleone, Palmiero; Kenna, George A.; Swift, Robert M.; Addolorato, Giovanni

    2016-01-01

    Animal studies suggest that the gut-brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics. This investigation consisted of two studies. Study 1 was a 12-week study with alcohol-dependent subjects, where plasma ghrelin determinations were assessed four times (T0-T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone (GH) levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case-control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol-dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non-abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol-dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant. This investigation suggests that ghrelin is potentially able to affect alcohol-seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD. PMID:21392177

  4. Supplier-dependent differences in intermittent voluntary alcohol intake and response to naltrexone in Wistar rats

    PubMed Central

    Momeni, Shima; Segerström, Lova; Roman, Erika

    2015-01-01

    Alcohol use disorder (AUD) is a worldwide public health problem and a polygenetic disorder displaying substantial individual variation. This work aimed to study individual differences in behavior and its association to voluntary alcohol intake and subsequent response to naltrexone in a seamless heterogenic group of animals. Thus, by this approach the aim was to more accurately recapitulate the existing heterogeneity within the human population. Male Wistar rats from three different suppliers (Harlan Laboratories B.V., RccHan™:WI; Taconic Farms A/S, HanTac:WH; and Charles River GmbH, Crl:WI) were used to create a heterogenic group for studies of individual differences in behavior, associations to intermittent voluntary alcohol intake and subsequent response to naltrexone. The rats were tested in the open field prior to the Y-maze and then given voluntary intermittent access to alcohol or water in the home cage for 6 weeks, where after, naltrexone in three different doses or saline was administered in a Latin square design over 4 weeks and alcohol intake and preference was measured. However, supplier-dependent differences and concomitant skew subgroup formations, primarily in open field behavior and intermittent alcohol intake, resulted in a shifted focus to instead study voluntary alcohol intake and preference, and the ensuing response to naltrexone in Wistar rats from three different suppliers. The results showed that outbred Wistar rats are diverse with regard to voluntary alcohol intake and preference in a supplier-dependent manner; higher in RccHan™:WI relative to HanTac:WH and Crl:WI. The results also revealed supplier-dependent differences in the effect of naltrexone that were dose- and time-dependent; evident differences in high-drinking RccHan™:WI rats relative to HanTac:WH and Crl:WI rats. Overall these findings render RccHan™:WI rats more suitable for studies of individual differences in voluntary alcohol intake and response to naltrexone and

  5. Self-Efficacy for Refusal Mediated by Outcome Expectancies in the Prediction of Alcohol-Dependence amongst Young Adults.

    ERIC Educational Resources Information Center

    Williams, Robert J.; Connor, Jason P.; Ricciardelli, Lina A.

    1998-01-01

    Examines the relative importance of outcome expectancies and self-efficacy in the production of alcohol dependence and alcohol consumption in a sample of young adult drinkers drawn from a milieu previously reported as supportive of risky drinking. Results suggest that heavy drinking women are particularly at risk of developing drinking-related…

  6. The First Alcohol Drink Triggers mTORC1-Dependent Synaptic Plasticity in Nucleus Accumbens Dopamine D1 Receptor Neurons.

    PubMed

    Beckley, Jacob T; Laguesse, Sophie; Phamluong, Khanhky; Morisot, Nadege; Wegner, Scott A; Ron, Dorit

    2016-01-20

    Early binge-like alcohol drinking may promote the development of hazardous intake. However, the enduring cellular alterations following the first experience with alcohol consumption are not fully understood. We found that the first binge-drinking alcohol session produced enduring enhancement of excitatory synaptic transmission onto dopamine D1 receptor-expressing neurons (D1+ neurons) in the nucleus accumbens (NAc) shell but not the core in mice, which required D1 receptors (D1Rs) and mechanistic target of rapamycin complex 1 (mTORC1). Furthermore, inhibition of mTORC1 activity during the first alcohol drinking session reduced alcohol consumption and preference of a subsequent drinking session. mTORC1 is critically involved in RNA-to-protein translation, and we found that the first alcohol session rapidly activated mTORC1 in NAc shell D1+ neurons and increased synaptic expression of the AMPAR subunit GluA1 and the scaffolding protein Homer. Finally, D1R stimulation alone was sufficient to activate mTORC1 in the NAc to promote mTORC1-dependent translation of the synaptic proteins GluA1 and Homer. Together, our results indicate that the first alcohol drinking session induces synaptic plasticity in NAc D1+ neurons via enhanced mTORC1-dependent translation of proteins involved in excitatory synaptic transmission that in turn drives the reinforcement learning associated with the first alcohol experience. Thus, the alcohol-dependent D1R/mTORC1-mediated increase in synaptic function in the NAc may reflect a neural imprint of alcohol's reinforcing properties, which could promote subsequent alcohol intake. Significance statement: Consuming alcohol for the first time is a learning event that drives further drinking. Here, we identified a mechanism that may underlie the reinforcing learning associated with the initial alcohol experience. We show that the first alcohol experience induces a persistent enhancement of excitatory synaptic transmission on NAc shell D1+ neurons

  7. The First Alcohol Drink Triggers mTORC1-Dependent Synaptic Plasticity in Nucleus Accumbens Dopamine D1 Receptor Neurons

    PubMed Central

    Beckley, Jacob T.; Laguesse, Sophie; Phamluong, Khanhky; Morisot, Nadege; Wegner, Scott A.

    2016-01-01

    Early binge-like alcohol drinking may promote the development of hazardous intake. However, the enduring cellular alterations following the first experience with alcohol consumption are not fully understood. We found that the first binge-drinking alcohol session produced enduring enhancement of excitatory synaptic transmission onto dopamine D1 receptor-expressing neurons (D1+ neurons) in the nucleus accumbens (NAc) shell but not the core in mice, which required D1 receptors (D1Rs) and mechanistic target of rapamycin complex 1 (mTORC1). Furthermore, inhibition of mTORC1 activity during the first alcohol drinking session reduced alcohol consumption and preference of a subsequent drinking session. mTORC1 is critically involved in RNA-to-protein translation, and we found that the first alcohol session rapidly activated mTORC1 in NAc shell D1+ neurons and increased synaptic expression of the AMPAR subunit GluA1 and the scaffolding protein Homer. Finally, D1R stimulation alone was sufficient to activate mTORC1 in the NAc to promote mTORC1-dependent translation of the synaptic proteins GluA1 and Homer. Together, our results indicate that the first alcohol drinking session induces synaptic plasticity in NAc D1+ neurons via enhanced mTORC1-dependent translation of proteins involved in excitatory synaptic transmission that in turn drives the reinforcement learning associated with the first alcohol experience. Thus, the alcohol-dependent D1R/mTORC1-mediated increase in synaptic function in the NAc may reflect a neural imprint of alcohol's reinforcing properties, which could promote subsequent alcohol intake. SIGNIFICANCE STATEMENT Consuming alcohol for the first time is a learning event that drives further drinking. Here, we identified a mechanism that may underlie the reinforcing learning associated with the initial alcohol experience. We show that the first alcohol experience induces a persistent enhancement of excitatory synaptic transmission on NAc shell D1+ neurons

  8. Efficacy of Medications Approved for the Treatment of Alcohol Dependence and Alcohol Withdrawal Syndrome in Female Patients: A Descriptive Review.

    PubMed

    Agabio, Roberta; Pani, Pier Paolo; Preti, Antonio; Gessa, Gian Luigi; Franconi, Flavia

    2016-01-01

    The aim of this study was to evaluate whether the number of women recruited for studies to establish the efficacy of medications approved for treatment of alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to reveal possible gender differences in the response to these medications and in suggesting the use of different doses in female patients. Our results show that the rates of women recruited for studies evaluating the efficacy of disulfiram (1%), benzodiazepines (3%), and anticonvulsants (13%) were too low to establish possible gender differences. The rates of women recruited for studies evaluating the efficacy of acamprosate (22%), naltrexone (23%), and nalmefene (30%) were higher and allowed evaluation of data obtained for female patients. Women receive medications for treatment of AD and/or AWS for which efficacy has been demonstrated in studies in which men were more largely represented. PMID:26314552

  9. Alcohol-Dependent Liver Cell Necrosis in vitro: A New Model

    NASA Astrophysics Data System (ADS)

    Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel

    1981-04-01

    In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.

  10. Deficits in Emotion-Regulation Skills Predict Alcohol Use during and after Cognitive-Behavioral Therapy for Alcohol Dependence

    ERIC Educational Resources Information Center

    Berking, Matthias; Margraf, Matthias; Ebert, David; Wupperman, Peggilee; Hofmann, Stefan G.; Junghanns, Klaus

    2011-01-01

    Objective: As emotion regulation is widely considered to be a primary motive in the misuse of alcohol, our aim in the study was to investigate whether deficits in adaptive emotion-regulation skills maintain alcohol dependence (AD). Method: A prospective study investigated whether emotion-regulation skills were associated with AD and whether these…

  11. General and Specific Predictors of Nicotine and Alcohol Dependence in Early Adulthood: Genetic and Environmental Influences

    PubMed Central

    Samek, Diana R; Keyes, Margaret A; Hicks, Brian M; Bailey, Jennifer; McGue, Matt; Iacono, William G

    2014-01-01

    Objective: This study builds on previous work delineating a hierarchical model of family environmental risk in relation to a hierarchical model of externalizing disorders (EXTs) by evaluating for gene–environment interplay in these relationships. The associations between parent–child relationship quality (conflict, bonding, and management) and substance-specific adolescent family environments (parental/sibling tobacco/alcohol use) in relation to young adult EXTs (age ∼22 years nicotine, alcohol, and other drug dependence; antisocial and risky sexual behavior) were evaluated. Method: The sample included 533 adopted offspring and 323 biological offspring. Because adopted youth do not share genes with their parents, a significant association between parent–child relationship quality and EXTs would provide evidence against passive gene–environment correlation (rGE). Significant associations between parental tobacco/alcohol use in relation to offspring nicotine/alcohol dependence in the adopted offspring support common environmental influence. Significant associations detected for the biological offspring only suggest common genetic influence. Results: For both adoptive and biological offspring, there was a significant association between parent–child relationship quality and EXTs. Parental tobacco/alcohol use was unrelated to EXTs. Sibling tobacco/alcohol use was related to EXTs, but only for the biological siblings. Parental tobacco use was associated with the residual variance in nicotine dependence in adopted offspring. Conclusions: Findings replicate a long-term influence of adolescent parent–child relationship quality on adult EXTs. Findings extend previous research by providing evidence against passive rGE in this association. The association between parental tobacco use and adult nicotine dependence appears to be environmentally mediated, but caution is warranted as we found this relationship only for adopted youth. PMID:24988261

  12. The metabolic syndrome in patients with alcohol dependency: Current research and clinical implications.

    PubMed

    Kahl, Kai G; Hillemacher, Thomas

    2016-10-01

    The relationship between alcohol dependency and disorders such as liver disease and cancer has been thoroughly researched. However, the effects of alcohol on cardiometabolic health remain controversial. Several reports found low to moderate alcohol consumption to be associated with a lower risk for cardiometabolic disorders. In contrast, excessive alcohol consumption has been related to an increased risk. Most of these studies were performed in non-clinical populations, therefore limiting the explanatory power to non-dependent patients. Only a few studies examined cardiovascular disorders and cardiovascular risk factors, in particular the metabolic syndrome (MetS), in alcohol dependent patients. We here present a narrative review of studies performed so far on the MetS in alcohol dependency, and provide current hypotheses on the association of alcohol dependency, appetite regulation and the development of the MetS. PMID:27174541

  13. PET imaging of the serotonin transporter and 5HT1A receptor in alcohol dependence

    PubMed Central

    Martinez, Diana; Slifstein, Mark; Gil, Roberto; Hwang, Dah-Ren; Huang, Yiyun; Perez, Audrey; Frankle, W. Gordon; Laruelle, Marc; Krystal, John; Abi-Dargham, Anissa

    2009-01-01

    Background Rodent models as well as studies in humans have suggested alterations in serotonin (5HT) innervation and transmission in early onset genetically determined or type II alcoholism. This study examines two indices of serotonergic transmission, 5HT transporter levels and 5-HT1A availability, in vivo, in type II alcoholism. This is the first report of combined tracers for pre and post-synaptic serotonergic transmission in the same alcoholic subjects and the first study of 5HT1A receptors in alcoholism. Method Fourteen alcohol dependent subjects were scanned (11 with both tracers, 1 with [11C]DASB only and two with [11C]WAY100635 only). Twelve healthy controls (HC) subjects were scanned with [11C]DASB and another 13 were scanned with [11C]WAY100635. Binding Potential (BPp, mL/cm3) and the specific to nonspecific partition coefficient (BPND, unitless) were derived for both tracers using 2 tissue compartment model and compared to HC across different brain regions. Relationships to severity of alcoholism were assessed. Results No significant differences were observed in regional BPp or BPND between patients and controls in any of the regions examined. No significant relationships were observed between regional 5HT transporter availability, 5-HT1A availability, and disease severity with the exception of a significant negative correlation between SERT and years of dependence in amygdala and insula. Conclusion This study did not find alterations in measures of 5-HT1A or 5HT transporter levels in patients with type II alcoholism. PMID:18962444

  14. TNF-α and IL-6 serum levels: neurobiological markers of alcohol consumption in alcohol-dependent patients?

    PubMed

    Heberlein, Annemarie; Käser, Marius; Lichtinghagen, Ralf; Rhein, Mathias; Lenz, Bernd; Kornhuber, Johannes; Bleich, Stefan; Hillemacher, Thomas

    2014-11-01

    We investigated the serum levels of IL-6 and TNF-α in 30 male alcohol-dependent patients during withdrawal (day 1, 7, and 14) and compared them with the levels obtained from 18 healthy male controls. IL-6 (day 1: T = 2,593, p = 0.013; day 7: T = 2,315, p = 0.037; day 14: T = 1,650, p = 0.112) serum levels were significantly increased at the beginning of alcohol withdrawal. TNF-α (T = 3,202, p = 0.03) serum levels were significantly elevated in the patients' group during the whole period of withdrawal. IL-6 serum levels decreased significantly during withdrawal (F = 16.507, p < 0.001), whereas TNF-α levels did not change significantly (day 1-14). IL-6 serum levels were directly associated with alcohol consumption (r = 0.392, p = 0.047) on day 1. Moreover, the IL-6 serum levels were associated with alcohol craving (PACS total score day 1: r = -0.417, p = 0.022, the score of the obsessive subscale of the OCDS on day 14 [r = -0.549, p = 0.022]), depression (r = -0.507, p = 0.005), and trait anxiety (r = -0.674, p < 0.001) on day 1. We found an association with the duration of active drinking following the last period of abstinence and the TNF-α serum levels (day 1:r = 0.354, p = 0.009; day 7: r = 0.323, p = 0.022; day 14: r = 0.303, p = 0.034) as well as an association with the severity of alcohol dependence measured by the SESA scale (r = 0.454, p = 0.015). Moreover, we found a significant association between the BDNF serum levels and the TNF-α serum levels (r = -0.426, p = 0.021). Our results support an association between alterations in TNF-α and IL-6 serum levels and alcohol consumption. PMID:25262503

  15. Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study

    PubMed Central

    Melroy, Whitney E.; Stephens, Sarah H.; Sakai, Joseph T.; Kamens, Helen M.; McQueen, Matthew B.; Corley, Robin P.; Stallings, Michael C.; Hopfer, Christian J.; Krauter, Kenneth S.; Brown, Sandra A.; Hewitt, John K.; Ehringer, Marissa A.

    2014-01-01

    Previous studies have shown associations between SNPs in GABRA2 and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 NPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility. PMID:24687270

  16. Alcohol-Adapted Anger Management Treatment: A Randomized Controlled Trial of an Innovative Therapy for Alcohol Dependence.

    PubMed

    Walitzer, Kimberly S; Deffenbacher, Jerry L; Shyhalla, Kathleen

    2015-12-01

    A randomized controlled trial for an innovative alcohol-adapted anger management treatment (AM) for outpatient alcohol dependent individuals scoring moderate or above on anger is described. AM treatment outcomes were compared to those of an empirically-supported intervention, Alcoholics Anonymous Facilitation treatment (AAF). Clients in AM, relative to clients in AAF, were hypothesized to have greater improvement in anger and anger-related cognitions and lesser AA involvement during the 6-month follow-up. Anger-related variables were hypothesized to be stronger predictors of improved alcohol outcomes in the AM treatment condition and AA involvement was hypothesized to be a stronger predictor of alcohol outcomes in the AAF treatment group. Seventy-six alcohol dependent men and women were randomly assigned to treatment condition and followed for 6 months after treatment end. Both AM and AAF treatments were followed by significant reductions in heavy drinking days, alcohol consequences, anger, and maladaptive anger-related thoughts and increases in abstinence and self-confidence regarding not drinking to anger-related triggers. Treatment with AAF was associated with greater AA involvement relative to treatment with AM. Changes in anger and AA involvement were predictive of posttreatment alcohol outcomes for both treatments. Change in trait anger was a stronger predictor of posttreatment alcohol consequences for AM than for AAF clients; during-treatment AA meeting attendance was a stronger predictor of posttreatment heavy drinking and alcohol consequences for AAF than for AM clients. Anger-related constructs and drinking triggers should be foci in treatment of alcohol dependence for anger-involved clients. PMID:26387049

  17. From genetic studies to precision medicine in alcohol dependence.

    PubMed

    Sun, Yan; Zhang, Yan; Wang, Fan; Sun, Yankun; Shi, Jie; Lu, Lin

    2016-04-01

    Genetic factors contribute to more than 50% of the variation in the vulnerability to alcohol dependence (AD). Although significant advances have been made in medications for AD, these medications do not work for all people. Precise tailoring of medicinal strategies for individual alcoholic patients is needed to achieve optimal outcomes. This review updates the most promising information on genetic variants in AD, which may be useful for improving diagnostic, therapeutic, and monitoring strategies. We describe genetic candidates of various neurotransmitter and enzyme systems. In addition to biological and allelic associations with AD, genetic effects on AD-related phenotypes and treatment responses have also been described. Gene-gene and gene-environment interactions have been considered. Potential applications of genomewide and epigenetic approaches for identifying genetic biomarkers of AD have been discussed. Overall, the application of genetic findings in precision medicine for AD will likely involve an integrated approach that distinguishes effect sizes of specific genetic predictors with regard to sex, pharmacotherapy, ethnicity, and AD-related aspects and considers gene-gene and gene-environment interactions. Our work may pave the way toward more precise treatment for AD that could ultimately improve clinical management and interventions. PMID:26580132

  18. Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans

    PubMed Central

    Wei, Ya-Ming; Du, Yan-Lei; Nie, Yu-Qiang; Li, Yu-Yuan; Wan, Yu-Jui

    2012-01-01

    AIM: To investigate the association of polymorphisms of nur-related receptor 1 (Nurr1) and development of alcohol dependence in Mexican Americans. METHODS: Peripheral blood samples were collected from 374 alcoholic and 346 nonalcoholic Mexican Americans; these two groups were sex- and age-matched. Sample DNA was extracted and genomic DNA was amplified by polymerase chain reaction. The -2922(C) 2-3 polymerase chain reaction products were digested with Sau96I, alleles of 1345(G/C), and -1198(C/G) in the regulatory region as well as Ex+132 (G/T/A/C) and Ex+715(T/-) in exon 3 were studied by sequencing. RESULTS: The C2/C2, C2/C3, C3/C3 genotype distribution of -2922(C) 2-3 was 34.4%, 38.2% and 27.5% in the nonalcoholic group compared to 23.3%, 51.2% and 25.4% in the alcoholic group (P = 0.001). The C/C, C/G, G/G genotype distribution of -1198(C/G) was 23.5%, 46.1% and 30.3% in the nonalcoholic group compared to 13.9%, 50.9% and 35.3% in the alcoholic group (P = 0.007). However, the -1345 (G/C), Ex3+132(G/T/A/C) and Ex3+715(T/-) alleles were not polymorphic in Mexican Americans, and all those studied had G/G, G/G and T/T genotype for these three alleles, respectively. The -2922(C) 2-3 did not show allele level difference between alcoholic and nonalcoholic individuals, but -1198 (C/G) showed a significant allele frequency difference between alcoholic (39.3%) and nonalcoholic (46.6%) populations (P = 0.005). Excluding obese individuals, significant differences were found at both genotypic and allelic levels for the -2922(C) 2-3 polymorphism (P = 0.000 and P = 0.049) and the -1198 (C/G) polymorphism (P = 0.008 and P = 0.032) between nonobese alcoholics and nonobese controls. Excluding smokers, a significant difference was found only at the genotypic level for the -2922(C) 2-3 polymorphism (P = 0.037) between nonsmoking alcoholics and nonsmoking controls, but only at the allelic level for the -1198(C/G) polymorphism (P = 0.034). CONCLUSION: Polymorphisms in the regulatory

  19. Neuronal Nicotinic Acetylcholine Receptors: Common Molecular Substrates of Nicotine and Alcohol Dependence

    PubMed Central

    Hendrickson, Linzy M.; Guildford, Melissa J.; Tapper, Andrew R.

    2013-01-01

    Alcohol and nicotine are often co-abused. As many as 80–95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels normally activated by endogenous acetylcholine (ACh), ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic) reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA) which project to the nucleus accumbens (NAc). Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from pre-clinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence. PMID:23641218

  20. Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population-based cohort.

    PubMed

    Clarke, Toni-Kim; Smith, Andrew H; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Hall, Lynsey S; Fernandez-Pujals, Ana M; MacIntyre, Donald J; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; Thomson, Pippa A; Porteous, David J; Deary, Ian J; McIntosh, Andrew M

    2016-03-01

    Alcohol dependence is frequently co-morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome-wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n = 2750; Yale-Penn GWAS: n = 2377) in a population-based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P = 0.009, β = -0.027; Yale-Penn: P = 0.001, β = -0.034) and VF (SAGE: P = 0.0008, β = -0.036; Yale-Penn: P = 0.00005, β = -0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P = 5.2 × 10(-7) , β = -0.054; Yale-Penn: P = 0.000012, β = -0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders. PMID:25865819

  1. Amphetamine Dependence and Co-Morbid Alcohol Abuse: Associations to Brain Cortical Thickness

    PubMed Central

    2010-01-01

    Background Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls. While all subjects were recruited to be free of alcohol dependence, structured clinical interviews revealed significant patterns of alcohol use in the patients. Structural magnetic resonance brain images were obtained from the subjects using a 1.5 Tesla GE Signa machine. Brain cortical thickness was measured with submillimeter precision at multiple finely spaced cortical locations using semi-automated post-processing (FreeSurfer). Contrast analysis of a general linear model was used to test for differences between the two groups at each cortical location. In addition to contrasting patients with controls, a number of analyses sought to identify possible confounding effects from alcohol. Results No significant cortical thickness differences were observed between the full patient group and controls, nor between non-drinking patients and controls. Patients with a history of co-morbid heavy alcohol use (n = 29) showed reductions in the superior-frontal right hemisphere and pre-central left hemisphere when compared to healthy controls (n = 40). Conclusions Amphetamine usage was associated with reduced cortical thickness only in patients co-morbid for heavy alcohol use. Since cortical thickness is but one measure of brain structure and does not capture brain function, further studies of brain structure and function in amphetamine dependence are warranted. PMID:20487539

  2. Loss in connectivity among regions of the brain reward system in alcohol dependence.

    PubMed

    Kuceyeski, Amy; Meyerhoff, Dieter J; Durazzo, Timothy C; Raj, Ashish

    2013-12-01

    A recently developed measure of structural brain connectivity disruption, the loss in connectivity (LoCo), is adapted for studies in alcohol dependence. LoCo uses independent tractography information from young healthy controls to project the location of white matter (WM) microstructure abnormalities in alcohol-dependent versus nondependent individuals onto connected gray matter (GM) regions. LoCo scores are computed from WM abnormality masks derived at two levels: (1) groupwise differences of alcohol-dependent individuals (ALC) versus light-drinking (LD) controls and (2) differences of each ALC individual versus the LD control group. LoCo scores based on groupwise WM differences show that GM regions belonging to the extended brain reward system (BRS) network have significantly higher LoCo (i.e., disconnectivity) than those not in this network (t = 2.18, P = 0.016). LoCo scores based on individuals' WM differences are also higher in BRS versus non-BRS (t = 5.26, P = 3.92 × 10(-6) ) of ALC. These results suggest that WM alterations in alcohol dependence, although subtle and spatially heterogeneous across the population, are nonetheless preferentially localized to the BRS. LoCo is shown to provide a more sensitive estimate of GM involvement than conventional volumetric GM measures by better differentiating between brains of ALC and LD controls (rates of 89.3% vs. 69.6%). However, just as volumetric measures, LoCo is not significantly correlated with standard metrics of drinking severity. LoCo is a sensitive WM measure of regional cortical disconnectivity that uniquely characterizes anatomical network disruptions in alcohol dependence. PMID:22815206

  3. The effects of polyunsaturated fatty acids in alcohol dependence treatment - a double-blind, placebo-controlled pilot study

    PubMed Central

    2011-01-01

    Background The lipid fraction of cell membranes consists of polyunsaturated fatty acids (PUFAS), and chronic alcohol use alters it, modifying its permeability, what might contribute for the dysfunctional metabolism observed in the central nervous system of alcohol dependent patients. Therefore, the supplementation of PUFAS can be an important adjuvant in alcoholism treatment. Methods This was a placebo controlled, double blind, randomized study where, 80 alcohol dependent patients, according to DSM-IV, were allocated in four groups with 20 patient each: 'PUFAS', 'Naltrexone', 'Naltrexone + PUFAS' and 'Placebo'. Those substances were administered for 90 days and scales were applied to assess patients craving (OCDS) and alcohol dependence severity (SADD) at baseline and after 90 days. PUFAS serum levels were assessed before and after treatment by high performance liquid chromatography assay. Results Forty-three patients completed the trial. There was a significant improvement over time on drinking days, SADD and OCDS scores in all groups (p < 0.001). The drinking days comparison between groups did not show statistical significant difference. The same effect was observed for compulsion (OCDS) and severity of dependence scale (SADD). The serum levels of PUFAS increased in all the supplemented groups after treatment, although not significantly. Conclusions The oral supplementation of 2 g PUFAS for 3 months did not significantly differ from placebo in reducing the amount of alcohol ingestion, or OCDS and SADD scores in a group of alcohol dependent patient. Trial registration NCT01211769 PMID:21787433

  4. Metacognitive and Meta-Emotional Styles in Patients With Alcohol and the Other Substance Dependence

    PubMed Central

    Ipek, Okan Ufuk; Yavuz, Kaasim Fatih; Ulusoy, Sevinc; Sahin, Oktay; Kurt, Erhan

    2015-01-01

    Background: Both alcohol and other substances are utilized for emotional and cognitive regulation. Objectives: The purpose of the present study was to compare metacognitive styles and distress intolerance in patients with alcohol and other substance dependence. Patients and Methods: According to DSM-IV TR criteria, 45 patients with alcohol dependence (AD), 44 patients with substance dependence (SD), and 43 volunteers without AD or SD (control group) were enrolled. Socio-demographic information form, Distress Tolerance Scale (DTS), and metacognitive questionaire-30 (MCQ-30) were used to evaluate the participants. Results: Patients with AD had significantly lower “tolerance” subscale and total DTS scores than those with SD and control group (P = 0.008 for SD sample and P = 0.004 for control group). Patients with SD had significantly higher scores in “appraisal” subscale DTS than control group (P = 0.005). Patients of both AD and SD groups had significantly higher scores in “positive beliefs” subscale of MCQ-30 than control group (P = 0.012 for AD group and P = 0. 001 for SD group). There was no significant difference between AD and SD groups in any MCQ-30 subscale and total scores (P = 0.440). Conclusions: Metacognitive regulation strategies are more considerable prediction than emotional regulation strategies in SD group than in AD group. Individuals with AD use alcohol as a means of both cognitive and emotional regulation strategy. PMID:26495260

  5. Role of the Serotonergic System in Alcohol Dependence: From Animal Models to Clinics

    PubMed Central

    Sari, Youssef; Johnson, Verity R.; Weedman, Jason M.

    2012-01-01

    Alcohol dependence remains among the most common substance abuse problems worldwide, and compulsive alcohol consumption is a significant public health concern. Alcohol is an addictive drug that alters brain function through interactions with multiple neurotransmitter systems. These neurotransmitter systems mediate the reinforcing effects of alcohol. Specifically, the serotonergic system is important in mediating alcohol reward, preference, dependence, and craving. In this review chapter, we first discuss the serotonin system as it relates to alcoholism, and then outline interactions between this system and other neurotransmitter systems. We emphasize the serotonin transporter and its possible role in alcoholism, then present several serotonergic receptors and discuss their contribution to alcoholism, and finally assess the serotonin system as a target for pharmacotherapy, with an emphasis on current and potential treatments. PMID:21199778

  6. Neonatal Binge Alcohol Exposure Produces Dose Dependent Deficits in Interstimulus Interval Discrimination Eyeblink Conditioning in Juvenile Rats

    PubMed Central

    Brown, Kevin L.; Burman, Michael A.; Duong, Huan B.; Stanton, Mark E.

    2009-01-01

    Alcohol consumption in neonatal rats produces cerebellar damage and is widely used to model 3rd-trimester human fetal alcohol exposure. Neonatal “binge-like” exposure to high doses of alcohol (5 g/kg/day or more) impairs acquisition of eyeblink classical conditioning (EBC), a cerebellar-dependent Pavlovian motor learning task. We have recently found impairments in interstimulus interval (ISI) discrimination – a complex task variant of EBC - in adult rats following postnatal day (PD) 4–9 alcohol exposure at doses of 3, 4, and 5 g/kg/day. Because robust developmental differences in conditioned response (CR) generation and CR latency measures are present between untreated juveniles and adults in this task, we sought to extend alcohol findings to juvenile rats (PD30). Five neonatal treatment groups were used: (1) undisturbed controls, (2) sham intubation controls, (3) 3 g/kg/day of alcohol (blood alcohol concentration {BAC} = 139.9 mg/dl), (4) 4 g/kg/day of alcohol (BAC = 237.3 mg/dl), or (5) 5 g/kg/day of alcohol (BAC = 301.8 mg/dl). Intubations occurred over PD4-9. ISI discrimination training in juveniles (PD30-33) revealed dose-dependent CR deficits in all three alcohol-exposed groups relative to controls. Contrary to expected outcomes, CR latency measures were not significantly affected as a function of neonatal treatment. Comparison of these findings with our recent study in adults suggests that alcohol-induced impairments in ISI discrimination EBC may be greater in adults relative to juveniles. The present findings provide further evidence that ISI discrimination may provide greater sensitivity to functional deficits resulting from moderate levels of neonatal alcohol exposure relative to single-cue EBC paradigms. PMID:19007754

  7. Rare missense variants in CHRNB3 and CHRNA3 are associated with risk of alcohol and cocaine dependence

    PubMed Central

    Haller, Gabe; Kapoor, Manav; Budde, John; Xuei, Xiaoling; Edenberg, Howard; Nurnberger, John; Kramer, John; Brooks, Andy; Tischfield, Jay; Almasy, Laura; Agrawal, Arpana; Bucholz, Kathleen; Rice, John; Saccone, Nancy; Bierut, Laura; Goate, Alison

    2014-01-01

    Previous findings have demonstrated that variants in nicotinic receptor genes are associated with nicotine, alcohol and cocaine dependence. Because of the substantial comorbidity, it has often been unclear whether a variant is associated with multiple substances or whether the association is actually with a single substance. To investigate the possible contribution of rare variants to the development of substance dependencies other than nicotine dependence, specifically alcohol and cocaine dependence, we undertook pooled sequencing of the coding regions and flanking sequence of CHRNA5, CHRNA3, CHRNB4, CHRNA6 and CHRNB3 in 287 African American and 1028 European American individuals from the Collaborative Study of the Genetics of Alcoholism (COGA). All members of families for whom any individual was sequenced (2504 African Americans and 7318 European Americans) were then genotyped for all variants identified by sequencing. For each gene, we then tested for association using FamSKAT. For European Americans, we find increased DSM-IV cocaine dependence symptoms (FamSKAT P = 2 × 10−4) and increased DSM-IV alcohol dependence symptoms (FamSKAT P = 5 × 10−4) among carriers of missense variants in CHRNB3. Additionally, one variant (rs149775276; H329Y) shows association with both cocaine dependence symptoms (P = 7.4 × 10−5, β = 2.04) and alcohol dependence symptoms (P = 2.6 × 10−4, β = 2.04). For African Americans, we find decreased cocaine dependence symptoms among carriers of missense variants in CHRNA3 (FamSKAT P = 0.005). Replication in an independent sample supports the role of rare variants in CHRNB3 and alcohol dependence (P = 0.006). These are the first results to implicate rare variants in CHRNB3 or CHRNA3 in risk for alcohol dependence or cocaine dependence. PMID:24057674

  8. Prodynorphin CpG-SNPs associated with alcohol dependence: elevated methylation in the brain of human alcoholics

    PubMed Central

    Taqi, Malik Mumtaz; Bazov, Igor; Watanabe, Hiroyuki; Sheedy, Donna; Harper, Clive; Alkass, Kanar; Druid, Henrik; Wentzel, Parri; Nyberg, Fred; Yakovleva, Tatjana; Bakalkin, Georgy

    2012-01-01

    The genetic, epigenetic and environmental factors may influence the risk for neuropsychiatric disease through their effects on gene transcription. Mechanistically, these effects may be integrated through regulation of methylation of CpG dinucleotides overlapping with single-nucleotide polymorphisms (SNPs) associated with a disorder. We addressed this hypothesis by analyzing methylation of prodynorphin (PDYN) CpG-SNPs associated with alcohol dependence, in human alcoholics. Postmortem specimens of the dorsolateral prefrontal cortex (dl-PFC) involved in cognitive control of addictive behavior were obtained from 14 alcohol-dependent and 14 control subjects. Methylation was measured by pyrosequencing after bisulfite treatment of DNA. DNA binding proteins were analyzed by electromobility shift assay. Three PDYN CpG-SNPs associated with alcoholism were found to be differently methylated in the human brain. In the dl-PFC of alcoholics, methylation levels of the C, non-risk variant of 3′-untranslated region (3′-UTR) SNP (rs2235749; C > T) were increased, and positively correlated with dynorphins. A DNA-binding factor that differentially targeted the T, risk allele and methylated and unmethylated C allele of this SNP was identified in the brain. The findings suggest a causal link between alcoholism-associated PDYN 3′-UTR CpG-SNP methylation, activation of PDYN transcription and vulnerability of individuals with the C, non-risk allele(s) to develop alcohol dependence. PMID:21521424

  9. Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence

    PubMed Central

    Richardson, Heather N.; Chan, Stephanie H.; Crawford, Elena F.; Lee, Youn Kyung; Funk, Cindy K.; Koob, George F.; Mandyam, Chitra D.

    2009-01-01

    Experimenter-delivered alcohol decreases adult hippocampal neurogenesis, and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis was observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggests a loss in neuronal turnover and indicates that the hippocampal neurogenic niche is highly vulnerable to alcohol. PMID:19501165

  10. HIV, Alcohol Dependence and the Criminal Justice System: A Review and Call for Evidence-Based Treatment

    PubMed Central

    Springer, Sandra A.; Azar, Marwan M.; Altice, Frederick L.

    2011-01-01

    People with both HIV and alcohol use disorders are disproportionately concentrated within the U.S. criminal justice system; approximately one-quarter of all people with HIV cycle through the system each year. HIV-infected prisoners with alcohol problems face many obstacles as they transition back to the community. Specifically, although they have impressive HIV treatment outcomes during the period of incarceration while they are free from alcohol, upon release, however, they face inordinate challenges including relapse to alcohol use resulting in significant morbidity and mortality. Randomized controlled trials affirm the role of pharmacotherapy using naltrexone (NTX) as the therapeutic option conferring the best treatment outcome for alcohol use disorders within the community. Absent from these trials were inclusion of prisoners or HIV-infected individuals. Relapse to alcohol use among HIV-infected prisoners is associated with reduced retention in care, poor adherence to antiretroviral therapy with consequential poor HIV treatment outcomes and higher levels of HIV risk behaviors. Untreated alcohol dependence, particularly for released HIV-infected prisoners, has both negative consequences for the individual and society and requires a concentrated effort and rethinking of our existing approaches for this vulnerable population. The specific aim of this manuscript is to review the existing literature regarding the relationship of HIV and treatment for alcohol use disorders in criminal justice populations in an effort to determine “best practices” that might effectively result in improved treatment of HIV and alcohol disorders for released prisoners. PMID:21171933

  11. The Cannabinoid Receptor 2 Protects Against Alcoholic Liver Disease Via a Macrophage Autophagy-Dependent Pathway

    PubMed Central

    Denaës, Timothé; Lodder, Jasper; Chobert, Marie-Noële; Ruiz, Isaac; Pawlotsky, Jean-Michel; Lotersztajn, Sophie; Teixeira-Clerc, Fatima

    2016-01-01

    Kupffer cells, the resident macrophages of the liver, play a major role in the pathogenesis of alcoholic liver disease. We have previously demonstrated that CB2 receptor protects against alcoholic liver disease by inhibiting alcohol-induced inflammation and steatosis via the regulation of Kupffer cell activation. Here, we explored the mechanism underlying these effects and hypothesized that the anti-inflammatory properties of CB2 receptor in Kupffer cells rely on activation of autophagy. For this purpose, mice invalidated for CB2 receptor (CB2Mye−/− mice) or for the autophagy gene ATG5 (ATG5Mye−/− mice) in the myeloid lineage, and their littermate wild-type mice were subjected to chronic-plus-binge ethanol feeding. CB2Mye−/− mice showed exacerbated alcohol-induced pro-inflammatory gene expression and steatosis. Studies in cultured macrophages demonstrated that CB2 receptor activation by JWH-133 stimulated autophagy via a heme oxygenase-1 dependent pathway. Moreover, JWH-133 reduced the induction of inflammatory genes by lipopolysaccharide in wild-type macrophages, but not in ATG5-deficient cells. The CB2 agonist also protected from alcohol-induced liver inflammation and steatosis in wild-type mice, but not in ATG5Mye−/− mice demonstrating that macrophage autophagy mediates the anti-inflammatory and anti-steatogenic effects of CB2 receptor. Altogether these results demonstrate that CB2 receptor activation in macrophages protects from alcohol-induced steatosis by inhibiting hepatic inflammation through an autophagy-dependent pathway. PMID:27346657

  12. A longitudinal mediational study on the stability of alexithymia among alcohol-dependent outpatients in cognitive-behavioral therapy.

    PubMed

    Thorberg, Fred Arne; Young, Ross McD; Sullivan, Karen A; Lyvers, Michael; Hurst, Cameron P; Connor, Jason P; Tyssen, Reidar; London, Edythe D; Noble, Ernest P; Feeney, Gerald F X

    2016-02-01

    Alexithymia is characterized by difficulty identifying feelings, difficulty describing feelings, and an externally oriented thinking style. Alexithymia has been described as a trait-like risk factor for the development of alcohol use disorders. Few studies have investigated the absolute (whether mean scores change over time) and relative (extent to which relative differences among individuals remain the same over time) stability of alexithymia among men and women with alcohol dependence, or have considered potential underlying mechanisms. Social learning processes contribute to and maintain alcohol problems. The reinforcement of alcohol expectancies is one plausible mechanism that links the difficulties in emotional processing associated with alexithymia and alcohol use. The present study investigated the stability of alexithymia as well as alcohol expectancy as a mediator of alexithymia. Three hundred fifty-five alcohol-dependent patients were enrolled in a cognitive behavioral treatment program. Ninety-two alcohol-dependent patients completed assessments at baseline and at 3-month follow-up. Results indicated that total Toronto Alexithymia Scale (TAS-20; Bagby, Parker, & Taylor, 1994) mean score, difficulty identifying feelings, and difficulty describing feelings decreased significantly over time with a larger decrease in alexithymia mean scores for females. Externally oriented thinking mean scores did not change. The TAS-20 and its subfactors demonstrated significant correlations, from baseline to follow-up, which were stronger for males than for females. Regression analyses showed that the total TAS-20 mean scores, difficulty identifying feelings, and difficulty describing feelings were partially mediated through assertion alcohol expectancies. In conclusion, this suggests that alexithymia has relative stability and is a trait-like factor among alcohol-dependent treatment seekers. PMID:26795394

  13. Outcomes of Treatment for Alcohol Problems: Current Methods, Problems, and Results.

    ERIC Educational Resources Information Center

    Nathan, Peter E.; Skinstad, Anne-Helene

    1987-01-01

    Discusses current methods, problems, and results of psychological treatment for alcohol abuse, including alcoholism. Addresses external and internal validity problems specific to issues regarding who is treated for alcohol problems, and treatment and patient factors that predict response to alcoholism treatment. Reviews current data on…

  14. Alcohol

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Alcohol KidsHealth > For Teens > Alcohol Print A A A ... you can make an educated choice. What Is Alcohol? Alcohol is created when grains, fruits, or vegetables ...

  15. Psychological changes in alcohol-dependent patients during a residential rehabilitation program

    PubMed Central

    Giorgi, Ines; Ottonello, Marcella; Vittadini, Giovanni; Bertolotti, Giorgio

    2015-01-01

    Background Alcohol-dependent patients usually experience negative affects under the influence of alcohol, and these affective symptoms have been shown to decrease as a result of alcohol-withdrawal treatment. A recent cognitive–affective model suggests an interaction between drug motivation and affective symptoms. The aim of this multicenter study was to evaluate the psychological changes in subjects undergoing a residential rehabilitation program specifically designed for alcohol addiction, and to identify at discharge patients with greater affective symptoms and therefore more at risk of relapse. Materials and methods The sample included 560 subjects (mean age 46.91±10.2 years) who completed 28-day rehabilitation programs for alcohol addiction, following a tailored routine characterized by short duration and high intensity of medical and psychotherapeutic treatment. The psychological clinical profiles of anxiety, depression, psychological distress, psychological well-being, and self-perception of a positive change were assessed using the Cognitive Behavioral Assessment – Outcome Evaluation questionnaire at the beginning and at the end of the program. The changes in the psychological variables of the questionnaire were identified and considered as outcome evaluation of the residential intervention. Moreover, differences in the psychological functioning between patients with different characteristics were investigated. Results The score measured by the Cognitive Behavioral Assessment – Outcome Evaluation showed significant improvements in all the psychological characteristics assessed, and the profile at discharge was within the normal scores. Some significant differences were found in relation to specific characteristics of the sample, such as age, sex, level of education, type of intervention, and polysubstance use. Conclusion This study shows the changes in psychological profile in subjects undergoing residential rehabilitation from alcohol and how this

  16. Effect of amines as activators on the alcohol-oxidizing activity of pyrroloquinoline quinone-dependent quinoprotein alcohol dehydrogenase.

    PubMed

    Takeda, Kouta; Ishida, Takuya; Igarashi, Kiyohiko; Samejima, Masahiro; Nakamura, Nobuhumi; Ohno, Hiroyuki

    2014-01-01

    Pyrroloquinoline quinone-dependent quinoprotein alcohol dehydrogenases (PQQ-ADH) require ammonia or primary amines as activators in in vitro assays with artificial electron acceptors. We found that PQQ-ADH from Pseudomonas putida KT2440 (PpADH) was activated by various primary amines, di-methylamine, and tri-methylamine. The alcohol oxidation activity of PpADH was strongly enhanced and the affinity for substrates was also improved by pentylamine as an activator. PMID:25229857

  17. Group management of pharmacotherapy for alcohol dependence: feasibility and impact on adoption.

    PubMed

    Robinson, Shannon; Bowe, Thomas; Harris, Alex H S

    2013-01-01

    One of the barriers to initiating patients on medications for alcohol dependence is concern about the work involved in providing ongoing medication management. In this brief report, we describe our initial experiences with a medication management group, initially implemented to provide continued access during a staffing shortage. We describe the group structure and functioning, and provide initial analysis of the groups' impact on access and adoption of pharmacotherapy for alcohol dependence. Results of an interrupted time series analysis in one Veterans Health Administration (VHA) facility provide support for the notion that the group format is not only feasible but can actually increase access to these under-utilized medications (e.g., naltrexone and acamprosate). The number of patients receiving these medications was already increasing in this facility before the switch to group appointments, but this rate of initiation increased almost 3-fold after the onset of the groups. PMID:23932227

  18. Meta-Analyses of ALDH2 and ADH1B with Alcohol Dependence in Asians

    ERIC Educational Resources Information Center

    Luczak, Susan E.; Glatt, Stephen J.; Wall, Tamara J.

    2006-01-01

    Meta-analyses were conducted to determine the magnitude of relationships between polymorphisms in 2 genes, ALDH2 and ADH1B, with alcohol dependence in Asians. For each gene, possession of 1 variant [asterisk]2 allele was protective against alcohol dependence, and possession of a 2nd [asterisk]2 allele did not offer significant additional…

  19. The Development of a Broad Spectrum Treatment for Patients with Alcohol Dependence in Early Recovery

    ERIC Educational Resources Information Center

    Gulliver, Suzy Bird; Longabaugh, Richard; Davidson, Dena; Swift, Robert

    2005-01-01

    Estimates of the prevalence of alcohol dependence among Americans approach 14% (Read, Kahler, & Stevenson, 2001). Alcohol dependence was once considered among the most recalcitrant of problem behaviors, with only 20% to 30% attaining sustained abstinence (Hunt Barnett & Branch 1971). Although current definitions of treatment success now consider…

  20. The Role of Therapeutic Alliance in Treatment for People with Mild to Moderate Alcohol Dependence

    ERIC Educational Resources Information Center

    Richardson, Deirdre F.; Adamson, Simon J.; Deering, Daryle E. A.

    2012-01-01

    In an exploratory study of Therapeutic Alliance (TA) in brief outpatient treatment for alcohol dependence the relationship was investigated between TA and treatment outcome (measured at 6 weeks and 6 months) for 69 alcohol dependent clients participating in a randomised control trial between Motivational Enhancement Therapy and Non Directive…

  1. Prefrontal Response and Frontostriatal Functional Connectivity to Monetary Reward in Abstinent Alcohol-Dependent Young Adults

    PubMed Central

    Forbes, Erika E.; Rodriguez, Eric E.; Musselman, Samuel; Narendran, Rajesh

    2014-01-01

    Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant

  2. Gut region-dependent alterations of nitrergic myenteric neurons after chronic alcohol consumption

    PubMed Central

    Bagyánszki, Mária; Bódi, Nikolett

    2015-01-01

    Chronic alcohol abuse damages nearly every organ in the body. The harmful effects of ethanol on the brain, the liver and the pancreas are well documented. Although chronic alcohol consumption causes serious impairments also in the gastrointestinal tract like altered motility, mucosal damage, impaired absorption of nutrients and inflammation, the effects of chronically consumed ethanol on the enteric nervous system are less detailed. While the nitrergic myenteric neurons play an essential role in the regulation of gastrointestinal peristalsis, it was hypothesised, that these neurons are the first targets of consumed ethanol or its metabolites generated in the different gastrointestinal segments. To reinforce this hypothesis the effects of ethanol on the gastrointestinal tract was investigated in different rodent models with quantitative immunohistochemistry, in vivo and in vitro motility measurements, western blot analysis, evaluation of nitric oxide synthase enzyme activity and bio-imaging of nitric oxide synthesis. These results suggest that chronic alcohol consumption did not result significant neural loss, but primarily impaired the nitrergic pathways in gut region-dependent way leading to disturbed gastrointestinal motility. The gut segment-specific differences in the effects of chronic alcohol consumption highlight the significance the ethanol-induced neuronal microenvironment involving oxidative stress and intestinal microbiota. PMID:26301118

  3. Dependence induced increases in intragastric alcohol consumption in mice.

    PubMed

    Fidler, Tara L; Powers, Matthew S; Ramirez, Jason J; Crane, Andrew; Mulgrew, Jennifer; Smitasin, Phoebe; Cunningham, Christopher L

    2012-01-01

    Three experiments used the intragastric alcohol consumption (IGAC) procedure to examine the effects of variations in passive ethanol exposure on withdrawal and voluntary ethanol intake in two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2). Experimental treatments were selected to induce quantitative differences in ethanol dependence and withdrawal severity by: (1) varying the periodicity of passive ethanol exposure (three, six or nine infusions/day); (2) varying the dose per infusion (low, medium or high); and (3) varying the duration of passive exposure (3, 5 or 10 days). All experiments included control groups passively exposed to water. B6 mice generally self-infused more ethanol than D2 mice, but passive ethanol exposure increased IGAC in both strains, with D2 mice showing larger relative increases during the first few days of ethanol access. Bout data supported the characterization of B6 mice as sippers and D2 mice as gulpers. Three larger infusions per day produced a stronger effect on IGAC than six or nine smaller infusions, especially in D2 mice. Increased IGAC was strongly predicted by cumulative ethanol dose and intoxication during passive exposure in both strains. Withdrawal during the passive exposure phase was also a strong predictor of increased IGAC in D2 mice. However, B6 mice showed little withdrawal, precluding analysis of its potential role. Overall, these data support the hypothesis that dependence-induced increases in IGAC are jointly determined by two processes that might vary across genotypes: (1) tolerance to aversive postabsorptive ethanol effects and (2) negative reinforcement (i.e. alleviation of withdrawal by self-administered ethanol). PMID:21955048

  4. The genetics of addiction: alcohol-dependence and D3 dopamine receptor gene.

    PubMed

    Gorwood, P; Limosin, F; Batel, P; Duaux, E; Gouya, L; Adès, J

    2001-11-01

    Alcohol-dependence is a complex phenotype, with behavioral, psychological, pharmacological, medical and social dimensions. Aggregation studies, adoption and twin researches have demonstrated that the vulnerability to alcohol-dependence is at least in part linked to genetic factors, the genetic vulnerability to alcoholism being mainly not substance-specific. There are numerous candidate genes, but the D3 dopamine receptor is specifically located in the limbic area, and in particular in the nucleus accumbens, which are involved in reward and reinforcement behavior. Furthermore, a previous collaborative study showed that homozygosity for the Ball DRD3 locus was more frequently observed in opiate dependent patients with high sensation seeking scores. In this study, we analyzed the distribution of Ball DRD3 polymorphism in a new sample of 131 French male alcoholic-patients (DSM III-R criteria) and 68 healthy controls matched for sex and origins. Although we replicated the higher sensation seeking score in alcohol-dependent patients with comorbid dependence, we found no significant difference in the DRD3 gene polymorphism between controls and alcoholic patients, regardless of sensation seeking score, addictive or psychiatric comorbidity, alcoholism typology, and clinical specificities of alcoholism. There is good evidence that gene coding for the dopamine receptor D3 does not play a major role in the genetic vulnerability to alcoholism. PMID:11762133

  5. Association between insulin-like growth factor-1 and cognitive functions in alcohol-dependent patients.

    PubMed

    Han, Changwoo; Kim, Dai Jin; Bae, Hwallip; Won, Sung-Doo; Lee, Hae Kook

    2014-11-01

    Studies in alcohol-dependent patients show that cognitive function can be influenced by chronic use of alcohol. Alcohol is a known neurotoxin that induces neurodegeneration in the brain. Although there are various causes of cognitive deficiency in alcohol-dependent patients, in this study we focus on the role of corticosteroids. The hypothalamus-pituitary-adrenal system (i.e., the HPA axis) plays a part in the control of corticosteroids. Recent studies show that insulin-like growth factor-1 (IGF-1) reflects the status of growth hormones under the action of the HPA axis. Therefore, IGF-1 is a potential indicator that reflects activity of the HPA axis, and a biomarker that may reflect the decline of cognitive function associated with alcohol-induced hypercortisolism. The purposes of this study are to identify an association between cognitive function and IGF-1, and to investigate IGF as the biological marker of cognitive decline in alcohol-dependent patients. Forty alcohol-dependent patients were selected as the subjects of this study. IGF-1 was measured through an enzyme-linked immunosorbent assay (ELISA). Clinical features were examined using the Korean version of the alcohol dependence scale (ADS-K). Cognitive functions were measured using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Comparative analysis was utilized to identify an association between CERAD measurement items and IGF-1. Alcohol-dependent patients demonstrated stable performance of most of the CERAD measures. Among the measures of the CERAD, only trail making test A showed a correlation to IGF-1. Compared to trail making test B, trail making test A is assumed to reflect basic cognitive functions including psychomotor speed, visual search and sequencing in alcohol-dependent patients, regardless of demographic characteristics such as the level of education of patients. Therefore, IGF-1 seems to play an important role in detecting the decline of basic cognitive functions in

  6. Pentylenetetrazol produces a state-dependent conditioned place aversion to alcohol withdrawal in mice.

    PubMed

    Chester, Julia A; Coon, Laran E

    2010-04-01

    The purpose of this study was to determine if aversive effects of alcohol withdrawal could be detected in mice using the place conditioning procedure and whether the GABA(A) receptor antagonist, pentylenetetrazol (PTZ), would increase the aversive effects of alcohol withdrawal and increase the probability of detecting conditioned place aversion. Subjects were alcohol-naïve mice from a specific line selectively bred for low alcohol preference (LAP1; n=91) and were assigned to three groups: alcohol withdrawal, PTZ alone, and PTZ+alcohol withdrawal. On four trials, mice received either a 4.0 g/kg intraperitoneal (i.p.) injection of alcohol (alcohol withdrawal, PTZ+alcohol withdrawal groups) or saline (PTZ group) 8 h prior to being placed on a distinctive floor texture for a 30-min conditioning session. Five minutes before these sessions, mice in the PTZ and PTZ+alcohol withdrawal groups received PTZ (5.0 mg/kg; i.p.) and the alcohol withdrawal group received saline. On intervening days mice received two saline injections at the same time points prior to being placed on a different floor texture. Post-conditioning floor preference was assessed in two 60-min tests; the first test was drug-free and the second test was state-dependent. Neither alcohol withdrawal nor PTZ produced significant place conditioning. The PTZ+alcohol withdrawal group showed a significant place aversion during the state-dependent test. These data suggest that the combined stimulus properties of PTZ and alcohol withdrawal facilitated the expression of conditioned place aversion to alcohol withdrawal. PMID:20138906

  7. Pentylenetetrazol Produces a State-Dependent Conditioned Place Aversion to Alcohol Withdrawal in Mice

    PubMed Central

    Chester, Julia A.; Coon, Laran E.

    2010-01-01

    The purpose of this study was to determine if aversive effects of alcohol withdrawal could be detected in mice using the place conditioning procedure and whether the GABAA receptor antagonist, pentylenetetrazol (PTZ), would increase the aversive effects of alcohol withdrawal and increase the probability of detecting conditioned place aversion. Subjects were alcohol-naïve mice from a specific line selectively bred for low alcohol preference (LAP1; n=91) and were assigned to three groups: alcohol withdrawal, PTZ alone, and PTZ + alcohol withdrawal. On four trials, mice received either a 4.0 g/kg intraperitoneal (i.p.) injection of alcohol (alcohol withdrawal, PTZ + alcohol withdrawal groups) or saline (PTZ group) 8 hrs prior to being placed on a distinctive floor texture for a 30-min conditioning session. Five min before these sessions, mice in the PTZ and PTZ + alcohol withdrawal groups received PTZ (5.0 mg/kg; i.p.) and the alcohol withdrawal group received saline. On intervening days mice received two saline injections at the same time points prior to being placed on a different floor texture. Post-conditioning floor preference was assessed in two 60-min tests; the first test was drug-free and the second test was state-dependent. Neither alcohol withdrawal nor PTZ produced significant place conditioning. The PTZ + alcohol withdrawal group showed a significant place aversion during the state-dependent test. These data suggest that the combined stimulus properties of PTZ and alcohol withdrawal facilitated the expression of conditioned place aversion to alcohol withdrawal. PMID:20138906

  8. Neural mechanisms of high-risk decisions-to-drink in alcohol dependent women

    PubMed Central

    Arcurio, Lindsay R.; Finn, Peter R.; James, Thomas W.

    2014-01-01

    A hallmark of alcohol dependence (AD) is continuing to drink despite the risk of negative consequences. Currently, it is not known if the pattern of disordered activation in AD is more compatible with an over-sensitive reward system, a deficit in control systems, or a combination of both to produce the high risk-taking behavior observed in ADs. Here, alcohol cues were used in an ecological decisions-to-drink task that involved high- and low-risk scenarios where the chance of serious negative imagined consequences was varied. Non-alcohol cues were included as control stimuli. fMRI was used to measure BOLD signal change in 15 AD and 16 control women. This design allowed us to address two major questions concerning alcohol dependence: first, is there a specific pattern of disordered activation that drives the heightened endorsement of high-risk decisions-to-drink in ADs? And, second, is that pattern specific to decisions-to-drink or does it generalize to other appetitive and/or neutral cues? The results showed that, during high-risk decisions-to-drink, AD women activated reward circuits, cognitive control circuits, and regions of the default-mode network (DMN), while control women deactivated approach circuits and showed enhanced activation in regions of the DMN. Group differences were found only for decisions-to-drink, suggesting that they are specific to alcohol cues. Simultaneous activation of reward networks, cognitive control networks, and the DMN in AD women suggests that over-endorsement of high-risk drinking decisions by AD women may be due to a problem with switching between different neural networks. PMID:24373127

  9. Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication.

    PubMed

    Winkler, M; Skopp, G; Alt, A; Miltner, E; Jochum, Th; Daenhardt, C; Sporkert, F; Gnann, H; Weinmann, W; Thierauf, A

    2013-07-01

    The importance of direct and indirect alcohol markers to evaluate alcohol consumption in clinical and forensic settings is increasingly recognized. While some markers are used to prove abstinence from ethanol, other markers are suitable for detection of alcohol misuse. Phosphatidyl ethanol (PEth) is ranked among the latter. There is only little information about the correlation between PEth and other currently used markers (ethyl glucuronide, ethyl sulfate, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, and methanol) and about their decline during detoxification. To get more information, 18 alcohol-dependent patients in withdrawal therapy were monitored for these parameters in blood and urine for up to 19 days. There was no correlation between the different markers. PEth showed a rapid decrease at the beginning of the intervention, a slow decline after the first few days, and could still be detected after 19 days of abstinence from ethanol. PMID:23274938

  10. Haplotype-Based Study of the Association of Alcohol Metabolizing Genes with Alcohol Dependence in Four Independent Populations

    PubMed Central

    Liu, Jixia; Zhou, Zhifeng; Hodgkinson, Colin A.; Yuan, Qiaoping; Shen, Pei-Hong; Mulligan, Connie J.; Wang, Alex; Gray, Rebecca R.; Roy, Alec; Virkkunen, Matti; Goldman, David; Enoch, Mary-Anne

    2010-01-01

    Background Ethanol is metabolized by two rate limiting reactions: alcohol dehydrogenases (ADH) convert ethanol to acetaldehyde, subsequently metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of East Asians have genetic variants that significantly impair this pathway and influence alcohol dependence (AD) vulnerability. We investigated whether variation in alcohol metabolism genes might alter the AD risk in four non-East Asian populations by performing systematic haplotype association analyses in order to maximize the chances of capturing functional variation. Methods Haplotype-tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the two ALDH genes in four diverse samples that included cases (lifetime AD) and controls (no Axis 1 disorders). The case, control sample sizes were: Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American Indians: 226, 110; Southwestern American (SW) Indians: 317, 72. Results In all four populations, as well as HapMap populations, five haplotype blocks were identified across the ADH gene cluster: (1) ADH5-ADH4; (2) ADH6-ADH1A-ADH1B; (3) ADH1C; (4) intergenic; (5) ADH7. The ALDH1A1 gene was defined by four blocks and ALDH2 by one block. No haplotype or SNP association results were significant after correction for multiple comparisons; however several results, particularly for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1 and 2 (extending from intron 5 to the 3′ UTR) yin yang haplotype (haplotypes that have opposite allelic configuration) association with AD in the Finns driven by SNPs rs3764435 and rs2303317 respectively, and an ALDH1A1 block 3 (including the promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs, all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains Indians. Conclusions The systematic evaluation of

  11. Pharmacological management of alcohol dependence: from mono-therapy to pharmacogenetics and beyond.

    PubMed

    Caputo, Fabio; Vignoli, Teo; Grignaschi, Alice; Cibin, Mauro; Addolorato, Giovanni; Bernardi, Mauro

    2014-02-01

    Almost 10% of the world's population is affected by alcohol use disorders, and the treatment of alcohol dependence (AD) still remains a challenge. Patients with AD can differ in many traits. Three drugs (disulfiram, naltrexone, and acamprosate) have been approved by the FDA for the treatment of AD, and in some European countries sodium oxybate is also approved for this purpose. Combined pharmacological therapy has not provided such convincing results. Considering the fact that the "ideal" and effective drug for all types of alcoholic patients does not exists, the future challenge will be to identify a personalized approach. Recent data has shown that this objective can be achieved by investigating the genetic variability of the patient. Moreover, the use of replacement molecules can probably be considered an advantageous therapeutic opportunity (i.e. sodium oxybate). In addition, reduction of alcohol consumption is increasingly accepted as a viable treatment goal, and the use of nalmefene "as-needed" (a pharmacological approach similar to naltrexone, but, possibly, with lower hepatotoxicity) may help in the treatment of AD. Thus, it is important to stress that a pharmacological approach to treat AD should be preceded by the definition of patient characteristics; this may help in the choice of the most appropriate drug and it can be done more easily when more pharmacological options approved for the treatment of AD are also available. PMID:24182622

  12. The Association between Cue-Reactivity in the Precuneus and Level of Dependence on Nicotine and Alcohol*

    PubMed Central

    Courtney, Kelly E.; Ghahremani, Dara G.; London, Edythe D.; Ray, Lara A.

    2014-01-01

    Background Given numerous reports implicating involvement of the precuneus in cue-reactivity paradigms, the goal of this investigation was to examine the relationship between activation of the precuneus in response to drug cues and measures of subjective craving and severity of dependence in volunteers who were comorbid for alcohol and nicotine abuse. Methods Forty research participants, who all reported heavy drinking and daily smoking, were recruited (15 women; 70% Caucasian; mean age = 31.2 years) for a functional magnetic resonance imaging (fMRI) session involving a cigarette video-cues task and an alcohol taste-cues task. Mean precuneus activation from both tasks during cue presentation was subjected to bivariate correlation analyses with indices of dependence severity and subjective craving. Results Precuneus activation in the contrast of Cigarette Cues vs. Control Cues was positively correlated with scores on the Fagerström Test of Nicotine Dependence (r=0.389, p=0.016), and activation in the Alcohol Cues vs. Control Cues contrast was positively correlated with Alcohol Dependence Scale scores (r=0.338, p=0.038). No correlations with subjective craving were observed (ps>0.05). Conclusions These findings indicate that the precuneus is involved in cue reactivity for both cigarettes and alcohol, and that this involvement is moderated by severity of drug dependence. The precuneus may be a cortical locus for neuroplastic changes related to drug dependence. PMID:24880692

  13. Serotonergic Systems in the Pathophysiology of Ethanol Dependence: Relevance to Clinical Alcoholism.

    PubMed

    Marcinkiewcz, Catherine A

    2015-07-15

    Alcoholism is a progressive brain disorder that is marked by increased sensitivity to the positive and negative reinforcing properties of ethanol, compulsive and habitual use despite negative consequences, and chronic relapse to alcohol drinking despite repeated attempts to reduce intake or abstain from alcohol. Emerging evidence from preclinical and clinical studies implicates serotonin (5-hydroxytryptamine; 5-HT) systems in the pathophysiology of alcohol dependence, suggesting that drugs targeting 5-HT systems may have utility in the treatment of alcohol use disorders. In this Review, we discuss the role of 5-HT systems in alcohol dependence with a focus on 5-HT interactions with neural circuits that govern all three stages of the addiction cycle. We attempt to clarify how 5-HT influences circuit function at these different stages with the goal of identifying neural targets for pharmacological treatment of this debilitating disorder. PMID:25654315

  14. Resting state connectivity in alcohol dependent patients and the effect of repetitive transcranial magnetic stimulation.

    PubMed

    Jansen, Jochem M; van Wingen, Guido; van den Brink, Wim; Goudriaan, Anna E

    2015-12-01

    Alcohol dependence is thought to result from an overactive neural motivation system and a deficient cognitive control system, and rebalancing these systems may mitigate excessive alcohol use. This study examines the differences in functional connectivity of the fronto-parietal cognitive control network (FPn) and the motivational network (striatum and orbitofrontal cortex) between alcohol dependent patients (ADPs) and healthy controls (HCs), and the effect of repetitive transcranial magnetic stimulation (rTMS) on these networks. This randomized controlled trial included 38 ADPs and 37 HCs, matched on age, gender and education. Participants were randomly assigned to sham or right dorsolateral prefrontal cortex (dlPFC) stimulation with rTMS. A 3T resting state functional Magnetic Resonance Imaging (fMRI) scan was acquired before and after active or sham 10Hz rTMS. Group differences of within and between network connectivity and the effect of rTMS on network connectivity was assessed using independent component analysis. Results showed higher connectivity within the left FPn (p=0.012) and the left fronto-striatal motivational network (p=0.03) in ADPs versus HCs, and a further increase in connectivity within the left FPn after active stimulation in ADPs. ADPs also showed higher connectivity between the left and the right FPns (p=0.025), and this higher connectivity was related to fewer alcohol related problems (r=0.30, p=0.06). The results show higher within and between network connectivity in ADPs and a further increase in fronto-parietal connectivity after right dlPFC rTMS in ADPs, suggesting that frontal rTMS may have a beneficial influence on cognitive control and may result in lower relapse rates. PMID:26481907

  15. Talking out of alcoholism: results from a survey of Alcoholics Anonymous in England and Wales

    PubMed Central

    Henry, Stuart; Robinson, David

    1978-01-01

    A national survey of Alcoholics Anonymous (AA) produced data on the way AA members talk about their experiences and the role this plays in achieving and maintaining sobriety. The survey was based on self-completion questionnaires given to one in four members attending meetings of a one in ten random sample of AA groups operating in England and Wales. Only 1·8 per cent of current members had never spoken at a meeting, while 62·5 per cent spoke regularly. Hearing other people's personal stories was felt by members to be the most useful part of AA meetings. At some time 81·9 per cent of members had told their own story and there was some relationship between dropping out and not telling personal stories. The great majority of those who had told stories reported changes in their content over time; 58·0 per cent of these changes involved a shift of emphasis from drinking to recovery. The results suggest that AA enables people to change the way they perceive and evaluate themselves. It enables them to talk themselves out of alcoholism. PMID:702456

  16. Low Digit Ratio 2D∶4D in Alcohol Dependent Patients

    PubMed Central

    Lenz, Bernd; Kraus, Thomas; Sperling, Wolfgang; Bayerlein, Kristina; Biermann, Teresa; Stoessel, Christina

    2011-01-01

    The ratio of the lengths of the second and fourth finger (2D∶4D) has been described as reflecting the degree of prenatal androgen exposure in humans. 2D∶4D is smaller for males than females and is associated with traits such as left-handedness, physical aggression, attention-deficit-hyperactivity disorder and a genetic polymorphism of the androgen receptor. All of these traits are known to be correlated to the vulnerability for alcohol dependency. We therefore hypothesized low 2D∶4D in patients with alcohol dependency. In the present study on 131 patients suffering from alcohol dependency and 185 healthy volunteers, we found that alcohol dependent patients had smaller 2D∶4D ratios compared to controls with preserved sexual dimorphism but with reduced right-left differences. The detection of alcohol dependency based on 2D∶4D ratios was most accurate using the right hand of males (ROC-analysis: AUC 0.725, sensitivity 0.667, specificity 0.723). These findings provide novel insights into the role of prenatal androgen exposure in the development of alcohol dependency and for the use of 2D∶4D as a possible trait marker in identifying patients with alcohol dependency. PMID:21547078

  17. Low digit ratio 2D:4D in alcohol dependent patients.

    PubMed

    Kornhuber, Johannes; Erhard, Gabriele; Lenz, Bernd; Kraus, Thomas; Sperling, Wolfgang; Bayerlein, Kristina; Biermann, Teresa; Stoessel, Christina

    2011-01-01

    The ratio of the lengths of the second and fourth finger (2D∶4D) has been described as reflecting the degree of prenatal androgen exposure in humans. 2D∶4D is smaller for males than females and is associated with traits such as left-handedness, physical aggression, attention-deficit-hyperactivity disorder and a genetic polymorphism of the androgen receptor. All of these traits are known to be correlated to the vulnerability for alcohol dependency. We therefore hypothesized low 2D∶4D in patients with alcohol dependency. In the present study on 131 patients suffering from alcohol dependency and 185 healthy volunteers, we found that alcohol dependent patients had smaller 2D∶4D ratios compared to controls with preserved sexual dimorphism but with reduced right-left differences. The detection of alcohol dependency based on 2D∶4D ratios was most accurate using the right hand of males (ROC-analysis: AUC 0.725, sensitivity 0.667, specificity 0.723). These findings provide novel insights into the role of prenatal androgen exposure in the development of alcohol dependency and for the use of 2D∶4D as a possible trait marker in identifying patients with alcohol dependency. PMID:21547078

  18. Alcohol

    MedlinePlus

    ... Text Size: A A A Listen En Español Alcohol Wondering if alcohol is off limits with diabetes? Most people with diabetes can have a moderate amount of alcohol. Research has shown that there can be some ...

  19. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  20. On the relationship between emotional state and abnormal unfairness sensitivity in alcohol dependence

    PubMed Central

    Brevers, Damien; Noël, Xavier; Hanak, Catherine; Verbanck, Paul; Kornreich, Charles

    2015-01-01

    Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls performed an ultimatum game (UG), in which participants had to respond to take-it-or-leave-it offers, ranging from fair to unfair and made by a fictive proposer. Emotional state was recorded during UG offers presentation and was indexed by the amplitude of skin conductance response (SCR). Results showed that AD decided to reject unfair offers more frequently than their controls, confirming previous data. The proportion of rejected unfair UG offers was correlated with SCR, in the AD but not in the control group. This finding suggests that deciding to accept or reject unfair UG offers is influenced by arousal-affective activity in AD, but not in controls. Heightened emotional reactivity may have driven AD to punish the proposer rather than acting as a rational economic agent. An implication of present findings is that AD might have difficult to cope with unfair situations triggered by social interactions. Future studies are needed in order to examine whether—emotional and behavioral—reactivity to unfairness during the UG could impact alcohol consumption and relapse in AD. PMID:26217293

  1. 49 CFR 40.255 - What happens next after the alcohol confirmation test result?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Alcohol Confirmation Tests § 40.255... means), you must establish a mechanism to establish the identity of the BAT sending you the results....

  2. A randomized, controlled study of treatment for alcohol dependence in patients awaiting liver transplantation.

    PubMed

    Weinrieb, Robert M; Van Horn, Deborah H A; Lynch, Kevin G; Lucey, Michael R

    2011-05-01

    Alcohol is the second most common cause of cirrhosis necessitating liver transplantation in the United States, yet rates of posttransplant drinking approach 50% and no controlled clinical trials of alcoholism treatment exist in this population. Eligible patients were randomly assigned to receive Motivational Enhancement Therapy (MET), or referral to local treatment sources ("treatment as usual" [TAU]). Addictive behavior, mood states, and general health were compared. Candor concerning alcohol use was encouraged by keeping drinking questionnaires in confidence, except in medical emergencies. Ninety-one subjects were studied; 46 received MET, 45 received TAU, 29 proceeded to transplantation (MET, n = 13; TAU, n = 16). A total of 69 subjects completed 24 weeks of observation, and 25 subjects were assessed at 96 weeks. No difference in study attendance was observed, but significantly more MET subjects attended 1 or more treatment sessions. Twenty-three subjects (25% of sample) drank after randomization but before transplant. Excluding an extreme outlier, MET drinkers had significantly fewer drinks per drinking days than TAU drinkers. Neither treatment plan resulted in significant variances in measures of psychosocial health. In conclusion, although MET afforded no significant benefit over TAU for mood or general health outcomes, this study provides some degree of support for MET to limit the quantity and frequency of pretransplant alcohol consumption among liver transplant candidates with alcohol dependence. However, because of the limited number of study subjects, these data must be interpreted cautiously. Further research to validate our findings or to identify better methods to identify and intervene with patients at risk of pretransplant and posttransplant drinking should continue. PMID:21506242

  3. 49 CFR 219.611 - Test result indicating prohibited alcohol concentration; procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Test result indicating prohibited alcohol... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.611 Test result indicating prohibited...

  4. Cross-Cultural Validity of Alcohol Dependence across Hispanics and Non-Hispanic Caucasians

    ERIC Educational Resources Information Center

    Carle, Adam C.

    2008-01-01

    Confirmatory factor analyses for ordered-categorical measures probed for differential item functioning on a standardized measure of alcohol dependence across Hispanics (n = 834) and non-Hispanic Caucasians (n = 14,001) in a nationally representative survey of alcohol use in the United States conducted in 1992. Analyses investigated whether 30…

  5. Industrialization Stresses, Alcohol Abuse & Substance Dependence: Differential Gender Effects in a Kenyan Rural Farming Community

    ERIC Educational Resources Information Center

    Walt, Lisa C.; Kinoti, Elias; Jason, Leonard A.

    2013-01-01

    Developing countries' industrialization and urbanization attempts have been linked to psychological distress and alcohol abuse. We used Hobfoll's COR theory to examine the relationship between gender, perceived resource loss (an indicator of industrialization stress), and alcohol abuse and dependence in a sample of Kenyan rural village men and…

  6. Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.

    PubMed

    Garbusow, Maria; Schad, Daniel J; Sebold, Miriam; Friedel, Eva; Bernhardt, Nadine; Koch, Stefan P; Steinacher, Bruno; Kathmann, Norbert; Geurts, Dirk E M; Sommer, Christian; Müller, Dirk K; Nebe, Stephan; Paul, Sören; Wittchen, Hans-Ulrich; Zimmermann, Ulrich S; Walter, Henrik; Smolka, Michael N; Sterzer, Philipp; Rapp, Michael A; Huys, Quentin J M; Schlagenhauf, Florian; Heinz, Andreas

    2016-05-01

    In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. PMID:25828702

  7. Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals

    PubMed Central

    Schacht, Joseph P.; Anton, Raymond F.; Randall, Patrick K.; Li, Xingbao; Henderson, Scott; Myrick, Hugh

    2014-01-01

    Rationale The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. Objectives This pilot study tested varenicline’s effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Methods Thirty-five such individuals (mean age = 30, 57% male, 76% heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Results Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. Conclusions These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption. PMID:24647921

  8. Alcoholic cardiomyopathy : The result of dosage and individual predisposition.

    PubMed

    Maisch, B

    2016-09-01

    The individual amount of alcohol consumed acutely or chronically decides on harm or benefit to a person's health. Available data suggest that one to two drinks in men and one drink in women will benefit the cardiovascular system over time, one drink being 17.6 ml 100 % alcohol. Moderate drinking can reduce the incidence and mortality of coronary artery disease, heart failure, diabetes, ischemic and hemorrhagic stroke. More than this amount can lead to alcoholic cardiomyopathy, which is defined as alcohol toxicity to the heart muscle itself by ethanol and its metabolites. Historical examples of interest are the Munich beer heart and the Tübingen wine heart. Associated with chronic alcohol abuse but having different etiologies are beriberi heart disease (vitamin B1 deficiency) and cardiac cirrhosis as hyperdynamic cardiomyopathies, arsenic poising in the Manchester beer epidemic, and cobalt intoxication in Quebec beer drinker's disease. Chronic heavy alcohol abuse will also increase blood pressure and cause a downregulation of the immune system that could lead to increased susceptibility to infections, which in turn could add to the development of heart failure. Myocardial tissue analysis resembles idiopathic cardiomyopathy or chronic myocarditis. In the diagnostic work-up of alcoholic cardiomyopathy, the confirmation of alcohol abuse by carbohydrate deficient transferrin (CDT) and increased liver enzymes, and the involvement of the heart by markers of heart failure (e.g., NT-proBNP) and of necrosis (e.g., troponins or CKMb) is mandatory. Treatment of alcoholic cardiomyopathy consists of alcohol abstinence and heart failure medication. PMID:27582365

  9. The Genetics of Alcohol Dependence: Advancing Towards Systems-based Approaches

    PubMed Central

    Palmer, RHC; McGeary, JE; Francazio, S; Raphael, BJ; Lander, AD; Heath, AC; Knopik, VS

    2012-01-01

    BACKGROUND Personalized treatment for psychopathologies, in particular alcoholism, is highly dependent upon our ability to identify patterns of genetic and environmental effects that influence a person’s risk. Unfortunately, array-based whole genome investigations into heritable factors that explain why one person becomes dependent upon alcohol and another does not, have indicated that alcohol’s genetic architecture is highly complex. That said, uncovering and interpreting the missing heritability in alcohol genetics research has become all the more important, especially since the problem may extend to our inability to model the cumulative and combinatorial relationships between common and rare genetic variants. As numerous studies begin to illustrate the dependency of alcohol pharmacotherapies on an individual’s genotype, the field is further challenged to identify new ways to transcend agnostic genomewide association approaches. We discuss insights from genetic studies of alcohol related diseases, as well as issues surrounding alcohol’s genetic complexity and etiological heterogeneity. Finally, we describe the need for innovative systems-based approaches (Systems Genetics) that can provide additional statistical power that can enhance future gene-finding strategies and help to identify heretofore-unrealized mechanisms that may provide new targets for prevention/treatments efforts. Emerging evidence from early studies suggest that Systems Genetics has the potential to organize our neurological, pharmacological, and genetic understanding of alcohol dependence into a biologically plausible framework that represents how perturbations across evolutionarily robust biological systems determine susceptibility to alcohol dependence. PMID:22854292

  10. Alcohol

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Alcohol KidsHealth > For Kids > Alcohol Print A A A Text Size What's in ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...