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Sample records for alcohol dependence represents

  1. Tianeptine and alcohol dependence.

    PubMed

    Favre, J D; Guelfi-Sozzi, C; Delalleau, B; Lôo, H

    1997-10-01

    Several arguments are in favour of the use of antidepressant drugs in alcohol-dependent patients, especially those acting on the serotoninergic system: (1) neurochemical data indicate the interaction between alcohol and 5-HT metabolism, (2) pharmacological studies show an improvement in the behaviour of alcoholized animals treated with antidepressants, (3) depression is a frequent disease in alcoholic patients. Tianeptine has been shown to be active in the treatment of depression in patients with history of alcohol abuse or dependence. In a first double-blind study performed versus amitryptiline, depression after withdrawal was improved by tianeptine, and biological abnormalities usually related to chronic alcohol intake tended to decrease. Similar results were found in an open study carried out on 277 alcoholic patients treated for 1 year. As these patients were depressed, no definite conclusion could be drawn from these results in respect of a specific action of tianeptine on alcohol dependence. Thus, a multicentre double-blind study has been performed which compared tianeptine (12.5 mg t.i.d) and placebo in 342 non-depressed patients fulfilling DSM-III-R criteria for Psychoactive Substance Dependence (alcohol). Other inclusion criteria were: daily alcohol intake higher than 80 g, minimum score of 3 on the Short-Mast Questionnaire, mean corpuscular volume above 98 fl and/or gamma Gt more than twice the upper limit of normal. The patients were treated for 9 months. The intention-to-treat population and the per protocol population were made up of 327 patients and 111 patients, respectively. The main efficacy criterion was the absence of alcoholic relapse (abstinence) defined by the patient's statements, the investigators clinical judgement and some biological parameters: alcohol blood levels, gamma Gt levels. Secondary criteria were the evolution of the alcohol consumption in the patients who relapsed, cumulative abstinence duration, a visual analogue scale for the

  2. [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

  3. Alcohol dependence--classificatory considerations.

    PubMed

    Lesch, O M; Ades, J; Badawy, A; Pelc, I; Sasz, H

    1993-01-01

    The term alcoholism or alcohol dependence has acquired a broad range of meanings. The Plinius Maior Society herewith presents new classificatory considerations and suggests additional recording of special dimensions according to the individual hypothesis and design of a study.

  4. 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

  5. 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

  6. Interpersonal dependency in alcoholic and obese men.

    PubMed

    Mills, J K

    1995-06-01

    While psychological conflict about dependency needs of alcoholic and obese persons has been widely observed, few studies have examined differences in dependency characteristics between these clinical groups. The Interpersonal Dependency Inventory was administered to 22 alcoholic and 8 morbidly obese men in intensive treatment for alcohol and obesity. The original hypothesis that alcoholic and obese men would show similar dependency needs was supported. Dependency correlates of personality may serve as useful predictor variables in the clinical treatment of alcoholic and obese persons.

  7. 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

  8. Driving Performance Under Alcohol in Simulated Representative Driving Tasks

    PubMed Central

    Kenntner-Mabiala, Ramona; Kaussner, Yvonne; Jagiellowicz-Kaufmann, Monika; Hoffmann, Sonja; Krüger, Hans-Peter

    2015-01-01

    Abstract Comparing drug-induced driving impairments with the effects of benchmark blood alcohol concentrations (BACs) is an approved approach to determine the clinical relevance of findings for traffic safety. The present study aimed to collect alcohol calibration data to validate findings of clinical trials that were derived from a representative test course in a dynamic driving simulator. The driving performance of 24 healthy volunteers under placebo and with 0.05% and 0.08% BACs was measured in a double-blind, randomized, crossover design. Trained investigators assessed the subjects’ driving performance and registered their driving errors. Various driving parameters that were recorded during the simulation were also analyzed. Generally, the participants performed worse on the test course (P < 0.05 for the investigators’ assessment) under the influence of alcohol. Consistent with the relevant literature, lane-keeping performance parameters were sensitive to the investigated BACs. There were significant differences between the alcohol and placebo conditions in most of the parameters analyzed. However, the total number of errors was the only parameter discriminating significantly between all three BAC conditions. In conclusion, data show that the present experimental setup is suitable for future psychopharmacological research. Thereby, for each drug to be investigated, we recommend to assess a profile of various parameters that address different levels of driving. On the basis of this performance profile, the total number of driving errors is recommended as the primary endpoint. However, this overall endpoint should be completed by a specifically sensitive parameter that is chosen depending on the effect known to be induced by the tested drug. PMID:25689289

  9. 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

  10. 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,…

  11. Alcohol consumption, alcohol dependence and related harms in Spain, and the effect of treatment-based interventions on alcohol dependence.

    PubMed

    Rehm, Jürgen; Rehm, Maximilien X; Shield, Kevin D; Gmel, Gerrit; Gual, Antoni

    2013-01-01

    Alcohol consumption in Spain has traditionally followed the Mediterranean drinking pattern, featuring daily drinking with meals, beer as the preferred beverage, and comparatively little drinking to intoxication. Alcohol dependence (AD), one of the most detrimental disorders caused by alcohol, was prevalent in 0.2% of women and 1.2% of men, corresponding to 31,200 women and 186,000 men in Spain with AD in 2005 in the age group of 15 to 64 year. These prevalence estimates of alcohol dependence are likely underestimated due to limitations in the World Mental Health Survey which cannot be fully corrected for; however, the estimates of AD for Spain represent the most accurate and up to date estimates available. Alcohol creates a significant health burden in Spain with 11.3 premature deaths in women per 100,000 aged 15 to 64 years, and 40.9 premature deaths in men per 100,000 in the same age group were due to alcohol consumption (data for 2004). This amounts to 8.4% of all female deaths and 12.3% of all the male deaths in this age group being attributable to alcohol consumption. A large percentage of these harms were due to heavy alcohol consumption and AD. AD is undertreated in Spain, with less than 10% of all people with AD treated. For those who are treated, psychotherapy is the most utilized form of treatment to avoid relapse. If 40% of AD patients in Spain were treated with pharmacological treatment (the most effective treatment method), 2.2% of female and 6.2% of male deaths due to AD would be prevented within one year. Thus by increasing treatment rates is an important means of reducing the alcohol-attributable mortality and health burden in Spain.

  12. ▼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.

  13. Brain pathways to recovery from alcohol dependence.

    PubMed

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

    2015-08-01

    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.

  14. 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

  15. Alcohol use dependence in fragile X syndrome

    PubMed Central

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-01-01

    Summary Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures. PMID:27672544

  16. Alcohol use dependence in fragile X syndrome.

    PubMed

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-08-01

    Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures. PMID:27672544

  17. Alcohol use dependence in fragile X syndrome

    PubMed Central

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-01-01

    Summary Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures.

  18. 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

  19. Alcohol dependence as a chronic pain disorder

    PubMed Central

    Egli, Mark; Koob, George F.; Edwards, Scott

    2013-01-01

    Dysregulation of pain neurocircuitry and neurochemistry has been increasingly recognized as playing a critical role in a diverse spectrum of diseases including migraine, fibromyalgia, depression, and PTSD. Evidence presented here supports the hypothesis that alcohol dependence is among the pathologies arising from aberrant neurobiological substrates of pain. In this review, we explore the possible influence of alcohol analgesia and hyperalgesia in promoting alcohol misuse and dependence. We examine evidence that neuroanatomical sites involved in the negative emotional states of alcohol dependence also play an important role in pain transmission and may be functionally altered under chronic pain conditions. We also consider possible genetic links between pain transmission and alcohol dependence. We propose an allostatic load model in which episodes of alcohol intoxication and withdrawal, traumatic stressors, and injury are each capable of dysregulating an overlapping set of neural substrates to engender sensory and affective pain states that are integral to alcohol dependence and comorbid conditions such as anxiety, depression, and chronic pain. PMID:22975446

  20. 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

  1. Representing higher-order dependencies in networks

    PubMed Central

    Xu, Jian; Wickramarathne, Thanuka L.; Chawla, Nitesh V.

    2016-01-01

    To ensure the correctness of network analysis methods, the network (as the input) has to be a sufficiently accurate representation of the underlying data. However, when representing sequential data from complex systems, such as global shipping traffic or Web clickstream traffic as networks, conventional network representations that implicitly assume the Markov property (first-order dependency) can quickly become limiting. This assumption holds that, when movements are simulated on the network, the next movement depends only on the current node, discounting the fact that the movement may depend on several previous steps. However, we show that data derived from many complex systems can show up to fifth-order dependencies. In these cases, the oversimplifying assumption of the first-order network representation can lead to inaccurate network analysis results. To address this problem, we propose the higher-order network (HON) representation that can discover and embed variable orders of dependencies in a network representation. Through a comprehensive empirical evaluation and analysis, we establish several desirable characteristics of HON, including accuracy, scalability, and direct compatibility with the existing suite of network analysis methods. We illustrate how HON can be applied to a broad variety of tasks, such as random walking, clustering, and ranking, and we demonstrate that, by using it as input, HON yields more accurate results without any modification to these tasks. PMID:27386539

  2. Representing higher-order dependencies in networks.

    PubMed

    Xu, Jian; Wickramarathne, Thanuka L; Chawla, Nitesh V

    2016-05-01

    To ensure the correctness of network analysis methods, the network (as the input) has to be a sufficiently accurate representation of the underlying data. However, when representing sequential data from complex systems, such as global shipping traffic or Web clickstream traffic as networks, conventional network representations that implicitly assume the Markov property (first-order dependency) can quickly become limiting. This assumption holds that, when movements are simulated on the network, the next movement depends only on the current node, discounting the fact that the movement may depend on several previous steps. However, we show that data derived from many complex systems can show up to fifth-order dependencies. In these cases, the oversimplifying assumption of the first-order network representation can lead to inaccurate network analysis results. To address this problem, we propose the higher-order network (HON) representation that can discover and embed variable orders of dependencies in a network representation. Through a comprehensive empirical evaluation and analysis, we establish several desirable characteristics of HON, including accuracy, scalability, and direct compatibility with the existing suite of network analysis methods. We illustrate how HON can be applied to a broad variety of tasks, such as random walking, clustering, and ranking, and we demonstrate that, by using it as input, HON yields more accurate results without any modification to these tasks. PMID:27386539

  3. Representing operations procedures using temporal dependency networks

    NASA Technical Reports Server (NTRS)

    Fayyad, Kristina E.; Cooper, Lynne P.

    1993-01-01

    DSN Link Monitor & Control (LMC) operations consist primarily of executing procedures to configure, calibrate, test, and operate a communications link between an interplanetary spacecraft and its mission control center. Currently the LMC operators are responsible for integrating procedures into an end-to-end series of steps. The research presented in this paper is investigating new ways of specifying operations procedures that incorporate the insight of operations, engineering, and science personnel to improve mission operations. The paper describes the rationale for using Temporal Dependency Networks (TDN's) to represent the procedures, a description of how the data is acquired, and the knowledge engineering effort required to represent operations procedures. Results of operational tests of this concept, as implemented in the LMC Operator Assistant Prototype (LMCOA), are also presented.

  4. National Council on Alcoholism and Drug Dependence

    MedlinePlus

    ... 2016 A new study finds the number of young children and teens hospitalized … NCADD Joins the Global #GIVINGTUESDAY Mo… 3 November, 2016 The National Council on Alcoholism and Drug Dependence (NCADD) has joi… State Votes ...

  5. 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

  6. Molecular and genetic determinants of alcohol dependence.

    PubMed

    Awofala, Awoyemi A

    2013-01-01

    Alcohol dependence is a complex disorder affecting all social and ethnic groups. Although the scientific understanding of the mechanism governing this multifactorial disease is still in its infancy, understanding its biological bases, including the potential contribution of genetic factors, is key to characterizing individual's risk and developing efficacious therapeutic target to combat the disease. This review provides an overview of different approaches that are being increasingly integrated to extend our knowledge of the genetic underpinnings of alcohol dependence.

  7. [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

  8. 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.

  9. 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.

  10. 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

  11. Pharmacological treatment of alcohol abuse/dependence with psychiatric comorbidity.

    PubMed

    Le Fauve, Charlene E; Litten, Raye Z; Randall, Carrie L; Moak, Darlene H; Salloum, Ihsan M; Green, Alan I

    2004-02-01

    This article represents the proceedings of a symposium at the 2003 annual meeting RSA in Fort Lauderdale, FL. It was organized and cochaired by Charlene E. Le Fauve and Carrie L. Randall. The presentations were (1) Introduction, by Charlene E. Le Fauve and Raye Z. Litten; (2) Treatment of co-occurring alcohol use and anxiety disorders, by Carrie L. Randall and Sarah W. Book; (3) Pharmacological treatment of alcohol dependent patients with comorbid depression, by Darlene H. Moak; (4) Efficacy of valproate in bipolar alcoholics: a double blind, placebo-controlled study, by Ihsan M. Salloum, Jack R. Cornelius, Dennis C. Daley, Levent Kirisci, Johnathan Himmelhoch, and Michael E. Thase; (5) Alcoholism and schizophrenia: effects of antipsychotics, by Alan I. Green, Robert E. Drake, Suzannah V. Zimmet, Rael D. Strous, Melinda Salomon, and Mark Brenner; and (6) Conclusions, by Charlene E. Le Fauve; discussant, Raye Z. Litten. Alcohol-dependent individuals have exceptionally high rates of co-occurring psychiatric disorders. Although this population is more likely to seek alcoholism treatment than noncomorbid alcoholics, the prognosis for treatment is often poor, particularly among patients with more severe psychiatric illnesses. Development of effective interventions to treat this population is in the early stages of research. Although the interaction between the psychiatric condition and alcoholism is complex, progress has been made. The NIAAA has supported a number of state-of-the-art pharmacological and behavioral trials in a variety of comorbid psychiatric disorders. Some of these trials have been completed and are presented here. The symposium presented some new research findings from clinical studies with the aim of facilitating the development of treatments that improve alcohol and psychiatric outcomes among individuals with alcohol-use disorders and co-occurring psychiatric disorders. The panel focused on social anxiety disorder, depression, bipolar disorder, and

  12. 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

  13. Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

    ERIC Educational Resources Information Center

    Graves, Erin; Goodwin, Lloyd R., Jr.

    2008-01-01

    Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…

  14. 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

  15. 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

  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. 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.

  18. 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)

  19. Is alcohol dependence best viewed as a chronic relapsing disorder?

    PubMed

    Cunningham, John A; McCambridge, Jim

    2012-01-01

    This 'For Debate' paper starts by recognizing the growing trend towards considering alcohol dependence as a chronic relapsing disorder. We argue that the adoption of this model results from focusing on those in treatment for alcohol dependence rather than considering the larger number of people in the general population who meet criteria for alcohol dependence at some point in their lives. The majority of the general population who ever experience alcohol dependence do not behave as though they have a chronic relapsing disorder: they do not seek treatment, resolve their dependence themselves and do not relapse repeatedly. We suggest that caution is therefore needed in using the chronic relapsing disorder label. Our primary concerns are that this formulation privileges biological aspects of dependence to the detriment of psychological and social contributions, it inhibits much-needed developments in understanding alcohol dependence and leads to inefficient distributions of public health and clinical care resources for alcohol dependence. We invite debate on this issue.

  20. Diagnosing alcohol abuse in alcohol dependent individuals: diagnostic and clinical implications

    PubMed Central

    Ray, Lara A.; Hutchison, Kent E.; Leventhal, Adam M.; Miranda, Robert; Francione, Caren; Chelminski, Iwona; Young, Diane; Zimmerman, Mark

    2013-01-01

    In DMS-IV, the diagnosis of alcohol abuse is precluded by the diagnosis of alcohol dependence. The goal of this study was to examine the diagnostic and clinical implications of diagnosing alcohol abuse among alcohol dependent individuals. Treatment-seeking psychiatric outpatients with a lifetime history of alcohol dependence (n = 544), some of whom (n = 45) did not meet lifetime criteria for alcohol abuse completed in-depth, face-to-face, semi-structured clinical assessments of DSM-IV axis I and axis II psychopathology. Alcohol dependent patients who did not meet criteria for alcohol abuse were significantly more likely to be female, have a later age of onset for alcohol dependence, have fewer dependence symptoms, and have a lower rate of positive family history for alcoholism, and were less likely to report a lifetime history of DSM-IV drug use disorders and PTSD. These findings suggest that diagnosing alcohol abuse among alcohol dependent patients may be clinically useful as an index of severity and higher likelihood of comorbid drug abuse and dependence. Future studies are needed to establish whether these differences are clinically significant in terms of the course of the disorder and response to treatment. PMID:19362427

  1. 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…

  2. 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

  3. Neuroimaging in Alcohol and Drug Dependence

    PubMed Central

    Niciu, Mark J.

    2014-01-01

    Neuroimaging, including PET, MRI, and MRS, is a powerful approach to the study of brain function. This article reviews neuroimaging findings related to alcohol and other drugs of abuse that have been published since 2011. Uses of neuroimaging are to characterize patients to determine who will fare better in treatment and to investigate the reasons underlying the effect on outcomes. Neuroimaging is also used to characterize the acute and chronic effects of substances on the brain and how those effects are related to dependence, relapse, and other drug effects. The data can be used to provide encouraging information for patients, as several studies have shown that long-term abstinence is associated with at least partial normalization of neurological abnormalities. PMID:24678450

  4. The community reinforcement approach with homeless alcohol-dependent individuals.

    PubMed

    Smith, J E; Meyers, R J; Delaney, H D

    1998-06-01

    Homeless alcohol-dependent individuals were randomly assigned to receive either a behavioral intervention (i.e., the Community Reinforcement Approach [CRA]) or the standard treatment (STD) at a large day shelter. Ninety-one men and 15 women participated. The majority of participants were White (64%), but both Hispanic (19%) and Native American (13%) individuals were represented as well. Overall, the decline in drinking levels from intake through follow-ups was significant. As predicted, CRA participants significantly outperformed STD group members on drinking measures across the 5 follow-ups, which ranged from 2 months to 1 year after intake. Both conditions showed marked improvement in employment and housing stability.

  5. [Treatment processes of pre-alcoholism and alcohol dependence targeted towards drinking reduction].

    PubMed

    Yoshimura, Atsushi; Maesato, Hitoshi; Hisatomi, Nobuko; Higuchi, Susumu

    2013-02-01

    Since the 1990s, we have suggested the concept of pre-alcoholism which encompasses patients who have drunk a great deal of alcohol leading to alcohol related problems such as health issues, domestic violence, drunken driving and black-outs. Pre-alcoholism excludes alcohol-dependent patients who have experienced continuous drinking or withdrawal symptoms. We have treated many outpatients with pre-alcoholism for several years. Our regimen demands that the patients must be abstinent for half a year at the beginning of their treatment. After half a year they can choose whether they will continue to be abstinent or they will resume drinking with the aim of reducing their total alcohol consumption. The study clarified the character of pre-alcoholism by investigation of the patients' background and re-diagnosis of the patients based on the International Classification of Diseases, 10th Revision (ICD-10). A remarkable ratio of pre-alcoholic patients was diagnosed with alcohol dependence under ICD-10. We classified pre-alcoholic patients into two groups, one diagnosed as having ICD-10-classed alcohol dependence and the other which did not fulfill the ICD-10 diagnostic criteria of alcohol dependence, and examined the therapeutic processes of the two groups. It was shown that most pre-alcoholic patients could finally take required courses of treatment by themselves without regard to diagnosis under ICD-10, even if they chose any treatment and made alcohol related mistakes on the way. Our findings suggested that pre-alcoholic patients, a portion of whom may have exhibited mild alcohol dependence, could select drinking reduction as a primary goal of treatment after a certain period of abstinence.

  6. Psychosocial predictors of impulsivity in alcohol-dependent patients

    PubMed Central

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

    2012-01-01

    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 the study was to identify psychosocial factors increasing the level of impulsivity in alcoholics. Levels of impulsivity were measured in 304 alcohol-dependent patients. Stop-signal task was used to assess behavioral impulsivity, and 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 were observed. Patients who reported childhood sexual or physical abuse, lower social support, more severe course of alcohol dependence were more impulsive, especially in 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

  7. 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.

  8. 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

  9. Impulsivity, risky behaviors and accidents in alcohol-dependent patients.

    PubMed

    Jakubczyk, Andrzej; Klimkiewicz, Anna; Wnorowska, Anna; Mika, Katarzyna; Bugaj, Marcin; Podgórska, Anna; Barry, Kristen; Blow, Frederic C; Brower, Kirk J; Wojnar, Marcin

    2013-03-01

    Impulsivity and alcohol drinking are both considered as important predictors of unintentional as well as intentional injuries. However, relationships of impulsivity with risky behaviors and a history of accidents have not been investigated in alcohol dependence. The aim of this study was to analyze relationships between the frequency of risky behaviors and level of behavioral as well as cognitive impulsivity in alcohol-dependent patients. By means of Barratt's Impulsiveness Scale (BIS) and stop-signal task, the levels of cognitive and behavioral impulsivity among 304 alcohol-dependent patients were measured. Also, patients were asked to answer questions from the Short Inventory of Problems applying to risky behaviors and accidents after alcohol drinking. In addition participants completed a questionnaire to assess frequency of other behaviors from the analyzed spectrum (use of other drugs, driving or aggressive behavior after alcohol drinking). The statistical analysis revealed a significant association between impulsivity and frequency of risky behaviors in alcohol-dependent patients. Individuals with higher scores in BIS behaved more frequently in a risky way and had significantly more accidents after alcohol drinking. The association with risky behaviors was strongest for non-planning and attentional impulsivity subscales, whereas frequency of accidents was particularly associated with motor impulsivity. A multivariate analysis revealed that impulsivity was the most important predictor of risky behaviors, but did not significantly predict a history of accidents. Our study confirms that impulsivity is an important correlate of risky behaviors in alcohol-dependent individuals, along with global psychopathology and severity of alcohol dependence.

  10. The psychosocial work environment and alcohol dependence: a prospective study

    PubMed Central

    Head, J; Stansfeld, S; Siegrist, J

    2004-01-01

    Aims: To examine whether a stressful psychosocial work environment predicts alcohol dependence. Methods: Alcohol dependence of participants in the Whitehall II occupational cohort of London based civil servants (1985–88) was measured in 1991–93 using the CAGE questionnaire. The psychosocial work environment was measured by self report questions on the job demand-support-control model and on the model of effort-reward imbalance. Potential mediators including physical illness and poor mental health (GHQ) were measured at follow up in 1989. Results: Effort-reward imbalance at work was associated with alcohol dependence in men after adjustment for employment grade and other baseline factors related to alcohol dependence. Although effort-reward imbalance predicted future longstanding illness, poor mental health and negative aspects of close relationships, the association between effort-reward imbalance and alcohol dependence in men was only partially mediated through these health and social support measures. In women, low decision latitude was related to alcohol dependence to some extent, but alcohol dependence among women was more prevalent in higher occupational grades. Men with high job demands or with low work social supports had a slightly reduced risk of alcohol dependence. No association was found between objectively assessed demands, job control, and alcohol dependence in either men or women. Conclusion: A stressful psychosocial work environment in terms of effort-reward imbalance was found to be a risk factor for alcohol dependence in men. In view of the public health importance of alcohol dependence in working populations these findings call for more emphasis on psychosocial factors in occupational health research and prevention. PMID:14985516

  11. 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)

  12. Craving and Physiological Reactivity to Trauma and Alcohol Cues in PTSD and Alcohol Dependence

    PubMed Central

    Coffey, Scott F.; Schumacher, Julie A.; Stasiewicz, Paul R.; Henslee, Amber M.; Baillie, Lauren E.; Landy, Noah

    2013-01-01

    The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) has been firmly established. Although laboratory studies have examined self-reported craving in response to trauma and alcohol cues, no studies have reported on alcohol-related physiological responding in response to trauma cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol-related responding (e.g., salivation, craving) in individuals with PTSD and AD (n=40). Participants displayed reactivity to both trauma and alcohol cues when compared to neutral cues, including increased self-reported craving and distress, as well as, greater salivation. These findings suggest that through repeated pairings of trauma memories and alcohol consumption, salivation may become classically conditioned to trauma cues. Moreover, the fact that the trauma-alcohol cue combination elicited greater alcohol craving, salivary responding, distress, and arousal than either the trauma-neutral or neutral-alcohol cue combinations, suggests that effects of the trauma and alcohol cues were additive in nature. Evidence that AD individuals with PTSD report increased alcohol craving and display greater salivation in response to trauma memories, supplements prior research indicating that PTSD-related negative emotion and trauma-related alcohol craving may play an important role in the maintenance of AD. PMID:20695690

  13. The role of neurotransmitters in alcohol dependence: animal research.

    PubMed

    De Witte, P

    1996-03-01

    Animal studies have demonstrated that alcohol changes neurotransmitter concentrations in the brain. These changes in levels of dopamine, serotonin, gamma-aminobutyric acid (GABA), endogenous opioid peptides, and noradrenaline are associated with activation of reward centres in the brain. It is this property of alcohol that is believed to be responsible for the reinforcing effect of alcohol consumption in rats. One class of neurotransmitters, the endogenous opioid peptides, are believed to play an important role in alcohol reinforcement. This view is supported by the reduced preference for alcohol consumption found in rats given an opiate agonist. The widely distributed inhibitory neurotransmitter GABA is also believed to play a fundamental role in mediating the effects of alcohol. A better understanding of the mechanisms that support alcohol dependence in animals offers hope for the development of pharmacological interventions to block these mechanisms, an approach that is now being explored in humans.

  14. A preliminary, randomized trial of aerobic exercise for alcohol dependence.

    PubMed

    Brown, Richard A; Abrantes, Ana M; Minami, Haruka; Read, Jennifer P; Marcus, Bess H; Jakicic, John M; Strong, David R; Dubreuil, Mary Ella; Gordon, Alan A; Ramsey, Susan E; Kahler, Christopher W; Stuart, Gregory L

    2014-07-01

    Interventions targeting physical activity may be valuable as an adjunct to alcohol treatment, but have been relatively untested. In the current study, alcohol dependent, physically sedentary patients were randomized to: a 12-week moderate-intensity, group aerobic exercise intervention (AE; n=25) or a brief advice to exercise intervention (BA-E; n=23). Results showed that individuals in AE reported significantly fewer drinking and heavy drinking days, relative to BA-E during treatment. Furthermore adherence to AE strengthened the beneficial effect of intervention on alcohol use outcomes. While high levels of moderate-intensity exercise appeared to facilitate alcohol recovery regardless of intervention arm, attending the group-based AE intervention seemed to further enhance the positive effects of exercise on alcohol use. Study findings indicate that a moderate intensity, group aerobic exercise intervention is an efficacious adjunct to alcohol treatment. Improving adherence to the intervention may enhance its beneficial effects on alcohol use.

  15. 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

  16. 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

  17. 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…

  18. Impulsivity, risky behaviors and accidents in alcohol-dependent patients

    PubMed Central

    Jakubczyk, Andrzej; Klimkiewicz, Anna; Wnorowska, Anna; Mika, Katarzyna; Bugaj, Marcin; Podgórska, Anna; Barry, Kristen; Blow, Frederic C.; Brower, Kirk J.; Wojnar, Marcin

    2013-01-01

    Impulsivity and alcohol drinking are both considered as important predictors of unintentional as well as intentional injuries. However, relationships of impulsivity with risky behaviors and a history of accidents have not been investigated in alcohol dependence. The aim of this study was to analyze relationships between the frequency of risky behaviors and level of behavioral as well as cognitive impulsivity in alcohol-dependent patients. By means of Barratt’s Impulsiveness Scale (BIS) and stop-signal task, the levels of cognitive and behavioral impulsivity among 304 alcohol-dependent patients were measured. Also, patients were asked to answer questions from the Short Inventory of Problems applying to risky behaviors and accidents after alcohol drinking. In addition participants completed a questionnaire to assess frequency of other behaviors from the analyzed spectrum (use of other drugs, driving or aggressive behavior after alcohol drinking). The statistical analysis revealed a significant association between impulsivity and frequency of risky behaviors in alcohol-dependent patients. Individuals with higher scores in BIS behaved more frequently in a risky way and had significantly more accidents after alcohol drinking. The association with risky behaviors was strongest for non-planning and attentional impulsivity subscales, whereas frequency of accidents was particularly associated with motor impulsivity. A multivariate analysis revealed that impulsivity was the most important predictor of risky behaviors, but did not significantly predict a history of accidents. Our study confirms that impulsivity is an important correlate of risky behaviors in alcohol-dependent individuals, along with global psychopathology and severity of alcohol dependence. PMID:23246707

  19. Nalmefene for the treatment of alcohol dependence: a current update.

    PubMed

    Soyka, Michael

    2014-04-01

    To date, few pharmacotherapies have been established for the treatment of alcoholism. There is a plethora of research concerning the involvement of the opioid-endorphin system in mediating the reinforcing effects of alcohol. The opioid antagonist naltrexone has been found to be effective in alcohol treatment. In addition, the mu-opioid antagonist and partial kappa agonist nalmefene was recently approved by the European Medicines Agency for the treatment of alcoholism. The relevant studies followed a harm-reduction, 'as needed' approach and showed a reduction in alcohol consumption with nalmefene 20 mg rather than increased abstinence rates, (which was not the primary goal of the relevant studies). The available literature is reviewed and discussed. Nalmefene appears to be a safe and effective treatment for alcohol dependence.

  20. 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

  1. A dysbiotic subpopulation of alcohol-dependent subjects.

    PubMed

    de Timary, Philippe; Leclercq, Sophie; Stärkel, Peter; Delzenne, Nathalie

    2015-01-01

    The vast majority of studies that assessed the importance of biological factors for the development of psychiatric disorders focused on processes occurring at the brain level. Alcohol-dependence is a very frequent psychiatric disorder where psycho-pharmacological interventions are only of moderate efficacy. Our laboratory has recently described that a subpopulation of alcohol-dependent subjects, that accounted for approximately 40% of individuals tested, presented with an increased intestinal permeability, with a dysbiosis, with alterations in the metabolomic content of faeces--that could play a role in the increased permeability--and finally with a more severe profile of alcohol-dependence than the other non-dysbiotic subpopulation. In this addendum, we discuss the implications of our observations for the pathophysiology of alcohol dependence where we try to discriminate which addiction dimensions are likely related to the gut microbiota alterations and whether these alterations are the cause or the consequence of drinking habits. PMID:26727422

  2. 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

  3. Thinking after Drinking: Impaired Hippocampal-Dependent Cognition in Human Alcoholics and Animal Models of Alcohol Dependence

    PubMed Central

    Staples, Miranda C.; Mandyam, Chitra D.

    2016-01-01

    Alcohol use disorder currently affects approximately 18 million Americans, with at least half of these individuals having significant cognitive impairments subsequent to their chronic alcohol use. This is most widely apparent as frontal cortex-dependent cognitive dysfunction, where executive function and decision-making are severely compromised, as well as hippocampus-dependent cognitive dysfunction, where contextual and temporal reasoning are negatively impacted. This review discusses the relevant clinical literature to support the theory that cognitive recovery in tasks dependent on the prefrontal cortex and hippocampus is temporally different across extended periods of abstinence from alcohol. Additional studies from preclinical models are discussed to support clinical findings. Finally, the unique cellular composition of the hippocampus and cognitive impairment dependent on the hippocampus is highlighted in the context of alcohol dependence. PMID:27746746

  4. 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

  5. ASTN1 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families.

    PubMed

    Hill, Shirley Y; Weeks, Daniel E; Jones, Bobby L; Zezza, Nicholas; Stiffler, Scott

    2012-06-01

    A previous genome-wide linkage study of alcohol dependence (AD) in multiplex families found a suggestive linkage result for a region on Chromosome 1 near microsatellite markers D1S196 and D1S2878. The ASTN1 gene is in this region, a gene previously reported to be associated with substance abuse, bipolar disorder and schizophrenia. Using the same family data consisting of 330 individuals with phenotypic data and DNA, finer mapping of a 26 cM region centered on D1S196 was undertaken using SNPs with minor allele frequency (MAF) ≥ 0.15 and pair-wise linkage disequilibrium (LD) of r(2) < 0.8 using the HapMap CEU population. Significant FBAT P-values for SNPs within the ASTN1 gene were observed for four SNPs (rs465066, rs228008, rs6668092, and rs172917), the most significant, rs228008, within intron 8 had a P-value of 0.001. Using MQLS, which allows for inclusion of all families, we find three of these SNPs with MQLS P-values < 0.003. In addition, two additional neighboring SNPs (rs10798496 and rs6667588) showed significance at P = 0.002 and 0.03, respectively. Haplotype analysis was performed using the haplotype-based test function of FBAT for a block that included rs228008, rs6668092, and rs172917. This analysis found one block (GCG) over-transmitted and another (ATA) under-transmitted to affected offspring. Linkage analysis identified a region consistent with the association results. Family-based association analysis shows the ASTN1 gene significantly associated with alcohol dependence. The potential importance of the ASTN1 gene for AD risk may be related its role in glial-guided neuronal migration.

  6. 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

  7. Coping Styles and Alcohol Dependence among Homeless People

    PubMed Central

    Opalach, Cezary; Romaszko, Jerzy; Jaracz, Marcin; Kuchta, Robert; Borkowska, Alina; Buciński, Adam

    2016-01-01

    Background and Objectives The ways in which homeless individuals cope with stress may differ from those relied upon by the members of the general population and these differences may either be the result or the cause of their living conditions. The aim of the study was to determine the preferred coping style among the homeless and its relationship with alcohol dependence. Methods The study included 78 homeless individuals and involved the collection of demographic, sociological, psychological and medical data from each participant. Coping styles relied upon when dealing with stressful situations were assessed using a Polish adaptation of the Coping Inventory for Stressful Situations. Alcohol dependence was assessed using the Michigan Alcoholism Screening Test (MAST) and a quantitative analysis of alcohol consumption. Results Men accounted for 91.93% of the study population. Nearly 75% of the subjects met the alcohol dependence criterion. Significant relationships were observed between the individual's age, preferred coping style and alcohol consumption level. As an individual’s age increased, the use of emotion-oriented coping styles decreased, while an increase in alcohol consumption was associated with a more frequent use of emotion- and avoidance-oriented strategies. Conclusions The findings of this study, similarly to those of many other studies of homeless individuals but investigating other areas (e.g. epidemiology of tuberculosis and traumatic injuries), are an exaggerated representation of associations observed in the general population. The results describe a group of people living on the margins of the society, often suffering from extremely advanced alcoholism, with clear evident psychodegradation. The presence of specific ways of coping with stress related to excessive alcohol consumption in this group of individuals may interfere with active participation in support programmes provided for the homeless and may further exacerbate their problems. PMID

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Discovering genes involved in alcohol dependence and other alcohol responses: role of animal models.

    PubMed

    Buck, Kari J; Milner, Lauren C; Denmark, Deaunne L; Grant, Seth G N; Kozell, Laura B

    2012-01-01

    The genetic determinants of alcoholism still are largely unknown, hindering effective treatment and prevention. Systematic approaches to gene discovery are critical if novel genes and mechanisms involved in alcohol dependence are to be identified. Although no animal model can duplicate all aspects of alcoholism in humans, robust animal models for specific alcohol-related traits, including physiological alcohol dependence and associated withdrawal, have been invaluable resources. Using a variety of genetic animal models, the identification of regions of chromosomal DNA that contain a gene or genes which affect a complex phenotype (i.e., quantitative trait loci [QTLs]) has allowed unbiased searches for candidate genes. Several QTLs with large effects on alcohol withdrawal severity in mice have been detected, and fine mapping of these QTLs has placed them in small intervals on mouse chromosomes 1 and 4 (which correspond to certain regions on human chromosomes 1 and 9). Subsequent work led to the identification of underlying quantitative trait genes (QTGs) (e.g., Mpdz) and high-quality QTG candidates (e.g., Kcnj9 and genes involved in mitochondrial respiration and oxidative stress) and their plausible mechanisms of action. Human association studies provide supporting evidence that these QTLs and QTGs may be directly relevant to alcohol risk factors in clinical populations.

  14. [Personality variables, psychopathological alterations and personality disorders in alcohol-dependent patients according to Cloninger's typology of alcohol abuse].

    PubMed

    Echeburúa, Enrique; Bravo de Medina, Ricardo; Aizpiri, Javier

    2008-11-01

    In this paper, an evaluation of Cloninger's typology of alcohol abuse in personality, psychopathology and personality disorders is carried out. The sample consisted of 158 alcoholics in treatment (56 Type I alcohol-dependent patients and 102 Type II alcohol-dependent patients). All subjects were assessed with diverse assessment tools related to personality (Impulsiveness Scale, Sensation Seeking Scale and STAI), psychopathology (SCL-90-R, BDI and Inadaptation Scale) and personality disorders (IPDE). The main findings were that Type II alcohol-dependent patients were more impulsive and sensation-seeking and they displayed more hostility and emotional distress than Type I alcohol-dependent patients. Personality disorders were not so prevalent in the case of Type I alcohol-dependent patients. The most specific personality disorders for Type II alcohol-dependent patients were narcissistic and paranoid. The implications of this study for further research are commented on.

  15. 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

  16. Oppositional defiant disorder (ODD), the forerunner of alcohol dependence: a controlled study.

    PubMed

    Ghosh, Abhishek; Malhotra, Savita; Basu, Debasish

    2014-10-01

    There are common genetic, neurobiological and psycho-social substrates for oppositional defiant disorder (ODD) and substance dependence. ODD can be regarded as the mildest and earliest form of disruptive behavioral disorder and also represents the threshold of vulnerability for substance dependence. But it is a less researched area. The aim of this research was to study any possible association between childhood ODD and adult alcohol dependence. Data are presented from a non probability sample of 100 adult alcohol dependent subjects and equal number of biologically unrelated control subjects. Assessment was conducted by the instrument Semi-Structured Assessment for the Genetics of Alcoholism for both the assessment of ODD and alcohol dependence. The results of this study demonstrated significant association between childhood ODD and adult alcohol dependence. The association remained significant even after the exclusion of the possible confounding effects of the presence of conduct disorder and attention deficit hyperactivity disorder. Our study should encourage further research in this area and is expected to open up an opportunity for preventive research.

  17. [Degrees of alcoholic dependency in patient's self evaluation].

    PubMed

    Bidzan, L; Debski, L

    The study involved a group of 33 males with diagnosed alcohol abuse. A degree of the disease was determined according to Standard Anamnesis Sheet and Auxilliary Alcohol Dependence Questionnaire (Woronowicz's Questionnaire). The patient's results were compared with their wives' results in order to determine trustworthiness. The goal of this study was to determine the factors influencing patient's critical assessment of their disease. The results reveal a relationship between patient's assessment and clinical manifestations of their dependence tend to underestimate the degree of their disease. PMID:8146056

  18. 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. PMID:27212829

  19. Salivary alcohol dehydrogenase in non-smoking and smoking alcohol-dependent persons.

    PubMed

    Waszkiewicz, Napoleon; Jelski, Wojciech; Zalewska, Anna; Szulc, Agata; Szmitkowski, Maciej; Zwierz, Krzysztof; Szajda, Sławomir Dariusz

    2014-09-01

    Increasing attention to the importance of saliva testing is not surprising because smoking and alcohol drinking act synergistically on oral tissues, and their metabolite levels, e.g., acetaldehyde, are much higher in saliva than in blood. The activity of salivary alcohol dehydrogenase (ADH) comes from oral microbiota, mucosa, and salivary glands. The purpose of this study was to investigate the involvement of ADH in the oral health pathology of smoking (AS) and non-smoking (ANS) alcohol-dependent males. The results indicated that the AS group had a more significant and longer duration (until the 30th day of alcohol abstinence) decrease in ADH activity and output than the ANS group (until the 15th day of alcohol abstinence) compared to controls (social drinkers; C). The decreased salivary flow (SF) in alcoholics was observed longer in the ANS group (until the 30th day of alcohol abstinence), whereas in the AS group SF normalized at the 15th day, probably due to the irritating effect of tobacco smoke on the oral mucosa. Because saliva was centrifuged to remove cells and debris (including microbial cells), the detected salivary ADH activity was derived from salivary glands and/or oral mucosa. A more profound and longer decrease in ADH activity/output in smoking than non-smoking alcoholics was likely due to the damaged salivary glands and/or oral mucosa, caused by the synergistic effect of alcohol drinking and smoking. The lower values of salivary ADH in smoking than non-smoking alcoholics might also be partly due to the reversed/inhibited ADH reaction by high levels of accumulated acetaldehyde.

  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. 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

  2. Rare ADH Variant Constellations are Specific for Alcohol Dependence

    PubMed Central

    Zuo, Lingjun; Zhang, Heping; Malison, Robert T.; Li, Chiang-Shan R.; Zhang, Xiang-Yang; Wang, Fei; Lu, Lingeng; Lu, Lin; Wang, Xiaoping; Krystal, John H.; Zhang, Fengyu; Deng, Hong-Wen; Luo, Xingguang

    2013-01-01

    Aims: Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference. Methods: A total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7–ADH1C–ADH1B–ADH1A–ADH6–ADH4–ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis. Results: We found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P = 0.045), European-Australians (Fp5: global P = 0.027; collapsing: P = 0.038) and African-Americans (Fp5: global P = 0.050; collapsing: P = 0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons. Conclusion: We conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence. PMID:23019235

  3. Dissociated Accumbens and Hippocampal Structural Abnormalities across Obesity and Alcohol Dependence

    PubMed Central

    Mak, Elijah; Chien, Yee; Voon, Valerie

    2016-01-01

    Background: Processing of food and drug rewards involves specific neurocircuitry, and emerging evidence implicates subcortical abnormalities, particularly the nucleus accumbens and hippocampus. We specifically hypothesized that these 2 established regions in addiction neurocircuitry are associated with distinctive in vivo structural abnormalities in obesity and alcohol dependence. Methods: To specifically investigate anatomically discrete volumetric changes associated with overconsumption of different rewards, we acquired T1 MRI data from 118 subjects in 3 groups comprising obesity (n=42), alcohol dependence (n=32), and healthy volunteer controls (n=44). To exploit novel methods of automated hippocampal subfield segmentation, we used Freesurfer software to generate volumetric data in subject groups for the hippocampal subiculum and its major striatal efferent target, the nucleus accumbens. Hypothesis-led, selective group difference comparisons were analyzed. Results: We found markedly greater accumbens volumes (P=.002) and relatively preserved hippocampal subfield volumes in obesity. Conversely, in alcohol dependence, we found preserved accumbens volumes but atrophy of specific ventral hippocampal subfields, the subiculum and presubiculum. Smaller global subcortical gray-matter volume was found in the alcohol dependence group only. Conclusions: Reward neurocircuitry including the accumbens and ventral hippocampus may show key structural abnormalities in disorders involving processing of both food and drug rewards, although the foci of disruption may vary as a function of reward modality. Structural differences may subserve altered reward and motivational processes in obesity and alcohol dependence and represent a potential biomarker for therapeutic targeting in key public health disorders. PMID:27207916

  4. 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

  5. Baclofen for alcohol dependence: Relationships between baclofen and alcohol dosing and the occurrence of major sedation.

    PubMed

    Rolland, Benjamin; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Gautier, Sophie; Auffret, Marine; Pignon, Baptiste; Valin, Thomas; Bordet, Régis; Cottencin, Olivier

    2015-10-01

    High-dose baclofen, i.e., 300 mg/d or more, has recently emerged as a strategy for treating alcohol dependence. The impact that the co-exposure of large amounts of alcohol and baclofen has on sedation is unclear. In a prospective cohort of 253 subjects with alcohol dependence, we collected daily alcohol and baclofen doses across the first year of baclofen treatment and the monthly maximum subjective sedation experienced by each patient (0-10 visual analog scale). For each patient-month, we determined the average weekly alcohol consumption (AWAC; standard-drinks/week) and the maximum daily dose of baclofen (DDB; mg/d). The occurrence of an episode of major sedation (EMS) during a patient-month was defined as a sedation score ≥7. The relationship between the EMS occurrence and the concurrent AWAC and DDB was investigated using a generalized estimating equation model. In total, 1528 patient-months were compiled (70 with an EMS). Univariate analyses demonstrated that the rate of patient-month to EMS increased gradually with AWAC (p<0.001), from 0.9% for AWAC=0 to 9.4% for AWAC >35. There was also a significant gradual risk for EMS associated with DDB (<0.001). Multivariate analysis demonstrated a significant interaction between DDB and AWAC on EMS risk (p=0.047). Each 20mg/d increase in DDB was associated with an OR of EMS in AWAC >35 of 1.22 (95%CI, 1.08-1.38) versus 1.11 (95%CI, 0.96-1.29) in AWAC=1-35, and 0.95 (95%CI, 0.76-1.19) in AWAC=0. The level of sedation observed in patients using baclofen for alcohol dependence appears to directly depend on the immediate doses of both the baclofen and the alcohol.

  6. Incubation of alcohol craving during abstinence in patients with alcohol dependence.

    PubMed

    Li, Peng; Wu, Ping; Xin, Xue; Fan, Yun-Li; Wang, Gui-Bin; Wang, Fan; Ma, Meng-Ying; Xue, Ming-Ming; Luo, Yi-Xiao; Yang, Fu-De; Bao, Yan-Ping; Shi, Jie; Sun, Hong-Qiang; Lu, Lin

    2015-05-01

    Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts. PMID:24698092

  7. Incubation of alcohol craving during abstinence in patients with alcohol dependence.

    PubMed

    Li, Peng; Wu, Ping; Xin, Xue; Fan, Yun-Li; Wang, Gui-Bin; Wang, Fan; Ma, Meng-Ying; Xue, Ming-Ming; Luo, Yi-Xiao; Yang, Fu-De; Bao, Yan-Ping; Shi, Jie; Sun, Hong-Qiang; Lu, Lin

    2015-05-01

    Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts.

  8. Characteristics of heart rate variability in alcohol-dependent subjects and nondependent chronic alcohol users.

    PubMed

    Karpyak, Victor M; Romanowicz, Magdalena; Schmidt, John E; Lewis, Kriste A; Bostwick, John M

    2014-01-01

    Heart rate variability (HRV) is an objective and sensitive measure of integrated physiological functioning reflective of heart rhythm responsivity to internal and external demands. Reduced HRV is associated with vulnerability to stress and deterioration of medical and/or psychiatric conditions, while increased HRV is associated with a favorable treatment response and recovery from various medical and/or psychiatric conditions. Our previous review found that acute alcohol consumption caused decreased parasympathetic and increased sympathetic HRV effects in both nonalcoholic and chronic alcohol users. This review investigates the effects of chronic alcohol consumption on HRV in alcohol-dependent subjects and nondependent users. MEDLINE, Scopus, and PubMed were searched for human experimental and clinical trials that measured the effects of chronic alcohol use on HRV. Only publications that included a description of their study designs and clearly stated methodologies for data collections, and outcome measures were reviewed. We have reviewed a total of 24 articles. In nondependent users, low dose (approximating the recommended daily amount of 1 standard drink in women and 2 in men) use is associated with increased HRV parameters compared to those who drink less frequently or abstain altogether. A further increase in consumption is associated with decreased HRV compared to both abstainers and more moderate drinkers. HRV changes during withdrawal generally follow the same negative direction but are more complex and less understood. In dependent subjects, an improvement in HRV was seen following abstinence but remained reduced compared to nonalcoholic controls. This review demonstrates that HRV changes associated with chronic use follow a J-shaped curve. It supports recommendations that limit daily alcohol intake to no more than 2 drinks for men and 1 drink for women. Future studies should investigate HRV as a biomarker of alcoholism development and treatment response as

  9. Neuropeptide Y Opposes Alcohol Effects on GABA Release in Amygdala and Blocks the Transition to Alcohol Dependence

    PubMed Central

    Gilpin, Nicholas W.; Misra, Kaushik; Herman, Melissa A.; Cruz, Maureen T.; Koob, George F.; Roberto, Marisa

    2011-01-01

    Background During the transition to alcohol and drug addiction, neuromodulator systems in the extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence on inhibitory GABA neurons in central amygdala (CeA). Methods This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking by making rats dependent on alcohol via alcohol vapor inhalation. This study also utilized intracellular and whole-cell recording techniques to determine the effects of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naïve and alcohol-dependent rats. Results Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated with alcohol dependence, as well as gradual increases in alcohol responding by intermittently tested non-dependent controls. NPY decreased baseline GABAergic transmission and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing GABA release via actions at presynaptic Y2 receptors. Conclusions These results highlight NPY modulation of GABAergic signaling in central amygdala as a promising pharmacotheraputic target for the treatment of alcoholism. GABA neurons in the CeA likely constitute a major point of convergence for neuromodulator systems recruited during the transition to alcohol dependence. PMID:21459365

  10. Depression, Alcohol Dependence and Abuse, and Drinking and Driving Behavior

    PubMed Central

    Zhang, Ye; Sloan, Frank A.

    2015-01-01

    Background Alcohol dependence/abuse and depression are positively related. Prior studies focused on relationships between drinking and driving and alcohol dependence/abuse, drinking and driving and problem drinking, or drinking and driving and depression separately. No study has addressed how depression is linked to drinking and driving through various underlying channels in the same study. Methods This study investigated relationships between depression, alcohol dependence/abuse, and the number of self-reported drinking and driving episodes. We also explored underlying behavioral channels between depression and alcohol dependence/abuse and binge drinking, reducing drinking amounts when planning to drive, and use of designated drivers. Data on 1,634 drinkers came from a survey fielded in eight U.S. cities. We employed ordinary least squares regression (OLS) and path analysis to assess drinking and driving and underlying channels. Results With OLS, being depressed increased the number of drinking and driving episodes during the past year by 0.572. This increase decreased to 0.411 episodes/year increase after adding socio-demographic characteristics and household income and lost statistical significance after controlling for alcohol dependence/abuse. The path analysis showed that depression is positively associated with drinking and driving, indirectly operating through not using a designated driver, but is not directly associated with drinking and driving. Alcohol dependence/abuse is directly associated with drinking and driving, and indirectly with drinking and driving through binge drinking. Conclusion Our results suggest that treatment should focus on helping individuals with depression to obtain assistance from others, such as obtaining a designated driver. Since self-control of drinking in anticipation of driving did not significantly reduce drinking and driving episodes, this study finds no empirical support for emphasizing improved self-control when the

  11. Are the effects of gamma-hydroxybutyrate (GHB) treatment partly physiological in alcohol dependence?

    PubMed

    Ameisen, Olivier

    2008-01-01

    It has been hypothesized that the therapeutic effects of Gamma-hydroxybutyrate (GHB) in alcohol dependence could be related to ethanol-mimicking action of the drug and that GHB could reduce alcohol craving, intake and withdrawal by acting as a "substitute" of the alcohol in the central nervous system. Nevertheless, alcohol being the strongest trigger of craving and intake, it is difficult to ascribe reduction of craving and intake to ethanol-mimicking activity of GHB. I have recently proposed that alcohol/substance dependence could result from a GHB-deficiency-related dysphoric syndrome in which alcohol/substances would be sought to "substitute" for insufficient GHB effect. GHB is the sole identified naturally occurring gamma-aminobutyric acid B (GABA (B)) receptor agonist. Here, I propose that exogenous GHB might in fact "substitute" for deficient endogeneous GHB and represent true substitutive treatment for GHB-deficiency. And that baclofen and GHB could both compensate for deficient effect of the physiological GABA (B) receptor agonist(s).

  12. ADDITIONAL DEMOGRAPHIC AND CLINICAL EVIDENCES ON THE RELEVANCE OF THE SYSTEMIC THERAPY IN ALCOHOL DEPENDENCE.

    PubMed

    Alexinschi, Ovidiu; Chirita, Roxana; Manuela, Padurariu; Ciobica, Alin; Dobrin, Romeo; Petrariu, F D; Timofte, Daniel; Chirita, Vasile

    2015-01-01

    The modern treatment for alcohol dependence is still problematic, in many cases with the costs exceeding benefits. In these conditions a new management approach was developed lately, known as the systemic therapy. In this way, the crystallization and practical transposition of this new treatment approach is represented by the Clubs of Alcoholics in Treatment. These clubs are in fact a form of psycho-social intervention consisting of multi-family communities in order to maintain long-term abstinence from alcohol and to change their lifestyle and behavior. Thus, in the present paper we were interested in understanding the demographics of this systemic theory and how these aspects are influencing the final results of the therapy, as well as studying/confirming how relevant is this systemic approach on the management of alcohol dependence. Our results presented in this report bring additional evidences for the superiority of the systemic, multi-family approach of alcohol-related problems, as complemented to the standard medicinal therapy. Moreover, the data collected from patients in this study might suggest that patients with a higher educational level and therefore better capacity of understanding the information, with family support, and also with a better occupational insertion, have accepted to follow The Clubs of Alcoholics in Treatment program, with a subsequently better evolution. PMID:26793858

  13. Sexual Dysfunction in Patients with Alcohol and Opioid Dependence

    PubMed Central

    Grover, Sandeep; Mattoo, Surendra K.; Pendharkar, Shreyas; Kandappan, Venkatesh

    2014-01-01

    There are limited numbers of studies which have evaluated the sexual dysfunction (SD) in patients with alcohol and opioids dependence. This article reviews the existing literature. Electronic searches were carried out using the PubMed, Google Scholar, and ScienceDirect to locate the relevant literature. Subjects addicted to heroin or on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT) show higher rates of SD in comparison to the general population. SD rates have ranged 34-85% for heroin addicts, 14-81% for MMT, 36-83% for BMT, and 90% for naltrexone maintenance. The rates of SD in alcohol-dependent population have ranged 40-95.2%, with rates being consistently much higher in alcohol-dependent population than in the healthy controls or social drinkers. The common SDs reported have been erectile dysfunction followed by premature ejaculation, retarded ejaculation and decreased sexual desire among men, and dyspareunia and vaginal dryness among women. This review suggests that long-term use of alcohol and opioids are associated with SD in almost all domains of sexual functioning. There is a need to increase the awareness of clinicians about this association as many times SD in patients with substance abuse lead to poor treatment compliance and relapse. Further, there is a need to carry out more number of studies to understand the relationship in a better way. PMID:25336765

  14. [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

  15. Operant alcohol self-administration in dependent rats: focus on the vapor model.

    PubMed

    Vendruscolo, Leandro F; Roberts, Amanda J

    2014-05-01

    Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be. PMID:24290310

  16. 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.

  17. 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

  18. Alcohol-dependence syndrome: Postural challenge on heart rate variability

    PubMed Central

    Sucharita, S.; Pradeep, Johnson; Vincent, Anoop; Vaz, M.; Srinivasan, K.

    2012-01-01

    Background: Cardiac autonomic involvement in Alcohol-Dependence Syndrome (ADS) patients has been demonstrated using conventional autonomic tests. Resting heart rate variability (HRV) without normalization has also been reported. Aims: To evaluate cardiac autonomic changes with postural challenge using HRV in ADS and controls while controlling for confounding factors. Settings and Design: Cross-sectional study involving 27 male subjects with ADS and age-matched healthy controls. Materials and Methods: Clinical assessments included Schedules for Clinical Assessment in Neuropsychiatry and Severity of Alcohol Dependence Questionnaire. Spectral measures of HRV while lying and with active standing were assessed. Results: There was an attenuated response in delta high-frequency (P=0.06) and delta low-frequency (P=0.04) power to standing in ADS subjects compared with controls. Conclusion: Patients with ADS appear to have attenuated cardiac vagal and sympathetic responses to standing. HRV with postural challenge may help earlier recognition of autonomic dysfunction in ADS. PMID:23226850

  19. 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.

  20. Resting-state functional connectivity and presynaptic monoamine signaling in Alcohol Dependence.

    PubMed

    Zhu, Xi; Dutta, Nisha; Helton, Sarah G; Schwandt, Melanie; Yan, Jia; Hodgkinson, Colin A; Cortes, Carlos R; Kerich, Mike; Hall, Samuel; Sun, Hui; Phillips, Monte; Momenan, Reza; Lohoff, Falk W

    2015-12-01

    Alcohol Dependence (AD) is a chronic relapsing disorder with high degrees of morbidity and mortality. While multiple neurotransmitter systems are involved in the complex symptomatology of AD, monoamine dysregulation and subsequent neuroadaptations have been long postulated to play an important role. Presynaptic monoamine transporters, such as the vesicular monoamine transporter 1 (VMAT1), are likely critical as they represent a key common entry point for monoamine regulation and may represent a shared pathway for susceptibility to AD. Excessive monoaminergic signaling as mediated by genetic variation in VMAT1 might affect functional brain connectivity in particular in alcoholics compared to controls. We conducted resting-state fMRI functional connectivity (FC) analysis using the independent component analysis (ICA) approach in 68 AD subjects and 72 controls. All subjects were genotyped for the Thr136Ile (rs1390938) variant in VMAT1. Functional connectivity analyses showed a significant increase of resting-state FC in 4 networks in alcoholics compared to controls (P < 0.05, corrected). The FC was significantly positively correlated with Alcohol Dependence Scale (ADS). The hyperfunction allele 136Ile was associated with a significantly decreased FC in the Default Mode Network, Prefrontal Cortex Network, and Executive Control Network in alcohol dependent participants (P < 0.05, corrected), but not in controls. Our data suggest that increased FC might represent a neuroadaptive mechanism relevant to AD that is furthermore mediated by genetic variation in VMAT1. The hyperfunction allele Thr136Ile might have a protective effect that is, in particular, relevant in AD by mechanism of increased monoamine transport into presynaptic storage vesicles.

  1. The effects of US state income inequality and alcohol policies on symptoms of depression and alcohol dependence.

    PubMed

    Henderson, Claire; Liu, Xinhua; Diez Roux, Ana V; Link, Bruce G; Hasin, Deborah

    2004-02-01

    Mental health is likely to be influenced by contextual variables that emerge only at the level of the group. We studied the effect of two such group-level variables, within-state income inequality and alcohol tax policy, on symptoms of current depression and alcohol dependence in a US national sample, controlling for state-level and individual characteristics. A cross-sectional US national probability sample provided the individual-level data. State income data were obtained from the 1990 US census. The Gini coefficient (raw and adjusted) indicated income inequality. Outcome measures included current symptoms of depression and alcohol dependence. Controlling for individual-level variables and state median income, the odds of depressive symptoms was not positively associated with state income inequality. Controlling for individual-level variables, state median income and alcohol distribution method, a weak negative association between Gini and alcohol dependence was observed in women, but this association disappeared after additional adjustment for beer tax. No association was observed in men. Higher state beer tax was significantly associated with lower prevalence of alcohol dependence symptoms for both men and women. The results suggest that state income inequality does not increase the experience of alcohol dependence or depression symptoms. However, evidence was found for a protective effect of increased beer taxation against alcohol dependence symptoms, suggesting the need to further consider the impact of alcohol policies on alcohol use disorders.

  2. Gender differences in interpersonal problems of alcohol-dependent patients and healthy controls.

    PubMed

    Mueller, Sandra E; Degen, Bigna; Petitjean, Sylvie; Wiesbeck, Gerhard A; Walter, Marc

    2009-12-01

    Alcohol dependence is a heavy burden on patients, their families, and society. Epidemiological studies indicate that alcohol dependence will affect many individuals at some time in their lives, with men affected more frequently than women. Since alcohol-dependent patients often exhibit a lack of social skills and suffer from interpersonal problems, the aim of this study is to elucidate whether men and women experience the same interpersonal problems. Eighty-five alcohol-dependent patients (48 men; 37 women) after detoxification and 62 healthy controls (35 men; 27 women) were recruited. Interpersonal problems were measured with the Inventory of Interpersonal Problems (IIP-64). Additionally, alcohol-dependent patients were interviewed with the Alcohol Use Disorders Identification Test (AUDIT) and were subtyped according to Lesch's Alcohol Typology (LAT). There were no significant gender differences in the AUDIT and LAT between alcohol-dependent men and women. Interpersonal problems of alcohol-dependent men differed significantly in one out of eight dimensions from controls; alcohol-dependent men perceive themselves as colder than male controls. Alcohol-dependent women differed in four out of eight interpersonal dimensions from female controls. Alcohol-dependent women rated themselves as significantly more vindictive, more introverted, more overly accommodating and more intrusive than female controls. Results suggest that alcohol-dependent men and women suffer from different interpersonal problems and furthermore alcohol-dependent women perceive more interpersonal problems, whereas the severity of alcohol dependence did not differ between the groups. Our findings indicate that alcohol-dependent women may profit more from a gender-specific treatment approach aimed at improving treatment outcome than alcohol-dependent men.

  3. Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence.

    PubMed

    Wang, J C; Grucza, R; Cruchaga, C; Hinrichs, A L; Bertelsen, S; Budde, J P; Fox, L; Goldstein, E; Reyes, O; Saccone, N; Saccone, S; Xuei, X; Bucholz, K; Kuperman, S; Nurnberger, J; Rice, J P; Schuckit, M; Tischfield, J; Hesselbrock, V; Porjesz, B; Edenberg, H J; Bierut, L J; Goate, A M

    2009-05-01

    Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability. Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3'-UTR of the CHRNA3 gene and nicotine dependence. In this study we performed a comprehensive association analysis of the CHRNA5-CHRNA3-CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence. Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence. These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation. Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.

  4. Continuum beliefs and stigmatizing attitudes towards persons with schizophrenia, depression and alcohol dependence.

    PubMed

    Schomerus, Georg; Matschinger, Herbert; Angermeyer, Matthias C

    2013-10-30

    Separation is a central step in the process of stigmatizing persons with mental disorders. We examine whether belief in a continuum of symptoms from mental health to mental illness is associated with less stigmatizing attitudes. In a representative population survey in Germany (n=3642), using case-vignettes of persons suffering from schizophrenia, depression or alcohol dependence, we measured belief in a continuity of symptoms, emotional reactions and desire for social distance related to the person described in the vignette. While 42% of respondents agreed in symptom continuity for depression, this percentage was 26% for schizophrenia and 27% for alcohol dependence. Continuum beliefs were associated in general with more positive emotional reactions and less desire for social distance. This relationship was strongest for schizophrenia, followed by alcohol dependence. Continuum beliefs thus seem to be associated with less stigmatizing attitudes, particularly regarding schizophrenia and alcohol dependence. Educational information on the continuous nature of most psychopathological phenomena could usefully be integrated in anti-stigma messages.

  5. PER3 Polymorphism and Insomnia Severity in Alcohol Dependence

    PubMed Central

    Brower, Kirk J.; Wojnar, Marcin; Sliwerska, Elzbieta; Armitage, Roseanne; Burmeister, Margit

    2012-01-01

    Study Objectives: Insomnia is common, persistent, and associated with relapse in alcohol-dependent (AD) patients. Although the underlying mechanisms are mostly unstudied, AD patients have impaired circadian rhythms and sleep drive, which may be genetically influenced. A polymorphism in the PER3 gene (PER34/4, PER34/5, PER35/5) has previously been associated with circadian preference and sleep homeostasis, and the PER34/4genotype has been characterized by evening preference and decreased sleep drive. The purpose of this study was to examine the influence of this polymorphism on insomnia severity in AD patients. We hypothesized that the PER3 polymorphism would be an independent predictor of insomnia severity with greatest severity observed in those with the PER34/4genotype. Design: Cross-sectional association of patient characteristics, genotype, and insomnia severity. Significant (P < 0.05) bivariate correlates were further analyzed by hierarchical, forced entry multiple linear regression. Setting: Alcohol treatment programs in Warsaw, Poland. Patients: Diagnosed with alcohol dependence (n = 285), according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Measurements and Results: Drinking frequency, mental and physical health status, childhood abuse, and PER3 genotype were independent predictors of insomnia severity, as measured by a 7-item subscale of the Sleep Disorders Questionnaire, explaining 28.9% of the variance. Addition of the genotype in the final step significantly increased the amount of variance explained by 1.1% (P = 0.027). Those with the PER34/4genotype had the greatest severity of insomnia symptoms. Conclusions: PER3 genotype contributed unique variance in predicting insomnia severity in AD patients. These results are consistent with genetically influenced impairment in sleep regulation mechanisms in AD patients with insomnia. Citation: Brower KJ; Wojnar M; Sliwerska E; Armitage R; Burmeister M. PER3 polymorphism and

  6. Conditioned learning in alcohol dependence: implications for cue exposure treatment.

    PubMed

    Drummond, D C; Cooper, T; Glautier, S P

    1990-06-01

    A review of the literature pertinent to cue exposure treatment in alcohol dependence is presented. Psychological models of relapse, based on conditioning and social learning theories, are critically evaluated. In particular, attention is drawn to the potential implications for cue exposure research and treatment of an interaction between Pavlovian and operant conditioning, problems with the application of the concepts of arousal and craving and the importance of a systems model to understand physiological responses. It is concluded that no study has so far demonstrated a link between conditioned responses to alcohol-related cues and relapse, an assumption on which cue exposure treatment is based. Further, the evidence for the effectiveness of cue exposure as a treatment is lacking. Promising research directions are identified.

  7. Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease1

    PubMed Central

    Halsted, Charles H.; Medici, Valentina

    2011-01-01

    Emerging evidence indicates that ethanol-induced alterations in hepatic methionine metabolism play a central role in the pathogenesis of alcoholic liver disease (ALD). Because malnutrition is a universal clinical finding in this disease and hepatic methionine metabolism is dependent upon dietary folate and vitamins B-6 and B-12, ALD can be considered an induced nutritional disorder that is conditioned by alcohol abuse. The present review describes the etiologies of these 3 vitamin deficiencies in ALD and how they interact with chronic ethanol exposure to alter hepatic methionine metabolism. Subsequent sections focus on molecular mechanisms for the interactions of aberrant methionine metabolism with ethanol in the pathogenesis of ALD, in particular the role of S-adenosylmethionine (SAM) in regulating the epigenetic expressions of genes relevant to pathways of liver injury. The review will conclude with descriptions of studies on the efficacy of SAM in the treatment of ALD and with discussion of potentially fruitful future avenues of research. PMID:22332083

  8. Does psychiatric comorbidity in alcohol-dependent patients affect treatment outcome?

    PubMed

    Mann, Karl; Hintz, Thomas; Jung, Martin

    2004-06-01

    Comorbidity in alcohol research refers to the presence of alcohol dependency and another major psychiatric disorder. The existence of additional disorders may have consequences for treatment planning and success. The aims of this paper are therefore: 1) to give an overview on prevalence rates in studies with representative cohorts and hospital-based samples; 2) to report results on gender differences and 3) to determine the impact of comorbidity on treatment outcome. Comorbidity was examined with the Composite International Diagnostic Interview (CIDI) in N = 118 (61 male and 57 female) alcohol-dependent patients who were socially well integrated. Results show that 65% of the female patients but only 28% of the male patients had a lifetime history of additional psychiatric disorders. Significantly more phobic/anxiety disorders, mood disorders occur in female patients. One year after inpatient treatment, overall 39% had suffered a relapse. More detailed analysis revealed that 55% of the non-comorbid but only 28% of the comorbid women suffered a relapse, thus contradicting our initial hypothesis that comorbid patients have a poorer prognosis with regard to their alcohol dependence. Male comorbid (40.9%) and non-comorbid (35.3%) patients showed no significant differences regarding relapse rates.

  9. Sex differences in alcohol consumption and alterations in nucleus accumbens endocannabinoid mRNA in alcohol-dependent rats.

    PubMed

    Henricks, Angela M; Berger, Anthony L; Lugo, Janelle M; Baxter-Potter, Lydia N; Bieniasz, Kennedy V; Craft, Rebecca M; McLaughlin, Ryan J

    2016-10-29

    Chronic intermittent alcohol (CIA) exposure produces altered motivational states characterized by anxiety and escalated alcohol consumption during withdrawal. The endocannabinoid (ECB) system contributes to these symptoms, and sex differences in alcohol dependence, as well as bidirectional interactions between ECBs and gonadal hormones have been documented. Thus, we evaluated sex differences in alcohol consumption, anxiety-like behavior, and ECB mRNA expression in the nucleus accumbens (NAc) of alcohol-dependent rats during acute withdrawal. Male rats exposed to six weeks of CIA showed escalated alcohol consumption during acute withdrawal and reductions in NAc N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), DAG lipase alpha (DAGLα), and monoacylglycerol lipase (MAGL) mRNA. Intact alcohol-dependent female rats also escalated their consumption, but notably, this effect was also present in non-dependent females. No differences in NAc ECB mRNA were observed between CIA- and air-exposed females during acute withdrawal. However, when these data were analyzed according to estrous stage, significant differences in NAPEPLD and MAGL mRNA expression emerged in the NAc of air-exposed control rats, which were absent in alcohol-dependent females. We subsequently measured alcohol consumption and NAc ECB mRNA in ovariectomized (OVX) females with or without estradiol (E2) replacement during withdrawal. Neither E2 nor CIA altered alcohol consumption in OVX females. However, E2 reduced both DAGLα and MAGL mRNA, suggesting that E2 may influence the biosynthesis and degradation of 2-arachidonoylglycerol (2-AG) in the NAc. Collectively, these studies indicate sexual dimorphism in alcohol consumption in non-dependent rats and suggest that E2-mediated alterations in NAc ECB mRNA expression during withdrawal may be a mechanism by which sex differences in alcohol dependence emerge. PMID:27578612

  10. Determination of the effects of alcohol dehydrogenase (ADH) 1B and ADH1C polymorphisms on alcohol dependence in Turkey.

    PubMed

    Aktas, Ekin Ozgur; Kocak, Aytaç; Senol, Ender; Celik, Handan Ak; Coskunol, Hakan; Berdeli, Afig; Aydin, Hikmet Hakan

    2012-03-01

    Alcoholism is a complex genetically influenced disorder which refers to alcohol abuse and alcohol dependence. There are controversial results on the role of gene polymorphisms in alcohol dependence in the literature. Differences in population groups and selective inclusion criteria for alcohol dependence may affect results. In this study, we investigated the role of ADH1B Arg48His (rs1229984) and, ADH1C Ile350Val (rs698) gene polymorphisms in Turkish population. 100 healthy volunteers and 75 patients who were admitted to Ege University Alcohol Dependence Unit enrolled in the study. We found significant increase both in ADH1B (Arg48His) polymorphism Arg allele and Arg/Arg genotype frequency in patients. No profound connection between alcohol dependence and ADH1C Ile350Val gene polymorphism was detected. Alcohol dependence is an important health problem that depends on many genetic and environmental factors but we think that it is possible to interpret genetic risk for developing early diagnostic methods and treatment strategies by comprehensive linkage and association studies.

  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. 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

  13. Cognitive functions in abstinent alcohol-dependent patients.

    PubMed

    Kopera, Maciej; Wojnar, Marcin; Brower, Kirk; Glass, Jennifer; Nowosad, Izabela; Gmaj, Bartłomiej; Szelenberger, Waldemar

    2012-11-01

    The objective of this cross-sectional study was to compare cognitive functioning of abstaining alcohol-dependent (AD) male patients and healthy controls as well as to investigate whether their cognitive performance varied by abstinence length. Forty-two maintaining abstinent (AD) patients and 34 healthy controls were examined. Tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess cognitive functions. Differences in cognitive performance were found between AD patients and healthy controls. Nonverbal tasks in cognitive domains such as attention, visual memory and working memory were impaired in AD patients who presented deficits in visual episodic memory, had slower reaction time and reduced working memory span. Patients who were abstinent for less than one year made more errors in both attentional set shifting and working memory tests than healthy controls and patients with longer durations of abstinence. Impairments identified in multiple cognitive domains in abstinent alcohol-dependent subjects suggest functional deficits in extensive brain networks connecting interrelated brain structures. Attentional control and spatial working memory were less impaired in those AD patients who maintained abstinence for at least one year.

  14. 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.

  15. Investigating biases of attention and memory for alcohol-related and negative words in alcohol-dependents with and without major depression after day-clinic treatment.

    PubMed

    Fridrici, Christina; Driessen, Martin; Wingenfeld, Katja; Kremer, Georg; Kissler, Johanna; Beblo, Thomas

    2014-08-30

    This study aimed to investigate attentional and memory biases in alcohol-dependents with and without major depression compared to healthy controls. We assumed that both groups of alcohol-dependents would show attentional and memory biases for alcohol-related words. For the alcohol-dependents with depression, we additionally expected both types of biases for negative words. Alcohol-dependents without co-morbidity (Alc) and alcohol-dependents with major depression (D-Alc) as well as control participants with a moderate consumption of alcohol (Con) completed an alcohol Stroop task and a directed forgetting paradigm using word stimuli from three categories: neutral, negative, and alcohol-related. Stroop effects showed that not only alcohol-dependents but also control participants were more distracted by alcohol-related than by negative words. In the directed forgetting procedure, all participants showed a significant effect for each word-category, including alcohol-related and negative words. The D-Alc-group memorized more alcohol-related than negative to-be-remembered words. The results do not corroborate the hypothesis of more pronounced attentional and memory biases in alcohol-dependents. However, in alcohol-dependents with depression a memory bias for alcohol-related material was found, suggesting that this group may be more pre-occupied with alcohol than patients without such co-morbidity.

  16. Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence

    PubMed Central

    Hirth, Natalie; Meinhardt, Marcus W.; Noori, Hamid R.; Salgado, Humberto; Torres-Ramirez, Oswaldo; Uhrig, Stefanie; Broccoli, Laura; Vengeliene, Valentina; Roßmanith, Martin; Perreau-Lenz, Stéphanie; Köhr, Georg; Sommer, Wolfgang H.; Spanagel, Rainer; Hansson, Anita C.

    2016-01-01

    A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior. Here we set out to study systematically the neuroadaptive changes in the DA system during the addiction cycle in alcohol-dependent patients and rats. In postmortem brain samples from human alcoholics we found a strong down-regulation of the D1 receptor- and DA transporter (DAT)-binding sites, but D2-like receptor binding was unaffected. To gain insight into the time course of these neuroadaptations, we compared the human data with that from alcohol-dependent rats at several time points during abstinence. We found a dynamic regulation of D1 and DAT during 3 wk of abstinence. After the third week the rat data mirrored our human data. This time point was characterized by elevated extracellular DA levels, lack of synaptic response to D1 stimulation, and augmented motor activity. Further functional evidence is given by a genetic rat model for hyperdopaminergia that resembles a phenocopy of alcohol-dependent rats during protracted abstinence. In summary, we provide a new dynamic model of abstinence-related changes in the striatal DA system; in this model a hyperdopaminergic state during protracted abstinence is associated with vulnerability for relapse. PMID:26903621

  17. Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence.

    PubMed

    Hirth, Natalie; Meinhardt, Marcus W; Noori, Hamid R; Salgado, Humberto; Torres-Ramirez, Oswaldo; Uhrig, Stefanie; Broccoli, Laura; Vengeliene, Valentina; Roßmanith, Martin; Perreau-Lenz, Stéphanie; Köhr, Georg; Sommer, Wolfgang H; Spanagel, Rainer; Hansson, Anita C

    2016-03-15

    A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior. Here we set out to study systematically the neuroadaptive changes in the DA system during the addiction cycle in alcohol-dependent patients and rats. In postmortem brain samples from human alcoholics we found a strong down-regulation of the D1 receptor- and DA transporter (DAT)-binding sites, but D2-like receptor binding was unaffected. To gain insight into the time course of these neuroadaptations, we compared the human data with that from alcohol-dependent rats at several time points during abstinence. We found a dynamic regulation of D1 and DAT during 3 wk of abstinence. After the third week the rat data mirrored our human data. This time point was characterized by elevated extracellular DA levels, lack of synaptic response to D1 stimulation, and augmented motor activity. Further functional evidence is given by a genetic rat model for hyperdopaminergia that resembles a phenocopy of alcohol-dependent rats during protracted abstinence. In summary, we provide a new dynamic model of abstinence-related changes in the striatal DA system; in this model a hyperdopaminergic state during protracted abstinence is associated with vulnerability for relapse.

  18. EFFECT OF NALTREXONE AND ONDANSETRON ON ALCOHOL CUE-INDUCED ACTIVATION OF THE VENTRAL STRIATUM IN ALCOHOL-DEPENDENT PEOPLE

    PubMed Central

    Myrick, Hugh; Anton, Raymond F.; Li, Xingbao; Henderson, Scott; Randall, Patrick K.; Voronin, Konstantin

    2008-01-01

    Context Medication treatment of alcoholism is presently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. Objective To explore the effect of naltrexone, ondansetron, or the combination of these medications on cue-induced craving and ventral striatum activation. Design, Setting, Participants Functional brain imaging (Phillips 1.5T scanner) was conducted during alcohol cue presentation in 90 non-treatment seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (less than 14 drinks per week) paid volunteers recruited through advertisements at an academic center. Interventions A taste of alcohol and a series of alcohol related pictures, neutral beverage pictures and visual control images were provided to volunteers after seven days of double blind randomly assigned daily dosing with 50mg naltrexone (n=23), 0.50mg ondansetron (n=23), the combination of the two medications (n=20), or matching placebos (n=24). Main Outcome Measures Difference in brain blood oxygen level-dependent (BOLD) magnetic resonance when viewing alcohol pictures versus neutral beverage pictures with a particular focus on ventral striatum activity comparison across medication groups. Self-ratings of alcohol craving. Results The combination treatment decreased craving for alcohol. Naltrexone with (p=0.02) or without (p=0.049) ondansetron decreased alcohol cue-induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a regions specific analysis. Conclusions Consistent with animal data suggesting that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy. PMID

  19. 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…

  20. [Creation of a scale for evaluating attitudes of partners toward alcohol dependency].

    PubMed

    Sugawara, Tazuko; Morita, Noriaki; Nakatani, Youji

    2013-12-01

    The aim of this study was to develop a scale to evaluate characteristics of how alcohol-dependent people perceive the attitudes of their partners toward alcohol dependency. Based on previous research, we created the "Attitudes of partners toward alcohol dependency" scale, from the perspective of the alcohol dependent individual. Using the new scale, 71 alcohol-dependent people (52 men, 19 women) were surveyed after obtaining their consent, and the reliability and validity of the scale were tested. The results identified 3 factors, "indifference", "acceptance" and "hypersensitivity", and factorial validity was verified. Relatively high reliability was obtained on each sub-scale (alpha = .60-.82). Furthermore, correlations were obtained with the alcohol-dependency "Denial and Awareness Scale (for alcohol-dependent people)" and with the 13-item "Usefulness of heterosexual love relations for recovery from alcohol dependency" questionnaire, which includes content on "beneficial" or "obstructive" to recovery, and with the satisfaction and the importance of relations. This demonstrates that the "Attitudes of partners toward alcohol dependency" scale has reliability and criterion-related validity. The scale facilitates evaluation of types of attitudes of partners toward alcohol dependency, and may thus be useful as one tool for investigating the influence of partners in heterosexual love relationships for recovery, and for providing advice.

  1. 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.

  2. 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.

  3. 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

  4. Women's alcohol dependence and abuse: the relation to social network and leisure time.

    PubMed

    Thundal, K L; Granbom, S; Allebeck, P

    1999-03-01

    The aim of this study was to analyse the occurrence of alcohol dependence and abuse in relation to variables reflecting social network and leisure time, social class, education, occupation and family conditions. The study was based on the second wave of interviews performed within the longitudinal study of Women and Alcohol in Göteborg. In this present study we analysed 416 face-to-face interviews performed in 1995 96. Women with only one or no friends for support had higher rates of alcohol dependence and abuse than did women with more friends. Women with high rates of alcohol dependence or abuse did not take part in cultural events as much as women with low rates of alcohol dependence and abuse. Women with homemaking skills and gardening as leisure time interests had lower prevalences of alcohol dependence and abuse. In general, women with diagnoses of alcohol dependence and abuse in this population-based sample were not alone and without a social network. However, their pattern of activity differed slightly from those without such diagnoses. The association between women with alcohol dependence and abuse and leisure time activities is probably circular: a poor social network and low participation in social activities increase the risk of alcohol dependence and abuse, and alcohol dependence and abuse lead to low participation in social activities.

  5. 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

  6. 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.

  7. Anticipatory 50 kHz ultrasonic vocalizations are associated with escalated alcohol intake in dependent rats

    PubMed Central

    Buck, Cara L.; Malavar, Jordan C.; George, Olivier; Koob, George F.; Vendruscolo, Leandro F.

    2014-01-01

    Rats emit 50 kHz ultrasonic vocalizations (USVs) in situations of increased motivation, such as during the anticipation of palatable food or drugs of abuse. Whether the same holds true for the anticipation of alcohol intake remains unknown. Alcohol drinking in a nondependent state is thought to be mediated by its rewarding effects (positive reinforcement), whereas drinking in the dependent state is motivated by alcohol’s stress-relieving effects (negative reinforcement). Here, we measured context-elicited 50 kHz USVs in alcohol-dependent (alcohol vapor-exposed) and nondependent rats immediately before operant alcohol self-administration sessions. Dependent rats showed escalated levels of alcohol intake compared with nondependent rats. Overall, dependent and nondependent rats showed similar levels of anticipatory 50 kHz USVs. However, the number of anticipatory USVs was positively correlated with alcohol intake in dependent rats but not nondependent rats. Additionally, dependent rats with higher alcohol intake displayed increased anticipatory 50 kHz USVs compared with rats that had lower alcohol intake, whereas no difference was observed between rats with high and low alcohol intake in the nondependent group. Increased 50 kHz USVs were specific for the anticipation of alcohol self-administration and did not generalize to a novel environment. These findings suggest that anticipatory 50 kHz USVs may be an indicator of context-elicited negative reinforcement learning. PMID:24914463

  8. Characteristics of adults involved in alcohol-related intimate partner violence: results from a nationally representative sample

    PubMed Central

    2014-01-01

    Background More than 12 million women and men are victims of partner violence each year. Although the health outcomes of partner violence have been well documented, we know very little about specific event-level characteristics that may provide implications for prevention and intervention of partner violence situations. Therefore, the purpose of this study is to evaluate substance abuse and dependence as risk factors for event-level alcohol-related intimate partner violence (IPV). Methods Data were derived from Wave II of the National Epidemiological Survey on Alcohol and Related Conditions (2004–2005). Eligible participants (N = 2,255) reported IPV the year before the survey. Negative binomial and ordinal regression methods were used to assess risk factors for alcohol use during IPV. Results Respondent PTSD was the only mental health diagnosis related to alcohol use during IPV (OR = 1.45). Marijuana use was related to respondents’ use of alcohol during IPV (OR = 2.68). Respondents’ meeting the criteria for alcohol abuse/dependence was strongly associated with respondent drinking (OR = 10.74) and partner drinking (OR = 2.89) during IPV. Conclusion Results indicate that PTSD, marijuana use disorders, alcohol abuse and dependence are associated with more frequent alcohol use during IPV. In addition, it is important to consider that the patient who presents in emergency settings (e.g., hospitals or urgent care facilities) may not be immediately identifiable as the victim or the perpetrator of partner violence. Therefore, screening and intervention programs should probe to further assess the event-level characteristics of partner violence situations to ensure the correct service referrals are made to prevent partner violence. PMID:24884943

  9. [Effect of comorbid depression on the development and course of alcohol dependence].

    PubMed

    Rybakova, K V; Rybakova, T G; Neznanov, N G; Eryshev, O F

    2013-01-01

    It was compared 72 patients with alcohol dependence (AD) and endogenous depression (ED) and 30 patients with AD without comorbid affective pathology. It has been shown that the development of alcohol dependence in individuals with ED is slower than in patients without ED. A lack of a family history of addictive pathology was noted to be a predictor of a more favorable course of alcohol dependence in patients with ED.

  10. Prazosin + naltrexone decreases alcohol drinking more effectively than does either drug alone in P rats with a protracted history of extensive voluntary alcohol drinking, dependence and multiple withdrawals

    PubMed Central

    Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C

    2015-01-01

    Background Prazosin (PRZ, an α1-adrenergic receptor antagonist) and naltrexone (NTX, a non-specific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively-bred for high voluntary alcohol drinking (alcohol-preferring, or “P”), and the combination of PRZ+NTX decreases alcohol drinking more effectively than does either drug alone. Since drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence and repeated withdrawals closely resembling human alcoholism. Methods Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/day access to food, water and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: 1) daily alcohol access with daily drug treatment, 2) intermittent alcohol access with daily drug treatment, 3) intermittent alcohol access with occasional drug treatment, and 4) post-deprivation reinstatement of alcohol access. Results The combination of PRZ+NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ+NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects or malaise. Conclusions Both daily and “as-needed” treatment with PRZ+NTX are highly effective in suppressing daily, intermittent and post-deprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence and

  11. 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

  12. Prevalence and Correlates of Drug/Alcohol-Facilitated and Incapacitated Sexual Assault in a Nationally Representative Sample of Adolescent Girls

    ERIC Educational Resources Information Center

    McCauley, Jenna L.; Conoscenti, Lauren M.; Ruggiero, Kenneth J.; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.

    2009-01-01

    Incapacitated/drug-alcohol facilitated sexual assault (IS/DAFS) is rapidly gaining recognition as a distinct form of assault with unique public health implications. This study reports the prevalence, case characteristics, and associated health risks of IS/DAFS using a large, nationally representative sample of 1,763 adolescent girls. Results…

  13. Polysubstance and Alcohol Dependence: Unique Abnormalities of Magnetic Resonance-Derived Brain Metabolite Levels

    PubMed Central

    Abé, Christoph; Mon, Anderson; Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Meyerhoff, Dieter J.

    2012-01-01

    BACKGROUND Although comorbid substance misuse is common in alcohol dependence, and polysubstance abusers (PSU) represent the largest group of individuals seeking treatment for drug abuse today, we know little about potential brain abnormalities in this population. Brain magnetic resonance spectroscopy studies of mono-substance use disorders (e.g., alcohol or cocaine) reveal abnormal levels of cortical metabolites (reflecting neuronal integrity, cell membrane turnover/synthesis, cellular bioenergetics, gliosis) and altered concentrations of glutamate and γ-aminobutyric acid (GABA). The concurrent misuse of several substances may have unique and different effects on brain biology and function compared to any mono-substance misuse. METHODS High field brain magnetic resonance spectroscopy at 4 Tesla and neurocognitive testing were performed at one month of abstinence in 40 alcohol dependent individuals (ALC), 28 alcohol dependent PSU and 16 drug-free controls. Absolute metabolite concentrations were calculated in anterior cingulate (ACC), parieto-occipital (POC) and dorsolateral prefrontal cortices (DLPFC). RESULTS Compared to ALC, PSU demonstrated significant metabolic abnormalities in the DLPFC and strong trends to lower GABA in the ACC. Metabolite levels in ALC and light drinking controls were statistically equivalent. Within PSU, lower DLPFC GABA levels related to greater cocaine consumption. Several cortical metabolite concentrations were associated with cognitive performance. CONCLUSIONS While metabolite concentrations in ALC at one month of abstinence were largely normal, PSU showed persistent and functionally significant metabolic abnormalities, primarily in the DLPFC. Our results point to specific metabolic deficits as biomarkers in polysubstance misuse and as targets for pharmacological and behavioral PSU-specific treatment. PMID:23122599

  14. 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

  15. [Comorbidity of alcohol dependence with other psychiatric disorders. Part I. Epidemiology of dual diagnosis].

    PubMed

    Klimkiewicz, Anna; Klimkiewicz, Jakub; Jakubczyk, Andrzej; Kieres-Salomoński, Ilona; Wojnar, Marcin

    2015-01-01

    The paper is a review of the literature on the comorbidity of alcohol dependence with other psychiatric disorders. A condition when alcohol dependence is accompanied by another mental disorder is much more common than it is commonly believed. It is estimated that more than one third of people diagnosed with mental disorders, abuses or is dependent on psychoactive substances, especially alcohol; among alcohol-dependent patients 37% suffer from other mental disorders. Alcohol dependence is associated with increased risk of mood disorders - more than three times higher, depression - almost four times higher, bipolar disorder - more than six times higher, anxiety disorders in general - more than twice, generalized anxiety disorder - more than four times higher, panic disorders - almost double, posttraumatic stress disorder - more than twice. Underestimating of comorbidity is an important problem during treatment of such population of patients. Social skills training can improve a stress management and decrease alcohol and drug use among dual diagnosed patients.

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

    PubMed

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

    2013-06-01

    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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. Pharmacological aversion treatment of alcohol dependence. I. Production and prediction of conditioned alcohol aversion.

    PubMed

    Howard, M O

    2001-08-01

    Eighty-two hospitalized alcoholics receiving pharmacological aversion therapy (PAT) over a 10-day treatment interval completed cognitive, behavioral, and psychophysiological measures evaluating conditioned aversion to alcohol. Pre-post assessments provided convergent support for the efficacy of PAT vis-à-vis production of conditioned aversion to alcohol. Positive alcohol-related outcome expectancies were significantly reduced, whereas confidence that drinking could be avoided in various high-risk situations for consumption was increased following PAT. Behavioral and cardiac rate assessments revealed significant changes following PAT that were specific to alcoholic beverages and potentially reflective of conditioned alcohol aversion. Patients with more extensive pretreatment experiences with alcohol-associated nausea and greater involvement in antisocial conduct appeared to be less susceptible to the PAT conditioning protocol.

  2. Prescription Pain Reliever Abuse and Dependence among Adolescents: A Nationally Representative Study

    ERIC Educational Resources Information Center

    Wu, Li-Tzy; Ringwalt, Christopher L.; Mannelli, Paolo; Patkar, Ashwin A.

    2008-01-01

    The study investigates the prevalence, patterns, and correlates of adolescents' abuse, sub-threshold dependence, and dependence on prescription pain relievers (PPRs) in a nationally representative sample. Results show dependence on PPRs can take place without abuse and that sub-threshold dependence could have implications for major diagnostic…

  3. Acute effects of nicotine on alcohol cue-reactivity in nondependent and dependent smokers.

    PubMed

    McGrath, Daniel S; Peloquin, Marcel P; Ferdinand, Justin C; Barrett, Sean P

    2015-02-01

    Evidence from alcohol self-administration studies suggests that nicotine replacement therapy may influence subjective and behavioral responses to alcohol. However, its effect on alcohol cue-reactivity is unknown. The present study examined the impact of acutely administered nicotine on subjective responses to alcohol-focused pictorial stimuli. In a mixed within/between-subjects design, nondependent smokers (n = 51) and dependent smokers (n = 45) who socially drink were assigned to either a nicotine (4 mg) or placebo lozenge condition following overnight tobacco abstinence. Following lozenge absorption, participants viewed neutral images followed by alcohol-focused pictures. Craving measures for alcohol and tobacco were completed at baseline, following lozenge absorption, following neutral cues, and following alcohol cues. The presentation of alcohol cues increased alcohol-related craving relative to neutral cues, especially among men, but the administration of nicotine did not influence the magnitude of these effects. Nicotine lozenges were found to decrease intentions to smoke and withdrawal-related craving in dependent but not in nondependent smokers. Finally, the presentation of alcohol cues was found to increase intentions to smoke relative to neutral cues across participants regardless of lozenge condition. Findings suggest that although the presentation of alcohol cues can increase alcohol- and tobacco-related cravings in smokers, such effects do not appear to be affected by acute nicotine administration. PMID:25643027

  4. Gene co-expression networks in human brain identify epigenetic modifications in alcohol dependence

    PubMed Central

    Ponomarev, Igor; Wang, Shi; Zhang, Lingling; Harris, R Adron; Mayfield, R Dayne

    2012-01-01

    Alcohol abuse causes widespread changes in gene expression in human brain, some of which contribute to alcohol dependence. Previous microarray studies identified individual genes as candidates for alcohol phenotypes, but efforts to generate an integrated view of molecular and cellular changes underlying alcohol addiction are lacking. Here, we applied a novel systems approach to transcriptome profiling in postmortem human brains and generated a systemic view of brain alterations associated with alcohol abuse. We identified critical cellular components and previously unrecognized epigenetic determinants of gene co-expression relationships and discovered novel markers of chromatin modifications in alcoholic brain. Higher expression levels of endogenous retroviruses and genes with high GC content in alcoholics were associated with DNA hypomethylation and increased histone H3K4 tri-methylation, suggesting a critical role of epigenetic mechanisms in alcohol addiction. Analysis of cell type – specific transcriptomes revealed remarkable consistency between molecular profiles and cellular abnormalities in alcoholic brain. Based on evidence from this study and others, we generated a systems hypothesis for the central role of chromatin modifications in alcohol dependence that integrates epigenetic regulation of gene expression with pathophysiological and neuroadaptive changes in alcoholic brain. Our results offer implications for epigenetic therapeutics in alcohol and drug addiction. PMID:22302827

  5. DSM-IV alcohol dependence and drug abuse/dependence in a treatment sample of whites, blacks and Mexican Americans.

    PubMed

    Caetano, R; Schafer, J

    1996-12-01

    This paper examines the association between DSM-IV alcohol dependence, drug use and DSM-IV drug/abuse dependence in a sample of White (n = 256), Black (n = 263) and Mexican American (n = 212) men consecutively admitted to five alcohol treatment programs in a Northern California county. Results show that drug use is higher among Blacks and Mexican Americans than among Whites. About 35% of the Whites 43% of the Blacks and 35% of the Mexican Americans are both alcohol and drug dependent. Among alcohol dependent individuals, about 44% of the Whites, 72% of the blacks and 52% of the Mexican Americans report using at least one drug other than alcohol once a week or more in the 12 months previous to the interview. The drug most frequently used by Whites is marijuana, followed by cocaine and amphetamines. The drug most frequently used by Blacks and Mexican Americans is cocaine, followed by marijuana. Severity of drug dependence is inversely related to severity of alcohol dependence among Whites. Alcohol treatment programs for Whites, Blacks and Mexican Americans must offer assessment, treatment matching and relapse prevention that takes into consideration this high prevalence of drug use and dependence.

  6. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment.

    PubMed

    Meikle, Peter J; Mundra, Piyushkumar A; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K; Duly, Alastair M P; Haber, Paul S; Whitfield, John B; Seth, Devanshi

    2015-01-01

    Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

  7. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment.

    PubMed

    Meikle, Peter J; Mundra, Piyushkumar A; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K; Duly, Alastair M P; Haber, Paul S; Whitfield, John B; Seth, Devanshi

    2015-01-01

    Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease. PMID:26107182

  8. Allelic variants of ADH, ALDH and the five factor model of personality in alcohol dependence syndrome

    PubMed Central

    Salujha, S. K.; Chaudhury, S.; Menon, P. K.; Srivastava, K.; Gupta, A.

    2014-01-01

    Background: The etiology of alcohol dependence is a complex interplay of biopsychosocial factors. The genes for alcohol-metabolizing enzymes: Alcohol dehydrogenase (ADH2 and ADH3) and aldehyde dehydrogenase (ALDH2) exhibit functional polymorphisms. Vulnerability of alcohol dependence may also be in part due to heritable personality traits. Aim: To determine whether any association exists between polymorphisms of ADH2, ADH3 and ALDH2 and alcohol dependence syndrome in a group of Asian Indians. In addition, the personality of these patients was assessed to identify traits predisposing to alcoholism. Materials and Methods: In this study, 100 consecutive males with alcohol dependence syndrome attending the psychiatric outpatient department of a tertiary care service hospital and an equal number of matched healthy controls were included with their consent. Blood samples of all the study cases and controls were collected and genotyped for the ADH2, ADH3 and ALDH2 loci. Personality was evaluated using the neuroticism, extraversion, openness (NEO) personality inventory and sensation seeking scale. Results: Allele frequencies of ADH2*2 (0.50), ADH3*1 (0.67) and ALSH2*2 (0.09) were significantly low in the alcohol dependent subjects. Personality traits of NEO personality inventory and sensation seeking were significantly higher when compared to controls. Conclusions: The functional polymorphisms of genes coding for alcohol metabolizing enzymes and personality traits of NEO and sensation seeking may affect the propensity to develop dependence. PMID:25535445

  9. Alcohol and Masculinity: A Review and Reformulaton of the Sex Role, Dependency, and Power Theories of Alcoholism.

    ERIC Educational Resources Information Center

    Lemle, Russell

    This review examines three theories of alcohol abuse by American males: (1) the sex role theory which states that men drink heavily because American culture accepts and encourages that activity in males; (2) the dependency theory, which interprets drinking as a means by which men secretly gratify their dependency needs while manifesting an…

  10. Boarding and Public Schools: Navajo Educational Attainment, Conduct Disorder, and Alcohol Dependency.

    ERIC Educational Resources Information Center

    Henderson, Eric; Kunitz, Stephen J.; Gabriel, K. Ruben; McCright, Aaron; Levy, Jerrold E.

    1998-01-01

    Interviews with over 1,000 Navajos aged 21-67 in 1992-95 found that alcohol dependency was less common among high school graduates than dropouts but was also disproportionately low among older men with no schooling. Despite abusive conditions that prevailed in some Indian boarding schools, alcohol dependency rates did not differ by type of school…

  11. 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…

  12. 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…

  13. 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.

  14. 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

  15. 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 ...

  16. Different Phenotypic and Genotypic Presentations in Alcohol Dependence: Age at Onset Matters*

    PubMed Central

    Chen, Yu-Chu; Prescott, Carol A.; Walsh, Dermot; Patterson, Diana G.; Riley, Brien P.; Kendler, Kenneth S.; Kuo, Po-Hsiu

    2011-01-01

    Objective: Several theoretical typology models have been proposed to classify alcoholism into more homogeneous subtypes using various criteria, for which age at onset of alcohol dependence is shared across many models. We investigated the evidence for the distinction between early- versus late-onset alcoholism by examining relevant phenotypic and genotypic variables. Method: Data are from 1,248 individuals with alcohol dependence, who were interviewed to collect detailed clinical information. Early versus late onset of alcohol dependence was defined by the age at onset of 22 years. Odds ratio (OR) and Cohen's d were calculated as effect size for comparisons of clinical features between the two groups. We adjusted interviewed age and gender in logistic regression models. Case-control genetic analyses were conducted for the association between HTR1B, SLC6A4, DRD2, and OPRμ1 genes and subgroups of alcohol dependence using a sample of 530 controls screened for alcohol problems. Results: Early-onset alcoholism exhibited significantly (p < .01) different clinical characteristics from late-onset alcoholism, including higher severity in alcohol dependence symptoms (d = 0.22) and maximum drinking quantity within 24 hours (d = 0.40), more rapid progression from regular drinking to meet alcohol dependence diagnosis (d = 1.73), higher expectancies for alcohol (d = 0.22−0.47), more comorbidity with externalizing disorders (ORs = 2.8−2.9), and greater prevalence of family alcohol use problems (d = 0.26−0.43). In addition, markers in the HTR1B and OPRμ1 genes showed genetic associations with subgroups of alcohol dependence (ORs = 1.5−2.4). Conclusions: Our findings support that subgroups of alcohol dependence defined by onset age have phenotypic and genetic differences. The early-onset subgroup had more severe features for almost every aspect we examined. Coupled with genetic association findings, age at onset of alcohol dependence may serve as a simple but important

  17. 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

  18. Prevalence of Alcohol Dependence Among US Adult Drinkers, 2009–2011

    PubMed Central

    Esser, Marissa B.; Hedden, Sarra L.; Brewer, Robert D.; Gfroerer, Joseph C.; Naimi, Timothy S.

    2014-01-01

    Introduction Excessive alcohol consumption is responsible for 88,000 deaths annually and cost the United States $223.5 billion in 2006. It is often assumed that most excessive drinkers are alcohol dependent. However, few studies have examined the prevalence of alcohol dependence among excessive drinkers. The objective of this study was to update prior estimates of the prevalence of alcohol dependence among US adult drinkers. Methods Data were analyzed from the 138,100 adults who responded to the National Survey on Drug Use and Health in 2009, 2010, or 2011. Drinking patterns (ie, past-year drinking, excessive drinking, and binge drinking) were assessed by sociodemographic characteristics and alcohol dependence (assessed through self-reported survey responses and defined as meeting ≥3 of 7 criteria for dependence in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Results Excessive drinking, binge drinking, and alcohol dependence were most common among men and those aged 18 to 24. Binge drinking was most common among those with annual family incomes of $75,000 or more, whereas alcohol dependence was most common among those with annual family incomes of less than $25,000. The prevalence of alcohol dependence was 10.2% among excessive drinkers, 10.5% among binge drinkers, and 1.3% among non-binge drinkers. A positive relationship was found between alcohol dependence and binge drinking frequency. Conclusion Most excessive drinkers (90%) did not meet the criteria for alcohol dependence. A comprehensive approach to reducing excessive drinking that emphasizes evidence-based policy strategies and clinical preventive services could have an impact on reducing excessive drinking in addition to focusing on the implementation of addiction treatment services. PMID:25412029

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Neurocognitive deficits, craving, and abstinence among alcohol-dependent individuals following detoxification.

    PubMed

    Naim-Feil, Jodie; Fitzgerald, Paul B; Bradshaw, John L; Lubman, Dan I; Sheppard, Dianne

    2014-02-01

    Alcohol dependence, a chronic relapsing disorder, is characterized by an impaired ability to regulate compulsive urges to consume alcohol. Very few empirical studies have examined the presence of these executive deficits, how they relate to craving, and the enduring nature of these deficits during abstinence. As such, the current study aimed to characterize these cognitive deficits within a sample of 24 alcohol-dependent participants post-detoxification and 23 non-alcohol-dependent participants. Participants were administered the Sustained Attention to Response Task to measure response inhibition and sustained attention and the Random Number Generation Task to examine executive deficits. Correlations between cognitive performance and clinical measures of alcohol dependence were examined. As predicted, the alcohol-dependent group exhibited poorer performance across the domains of response inhibition, executive function, and attentional control. Cognitive performance was related to clinical measures of craving and years of alcohol consumption, whereas the duration of abstinence was not associated with improved cognitive performance. These findings highlight the need for therapeutic strategies to target these enduring neurocognitive deficits in improving the treatment of alcohol dependence. PMID:24334264

  5. Borderline Personality Symptoms in Short-Term and Long-Term Abstinent Alcohol Dependence

    PubMed Central

    Fein, George; Nip, Vincent

    2011-01-01

    Background Comorbidity of Borderline Personality Disorder (BPD) and Substance and Alcohol Use Disorders (SUDs and AUDs is very high. The literature suggests a negative synergy between BPD and SUDs, which may impact an individual’s ability to achieve and maintain remission of either disorder in the face of the other. Methods We examined lifetime and current (past year) BPD symptom counts in three gender- and age-comparable groups: short-term abstinent alcoholics (STA, 6–15 weeks abstinent), long-term abstinent alcoholics (LTA, more than 18 months abstinent), and non-substance-abusing controls (NSAC). Abstinent individuals were recruited primarily from mutual-help recovery networks and about half had comorbid drug dependence. BPD symptoms were obtained using the SCID-II, followed up with questions regarding currency, but did not require that BPD symptoms represent persistent or pervasive behavior such as would meet criteria for BPD diagnosis. Thus our study dealt only with BPD symptoms, not BPD diagnoses. Results Alcoholics had more lifetime and current symptoms for most all BPD criteria than NSAC. In general, STA and LTA did not differ in BPD symptoms, except for a group-by-gender effect for both lifetime and current anger-associated symptoms and for lifetime abandonment-avoidance symptoms. For these cases, there were much higher symptom counts for STA women vs. men, with comparable symptom counts for LTA women vs. men. Conclusions Our results suggest for the most part that BPD symptoms do not prevent the maintenance of recovery in AUD and SUD individuals who have established at least six weeks abstinence within the mutual-help recovery network – in fact the presence of BPD symptoms is the norm. However, we did find difficulty in establishing longer-term abstinence in women with anger-associated symptoms and abandonment avoidance symptoms. PMID:22309234

  6. 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

  7. Observing nurses has improved my alcohol dependency care.

    PubMed

    Jaques, Ellise

    2016-09-21

    My first placement in my first year of nursing training was on a gastrointestinal/hepatology ward. Alongside my mentor, I was caring for a patient who had been withdrawing from alcohol since admission to hospital the previous evening.

  8. Sexual Orientation Disparities in Psychiatric and Drug Use Disorders among a Nationally Representative Sample of Women with Alcohol Use Disorders

    PubMed Central

    Mereish, Ethan H.; Lee, Ji Hyun; Gamarel, Kristi E.; Zaller, Nickolas D.; Operario, Don

    2015-01-01

    Background and Aims Sexual minority women (SMW) are at greater risk for alcohol use disorders (AUDs) compared to heterosexual women. However, there is a dearth of research on sexual orientation disparities in co-occurring disorders among women with AUDs. We examined disparities in lifetime co-occurring psychiatric and drug use disorders among a nationally representative sample of women with lifetime AUDs. Methods Data were analyzed from the 2004–2005 (Wave 2) of the National Epidemiological Survey on Alcohol and Related Condition (NESARC), which was collected in structured diagnostic face-to-face interviews. Adult women with AUDs (N = 4,342) were included in the analyses and approximately 191 of those women self-identified as SMW. Lifetime alcohol and drug use disorders and psychiatric disorders were assessed using DSM-IV criteria. We conducted multivariate logistic regression analyses to compare SMW and heterosexual women with lifetime AUDs on lifetime psychiatric disorders and drug use disorders, while adjusting for sociodemographic variables. Findings While accounting for several covariates, SMW with lifetime AUDs were more likely than heterosexual women with lifetime AUDs to have lifetime psychiatric disorders (e.g., mood, anxiety, panic disorders) and drug use disorders (e.g., prescription drugs, cannabis use disorders). Conclusions Sexual minority women with lifetime alcohol use disorders are at heightened risk for co-occurring psychiatric and drug use disorders than heterosexual women with lifetime alcohol use disorders. The findings warrant the need for more research and empirically based interventions for the comprehensive treatment and prevention of alcohol use disorders among sexual minority women. PMID:25899096

  9. 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

  10. Posttraumatic Stress Disorder and Alcohol Dependence in Young Women*

    PubMed Central

    Sartor, Carolyn E.; Mccutcheon, Vivia V.; Pommer, Nicole E.; Nelson, Elliot C.; Duncan, Alexis E.; Waldron, Mary; Bucholz, Kathleen K.; Madden, Pamela A. F.; Heath, Andrew C.

    2010-01-01

    Objective: The aim of the current study is to characterize the relationship between posttraumatic stress disorder (PTSD) and alcohol dependence (AD) in women, distinguishing PTSD-specific influences on AD from the contribution of co-occurring psychiatric conditions and from the influences of trauma more generally. Method: Trauma histories and DSM-IV lifetime diagnoses, including PTSD and AD, were obtained via telephone interview from 3,768 female twins. Based on PTSD status and trauma history, participants were categorized as no trauma (43.7%), trauma without PTSD (52.6%), or trauma with PTSD (3.7%). Cox proportional hazards regression analyses were conducted using trauma/PTSD status to predict AD, first adjusting only for ethnicity and parental problem drinking, then including conduct disorder, major depressive disorder, regular smoking, and cannabis abuse. Results: Before accounting for psychiatric covariates, elevated rates of AD were evident in both trauma-exposed groups, but those with PTSD were at significantly greater risk for AD than those without PTSD. This distinction was no longer statistically significant when psychiatric covariates were included in the model, but both trauma-exposed groups continued to show elevated odds of developing AD compared with the no trauma group. Conclusions: The elevated rates of AD in women who have experienced trauma are not accounted for in full by psychiatric conditions that commonly co-occur with AD and trauma exposure. The greater likelihood of developing AD in the subset of trauma-exposed individuals who develop PTSD may reflect higher levels of distress and/ or higher rates of psychopathology associated with traumas that lead to PTSD rather than PTSD-specific influences. PMID:20946737

  11. Nalmefene: a review of its use in the treatment of alcohol dependence.

    PubMed

    Keating, Gillian M

    2013-09-01

    The opioid system modulator nalmefene (Selincro®) is approved in the EU for as-needed use to reduce alcohol consumption in alcohol-dependent adults with a high drinking risk level. This article reviews the efficacy and tolerability of as-needed oral nalmefene in the treatment of alcohol dependence, as well as summarizing its pharmacological properties. In two randomized, double-blind, multinational trials (ESENSE 1 and ESENSE 2), as-needed nalmefene significantly reduced the number of heavy drinking days (in both trials) and total alcohol consumption (in ESENSE 1) at month 6. In the randomized, double-blind, multinational SENSE trial, as-needed nalmefene significantly improved both of these endpoints at month 13, but not at month 6. As-needed nalmefene had a greater beneficial effect in the target population (i.e. alcohol-dependent patients with at least a high drinking risk level at screening and randomization), with post hoc analyses revealing significant reductions in both the number of heavy drinking days and total alcohol consumption at month 6 (in ESENSE 1 and ESENSE 2) and at month 13 (in SENSE). Oral nalmefene was generally well tolerated in patients with alcohol dependence, with the most commonly occurring adverse events including nausea, insomnia and dizziness. In conclusion, as-needed nalmefene provides an important new option for use in the treatment of alcohol dependence.

  12. Alcohol consumption and binge drinking in adolescents: comparison of different migration backgrounds and rural vs. urban residence - a representative study

    PubMed Central

    2011-01-01

    Background Binge drinking is a constant problem behavior in adolescents across Europe. Epidemiological investigations have been reported. However, epidemiological data on alcohol consumption of adolescents with different migration backgrounds are rare. Furthermore representative data on rural-urban comparison concerning alcohol consumption and binge drinking are lacking. The aims of the study are the investigation of alcohol consumption patterns with respect to a) urban-rural differences and b) differences according to migration background. Methods In the years 2007/2008, a representative written survey of N = 44,610 students in the 9th. grade of different school types in Germany was carried out (net sample). The return rate of questionnaires was 88% regarding all students whose teachers respectively school directors had agreed to participate in the study. Weighting factors were specified and used to make up for regional and school-type specific differences in return rates. 27.4% of the adolescents surveyed have a migration background, whereby the Turkish culture is the largest group followed by adolescents who emigrated from former Soviet Union states. The sample includes seven large cities (over 500,000 inhabitants) (12.2%), independent smaller cities ("urban districts") (19.0%) and rural areas ("rural districts") (68.8%). Results Life-time prevalence for alcohol consumption differs significantly between rural (93.7%) and urban areas (86.6% large cities; 89.1% smaller cities) with a higher prevalence in rural areas. The same accounts for 12-month prevalence for alcohol consumption. 57.3% of the rural, re-spectively 45.9% of the urban adolescents engaged in binge drinking in the 4 weeks prior to the survey. Students with migration background of the former Soviet Union showed mainly drinking behavior similar to that of German adolescents. Adolescents with Turkish roots had engaged in binge drinking in the last four weeks less frequently than adolescents of German

  13. Neuropeptide Y (NPY) in the extended amygdala is recruited during the transition to alcohol dependence.

    PubMed

    Gilpin, Nicholas W

    2012-12-01

    Neuropeptide Y (NPY) is abundant in the extended amygdala, a conceptual macrostructure in the basal forebrain important for regulation of negative affective states. NPY has been attributed a central role in anxiety-like behavior, fear, nociception, and reward in rodents. Deletion of the NPY gene in mice produces a high-anxiety high-alcohol-drinking phenotype. NPY infused into the brains of rats selectively bred to consume high quantities of alcohol suppresses alcohol drinking by those animals, an effect that is mediated by central amygdala (CeA). Likewise, alcohol-preferring rats exhibit basal NPY deficits in CeA. NPY infused into the brains of alcohol-dependent rats blocks excessive alcohol drinking by those animals, an effect that also has been localized to the CeA. NPY in CeA may rescue dependence-induced increases in anxiety and alcohol drinking via inhibition of downstream effector regions that receive GABAergic inputs from CeA. It is hypothesized here that NPY modulates anxiety-like behavior via Y2R regulation of NPY release, whereas NPY modulation of alcohol-drinking behavior in alcohol-dependent animals occurs via Y2R regulation of GABA release.

  14. 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

  15. Integration of miRNA and Protein Profiling Reveals Coordinated Neuroadaptations in the Alcohol-Dependent Mouse Brain

    PubMed Central

    Gorini, Giorgio; Nunez, Yury O.; Mayfield, R. Dayne

    2013-01-01

    The molecular mechanisms underlying alcohol dependence involve different neurochemical systems and are brain region-dependent. Chronic Intermittent Ethanol (CIE) procedure, combined with a Two-Bottle Choice voluntary drinking paradigm, represents one of the best available animal models for alcohol dependence and relapse drinking. MicroRNAs, master regulators of the cellular transcriptome and proteome, can regulate their targets in a cooperative, combinatorial fashion, ensuring fine tuning and control over a large number of cellular functions. We analyzed cortex and midbrain microRNA expression levels using an integrative approach to combine and relate data to previous protein profiling from the same CIE-subjected samples, and examined the significance of the data in terms of relative contribution to alcohol consumption and dependence. MicroRNA levels were significantly altered in CIE-exposed dependent mice compared with their non-dependent controls. More importantly, our integrative analysis identified modules of coexpressed microRNAs that were highly correlated with CIE effects and predicted target genes encoding differentially expressed proteins. Coexpressed CIE-relevant proteins, in turn, were often negatively correlated with specific microRNA modules. Our results provide evidence that microRNA-orchestrated translational imbalances are driving the behavioral transition from alcohol consumption to dependence. This study represents the first attempt to combine ex vivo microRNA and protein expression on a global scale from the same mammalian brain samples. The integrative systems approach used here will improve our understanding of brain adaptive changes in response to drug abuse and suggests the potential therapeutic use of microRNAs as tools to prevent or compensate multiple neuroadaptations underlying addictive behavior. PMID:24358208

  16. Dependency conflict, marital threat, and alcohol consumption in a middle-aged sample.

    PubMed

    Schwarz, J C; Wheeler, D S

    1992-09-01

    The hypothesis that dependency conflict is associated with higher levels of alcohol consumption when dependency needs are threatened or thwarted was tested with a sample of 672 middle-aged, married adults with college-age children. The subjects' current level of alcohol consumption was predicted based on the present level of threat to the marital relationship (assessed by reports from several family members) and on indices of dependency need and inhibition of dependent behavior estimated from sibship size, sibship density, and sibling position. A multiple regression analysis yielded a significant two-way interaction (p less than .05) between marital threat and subject sex, and a significant three-way interaction of dependency need, inhibition of dependent behavior, and marital threat. High marital threat was associated with higher levels of alcohol consumption in men and slightly lower levels of alcohol consumption in women. Additionally, when dependency need was high, alcohol consumption was generally low, except when both inhibition of dependent behavior and marital threat were high. However, when dependency need was low, the highest alcohol consumption score occurred when marital threat was low and inhibition was high.

  17. 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

  18. An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

    PubMed Central

    Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

    2016-01-01

    Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides.

  19. Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence.

    PubMed

    Wu, Jie; Gao, Ming; Taylor, Devin H

    2014-03-01

    Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence. Alcoholism is a serious public health problem and has been identified as the third major cause of preventable mortality in the world. Worldwide, about 2 billion people consume alcohol, with 76.3 million having diagnosable alcohol use disorders. Alcohol is currently responsible for the death of 4% of adults worldwide (about 2.5 million deaths each year), and this number will be significantly increased by 2020 unless effective action is taken. Alcohol is the most commonly abused substance by humans. Ethanol (EtOH) is the intoxicating agent in alcoholic drinks that can lead to abuse and dependence. Although it has been extensively studied, the mechanisms of alcohol reward and dependence are still poorly understood. The major reason is that, unlike other addictive drugs (eg, morphine, cocaine or nicotine) that have specific molecular targets, EtOH affects much wider neuronal functions. These functions include phospholipid membranes, various ion channels and receptors, synaptic and network functions, and intracellular signaling molecules. The major targets in the brain that mediate EtOH's effects remain unclear. This knowledge gap results in a therapeutic barrier in the treatment of alcoholism. Interestingly, alcohol and nicotine are often co-abused, which suggests that neuronal nicotinic acetylcholine receptors (nAChRs), the molecular targets for nicotine, may also contribute to alcohol's abusive properties. Here, we briefly summarize recent lines of evidence showing how EtOH modulates nAChRs in the mesolimbic pathway, which provides a perspective that nAChRs are important targets mediating alcohol abuse.

  20. 32 CFR 728.78 - American Red Cross representatives and their dependents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false American Red Cross representatives and their... § 728.78 American Red Cross representatives and their dependents. (a) Potential beneficiaries. (1..., including Alaska, Hawaii, and Puerto Rico. (b) Care authorized. (1) When services of the American Red...

  1. 32 CFR 728.78 - American Red Cross representatives and their dependents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false American Red Cross representatives and their... § 728.78 American Red Cross representatives and their dependents. (a) Potential beneficiaries. (1..., including Alaska, Hawaii, and Puerto Rico. (b) Care authorized. (1) When services of the American Red...

  2. The Use of Gestalt Interventions in the Treatment of the Resistant Alcohol-Dependent Client.

    ERIC Educational Resources Information Center

    Ramey, Luellen

    1998-01-01

    Reviews ethical and practical dilemmas associated with clients who have hidden alcohol dependencies, and proposes an approach rooted in Gestalt counseling theory which confronts these issues and is compatible with a current emerging alcohol-treatment model. Suggests specific activities for addressing client resistance to revealing a hidden alcohol…

  3. 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…

  4. 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.

  5. 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 ...

  6. 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 ...

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

    PubMed Central

    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.

    2015-01-01

    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 increased 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 to 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

  8. 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.

  9. Repeated seizures in an elderly patient with alcohol dependence and mild cognitive impairment.

    PubMed

    Ishii, Nobuyoshi; Terao, Takeshi; Araki, Yasuo; Hatano, Koji

    2013-11-22

    A 69-year-old man with alcohol dependence and mild cognitive impairment (MCI) suffered from repeated tonic-clonic seizures. The seizures typically occurred several hours after his last alcohol intake at home (early withdrawal seizure) and 22 days after his last intake of alcohol (14 days after the last dose of diazepam substituting for alcohol: late withdrawal seizure) on the ward. Psychiatrists in charge of this patient found it difficult to attribute his seizures to alcohol withdrawal syndrome (AWS) because of the atypical onset. The patient responded to diazepam resumption and valproate combination. This case highlights the need to always consider AWS as a possible cause of seizures and to gradually decrease diazepam as a substitute for alcohol. Moreover, in this patient, MCI may have induced vulnerability in the brain for AWS and the patients' older age might have decreased liver function leading to delayed onset of the seizures after diazepam withdrawal.

  10. Observing nurses has improved my alcohol dependency care.

    PubMed

    Jaques, Ellise

    2016-09-21

    My first placement in my first year of nursing training was on a gastrointestinal/hepatology ward. Alongside my mentor, I was caring for a patient who had been withdrawing from alcohol since admission to hospital the previous evening. PMID:27654556

  11. The association between DSM-III-R alcohol dependence, psychological distress and drug use.

    PubMed

    Caetano, R; Weisner, C

    1995-03-01

    This paper examines the association between DSM-III-R alcohol dependence, psychological distress and the frequency of drug use in a sample of 219 men and 162 women consecutively admitted to nine alcohol treatment programs in a Northern California county. Results show that psychological distress is higher among men who are more severely dependent on alcohol and among those who have lower education; women who are less alcohol dependent and women who are younger have higher scores in psychological distress than other women. With regard to drug use, about 65% of the men and 64% of the women report using a drug other than alcohol at least once a week during the 12 months prior to admission into treatment. Among both men and women, the drugs most frequently used are crack/cocaine, marijuana and methamphetamine. Among men, regression analysis shows that drug use is associated with being younger. Among women results show that the predictors of drug use are being younger, being unemployed, having a higher income, being a heavier drinker and having fewer symptoms of alcohol dependence. These results show a complex pattern of association across alcohol dependence, drug use and psychological distress. Knowledge of this pattern is necessary for tailoring effective clinical interventions to clients with different kinds of comorbidity.

  12. Further Analyses of Genetic Association Between GRM8 and Alcohol Dependence Symptoms Among Young Adults

    PubMed Central

    Long, Elizabeth C.; Aliev, Fazil; Wang, Jen-Chyong; Edenberg, Howard J.; Nurnberger, John; Hesselbrock, Victor; Porjesz, Bernice; Dick, Danielle M.

    2015-01-01

    Objective: The gene GRM8, a metabotropic glutamate receptor, has emerged as a gene of interest for its possible role in the development of alcohol dependence, with evidence of association with an electrophysiological endophenotype and level of response to alcohol as well as suggestive evidence of association with alcohol dependence. Method: The present study further investigated the association between GRM8 and alcohol dependence symptom counts among young adults using a new sample of individuals collected as part of the prospective sample (ages 18–26 years; N = 842) from the Collaborative Study on the Genetics of Alcoholism (COGA). Results: Two single-nucleotide polymorphisms were significantly associated with alcohol dependence in European Americans using the Nyholt corrected p value of .007: rs886003 (β = -.212, p = .0002) and rs17862325 (β = -.234, p < .0001), but not in African Americans, likely because of the lower power to detect association in this group. Conclusions: These results further implicate the role of glutamate receptor genes such as GRM8 in the development of alcohol dependence. PMID:25978827

  13. Crystal structure of quinone-dependent alcohol dehydrogenase from Pseudogluconobacter saccharoketogenes. A versatile dehydrogenase oxidizing alcohols and carbohydrates.

    PubMed

    Rozeboom, Henriëtte J; Yu, Shukun; Mikkelsen, Rene; Nikolaev, Igor; Mulder, Harm J; Dijkstra, Bauke W

    2015-12-01

    The quinone-dependent alcohol dehydrogenase (PQQ-ADH, E.C. 1.1.5.2) from the Gram-negative bacterium Pseudogluconobacter saccharoketogenes IFO 14464 oxidizes primary alcohols (e.g. ethanol, butanol), secondary alcohols (monosaccharides), as well as aldehydes, polysaccharides, and cyclodextrins. The recombinant protein, expressed in Pichia pastoris, was crystallized, and three-dimensional (3D) structures of the native form, with PQQ and a Ca(2+) ion, and of the enzyme in complex with a Zn(2+) ion and a bound substrate mimic were determined at 1.72 Å and 1.84 Å resolution, respectively. PQQ-ADH displays an eight-bladed β-propeller fold, characteristic of Type I quinone-dependent methanol dehydrogenases. However, three of the four ligands of the Ca(2+) ion differ from those of related dehydrogenases and they come from different parts of the polypeptide chain. These differences result in a more open, easily accessible active site, which explains why PQQ-ADH can oxidize a broad range of substrates. The bound substrate mimic suggests Asp333 as the catalytic base. Remarkably, no vicinal disulfide bridge is present near the PQQ, which in other PQQ-dependent alcohol dehydrogenases has been proposed to be necessary for electron transfer. Instead an associated cytochrome c can approach the PQQ for direct electron transfer.

  14. 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

  15. 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

  16. Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors.

    PubMed

    Kissler, Jessica L; Walker, Brendan M

    2016-01-01

    Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence.

  17. Childhood ADHD and Conduct Disorder as Independent Predictors of Male Alcohol Dependence at Age 40*

    PubMed Central

    Knop, Joachim; Penick, Elizabeth C.; Nickel, Elizabeth J.; Mortensen, Erik L.; Sullivan, Margaret A.; Murtaza, Syed; Jensen, Per; Manzardo, Ann M.; Gabrielli, William F.

    2009-01-01

    Objective: The Danish Longitudinal Study on Alcoholism was designed to identify antecedent predictors of adult male alcoholism. The influence of premorbid behaviors consistent with childhood conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD) on the development of alcohol misuse was examined. Method: Subjects were selected from a Danish birth cohort (9,125), which included 223 sons of alcoholic fathers (high risk) and 106 matched sons of nonalcoholic fathers (low risk). These subjects have been studied systematically over the past 40 years. They were evaluated in their teens (n = 238), later as adults at age 30 (n = 241), and more recently at age 40 (n = 202). At 19-year/20-year follow-ups, an ADHD scale was derived from teacher ratings and a CD scale was derived from a social worker interview. At 30-year and 40-year follow-ups, a psychiatrist used structured interviews and criteria from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, to quantify lifetime alcoholism severity and to diagnose alcohol-use disorder. Of the original subjects, 110 had complete data for the two childhood measures and the adult alcoholism outcomes. Results: In this smaller subsample, paternal risk did not predict adult alcohol dependence. Subjects who were above a median split on both the ADHD and the CD scales were more than six times more likely to develop alcohol dependence than subjects who scored below the median on both. Although the two childhood measures were correlated, a multiple regression showed that each independently predicted a measure of lifetime alcoholism severity. Conclusions: ADHD comorbid with CD was the strongest predictor of later alcohol dependence. PMID:19261228

  18. [Comorbidity of alcohol dependence with other psychiatric disorders. Part II. Pathogenesis and treatment].

    PubMed

    Klimkiewicz, Anna; Klimkiewicz, Jakub; Jakubczyk, Andrzej; Kieres-Salomoński, Ilona; Wojnar, Marcin

    2015-01-01

    Co-occurrence of alcohol dependence with other mental disorders is very common, being important cause of diagnostic and therapeutic difficulties. There is a lack of systemic solutions in mental health care dedicated to the patients with dual diagnosis. The literature on the topic of treatment of patients with dual diagnosis is limited. While comorbidity of alcohol dependence with mental disorders is prevalent, there is rising interest among researchers on that issue. In this paper we present current hypotheses on pathogenesis of dual diagnosis as well as recommendations for its treatment. The role of disturbances in functioning of hypothalamic-pituitary-adrenal axis in pathogenesis of co-occurrence of alcohol dependence with anxiety and affective disorders is presented. Researchers studying dual diagnosis underline the fact that simultaneous treatment of alcohol dependence and co-occurring psychiatric disorders increases the chance to improve patients` functioning. Inappropriate treatment without complete management of all existing problems may make full recovery impossible.

  19. Self-mutilation among male patients with alcohol dependency: the role of dissociation.

    PubMed

    Evren, Cuneyt; Sar, Vedat; Evren, Bilge; Dalbudak, Ercan

    2008-01-01

    The aim of this study was to investigate the relationship of self-mutilative behavior with dissociative experiences among men who are alcohol dependent. Participants were 176 inpatients consecutively admitted to an alcohol dependency treatment center. Dissociative Experiences Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, Symptom Checklist-Revised, and Michigan Alcoholism Screening Test were conducted to all participants. A sizable proportion of patients (29.0%) reported self-mutilation (SM). Childhood abuse, younger age, early onset of alcoholism, and dissociative taxon membership predicted SM. The overall severity of clinical condition and the frequency of suicide attempts among those who reported SM were higher than those of the remaining patients. The Dissociative Experiences Scale-Taxon item "auditory verbal hallucinations" and the Symptom Checklist-Revised dimension "hostility" were predictors of SM. There is a complex relationship between dissociation, alcohol use, and SM. Increased awareness among clinicians on this relationship may increase the effectiveness of treatment interventions.

  20. Physical Pain in Alcohol-Dependent Patients Entering Treatment in Poland—Prevalence and Correlates

    PubMed Central

    Jakubczyk, Andrzej; Ilgen, Mark A.; Bohnert, Amy S. B.; Kopera, Maciej; Krasowska, Aleksandra; Klimkiewicz, Anna; Blow, Frederic C.; Brower, Kirk J.; Wojnar, Marcin

    2015-01-01

    Objective: Chronic pain and problematic alcohol use commonly co-exist, as the use of alcohol is commonly considered a useful pain self-management strategy. The purpose of this study was to characterize pain and pain-related problems in a group of primary alcohol-dependent individuals entering treatment facilities. Method: A sample of 366 (73.5% men and 26.5% women) alcohol-dependent (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria) subjects was recruited in alcohol treatment centers in Warsaw, Poland. Information was obtained about demographics, social functioning, sexual and physical abuse during childhood, and severity of alcohol and sleep problems as well as level of impulsivity and general psychopathology. The study group was divided into a “mild or no pain” group and a “moderate or greater pain” group. Results: Among the study group, 34.4% of individuals reported moderate or greater physical pain during the last 4 weeks. The statistical analysis revealed that the experience of physical pain was significantly associated with lower level of education, unemployment, experience of sexual abuse before 18 years of age, and severity of alcohol dependence as well as other potential predictors of relapse (impulsivity, sleep problems, general psychopathology). When entered into logistic regression analysis with other dependent variables, the level of general psychopathology, severity of sleep problems, age, and education were all significantly associated with pain severity. Conclusions: Physical pain is a prevalent and potentially impairing experience in adults seeking treatment for alcohol dependence. Therapeutic interventions aimed at reducing pain in alcohol-dependent individuals should be studied to evaluate their impact on improving overall treatment outcomes. PMID:26098037

  1. Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis☆

    PubMed Central

    Laramée, Philippe; Leonard, Saoirse; Buchanan-Hughes, Amy; Warnakula, Samantha; Daeppen, Jean-Bernard; Rehm, Jürgen

    2015-01-01

    Background Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. Methods MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. Findings We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). Interpretation AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption. PMID:26629534

  2. Alcohol dependence, family history, and D2 dopamine receptor function as neuroendocrinologically assessed with apomorphine.

    PubMed

    Wiesbeck, G A; Mauerer, C; Thome, J; Jakob, F; Boening, J

    1995-11-01

    Fifteen alcohol dependent men with an alcohol dependent first degree relative (i.e. family history positive or FHP), 15 well matched alcohol dependent men without a family history for alcohol dependence (i.e. family history negative or FHN), and 15 healthy controls (CONTR) participated in this study. The three groups were compared according to their postsynaptic D2 dopamine receptor function as assessed by growth hormone release after stimulation with the dopamine receptor agonist apomorphine. Statistical evaluation was done by planned comparisons within a one-way ANOVA. Alcohol dependent subjects significantly differed from CONTRs as long as family history was not taken into account (t(42) = 2.38; P = 0.022*). When differentiating according to family history, both FHPs and FHNs maintained a blunted growth hormone response. However, the difference between FHNs and CONTRs, though present, dropped out of statistical significance (t(42) = 1.65; P = 0.105); at the same time, the difference between FHPs and CONTRs became slightly stronger (t(42) = 2.47; p = 0.017*). In conclusion, our data give neuroendocrinological support to the assumption that a reduced D2 dopamine receptor function in alcohol dependent men is not only a state marker of residual heavy drinking but also a genetically determined trait marker.

  3. 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 ...

  4. Sweet preference, sugar addiction and the familial history of alcohol dependence: shared neural pathways and genes.

    PubMed

    Fortuna, Jeffrey L

    2010-06-01

    Contemporary research has shown that a high number of alcohol-dependent and other drug-dependent individuals have a sweet preference, specifically for foods with a high sucrose concentration. Moreover, both human and animal studies have demonstrated that in some brains the consumption of sugar-rich foods or drinks primes the release of euphoric endorphins and dopamine within the nucleus accumbens, in a manner similar to some drugs of abuse. The neurobiological pathways of drug and "sugar addiction" involve similar neural receptors, neurotransmitters, and hedonic regions in the brain. Craving, tolerance, withdrawal and sensitization have been documented in both human and animal studies. In addition, there appears to be cross sensitization between sugar addiction and narcotic dependence in some individuals. It has also been observed that the biological children of alcoholic parents, particularly alcoholic fathers, are at greater risk to have a strong sweet preference, and this may manifest in some with an eating disorder. In the last two decades research has noted that specific genes may underlie the sweet preference in alcohol- and drug-dependent individuals, as well as in biological children of paternal alcoholics. There also appears to be some common genetic markers between alcohol dependence, bulimia, and obesity, such as the A1 allele gene and the dopamine 2 receptor gene.

  5. 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

  6. [Alcohol dependence mediated by monoamine neurotransmitters in the central nervous system].

    PubMed

    Yang, Xiaohua; Zhang, Huafeng; Lai, Jianghua

    2014-01-01

    Alcohol dependence, a chronic relapsing brain disease with the characteristics of drinking alcohol out of control, has become a serious social problem. Monoamine neurotransmitters, mainly including dopamine and 5-hydroxytryp¬tamine, play important roles in the occurrence, development and neural dysfunction of alcohol dependence syndrome. In this review, the roles of key factors of the monoamine system (dopamine receptor genes, 5-hydroxytryptamine receptor genes, transporter genes, tyrosine hydroxylase gene, tryptophanhydroxylase gene and monoamine oxidase gene) in alcohol dependence were discussed, and strategies for further studies of molecular mechanisms were proposed based on gene knockout mice models generated in our laboratory. Then, combining with studies on tyrosine hydroxylase activator CaMKII in our lab, therapeutic targets were discussed. Besides, epigenetic strategies for prevention and treatment of alcohol dependence syndrome were proposed. Furthermore, manipulating methylation levels in gene regulatory regions and alternative splicing of pre-mRNAs might also have clinical implications. Finally, based on new findings on genetic polymorphism, it is of great potential to carry out individual prevention and treatment for patients suffering from alcohol dependence.

  7. Cognitive control moderates the association between emotional instability and alcohol dependence symptoms.

    PubMed

    Stevenson, Brittany L; Dvorak, Robert D; Kuvaas, Nicholas J; Williams, Thomas J; Spaeth, Destini T

    2015-06-01

    Previous research has linked emotional instability with problematic alcohol use. This may be a function of increased "hot" information processing (which is relatively automatic in nature and highly influenced by emotional states) for individuals with more emotional instability. According to dual-process models, cognitive control may attenuate the impact of emotional instability by preventing an overreliance on hot information processing. It was hypothesized that emotional instability would be positively associated with alcohol-related consequences, but that cognitive control would moderate this association. Participants were undergraduate students (n = 80) who endorsed drinking at moderate levels. Participants completed laboratory assessments of emotional instability, alcohol use and its consequences, and cognitive control. An observed variable path model examined the association between emotional instability and alcohol problems. Consistent with hypotheses, emotional instability was positively associated with alcohol consequences, and this relationship was moderated by cognitive control, at least for dependence symptoms. At low levels of cognitive control, there was a positive association between emotional instability and dependence symptoms (β = 0.514, p < .001), however, this association was attenuated and no longer significant at high levels of cognitive control (β = 0.095, p = .302). Emotional instability may promote alcohol dependence via an overreliance on hot information processing. Consistent with dual-process theory, this relationship is diminished among individuals with more cognitive control. Interventions focusing on increasing cognitive control may be effective in reducing alcohol pathology associated with emotional instability. (PsycINFO Database Record

  8. 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

  9. 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

  10. The roles of familial alcoholism and adolescent family harmony in young adults' substance dependence disorders: mediated and moderated relations.

    PubMed

    Zhou, Qing; King, Kevin M; Chassin, Laurie

    2006-05-01

    This study examined the prospective relations among family history density of alcoholism (FHD), adolescent family harmony, and young adults' alcohol and drug dependence. Family harmony was rated by mothers and fathers in adolescence, and young adults' substance dependence diagnoses were obtained through structured interviews. Higher FHD predicted lower adolescent family harmony, which in turn increased young adults' odds of being diagnosed with drug dependence (with and without alcohol dependence) compared to no diagnoses or to alcohol dependence only. Family harmony also interacted with FHD such that the protective effect of family harmony on young adults' drug dependence with or without alcohol dependence decreased as FHD rose, and was nonsignificant at high levels of FHD. The findings suggest the importance of distinguishing among alcohol and drug dependence disorders and examining their differential etiological pathways, and also suggest that the protective effects of harmonious family environments on substance dependence may be limited at high levels of FHD.

  11. Dose-dependent effects of alcohol administration on behavioral profiles in the MCSF test.

    PubMed

    Karlsson, Oskar; Roman, Erika

    2016-02-01

    The acute effects of alcohol administration are age-, dose-, time- and task-dependent. Although generally considered to be a sedative drug, alcohol has both stimulatory and depressant effects on behavior, depending on dose and time. Alcohol-induced motor activating effects are consistently shown in mice but rarely demonstrated in adult, outbred rats using conventional behavioral tests. The aim of the present experiment was to study acute alcohol-induced effects on behavioral profiles in a more complex environment using the novel multivariate concentric square field™ (MCSF) test, designed for assessing different behaviors in the same trial including locomotor activity. Adult male Wistar rats (Sca:WI) were administered one intraperitoneal (i.p.) injection of alcohol (0.0 g/kg, 0.5 g/kg, 1.0 g/kg, or 1.5 g/kg) 5 min prior to the 30-min MCSF test. The two highest doses induced marked motor-suppressing effects. A significant interaction between group and time was found in general activity when comparing rats exposed to alcohol at 0.0 g/kg and 0.5 g/kg. In contrast to the 0.0 g/kg dose that increased the activity over time, animals administered the low dose (0.5 g/kg) demonstrated an initial high activity followed by a decline over time. No indications for acute alcohol-induced anxiolytic-like effects were found. The multivariate setting in the MCSF test appears to be sensitive for detecting motor-activating effects of low doses of alcohol as well as reduced locomotion at doses lower than in other behavioral tasks. The detection of subtle changes in behavior across time and dose is important for understanding alcohol-induced effects. This approach may be useful in evaluating alcohol doses that correspond to different degrees of intoxication in humans. PMID:26695588

  12. 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

  13. 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

  14. Transcranial Magnetic Stimulation and Deep Brain Stimulation in the treatment of alcohol dependence

    PubMed Central

    Alba-Ferrara, L.; Fernandez, F.; Salas, R.; de Erausquin, G. A.

    2013-01-01

    Alcohol dependence is a major social, economic, and public health problem. Alcoholism can lead to damage of the gastrointestinal, nervous, cardiovascular, and respiratory systems and it can be lethal, costing hundreds of billions to the health care system. Despite the existence of cognitive-behavioral therapy, psychosocial interventions, and spiritually integrated treatment to treat it, alcohol dependence has a high relapse rate and poor prognosis, albeit with high interindividual variability. In this review, we discuss the use of two neuromodulation techniques, namely repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), and their advantages and disadvantages compared to first-line pharmacological treatment for alcohol dependence. We also discuss rTMS and DBS targets for alcohol dependence treatment, considering experimental animal and human evidence, with careful consideration of methodological issues preventing the identification of feasible targets for neuromodulation treatments, as well as inter-individual variability factors influencing alcoholism prognosis. Lastly, we anticipate future research aiming to tailor the treatment to each individual patient by combining neurofunctional, neuroanatomical and neurodisruptive techniques optimizing the outcome. PMID:25598743

  15. 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

  16. Prevalence and Correlates of Alcohol Dependence Disorder among TB and HIV Infected Patients in Zambia

    PubMed Central

    O’Connell, Rebecca; Chishinga, Nathaniel; Kinyanda, Eugene; Patel, Vikram; Ayles, Helen; Weiss, Helen A.; Seedat, Soraya

    2013-01-01

    Objectives To determine the prevalence and correlates of alcohol dependence disorders in persons receiving treatment for HIV and Tuberculosis (TB) at 16 Primary Health Care centres (PHC) across Zambia. Methods 649 adult patients receiving treatment for HIV and/or TB at PHCs in Zambia (363 males, 286 females) were recruited between 1st December 2009 and 31st January 2010. Data on socio-demographic variables, clinical disease features (TB and HIV), and psychopathological status were collected. The Mini International Neuropsychiatric Interview (MINI) was used to diagnose alcohol dependence disorder. Correlates of alcohol dependence were analyzed for men only, due to low prevalence in women. Univariable and multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using general estimating equations to allow for within-PHC clustering. Results The prevalence of alcohol dependence was 27.2% (95%CI: 17.7-39.5%) for men and 3.9% (95%CI: 1.4-0.1%) for women. Factors associated with alcohol dependence disorder in men included being single, divorced or widowed compared with married (adjusted OR = 1.47, 95%CI: 1.00-2.14) and being unemployed (adjusted OR=1.30, 95%CI: 1.01-1.67). The highest prevalence of alcohol dependence was among HIV-test unknown TB patients (34.7%), and lowest was among HIV positive patients on treatment but without TB (14.1%), although the difference was not statistically significant (p=0.38). Conclusions Male TB/HIV patients in this population have high prevalence of alcohol dependence disorder, and prevalence differs by HIV/TB status. Further work is needed to explore interventions to reduce harmful drinking in this population. PMID:24069309

  17. Prevalence and Correlates of Insomnia in a Polish Sample of Alcohol-Dependent Patients

    PubMed Central

    Zhabenko, Nataliya; Wojnar, Marcin; Brower, Kirk J.

    2012-01-01

    Background Insomnia is an important symptom in alcohol-dependent patients because it may persist despite abstinence and predispose to relapse to drinking. The goal of the present study was to evaluate the prevalence and clinical correlates of insomnia in a sample of 302 alcohol-dependent patients admitted to treatment programs in Poland. Methods Participants were mostly men (73.8%) with a mean (SD) age of 43.5 (9.7) years. Insomnia in the past 1 month was assessed using a total score of 6 or higher on the Athens Insomnia Scale. Results Insomnia affected 62.9% of patients, and delayed sleep induction was the most common subtype. Insomnia was associated in bivariate analyses with less education, inadequate finances, problem drinking at an earlier age of onset, drinking frequency and quantity, drinking-related consequences, severity of alcohol and nicotine dependence, psychiatric and physical severity, and a childhood history of sexual or physical abuse (p < 0.05). Logistic regression analysis showed that mental and physical health status, severity of alcohol dependence, number of drinking days in the past 3 months, and childhood abuse were independent predictors of insomnia, explaining approximately 30 to 40% of the variance. Conclusions More than 60% of alcohol-dependent patients in a Polish sample screened positive for insomnia using a validated scale, a rate similar to those assessed with other scales in other countries. The study also showed that insomnia in alcohol-dependent patients is associated with poor physical health and childhood abuse, similar to the general population. The multifactorial nature of insomnia in alcohol-dependent patients has treatment implications. PMID:22471339

  18. 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

  19. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence

    PubMed Central

    Shaw, Daniel S.; Sitnick, Stephanie L.; Musselman, Samuel C.; Forbes, Erika E.

    2015-01-01

    Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function. PMID:24795442

  20. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence.

    PubMed

    Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L; Musselman, Samuel C; Forbes, Erika E

    2015-03-01

    Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.

  1. The Influence of Gene–Environment Interactions on the Development of Alcoholism and Drug Dependence

    PubMed Central

    2012-01-01

    Alcoholism and drug dependence are common psychiatric disorders with a heritability of about 50%; therefore genetic and environmental influences are equally important. Early-life stress is a predictor of adolescent problem drinking/drug use and alcohol/drug dependence in adulthood, but moderating factors governing the availability of alcohol/drug are important. The risk–resilience balance for addiction may be due in part to the interaction between genetic variation and environment stressors (G×E); this has been confirmed by twin studies of inferred genetic risk. Measured genotype studies to detect G×E effects have used a range of alcohol consumption and diagnostic phenotypes and stressors ranging from early-life to adulthood past year life events. In this article, the current state of the field is critically reviewed and suggestions are put forth for future research. PMID:22367454

  2. Alcoholism

    PubMed Central

    Girard, Donald E.; Carlton, Bruce E.

    1978-01-01

    There are important measurements of alcoholism that are poorly understood by physicians. Professional attitudes toward alcoholic patients are often counterproductive. Americans spend about $30 billion on alcohol a year and most adults drink alcohol. Even though traditional criteria allow for recognition of the disease, diagnosis is often made late in the natural course, when intervention fails. Alcoholism is a major health problem and accounts for 10 percent of total health care costs. Still, this country's 10 million adult alcoholics come from a pool of heavy drinkers with well defined demographic characteristics. These social, cultural and familial traits, along with subtle signs of addiction, allow for earlier diagnosis. Although these factors alone do not establish a diagnosis of alcoholism, they should alert a physician that significant disease may be imminent. Focus must be directed to these aspects of alcoholism if containment of the problem is expected. PMID:685264

  3. 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.

  4. COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence.

    PubMed

    Schellekens, Arnt F A; Franke, Barbara; Ellenbroek, Bart; Cools, Alexander; de Jong, Cor A J; Buitelaar, Jan K; Verkes, Robbert-Jan

    2013-03-01

    Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene-environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene-environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.

  5. [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

  6. Research opportunities for medications to treat alcohol dependence: addressing stakeholders' needs.

    PubMed

    Litten, Raye Z; Falk, Daniel; Ryan, Megan; Fertig, Joanne

    2014-01-01

    During the past decade, significant advances have been made in the development of medications to treat alcohol dependence. Four medications have been approved by the U.S. Food and Drug Administration for treating alcohol dependence-naltrexone, injectable naltrexone, acamprosate, and disulfiram-and several others show promise. The fact remains, however, that because of the heterogeneity of alcohol dependence, these medications will not work for all people, in all circumstances. Moreover, clinicians are not routinely prescribing these medications for alcohol treatment. This commentary poses a number of issues that must be addressed in order to advance the alcohol research field and to make medications a mainstream treatment for problematic drinking. These issues are framed from the perspective of the various stakeholders involved, including clinicians, patients, regulatory agencies, the pharmaceutical industry, and third-party payers. Addressing these issues will not only help to improve treatment but, as further described, will also open up many new research opportunities for alcohol investigators in the coming decade.

  7. Clinical relevance of as-needed treatment with nalmefene in alcohol-dependent patients.

    PubMed

    Aubin, Henri-Jean; Reimer, Jens; Nutt, David J; Bladström, Anna; Torup, Lars; François, Clément; Chick, Jonathan

    2015-01-01

    Nalmefene is the first drug approved for reduction of alcohol consumption. The aim of this study was to evaluate the clinical relevance of treatment with nalmefene in alcohol-dependent patients with a high drinking risk level from two randomised placebo-controlled 6-month studies (NCT00811720 and NCT00812461). Response criteria were based on alcohol consumption, Clinical Global Impression, and Short Form Health Survey mental component summary scores at month 6, analysed using logistic regression. The proportion of responders was higher in the nalmefene group than in the placebo group with odds ratios significantly in favour of nalmefene for all responder criteria; numbers-needed-to-treat ranged from 6 to 10. Significant differences from placebo in clinician-rated and patient-reported outcomes, and liver enzymes further supported the clinical relevance of the treatment effect. In conclusion, this study supports the clinical relevance of nalmefene treatment in patients with alcohol dependence. Nalmefene may help to reduce the alcohol-related burden and the large treatment gap, with currently less than 10% of alcohol-dependent patients in Europe receiving treatment.

  8. [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.

  9. Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

    PubMed

    Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

    2014-10-29

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism.

  10. History of sexual abuse and suicide attempts in alcohol-dependent patients.

    PubMed

    Jakubczyk, A; Klimkiewicz, A; Krasowska, A; Kopera, M; Sławińska-Ceran, A; Brower, K J; Wojnar, M

    2014-09-01

    History of child abuse is considered one of the important risk factors of suicide attempt in general population. At the same time it has been shown that suicide attempts appear significantly more frequently in alcoholics than in healthy individuals. The objective of this study was to investigate associations between history of childhood sexual abuse and suicide attempts in a sample of Polish alcohol dependent patients. A sample of 364 alcohol-dependent subjects was recruited in alcohol treatment centers in Warsaw, Poland. Information was obtained about demographics, family history of psychiatric problems, history of suicide attempts, sexual and physical abuse during childhood and adulthood and severity of alcohol problems. When analyzed by gender, 7.4% of male and 39.2% of female patients had a lifetime history of sexual abuse; 31.9% of the study group reported at least one suicide attempt during their lifetime. Patients who reported suicide attempts were significantly younger (p=0.0008), had greater severity of alcohol dependence (p=0.0002), lower social support (p=0.003), and worse economic status (p=0.002). Moreover, there was a significant association between history of suicide attempts and family history of psychiatric problems (p=0.00025), suicide attempts in the family (p=0.0073), childhood history of sexual abuse (p=0.009) as well as childhood history of physical abuse (p=0.002). When entered into linear regression analysis with other dependent variables history of childhood sexual abuse remained a significant predictor of suicide attempt (OR=2.52; p=0.035). Lifetime experience of sexual abuse is a significant and independent risk factor of suicide attempts in alcohol-dependent individuals.

  11. History of sexual abuse and suicide attempts in alcohol-dependent patients.

    PubMed

    Jakubczyk, A; Klimkiewicz, A; Krasowska, A; Kopera, M; Sławińska-Ceran, A; Brower, K J; Wojnar, M

    2014-09-01

    History of child abuse is considered one of the important risk factors of suicide attempt in general population. At the same time it has been shown that suicide attempts appear significantly more frequently in alcoholics than in healthy individuals. The objective of this study was to investigate associations between history of childhood sexual abuse and suicide attempts in a sample of Polish alcohol dependent patients. A sample of 364 alcohol-dependent subjects was recruited in alcohol treatment centers in Warsaw, Poland. Information was obtained about demographics, family history of psychiatric problems, history of suicide attempts, sexual and physical abuse during childhood and adulthood and severity of alcohol problems. When analyzed by gender, 7.4% of male and 39.2% of female patients had a lifetime history of sexual abuse; 31.9% of the study group reported at least one suicide attempt during their lifetime. Patients who reported suicide attempts were significantly younger (p=0.0008), had greater severity of alcohol dependence (p=0.0002), lower social support (p=0.003), and worse economic status (p=0.002). Moreover, there was a significant association between history of suicide attempts and family history of psychiatric problems (p=0.00025), suicide attempts in the family (p=0.0073), childhood history of sexual abuse (p=0.009) as well as childhood history of physical abuse (p=0.002). When entered into linear regression analysis with other dependent variables history of childhood sexual abuse remained a significant predictor of suicide attempt (OR=2.52; p=0.035). Lifetime experience of sexual abuse is a significant and independent risk factor of suicide attempts in alcohol-dependent individuals. PMID:24997776

  12. 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

  13. The association between insomnia and suicidal thoughts in adults treated for alcohol dependence in Poland

    PubMed Central

    Klimkiewicz, Anna; Bohnert, Amy S.B.; Jakubczyk, Andrzej; Ilgen, Mark A.; Wojnar, Marcin; Brower, Kirk

    2011-01-01

    Background Suicidal ideation is elevated for individuals with alcohol use disorders. Sleep problems are associated with suicide risk and alcohol use, and sleep problems may be associated with suicide risk in those with alcohol use disorders. For the present study, we hypothesized that self-reported sleep problems are associated with suicidal thoughts in a sample of adults seeking treatment for alcohol dependence in Poland. Methods The sample included 304 patients in addiction treatment programs in Warsaw, Poland who met criteria for alcohol dependence. Measures included demographic characteristics, frequency of alcohol use, psychiatric symptoms, suicidal ideation and two measures of insomnia, which differed by time frame: the Athens Insomnia Scale (AIS, past 1 month) and the Sleep Disorders Questionnaire (SDQ-7, past 6 months). Multivariable logistic regression models tested the association between insomnia and suicidal thoughts. Results In models that controlled for age, gender, and days of recent drinking, both measures of sleep problems were associated with suicidal ideation: AOR= 2.01 (95% CI: 1.50-2.70) [AIS] and 1.73 (95% CI: 1.29-2.31) [SDQ-7]. The association of sleep problems, as measured by the AIS, with suicide remained significant after adjusting for psychiatric symptoms, although the estimated effect size was smaller (AOR= 1.47; 95% CI: 1.05-2.06). Conclusions Among Polish adults with alcohol dependence, insomnia severity was associated with suicidal ideation. This finding highlights the need to assess for sleep problems, in addition to suicidal thoughts, in alcohol treatment settings and to further examine the potential consequences of poor sleep in this population. PMID:21996494

  14. Association of ADH and ALDH Genes With Alcohol Dependence in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) Sample

    PubMed Central

    Kuo, Po-Hsiu; Kalsi, Gursharan; Prescott, Carol A.; Hodgkinson, Colin A.; Goldman, David; van den Oord, Edwin J.; Alexander, Jeffry; Jiang, Cizhong; Sullivan, Patrick F.; Patterson, Diana G.; Walsh, Dermot; Kendler, Kenneth S.; Riley, Brien P.

    2008-01-01

    Background: The genes coding for ethanol metabolism enzymes [alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] have been widely studied for their influence on the risk to develop alcohol dependence (AD). However, the relation between polymorphisms of these metabolism genes and AD in Caucasian subjects has not been clearly established. The present study examined evidence for the association of alcohol metabolism genes with AD in the Irish Affected Sib Pair Study of alcohol dependence. Methods: We conducted a case–control association study with 575 independent subjects who met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, AD diagnosis and 530 controls. A total of 77 single nucleotide polymorphisms (SNPs) in the seven ADH (ADH1-7) and two ALDH genes (ALDH1A1 and ALDH2) were genotyped using the Illumina GoldenGate protocols. Several statistical procedures were implemented to control for false discoveries. Results: All markers with minor allele frequency greater than 0.01 were in Hardy–Weinberg equilibrium. Numerous SNPs in ADH genes showed association with AD, including one marker in the coding region of ADH1C (rs1693482 in exon6, Ile271Gln). Haplotypic association was observed in the ADH5 and ADH1C genes, and in a long haplotype block formed by the ADH1A and ADH1B loci. We detected two significant interactions between pairs of markers in intron 6 of ADH6 and intron 12 of ALDH2 (p = 5 × 10−5), and 5′ of both ADH4 and ADH1A (p = 2 × 10−4). Conclusion: We found evidence for the association of several ADH genes with AD in a sample of Western European origin. The significant interaction effects between markers in ADH and ALDH genes suggest possible epistatic roles between alcohol metabolic enzymes in the risk for AD. PMID:18331377

  15. 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

  16. Impaired emotional facial expression recognition in alcoholics, opiate dependence subjects, methadone maintained subjects and mixed alcohol-opiate antecedents subjects compared with normal controls.

    PubMed

    Kornreich, Charles; Foisy, Marie-Line; Philippot, Pierre; Dan, Bernard; Tecco, Juan; Noël, Xavier; Hess, Ursula; Pelc, Isidore; Verbanck, Paul

    2003-08-01

    The present study aims to explore whether an impairment in emotional facial expressions (EFE) decoding is specific to alcoholism compared with opiate dependence. An EFE decoding test consisting of 16 photographs of EFE portraying happiness, anger, sadness and disgust was administered to five different groups of 30 subjects each: recently detoxified alcoholics (RA); opiate addicts under methadone maintenance treatment (OM); detoxified opiate addicts (OA); detoxified subjects with both alcohol and opiate dependence antecedents (DAO); and normal controls (NC). Repeated measures analysis of variance using a multivariate approach was conducted on EFE decoding accuracy scores with group as the between-subjects factor. Accuracy scores were significantly lower in RA and DAO than in OM and OA, which had significantly lower scores than NC. Low accuracy scores in RA and DAO confirm previous results indicating that alcoholism is associated with impaired EFE recognition. Results in OM and OA indicate that opiate dependence is also associated with an impaired EFE decoding but less than in alcoholism. Alcohol and opiate chronic consumption could both exercise a deleterious effect on EFE-decoding brain function, alcohol having the most severe impact. Alternatively, EFE-decoding problems could be present before the development of alcohol and opiate dependence, with an additional effect of chronic alcohol consumption on EFE decoding. In this context, EFE-decoding impairment could reflect a more general emotional intelligence deficit in addicted populations.

  17. Real-time assessment of alcohol drinking and drug use in opioid-dependent polydrug users.

    PubMed

    Preston, Kenzie L; Jobes, Michelle L; Phillips, Karran A; Epstein, David H

    2016-10-01

    We investigated relationships between drinking, other drug use, and drug craving, using ecological momentary assessment (EMA), in a sample of polydrug users who were not heavy drinkers. In a prospective longitudinal cohort study, 114 heroin and cocaine users on methadone-maintenance treatment carried handheld electronic diaries during waking hours and were screened for drug and alcohol use for up to 25 weeks. Individuals who fulfilled the Diagnostic and Statistical Manual of Mental Disorders criteria for alcohol abuse or dependence were excluded. Participants responded to 2-5 random prompts per day to report on their moods, cravings, and activities and initiated entries when they used or acutely craved heroin or cocaine. Drinking alcohol was assessed in both types of entries. Breath alcohol was measured three times weekly. Participants reported drinking alcohol in 1.6% of random-prompt entries, 3.7% of event-contingent entries when craving cocaine and/or heroin, and 11.6% of event-contingent entries when using cocaine and/or heroin. Alcohol drinking was also associated with higher craving ratings and prestudy alcohol use. More drinking was detected by ambulatory self-report than by in-clinic breath testing. Even though we had screened out heavy drinkers from our sample of polydrug users, drinking was associated with heroin and cocaine craving and actual use. PMID:27579810

  18. Alcohol marketing and drunkenness among students in the Philippines: findings from the nationally representative Global School-based Student Health Survey

    PubMed Central

    2013-01-01

    Background A largely unaddressed issue in lower income countries and the Philippines, in particular, is the role of alcohol marketing and its potential link to early alcohol use among youth. This study examines the associations between exposures to alcohol marketing and Filipino youths’ drinking prevalence and drunkenness. Methods Cross-sectional analyses were used to examine the Global School-based Student Health Survey (GSHS) conducted in Philippines (2011). The self-administered questionnaires were completed by students primarily 13 to 16 years of age (N = 5290). Three statistical models were computed to test the associations between alcohol marketing and alcohol use, while controlling for possible confounding factors. Results Alcohol marketing, specifically through providing free alcohol through a company representative, was associated with drunkenness (AOR: 1.84; 95% CI = 1.06–3.21) among youths after controlling for demographic and psychosocial characteristics, peer environment, and risky behaviors. In addition, seeing alcohol ads in newspapers and magazines (AOR: 1.65, 95% CI = 1.05–2.58) and seeing ads at sports events, concerts or fairs (AOR: 1.50, 95% CI = 1.06–2.12) were significantly associated with increased reports of drunkenness. Conclusions There are significant associations between alcohol marketing exposure and increased alcohol use and drunkenness among youth in the Philippines. These findings highlight the need to put policies into effect that restrict alcohol marketing practices as an important prevention strategy for reducing alcohol use and its dire consequences among vulnerable youth. PMID:24325264

  19. 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

  20. 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

  1. IMPULSIVE SUICIDE ATTEMPTS PREDICT POST-TREATMENT RELAPSE IN ALCOHOL DEPENDENT PATIENTS

    PubMed Central

    Wojnar, Marcin; Ilgen, Mark A.; Jakubczyk, Andrzej; Wnorowska, Anna; Klimkiewicz, Anna; Brower, Kirk J.

    2010-01-01

    Background The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined. Methods A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months. Results Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, df=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95%C.I. = 1.13–6.95, p=0.026) and time to relapse (OR=2.10, 95% C.I. = 1.18–3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity. Conclusions This study is the first to document the relationship between pre-treatment impulsive suicide attempts and higher likelihood of post-treatment relapse in alcohol-dependent patents. Clinicians should routinely conduct an assessment for previous suicide attempts in patients with alcohol use disorders, and when impulsive suicidality is reported, they should recognize the increased risk for relapse and formulate their patients' treatment plans accordingly with the goals of reducing both alcoholic relapse and suicide rates. PMID:18556146

  2. Sleep abnormalities during abstinence in alcohol-dependent patients. Aetiology and management.

    PubMed

    Landolt, H P; Gillin, J C

    2001-01-01

    Virtually every type of sleep problem occurs in alcohol-dependent patients. Typically, these individuals take a longer time to fall asleep and show decreased sleep efficiency, shorter sleep duration and reduced amounts of slow wave sleep when compared with healthy controls. Their sleep patterns are fragmented, and the typical time course of electroencephalogram (EEG) delta wave activity is severely disrupted. The amount of rapid eye movement (REM) sleep may be reduced or increased. Sleep changes can persist during months or years of abstinence, and recent studies indicate that certain alterations in sleep architecture, as well as subjective sleep complaints, predict relapse to alcoholism. The mechanisms of action of short and long term alcohol administration on sleep are incompletely understood. They may arise from an interaction with gamma-aminobutyric acid (GABA), serotonin (5-hydroxytryptamine; 5-HT), adenosine or other neurotransmitter systems. While only a few pharmacological and nonpharmacological strategies to improve or normalise disturbed sleep in individuals who have recovered from alcoholism have been studied, the use of benzodiazepines, other hypnosedatives or selective serotonin reuptake inhibitors is not recommended. Therapies include sleep hygiene, bright light therapy, meditation, relaxation methods, and other nonpharmacological approaches. Further studies are needed to clarify the relationship between sleep, sleep abnormalities and alcoholism, and to establish new approaches to improve sleep in alcohol-dependent patients and to prevent withdrawal reactions that affect sleep during abstinence.

  3. Disease recognition is related to specific autobiographical memory deficits in alcohol-dependence.

    PubMed

    Poncin, Marie; Neumann, Aurore; Luminet, Olivier; Vande Weghe, Noémie; Philippot, Pierre; de Timary, Philippe

    2015-12-15

    The particularly high treatment gap in alcohol-dependence suggests the existence of important barriers to treatment decision and in particular difficulties in problem recognition. This study tested the relation between problem recognition and self-related memories. Forty-one recently detoxified alcohol-dependent individuals (AD) were compared to twenty alcoholic subjects that were abstinent for 6 months or more (recruited among alcoholics-anonymous (AA)), and to twenty controls on autobiographical memories elicited by pictures depicting or not alcohol using the autobiographical memory test. Autonoetic consciousness was measured with the Remember/Know paradigm. We tested whether memories performances were related with data obtained on the readiness to change questionnaire (RCQ) or with consciousness of the severity of drinking. AD subjects provided less specific memories than control and AA subjects, and fewer Remember responses than controls. The deficits in AD subjects were not specific for memories elicited by pictures depicting alcohol, suggesting a global deficit. Autobiographical memories specificity was negatively correlated to scores of consciousness of the severity of drinking but not to RCQ. Our results support potential recovery of autobiographical memory with abstinence. AD's deficits in autobiographical memory were related to capacities to recognize the severity and therefore may be a barrier to treatment decision. PMID:26365688

  4. 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

  5. 38 CFR 17.82 - Contracts for outpatient services for veterans with alcohol or drug dependence or abuse...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements of the “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR part 2) and the... Alcohol and Drug Abuse Patient Records” (42 CFR part 2) and the “Confidentiality of Certain Medical... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82...

  6. Relationships between the emotional and cognitive components of alexithymia and dependency in alcoholics.

    PubMed

    Loas, G; Otmani, O; Lecercle, C; Jouvent, R

    2000-09-25

    Several authors have shown that alexithymia, emotional and perceptual dependency characterize patients suffering from substance abuse. The aim of the study is to test the hypothesis that the emotional and cognitive components of alexithymia are associated with dependency in alcoholics. Three groups were investigated: 60 inpatients meeting the DSM-IV criteria for alcohol dependence, 57 healthy subjects, 144 university students. All subjects completed the following rating scales: The 20-item Toronto Alexithymia Scale (TAS-20), the Interpersonal Dependency Inventory (IDI), the Beck Depression Inventory (BDI), and the Embedded Figures Test (EFT). Partial correlations, using the BDI score as constant, were calculated. In normal subjects, the 'Emotion' subscale of the TAS-20 correlated with the 'Lack of social self-confidence' subscale of the IDI and the 'Cognitive' subscale of the TAS-20 did not correlate with the EFT score. In alcoholics, the 'Cognitive' subscale of the TAS-20 correlated with the 'Lack of social self-confidence' subscale, with the EFT score and with the 'Affirmation of autonomy' subscale. A particular cognitive style characterized by externally oriented thinking, affirmation of autonomy as denial of emotional dependency and field dependence could characterize alcoholics.

  7. Elderly: Alcohol and Drugs. Hearing before the Select Committee on Aging. House of Representatives, Ninety-Eighth Congress, First Session (Port Richey, Fla.)

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Select Committee on Aging.

    This document contains prepared statements and witness testimony from the Congressional hearing on the elderly and alcohol and drug use. Opening statements are given by Committe on Aging representatives Edward Roybal and Michael Bilirakis. Witness testimony is given by representatives of the University of South Florida Gerontology Center; the…

  8. The activity of lysosomal exoglycosidases in serum of alcohol-dependent men supplemented with borage oil enriched with vitamin E.

    PubMed

    Zaniewska, Agnieszka; Borzym-Kluczyk, Malgorzata; Szajda, Slawomir D; Romatowski, Jacek; Gil, Andrzej; Knas, Malgorzata; Dobryniewski, Jacek; Zwierz, Krzysztof

    2009-08-01

    The aim of this study was to determine the activity of the lysosomal exoglycosidases: alpha-mannosidase (MAN), alpha-fucosidase (FUC), and beta-glucuronidase (GLUCUR) in serum of alcohol-dependent men supplemented and not supplemented with borage oil enriched with vitamin E. Serum was collected from eight social drinkers and 16 alcohol-dependent men after a drinking period. The activity of exoglycosidases and the concentration of protein in serum were determined. The increase in specific activity of MAN and GLUCUR was significant in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E, in comparison with the specific activity in serum of social drinkers. In serum of alcohol-dependent men treated with borage oil enriched with vitamin E, specific activity of MAN and GLUCUR fluctuated in comparison with alcohol-dependent men not supplemented. Specific activity of FUC in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E showed a tendency to increase, in comparison with social drinkers. Specific activity of FUC had a tendency to decrease in serum of alcohol-dependent men supplemented with borage oil enriched with vitamin E, in comparison with alcohol-dependent men not supplemented. Thus, supplementation of alcohol-dependent men after a long-lasting drinking period with borage oil and vitamin E did not change the rate of catabolism of the oligosaccharide chains of glycoconjugates, as evaluated by serum activity of exoglycosidases. PMID:19735195

  9. The activity of lysosomal exoglycosidases in serum of alcohol-dependent men supplemented with borage oil enriched with vitamin E.

    PubMed

    Zaniewska, Agnieszka; Borzym-Kluczyk, Malgorzata; Szajda, Slawomir D; Romatowski, Jacek; Gil, Andrzej; Knas, Malgorzata; Dobryniewski, Jacek; Zwierz, Krzysztof

    2009-08-01

    The aim of this study was to determine the activity of the lysosomal exoglycosidases: alpha-mannosidase (MAN), alpha-fucosidase (FUC), and beta-glucuronidase (GLUCUR) in serum of alcohol-dependent men supplemented and not supplemented with borage oil enriched with vitamin E. Serum was collected from eight social drinkers and 16 alcohol-dependent men after a drinking period. The activity of exoglycosidases and the concentration of protein in serum were determined. The increase in specific activity of MAN and GLUCUR was significant in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E, in comparison with the specific activity in serum of social drinkers. In serum of alcohol-dependent men treated with borage oil enriched with vitamin E, specific activity of MAN and GLUCUR fluctuated in comparison with alcohol-dependent men not supplemented. Specific activity of FUC in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E showed a tendency to increase, in comparison with social drinkers. Specific activity of FUC had a tendency to decrease in serum of alcohol-dependent men supplemented with borage oil enriched with vitamin E, in comparison with alcohol-dependent men not supplemented. Thus, supplementation of alcohol-dependent men after a long-lasting drinking period with borage oil and vitamin E did not change the rate of catabolism of the oligosaccharide chains of glycoconjugates, as evaluated by serum activity of exoglycosidases.

  10. SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans.

    PubMed

    Mathies, Laura D; Blackwell, GinaMari G; Austin, Makeda K; Edwards, Alexis C; Riley, Brien P; Davies, Andrew G; Bettinger, Jill C

    2015-03-10

    Alcohol abuse is a widespread and serious problem. Understanding the factors that influence the likelihood of abuse is important for the development of effective therapies. There are both genetic and environmental influences on the development of abuse, but it has been difficult to identify specific liability factors, in part because of both the complex genetic architecture of liability and the influences of environmental stimuli on the expression of that genetic liability. Epigenetic modification of gene expression can underlie both genetic and environmentally sensitive variation in expression, and epigenetic regulation has been implicated in the progression to addiction. Here, we identify a role for the switching defective/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in regulating the behavioral response to alcohol in the nematode Caenorhabditis elegans. We found that SWI/SNF components are required in adults for the normal behavioral response to ethanol and that different SWI/SNF complexes regulate different aspects of the acute response to ethanol. We showed that the SWI/SNF subunits SWSN-9 and SWSN-7 are required in neurons and muscle for the development of acute functional tolerance to ethanol. Examination of the members of the SWI/SNF complex for association with a diagnosis of alcohol dependence in a human population identified allelic variation in a member of the SWI/SNF complex, suggesting that variation in the regulation of SWI/SNF targets may influence the propensity to develop abuse disorders. Together, these data strongly implicate the chromatin remodeling associated with SWI/SNF complex members in the behavioral responses to alcohol across phyla.

  11. The outcome of patients sustaining a proximal femur fracture who suffer from alcohol dependency.

    PubMed

    Faroug, R; Amanat, S; Ockendon, M; Shah, S V; Gregory, J J

    2014-07-01

    There are many negative health consequences associated with alcohol dependency. Fractures of the proximal femur carry significant morbidity and mortality. This study examines the outcomes in patients with alcohol dependency, who sustain a fracture of the proximal femur. Twenty-eight consecutive alcohol dependent patients who suffered a fracture of the proximal femur were identified over a three year period. Data were collected on demographics, co-morbidity, surgical factors, mobility and mortality. The median age of patients was 61 years. The median weekly alcohol intake was 158 units. Thirteen patients sustained an extra-capsular fracture and 15 an intra-capsular proximal femoral fracture. Twenty-two fractures were treated with internal fixation and six with arthroplasty. The overall mortality rate was 29% at a median of 15 months post fracture. The failure rate of intra-capsular fractures fixed with cannulated screws was 56% at a median time of 43 days. All patients had a reduction in mobility compared to their pre-operative function. The reduction in mobility was greatest in patients with intra-capsular fractures treated with cannulated screw fixation. Alcohol dependent patients sustaining a fracture of the proximal femur are significantly younger than non-alcohol dependent patients sustaining the same injury. Despite the younger age at presentation the one year mortality rate of this group was high (29%). The high rate of complications with fracture fixation and high one year mortality suggest that hemiarthroplasty may be the best treatment option for intra-capsular fractures in this patient group.

  12. Treatment in hospital for alcohol-dependent patients decreases attentional bias

    PubMed Central

    Flaudias, Valentin; Brousse, Georges; de Chazeron, Ingrid; Planche, François; Brun, Julien; Llorca, Pierre-Michel

    2013-01-01

    Background and objectives: Previous studies in alcohol-dependent patients have shown an attentional bias (AB) under related substance cues, which can lead to relapse. This AB can be evaluated by the alcohol Stroop test (AST). The AST is a modified Stroop task in which participants have to name the color of an alcohol-related word or a neutral word. AB is the response-time difference between these two types of words. The goal of the current study was to examine modification of AB during specialized hospitalization for alcohol dependence, with the suppression of a training bias that could be present in within-subject design. Methods: Individuals with alcohol-dependence disorders (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) and admitted for withdrawal in the addiction unit of the University Hospital of Clermont-Ferrand (test group, n = 42) and persons with no alcohol or psychiatric disorder (control group, n = 16), recruited among colleagues and friends of the staff, performed the AST. A subgroup of the test group performed the AST in admission (admission group, n = 19), and another subgroup undertook the test immediately before discharge (discharge group, n = 23). Results: Results showed an AB only for patients seen at admission (F[1,55] = 3.283, P = 0.075). Moreover, we observed that the AB in the admission group (mean = 34 ms, standard deviation [SD] = 70.06) was greater than the AB in the control group (mean = 23 ms, SD = 93.42), itself greater than the AB in the discharge group (mean = −12 ms, SD = 93.55) (t[55] = −1.71; P = 0.09). Conclusion: Although the results are preliminary, the present study provides evidence for changes in the AB during alcohol-addiction treatment and for the value of these methods to diminish AB during detoxification. PMID:23785237

  13. Neuropeptide YY(2)R blockade in the central amygdala reduces anxiety-like behavior but not alcohol drinking in alcohol-dependent rats.

    PubMed

    Kallupi, Marsida; Vendruscolo, Leandro F; Carmichael, Casey Y; George, Olivier; Koob, George F; Gilpin, Nicholas W

    2014-09-01

    Electrophysiological data suggest a dual role of Y2 receptors (Y2 Rs) as autoreceptors regulating neuropeptide Y release and heteroceptors regulating gamma-aminobutyric acid release in the central amygdala (CeA). Here, we report that neither systemic (JNJ-31020028) nor intra-CeA (BIIE0246) Y2 R antagonism altered operant alcohol responding by alcohol-dependent or non-dependent rats. Conversely, BIIE0246 in the CeA reduced anxiety-like behavior in alcohol-dependent and alcohol-naïve rats. The finding that Y2 R antagonism reduces anxiety-like behavior but not alcohol drinking suggests that these two effects may occur via different functions of the Y2 R (e.g. autoreceptor versus heteroceptor function).

  14. Use of Pharmacotherapies in the Treatment of Alcohol Use Disorders and Opioid Dependence in Primary Care

    PubMed Central

    Lee, Jinhee; Kresina, Thomas F.; Campopiano, Melinda; Lubran, Robert; Clark, H. Westley

    2015-01-01

    Substance-related and addictive disorders are chronic relapsing conditions that substantially impact public health. Effective treatments for these disorders require addressing substance use/dependence comprehensively as well as other associated comorbidities. Comprehensive addressing of substance use in a medical setting involves screening for substance use, addressing substance use directly with the patient, and formulating an appropriate intervention. For alcohol dependence and opioid dependence, pharmacotherapies are available that are safe and effective when utilized in a comprehensive treatment paradigm, such as medication assisted treatment. In primary care, substance use disorders involving alcohol, illicit opioids, and prescription opioid abuse are common among patients who seek primary care services. Primary care providers report low levels of preparedness and confidence in identifying substance-related and addictive disorders and providing appropriate care and treatment. However, new models of service delivery in primary care for individuals with substance-related and addictive disorders are being developed to promote screening, care and treatment, and relapse prevention. The education and training of primary care providers utilizing approved medications for the treatment of alcohol use disorders and opioid dependence in a primary care setting would have important public health impact and reduce the burden of alcohol abuse and opioid dependence. PMID:25629034

  15. 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

  16. [Psychometric properties of the Nicotine Dependence Syndrome Scale (NDSS) in a sample of smokers treated for their alcohol dependence].

    PubMed

    Becoña, Elisardo; Nogueiras, Luis; Flórez, Gerardo; Alvarez, Sandra; Vázquez, Dolores

    2010-01-01

    The assessment of nicotine dependence with brief instruments is of great relevance for the better detection of this disorder. Here we present the results with the Nicotine Dependence Syndrome Scale (NDSS) by Shiffman, Waters and Hickcox (2004) in a sample of 183 patients treated at an Alcohol Dependence Unit who were also cigarette smokers. The results indicate that the general factor which evaluates nicotine dependence (NDSS-T) has good reliability (Cronbach's alpha = 0.80). Factor analysis identifies four of the five factors proposed in the original version, those of drive, priority, continuity and stereotypy. Reliability of the scales derived ranges from very good (0.80) to moderate (0.63). The NDSS-T correlates significantly with the Fagerström Tolerance Questionnaire (FTQ), with the DSM-IV criteria for nicotine dependence assessed through the SCID, and with the number of cigarettes smoked per day. The ROC curves indicate an NDSS-T score of 0.80 under the curve (0.70 for the FTND), showing that it adequately predicts nicotine dependence. This study confirms the utility of this new instrument for assessing nicotine dependence in smokers who also abuse or depend upon alcohol.

  17. 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

  18. Alcohol abuse-duration dependent decrease in plasma testosterone and antioxidants in males.

    PubMed

    Maneesh, M; Dutta, Sanjiba; Chakrabarti, Amit; Vasudevan, D M

    2006-01-01

    Ethanol is a testicular toxin and it causes fertility abnormalities with low sperm count and impaired sperm motility in men. The present study was designed to investigate plasma testosterone level and hypothalamic pituitary gonadal (HPG) axis function in alcoholic men and also effect of ethanol on systemic oxidative stress. Forty six male alcohol abusers in the age group 20-40 years were selected. Fifty five, males in the same age group served as control. Alcohol abusers had significantly low plasma testosterone with low luteinizing hormone and follicle stimulating hormone. In addition they had significantly high thiobarbituric acid reactive substances (TBARS), superoxide dismutase and glutathione S-transferase, and low glutathione, ascorbic acid, catalase, glutathione reductase and glutathione peroxidase. Moreover, serum testosterone level in alcoholics negatively correlated with duration of alcohol abuse, and TBARS. Duration dependent decreased serum testosterone level in alcohol abusers might be due to 1) increased oxidative stress which can damage Leydig and supporting Sertoli cells and 2) impaired HPG axis.

  19. A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence

    PubMed Central

    Guerrini, Irene; Gentili, Claudio; Nelli, Gloria; Guazzelli, Mario

    2006-01-01

    Background We carried out a three months follow-up study on the efficacy of metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term Treatment (ALT) Unit – University of Pisa (Italy). We analyzed the clinical data, psychometric tests and blood tests of 160 alcoholics on admission and after 3 months of treatment. We compared 58 pts treated with metadoxine (MET) with 102 pts who did not receive (NULL) any drug as an adjunct to the psycho-educational interventions provided by the ALT Unit. Results At follow-up, the patients in treatment with metadoxine showed a significant improvement in the rate of complete abstinence (44.8% vs. 21.6%; chi square: 8.45, df = 1, p < 0.0037). Furthermore, the number of drop-outs at three months of treatment was also significantly lower in the MET than in the NULL group (17% vs. 57%; chi square of 23.22, df = 1, p < 0.001). Conclusion Our findings support the use of metadoxine in the management of alcohol dependence. However, randomized clinical trials are necessary to confirm and replicate them. This study raises the importance of identifying new pharmacological compounds effective on the outcome of alcoholism in order to help patients to best adhere to treatment programs and to prevent the development of mental and physical complications due to chronic and heavy use of alcohol. PMID:17176456

  20. Suppression of Alcohol Dependence Using Baclofen: A 2-Year Observational Study of 100 Patients

    PubMed Central

    de Beaurepaire, Renaud

    2012-01-01

    Aims: The purpose of this study was to examine the long-term effects of baclofen in a large cohort of alcohol-dependent patients compliant to baclofen treatment. Methods: A hundred patients with alcohol dependence, resistant to usual treatments, were treated with escalating doses of baclofen (no superior limit). Alcohol consumption (in grams) and craving for alcohol were assessed before treatment and at 3, 6, 12, and 24 months. Assessments were simply based on patients’ statements. The outcome measure was the consumption of alcohol, rated according to the World Health Organization criteria for risk of chronic harm. Results: While all patients were rated “at high risk” at baseline, approximately half of them were rated “at low risk” at 3, 6, 12, and 24 months. The sum of patients who were at “low risk” and at “moderate risk” (improved patients) was 84% at 3 months, 70% at 6 months, 63% at 1 year, and 62% at 2 years. The constancy of improvement over the 2-years was remarkable. The average maximal dose of baclofen taken was 147 mg/day. Ninety-two percentage of patients reported that they experienced the craving-suppressing effect of baclofen. Significant relationships were found between the amount in grams of alcohol taken before treatment and the maximal dose of baclofen required, and between the existence of a mental disorder and a lesser effect of baclofen. Conclusion: Baclofen produces an effortless decrease or suppression of alcohol craving when it is prescribed with no superior limit of dose. Potential limitations in the effectiveness of baclofen include the coexistence of a mental disorder, the concomitant use of other psychotropic drugs, a lack of real motivation in patients to stop drinking, and the impossibility to reach the optimal dose of baclofen because of unbearable side-effects (sometimes possibly related to too sharp a protocol of dose escalation). PMID:23316172

  1. Field Dependency, n Power and Locus of Control Variables in Alcohol Aversion.

    ERIC Educational Resources Information Center

    Query, William T.

    1983-01-01

    Compared individual differences and treatment effectiveness in male volunteer alcoholics (N=47) in a 10-day electroconditioning aversion program. Follow-up showed combination therapy was more successful. Internals and hard liquor drinkers tended to be abstinent as predicted. Field dependency was a more unstable variable for outcome. (Author/JAC)

  2. [Psychopathological symptoms and personality traits in alcohol-dependent patients: a comparative study].

    PubMed

    Bravo de Medina, Ricardo; Echeburúa, Enrique; Aizpiri, Javier

    2007-01-01

    The aim of this paper was to describe the psychopathological and personality profile associated with alcohol dependence and to compare it with those of non-addictive disorders and the normal population. The sample consisted of 158 alcohol-dependent participants attending a psychiatric outpatient clinic, 120 psychiatric patients with non-addictive disorders and 103 participants from the general population chosen to match the patient samples for age, gender and socioeconomic level. All participants were assessed with different instruments related to personality (Impulsiveness Scale, Sensation-Seeking Scale and STAI), psychopathology (SCL-90-R, BDI and Maladjustment Scale) and personality disorders (MCMI-II). Patients from the clinical groups presented more symptoms of anxiety and depression than the healthy participants and had more problems adjusting to everyday life, but there were no differences between the two clinical groups. Alcohol-dependent patients were more impulsive and sensation-seeking than the other two groups. Histrionic, narcissistic and antisocial personality disorders were specific to the alcohol-dependent patients. The implications of this study for further research are discussed.

  3. Neuropsychological Impairment and Relapse Following Inpatient Detoxification in Severe Alcohol Dependence

    ERIC Educational Resources Information Center

    Morrison, Fraser

    2011-01-01

    The aim of the study was to examine the relationship between neuropsychological impairment in severe alcohol dependence and relapse. This was assessed following inpatient detoxification over a period of three months. Participants were tested on measures of neuropsychological functioning at the end of a seven to ten day stay in an inpatient alcohol…

  4. Integrated Psychosocial and Opioid-Antagonist Treatment for Alcohol Dependence: A Systematic Review of Controlled Evaluations

    ERIC Educational Resources Information Center

    Vaughn, Michael G.; Howard, Matthew O.

    2004-01-01

    Methodological characteristics and outcomes of 14 controlled clinical investigations of integrated psychosocial and opioid-antagonist alcohol dependence treatment were evaluated. The 14 studies were identified through computerized bibliographic and manual literature searches. Clients receiving integrated psychosocial and opioid-antagonist…

  5. Empirically defined subtypes of alcohol dependence in an Irish family sample.

    PubMed

    Sintov, Nicole D; Kendler, Kenneth S; Young-Wolff, Kelly C; Walsh, Dermot; Patterson, Diana G; Prescott, Carol A

    2010-03-01

    Alcohol dependence (AD) is clinically and etiologically heterogeneous. The goal of this study was to explore AD subtypes among a sample of 1221 participants in the Irish Affected Sib Pair Study of Alcohol Dependence, all of whom met DSM-IV criteria for AD. Variables used to identify the subtypes included major depressive disorder, antisocial personality disorder, illicit drug dependence (cannabis, sedatives, stimulants, cocaine, opioids, and hallucinogens), nicotine dependence, the personality traits of neuroticism and novelty seeking, and early alcohol use. Using latent class analysis, a 3-class solution was identified as the most parsimonious description of the data. Individuals in a Mild class were least likely to have comorbid psychopathology, whereas a severe class had highest probabilities of all comorbid psychopathology. The third class was characterized by high probabilities of major depression and higher neuroticism scores, but lower likelihood of other comorbid disorders than seen in the severe class. Overall, sibling pair resemblance for class was stronger within than between classes, and was greatest for siblings within the severe class, suggesting a stronger familial etiology for this class. These findings are consistent with the affective regulation and behavioral disinhibition subtypes of alcoholism, and are in line with prior work suggesting familial influences on subtype etiology.

  6. The contribution of emotional maltreatment to alcohol dependence in a treatment-seeking sample.

    PubMed

    Potthast, Nadine; Neuner, Frank; Catani, Claudia

    2014-05-01

    Studies reporting a link between child maltreatment and addiction have typically focused on physical and sexual abuse. In contrast, emotional maltreatment has rarely been studied in substance-abusing samples although it is associated with a wide range of dysfunction. The current study aimed to determine the specific impact of different types of maltreatment and peer victimization on alcohol dependence and to examine the potentially mediating role of psychopathology. A sample of treatment seeking adults with alcohol dependence (N=72) underwent an extensive clinical examination including both a standardized interview and self-report measures. Child maltreatment, peer victimization, severity of alcohol dependence, and general psychopathology were assessed. Regression analyses revealed that emotional maltreatment was the strongest predictor of alcohol dependence severity whereas a unique contribution of peer victimization was not found. Our findings suggest that emotional maltreatment might have a major role in the etiology of AD that seems to exceed the contribution of other abuse and victimization experiences. Thereby, the study underscores the need for considering child maltreatment experiences in the prevention and treatment of AD. PMID:24561015

  7. Stress system changes associated with marijuana dependence may increase craving for alcohol and cocaine

    PubMed Central

    Fox, Helen C.; Tuit, Keri L.; Sinha, Rajita

    2013-01-01

    Objective To date, little research exists defining bio-behavioral adaptations associated with both marijuana abuse and risk of craving and relapse to other drugs of abuse during early abstinence. Method Fifty-nine treatment-seeking individuals dependent on alcohol and cocaine were recruited. Thirty of these individuals were also marijuana (MJ) dependent; 29 were not. Twenty-six socially drinking healthy controls were also recruited. All participants were exposed to three 5-min guided imagery conditions (stress, alcohol/cocaine cue and relaxing), presented randomly, one per day across three consecutive days. Measures of craving, anxiety, heart rate, blood pressure, plasma adrenocorticotrophic hormone and cortisol were collected at baseline and subsequent recovery time points. Results The MJ-dependent group showed increased basal anxiety ratings and cardiovascular output alongside enhanced alcohol craving and cocaine craving, and dampened cardiovascular response to stress and cue. They also demonstrated elevated cue-induced anxiety and stress-induced cortisol and adrenocorticotrophic hormone levels, which were not observed in the non-MJ-dependent group or controls. Cue-related alcohol craving and anxiety were both predictive of a shorter number of days to marijuana relapse following discharge from inpatient treatment. Conclusions Findings provide some support for drug cross-sensitization in terms of motivational processes associated with stress-related and cue-related craving and relapse. PMID:23280514

  8. Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure

    PubMed Central

    2013-01-01

    Background Maternal alcohol consumption is known to adversely affect fetal neurodevelopment. While it is known that alcohol dose and timing play a role in the cognitive and behavioral changes associated with prenatal alcohol exposure, it is unclear what developmental processes are disrupted that may lead to these phenotypes. Methods Mice (n=6 per treatment per developmental time) were exposed to two acute doses of alcohol (5 g/kg) at neurodevelopmental times representing the human first, second, or third trimester equivalent. Mice were reared to adulthood and changes to their adult brain transcriptome were assessed using expression arrays. These were then categorized based on Gene Ontology annotations, canonical pathway associations, and relationships to interacting molecules. Results The results suggest that ethanol disrupts biological processes that are actively occurring at the time of exposure. These include cell proliferation during trimester one, cell migration and differentiation during trimester two, and cellular communication and neurotransmission during trimester three. Further, although ethanol altered a distinct set of genes depending on developmental timing, many of these show interrelatedness and can be associated with one another via ‘hub’ molecules and pathways such as those related to huntingtin and brain-derived neurotrophic factor. Conclusions These changes to brain gene expression represent a ‘molecular footprint’ of neurodevelopmental alcohol exposure that is long-lasting and correlates with active processes disrupted at the time of exposure. This study provides further support that there is no neurodevelopmental time when alcohol cannot adversely affect the developing brain. PMID:23497526

  9. Prevalence of alcohol and drug dependence in rural and slum population of Chandigarh: A community survey

    PubMed Central

    Chavan, B. S.; Arun, Priti; Bhargava, Rachna; Singh, Gurvinder Pal

    2007-01-01

    The present epidemiological survey was conducted by the department of psychiatry, Govt. Medical College and Hospital, Chandigarh to estimate the pattern of alcohol and other substance dependence in rural and slum dwellers population of Chandigarh. In this survey 6.88% individuals of the total population surveyed (2992) fulfilled dependence criteria of ICD-10. Alcohol was the primary substance of dependence for majority of urban slum substance users and rural areas users. Age at first drug use was 20.89 ± 5.31 years (mean ± S.D) among rural population and 19.75 ± 5.4 years (mean ± SD) in urban slums. Majority of them reported having health related complications (85.71%) followed by family problems (77.31%) due to drug dependence. This survey reflects the need to intensify efforts at the community level to reach the unreached. PMID:20640064

  10. Alcohol Consumption, Craving, and Craving Control Efforts Assessed Daily in the Context of Readiness to Change Among Individuals with Alcohol Dependence and PTSD.

    PubMed

    Browne, Kendall C; Wray, Tyler B; Stappenbeck, Cynthia A; Krenek, Marketa; Simpson, Tracy L

    2016-02-01

    Research has demonstrated the positive association between alcohol craving and alcohol use and has identified craving as a central component of alcohol use disorders (AUD). Despite potential clinical implications, few studies have examined the relationship between craving and alcohol use in individuals with AUD and common psychiatric comorbidities or explored possible moderators of the craving-alcohol use relationship. The current study used daily monitoring data to: 1) replicate previous findings detecting a positive relationship between craving and alcohol use in individuals with AUD and co-occurring posttraumatic stress disorder (PTSD) and 2) extend these findings by examining the influence of initial change motivation on the craving-use relationship and within-day associations among craving, efforts to control craving, and alcohol consumption. Participants were 84 individuals with alcohol dependence and PTSD enrolled in an intervention study. Generalized estimating equations using pre-treatment baseline daily data revealed significant main effects for craving, craving control, and motivation to change alcohol use. Daily craving was positively related to alcohol use. Greater change motivation and craving control (i.e., efforts to resist craving, avoidance of thoughts and feelings related to craving) were negatively related to alcohol use. A significant interaction was detected between baseline change motivation and daily craving indicating that the association between craving and alcohol use was significantly stronger for those with low baseline change motivation. A significant interaction was also detected between craving control and daily craving, suggesting that participants were more likely to consume alcohol when experiencing high levels of craving if they reported low levels of craving control. Findings bolster the idea that efforts to prevent or ameliorate craving are critical to treatment success for individuals with AUD and PTSD who are seeking to

  11. Personality disorders among alcohol-dependent patients manifesting or not manifesting cocaine abuse: a comparative pilot study.

    PubMed

    Echeburúa, Enrique; De Medina, Ricardo Bravo; Aizpiri, Javier

    2009-01-01

    This study assessed personality disorders (PDs) in 158 alcohol-dependent outpatients (62 manifesting cocaine abuse and 96 without cocaine abuse) with the International Personality Disorders Examination interview between 2003 and 2006. Thirty-nine alcohol-dependent/cocaine abusers (62.9% of this group) and 51 only alcohol-dependent patients (53.1% of this group) manifested at least one PD. There were no statistically significant differences between groups in the overall prevalence rate of PDs. The most prevalent PDs, among the alcohol-dependent/cocaine abusers, were antisocial (21%), narcissistic (14.5%), and borderline (11.3%) PDs. The most frequently diagnosed PDs among the only alcohol-dependent patients were obsessive-compulsive (20.8%), paranoid (10.4%), and dependent (9.4%) PDs. There were significant differences between the groups. The study limitations are discussed.

  12. Predicting the future relapse of alcohol-dependent patients from structural and functional brain images.

    PubMed

    Seo, Sambu; Mohr, Johannes; Beck, Anne; Wüstenberg, Torsten; Heinz, Andreas; Obermayer, Klaus

    2015-11-01

    In alcohol dependence, individual prediction of treatment outcome based on neuroimaging endophenotypes can help to tailor individual therapeutic offers to patients depending on their relapse risk. We built a prediction model for prospective relapse of alcohol-dependent patients that combines structural and functional brain images derived from an experiment in which 46 subjects were exposed to alcohol-related cues. The patient group had been subdivided post hoc regarding relapse behavior defined as a consumption of more than 60 g alcohol for male or more than 40 g alcohol for female patients on one occasion during the 3-month assessment period (16 abstainers and 30 relapsers). Naïve Bayes, support vector machines and learning vector quantization were used to infer prediction models for relapse based on the mean and maximum values of gray matter volume and brain responses on alcohol-related cues within a priori defined regions of interest. Model performance was estimated by leave-one-out cross-validation. Learning vector quantization yielded the model with the highest balanced accuracy (79.4 percent, p < 0.0001; 90 percent sensitivity, 68.8 percent specificity). The most informative individual predictors were functional brain activation features in the right and left ventral tegmental areas and the right ventral striatum, as well as gray matter volume features in left orbitofrontal cortex and right medial prefrontal cortex. In contrast, the best pure clinical model reached only chance-level accuracy (61.3 percent). Our results indicate that an individual prediction of future relapse from imaging measurement outperforms prediction from clinical measurements. The approach may help to target specific interventions at different risk groups.

  13. Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate

    PubMed Central

    Karpyak, V M; Biernacka, J M; Geske, J R; Jenkins, G D; Cunningham, J M; Rüegg, J; Kononenko, O; Leontovich, A A; Abulseoud, O A; Hall-Flavin, D K; Loukianova, L L; Schneekloth, T D; Skime, M K; Frank, J; Nöthen, M M; Rietschel, M; Kiefer, F; Mann, K F; Weinshilboum, R M; Frye, M A; Choi, D S

    2014-01-01

    Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P=4.6 × 10−5). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P=0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P=0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow. PMID:25290263

  14. 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.

  15. Overview of Alcohol Consumption

    MedlinePlus

    ... Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol ... other questions about alcohol. Here’s what we know: Alcohol’s effects vary from person to person, depending on a ...

  16. Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol Dependence

    PubMed Central

    Suh, Jesse J.; Pettinati, Helen M.; Kampman, Kyle M.; O’Brien, Charles P.

    2008-01-01

    Recently, we reported that naltrexone at 150mg/day significantly decreased cocaine and alcohol use for men, but not women with co-occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender response to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems, or nausea while in treatment. Further research on the impact of pre-treatment and in-treatment gender differences with naltrexone is warranted. PMID:19034737

  17. Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence.

    PubMed

    Crabbe, J C

    2001-02-01

    Various explanations for the dependence on alcohol are attributed to the development of tolerance to some of alcohol's effects, alterations in sensitivity to its rewarding effects, and unknown pathologic consequences of repeated exposure. All these aspects of dependence have been modeled in laboratory rodents, and these studies have consistently shown a significant influence of genetics. Genetic mapping studies have identified the genomic location of the specific genes for some of these contributing phenotypes. In addition, studies have shown that some genes in mice seem to affect both alcohol self-administration and alcohol withdrawal severity: genetic predisposition to high levels of drinking covaries with genetic predisposition to low withdrawal severity, and vice versa. Finally, the role of genetic background on which genes are expressed is important, as are the specifics of the environment in which genetically defined animals are tested. Understanding dependence will require disentangling the multiple interactions of many contributing phenotypes, and genetic analyses are proving very helpful. However, rigorous understanding of both gene-gene and gene-environment interactions will be required to interpret genetic experiments clearly.

  18. Development of an acceptance-based coping intervention for alcohol dependence relapse prevention.

    PubMed

    Vieten, Cassandra; Astin, John A; Buscemi, Raymond; Galloway, Gantt P

    2010-04-01

    Both psychological and neurobiological findings lend support to the long-standing clinical observation that negative affect is involved in the development and maintenance of alcohol dependence, and difficulty coping with negative affect is a common precipitant of relapse after treatment. Although many current approaches to relapse prevention emphasize change-based strategies for managing negative cognitions and affect, acceptance-based strategies for preventing relapse to alcohol use are intended to provide methods for coping with distress that are fundamentally different from, though in theory complementary to, approaches that emphasize control and change. This paper describes the development of Acceptance-Based Coping for Relapse Prevention (ABCRP), a new intervention for alcohol-dependent individuals who are within 6 months of having quit drinking. Results of preliminary testing indicate that the intervention is feasible with this population; and a small uncontrolled pilot study (N = 23) showed significant (P < .01) improvements in self-reported negative affect, emotional reactivity, perceived stress, positive affect, psychological well-being, and mindfulness level, as well as a trend (P = .06) toward reduction in craving severity between pre- and postintervention assessments. The authors conclude that this acceptance-based intervention seems feasible and holds promise for improving affect and reducing relapse in alcohol-dependent individuals, warranting further research.

  19. 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

  20. Predicting Vocational Rehabilitation Outcomes for People with Alcohol Abuse/Dependence: An Application of Chi-Squared Automatic Interaction Detector

    ERIC Educational Resources Information Center

    Brickham, Dana M.

    2012-01-01

    People with alcohol abuse/dependence disabilities are often faced with a complex recovery process due to the exacerbating and chronic aspects of their condition. Vocational rehabilitation for people with alcohol abuse/dependence can help individuals access and maintain employment, and through employment can enhance physical and psychological…

  1. 38 CFR 17.80 - Alcohol and drug dependence or abuse treatment and rehabilitation in residential and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract....

  2. 38 CFR 17.83 - Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...

  3. 38 CFR 17.83 - Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...

  4. Interaction between the DRD4 VNTR Polymorphism and Proximal and Distal Environments in Alcohol Dependence during Emerging and Young Adulthood

    PubMed Central

    Park, Aesoon; Sher, Kenneth J.; Todorov, Alexandre A.; Heath, Andrew C.

    2011-01-01

    The manifestation of alcohol dependence at different developmental stages may be associated with different genetic and environmental factors. Taking a developmental approach, the current study characterized interaction between the dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism and developmentally specific environmental factors (childhood adversity, college/Greek involvement, and delayed adult role transition) on alcohol dependence during emerging and young adulthood. Prospective data were obtained from a cohort of 234 Caucasian individuals (56% female) followed up at ages 18 through 34. A longitudinal hierarchical factor model was estimated to model a trait-like persistent alcohol dependence factor throughout emerging and young adulthood and two residual state-like alcohol dependence factors limited to emerging adulthood and young adulthood, respectively. To account for those alcohol dependence factors, three two-way interaction effects between the DRD4 VNTR polymorphism and the three developmentally specific environment factors were modeled. Carriers of the DRD4 long allele showed greater susceptibility to environmental effects; they showed more persistent alcohol dependence symptoms as childhood adversity increased and more alcohol dependence symptoms limited to emerging adulthood as college/Greek involvement increased. Alcohol dependence among non-carriers of the long allele, however, did not differ as a function of those environments. Although replication is necessary, these findings highlight the importance of repeated phenotypic assessments across development and modeling both distal and proximal environments and their interaction with genetic susceptibility at specific developmental stages. PMID:21381802

  5. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  6. An empirical description of phases of maintenance following treatment for alcohol dependence.

    PubMed

    Murphy, S A; Hoffman, A L

    1993-01-01

    This article reports two longitudinal prospective studies conducted sequentially to describe participants' maintenance of abstinence experiences up to 36 months posttreatment. Study 1 reports responses of 102 subjects who maintained alcohol abstinence following treatment and who were assessed for duration and intensity of symptoms associated with postacute withdrawal at baseline, 3, 6, and 12 months. A decreasing linear trend of symptoms was found as time of alcohol abstinence increased. Study 2 obtained interview and survey data from 23 successful abstainers from Study 1 at 12, 18, and 36 months posttreatment to describe coping strategies, perceptions of relapse risk, extent and duration of "aftercare," and substitute addictions as these phenomena developed and changed over time. Multiple occasions of data collection supported the description of three phases of maintenance: symptom stabilization/management accompanied by a cognitive paradigm shift, distancing self from alcohol-dependent behavior, and normalization of life processes.

  7. Neurophysiological endophenotypes, CNS disinhibition, and risk for alcohol dependence and related disorders.

    PubMed

    Porjesz, Bernice; Rangaswamy, Madhavi

    2007-01-01

    Biological endophenotypes are more proximal to gene function than psychiatric diagnosis, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. The Collaborative Study on the Genetics of Alcoholism (COGA) has employed heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We found significant linkage and association between brain oscillations and genes involved with inhibitory neural networks (e.g., GABRA2, CHRM2), including frontal networks that are deficient in individuals with alcohol dependence, impulsivity, and related disinhibitory disorders. We reported significant linkage and linkage disequilibrium for the beta frequency of the EEG and GABRA2, a GABAA receptor gene on chromosome 4, which we found is also associated with diagnosis of alcohol dependence and related disorders. More recently, we found significant linkage and association with GABRA2 and interhemispheric theta coherence. We also reported significant linkage and linkage disequilibrium between the theta and delta event-related oscillations underlying P3 to target stimuli and CHRM2, a cholinergic muscarinic receptor gene on chromosome 7, which we found is also associated with diagnosis of alcohol dependence and related disorders. Thus, the identification of genes important for the expression of the endophenotypes (brain oscillations) helps when identifying genes that increase the susceptibility for risk of alcohol dependence and related disorders. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of complex disorders. We will present our recent genetic findings related to

  8. Serum Insulin Levels Are Reduced by Intravenous Ghrelin Administration but Do Not Correlate with Alcohol Craving in Alcohol-Dependent Individuals

    PubMed Central

    Giovenco, Danielle E.; Lee, Mary R.; Zywiak, William H.; de la Monte, Suzanne M.; Kenna, George A.; Swift, Robert M.

    2016-01-01

    Background: Increasing evidence supports a role for appetite-regulating pathways like ghrelin, insulin, and leptin in alcoholism. We previously reported that intravenous (i.v.) exogenous ghrelin increases alcohol craving. We also reported i.v. ghrelin reduces endogenous serum leptin, whose levels, in turn, negatively correlated with alcohol craving. Exogenous ghrelin administration decreases insulin secretion both in vitro and in vivo experiments. This study tested the hypothesis that i.v. ghrelin may also decrease endogenous serum insulin levels in alcoholic individuals. Additionally, we explored possible correlations between serum insulin and alcohol craving, since a correlation between insulin and alcohol craving was previously reported. Methods: This was a double-blind, placebo-controlled human laboratory study (n=43). Non-treatment-seeking, alcohol-dependent, heavy drinkers were randomized to receive i.v. ghrelin or placebo, followed by an alcohol cue-reactivity procedure. Results: There was a main effect for i.v. ghrelin, compared to placebo in reducing serum insulin (P<.05). There was also a time effect (P<.001) but not ghrelin x time interaction (P>.05). We did not find a correlation between the reduction of serum insulin and alcohol craving (P>.05). The change in serum insulin was consistent with a parallel reduction in serum connective-peptide in the ghrelin group compared with placebo, although this difference did not reach statistical significance (P=.076). No similar effects were found for other glucose-regulating hormones analyzed i.e. glucagon, glucagon-like peptide-1, and gastric inhibitory peptide (Ps>.05). Conclusions: These findings indicate i.v. ghrelin administration has an effect on reducing serum insulin in alcohol-dependent individuals; however, the reduction of insulin did not correlate with changes in alcohol cue-elicited craving. We speculate that, unlike for leptin, the interactions between ghrelin and insulin relationship are limited at

  9. Improving personality/character traits in individuals with alcohol dependence: the influence of mindfulness-oriented meditation.

    PubMed

    Crescentini, Cristiano; Matiz, Alessio; Fabbro, Franco

    2015-01-01

    The study of personality is critical to enhance current knowledge of the psychological characteristics of alcohol dependence. Recent evidence shows that mindfulness-oriented meditation positively influences healthy individuals' character. Here, it was assessed whether 8-week mindfulness-oriented meditation promotes similar changes in a group of alcohol-dependent individuals. A control group with alcohol dependence was also tested. Mindfulness-oriented meditation participants showed an increase in the character scores of the temperament and character inventory together with reduced risks of relapse. These longitudinal data highlight the importance of assessing personality in alcohol-dependent individuals and support the utility of therapeutic interventions for alcohol dependence aimed at enhancing individuals' character.

  10. [Gender differences in alcohol dependence: personality variables, psychopathological profile and personality disorders].

    PubMed

    Bravo de Medina, Ricardo; Echeburúa, Enrique; Aizpiri, Javier

    2008-05-01

    In this paper, gender differences in personality, psychopathology and personality disorders of alcohol-dependent patients are described. The sample consisted of 158 alcohol-dependent patients attending a psychiatric outpatient clinic (105 men and 55 women). All participants were assessed with various assessment tools related to personality (Impulsiveness Scale, Sensation Seeking Scale and STAI), psychopathology (SCL-90-R, BDI and Inadaptation Scale) and personality disorders (IPDE). There were no differences in personality variables, but the women had more anxiety and depressive symptoms and also more problems to adapt to everyday life than did the men. Personality disorders were not as prevalent as in the case of men, and the most frequent among women were obsessive-compulsive, dependent and histrionic personality disorders. Implications of this study for further research are commented on.

  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. Cupriavidus necator JMP134 rapidly reduces furfural with a Zn-dependent alcohol dehydrogenase.

    PubMed

    Li, Qunrui; Metthew Lam, L K; Xun, Luying

    2011-11-01

    Ethanol is a renewable biofuel, and it can be produced from lignocellulosic biomass. The biomass is usually converted to hydrolysates that consist of sugar and sugar derivatives, such as furfural. Yeast ferments sugar to ethanol, but furfural higher than 3 mM is inhibitory. It can take several days for yeast cells to reduce furfural to non-inhibitory furfuryl alcohol before producing ethanol. Bioreduction of furfural to furfuryl alcohol before fermentation may relieve yeast from furfural toxicity. We observed that Cupriavidus necator JMP134, a strict aerobe, rapidly reduced 17 mM furfural to less than 3 mM within 14 min with cell turbidity of 1.0 at 600 nm at 50°C. The rapid reduction consumed ethanol. The "furfural reductase" (FurX) was purified, and it oxidized ethanol to acetaldehyde and reduced furfural to furfuryl alcohol with NAD(+) as the cofactor. The protein was identified with mass spectrometry fingerprinting to be a hypothetical protein belonging to Zn-dependent alcohol dehydrogenase family. The furX-inactivation mutant of C. necator JMP134 lost the ability to rapidly reduce furfural, and Escherichia coli producing recombinant FurX gained the ability. Thus, an alcohol dehydrogenase enabled bacteria to rapidly reduce furfural with ethanol as the reducing power.

  13. Methods for inducing alcohol craving in individuals with co-morbid alcohol dependence and posttraumatic stress disorder: behavioral and physiological outcomes.

    PubMed

    Kwako, Laura E; Schwandt, Melanie L; Sells, Joanna R; Ramchandani, Vijay A; Hommer, Daniel W; George, David T; Sinha, Rajita; Heilig, Markus

    2015-07-01

    Alcohol addiction is a chronic relapsing disorder that presents a substantial public health problem, and is frequently co-morbid 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. The present study compares two methods for induction of craving via stress and alcohol cues in individuals with co-morbid 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. Subjects were 52 individuals diagnosed with co-morbid AD and PTSD seeking treatment at the National Institute on Alcohol Abuse and Alcoholism inpatient research facility. They participated in a 4-week inpatient study of the efficacy of a neurokinin 1 antagonist to treat co-morbid AD and PTSD, and which included the two challenge procedures. 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 adrenocorticotropic hormone and cortisol, while the Scripts did not. 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 versus alcohol cues, as well as to understand the impact of co-morbid PTSD and AD on craving.

  14. Nicotine Modulates Alcohol-Seeking and Relapse by Alcohol-Preferring (P) Rats in a Time Dependent Manner

    PubMed Central

    Hauser, Sheketha R.; Getachew, Bruk; Oster, Scott M.; Dhaher, Ronnie; Ding, Zheng-Ming; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.

    2015-01-01

    Background Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at two different time points. Method Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5 – fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hr sessions. Following 10 weeks of daily 1-hr sessions, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0 mg/kg) was injected s.c. immediately or 4-hr prior to PSR or relapse testing. Results Injections of nicotine immediately prior to testing reduced (5–10 responses PSR; 50–60 responses relapse), whereas injections of nicotine 4-hr prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0 mg/kg dose) responses on the EtOH lever during PSR and relapse tests. Discussion The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time-dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH whereas, with a delay of 4-hr, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine’s metabolites (i.e., cotinine, nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors. PMID:21689122

  15. Biochemical characterization of ethanol-dependent reduction of furfural by alcohol dehydrogenases.

    PubMed

    Li, Qunrui; Metthew Lam, L K; Xun, Luying

    2011-11-01

    Lignocellulosic biomass is usually converted to hydrolysates, which consist of sugars and sugar derivatives, such as furfural. Before yeast ferments sugars to ethanol, it reduces toxic furfural to non-inhibitory furfuryl alcohol in a prolonged lag phase. Bioreduction of furfural may shorten the lag phase. Cupriavidus necator JMP134 rapidly reduces furfural with a Zn-dependent alcohol dehydrogenase (FurX) at the expense of ethanol (Li et al. 2011). The mechanism of the ethanol-dependent reduction of furfural by FurX and three homologous alcohol dehydrogenases was investigated. The reduction consisted of two individual reactions: ethanol-dependent reduction of NAD(+) to NADH and then NADH-dependent reduction of furfural to furfuryl alcohol. The kinetic parameters of the coupled reaction and the individual reactions were determined for the four enzymes. The data indicated that limited NADH was released in the coupled reaction. The enzymes had high affinities for NADH (e.g., K ( d ) of 0.043 μM for the FurX-NADH complex) and relatively low affinities for NAD(+) (e.g., K ( d ) of 87 μM for FurX-NAD(+)). The kinetic data suggest that the four enzymes are efficient "furfural reductases" with either ethanol or NADH as the reducing power. The standard free energy change (ΔG°') for ethanol-dependent reduction of furfural was determined to be -1.1 kJ mol(-1). The physiological benefit for ethanol-dependent reduction of furfural is likely to replace toxic and recalcitrant furfural with less toxic and more biodegradable acetaldehyde.

  16. The effects of the monoamine stabilizer (-)-OSU6162 on craving in alcohol dependent individuals: A human laboratory study.

    PubMed

    Khemiri, Lotfi; Steensland, Pia; Guterstam, Joar; Beck, Olof; Carlsson, Arvid; Franck, Johan; Jayaram-Lindström, Nitya

    2015-12-01

    Alcohol dependence is associated with a dysregulated dopamine system modulating reward, craving and cognition. The monoamine stabilizer (-)-OSU6162 (OSU6162) can counteract both hyper- and hypo-dopaminergic states and we recently demonstrated that it attenuates alcohol-mediated behaviors in long-term drinking rats. The present Phase II exploratory human laboratory study investigated to our knowledge for the first time the effects of OSU6162 on cue- and priming-induced craving in alcohol dependent individuals. Fifty-six alcohol dependent individuals were randomized to a 14-day-treatment period of OSU6162 or placebo after their baseline impulsivity levels had been determined using the Stop Signal Task. On Day 15, participants were subjected to a laboratory alcohol craving test comprised of craving sessions induced by: i) active - alcohol specific cues, ii) neutral stimuli and iii) priming - intake of an alcoholic beverage (0.20g ethanol/kg bodyweight). Subjective ratings of alcohol craving were assessed using the shortened version of the Desire for Alcohol Questionnaire and visual analog scales (VAS). OSU6162 treatment had no significant effect on cue-induced alcohol craving, but significantly attenuated priming-induced craving. Exploratory analysis revealed that this effect was driven by the individuals with high baseline impulsivity. In addition, OSU6162 significantly blunted the subjective liking of the consumed alcohol (VAS). Although the present 14-day-treatment period, showed that OSU6162 was safe and well tolerated, this exploratory human laboratory study was not designed to evaluate the efficacy of OSU6162 to affect alcohol consumption. Thus a larger placebo-controlled efficacyclinical trial is needed to further investigate the potential of OSU6162 as a novel medication for alcohol dependence.

  17. A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence.

    PubMed

    Anton, Raymond F; Pettinati, Helen; Zweben, Allen; Kranzler, Henry R; Johnson, Bankole; Bohn, Michael J; McCaul, Mary E; Anthenelli, Robert; Salloum, Ihsan; Galloway, Gantt; Garbutt, James; Swift, Robert; Gastfriend, David; Kallio, Antero; Karhuvaara, Sakari

    2004-08-01

    The opiate antagonist nalmefene has been shown in 2 single-site studies to reduce alcohol consumption and relapse drinking in alcohol-dependent individuals. This safety and preliminary multisite efficacy study evaluated 3 doses of nalmefene (5, 20, or 40 mg) in a double-blind comparison to placebo over a 12-week treatment period in 270 recently abstinent outpatient alcohol-dependent individuals. Participants concomitantly received 4 sessions of a motivational enhancement therapy (with a medication compliance component) delivered from trained counselors. Although more subjects in the active medication groups terminated the study early secondary to adverse events, the rates did not differ significantly from that of placebo. The 20-mg/d group experienced more insomnia, dizziness, and confusion, while the 5-mg group also had more dizziness and the 40-mg group had more nausea than the placebo group. Most of these symptoms were mild and improved over time. Although all subjects had a reduction in heavy drinking days, craving, gamma-glutamyl transferase, and carbohydrate-deficient transferrin concentrations over the course of the study, there was no difference between the active medication and placebo groups on these measures. The time to first heavy drinking day was also not significantly different between the placebo and the active treatment groups. This relatively small multisite trial showed that nalmefene was reasonably well tolerated in recently abstinent alcoholics. However, possibly because of variation among the sites or the comparatively small sample size, there was no evidence of superior efficacy outcomes with nalmefene treatment.

  18. Neural Correlates of Impulsive Aggressive Behavior in Subjects With a History of Alcohol Dependence

    PubMed Central

    Kose, Samet; Steinberg, Joel L.; Moeller, F. Gerard; Gowin, Joshua L.; Zuniga, Edward; Kamdar, Zahra N.; Schmitz, Joy M.; Lane, Scott D.

    2015-01-01

    Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM–IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity. PMID:25664566

  19. A Review of the Interactions between Alcohol and the Endocannabinoid System: Implications for Alcohol Dependence and Future Directions for Research

    PubMed Central

    Pava, Matthew J.; Woodward, John J.

    2012-01-01

    Over the past fifty years a significant body of evidence has been compiled suggesting an interaction between the endocannabinoid (EC) system and alcohol dependence. However, much of this work has been conducted only in the past two decades following the elucidation of the molecular constituents of the EC system that began with the serendipitous discovery of the cannabinoid 1 receptor (CB1). Since then, novel pharmacological and genetic tools have enabled researchers to manipulate select components of the EC system, to determine their contribution to the motivation to consume ethanol. From these preclinical studies, it is evident that CB1 contributes the motivational and reinforcing properties of ethanol, and chronic consumption of ethanol alters EC transmitter levels and CB1 expression in brain nuclei associated with addiction pathways. These results are augmented by in vitro and ex vivo studies showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the EC system. This report provides a current and comprehensive review of the literature regarding the interactions between ethanol and the EC system. We begin be reviewing the studies published prior to the discovery of the EC system that compared the behavioral and physiological effects of cannabinoids with ethanol in addition to cross-tolerance between these drugs. Next, a brief overview of the molecular constituents of the EC system is provided as context for the subsequent review of more recent studies examining the interaction of ethanol with the EC system. These results are compiled into a summary providing a scheme for the known changes to the components of the EC system in different stages of alcohol dependence. Finally, future directions for research are discussed. PMID:22459871

  20. Parental alcoholism as a risk factor for DSM-IV-defined alcohol abuse and dependence in American women: the protective benefits of dyadic cohesion in marital communication.

    PubMed

    Jennison, K M; Johnson, K A

    2001-05-01

    Important trends in research over the past decade indicate that women are as greatly affected by familial alcoholism as are men. Although it is increasingly recognized that the adverse drinking outcomes predicted for adult children of alcoholics (COAs) are not inevitable, and only a small percentage develop alcohol dependence or grow up to be alcoholic, relatively little knowledge exists regarding moderating factors that reduce their vulnerability. This study identifies a multiple mediator latent structural model of the intergenerational transmission of risk for DSM-IV-assessed alcohol abuse and dependence among women COAs in adulthood. The effects of both parental alcoholism and family environment are estimated at three time points spanning 10 years across 5-year intervals (1984, 1989, and 1994) using data from a subsample of 4,449 women in the National Longitudinal Survey of Youth (NLSY). Dyadic cohesion in marital communication (greater marital cohesion, harmony, and less verbal disagreement, discord, and conflict) is a proposed moderating factor that may operate in adulthood to lower the risk of female COAs developing alcohol abuse and dependence. Maximum likelihood standardized estimates of the effects of alcohol mediators measured over time indicate that direct parental effects for adverse outcomes decline when COAs are in their late 20s and early 30s. Indirect parental effects through environmental influences dramatically increase the risk of abuse and dependence among COAs at this time if they have one or more alcoholic siblings, especially an alcoholic sister. Dyadic cohesion and positive interpersonal communication patterns were found to moderate effectively the relationship that existed among parental alcoholism, environmental influences, and adverse alcohol consequences. COAs with satisfactory marital communication also evidenced higher levels of intimacy with their partners, perceived the division of housework to be fairer, shared more responsibilities

  1. Representing the thermal state in time-dependent density functional theory

    SciTech Connect

    Modine, N. A.; Hatcher, R. M.

    2015-05-28

    Classical molecular dynamics (MD) provides a powerful and widely used approach to determining thermodynamic properties by integrating the classical equations of motion of a system of atoms. Time-Dependent Density Functional Theory (TDDFT) provides a powerful and increasingly useful approach to integrating the quantum equations of motion for a system of electrons. TDDFT efficiently captures the unitary evolution of a many-electron state by mapping the system into a fictitious non-interacting system. In analogy to MD, one could imagine obtaining the thermodynamic properties of an electronic system from a TDDFT simulation in which the electrons are excited from their ground state by a time-dependent potential and then allowed to evolve freely in time while statistical data are captured from periodic snapshots of the system. For a variety of systems (e.g., many metals), the electrons reach an effective state of internal equilibrium due to electron-electron interactions on a time scale that is short compared to electron-phonon equilibration. During the initial time-evolution of such systems following electronic excitation, electron-phonon interactions should be negligible, and therefore, TDDFT should successfully capture the internal thermalization of the electrons. However, it is unclear how TDDFT represents the resulting thermal state. In particular, the thermal state is usually represented in quantum statistical mechanics as a mixed state, while the occupations of the TDDFT wavefunctions are fixed by the initial state in TDDFT. We work to address this puzzle by (A) reformulating quantum statistical mechanics so that thermodynamic expectations can be obtained as an unweighted average over a set of many-body pure states and (B) constructing a family of non-interacting (single determinant) TDDFT states that approximate the required many-body states for the canonical ensemble.

  2. Increased risk of alcohol dependency in a cohort of National Guard troops with PTSD: a longitudinal study.

    PubMed

    Kline, Anna; Weiner, Marc D; Ciccone, Donald S; Interian, Alejandro; St Hill, Lauren; Losonczy, Miklos

    2014-03-01

    Studies show high rates of co-morbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) but there is no consensus on the causal direction of the relationship. Some theories suggest AUD develops as a coping mechanism to manage PTSD symptoms and others that AUD is a vulnerability factor for PTSD. A third hypothesis posits independent developmental pathways stemming from a shared etiology, such as the trauma exposure itself. We examined these hypotheses using longitudinal data on 922 National Guard soldiers, representing a subsample (56%) of a larger pre- and post-deployment cross-sectional study of New Jersey National Guard soldiers deployed to Iraq. Measures included the PTSD Checklist (PCL), DSM-IV-based measures of alcohol use/misuse from the National Household Survey of Drug Use and Health and other concurrent mental health, military and demographic measures. Results showed no effect of pre-deployment alcohol status on subsequent positive screens for new onset PTSD. However, in multivariate models, baseline PTSD symptoms significantly increased the risk of screening positive for new onset alcohol dependence (AD), which rose 5% with each unit increase in PCL score (AOR = 1.05; 95% CI = 1.02-1.07). Results also supported the shared etiology hypothesis, with the risk of a positive screen for AD increasing by 9% for every unit increase in combat exposure after controlling for baseline PTSD status (AOR = 1.09; 95% CI = 1.03-1.15) and, in a subsample with PCL scores <34, by 17% for each unit increase in exposure (AOR = 1.17; 95% CI = 1.05-1.31). These findings have implications for prevention, treatment and compensation policies governing co-morbidity in military veterans.

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

    PubMed

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

    2010-06-01

    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 less than $20,000 annually (52.8%). Self-report measures, psychophysiological cue-reactivity, and alcohol attentional bias were analyzed via repeated measures ANOVA. Thirty-seven 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.

  4. Cumulative gains enhance striatal response to reward opportunities in alcohol-dependent patients

    PubMed Central

    Gilman, Jodi M.; Smith, Ashley R.; Bjork, James M.; Ramchandani, Vijay A.; Momenan, Reza; Hommer, Daniel W.

    2016-01-01

    Substance use disorder is characterized by a transition from volitional to compulsive responding for drug reward. A possible explanation for this transition may be that alcohol-dependent patients (ADP) show a general propensity for a history of rewarded instrumental responses, and these rewarded responses may boost the activation of motivational neurocircuitry for additional reward. Brain imaging studies of decision-making have demonstrated that ADP relative to controls (CON) often show altered neural activation in response to anticipating and receiving rewards, but the majority of studies have not investigated how past performance affects activation. A potential exists for ADP to show increased sensitivity to reward as a function of reward delivery history. In the current study, we used functional magnetic resonance imaging to investigate the neural correlates of risky decision-making in ADP (n = 18) and CON (n = 18) while they played a two-choice monetary risk-taking game. In addition to investigating general neural recruitment by risky decision-making, we also modeled each participant’s running total of monetary earnings in order to determine areas of activation that correlated with cumulative reward. We found that ADP and CON showed few differences in behavior or in mesolimbic activation by choice for, and receipt of, risky gains. However, when including a cumulative-earnings covariate, ADP exhibited heightened striatal activation that correlated with total earnings during the choice event in the task. The heightened contextual sensitivity of striatal responses to cumulative earnings in ADP may represent a general neurobiological affective substrate for development of automatized instrumental behavior. PMID:24754451

  5. 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

  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

    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

  8. 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

  9. A randomised controlled trial of extended brief intervention for alcohol dependent patients in an acute hospital setting (ADPAC)

    PubMed Central

    2011-01-01

    Background Alcohol dependence affects approximately 3% of the English population, and accounts for significant medical and psychiatric morbidity. Only 5.6% of alcohol-dependent individuals ever access specialist treatment and only a small percentage ever seek treatment. As people who are alcohol dependent are more likely to have experienced health problems leading to frequent attendance at acute hospitals it would seem both sensible and practical to ensure that this setting is utilised as a major access point for treatment, and to test the effectiveness of these treatments. Methods/Design This is a randomised controlled trial with a primary hypothesis that extended brief interventions (EBI) delivered to alcohol-dependent patients in a hospital setting by an Alcohol Specialist Nurse (ASN) will be effective when compared to usual care in reducing overall alcohol consumption and improving on the standard measures of alcohol dependence. Consecutive patients will be screened for alcohol misuse in the Emergency Department (ED) of a district general hospital. On identification of an alcohol-related problem, following informed written consent, we aim to randomize 130 patients per group. The ASN will discharge to usual clinical care all control group patients, and plan a programme of EBI for treatment group patients. Follow-up interview will be undertaken by a researcher blinded to the intervention at 12 and 24 weeks. The primary outcome measure is level of alcohol dependence as determined by the Severity of Alcohol Dependence Questionnaire (SADQ) score. Secondary outcome measures include; Alcohol Use Disorders Identification Test (AUDIT) score, quantity and frequency of alcohol consumption, health-related quality of life measures, service utilisation, and patient experience. The trial will also allow an assessment of the cost-effectiveness of EBI in an acute hospital setting. In addition, patient experience will be assessed using qualitative methods. Discussion This paper

  10. Family dysfunction differentially affects alcohol and methamphetamine dependence: a view from the Addiction Severity Index in Japan.

    PubMed

    Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka

    2011-10-01

    We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.

  11. Representing the thermal state in time-dependent density functional theory

    DOE PAGES

    Modine, N. A.; Hatcher, R. M.

    2015-05-28

    Classical molecular dynamics (MD) provides a powerful and widely used approach to determining thermodynamic properties by integrating the classical equations of motion of a system of atoms. Time-Dependent Density Functional Theory (TDDFT) provides a powerful and increasingly useful approach to integrating the quantum equations of motion for a system of electrons. TDDFT efficiently captures the unitary evolution of a many-electron state by mapping the system into a fictitious non-interacting system. In analogy to MD, one could imagine obtaining the thermodynamic properties of an electronic system from a TDDFT simulation in which the electrons are excited from their ground state bymore » a time-dependent potential and then allowed to evolve freely in time while statistical data are captured from periodic snapshots of the system. For a variety of systems (e.g., many metals), the electrons reach an effective state of internal equilibrium due to electron-electron interactions on a time scale that is short compared to electron-phonon equilibration. During the initial time-evolution of such systems following electronic excitation, electron-phonon interactions should be negligible, and therefore, TDDFT should successfully capture the internal thermalization of the electrons. However, it is unclear how TDDFT represents the resulting thermal state. In particular, the thermal state is usually represented in quantum statistical mechanics as a mixed state, while the occupations of the TDDFT wave functions are fixed by the initial state in TDDFT. Two key questions involve (1) reformulating quantum statistical mechanics so that thermodynamic expectations can be obtained as an unweighted average over a set of many-body pure states and (2) constructing a family of non-interacting (single determinant) TDDFT states that approximate the required many-body states for the canonical ensemble. In Section II, we will address these questions by first demonstrating that thermodynamic

  12. Representing the thermal state in time-dependent density functional theory

    SciTech Connect

    Modine, N. A.; Hatcher, R. M.

    2015-05-28

    Classical molecular dynamics (MD) provides a powerful and widely used approach to determining thermodynamic properties by integrating the classical equations of motion of a system of atoms. Time-Dependent Density Functional Theory (TDDFT) provides a powerful and increasingly useful approach to integrating the quantum equations of motion for a system of electrons. TDDFT efficiently captures the unitary evolution of a many-electron state by mapping the system into a fictitious non-interacting system. In analogy to MD, one could imagine obtaining the thermodynamic properties of an electronic system from a TDDFT simulation in which the electrons are excited from their ground state by a time-dependent potential and then allowed to evolve freely in time while statistical data are captured from periodic snapshots of the system. For a variety of systems (e.g., many metals), the electrons reach an effective state of internal equilibrium due to electron-electron interactions on a time scale that is short compared to electron-phonon equilibration. During the initial time-evolution of such systems following electronic excitation, electron-phonon interactions should be negligible, and therefore, TDDFT should successfully capture the internal thermalization of the electrons. However, it is unclear how TDDFT represents the resulting thermal state. In particular, the thermal state is usually represented in quantum statistical mechanics as a mixed state, while the occupations of the TDDFT wave functions are fixed by the initial state in TDDFT. Two key questions involve (1) reformulating quantum statistical mechanics so that thermodynamic expectations can be obtained as an unweighted average over a set of many-body pure states and (2) constructing a family of non-interacting (single determinant) TDDFT states that approximate the required many-body states for the canonical ensemble. In Section II, we will address these questions by first demonstrating that thermodynamic expectations

  13. Prazosin Effects on Stress- and Cue-Induced Craving and Stress Response in Alcohol Dependent Individuals: Preliminary Findings

    PubMed Central

    Anderson, George M; Tuit, Keri; Hansen, Julie; Kimmerling, Anne; Siedlarz, Kristen M; Morgan, Peter T; Sinha, Rajita

    2011-01-01

    Background Stress, alcohol cues and dysregulated stress responses increase alcohol craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress and cue-induced alcohol craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha1 receptor antagonist, prazosin, in modulating these relapse-relevant factors in alcohol dependent (AD) individuals. Methods Seventeen early abstinent, treatment-seeking alcohol dependent individuals (12 Males /5 Females) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double-blind, placebo controlled manner over four weeks. During week 4, all patients participated in a 3-day laboratory experiment involving 5-min guided imagery exposure to stress, alcohol cue and neutral-relaxing/control conditions, one exposure per day, on consecutive days in a random, counterbalanced order. Alcohol craving, anxiety and negative emotion, cardiovascular measures, plasma hypothalamic-pituitary-adrenal (HPA; cortisol, ACTH) were assessed repeatedly in each session. Results The prazosin group (n=9) versus the placebo group (n=8) showed significantly lower alcohol craving, anxiety and negative emotion following stress exposure. The placebo group also showed significantly increased stress and cue-induced alcohol craving, anxiety, negative emotion and blood pressure as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in craving, anxiety, negative emotion and blood pressure, and no blunted HPA response to stress and alcohol cue exposure. Conclusions Prazosin appears efficacious in decreasing stress- and cue-induced alcohol craving and may normalize the stress dysregulation associated with early recovery from alcoholism. Further research to assess the efficacy of prazosin in reducing alcohol craving and stress-related relapse risk is warranted. PMID:21919922

  14. Personality pathology and alcohol dependence at midlife in a community sample.

    PubMed

    Agrawal, Arpana; Narayanan, Gitanjali; Oltmanns, Thomas F

    2013-01-01

    The present study examined the association between personality pathology (PP) and alcohol dependence (AD; both lifetime and in the past 12 months) among middle-aged to older adults incorporating three sources of assessment, specifically, diagnostic interviews as well as self- and informant reports. We collected data from a representative sample of community participants (N = 1,630; ages 54-65 years) and their informants (N = 1,462). Measures employed were the substance use disorder sections of the Mini-International Neuropsychiatric Interview Schedule for Mental Disorders, the Structured Interview for DSM-IV Personality (American Psychiatric Association, 2000, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text rev.; DSM-IV-TR SIDP) and the NEO-Personality Inventory-Revised (Costa, P. T., & McCrae, R. R., Revised NEO-Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) manual, 1992, Odessa, FL, Psychological Assessment Resources; self-report and informant versions). To complement the diagnostic interview for personality disorders (PDs), we utilized a PD-count technique derived from the five-factor model (FFM), which provided an index of PP liability. Factors representing lifetime and past-12 month AD were regressed on each of the 10 PP factors constructed from the SIDP interview, as well as self-report and informant FFM-count scores. Lifetime diagnosis of AD was positively associated with higher scores on several PP measures, including paranoid, schizotypal, antisocial, borderline, histrionic, and narcissistic PP. There was an inverse relation between lifetime AD and the factor score for obsessive-compulsive PP. With regard to AD in the past 12 months, antisocial, borderline, histrionic, and narcissistic PP factors were significantly associated with increased risk for AD, whereas the obsessive-compulsive and schizoid PP factors were associated with decreased risk for AD. The present data indicate that features of antisocial and

  15. 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…

  16. 38 CFR 17.81 - Contracts for residential treatment services for veterans with alcohol or drug dependence or...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements of the “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR part II) and the... CFR part 2) and the “Confidentiality of Certain Medical Records” (38 U.S.C. 7332), and will be made... treatment services for veterans with alcohol or drug dependence or abuse disabilities. 17.81 Section...

  17. Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

    PubMed

    Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

    2012-06-01

    Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol.

  18. A Functional Vesicular Monoamine Transporter 1 (VMAT1) Gene Variant Is Associated with Affect and the Prevalence of Anxiety, Affective, and Alcohol Use Disorders in a Longitudinal Population-Representative Birth Cohort Study

    PubMed Central

    Vaht, Mariliis; Kiive, Evelyn; Veidebaum, Toomas

    2016-01-01

    Background: Inter-individual differences in the monoaminergic systems have been shown to moderate the risk for a lifetime history of anxiety, affective, and alcohol use disorders. A common single nucleotide polymorphism in the vesicular monoamine transporter 1 gene (VMAT1 rs1390938 G/A; Thr136Ile) has been reported as functional in vitro and associated with bipolar disorder and anxiety. We aimed at assessing the association between the VMAT1 genotype, affect, and affect-related psychiatric disorders in a longitudinal population-representative study. Methods: We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9- (recalled at ages 15 and 18 years, n=579) and 15- (recalled at ages 18 and 25 years; n=654) year-old children provided self-reports on impulsivity, anxiety, depressiveness, neuroticism, and alcohol use. In addition, psychiatric assessment based on DSM-IV was carried out in the older cohort at age 25 years. Results: Subjects homozygous for the less prevalent A (136Ile) allele reported lower maladaptive impulsivity, state and trait anxiety, depressiveness, and neuroticism and were less likely to have been diagnosed with an affective, anxiety, and/or alcohol use disorder by young adulthood. While in the younger cohort alcohol use started at younger age, this birth cohort effect was dependent on genotype: only G allele carriers and in particular the GG homozygotes started alcohol use earlier. Conclusions: VMAT1 rs1390938/Thr136Ile is associated with mood, personality, and alcohol use in the general population. Subjects homozygous for the “hyperfunction” allele (AA; Ile/Ile) appear to be more resilient to these disorders. PMID:26861143

  19. Assessing the Representativeness of Population-Sampled Health Surveys Through Linkage to Administrative Data on Alcohol-Related Outcomes

    PubMed Central

    Gorman, Emma; Leyland, Alastair H.; McCartney, Gerry; White, Ian R.; Katikireddi, Srinivasa Vittal; Rutherford, Lisa; Graham, Lesley; Gray, Linsay

    2014-01-01

    Health surveys are an important resource for monitoring population health, but selective nonresponse may impede valid inference. This study aimed to assess nonresponse bias in a population-sampled health survey in Scotland, with a focus on alcohol-related outcomes. Nonresponse bias was assessed by examining whether rates of alcohol-related harm (i.e., hospitalization or death) and all-cause mortality among respondents to the Scottish Health Surveys (from 1995 to 2010) were equivalent to those in the general population, and whether the extent of any bias varied according to sociodemographic attributes or over time. Data from consenting respondents (aged 20–64 years) to 6 Scottish Health Surveys were confidentially linked to death and hospitalization records and compared with general population counterparts. Directly age-standardized incidence rates of alcohol-related harm and all-cause mortality were lower among Scottish Health Survey respondents compared with the general population. For all years combined, the survey-to-population rate ratios were 0.69 (95% confidence interval: 0.61, 0.76) for the incidence of alcohol-related harm and 0.89 (95% confidence interval: 0.83, 0.96) for all-cause mortality. Bias was more pronounced among persons residing in more deprived areas; limited evidence was found for regional or temporal variation. This suggests that corresponding underestimation of population rates of alcohol consumption is likely to be socially patterned. PMID:25227767

  20. 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

  1. 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

  2. Give them prizes, and they will come: contingency management for treatment of alcohol dependence.

    PubMed

    Petry, N M; Martin, B; Cooney, J L; Kranzler, H R

    2000-04-01

    This study evaluated the efficacy of a contingency management (CM) procedure that provided opportunities to win prizes as reinforcers. At intake to outpatient treatment, 42 alcohol-dependent veterans were randomly assigned to receive standard treatment or standard treatment plus CM, in which they earned the chance to win prizes for submitting negative Breathalyzer samples and completing steps toward treatment goals. Eighty-four percent of the CM participants were retained in treatment for an 8-week period compared with 22% of the standard treatment participants (p < .001). By the end of the treatment period, 69% of those receiving CM were still abstinent, but 61% of those receiving standard treatment had used alcohol (p < .05). These results support the efficacy of this CM procedure. Participants earned an average of $200 in prizes. This CM procedure may be suitable for use in standard treatment settings because prizes can be solicited from the community. PMID:10780125

  3. Effect of functionally significant deiodinase single nucleotide polymorphisms on drinking behavior in alcohol dependence: an exploratory investigation

    PubMed Central

    Lee, MR; Schwandt, ML; Bollinger, JW; Dias, AA; Oot, EN; Goldman, D; Hodgkinson, CA; Leggio, L

    2016-01-01

    Background Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism, however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence (AD). The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes D1, D2 and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNP’s) of these deiodinase genes may play a role in HPT dysfunction. Methods The present study explored the effect of three functionally significant SNP’s (D1: rs2235544, D2: rs225014 and rs12885300) of deiodinase genes on drinking behavior and thyroid stimulating hormone (TSH) levels in alcohol dependent (N=521) and control subjects (N=228). Results Rs225014 was associated with significant differences in the amount of naturalistic alcohol drinking assessed by the Timeline Follow-Back (TLFB). Alcohol-dependent subjects had significantly higher thyroid stimulating hormone levels compared to controls; however, there was no effect of genotype on TSH levels for either group. Conclusions These findings extend previous studies on thyroid dysfunction in alcoholism and provide novel, albeit preliminary, information by linking functionally significant genetic polymorphisms of the deiodinase enzymes with alcohol drinking behavior. PMID:26207529

  4. 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.

  5. The Hispanic Americans Baseline Alcohol Survey (HABLAS): the association between birthplace, acculturation and alcohol abuse and dependence across Hispanic national groups.

    PubMed

    Caetano, Raul; Ramisetty-Mikler, Suhasini; Rodriguez, Lori A

    2009-01-01

    Hispanics are heterogeneous in national origin, evidenced by wide ranges of alcohol abuse and dependence rates across different Hispanic national groups. This paper examines associations between 12-month rates of DSM-IV alcohol abuse and dependence with birthplace and acculturation. The 2006 Hispanic Americans Baseline Alcohol Survey, using a multistage cluster sample design, interviewed 5224 adults (18+ years) in five selected U.S. metropolitan areas: Miami, New York, Philadelphia, Houston, and Los Angeles. Comprehensive data on drinking behavior were collected and the analyses include bivariate and multivariate regression techniques. Alcohol abuse and dependence rates were higher among U.S.-born Puerto Ricans and South/Central Americans compared to their foreign-born counterparts, while no such differences were found for Cuban and Mexican Americans. Overall, those with higher acculturation report higher rates of abuse and dependence (statistically significant only for abuse among Puerto Ricans). Risk factors for abuse include being male and being in the high acculturation group. Risk factors for dependence include being male, being Puerto Rican or Mexican American, having less than a college education, and being U.S.-born. Hispanics were found to share several common risk factors with the larger U.S. population for abuse and dependence, such as male gender, lower education, and lower income.

  6. 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

  7. Cost and Cost-Effectiveness of the COMBINE Study for Alcohol-Dependent Patients

    PubMed Central

    Zarkin, Gary A.; Bray, Jeremy W.; Aldridge, Arnie; Mitra, Debanjali; Couper, David J.; Cisler, Ron A.

    2011-01-01

    Context The COMBINE clinical trial recently evaluated the efficacy of medications, behavioral therapies, and their combinations for the outpatient treatment of alcohol dependence. The costs and cost-effectiveness of these combinations are unknown and of interest to clinicians and policy makers. Objective To evaluate the costs and cost-effectiveness of the COMBINE interventions at the end of 16 weeks of treatment. Design, Setting, and Participants A prospective cost and cost-effectiveness study of patients in COMBINE, a randomized controlled clinical trial (RCT) involving 1383 patients with diagnoses of primary alcohol dependence across 11 US clinical sites. Interventions Nine treatment arms, with 4 arms receiving medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or placebo; 4 arms receiving the same options as above but delivered with combined behavioral intervention (CBI); and 1 arm receiving CBI only. Main Outcomes Measures Incremental cost per percentage point increase in percent days abstinent (PDA), incremental cost per patient of avoiding heavy drinking, and incremental cost per patient of achieving a good clinical outcome. Results Based on the mean values of cost and effectiveness, 3 interventions are cost-effective options relative to the other interventions for all three outcomes: medical management (MM) with placebo ($409 cost per patient), MM + naltrexone ($671 cost per patient), and MM + naltrexone + acamprosate ($1003 cost per patient). Conclusions This is only the second prospective RCT-designed cost-effectiveness study that has been performed for the treatment of alcohol dependence. Focusing just on effectiveness, MM + naltrexone + acamprosate is not significantly better than MM + naltrexone. However, looking at cost and effectiveness, MM + naltrexone + acamprosate may be a cost-effective choice, depending on whether the cost of the incremental increase in effectiveness is worth it to the decision maker. PMID

  8. A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence

    PubMed Central

    Kampman, Kyle M.; Pettinati, Helen M.; Lynch, Kevin G.; Spratt, Kelly; Wierzbicki, Michael R.; O’Brien, Charles P.

    2013-01-01

    BACKGROUND Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs. METHODS The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings. RESULTS Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate. DISCUSSION Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence. PMID:23810644

  9. 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

  10. Validation of the MINI (DSM IV) Tool for the Assessment of Alcohol Dependence among Young People in Northern Tanzania Using the Alcohol Biomarker Phosphatidylethanol (PEth).

    PubMed

    Francis, Joel M; Helander, Anders; Kapiga, Saidi H; Weiss, Helen A; Grosskurth, Heiner

    2015-11-01

    The alcohol dependence section of the Mini International Neuropsychiatric Interview questionnaire (MINI) has not been evaluated in young Africans. We applied the MINI in a cross-sectional study of 202 alcohol users from northern-Tanzania, aged 18-24 years (103 male casual workers and 99 students), and validated it against phophatidylethanol (PEth) at a cut-off suggesting heavy chronic alcohol use (≥0.30 µmol/L). Blood was assayed for PEth (16:0/18:1-subform) by liquid chromatography-tandem mass spectrometry. The MINI dependence criteria (≥3 positive responses) were met by 39% participants although their PEth levels were low. Contrary, many young people with high PEth levels were not classified as dependent. The sensitivity of the MINI ranged from 0% to 69% (female students and male workers, respectively) and specificity from 52% to 85% (workers and female students, respectively). The highest AUROC (0.68) occurred with a cut-off of ≥4 positive responses. A modified MINI with three affirmative responses to five questions increased specificity to 92%-97%; however, sensitivity remained low. The performance of the MINI in detecting dependence among young people from northern-Tanzania is unsatisfactory. Specificity was improved using a modified version but sensitivity remained low. An accurate tool for the diagnosis of alcohol dependence is needed for epidemiological and clinical purposes. PMID:26529004

  11. Startle Response to Unpredictable Threat in Comorbid Panic Disorder and Alcohol Dependence

    PubMed Central

    Gorka, Stephanie M.; Nelson, Brady D.; Shankman, Stewart A.

    2013-01-01

    Background Although the adverse consequences of comorbid panic disorder (PD) and alcohol dependence (AD) are well-established, relatively little is known about the mechanisms underlying their co-occurrence. Several researchers have postulated that alcohol's ability to dampen response to unpredictable threat may be an important motivational factor in comorbid PD and AD. To date, no research has examined these processes using a clinical sample and it is unclear whether individuals with PD and AD evidence different reactivity to unpredictable threat relative to individuals with PD-only. Methods The aim of the current study was to examine differences in aversive responding during predictable and unpredictable threat-of-shock in three groups of individuals with: 1) current PD and remitted AD (PD and AD), 2) current PD but no lifetime diagnosis of AD (PD-only), and 3) no lifetime diagnoses of PD or AD (controls). Aversive responding was assessed using a well-established electromyography (EMG) startle paradigm. Results Results indicated that PD and AD individuals evidenced greater startle potentiation during unpredictable (but not predictable) threat relative to controls and PD-only individuals (who did not differ). Conclusions These findings suggest that heightened reactivity to unpredictable threat may be an important process in PD and AD comorbidity and a possible key motivational factor underlying engagement in alcohol use. PMID:23465734

  12. Cortical and subcortical volumes in adolescents with alcohol dependence but without substance or psychiatric comorbidities

    PubMed Central

    Fein, George; Greenstein, David; Cardenas, Valerie A.; Cuzen, Natalie L.; Foucheb, Jean-Paul; Ferrett, Helen; Thomas, Keven; Stein, Dan J.

    2013-01-01

    Most prior studies of the effects of excessive alcohol intake on the adolescent brain examined alcohol use dependent samples with comorbid psychiatric and substance use disorders. In the Cape Town region, we identified a sizeable cohort of adolescents with alcohol use disorders (AUD) without externalizing or other psychiatric disorders. We examined brain morphology in 64 such adolescents compared to age and gender matched healthy controls. Magnetic resonance imaging data were analyzed using FSL’s FIRST software for subcortical volumes, and cortical gray matter (GM) was analyzed using voxel based morphometry (VBM) and regions of interest (ROI) analysis. AUD boys had smaller thalamic and putamen volumes compared to non-drinking boys, while AUD girls had larger thalamic and putamen volumes compared to non-drinking girls. VBM revealed a large region of decreased GM density in AUDs compared to controls located in the left lateral frontal, temporal, and parietal lobes, extending medially deep into the parietal lobe. Smaller GM volume in this region was also present when examined using ROI analysis. Our lack of findings in other brain regions, particularly hippocampus, suggests that reports of smaller brain volumes in adolescent AUDs in the literature are a consequence of psychiatric and substance abuse comorbidities. PMID:23916536

  13. Internet Addictive Individuals Share Impulsivity and Executive Dysfunction with Alcohol-Dependent Patients

    PubMed Central

    Zhou, Zhenhe; Zhu, Hongmei; Li, Cui; Wang, Jun

    2014-01-01

    Internet addiction disorder (IAD) should belong to a kind of behavioral addiction. Previous studies indicated that there are many similarities in the neurobiology of behavior and substance addictions. Up to date, although individuals with IAD have difficulty in suppressing their excessive online behaviors in real life, little is known about the patho-physiological and cognitive mechanisms responsible for IAD. Neuropsychological test studies have contributed significantly to our understanding of the effect of IAD on the cognitive function. The purpose of the present study was to examine whether Internet addictive individuals share impulsivity and executive dysfunction with alcohol-dependent individuals. Participants include 22 Internet addictive individuals, 22 patients with alcohol dependence (AD), and 22 normal controls (NC). All participants were measured with BIS-11, go/no-go task, Wisconsin Card Sorting Test, and Digit span task under the same experimental condition. Results showed that Barratt impulsiveness scale 11 scores, false alarm rate, the total response errors, perseverative errors, failure to maintain set of IAD and AD group were significantly higher than that of NC group, and hit rate, percentage of conceptual level responses, the number of categories completed, forwards scores, and backwards scores of IAD and AD group were significantly lower than that of NC group, however, no differences in above variables between IAD group and AD group were observed. These results revealed that the existence of impulsivity, deficiencies in executive function and working memory in an IAD and an AD sample, namely, Internet addictive individuals share impulsivity and executive dysfunction with alcohol-dependent patients. PMID:25202248

  14. Differences in treatment outcome between male alcohol dependent offenders of domestic violence with and without positive drug screens.

    PubMed

    Easton, Caroline J; Mandel, Dolores; Babuscio, Theresa; Rounsaville, Bruce J; Carroll, Kathleen M

    2007-10-01

    Men who are violent toward their partners tend to have a dual problem with alcohol and drug use, yet little is known about differences between men with single rather than dual problems. This study was one of the first to evaluate differences between alcohol dependent men who were arrested for Intimate Partner Violence (IPV) with and without concurrent illicit drug use. Seventy-eight participants were randomly assigned to manual-guided group behavioral therapies (Cognitive Behavioral Therapy or Twelve Step Facilitation) and assessed across 12 weeks of treatment. Despite denying drug use at baseline, thirty-two clients (43%) tested positive for illicit drug use (cocaine and marijuana) during the 12 weeks of treatment. The study specifically addressed whether there were differences between clients using alcohol only versus individuals using both alcohol + drugs in terms of 1) baseline characteristics; 2) treatment compliance (e.g., attendance and substance use during treatment; and 3) treatment outcomes (alcohol, drug use, anger management, and aggression at the completion of treatment). The results showed that there were comparatively few differences between the alcohol versus the alcohol + drug using groups at baseline. Regarding treatment compliance and retention, alcohol + drug using participants attended significantly fewer sessions, had significantly fewer percent days abstinence from alcohol use, significantly more total days of positive breathalyzer results. Regarding treatment outcomes across anger management and aggression scores, the alcohol + drug using participants had significantly more impairments in anger management styles from pre- to post-treatment. However, there were no differences between the groups across verbal or physical aggression. Both groups improved in their verbal aggression from pre- to post-treatment. The findings suggest that alcohol dependent men who continue to use illicit drugs may require additional interventions to effectively

  15. A History of Alcohol Dependence Augments HIV-associated Neurocognitive Deficits in Persons Aged 60 and Older

    PubMed Central

    Gongvatana, Assawin; Morgan, Erin E.; Iudicello, Jennifer E.; Letendre, Scott L.; Grant, Igor; Woods, Steven Paul

    2014-01-01

    Background Excessive alcohol use is common among people living with HIV. Given the growing prevalence of older HIV+ adults, and observations indicating higher risk for neurocognitive impairment in older adults with either HIV infection or alcoholism, an increased understanding of their combined impact in the context of this increasingly aged population is crucial. Methods We conducted comprehensive neurocognitive assessment in 112 older HIV+ individuals aged 50 to 69 years. Regression analyses were conducted to examine the interaction between age and the presence of lifetime alcohol dependence on neurocognitive measures, controlling for years of education, hepatitis C serostatus, and lifetime non-alcohol substance use disorder. Results Significant interactions of age and alcohol dependence history were found for global neurocognitive function, which was driven by the domains of executive function, processing speed, and semantic memory. Follow-up analyses indicated adverse effects of alcohol use history on neurocognitive measures that were evident only in HIV+ individuals 60 years and older. Conclusions While mounting evidence in younger cohorts indicates adverse synergistic HIV/alcohol effects on neurocognitive function, our novel preliminary findings in this elderly HIV+ cohort demonstrated the importance of even a relatively distant alcohol use history on the expression of HIV-associated neurocognitive disorders that may not become apparent until much later in life. PMID:25201556

  16. Frequency dependence of electron spin-lattice relaxation for semiquinones in alcohol solutions

    NASA Astrophysics Data System (ADS)

    Elajaili, Hanan B.; Biller, Joshua R.; Eaton, Sandra S.; Eaton, Gareth R.

    2014-10-01

    The spin-lattice relaxation rates at 293 K for three anionic semiquinones (2,5-di-t-butyl-1,4-benzosemiquinone, 2,6-di-t-butyl-1,4-benzosemiquinone, and 2,3,5,6-tetramethoxy-1,4-benzosemiquinone) were studied at up to 8 frequencies between 250 MHz and 34 GHz in ethanol or methanol solution containing high concentrations of OH-. The relaxation rates are about a factor of 2 faster at lower frequencies than at 9 or 34 GHz. However, in perdeuterated alcohols the relaxation rates exhibit little frequency dependence, which demonstrates that the dominant frequency-dependent contribution to relaxation is modulation of dipolar interactions with solvent nuclei. The relaxation rates were modeled as the sum of two frequency-independent contributions (spin rotation and a local mode) and two frequency-dependent contributions (modulation of dipolar interaction with solvent nuclei and a much smaller contribution from modulation of g anisotropy). The correlation time for modulation of the interaction with solvent nuclei is longer than the tumbling correlation time of the semiquinone and is consistent with hydrogen bonding of the alcohol to the oxygen atoms of the semiquinones.

  17. PSYCHO-EDUCATIONAL GROUP THERAPY FOR ALCOHOL AND DRUG DEPENDENCE RECOVERY

    PubMed Central

    Chandiramani, Kishore; Tripathi, B.M.

    1993-01-01

    SUMMARY A brief psychosocial intervention model for alcohol and drug dependence recovery has been evolved in the form of psycho-educational group therapy. The package comprises of eight sessions conducted thrice a week over a period of about three weeks following detoxification. It aims to equip the patients with information and knowledge relevant to the needs of recovery. The program covers topics such as craving and relapse, medical complications, treatment process and recovery, family, social and job problems and structuring free time. Apart from achieving abstinence, the objectives of the program include enhancing functioning in personal, social and professional spheres by developing healthy and intimate relationships and promoting alternate activities. PMID:21743631

  18. Development and Implementation of an Ambulatory Integrated Care Pathway for Major Depressive Disorder and Alcohol Dependence.

    PubMed

    Awan, Saima; Samokhvalov, Andriy V; Aleem, Nadia; Hendershot, Christian S; Irving, Julie Anne; Kalvik, Anne; Lefebvre, Lisa; Le Foll, Bernard; Quilty, Lena; Voore, Peter

    2015-12-01

    Integrated care pathways (ICPs) provide an approach for delivering evidence-based treatment in a hospital setting. This column describes the development and pilot implementation in a clinical setting of an ICP for patients with concurrent major depressive disorder and alcohol dependence at the Centre for Addiction and Mental Health (CAMH), an academic tertiary care hospital, in Toronto, Canada. The ICP methodology includes evidence reviews, knowledge translation, process reengineering, and change management. Pilot results indicate high patient satisfaction, evidence of symptom improvement, and excellent retention. PMID:26278235

  19. Using a factor mixture modeling approach in alcohol dependence in a general population sample.

    PubMed

    Kuo, Po-Hsiu; Aggen, Steven H; Prescott, Carol A; Kendler, Kenneth S; Neale, Michael C

    2008-11-01

    Alcohol dependence (AD) is a complex and heterogeneous disorder. The identification of more homogeneous subgroups of individuals with drinking problems and the refinement of the diagnostic criteria are inter-related research goals. They have the potential to improve our knowledge of etiology and treatment effects, and to assist in the identification of risk factors or specific genetic factors. Mixture modeling has advantages over traditional modeling that focuses on either the dimensional or categorical latent structure. The mixture modeling combines both latent class and latent trait models, but has not been widely applied in substance use research. The goal of the present study is to assess whether the AD criteria in the population could be better characterized by a continuous dimension, a few discrete subgroups, or a combination of the two. More than seven thousand participants were recruited from the population-based Virginia Twin Registry, and were interviewed to obtain DSM-IV (Diagnostic and Statistical Manual of Mental Disorder, version IV) symptoms and diagnosis of AD. We applied factor analysis, latent class analysis, and factor mixture models for symptom items based on the DSM-IV criteria. Our results showed that a mixture model with 1 factor and 3 classes for both genders fit well. The 3 classes were a non-problem drinking group and severe and moderate drinking problem groups. By contrast, models constrained to conform to DSM-IV diagnostic criteria were rejected by model fitting indices providing empirical evidence for heterogeneity in the AD diagnosis. Classification analysis showed different characteristics across subgroups, including alcohol-caused behavioral problems, comorbid disorders, age at onset for alcohol-related milestones, and personality. Clinically, the expanded classification of AD may aid in identifying suitable treatments, interventions and additional sources of comorbidity based on these more homogenous subgroups of alcohol use

  20. Medications Development to Treat Alcohol Dependence: A Vision for the Next Decade

    PubMed Central

    Litten, Raye Z.; Egli, Mark; Heilig, Markus; Cui, Changhai; Fertig, Joanne B.; Ryan, Megan L.; Falk, Daniel E.; Moss, Howard; Huebner, Robert; Noronha, Antonio

    2012-01-01

    More than 76 million people worldwide are estimated to have diagnosable Alcohol Use Disorders (AUDs) (alcohol abuse or dependence), making these disorders a major global health problem. Pharmacotherapy offers promising means for treating AUDs, and significant progress has been made in the past 20 years. The U.S. Food and Drug Administration approved three of the four medications for alcoholism in the last two decades. Unfortunately, these medications do not work for everyone, prompting the need for a personalized approach to optimize clinical benefit or more efficacious medications that can treat a wider range of patients, or both. To promote global health, the potential reorganization of the National Institutes of Health (NIH) must continue to support the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA’s) vision of ensuring the development and delivery of new and more efficacious medications to treat AUDs in the coming decade. To achieve this objective, the NIAAA Medications Development Team has identified three fundamental long-range goals: 1) to make the drug development process more efficient; 2) to identify more efficacious medications, personalize treatment approaches, or both, and 3) to facilitate the implementation and adaptation of medications in real-world treatment settings. These goals will be carried out through seven key objectives. This paper describes those objectives in terms of rationale and strategy. Successful implementation of these objectives will result in the development of more efficacious and safe medications, provide a greater selection of therapy options, and ultimately lessen the impact of this devastating disorder. PMID:22458728

  1. Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

    PubMed Central

    Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

    2016-01-01

    Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

  2. Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis

    PubMed Central

    Macgregor, Stuart; Lind, Penelope A.; Bucholz, Kathleen K.; Hansell, Narelle K.; Madden, Pamela A.F.; Richter, Melinda M.; Montgomery, Grant W.; Martin, Nicholas G.; Heath, Andrew C.; Whitfield, John B.

    2009-01-01

    Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. There were study-wide significant associations (P < 2.3 × 10−4) between ADH1B-Arg48His (rs1229984) and flushing and consumption, but only nominally significant associations (P < 0.01) with dependence. Individuals carrying the rs1229984 G-allele (48Arg) reported a lower prevalence of flushing after alcohol (P = 8.2 × 10−7), consumed alcohol on more occasions (P = 2.7 × 10−6), had a higher maximum number of alcoholic drinks in a single day (P = 2.7 × 10−6) and a higher overall alcohol consumption (P = 8.9 × 10−8) in the previous year than those with the less common A-allele (48His). After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (P = 4.7 × 10−5) and suggestive associations (P < 0.001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with AD measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. The absence of study-wide significant effects on AD results from the low P-value required when testing multiple single nucleotide polymorphisms and phenotypes. PMID:18996923

  3. Chronic Care Management for Dependence on Alcohol and Other Drugs: The AHEAD Randomized Trial

    PubMed Central

    Saitz, Richard; Cheng, Debbie M.; Winter, Michael; Kim, Theresa W.; Meli, Seville M.; Allensworth-Davies, Don; Lloyd-Travaglini, Christine A.; Samet, Jeffrey H.

    2014-01-01

    Importance People with substance dependence have health consequences, high healthcare utilization and frequent comorbidity but often receive poor quality care overall and for dependence. Chronic care management has been proposed as an approach to improve care and outcomes. Objective To determine whether chronic care management (CCM) for alcohol and other drug (AOD) dependence improves substance use outcomes compared to usual primary care. Design, Setting, and Participants The AHEAD study was a randomized trial in people with AOD dependence, not necessarily seeking treatment, at a Boston hospital-based primary care practice. Of the 655 eligible participants, 563 (86%) were randomized. Study participants were recruited from September 2006 to September 2008 from a free-standing residential detoxification unit (74%) and referrals from an urban teaching hospital and advertisements (26%). Participants were randomized to CCM (n=282) or no CCM (n=281). Intervention CCM included longitudinal care coordinated with a primary care clinician, motivational enhancement therapy, relapse prevention counseling, and on-site medical, addiction and psychiatric treatment, social work assistance and referrals (including mutual help). The no CCM group received a primary care appointment, and a list of treatment resources including a phone number to arrange counseling. Main Outcome and Measure The primary outcome was self-reported abstinence from opioids, stimulants or heavy drinking. Biomarkers were secondary outcomes. We employed longitudinal analyses for data from 3, 6 and 12 months (last interview January 21, 2010). Results Of 563 participants, 95% completed 12-month follow-up. Baseline characteristics of the study participants were similar across randomization groups, but differed significantly for race and depressive symptoms. There was no significant difference in abstinence from opioids, stimulants or heavy drinking between the CCM (44%) and control (42%) groups (adjusted odds

  4. Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence*

    PubMed Central

    Durazzo, Timothy C.; Pathak, Varsha; Gazdzinski, Stefan; Mon, Anderson; Meyerhoff, Dieter J.

    2010-01-01

    Objective: This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence. Method: Fifty-one treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, choline-containing compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classified as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest. Results: Resumers demonstrated significantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest. Conclusions: The significantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite

  5. Improved production of isoamyl acetate by a sake yeast mutant resistant to an isoprenoid analog and its dependence on alcohol acetyltransferase activity, but not on isoamyl alcohol production.

    PubMed

    Hirooka, Kiyoo; Yamamoto, Yoshihiro; Tsutsui, Nobuo; Tanaka, Toshio

    2005-02-01

    1-Farnesylpyridinium (FPy), an analog of isoprenoid farnesol, strongly inhibited the growth of sake yeast at 120 microM in YPD medium, whereas at 30 microM it reduced cellular production of isoamyl acetate to 20% of the control level despite the absence of inhibitory effect on CO2 evolution. The FPy-resistant mutant A1 was characterized by the high production of flavor compounds represented by a nearly threefold increase in the level of isoamyl acetate in YPD medium in which the level of isoamyl alcohol as its precursor remained almost unchanged. The FPy resistance phenotype of strain A1 was not accompanied by cellular resistance to either the L-leucine analog or L-canavanine, which alters yeast amino acid metabolism in favor of isoamyl alcohol production. Alcohol acetyltransferase (AATase) activity was high in strain A1, which further increased in response to isoamyl alcohol accumulation in medium. Flavor compound production in sake brewing could be improved using strain A1, resulting in a 1.4-fold increase in isoamyl acetate production in spite of a limited production of isoamyl alcohol. PMID:16233768

  6. [Sexual addiction in alcohol abuse and dependence. Clinical, nosologic and psychoanalytic aspects].

    PubMed

    Roth, K

    1992-03-01

    DSM-III-R names sexual addiction for the first time as a sexual disorder. In this study a group of alcoholics was examined who described their own sexual behavior as being addictive and self-destructive. In this nearly all male patient group sexual addiction manifested itself mostly in excessive masturbation and obsessional sexual fantasies often in combination with use of pornography. Promiscuity, prostitute contacts and excessive sexual demands on a steady partner and sexually deviant behavior, were less often reported in this population. The addictive sexual behavior was said to be usually provoked by emotional distress and unresolved conflicts. More than 80% of these patients were dependent upon at least one other substance beside alcohol. Two-thirds considered their sexual addictive behavior to be their primary and earliest dependency. The nosology of this disorder seems to be unspecific, since a number of forms of neurosis and personality disorder are diagnosed. A psychodynamic interpretation of sexual addiction points to defence mechanisms against inner psychic conflicts, as seen both in addiction and sexual perversion. Aspects of differential diagnosis and classification are also discussed. PMID:1579173

  7. Rescue of infralimbic mGluR2 deficit restores control over drug-seeking behavior in alcohol dependence

    PubMed Central

    Meinhardt, Marcus W; Hansson, Anita C; Perreau-Lenz, Stephanie; Bauder, Christina; Stählin, Oliver; Heilig, Markus; Harper, Clive; Drescher, Karla U; Spanagel, Rainer; Sommer, Wolfgang H

    2013-01-01

    A key deficit in alcohol dependence is disrupted prefrontal function leading to excessive alcohol seeking, but the molecular events underlying the emergence of addictive responses remain unknown. Here we show by convergent transcriptome analysis that the pyramidal neurons of the infralimbic cortex are particularly vulnerable for the long-term effects of chronic intermittent ethanol intoxication. These neurons exhibit a pronounced deficit in mGluR2. Also, alcohol dependent rats do not respond to mGluR2/3 agonist treatment with reducing extracellular glutamate levels in the nucleus accumbens. Together these data imply a loss of autoreceptor feedback control. Alcohol dependent rats show escalation of ethanol seeking, which was abolished by restoring mGluR2 expression in the infralimbic cortex via viral-mediated gene transfer. Human anterior cingulate cortex from alcoholic patients shows a significant reduction in mGluR2 transcripts compared to control subjects suggesting that mGluR2 loss in the rodent and human cortico-accumbal neurocircuitry may be a major consequence of alcohol dependence and a key pathophysiological mechanism mediating increased propensity to relapse. Normalization of mGluR2 function within this brain circuit may be of therapeutic value. PMID:23407939

  8. 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

  9. A genome wide association study of alcohol dependence symptom counts in extended pedigrees identifies C15orf53

    PubMed Central

    Wang, Jen-Chyong; Foroud, Tatiana; Hinrichs, Anthony L; Le, Nhung XH; Bertelsen, Sarah; Budde, John P; Harari, Oscar; Koller, Daniel L; Wetherill, Leah; Agrawal, Arpana; Almasy, Laura; Brooks, Andrew I; Bucholz, Kathleen; Dick, Danielle; Hesselbrock, Victor; Johnson, Eric O; Kang, Sun; Kapoor, Manav; Kramer, John; Kuperman, Samuel; Madden, Pamela AF; Manz, Niklas; Martin, Nicholas G; McClintick, Jeanette N; Montgomery, Grant W; Nurnberger, John I; Rangaswamy, Madhavi; Rice, John; Schuckit, Marc; Tischfield, Jay A; Whitfield, John B; Xuei, Xiaoling; Porjesz, Bernice; Heath, Andrew C; Edenberg, Howard J; Bierut, Laura J; Goate, Alison M

    2013-01-01

    Several studies have identified genes associated with alcohol use disorders, but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism (COGA) to identify novel genes affecting risk for alcohol dependence. To maximize the power of the extended family design we used a quantitative endophenotype, measured in all individuals: number of alcohol dependence symptoms endorsed (symptom count). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with symptom count were also associated with the dichotomous phenotype, DSM-IV alcohol dependence. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol (p=4.5×10−8, inflation corrected p=9.4×10−7). Results with DSM-IV alcohol dependence in the regions of interest support our findings with symptom count, though the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: non-overlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian twin-family study of alcohol use disorders (OZALC). Nominal association of C15orf53 with symptom count was observed in SAGE. The variant that showed strongest association with symptom count, rs12912251 and its highly correlated variants (D′=1, r2≥ 0.95), has previously been associated with risk for bipolar disorder. PMID:23089632

  10. Patterns of alcohol dependence in Thai drinkers: a differential item functioning analysis of gender and age bias.

    PubMed

    Srisurapanont, Manit; Kittiratanapaiboon, Phunnapa; Likhitsathian, Surinporn; Kongsuk, Thoranin; Suttajit, Sirijit; Junsirimongkol, Boonsiri

    2012-02-01

    In Caucasians, the patterns of alcohol use disorders in women and adolescents are likely to be different from those in men and adults, respectively. The authors examined these differences in a Southeast Asian sample of Thai people living in communities. A two-parameter logistic model of the IRT log-likelihood-ratio (IRTLR) test for differential item functioning (DIF) procedure was used. Participants were a subsample of 3718 current drinkers participating in the 2008 Thai National Mental Health Survey (n=17,140). The 1-year prevalence rates of alcohol dependence were 1.4% in women and 13.7% in men. Based on the Mini International Neuropsychiatric Interview (MINI), alcohol dependence and abuse module, all current drinkers were interviewed for a yes/no response to each of seven alcohol dependence criteria. Confirmatory factor analysis suggested a single-factor model of alcohol dependence criteria (χ2=211.51, RMSEA=0.06, SRMR=0.03 and CFI=0.96). Compared with 3174 men, 544 women had a significantly higher threshold estimate for quit/control problems and a lower threshold value for drinking despite physical/mental problems (b parameter difference of 0.25 and -0.30, respectively). Thai adolescents (n=272) and Thai adults (n=3446) had no statistically significant DIF on any criterion. The criterion of time spent drinking had significantly high discrimination estimates in women, men, adolescent and adults (a parameters of 2.50, 2.08, 2.33 and 2.16, respectively). Gender bias on alcohol dependence criteria can be found in Thai drinkers. Time spent drinking may be the most useful criterion for discriminating the severity of alcohol dependence across age and gender groups of Thai drinkers.

  11. Prospective Developmental Subtypes of Alcohol Dependence from Age 18 to 32 Years: Implications for Nosology, Etiology, and Intervention

    PubMed Central

    Meier, Madeline H.; Caspi, Avshalom; Houts, Renate; Slutske, Wendy S.; Harrington, HonaLee; Jackson, Kristina M.; Belsky, Daniel W.; Poulton, Richie; Moffitt, Terrie E.

    2012-01-01

    The purpose of the present study was to identify child and adult correlates that differentiate (a) individuals with persistent alcohol dependence from individuals with developmentally-limited alcohol dependence and (b) individuals with adult-onset alcohol dependence from individuals who never diagnose. Participants are 1,037 members of the Dunedin longitudinal study, a birth cohort followed prospectively from birth until age 32. Past-year DSM-IV alcohol dependence diagnoses were ascertained with structured diagnostic interviews at ages 18, 21, 26, and 32. Individuals were classified as developmentally-limited, persistent, or adult-onset subtypes based on their time-ordered pattern of diagnoses. The persistent subtype generally exhibited the worst scores on all correlates, including family psychiatric history, adolescent and adult externalizing and internalizing problems, adolescent and adult substance use, adult quality of life, and coping strategies. The prospective predictors that distinguished them from the developmentally-limited subtype involved family liability, adolescent negative affectivity, daily alcohol use, and frequent marijuana use. Furthermore, young people who developed the persistent subtype of alcohol dependence were distinguished from the developmentally-limited subtype by an inability to reduce drinking and by continued use despite problems, already by age 18. The adult-onset group members were virtually indistinguishable from ordinary cohort members as children or adolescents, but, in adulthood, adult-onset cases were distinguished by problems with depression, substance use, stress, and strategies for coping with stress. Information about age-of-onset and developmental course is fundamental for identifying subtypes of alcohol dependence. Subtype-specific etiologies point to targeted prevention and intervention efforts based on characteristics of each subtype. PMID:23880392

  12. Health risks of alcohol use

    MedlinePlus

    Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... Beer, wine, and liquor all contain alcohol. If you are drinking any of these, you are using alcohol. Your drinking patterns may vary, depending on who you are with ...

  13. Plasticity of GABAA receptor-mediated neurotransmission in the nucleus accumbens of alcohol-dependent rats

    PubMed Central

    Liang, Jing; Lindemeyer, A. Kerstin; Suryanarayanan, Asha; Meyer, Edward M.; Marty, Vincent N.; Ahmad, S. Omar; Shao, Xuesi Max; Olsen, Richard W.

    2014-01-01

    Chronic alcohol exposure-induced changes in reinforcement mechanisms and motivational state are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Here we describe the long-lasting alterations of γ-aminobutyric acid type A receptors (GABAARs) of medium spiny neurons (MSNs) in the NAcc after chronic intermittent ethanol (CIE) treatment, a rat model of alcohol dependence. CIE treatment and withdrawal (>40 days) produced decreases in the ethanol and Ro15-4513 potentiation of extrasynaptic GABAARs, which mediate the picrotoxin-sensitive tonic current (Itonic), while potentiation of synaptic receptors, which give rise to miniature inhibitory postsynaptic currents (mIPSCs), was increased. Diazepam sensitivity of both Itonic and mIPSCs was decreased by CIE treatment. The average magnitude of Itonic was unchanged, but mIPSC amplitude and frequency decreased and mIPSC rise time increased after CIE treatment. Rise-time histograms revealed decreased frequency of fast-rising mIPSCs after CIE treatment, consistent with possible decreases in somatic GABAergic synapses in MSNs from CIE rats. However, unbiased stereological analysis of NeuN-stained NAcc neurons did not detect any decreases in NAcc volume, neuronal numbers, or neuronal cell body volume. Western blot analysis of surface subunit levels revealed selective decreases in α1 and δ and increases in α4, α5, and γ2 GABAAR subunits after CIE treatment and withdrawal. Similar, but reversible, alterations occurred after a single ethanol dose (5 g/kg). These data reveal CIE-induced long-lasting neuroadaptations in the NAcc GABAergic neurotransmission. PMID:24694935

  14. Which treatment for alcohol dependence: naltrexone, acamprosate and/or behavioural intervention?

    PubMed

    Doggrell, Sheila A

    2006-10-01

    Alcoholism is the third leading cause of preventable mortality and morbidity in the US. In the COMBINE (Combined Pharmacotherapies and Behavioural Interventions) study, the co-primary end points were the percentage of days abstinent and the time to first heavy drinking day after 16 weeks, and 1 year. The biggest difference observed in COMBINE was that seen between combined behavioural intervention (CBI; percentage of abstinent days = 66.6%) and CBI and medical management with placebos (79.8%). This illustrated a major effect of the medical management of nine sessions and/or the placebo pills. Acamprosate had no effect alone or in combination with naltrexone. At 16 weeks with medical management, there were 75.1% of the patients who were abstinent for placebos, and this was improved by naltrexone, CBI, and naltrexone with CBI (80.6, 78.2 and 77.1%, respectively). There was a follow up after 1 year, which showed that, with medical management, the amount of those who were abstinent for placebos was 61.4%, and this was improved by naltrexone, CBI, and naltrexone with CBI (66.2, 66.6 and 67.3%, respectively), but this improvement no longer reached statistical significance. After 1 year, there was no difference between groups in the overall frequency of hospitalisation, emergency treatment for alcohol problems, use of medication for drinking or emotional problems and detoxification. Being part of a study for alcohol dependence is known to increase the percentage of abstinent days. In COMBINE, this percentage was high in the group having medical management and placebo pills, and naltrexone or additional behavioural therapy only had modest additional effects.

  15. Analysis of extreme drinking in patients with alcohol dependence using Pareto regression.

    PubMed

    Das, Sourish; Harel, Ofer; Dey, Dipak K; Covault, Jonathan; Kranzler, Henry R

    2010-05-20

    We developed a novel Pareto regression model with an unknown shape parameter to analyze extreme drinking in patients with Alcohol Dependence (AD). We used the generalized linear model (GLM) framework and the log-link to include the covariate information through the scale parameter of the generalized Pareto distribution. We proposed a Bayesian method based on Ridge prior and Zellner's g-prior for the regression coefficients. Simulation study indicated that the proposed Bayesian method performs better than the existing likelihood-based inference for the Pareto regression.We examined two issues of importance in the study of AD. First, we tested whether a single nucleotide polymorphism within GABRA2 gene, which encodes a subunit of the GABA(A) receptor, and that has been associated with AD, influences 'extreme' alcohol intake and second, the efficacy of three psychotherapies for alcoholism in treating extreme drinking behavior. We found an association between extreme drinking behavior and GABRA2. We also found that, at baseline, men with a high-risk GABRA2 allele had a significantly higher probability of extreme drinking than men with no high-risk allele. However, men with a high-risk allele responded to the therapy better than those with two copies of the low-risk allele. Women with high-risk alleles also responded to the therapy better than those with two copies of the low-risk allele, while women who received the cognitive behavioral therapy had better outcomes than those receiving either of the other two therapies. Among men, motivational enhancement therapy was the best for the treatment of the extreme drinking behavior.

  16. 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

  17. Optical isopropanol biosensor using NADH-dependent secondary alcohol dehydrogenase (S-ADH).

    PubMed

    Chien, Po-Jen; Ye, Ming; Suzuki, Takuma; Toma, Koji; Arakawa, Takahiro; Iwasaki, Yasuhiko; Mitsubayashi, Kohji

    2016-10-01

    Isopropanol (IPA) is an important solvent used in industrial activity often found in hospitals as antiseptic alcohol rub. Also, IPA may have the potential to be a biomarker of diabetic ketoacidosis. In this study, an optical biosensor using NADH-dependent secondary alcohol dehydrogenase (S-ADH) for IPA measurement was constructed and evaluated. An ultraviolet light emitting diode (UV-LED, λ=340nm) was employed as the excitation light to excite nicotinamide adenine dinucleotide (NADH). A photomultiplier tube (PMT) was connected to a two-way branch optical fiber for measuring the fluorescence emitted from the NADH. S-ADH was immobilized on the membrane to catalyze IPA to acetone and reduce NAD(+) to be NADH. This IPA biosensor shows highly sensitivity and selectivity, the calibration range is from 500 nmol L(-1) to 1mmolL(-1). The optimization of buffer pH, temperature, and the enzyme-immobilized method were also evaluated. The detection of IPA in nail related cosmetic using our IPA biosensor was also carried out. The results showed that large amounts of IPA were used in these kinds of cosmetics. This IPA biosensor comes with the advantages of rapid reaction, good reproducibility, and wide dynamic range, and is also expected to use for clinical IPA detections in serum or other medical and health related applications.

  18. Optical isopropanol biosensor using NADH-dependent secondary alcohol dehydrogenase (S-ADH).

    PubMed

    Chien, Po-Jen; Ye, Ming; Suzuki, Takuma; Toma, Koji; Arakawa, Takahiro; Iwasaki, Yasuhiko; Mitsubayashi, Kohji

    2016-10-01

    Isopropanol (IPA) is an important solvent used in industrial activity often found in hospitals as antiseptic alcohol rub. Also, IPA may have the potential to be a biomarker of diabetic ketoacidosis. In this study, an optical biosensor using NADH-dependent secondary alcohol dehydrogenase (S-ADH) for IPA measurement was constructed and evaluated. An ultraviolet light emitting diode (UV-LED, λ=340nm) was employed as the excitation light to excite nicotinamide adenine dinucleotide (NADH). A photomultiplier tube (PMT) was connected to a two-way branch optical fiber for measuring the fluorescence emitted from the NADH. S-ADH was immobilized on the membrane to catalyze IPA to acetone and reduce NAD(+) to be NADH. This IPA biosensor shows highly sensitivity and selectivity, the calibration range is from 500 nmol L(-1) to 1mmolL(-1). The optimization of buffer pH, temperature, and the enzyme-immobilized method were also evaluated. The detection of IPA in nail related cosmetic using our IPA biosensor was also carried out. The results showed that large amounts of IPA were used in these kinds of cosmetics. This IPA biosensor comes with the advantages of rapid reaction, good reproducibility, and wide dynamic range, and is also expected to use for clinical IPA detections in serum or other medical and health related applications. PMID:27474326

  19. Alcohol Dependence Associated with Increased Utilitarian Moral Judgment: A Case Control Study

    PubMed Central

    Khemiri, Lotfi; Guterstam, Joar; Franck, Johan; Jayaram-Lindström, Nitya

    2012-01-01

    Recent studies indicate that emotional processes, mediated by the ventromedial prefrontal cortex (VMPC), are of great importance for moral judgment. Neurological patients with VMPC dysfunction have been shown to generate increased utilitarian moral judgments, i.e. are more likely to endorse emotionally aversive actions in order to maximize aggregate welfare, when faced with emotionally salient personal moral dilemmas. Patients with alcohol dependence (AD) also exhibit impairments in functions mediated by the prefrontal cortex, but whether they exhibit increased utilitarian moral reasoning has not previously been investigated. The aim of this study was to investigate moral judgment in AD patients (n = 20) compared to healthy controls (n = 20) matched by sex, age and education years. Each subject responded to a battery of 50 hypothetical dilemmas categorized as non-moral, moral impersonal and moral personal. They also responded to a questionnaire evaluating explicit knowledge of social and moral norms. Results confirmed our hypothesis that AD patients generated increased utilitarian moral judgment compared to controls when faced with moral personal dilemmas. Crucially, there was no difference in their responses to non-moral or impersonal moral dilemmas, nor knowledge of explicit social and moral norms. One possible explanation is that damage to the VMPC, caused by long term repeated exposure to alcohol results in emotional dysfunction, predisposing to utilitarian moral judgment. This work elucidates a novel aspect of the neuropsychological profile of AD patients, namely a tendency to generate utilitarian moral judgment when faced with emotionally salient moral personal dilemmas. PMID:22761922

  20. Prevalence of and potential influencing factors for alcohol dependence in Europe.

    PubMed

    Rehm, Jürgen; Anderson, Peter; Barry, Joe; Dimitrov, Plamen; Elekes, Zsuzsanna; Feijão, Fernanda; Frick, Ulrich; Gual, Antoni; Gmel, Gerrit; Kraus, Ludwig; Marmet, Simon; Raninen, Jonas; Rehm, Maximilien X; Scafato, Emanuele; Shield, Kevin D; Trapencieris, Marcis; Gmel, Gerhard

    2015-01-01

    Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.4% among people 18-64 years of age in Europe (women 1.7%, men 5.2%), resulting in close to 11 million affected people. Taking into account all people of all ages, AD, abuse and harmful use resulted in an estimate of 23 million affected people. Prevalence of AD varied widely between European countries, and was significantly impacted by drinking cultures and social norms. Correlations with level of drinking and other drinking variables and with major known outcomes of heavy drinking, such as liver cirrhosis or injury, were moderate. These results suggest a need to rethink the definition of AUDs.

  1. The Role of Constraint in the Development of Nicotine, Marijuana, and Alcohol Dependence in Young Adulthood

    PubMed Central

    Vrieze, Scott I.; Vaidyanathan, Uma; Hicks, Brian M.; Iacono, William G.; McGue, Matt

    2014-01-01

    The personality-related construct of behavioral disinhibition is hypothesized to confer a generalized risk for alcohol and drug dependence. On average, rates of substance use and scores on measures of disinhibition peak in adolescence and decline as people mature into adulthood. The present study investigated this developmental change by evaluating the relationship between disinhibition and substance use disorders using a longitudinal study of 2,608 twins assessed at ages 17, 24, and 29. These ages include the period of highest risk for substance use disorders (ages 17-24) as well as when substance dependence symptoms typically decline (ages 24-29). Disinhibition was measured with the Multidimensional Personality Questionnaire higher-order scale of Constraint, as well as its constituent facet scales of Harm Avoidance, Control, and Traditionalism. Constraint’s relationship with substance dependence was statistically significant but small and largely genetic, with the genetic relationship declining from adolescence into adulthood. However, this result appeared to be almost entirely driven by Traditionalism, a propensity to hold traditional moral and social values, and not an obvious component of behavioral disinhibition. The results suggest that personality measures of Control and Harm Avoidance play only a small role in the development of substance dependence during late adolescence, and previous findings linking personality measures of disinhibition and substance use may be driven significantly by social and moral values than deficits in impulse control. PMID:24343204

  2. Disulfiram Efficacy in the Treatment of Alcohol Dependence: A Meta-Analysis

    PubMed Central

    Skinner, Marilyn D.; Lahmek, Pierre; Pham, Héloïse; Aubin, Henri-Jean

    2014-01-01

    supportive pharmacological treatments or to no disulfiram in supervised studies for problems of alcohol abuse or dependence. PMID:24520330

  3. Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.

    PubMed

    Zlojutro, Mark; Manz, Niklas; Rangaswamy, Madhavi; Xuei, Xiaoling; Flury-Wetherill, Leah; Koller, Daniel; Bierut, Laura J; Goate, Alison; Hesselbrock, Victor; Kuperman, Samuel; Nurnberger, John; Rice, John P; Schuckit, Marc A; Foroud, Tatiana; Edenberg, Howard J; Porjesz, Bernice; Almasy, Laura

    2011-01-01

    Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype-frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two-stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10⁻⁶). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10⁻⁴), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM-IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case-controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case-control and family-based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders.

  4. Polysomnographic measures of sleep in cocaine dependence and alcohol dependence: Implications for age‐related loss of slow wave, stage 3 sleep

    PubMed Central

    Bjurstrom, Martin F.; Olmstead, Richard

    2016-01-01

    Abstract Background and aims Sleep disturbance is a prominent complaint in cocaine and alcohol dependence. This controlled study evaluated differences of polysomnographic (PSG) sleep in cocaine‐ and alcohol‐dependent subjects, and examined whether substance dependence interacts with age to alter slow wave sleep and rapid eye movement (REM) sleep. Design Cross‐sectional comparison. Setting Los Angeles and San Diego, CA, USA. Participants Abstinent cocaine‐dependent subjects (n = 32), abstinent alcohol‐dependent subjects (n = 73) and controls (n = 108); mean age 40.3 years recruited 2005–12. Measurements PSG measures of sleep continuity and sleep architecture primary outcomes of Stage 3 sleep and REM sleep. Covariates included age, ethnicity, education, smoking, body mass index and depressive symptoms. Findings Compared with controls, both groups of substance dependent subjects showed loss of Stage 3 sleep (P < 0.001). A substance dependence × age interaction was found in which both cocaine‐ and alcohol‐dependent groups showed loss of Stage 3 sleep at an earlier age than controls (P < 0.05 for all), and cocaine‐dependent subjects showed loss of Stage 3 sleep at an earlier age than alcoholics (P < 0.05). Compared with controls, REM sleep was increased in both substance‐dependent groups (P < 0.001), and cocaine and alcohol dependence were associated with earlier age‐related increase in REM sleep (P < 0.05 for all). Conclusions Cocaine and alcohol dependence appear to be associated with marked disturbances of sleep architecture, including increased rapid eye movement sleep and accelerated age‐related loss of slow wave, Stage 3 sleep. PMID:26749502

  5. Alcohol and the Elderly. Hearing before the Subcommittee on Health and Long-Term Care of the Select Committee on Aging. House of Representatives, Ninety-Eighth Congress, First Session (June 10, 1983, Astoria, N.Y.).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Select Committee on Aging.

    The proceedings of the Congressional hearing on alcohol and the elderly are presented. Following introductory statements by the committee chairman, Senator Claude Pepper, and Representatives Mario Biaggi and Geraldine Ferraro, the briefing paper, "Crisis in Health Care Part 2: Alcoholism," prepared by the subcommittee staff is presented. Issues…

  6. Time-dependent effects of alcohol on the hypothalamic-hypophyseal-testicular function in the rat.

    PubMed

    Esquifino, A I; Mateos, A; Agrasal, C; Martin, I; Canovas, J M; Fermoso, J

    1989-04-01

    Adult male rats were followed throughout ethanol administration, in order to examine the time-dependent effects of ethanol on the hypothalamic-pituitary-gonadal axis. The results indicate that there is an increase in plasma prolactin levels together with a reduction in basal plasma luteinizing hormone (LH) levels, which are evident from the beginning of the intoxication period. An exaggerated response of LH to luteinizing hormone-releasing hormone was also evident from 2nd week on, in ethanol-treated rats. Basal and human chorionic gonadotropin-stimulated plasma testosterone levels were decreased in alcohol-treated as compared to control rats, at all time points studied. In addition, plasma estradiol levels were increased in ethanol-fed rats. These data suggest a direct suppressive effect of ethanol on LH release in the beginning of the intoxication period. Subsequent elevations of plasma estradiol and prolactin levels may have contributed to the maintenance of hypogonadism at the end of the intoxication period.

  7. Interactions between DRD4 and Developmentally Specific Environments in Alcohol Dependence Symptoms

    PubMed Central

    Carlson, Marie D.; Harden, K. Paige; Kretsch, Natalie; Corbin, William R.; Fromme, Kim

    2015-01-01

    Social experiences may moderate genetic influences on alcohol dependence (AD) symptoms. Consistent with this hypothesis, Park, Sher, Todorov, and Heath (2011) previously reported interactions between the dopamine D4 receptor gene (DRD4) and developmentally specific environments in the etiology of AD symptoms during emerging and young adulthood. Using a longitudinal cohort of n = 367 White participants followed from ages 18–27 we examine a series of similar interactions between DRD4 and developmentally sensitive contexts including childhood adversity and work and family roles. In contrast to previous results, we observed no significant interactions between DRD4 and childhood adversity. Overall, results further highlight the need for longitudinal studies of gene × environment interaction in the behavioral sciences and the difficulty of identifying candidate gene × environment interaction effects that are consistent across studies. PMID:26595480

  8. Experiences of everyday life in men with alcohol dependency--a qualitative study.

    PubMed

    Thurang, Anna Maria; Palmstierna, Tom; Tops, Anita Bengtsson

    2014-08-01

    The aim of the present study is to describe and understand the meaning of living with alcohol dependency (AD) as a man. Studies point out a high prevalence of AD in men and the reasons for, and consequences of, that are complex. However, today there is a lack of knowledge about men's lived experiences of having AD. In-depth interviews were conducted with 15 alcohol dependent men and analyzed using a phenomenological-hermeneutic approach. In the comprehensive understanding, findings from the naïve understanding and the structural analysis were interpreted with help from both gender and caring theoretical perspectives. "A Fallible Man" and "A Man with Powerfulness" were disclosed as two main gender formations influencing senses of well-being. A Fallible Man involved varying experiences of restrictions, being in control, and meaninglessness. Being in control promoted a sense of well-being. A Man with Powerfulness involved energetic activity, and the development and maintaining of interests as well as risk-taking. Being powerful diminished feelings of meaninglessness, cravings, and social alienation. The results show, among other things, that the men live an incompatible life and, because of that, need support and guidance to find a more meaningful life. This can be accomplished if caregivers allow men to be in focus and involved in planning their own care. To avoid limiting the men while they are in treatment, the health care professionals also need to focus on the men's everyday life. This focus involves acknowledging the men's individual experiences of what enriches and limits their everyday lives.

  9. Alcohol Dependence and Altered Engagement of Brain Networks in Risky Decisions

    PubMed Central

    Zhu, Xi; Sundby, Kelsey; Bjork, James M.; Momenan, Reza

    2016-01-01

    Alcohol dependence is associated with heightened risk tolerance and altered decision-making. This raises the question as to whether alcohol dependent patients (ADP) are incapable of proper risk assessment. We investigated how healthy controls (HC) and ADP engage neural networks to cope with the increased cognitive demands of risky decisions. We collected fMRI data while 34 HC and 16 ADP played a game that included “safe” and “risky” trials. In safe trials, participants accrued money at no risk of a penalty. In risky trials, reward and risk simultaneously increased as participants were instructed to decide when to stop a reward accrual period. If the participant failed to stop before an undisclosed time, the trial would “bust” and participants would not earn the money from that trial. Independent Component Analysis was used to identify networks engaged during the anticipation and the decision execution of risky compared with safe trials. Like HC, ADP demonstrated distinct network engagement for safe and risky trials at anticipation. However, at decision execution, ADP exhibited severely reduced discrimination in network engagement between safe and risky trials. Although ADP behaviorally responded to risk they failed to appropriately modify network engagement as the decision continued, leading ADP to assume similar network engagement regardless of risk prospects. This may reflect disorganized network switching and a facile response strategy uniformly adopted by ADP across risk conditions. We propose that aberrant salience network (SN) engagement in ADP might contribute to ineffective network switching and that the role of the SN in risky decisions warrants further investigation. PMID:27064561

  10. Family-based association analysis of alcohol dependence criteria and severity

    PubMed Central

    Wetherill, Leah; Kapoor, Manav; Agrawal, Arpana; Bucholz, Kathleen; Koller, Daniel; Bertelsen, Sarah E.; Le, Nhung; Wang, Jen-Chyong; Almasy, Laura; Hesselbrock, Victor; Kramer, John; Nurnberger, John I.; Schuckit, Marc; Tischfield, Jay A.; Xuei, Xiaoling; Porjesz, Bernice; Edenberg, Howard J.; Goate, Alison M.; Foroud, Tatiana

    2013-01-01

    Background Despite the high heritability of alcohol dependence (AD), the genes found to be associated with it account for only a small proportion of its total variability. The goal of this study was to identify and analyze phenotypes based on homogeneous classes of individuals to increase the power to detect genetic risk factors contributing to the risk of AD. Methods The 7 individual DSM-IV criteria for AD were analyzed using latent class analysis (LCA) to identify classes defined by the pattern of endorsement of the criteria. A genome-wide association study was performed in 118 extended European American families (n = 2,322 individuals) densely affected with AD to identify genes associated with AD, with each of the seven DSM-IV criteria, and with the probability of belonging to two of three latent classes. Results Heritability for DSM-IV AD was 61%, and ranged from 17-60% for the other phenotypes. A SNP in the olfactory receptor OR51L1 was significantly associated (7.3 × 10−8) with the DSM-IV criterion of persistent desire to, or inability to, cut down on drinking. LCA revealed a three-class model: the “low risk” class (50%) rarely endorsed any criteria, and none met criteria for AD; the “moderate risk” class (33) endorsed primarily 4 DSM-IV criteria, and 48% met criteria for AD; the “high risk” class (17%) manifested high endorsement probabilities for most criteria and nearly all (99%) met criteria for AD One single nucleotide polymorphism (SNP) in a sodium leak channel NALCN demonstrated genome-wide significance with the high risk class (p=4.1 × 10−8). Analyses in an independent sample did not replicate these associations. Conclusion We explored the genetic contribution to several phenotypes derived from the DSM-IV alcohol dependence criteria. The strongest evidence of association was with SNPs in NALCN and OR51L1. PMID:24015780

  11. Gender Differences in Early Maladaptive Schemas in a Treatment-Seeking Sample of Alcohol-Dependent Adults

    PubMed Central

    Shorey, Ryan C.; Anderson, Scott E.; Stuart, Gregory L.

    2012-01-01

    The current study examined early maladaptive schemas among alcohol-dependent men and women and sought to determine whether men and women differed in their early maladaptive schemas. Using preexisting patient records of adults diagnosed with alcohol dependence from a residential treatment center in the Southeastern United States, from 2005 to 2010 (N = 854), results showed that women scored significantly higher than men on 14 of the 18 early maladaptive schemas assessed. Both women and men endorsed having a number of early maladaptive schemas, with four schemas being particularly prevalent across gender. Study limitations are noted and implications of these findings for treatment and future research are discussed. PMID:22060801

  12. Topography, Power and Current Source Density of Theta Oscillations during Reward Processing as Markers for Alcohol Dependence

    PubMed Central

    Kamarajan, Chella; Rangaswamy, Madhavi; Manz, Niklas; Chorlian, David B.; Pandey, Ashwini K.; Roopesh, Bangalore N.; Porjesz, Bernice

    2013-01-01

    Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol dependent individuals are quite rare. The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task which involved outcomes of either loss or gain of an amount (10¢ or 50¢) that was bet. Event-related theta band (3.0–7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200–500 ms) was compared across groups and outcome conditions. Additionally, behavioral data of impulsivity and task performance were analyzed. The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current Source Density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition as compared to controls who manifested stronger and focused midline sources. Further, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures. A strong association between reduced anterior theta power and impulsive task-performance was observed. It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control. PMID:21520344

  13. Topography, power, and current source density of θ oscillations during reward processing as markers for alcohol dependence.

    PubMed

    Kamarajan, Chella; Rangaswamy, Madhavi; Manz, Niklas; Chorlian, David B; Pandey, Ashwini K; Roopesh, Bangalore N; Porjesz, Bernice

    2012-05-01

    Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol-dependent individuals are quite rare. The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task, which involved outcomes of either loss or gain of an amount (10 or 50¢) that was bet. Event-related theta band (3.0-7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200-500 ms) was compared across groups and outcome conditions. Additionally, behavioral data of impulsivity and task performance were analyzed. The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current source density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition when compared with controls who manifested stronger and focused midline sources. Furthermore, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures. A strong association between reduced anterior theta power and impulsive task-performance was observed. It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing, and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control.

  14. Furfural reduction mechanism of a zinc-dependent alcohol dehydrogenase from Cupriavidus necator JMP134

    PubMed Central

    Kang, ChulHee; Hayes, Robert; Sanchez, Emiliano J.; Webb, Brian N.; Li, Qunrui; Hooper, Travis; Nissen, Mark S.; Xun, Luying

    2012-01-01

    Summary FurX is a tetrameric Zn-dependent alcohol dehydrogenase (ADH) from Cupriavidus necator JMP134. The enzyme rapidly reduces furfural with NADH as the reducing power. For the first time among characterized ADHs, the high-resolution structures of all reaction steps were obtained in a time-resolved manner, thereby illustrating the complete catalytic events of NADH-dependent reduction of furfural and the dynamic Zn2+ coordination among Glu66, water, substrate and product. In the fully closed conformation of the NADH complex, the catalytic turnover proved faster than observed for the partially closed conformation due to an effective proton transfer network. The domain motion triggered by NAD(H) association/dissociation appeared to facilitate dynamic interchanges in Zn2+ coordination with substrate and product molecules, ultimately increasing the enzymatic turnover rate. NAD+ dissociation appeared to be a slow process, involving multiple steps in concert with a domain opening and reconfiguration of Glu66. This agrees with the report that the cofactor is not dissociated from FurX during ethanol-dependent reduction of furfural, in which ethanol reduces NAD+ to NADH that is subsequently used for furfural reduction. PMID:22081946

  15. Association of Smoking with Mu- Opioid Receptor Availability Before and During Naltrexone Blockade in Alcohol-Dependent Subjects

    PubMed Central

    Weerts, Elise M.; Wand, Gary S.; Kuwabara, Hiroto; Xu, Xiaoqiang; Frost, J.James; Wong, Dean F.; McCaul, Mary E.

    2012-01-01

    Persons with a history of alcohol dependence are more likely to use tobacco and to meet criteria for nicotine dependence compared to social drinkers or nondrinkers. The high levels of comorbidity of nicotine and alcohol use and dependence are thought to be related to interactions between nicotinic, opioid and dopamine receptors in mesolimbic regions. The current study examined whether individual differences in regional mu-opioid receptor (MOR) availability were associated with tobacco use, nicotine dependence, and level of nicotine craving in 25 alcohol dependent (AD) subjects. AD subjects completed an inpatient protocol, which included medically supervised alcohol withdrawal, monitored alcohol abstinence, transdermal nicotine maintenance (21 mg/day), and Positron Emission Tomography (PET) imaging using the MOR agonist [11C]-carfentanil (CFN) before (basal scan) and during treatment with 50 mg/day naltrexone (naltrexone scan). Subjects who had higher scores on the Fagerström Nicotine Dependence Test had significantly lower basal scan binding potential (BPND) across mesolimbic regions including the amygdala, cingulate, globus pallidus, thalamus and insula. Likewise, the number of cigarettes per day was negatively associated with basal scan BPND in mesolimbic regions Higher nicotine craving was significantly associated with lower BPND in amygdala, globus pallidus, putamen, thalamus and ventral striatum. Although blunted during naltrexone treatment, the negative association was maintained for nicotine dependence and cigarettes per day, but not for nicotine craving. These findings suggest that intensity of cigarette smoking and severity of nicotine dependence symptoms are systematically related to reduced BPND across multiple brain regions in AD subjects. PMID:23252742

  16. An ongoing process: A qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence

    PubMed Central

    2009-01-01

    Background Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent. Methods Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan. Results We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle. Conclusion This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services. PMID:19930698

  17. Describing Temperature-Dependent Self-Diffusion Coefficients and Fluidity of 1- and 3-Alcohols with the Compensated Arrhenius Formalism.

    PubMed

    Fleshman, Allison M; Forsythe, Grant E; Petrowsky, Matt; Frech, Roger

    2016-09-22

    The location of the hydroxyl group in monohydroxy alcohols greatly affects the temperature dependence of the liquid structure due to hydrogen bonding. Temperature-dependent self-diffusion coefficients, fluidity (the inverse of viscosity), dielectric constant, and density have been measured for several 1-alcohols and 3-alcohols with varying alkyl chain lengths. The data are modeled using the compensated Arrhenius formalism (CAF). The CAF follows a modified transition state theory using an Arrhenius-like expression to describe the transport property, which consists of a Boltzmann factor containing an energy of activation, Ea, and an exponential prefactor containing the temperature-dependent solution dielectric constant, εs(T). Both 1- and 3-alcohols show the Ea of diffusion coefficients (approximately 43 kJ mol(-1)) is higher than the Ea of fluidity (approximately 35 kJ mol(-1)). The temperature dependence of the exponential prefactor in these associated liquids is explained using the dielectric constant and the Kirkwood-Frölich correlation factor, gk. It is argued that the dielectric constant must be used to account for the additional temperature dependence due to variations in the liquid structure (e.g., hydrogen bonding) for the CAF to accurately model the transport property. PMID:27580069

  18. A follow-up study on the quality of alcohol dependence-related information on the web.

    PubMed

    Coquard, Olivier; Fernandez, Sebastien; Zullino, Daniele; Khazaal, Yasser

    2011-01-01

    In order to evaluate the one-year evolution of web-based information on alcohol dependence, we re-assessed alcohol-related sites in July 2007 with the same evaluating tool that had been used to assess these sites in June 2006. Websites were assessed with a standardized form designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. The DISCERN scale was also used, which aimed to assist persons without content expertise in assessing the quality of written health publications. Scores were highly stable for all components of the form one year later (r = .77 to .95, p < .01). Analysis of variance for repeated measures showed no time effect, no interaction between time and scale, no interaction between time and group (affiliation categories), and no interaction between time, group, and scale. The study highlights lack of change of alcohol-dependence-related web pages across one year.

  19. Eye color: A potential indicator of alcohol dependence risk in European Americans.

    PubMed

    Sulovari, Arvis; Kranzler, Henry R; Farrer, Lindsay A; Gelernter, Joel; Li, Dawei

    2015-07-01

    In archival samples of European-ancestry subjects, light-eyed individuals have been found to consume more alcohol than dark-eyed individuals. No published population-based studies have directly tested the association between alcohol dependence (AD) and eye color. We hypothesized that light-eyed individuals have a higher prevalence of AD than dark-eyed individuals. A mixture model was used to select a homogeneous sample of 1,263 European-Americans and control for population stratification. After quality control, we conducted an association study using logistic regression, adjusting for confounders (age, sex, and genetic ancestry). We found evidence of association between AD and blue eye color (P = 0.0005 and odds ratio = 1.83 (1.31-2.57)), supporting light eye color as a risk factor relative to brown eye color. Network-based analyses revealed a statistically significant (P = 0.02) number of genetic interactions between eye color genes and AD-associated genes. We found evidence of linkage disequilibrium between an AD-associated GABA receptor gene cluster, GABRB3/GABRG3, and eye color genes, OCA2/HERC2, as well as between AD-associated GRM5 and pigmentation-associated TYR. Our population-phenotype, network, and linkage disequilibrium analyses support association between blue eye color and AD. Although we controlled for stratification we cannot exclude underlying occult stratification as a contributor to this observation. Although replication is needed, our findings suggest that eye pigmentation information may be useful in research on AD. Further characterization of this association may unravel new AD etiological factors. © 2015 Wiley Periodicals, Inc.

  20. Effect of 15% Alcohol Dependence on Alveolar Bone Loss and TNF-α Secretion in Wistar Rats.

    PubMed

    Wagner, Marcius Comparsi; Rocha, José Mariano da; Gaio, Eduardo José; Cavagni, Juliano; Carrard, Vinícius Coelho; Rösing, Cassiano Kuchenbecker

    2016-01-01

    The aim of the present study was to evaluate the effect of 15% alcohol dependence on ligature-induced alveolar bone loss and TNF-α secretion in Wistar rats. Thirty-three male Wistar rats aged 45-60 days (mean weight=253 g) were randomly allocated test or control groups. Test group (n=18) received 15% alcohol as liquid intake and control group (n=15) received water during the experimental period. TNF-α was analyzed by ELISA assay in 11 animals per group. After 14 days of alcohol/water intake, alcohol dependency was assessed and silk ligatures were placed around the left second upper molars. Ligature presence and body weight were checked weekly. After 40 days, animals were sacrificed and the maxillae were defleshed for morphometric analysis using standardized images. All animals in the test group displayed signs of alcohol dependency at day 14. No statistically significant differences in final body weight (334.83±21.38 vs. 322.48±30.65 g, p=0.20) were observed between groups. In relation to alveolar bone loss, no statistically significant difference was observed among test and control groups both for ligated teeth (0.76±0.06 vs. 0.74±0.10 mm, p=0.60) and unligated teeth (0.41±0.16 vs. 0.35±0.05 mm, p=0.22). The TNF-α secretion also did not display statistically significant differences between test and control groups (10.78±1.84 vs. 12.13±2.11 pg/mL, p=0.12). It may be concluded that 15% alcohol dependency was not capable to alter alveolar bone loss and TNF-α secretion in Wistar rats.

  1. The ADH gene cluster SNP rs1789891 and temperamental dimensions in patients with alcohol dependence and affective disorders.

    PubMed

    Oniszczenko, Włodzimierz; Rybakowski, Janusz K; Dragan, Wojciech Ł; Grzywacz, Anna; Samochowiec, Jerzy

    2015-08-01

    This study had three objectives: (1) to assess the relationship between the single nucleotide polymorphism (SNP) rs1789891 in the alcohol dehydrogenase gene cluster and alcohol dependence and affective disorders; (2) to assess the differences in the Regulative Theory of Temperament (RTT) traits between an alcohol dependent group, an affective disorders group, and a healthy group; and (3) to assess the relationship between rs1789891 and temperament traits in a healthy group, taking into account the interaction of genotype and sex. The SNP rs1789891 was genotyped in a group of 194 alcohol dependent men, aged 21 to 71 years; 137 patients with affective disorders, including 51 males and 86 females, aged 19 to 85 years; and a group of 207 healthy individuals, including 89 males and 118 females, aged 18 to 71 years. Temperament traits (briskness, perseveration, sensory sensitivity, emotional reactivity, endurance, and activity) were assessed in all groups using the Formal Characteristics of Behaviour-Temperament Inventory. The comparative analysis of genotypic frequencies showed no significant differences between patients with alcoholism or affective disorders and those in the control group. Alcohol dependent men and the affective disorder group were characterised by higher levels of emotional reactivity (p-value 1.4e-5 and 9.84e-7, respectively) and lower levels of briskness, sensory sensitivity, endurance, and activity (p-value from 3.76e-8 to 0.012) when compared to the healthy group. The rs1789891 polymorphism was associated with briskness (p = 0.02), sensory sensitivity (p = 0.036), and activity (p = 0.049). None of the results were statistically significant after Bonferroni correction.

  2. High current density PQQ-dependent alcohol and aldehyde dehydrogenase bioanodes.

    PubMed

    Aquino Neto, Sidney; Hickey, David P; Milton, Ross D; De Andrade, Adalgisa R; Minteer, Shelley D

    2015-10-15

    In this paper, we explore the bioelectrooxidation of ethanol using pyrroloquinoline quinone (PQQ)-dependent alcohol and aldehyde dehydrogenase (ADH and AldDH) enzymes for biofuel cell applications. The bioanode architectures were designed with both direct electron transfer (DET) and mediated electron transfer (MET) mechanisms employing high surface area materials such as multi-walled carbon nanotubes (MWCNTs) and MWCNT-decorated gold nanoparticles, along with different immobilization techniques. Three different polymeric matrices were tested (tetrabutyl ammonium bromide (TBAB)-modified Nafion; octyl-modified linear polyethyleneimine (C8-LPEI); and cellulose) in the DET studies. The modified Nafion membrane provided the best electrical communication between enzymes and the electrode surface, with catalytic currents as high as 16.8 ± 2.1 µA cm(-2). Then, a series of ferrocene redox polymers were evaluated for MET. The redox polymer 1,1'-dimethylferrocene-modified linear polyethyleneimine (FcMe2-C3-LPEI) provided the best electrochemical response. Using this polymer, the electrochemical assays conducted in the presence of MWCNTs and MWCNTs-Au indicated a Jmax of 781 ± 59 µA cm(-2) and 925 ± 68 µA cm(-2), respectively. Overall, from the results obtained here, DET using the PQQ-dependent ADH and AldDH still lacks high current density, while the bioanodes that operate via MET employing ferrocene-modified LPEI redox polymers show efficient energy conversion capability in ethanol/air biofuel cells.

  3. Effect of modafinil on cognitive functions in alcohol dependent patients: a randomized, placebo-controlled trial.

    PubMed

    Joos, Leen; Goudriaan, Anna E; Schmaal, Lianne; van den Brink, Wim; Sabbe, Bernard G C; Dom, Geert

    2013-11-01

    Cognitive deficits are highly prevalent in alcohol-dependent (AD) patients and may have a detrimental impact on treatment response and treatment outcome. Enhancing cognitive functions may improve treatment success. Modafinil is a promising compound in this respect. Therefore, a randomized double-blind placebo-controlled trial was conducted with modafinil (300 mg/d) or placebo in 83 AD patients for 10 weeks. Various cognitive functions (digit span task, Tower of London task, Stroop task) were measured at baseline, during and after treatment. Compared to placebo, modafinil improved verbal short-term memory (number of forward digit spans) (p=0.030), but modafinil exerted a negative effect on the working memory score of the digit span task (p=0.003). However, subgroup analyses revealed that modafinil did improve both working memory and verbal short-term memory in AD patients with a poor working memory ability at baseline (25% worst performers), whereas no significant treatment effect of modafinil was found on these two dependent variables in patients with good working memory skills at baseline (25% best performers). No effect of modafinil was found on measures of planning (Tower of London task) and selective attention (Stroop task). Further research is needed to better understand the relationship between cognitive remediation and treatment outcome in order to design targeted treatments.

  4. Subcellular localization of the NAD+-dependent alcohol dehydrogenase in Entamoeba histolytica trophozoites.

    PubMed

    Avila, Eva E; Martínez-Alcaraz, Edith R; Barbosa-Sabanero, Gloria; Rivera-Baron, Elda I; Arias-Negrete, Sergio; Zazueta-Sandoval, Roberto

    2002-04-01

    The protozoan parasite Entamoeba histolytica is an ancient eukaryotic cell that shows morphologically atypical organelles and differs metabolically from higher eukaryotic cells. The aim of this study was to determine the subcellular localization of ameba NAD+-dependent alcohol dehydrogenase (ADH2). The enzyme activity was present in soluble and mainly in particulate material whose density was 1.105 in a sucrose gradient. By differential centrifugation, most of the ADH activity sedimented at 160,000 g (160,000-g pellet), similar to the Escherichia coli polymeric ADHE. In the Coomassie staining of the 160,000-g pellet analyzed by electrophoresis, a 96-kDa protein was more prominent than in other fractions; this band was recognized by antibodies against Lactococcus lactis ADHE. By gold labeling, the antibodies recognized the granular material that mainly constitutes the 160,000-g pellet and a material that sedimented along with the internal membrane vesicles. By negative staining, the 160,000-g fraction showed helical rodlike structures with an average length of 103 nm; almost no membrane vesicles were observed in this pellet. In internal membrane fractions, no rodlike structures were found, but protomerlike round structures were observed. These results indicate that the main amebic NAD+-dependent ADH2 activity is naturally organized as rodlike helical particles, similar to bacterial ADHE. Detection of ADH2 in membrane fractions might be explained by cosedimentation of the multimeric ADH during membrane purification.

  5. Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin-dependent diabetes.

    PubMed

    Pyke, D A; Leslie, R D

    1978-12-01

    The single-challenge test for chlorpropamide-alcohol flushing (CPAF) was used to study two groups of patients with non-insulin-dependent diabetes and a family history of the disease who were distinguished only by their age at diagnosis (under and over 30). Their relatives were also studied. The proportions of patients showing CPAF in both groups were similar, and the family histories suggested dominant inheritance. When offspring of diabetics in whom the disease was diagnosed early were studied CPAF seemed to precede the appearance of diabetes. We conclude that the patients in both groups had the same, distinct syndrome, which is characterised by diabetes diagnosed at any age that is inherited as an autosomal dominant trait and associated with CPAF. This syndrome, which constitutes about one-fifth of all cases of non-insulin-dependent diabetes, may be detected with a single-challenge CPAF test before the onset of glucose intolerance. CPAF therefore acts as a genetic marker for the syndrome. PMID:728708

  6. A genome-wide linkage analysis of alcoholism on microsatellite and single-nucleotide polymorphism data, using alcohol dependence phenotypes and electroencephalogram measures.

    PubMed

    Zhang, Chun; Cawley, Simon; Liu, Guoying; Cao, Manqiu; Gorrell, Harley; Kennedy, Giulia C

    2005-01-01

    The Collaborative Study on the Genetics of Alcoholism (COGA) is a large-scale family study designed to identify genes that affect the risk for alcoholism and alcohol-related phenotypes. We performed genome-wide linkage analyses on the COGA data made available to participants in the Genetic Analysis Workshop 14 (GAW 14). The dataset comprised 1,350 participants from 143 families. The samples were analyzed on three technologies: microsatellites spaced at 10 cM, Affymetrix GeneChip Human Mapping 10 K Array (HMA10K) and Illumina SNP-based Linkage III Panel. We used ALDX1 and ALDX2, the COGA definitions of alcohol dependence, as well as electrophysiological measures TTTH1 and ECB21 to detect alcoholism susceptibility loci. Many chromosomal regions were found to be significant for each of the phenotypes at a p-value of 0.05. The most significant region for ALDX1 is on chromosome 7, with a maximum LOD score of 2.25 for Affymetrix SNPs, 1.97 for Illumina SNPs, and 1.72 for microsatellites. The same regions on chromosome 7 (96-106 cM) and 10 (149-176 cM) were found to be significant for both ALDX1 and ALDX2. A region on chromosome 7 (112-153 cM) and a region on chromosome 6 (169-185 cM) were identified as the most significant regions for TTTH1 and ECB21, respectively. We also performed linkage analysis on denser maps of markers by combining the SNPs datasets from Affymetrix and Illumina. Adding the microsatellite data to the combined SNP dataset improved the results only marginally. The results indicated that SNPs outperform microsatellites with the densest marker sets performing the best.

  7. A Randomized Trial of Extended Telephone-Based Continuing Care for Alcohol Dependence: Within-Treatment Substance Use Outcomes

    ERIC Educational Resources Information Center

    McKay, James R.; Van Horn, Deborah H. A.; Oslin, David W.; Lynch, Kevin G.; Ivey, Megan; Ward, Kathleen; Drapkin, Michelle L.; Becher, Julie R.; Coviello, Donna M.

    2010-01-01

    Objective: The study tested whether adding up to 18 months of telephone continuing care, either as monitoring and feedback (TM) or longer contacts that included counseling (TMC), to intensive outpatient programs (IOPs) improved outcomes for alcohol-dependent patients. Method: Participants (N = 252) who completed 3 weeks of IOP were randomized to…

  8. Psychological Evaluation of Animal-assisted Intervention (AAI) Programs Involving Visiting Dogs and Cats for Alcohol Dependents: A Pilot Study.

    PubMed

    Ohtani, Nobuyo; Narita, Shin; Yoshihara, Eiji; Ohta, Mitsuaki; Iwahashi, Kazuhiko

    2015-12-01

    The purpose of this study was to develop an evaluation method for animal-assisted intervention (AAI) programs involving Mood Check List-Short form.2 (MCL-S.2) and the State-Trait Anxiety Inventory (STAI) for psychiatric daycare of Japanese alcohol. dependents. A total of 36 alcohol dependents completed the study and questionnaires assessing their state. A single session of AAI reduced both subjective and physiological measures of state anxiety (A-State); and this program induced a significant reduction in the anxiety after an AAI program session with the dogs and cats involved in the intervention (p = 0.001). The Wilcoxon t-test showed that there were also significant differences in the "anxiety", "pleasantness", and "relaxation". scores for MCL-S.2 among the alcohol dependents, before and after AAI; a significantly decreased "anxiety" score (p = 0.006), and increased "pleasantness" (p = 0.002) and "relaxation" (p=0.012) scores for MCL-S.2 after AAI. The results of this study indicated that alcohol dependents who experienced a group AAI session-program exhibited significant improvements in their feeling; decreased anxiety, and increased pleasantness and relaxation.

  9. Alcohol and Drug Use, Abuse, and Dependence in Urban Areas and Colonias of the Texas-Mexico Border

    ERIC Educational Resources Information Center

    Wallisch, Lynn S.; Spence, Richard T.

    2006-01-01

    This study describes the prevalence of alcohol and drug use, abuse, and dependence among adults on the Texas-Mexico border in 2002-2003. The findings are based on survey responses from a random sample of 1,200 adults living in households in three communities: El Paso, a densely populated city in west Texas; the less dense urbanized areas of the…

  10. Pathways to Care of Alcohol -Dependent Patients: An Exploratory Study From a Tertiary Care Substance Use Disorder Treatment Center

    PubMed Central

    Pal Singh Balhara, Yatan; Prakash, Sathya; Gupta, Rishab

    2016-01-01

    Background No study from India has examined pathways to care in alcohol using population systematically. Objectives The present study aimed to understand the pathways to care among alcohol-dependent individuals seeking help at a tertiary care center. Patients and Methods It was a cross-sectional, observational study. A total of 58 subjects diagnosed with alcohol- dependence syndrome as per DSM-IV-TR were included in the study. Pathways to care were assessed using the world health organization encounter form. Results For 56.9% of the subjects, first point of contact was with a tertiary care addiction psychiatrist. Traditional healers were consulted by about 5.2% of the patients seeking help for the first time. The mean duration of main problems due to alcohol use was 5.82 ± 4.95 years. The first contact tended to be at place nearer to the patient’s residence while further contacts tended to be farther away. Family, friends and neighbours together constituted the single largest group suggesting patients to seek care. Conclusions There is a long time lag between the onset of alcohol use related problems and the first help seeking attempt. Of those who do decide to seek help, the proportion of those obtaining specialist help is higher than commonly believed. PMID:27803893

  11. Histamine H3 Receptor: A Novel Therapeutic Target in Alcohol Dependence?

    PubMed Central

    Nuutinen, Saara; Vanhanen, Jenni; Mäki, Tiia; Panula, Pertti

    2012-01-01

    The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders. PMID:22629238

  12. Alcoholics Anonymous attendance following 12-step treatment participation as a link between alcohol-dependent fathers' treatment involvement and their children's externalizing problems.

    PubMed

    Andreas, Jasmina Burdzovic; O'Farrell, Timothy J

    2009-01-01

    We investigated longitudinal associations between alcohol-dependent fathers' 12-step treatment involvement and their children's internalizing and externalizing problems (N = 125, M(age) = 9.8 +/- 3.1), testing the hypotheses that fathers' greater treatment involvement would benefit later child behavior and that this effect would be mediated by fathers' posttreatment behaviors. The initial association was established between fathers' treatment involvement and children's externalizing problems only, whereas Structural Equation Modeling (SEM) results supported mediating hypotheses. Fathers' greater treatment involvement predicted children's lower externalizing problems 12 months later, and fathers' posttreatment behaviors mediated this association: Greater treatment involvement predicted greater posttreatment Alcoholics Anonymous attendance, which in turn predicted greater abstinence. Finally, fathers' abstinence was associated with lower externalizing problems in children. Theoretical and practical implications of these findings are discussed. PMID:18715745

  13. Heart rate variability biofeedback in patients with alcohol dependence: a randomized controlled study

    PubMed Central

    Penzlin, Ana Isabel; Siepmann, Timo; Illigens, Ben Min-Woo; Weidner, Kerstin; Siepmann, Martin

    2015-01-01

    Background and objective In patients with alcohol dependence, ethyl-toxic damage of vasomotor and cardiac autonomic nerve fibers leads to autonomic imbalance with neurovascular and cardiac dysfunction, the latter resulting in reduced heart rate variability (HRV). Autonomic imbalance is linked to increased craving and cardiovascular mortality. In this study, we sought to assess the effects of HRV biofeedback training on HRV, vasomotor function, craving, and anxiety. Methods We conducted a randomized controlled study in 48 patients (14 females, ages 25–59 years) undergoing inpatient rehabilitation treatment. In the treatment group, patients (n=24) attended six sessions of HRV biofeedback over 2 weeks in addition to standard rehabilitative care, whereas, in the control group, subjects received standard care only. Psychometric testing for craving (Obsessive Compulsive Drinking Scale), anxiety (Symptom Checklist-90-Revised), HRV assessment using coefficient of variation of R-R intervals (CVNN) analysis, and vasomotor function assessment using laser Doppler flowmetry were performed at baseline, immediately after completion of treatment or control period, and 3 and 6 weeks afterward (follow-ups 1 and 2). Results Psychometric testing showed decreased craving in the biofeedback group immediately postintervention (OCDS scores: 8.6±7.9 post-biofeedback versus 13.7±11.0 baseline [mean ± standard deviation], P<0.05), whereas craving was unchanged at this time point in the control group. Anxiety was reduced at follow-ups 1 and 2 post-biofeedback, but was unchanged in the control group (P<0.05). Following biofeedback, CVNN tended to be increased (10.3%±2.8% post-biofeedback, 10.1%±3.5% follow-up 1, 10.1%±2.9% follow-up 2 versus 9.7%±3.6% baseline; P=not significant). There was no such trend in the control group. Vasomotor function assessed using the mean duration to 50% vasoconstriction of cutaneous vessels after deep inspiration was improved following biofeedback

  14. The predictive validity of the Drinking-Related Cognitions Scale in alcohol-dependent patients under abstinence-oriented treatment

    PubMed Central

    2012-01-01

    Background Cognitive factors associated with drinking behavior such as positive alcohol expectancies, self-efficacy, perception of impaired control over drinking and perception of drinking problems are considered to have a significant influence on treatment effects and outcome in alcohol-dependent patients. However, the development of a rating scale on lack of perception or denial of drinking problems and impaired control over drinking has not been substantial, even though these are important factors in patients under abstinence-oriented treatment as well as participants in self-help groups such as Alcoholics Anonymous (AA). The Drinking-Related Cognitions Scale (DRCS) is a new self-reported rating scale developed to briefly measure cognitive factors associated with drinking behavior in alcohol-dependent patients under abstinence-oriented treatment, including positive alcohol expectancies, abstinence self-efficacy, perception of impaired control over drinking, and perception of drinking problems. Here, we conducted a prospective cohort study to explore the predictive validity of DRCS. Methods Participants in this study were 175 middle-aged and elderly Japanese male patients who met the DSM-IV Diagnostic Criteria for Alcohol Dependence. DRCS scores were recorded before and after the inpatient abstinence-oriented treatment program, and treatment outcome was evaluated one year after discharge. Results Of the 175 participants, 30 were not available for follow-up; thus the number of subjects for analysis in this study was 145. When the total DRCS score and subscale scores were compared before and after inpatient treatment, a significant increase was seen for both scores. Both the total DRCS score and each subscale score were significantly related to total abstinence, percentage of abstinent days, and the first drinking occasion during the one-year post-treatment period. Therefore, good treatment outcome was significantly predicted by low positive alcohol expectancies

  15. Ethanol affects acylated and total ghrelin levels in peripheral blood of alcohol-dependent rats.

    PubMed

    Szulc, Michal; Mikolajczak, Przemyslaw L; Geppert, Bogna; Wachowiak, Roman; Dyr, Wanda; Bobkiewicz-Kozlowska, Teresa

    2013-07-01

    There is a hypothesis that ghrelin could take part in the central effects of alcohol as well as function as a peripheral indicator of the changes which occur during long-term alcohol consumption. The aim of this study was to determine a correlation between alcohol concentration and acylated and total form of ghrelin after a single administration of alcohol (intraperitoneal, i.p.) (experiment 1) and prolonged ethanol consumption (experiment 2). The study was performed using Wistar alcohol preferring (PR) and non-preferring (NP) rats and rats from inbred line (Warsaw High Preferring, WHP; Warsaw Low Preferring, WLP). It was found that ghrelin in ethanol-naive WHP animals showed a significantly lower level when compared with the ethanol-naive WLP or Wistar rats. After acute ethanol administration in doses of 1.0; 2.0 and 4.0 g/kg, i.p., the simple (WHP) or inverse (WLP and Wistar) relationship between alcohol concentration and both form of ghrelin levels in plasma were found. Chronic alcohol intake in all groups of rats led to decrease of acylated ghrelin concentration. PR and WHP rats, after chronic alcohol drinking, had lower levels of both form of ghrelin in comparison with NP and WLP rats, respectively, and the observed differences in ghrelin levels were in inverse relationship with their alcohol intake. In conclusion, it is suggested that there is a strong relationship between alcohol administration or intake, ethanol concentration in blood and both active and total ghrelin level in the experimental animals, and that ghrelin plasma concentration can be a marker of alcohol drinking predisposition.

  16. Collective Efficacy, Alcohol Outlet Density, and Young Men's Alcohol Use in Rural South Africa

    PubMed Central

    Leslie, Hannah H; Ahern, Jennifer; Pettifor, Audrey E.; Twine, Rhian; Kahn, Kathleen; Gómez-Olivé, F. Xavier; Lippman, Sheri A.

    2015-01-01

    Alcohol use contributes to morbidity and mortality in developing countries by increasing the risk of trauma and disease, including alcohol dependence. Limited research addresses determinants of alcohol use beyond the individual level in sub-Saharan Africa. We test the association of community collective efficacy and alcohol outlet density with young men's drinking in a cross-sectional, locally representative survey conducted in rural northeast South Africa. Informal social control and cohesion show protective associations with men's heavy drinking, while alcohol outlet density is associated with more potential problem drinking. These findings provide initial support for intervening at the community level to promote alcohol reduction. PMID:26071651

  17. Relations of Alcohol Consumption with Smoking Cessation Milestones and Tobacco Dependence

    ERIC Educational Resources Information Center

    Cook, Jessica W.; Fucito, Lisa M.; Piasecki, Thomas M.; Piper, Megan E.; Schlam, Tanya R.; Berg, Kristin M.; Baker, Timothy B.

    2012-01-01

    Objective: Alcohol consumption is associated with smoking cessation failure in both community and clinical research. However, little is known about the relation between alcohol consumption and smoking cessation milestones (i.e., achieving initial abstinence, avoiding lapses and relapse). Our objective in this research was to examine the relations…

  18. Readiness for Change and Treatment Outcome among Individuals with Alcohol Dependency.

    ERIC Educational Resources Information Center

    Hewes, Robert L.; Janikowski, Timothy P.

    1998-01-01

    Uses the Addiction Severity Index and Stage of Change Readiness and Treatment Eagerness Scale to evaluate individuals with primary alcohol-abuse problems involved in treatment programs. Results indicate that participants showed significant improvement in problems related to alcohol use. No significant differences were found between participants…

  19. Analyzing repeated measures semi-continuous data, with application to an alcohol dependence study.

    PubMed

    Liu, Lei; Strawderman, Robert L; Johnson, Bankole A; O'Quigley, John M

    2016-02-01

    Two-part random effects models (Olsen and Schafer,(1) Tooze et al.(2)) have been applied to repeated measures of semi-continuous data, characterized by a mixture of a substantial proportion of zero values and a skewed distribution of positive values. In the original formulation of this model, the natural logarithm of the positive values is assumed to follow a normal distribution with a constant variance parameter. In this article, we review and consider three extensions of this model, allowing the positive values to follow (a) a generalized gamma distribution, (b) a log-skew-normal distribution, and (c) a normal distribution after the Box-Cox transformation. We allow for the possibility of heteroscedasticity. Maximum likelihood estimation is shown to be conveniently implemented in SAS Proc NLMIXED. The performance of the methods is compared through applications to daily drinking records in a secondary data analysis from a randomized controlled trial of topiramate for alcohol dependence treatment. We find that all three models provide a significantly better fit than the log-normal model, and there exists strong evidence for heteroscedasticity. We also compare the three models by the likelihood ratio tests for non-nested hypotheses (Vuong(3)). The results suggest that the generalized gamma distribution provides the best fit, though no statistically significant differences are found in pairwise model comparisons.

  20. Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients

    PubMed Central

    Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

    2016-01-01

    Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730

  1. Empathy and social problem solving in alcohol dependence, mood disorders and selected personality disorders.

    PubMed

    Thoma, Patrizia; Friedmann, Christine; Suchan, Boris

    2013-03-01

    Altered empathic responding in social interactions in concert with a reduced capacity to come up with effective solutions for interpersonal problems have been discussed as relevant factors contributing to the development and maintenance of psychiatric disorders. The aim of the current work was to review and evaluate 30 years of empirical evidence of impaired empathy and social problem solving skills in alcohol dependence, mood disorders and selected personality disorders (borderline, narcissistic, antisocial personality disorders/psychopathy), which have until now received considerably less attention than schizophrenia or autism in this realm. Overall, there is tentative evidence for dissociations of cognitive (e.g. borderline personality disorder) vs. emotional (e.g. depression, narcissism, psychopathy) empathy dysfunction in some of these disorders. However, inconsistencies in the definition of relevant concepts and their measurement, scarce neuroimaging data and rare consideration of comorbidities limit the interpretation of findings. Similarly, although impaired social problem solving appears to accompany all of these disorders, the concept has not been well integrated with empathy or other cognitive dysfunctions as yet. PMID:23396051

  2. Empathy and social problem solving in alcohol dependence, mood disorders and selected personality disorders.

    PubMed

    Thoma, Patrizia; Friedmann, Christine; Suchan, Boris

    2013-03-01

    Altered empathic responding in social interactions in concert with a reduced capacity to come up with effective solutions for interpersonal problems have been discussed as relevant factors contributing to the development and maintenance of psychiatric disorders. The aim of the current work was to review and evaluate 30 years of empirical evidence of impaired empathy and social problem solving skills in alcohol dependence, mood disorders and selected personality disorders (borderline, narcissistic, antisocial personality disorders/psychopathy), which have until now received considerably less attention than schizophrenia or autism in this realm. Overall, there is tentative evidence for dissociations of cognitive (e.g. borderline personality disorder) vs. emotional (e.g. depression, narcissism, psychopathy) empathy dysfunction in some of these disorders. However, inconsistencies in the definition of relevant concepts and their measurement, scarce neuroimaging data and rare consideration of comorbidities limit the interpretation of findings. Similarly, although impaired social problem solving appears to accompany all of these disorders, the concept has not been well integrated with empathy or other cognitive dysfunctions as yet.

  3. Posttraumatic stress disorder and alcohol dependence: does order of onset make a difference?

    PubMed

    McLean, Carmen P; Su, Yi-Jen; Foa, Edna B

    2014-12-01

    Posttraumatic stress disorder (PTSD) and alcohol dependence (AD) are frequently comorbid and the order in which they develop may affect the clinical presentation and response to treatment. This study compared 73 treatment-seeking participants who developed PTSD prior to developing AD ("PTSD-first") with 64 participants who developed AD prior to developing PTSD ("AD-first") on demographics, clinical presentation, and response to treatment for PTSD and AD. All participants received BRENDA, a medication management and motivational enhancement intervention and were randomly assigned to either prolonged exposure (PE) for PTSD plus BRENDA or BRENDA alone and to either naltrexone (NAL) for AD or placebo (PBO). Results showed that participants with AD-first were more likely to report low income, meet criteria for antisocial or borderline personality disorder, report an index trauma of physical assault, compared to those with PTSD-first. Conversely, participants with PTSD-first were more likely to report an index trauma of sexual assault or a combat experience. Notably, no group differences were observed in treatment outcome despite some differences in clinical presentation.

  4. Alcohol and Marijuana Use in the Context of Tobacco Dependence Treatment: Impact on Outcome and Mediation of Effect

    PubMed Central

    Delucchi, Kevin L.; Humfleet, Gary L.; Hall, Sharon M.

    2012-01-01

    Introduction: Alcohol and marijuana are among the most commonly used substances together with tobacco worldwide, but their relationship to smoking cessation is unclear. Although alcohol use decreases the likelihood of abstinence from tobacco, mechanisms of this effect have not been identified. Moreover, a small literature has yielded inconsistent findings regarding the effect of marijuana use on tobacco dependence treatment outcome. The aims of this study were to test increased positive-reinforcement smoking urge as a mediator of the relationship between alcohol and cigarette use and evaluate the impact of marijuana use on abstinence from tobacco. Methods: Participants were adult cigarette smokers (N = 739) from 3 randomized clinical trials of smoking cessation treatment. Alcohol consumption and marijuana use were assessed at pretreatment and postcessation. Biochemically verified, 7-day point prevalence smoking abstinence was determined at Weeks 12, 24, 36, and 52, as were urges to smoke as measured by the Questionnaire of Smoking Urges. Results: Increased positive-reinforcement urge mediated the effect of postcessation alcohol use on smoking abstinence. Although pretreatment alcohol use was associated with a decreased likelihood of abstinence from tobacco, increased positive-reinforcement urge did not account for this relationship. Marijuana use was not associated with abstinence from tobacco. Conclusions: Smoking cessation treatments should provide those who drink during a quit attempt techniques designed to mitigate positive-reinforcement urge to smoke. Additional research is needed to determine how pretreatment alcohol consumption exerts its effect on cigarette use. Modifying the use of marijuana might not be critical to the success of tobacco interventions. PMID:22259148

  5. Modeling the impact of alcohol dependence on mortality burden and the effect of available treatment interventions in the European Union.

    PubMed

    Rehm, J; Shield, K D; Gmel, G; Rehm, M X; Frick, U

    2013-02-01

    Alcohol consumption is a major risk factor for the burden of disease, and Alcohol Dependence (AD) is the most important disorder attributable to this behavior. The objective of this study was to quantify mortality associated with AD and the potential impact of treatment. For the EU countries, for the age group 15-64 years, mortality attributable to alcohol consumption in general, to heavy drinking, and to AD were estimated based on the latest data on exposure and mortality. Potential effects of AD treatment were modeled based on Cochrane and other systematic reviews of the effectiveness of the best known and most effective interventions. In the EU 88.9% of men and 82.1% of women aged 15-64 years were current drinkers; and 15.3% of men and 3.4% of women in this age group were heavy drinkers. AD affected 5.4% of men and 1.5% of women. The net burden caused by alcohol consumption was 1 in 7 deaths in men and 1 in 13 deaths in women. The majority of this burden was due to heavy drinking (77%), and 71% of this burden was due to AD. Increasing treatment coverage for the most effective treatments to 40% of all people with AD was estimated to reduce alcohol-attributable mortality by 13% for men and 9% for women (annually 10,000 male and 1700 female deaths avoided). Increasing treatment rates for AD was identified as an important issue for future public health strategies to reduce alcohol-attributable harm and to complement the current focus of alcohol policy.

  6. The Associations between Self-Consciousness, Depressive State and Craving to Drink among Alcohol Dependent Patients Undergoing Protracted Withdrawal

    PubMed Central

    Denoël, Catherine; Hebborn, Ludger; Derely, Marc; Desseilles, Martin; Luminet, Olivier

    2013-01-01

    Context In order to understand how certain personality traits influence the relation between depression symptoms and craving for alcohol, trait self-consciousness (trait SC) was examined during a withdrawal and detoxification program. Methods Craving (Obsessive and Compulsive Drinking Scale), depressive state (Beck Depression Inventory) and trait SC (Revised Self-Consciousness Scale) were assessed in alcohol-dependent inpatients (DSM-IV, N = 30) both at the beginning (T1: day 1 or 2) and at the end (T2: day 14 to18) of protracted withdrawal during rehabilitation. Results A significant decrease in craving and depressive symptoms was observed from T1 to T2, while SC scores remained stable. At both times, strong positive correlations were observed between craving and depression. Moreover, regression analyses indicated that trait SC significantly moderated the impact of depression on cravings for alcohol. Limitations This study was performed on a relatively small sample size. Administration of medications during detoxification treatment can also be a confounding factor. Finally, craving could have been evaluated through other types of measurements. Conclusions During protracted withdrawal, alcohol craving decreased with the same magnitude as depressive mood. Depressive symptoms were related to alcohol craving but only among patients with high trait SC scores. Our results suggest that metacognitive approaches targeting SC could decrease craving and, in turn, prevent future relapses. PMID:24013131

  7. Lack of association between alcohol-dependence and D3 dopamine receptor gene in three independent samples

    SciTech Connect

    Gorwood, P.; Feingold, J.; Ades, J.

    1995-12-18

    Numerous studies on the involvement of dopamine receptors in the genetics of alcoholism focused on associations between a polymorphism of the D2 dopamine receptor (DRD2) gene and alcohol dependence. However, the results of these studies are conflicting. Another receptor, the D3 dopamine receptor (DRD3), may be of additional interest since it is specifically located in the limbic area, and in particular in the nucleus accumbens which plays a significant role in the reward process of addiction behavior. We thus tested the association in three independent samples of alcoholic patients, with different origins and various inclusion criteria. No difference in the DRD3 gene polymorphism emerged between controls and alcoholic patients, regardless of their origin, inclusion criteria, or presence or absence of the DRD2 TaqI A1-allele. Despite the fact that more information could have been considered and that association studies provide limited information, there is good evidence that this DRD3 polymorphism does not play a major role in the genetic component of alcoholism. 17 refs., 2 tabs.

  8. Alcohol in Primary Care. Differential characteristics between alcohol-dependent patients who are receiving or not receiving treatment.

    PubMed

    Barrio, Pablo; Miquel, Laia; Moreno-España, Jose; Martínez, Alicia; Ortega, Lluisa; Teixidor, Lidia; Manthey, Jakob; Rehm, Jürgen; Gual, Antoni

    2016-03-02

    primary health care services for other reasons. The aim of the present study is to describe the differential characteristics of AD patients in primary care, distinguishing between those who receive treatment and those who do not, and their reasons for not seeking it. In a cross-sectional study patients were evaluated by their general practitioner (GP) and interviewed by a member of the research team. Sociodemographic, diagnostic and clinical data were collected. From 1,372 patients interviewed in Catalonia, 118 (8.6%) were diagnosed as AD. These patients showed a lower socioeconomic status (48.3% vs 33.3%, odds ratio 2.02), higher unemployment rates (32.2% vs 19.2 %, odds ratio 2.11), and greater psychological distress and disability. Patients with AD receiving treatment (16.9%), were older (44 vs 36 years of age), reported higher unemployment rates (66% vs 25.5%, odds ratio 6.32) and higher daily alcohol consumption (61.5 vs 23.7 grams), suggesting a more advanced disease. Patients with AD in general showed a higher degree of comorbidity compared to other patients, with patients in treatment showing the most elevated level. The main reasons given for not seeking treatment were shame, fear of giving up drinking and barriers to treatment. Taken together, the data suggest the need to implement earlier strategies for the detection and treatment of AD.

  9. Alcohol in Primary Care. Differential characteristics between alcohol-dependent patients who are receiving or not receiving treatment.

    PubMed

    Barrio, Pablo; Miquel, Laia; Moreno-España, Jose; Martínez, Alicia; Ortega, Lluisa; Teixidor, Lidia; Manthey, Jakob; Rehm, Jürgen; Gual, Antoni

    2016-01-01

    primary health care services for other reasons. The aim of the present study is to describe the differential characteristics of AD patients in primary care, distinguishing between those who receive treatment and those who do not, and their reasons for not seeking it. In a cross-sectional study patients were evaluated by their general practitioner (GP) and interviewed by a member of the research team. Sociodemographic, diagnostic and clinical data were collected. From 1,372 patients interviewed in Catalonia, 118 (8.6%) were diagnosed as AD. These patients showed a lower socioeconomic status (48.3% vs 33.3%, odds ratio 2.02), higher unemployment rates (32.2% vs 19.2 %, odds ratio 2.11), and greater psychological distress and disability. Patients with AD receiving treatment (16.9%), were older (44 vs 36 years of age), reported higher unemployment rates (66% vs 25.5%, odds ratio 6.32) and higher daily alcohol consumption (61.5 vs 23.7 grams), suggesting a more advanced disease. Patients with AD in general showed a higher degree of comorbidity compared to other patients, with patients in treatment showing the most elevated level. The main reasons given for not seeking treatment were shame, fear of giving up drinking and barriers to treatment. Taken together, the data suggest the need to implement earlier strategies for the detection and treatment of AD. PMID:26990264

  10. The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence.

    PubMed

    Suchankova, P; Yan, J; Schwandt, M L; Stangl, B L; Caparelli, E C; Momenan, R; Jerlhag, E; Engel, J A; Hodgkinson, C A; Egli, M; Lopez, M F; Becker, H C; Goldman, D; Heilig, M; Ramchandani, V A; Leggio, L

    2015-06-16

    The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case-control analysis (N = 908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N = 3803) was used for confirmation purposes. Post hoc analyses were carried out on data from a human laboratory study of intravenous alcohol self-administration (IV-ASA; N = 81) in social drinkers and from a functional magnetic resonance imaging study in alcohol-dependent individuals (N = 22) subjected to a Monetary Incentive Delay task. In the preclinical study, a GLP-1R agonist was evaluated in a mouse model of alcohol dependence to demonstrate the role of GLP-1R for alcohol consumption. The previously reported functional allele 168Ser (rs6923761) was nominally associated with AUD (P = 0.004) in the NIAAA sample, which was partially replicated in males of the SAGE sample (P = 0.033). The 168 Ser/Ser genotype was further associated with increased alcohol administration and breath alcohol measures in the IV-ASA experiment and with higher BOLD response in the right globus pallidus when receiving notification of outcome for high monetary reward. Finally, GLP-1R agonism significantly reduced alcohol consumption in a mouse model of alcohol dependence. These convergent findings suggest that the GLP-1R may be an attractive target for personalized pharmacotherapy treatment of AUD.

  11. The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence

    PubMed Central

    Suchankova, P; Yan, J; Schwandt, M L; Stangl, B L; Caparelli, E C; Momenan, R; Jerlhag, E; Engel, J A; Hodgkinson, C A; Egli, M; Lopez, M F; Becker, H C; Goldman, D; Heilig, M; Ramchandani, V A; Leggio, L

    2015-01-01

    The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case–control analysis (N=908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N=3803) was used for confirmation purposes. Post hoc analyses were carried out on data from a human laboratory study of intravenous alcohol self-administration (IV-ASA; N=81) in social drinkers and from a functional magnetic resonance imaging study in alcohol-dependent individuals (N=22) subjected to a Monetary Incentive Delay task. In the preclinical study, a GLP-1R agonist was evaluated in a mouse model of alcohol dependence to demonstrate the role of GLP-1R for alcohol consumption. The previously reported functional allele 168Ser (rs6923761) was nominally associated with AUD (P=0.004) in the NIAAA sample, which was partially replicated in males of the SAGE sample (P=0.033). The 168Ser/Ser genotype was further associated with increased alcohol administration and breath alcohol measures in the IV-ASA experiment and with higher BOLD response in the right globus pallidus when receiving notification of outcome for high monetary reward. Finally, GLP-1R agonism significantly reduced alcohol consumption in a mouse model of alcohol dependence. These convergent findings suggest that the GLP-1R may be an attractive target for personalized pharmacotherapy treatment of AUD. PMID:26080318

  12. Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study

    PubMed Central

    Barateau, Lucie; Jaussent, Isabelle; Lopez, Régis; Boutrel, Benjamin; Leu-Semenescu, Smaranda; Arnulf, Isabelle; Dauvilliers, Yves

    2016-01-01

    Study Objectives: Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. Methods: We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. Results: An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. Conclusions: We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were

  13. Private peer group settings as an environmental determinant of alcohol use in Dutch adolescents: results from a representative survey in the region of Twente.

    PubMed

    Korte, Jojanneke; Pieterse, Marcel E; Postel, Marloes G; Van Hoof, Joris J

    2012-07-01

    This study supports the hypothesis that the drinking setting can be an environmental risk factor for hazardous alcohol use. In a survey of Dutch adolescents (n = 1516), alcohol consumption and participation in private peer group settings (PPSs), environments where adolescents meet and drink alcohol without direct adult supervision, were measured. After controlling for demographic variables, adolescents visiting PPSs as compared to non-visitors, appeared to have a significantly higher lifetime prevalence of alcohol use, average weekly consumption, and frequency of heavy episodic drinking. Moreover, accounting for school clustering, the frequency of PPS visits was associated with increased alcohol consumption. PMID:22429488

  14. Corticotropin Releasing Factor–Induced Amygdala Gamma-Aminobutyric Acid Release Plays a Key Role in Alcohol Dependence

    PubMed Central

    Roberto, Marisa; Cruz, Maureen T.; Gilpin, Nicholas W.; Sabino, Valentina; Schweitzer, Paul; Bajo, Michal; Cottone, Pietro; Madamba, Samuel G.; Stouffer, David G.; Zorrilla, Eric P.; Koob, George F.; Siggins, George R.; Parsons, Loren H.

    2010-01-01

    Background Corticotropin-releasing factor (CRF) and gamma-aminobutyric acid (GABA)ergic systems in the central amygdala (CeA) are implicated in the high-anxiety, high-drinking profile associated with ethanol dependence. Ethanol augments CeA GABA release in ethanol-naive rats and mice. Methods Using naive and ethanol-dependent rats, we compared electrophysiologic effects and interactions of CRF and ethanol on CeA GABAergic transmission, and we measured GABA dialyzate in CeA after injection of CRF1 antagonists and ethanol. We also compared mRNA expression in CeA for CRF and CRF1 using real-time polymerase chain reaction. We assessed effects of chronic treatment with a CRF1 antagonist on withdrawal-induced increases in alcohol consumption in dependent rats. Results CRF and ethanol augmented CeA GABAergic transmission in naive rats via increased GABA release. Three CRF1 receptor (CRF1) antagonists decreased basal GABAergic responses and abolished ethanol effects. Ethanol-dependent rats exhibited heightened sensitivity to CRF and CRF1 antagonists on CeA GABA release. Intra-CeA CRF1 antagonist administration reversed dependence–related elevations in GABA dialysate and blocked ethanol-induced increases in GABA dialyzate in both dependent and naive rats. Polymerase chain reaction studies indicate increased expression of CRF and CRF1 in CeA of dependent rats. Chronic CRF1 antagonist treatment blocked withdrawal-induced increases in alcohol drinking by dependent rats and tempered moderate increases in alcohol consumption by nondependent rats in intermittent testing. Conclusions These combined findings suggest a key role for specific presynaptic CRF-GABA interactions in CeA in the development and maintenance of ethanol dependence. PMID:20060104

  15. Mental Health Problems in Adolescent Children of Alcohol Dependent Parents: Epidemiologic Research with a Nationally Representative Sample

    ERIC Educational Resources Information Center

    Obot, Isidore S.; Anthony, James C.

    2004-01-01

    This article analyzes recent empirical studies of welfare-to-work programs implemented by nonprofit organizations as a first step in understanding potential shifts in the political, social, and economic environments of nonprofit organizations in a post-welfare era. Using the political economy as a conceptual framework, the literature review…

  16. Alcohol and homicide in the United States – is the link dependent on wetness?

    PubMed Central

    Norström, Thor

    2011-01-01

    Introduction Several aggregate-level studies have suggested that the relationship between alcohol and homicide is stronger in countries with an intoxication-oriented drinking pattern than in countries where drinking is more tempered. The present paper extends this research tradition by analysing the alcohol-homicide link in various regions in the U.S. Design and Methods I used annual time-series data for the U.S. states covering the period 1950-2002. Alcohol sales figures were used as proxy for alcohol consumption. Mortality data were used as indicators of homicide. The states were sorted into 3 groups labelled Dry, Moderate and Wet, where the last group has the highest prevalence of hazardous drinking according to survey data. Group-specific data were analysed using (i) ARIMA modelling and (ii) fixed-effects modelling. All modelling was based on differenced data, thus eliminating time trends and interstate correlations, both of which may bias estimates. Results The ARIMA estimates displayed a statistically significant gradient in alcohol effects; the effect was strongest in Wet, and weakest and insignificant in Dry states. The fixed-effects estimates showed a corresponding pattern, although the gradient was less steep and insignificant. The gradient was also weakened if the effects were expressed in absolute rather than relative terms. The spatial pattern revealed no ecological correlation between alcohol and homicide. Conclusions Results provided mixed support for the hypothesis that the relationship between alcohol and homicide is stronger in wet than in dry states in the U.S. Future research should probe more specific indicators of homicide as well as alcohol consumption. PMID:21896067

  17. Incongruent reduction of dopamine transporter availability in different subgroups of alcohol dependence.

    PubMed

    Yen, Che-Hung; Shih, Mei-Chen; Cheng, Cheng-Yi; Ma, Kuo-Hsing; Lu, Ru-Band; Huang, San-Yuan

    2016-08-01

    The dopamine transporter (DAT) plays a crucial role in the pathogenesis of alcohol dependence (AD) and major depression (MD), and males have more risk factors for the development of AD. However, imaging studies on brain DAT availability in males with AD comorbid with MD (AD/MD) are limited, and the association of DAT availability with cognitive function and depressive scores in patients with AD/MD has not been analyzed. Hence, this study examined the relationship between brain DAT availability, cognitive function, and depressive symptoms in different subgroups of males with AD.Single-photon emission computed tomography imaging with Tc-TRODAT-1 as a ligand was used to measure striatal DAT availability in 49 patients with AD (28 pure AD and 21 AD/MD) and 24 age- and sex-matched healthy volunteers. The Wisconsin Card Sorting Test (WCST) and 17-item Hamilton Depression Rating Scale were used to assess neurocognitive function and depressive scores, respectively. Patients with AD showed a significant reduction of DAT availability in 3 brain regions (P < 0.001), and this reduction was more pronounced in the patients with pure AD compared to healthy controls. The patients with AD showed significantly poorer performance on the WCST, but only in the control group was DAT availability significantly negatively correlated with total errors and perseverative errors (P < 0.001).These preliminary findings suggest that DAT availability is associated with neurocognitive function, and incongruent reduction of DAT may play a pathophysiological role in different subgroups of AD. In addition, decreased DAT availability may be associated with the severity of depressive symptoms in patients with AD/MD. PMID:27537550

  18. Genome-Wide Significant Association between Alcohol Dependence and a Variant in the ADH Gene Cluster

    PubMed Central

    Frank, Josef; Cichon, Sven; Treutlein, Jens; Ridinger, Monika; Mattheisen, Manuel; Hoffmann, Per; Herms, Stefan; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Kiefer, Falk; Rietschel, Marcella

    2011-01-01

    Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1,333 male in-patients with severe DSM-IV AD and 2,168 controls. These included 487 patients and 1,358 controls from a previous GWAS study by our group. All individuals were of German descent. Single marker tests and a polygenic score based analysis to assess the combined contribution of multiple markers with small effects were performed. The SNP rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance (p=1.27E–8; OR=1.46). Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (p=1.24E–7, OR=1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score based approach produced a significant result (p=9.66E–9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result suggests that many more AD susceptibility genes still await identification. PMID:22004471

  19. Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster.

    PubMed

    Frank, Josef; Cichon, Sven; Treutlein, Jens; Ridinger, Monika; Mattheisen, Manuel; Hoffmann, Per; Herms, Stefan; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Kiefer, Falk; Rietschel, Marcella

    2012-01-01

    Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1333 male in-patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls. These included 487 patients and 1358 controls from a previous GWAS study by our group. All individuals were of German descent. Single-marker tests and a polygenic score-based analysis to assess the combined contribution of multiple markers with small effects were performed. The single nucleotide polymorphism (SNP) rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance [P = 1.27E-8, odds ratio (OR) = 1.46]. Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (P = 1.24E-7, OR = 1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score-based approach produced a significant result (P = 9.66E-9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result may indicate that many more AD susceptibility genes still await identification.

  20. Conversion of isoamyl alcohol over acid catalysts: Reaction dependence on nature of active centers

    SciTech Connect

    Babu, G.P.; Murthy, R.S.; Krishnan, V.

    1997-02-01

    Acid catalysts are known to catalyze the dehydration of alcohols. In addition some oxide catalysts with basic properties have also been shown to play an important role in such dehydration reactions. The dehydration of aliphatic alcohols to olefins has been studied in detail using alumina silica-alumina and zeolite catalysts. The olefin products further undergo isomerization in presence of acidic sites. The reaction of isoamyl alcohol on catalytic surfaces has not been investigated in greater detail. The dehydration of isoamyl alcohol is of considerable interest in fine chemicals. Isoamyl alcohol may also undergo dehydrogenation as observed in the case of n-butanol. The scope of the present work is to identify the nature of the active sites selective for dehydration and dehydrogenation of isoamyl alcohol and to modify the active sites to promote isomerization of dehydrated products. Four catalytic surfaces on which the acidic strength can be varied, as well as selectively suppressed, are chosen for this study. 17 refs., 1 fig., 3 tabs.

  1. NAD(P)-Dependent Aldehyde Dehydrogenases Induced during Growth of Ralstonia eutropha Strain Bo on Tetrahydrofurfuryl Alcohol

    PubMed Central

    Schräder, Thomas; Zarnt, Grit; Andreesen, Jan R.

    2001-01-01

    Different aldehyde dehydrogenases (AlDHs) were formed during growth of Ralstonia eutropha Bo on tetrahydrofurfuryl alcohol (THFA). One of these enzymes, AlDH 4, was purified and characterized as a homodimer containing no prosthetic groups, showing a strong substrate inhibition, and having an N-terminal sequence similar to those of various NAD(P)-dependent AlDHs. The conversion rate of THFA by the quinohemoprotein THFA dehydrogenase was increased by AlDH 4. PMID:11717302

  2. Moderators of Varenicline Treatment Effects in a Double-Blind, Placebo-Controlled Trial for Alcohol Dependence: an Exploratory Analysis

    PubMed Central

    Falk, Daniel E.; Castle, I-Jen P.; Ryan, Megan; Fertig, Joanne; Litten, Raye Z.

    2015-01-01

    Objectives To explore if varenicline (Chantix®) showed more efficacy in treating certain subgroups of patients. In a recent multi-site trial, varenicline was shown to be effective in reducing drinking in alcohol dependent patients, both smokers and nonsmokers. Given the heterogeneity among alcohol dependent patients, secondary analyses were conducted to determine if certain subgroups responded more favorably than others to treatment with varenicline. Methods Data were drawn from a Phase 2 randomized, double-blind, placebo-controlled multi-site 13-week trial of varenicline in alcohol dependent patients (Litten et al., 2013). Seventeen moderator variables were selected for exploratory testing on the basis of theoretical and scientific interest. Results Of the 17 moderator variables assessed, four were statistically significant, including cigarettes per day reduction, treatment drinking goal, years drinking regularly, and age of patient. Two other variables—the type of adverse events experienced by patients and the severity of alcohol-related consequences—appeared to moderate the varenicline treatment effect at borderline statistical significance. Individuals who reduced the number of cigarettes per day experienced a significant effect from varenicline in reducing drinking, whereas those who did not change or who increased their number of cigarettes observed no beneficial effect. Reviewing the moderators related to severity, varenicline appeared to have greater efficacy than placebo among less severely-dependent patients. Conclusions Varenicline appears to be more efficacious in certain subgroups, particularly in those who reduced their smoking and in the “less severe” patient. Additional studies are warranted to confirm the results of these exploratory analyses. PMID:26083958

  3. Iron-dependent activation of NF-kappaB in Kupffer cells: a priming mechanism for alcoholic liver disease.

    PubMed

    Xiong, Shigang; She, Hongyun; Sung, Chin K; Tsukamoto, Hidekazu

    2003-06-01

    Alcoholic liver disease is associated with hepatic iron accumulation, and iron supplementation exacerbates alcoholic liver disease, suggesting the pathogenic role of iron in alcoholic liver disease. We have tested a hypothesis that iron plays a signaling role in activation of redox-sensitive nuclear factor-kappa B (NF-kappaB) and that increased iron content results in heightened expression of proinflammatory cytokines in Kupffer cells because of this signaling. In cultured Kupffer cells isolated from normal rats, treatment with a lipophilic iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), markedly reduced lipopolysaccharide (LPS)-induced NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6. Kupffer cells, isolated from rats with experimentally induced alcoholic liver disease, had significant increases in nonheme iron content, NF-kappaB binding, and mRNA expression for TNF-alpha and macrophage inflammatory protein-1. Ex vivo L1 treatment normalized all these parameters. Addition of ferrous iron to cultured normal rat Kupffer cells increased I-kappa B kinase (IKK) activity at 15 min and NF-kappaB binding at 30 min. L1 pretreatment completely abrogated both effects. Moreover, the iron treatment increased TNF-alpha release and TNF-alpha promoter activity in a NF-kappaB-dependent manner. Ferrous iron also transiently decreased cytoplasmic I-kappa B-alpha (IkappaB-alpha), with concomitant increases in nuclear p65 protein and DNA binding of p65/p50. Taken together, these results support the existence of iron-dependent signaling for activation of IKK/NF-kappaB in Kupffer cells, and this iron signaling serves as a target for a potential priming effect for the pathogenesis of experimental alcoholic liver disease.

  4. Association between Fok I vitamin D receptor gene (VDR) polymorphism and impulsivity in alcohol-dependent patients.

    PubMed

    Wrzosek, Małgorzata; Jakubczyk, Andrzej; Wrzosek, Michał; Kaleta, Beata; Łukaszkiewicz, Jacek; Matsumoto, Halina; Brower, Kirk; Nowicka, Grażyna; Wojnar, Marcin

    2014-11-01

    Vitamin D appears to have an important role in the modulation of the central nervous system. Vitamin D exerts its biological effects through its interaction with the vitamin D receptor (VDR). Located on chromosome 12 (12q13.1), the VDR gene has many different polymorphisms. Some of them are known to affect the VDR function, such as FokI (rs2228570, T/C) single nucleotide polymorphism. We aimed to explore a potential relationship between FokI VDR polymorphism and impulsiveness in alcohol-dependent (AD) patients. The study population consisted of 148 patients diagnosed with alcohol dependence (DSM-IV criteria) and 212 healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotypes were analyzed using a real-time PCR method. We found that FokI VDR gene polymorphism was associated with impulsivity [Barratt Impulsiveness Scale (BIS)-11 total score; P = 0.014], and with attentional impulsivity (BIS-11 subscale; P = 0.002) in the male AD patients. Our results suggest that CC FokI genotype of the VDR gene is associated with a higher level of impulsivity in these patients. This finding supports the hypothesis that impulsiveness, which significantly contributes to development of alcohol dependence, has a genetic background.

  5. Using rain-on-snow events to evaluate the quality of bias correction to represent complex inter-variable dependencies

    NASA Astrophysics Data System (ADS)

    Rössler, Ole; Bosshard, Thomas; Weingartner, Rolf

    2016-04-01

    A key issue for adaptation planning is the information of projections about changes of extremes. Climate projections of meteorological extremes and their downscaling are a challenge on their own. Yet - at least in hydrology - meteorological extremes are not necessarily hydrological extremes. These can also result from a sequence of days with only moderate meteorological conditions, too. This sequences are called "storylines". In climate change impact assess studies it is relevant to know, whether these meteorological storylines are represented in regional climate models, and how well can bias correction preserve or improve the representation. One storyline leading to hydrological extremes are rain-on-snow events, and more specifically rain-on-snowfall events. These events challenge the regional climate model and the bias correction in terms of representing absolute values and inter-variable dependences. This study makes use of the rain-on-snow-storylines to evaluate the performance of regional climate models and a bias correction method in reproducing complex inter-variable dependencies. At first, we applied a hydrological model to a mesoscale catchment in Switzerland that is known to be effected by rain-on-snow events. At second, the ERA-Interim driven regional climate model RCA4.5 - developed at SMHI - with a spatial resolution of 0.11 * 0.11 degree was used to drive the hydrological model. At third, bias-correction of the RCM was done applying the distribution based scaling (DBS) bias-correction method (Yang et al., 2010) developed at the SMHI. The bias-corrected data then also served as driving input data to the hydrological model. Based on the simulated runoff, as well as simulated precipitation, temperature, and snow pack data, an algorithm to detect rain-on-snow events was applied. Finally, the presence or absents of rain-on-snow events for the three different climate input data, ERA.RCA4.5, DBS corrected ERA.RC4 and observed climate, are evaluated within

  6. Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

    PubMed Central

    Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

    2015-01-01

    Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

  7. Web-based self-help intervention reduces alcohol consumption in both heavy-drinking and dependent alcohol users: A pilot study.

    PubMed

    Andrade, André Luiz Monezi; de Lacerda, Roseli Boerngen; Gomide, Henrique Pinto; Ronzani, Telmo Mota; Sartes, Laisa Marcorela Andreoli; Martins, Leonardo Fernandes; Bedendo, André; Souza-Formigoni, Maria Lucia Oliveira

    2016-12-01

    As part of a multicenter project supported by the World Health Organization, we developed a web-based intervention to reduce alcohol use and related problems. We evaluated the predictors of adherence to, and the outcomes of the intervention. Success was defined as a reduction in consumption to low risk levels or to <50% of the baseline levels of number of drinks. From the 32,401 people who accessed the site, 3389 registered and 929 completed the full Alcohol Use Disorders Identification Test (AUDIT), a necessary condition to be considered eligible to take part in the intervention. Based on their AUDIT scores, these participants were classified into: low risk users (LRU; n=319) harmful/hazardous users (HHU; n=298) or suggestive of dependence users (SDU; n=312). 29.1% of the registered users (LRU=42; HHU=90; SDU=82) completed the evaluation form at the end of the six-week period, and 63.5% reported low-risk drinking levels. We observed a significant reduction in alcohol consumption in the HHU (62.5%) and SDU (64.5%) groups in relation to baseline. One month after the intervention, in the follow-up, 94 users filled out the evaluation form, and their rate of success was similar to the one observed in the previous evaluation. Logistic regression analyses indicated that HHU participants presented higher adherence than LRU. Despite a relatively low adherence to the program, its good outcomes and low cost, as well as the high number of people that can be reached by a web-based intervention, suggest it has good cost-effectiveness. PMID:27424165

  8. Web-based self-help intervention reduces alcohol consumption in both heavy-drinking and dependent alcohol users: A pilot study.

    PubMed

    Andrade, André Luiz Monezi; de Lacerda, Roseli Boerngen; Gomide, Henrique Pinto; Ronzani, Telmo Mota; Sartes, Laisa Marcorela Andreoli; Martins, Leonardo Fernandes; Bedendo, André; Souza-Formigoni, Maria Lucia Oliveira

    2016-12-01

    As part of a multicenter project supported by the World Health Organization, we developed a web-based intervention to reduce alcohol use and related problems. We evaluated the predictors of adherence to, and the outcomes of the intervention. Success was defined as a reduction in consumption to low risk levels or to <50% of the baseline levels of number of drinks. From the 32,401 people who accessed the site, 3389 registered and 929 completed the full Alcohol Use Disorders Identification Test (AUDIT), a necessary condition to be considered eligible to take part in the intervention. Based on their AUDIT scores, these participants were classified into: low risk users (LRU; n=319) harmful/hazardous users (HHU; n=298) or suggestive of dependence users (SDU; n=312). 29.1% of the registered users (LRU=42; HHU=90; SDU=82) completed the evaluation form at the end of the six-week period, and 63.5% reported low-risk drinking levels. We observed a significant reduction in alcohol consumption in the HHU (62.5%) and SDU (64.5%) groups in relation to baseline. One month after the intervention, in the follow-up, 94 users filled out the evaluation form, and their rate of success was similar to the one observed in the previous evaluation. Logistic regression analyses indicated that HHU participants presented higher adherence than LRU. Despite a relatively low adherence to the program, its good outcomes and low cost, as well as the high number of people that can be reached by a web-based intervention, suggest it has good cost-effectiveness.

  9. [The level of 8-iso-prostaglandin F2 alpha, 4-hydroxynonenal and malondialdehyde in alcohol dependent men during combined therapy].

    PubMed

    Kopczyńska, Ewa; Lampka, Magdalena; Torliński, Lech; Ziółkowski, Marcin

    2002-01-01

    The aim of the study was the estimation of intensity of lipid peroxidation in alcohol dependent male patients after three months of therapy with naltrexone or tianeptine and the next three months follow-up. 61 males with clinical diagnosis of alcohol dependence (ICD-10) have been examined. The investigated parameters have been determined in blood serum, the 8-iso-prostaglandin F2 alpha by means of immunoenzymatic assay (ELISA) and malondialdehyde with 4-hydroxynonenal by means of colorimetric method. In alcohol dependent men before pharmacotherapy the mean concentration of 8-iso-PGF2 alpha and [MDA + 4-HNE] was higher than the reference interval. Both, after three months of applied drugs and the next three months follow-up, the concentration of studied parameters decreased considerably. The above results show intensification of lipid peroxidation in alcohol abusers and advantageous influence of abstinence from alcohol and treatment of naltrexone or tianeptine on free-radical changes of lipids as well.

  10. Nalmefene for Reducing Alcohol Consumption in People with Alcohol Dependence: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    PubMed

    Stevenson, Matt; Pandor, Abdullah; Stevens, John W; Rawdin, Andrew; Rice, Peter; Thompson, Jez; Morgan, Marsha Y

    2015-08-01

    As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company (Lundbeck) marketing nalmefene (Selincro) to submit evidence of its clinical and cost effectiveness for reducing alcohol consumption in people with alcohol dependence. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG) and to produce a critical review of the company's submission to NICE. The clinical evidence was derived from three phase III, company-sponsored, randomised, double-blind, placebo-controlled trials in adults with a diagnosis of alcohol dependence comparing nalmefene, taken on an as-needed basis, in conjunction with psychosocial support with placebo in conjunction with psychosocial support. Psychosocial support was provided in the form of BRENDA, an intervention of lower intensity than that recommended in NICE Clinical Guideline 115 (NICE CG115). Post-hoc subgroup analyses were conducted in people who were drinking at high or very high risk levels at baseline and maintained this level of drinking during the screening phase prior to randomisation. This subgroup forms the licensed population. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the three nalmefene studies meant that the inference of treatment effects might be confounded. The company's economic evaluation showed that use of nalmefene in conjunction with psychosocial support in the form of BRENDA dominated the use of BRENDA in conjunction with placebo, providing more quality-adjusted life-years (QALYs) at a reduced cost. However, this evaluation did not meet the final scope issued by NICE, which specified that the comparator should be psychological intervention as defined in NICE CG115. The ERG

  11. Thought suppression, impaired regulation of urges, and Addiction-Stroop predict affect-modulated cue-reactivity among alcohol dependent adults.

    PubMed

    Garland, Eric L; Carter, Kristin; Ropes, Katie; Howard, Matthew O

    2012-01-01

    Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention towards alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age=39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state × trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention.

  12. How Accurate Are Blood (or Breath) Tests for Identifying Self-Reported Heavy Drinking Among People with Alcohol Dependence?

    PubMed Central

    Bertholet, Nicolas; Winter, Michael R.; Cheng, Debbie M.; Samet, Jeffrey H.; Saitz, Richard

    2014-01-01

    Aims Managing patients with alcohol dependence includes assessment for heavy drinking, typically by asking patients. Some recommend biomarkers to detect heavy drinking but evidence of accuracy is limited. Methods Among people with dependence, we assessed the performance of disialo-carbohydrate-deficient transferrin (%dCDT, ≥1.7%), gamma-glutamyltransferase (GGT, ≥66 U/l), either %dCDT or GGT positive, and breath alcohol (> 0) for identifying 3 self-reported heavy drinking levels: any heavy drinking (≥4 drinks/day or >7 drinks/week for women, ≥5 drinks/day or >14 drinks/week for men), recurrent (≥5 drinks/day on ≥5 days) and persistent heavy drinking (≥5 drinks/day on ≥7 consecutive days). Subjects (n = 402) with dependence and current heavy drinking were referred to primary care and assessed 6 months later with biomarkers and validated self-reported calendar method assessment of past 30-day alcohol use. Results The self-reported prevalence of any, recurrent and persistent heavy drinking was 54, 34 and 17%. Sensitivity of %dCDT for detecting any, recurrent and persistent self-reported heavy drinking was 41, 53 and 66%. Specificity was 96, 90 and 84%, respectively. %dCDT had higher sensitivity than GGT and breath test for each alcohol use level but was not adequately sensitive to detect heavy drinking (missing 34–59% of the cases). Either %dCDT or GGT positive improved sensitivity but not to satisfactory levels, and specificity decreased. Neither a breath test nor GGT was sufficiently sensitive (both tests missed 70–80% of cases). Conclusions Although biomarkers may provide some useful information, their sensitivity is low the incremental value over self-report in clinical settings is questionable. PMID:24740846

  13. Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome.

    PubMed

    Brückmann, Christof; Di Santo, Adriana; Karle, Kathrin Nora; Batra, Anil; Nieratschker, Vanessa

    2016-06-01

    Alcohol dependence is a severe disorder contributing substantially to the global burden of disease. Despite the detrimental consequences of chronic alcohol abuse and dependence, effective prevention strategies as well as treatment options are largely missing to date. Accumulating evidence suggests that gene-environment interactions, including epigenetic mechanisms, play a role in the etiology of alcohol dependence. A recent epigenome-wide study reported widespread alterations of DNA methylation patterns in alcohol dependent patients compared to control individuals. In the present study, we validate and replicate one of the top findings from this previous investigation in an independent cohort: the hypomethylation of GDAP1 in patients. To our knowledge, this is the first independent replication of an epigenome-wide finding in alcohol dependence. Furthermore, the AUDIT as well as the GSI score were negatively associated with GDAP1 methylation and we found a trend toward a negative association between GDAP1 methylation and the years of alcohol dependency, pointing toward a potential role of GDAP1 hypomethylation as biomarker for disease severity. In addition, we show that the hypomethylation of GDAP1 in patients reverses during a short-term alcohol treatment program, suggesting that GDAP1 DNA methylation could also serve as a potential biomarker for treatment outcome. Our data add to the growing body of knowledge on epigenetic effects in alcohol dependence and support GDAP1 as a novel candidate gene implicated in this disorder. As the role of GDAP1 in alcohol dependence is unknown, this novel candidate gene should be followed up in future studies.

  14. A 16-Year-old Boy with Combined Volatile and Alcohol Dependence: A Case Report

    PubMed Central

    Gandhi, Raghu; Verma, Pankaj; Kaur, Arshdeep; Kapoor, Rohit

    2015-01-01

    Substance abuse has been defined as the use of chemical substances for non medical purposes in order to achieve alterations in psychological functioning. The substances commonly abused in India include nicotine, alcohol, cannabis and opioids. However, the use of solvents and propellants is also on the rise as these are inexpensive, legally available household, industrial, office and automobile products; which are more commonly available to children and adolescents. We hereby describe a 16-year-old boy with combined volatile and alcohol abuse; who presented with increasing ataxia, visual and hearing disturbances. PMID:26436026

  15. Brain-Specific Inactivation of the Crhr1 Gene Inhibits Post-Dependent and Stress-Induced Alcohol Intake, but Does Not Affect Relapse-Like Drinking

    PubMed Central

    Molander, Anna; Vengeliene, Valentina; Heilig, Markus; Wurst, Wolfgang; Deussing, Jan M; Spanagel, Rainer

    2012-01-01

    Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic–pituitary–adrenal (HPA) axis activity might be involved as well. Here we examined the role of CRHR1 in various drinking conditions in relation to HPA and extra-HPA sites, and studied relapse-like drinking behavior in the alcohol deprivation model (ADE). To dissect CRH/CRHR1 extra-HPA and HPA signaling on a molecular level, a conditional brain-specific Crhr1-knockout (Crhr1NestinCre) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1 antagonists in the ADE model. Stress-induced augmentation of alcohol intake was lower in Crhr1NestinCre mice as compared with control animals. Crhr1NestinCre mice were also resistant to escalation of alcohol intake in the post-dependent state. Contrarily, global Crhr1 knockouts showed enhanced stress-induced alcohol consumption and a more pronounced escalation of intake in the post-dependent state than their control littermates. Basal intake and deprivation-induced intake were unaltered in both knockout models when compared with their respective controls. In line with these findings, CRHR1 antagonists did not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load. PMID:22113086

  16. Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking.

    PubMed

    Molander, Anna; Vengeliene, Valentina; Heilig, Markus; Wurst, Wolfgang; Deussing, Jan M; Spanagel, Rainer

    2012-03-01

    Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic-pituitary-adrenal (HPA) axis activity might be involved as well. Here we examined the role of CRHR1 in various drinking conditions in relation to HPA and extra-HPA sites, and studied relapse-like drinking behavior in the alcohol deprivation model (ADE). To dissect CRH/CRHR1 extra-HPA and HPA signaling on a molecular level, a conditional brain-specific Crhr1-knockout (Crhr1(NestinCre)) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1 antagonists in the ADE model. Stress-induced augmentation of alcohol intake was lower in Crhr1(NestinCre) mice as compared with control animals. Crhr1(NestinCre) mice were also resistant to escalation of alcohol intake in the post-dependent state. Contrarily, global Crhr1 knockouts showed enhanced stress-induced alcohol consumption and a more pronounced escalation of intake in the post-dependent state than their control littermates. Basal intake and deprivation-induced intake were unaltered in both knockout models when compared with their respective controls. In line with these findings, CRHR1 antagonists did not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load.

  17. Cortical Perfusion in Alcohol Dependent Individuals During Short-term Abstinence: Relationships to Resumption of Hazardous Drinking Following Treatment

    PubMed Central

    Durazzo, Timothy C.; Gazdzinski, Stefan; Mon, Anderson; Meyerhoff, Dieter J.

    2010-01-01

    Relapse to hazardous levels of alcohol consumption following treatment for an alcohol use disorders is common. Investigation of the neurobiological correlates of resumption of hazardous drinking is necessary to clarify the mechanisms contributing to relapse. Fifty-seven treatment-seeking alcohol dependent participants (ALC) completed arterial spin labeling perfusion MRI of the frontal and parietal gray matter (GM) at 7 ± 3 days of abstinence (baseline). ALC participants were restudied after 35 ± 11 days of abstinence (assessment point 2: AP2). Twenty-eight non-smoking, light drinking controls (nsLD) from the community were studied with perfusion MRI. ALC Participants were followed over 12-months after baseline study and were classified as Abstainers (no alcohol consumption; n = 19) and Resumers (any alcohol consumption; n = 38) at follow-up. Cross-sectional and longitudinal perfusion was compared in Abstainers, Resumers and nsLD. At baseline Resumers demonstrated significantly lower frontal and parietal GM perfusion than nsLD and Abstainers. Abstainers and nsLD were not different on frontal or parietal GM perfusion. No significant longitudinal perfusion changes were observed in Abstainers and Resumers. At AP2, Resumers showed significantly lower frontal GM perfusion than nsLD and Abstainers, while no group differences were observed for parietal GM. Abstainers and nsLD were not different on frontal GM perfusion. The significantly decreased frontal GM perfusion in Resumers compared to both Abstainers and nsLD across the assessment interval suggests premorbid and/or acquired neurobiological abnormalities of the frontal GM in Resumers. PMID:20682188

  18. Serum levels of brain-derived neurotrophic factor in alcohol-dependent patients receiving high-dose baclofen.

    PubMed

    Geisel, Olga; Hellweg, Rainer; Müller, Christian A

    2016-06-30

    The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders. PMID:27107672

  19. Unexpected properties of NADP-dependent secondary alcohol dehydrogenase (ADH-1) in Trichomonas vaginalis and other microaerophilic parasites.

    PubMed

    Leitsch, David; Williams, Catrin F; Lloyd, David; Duchêne, Michael

    2013-07-01

    Our previous observation that NADP-dependent secondary alcohol dehydrogenase (ADH-1) is down-regulated in metronidazole-resistant Trichomonas vaginalis isolates prompted us to further characterise the enzyme. In addition to its canonical enzyme activity as a secondary alcohol dehydrogenase, a pronounced, so far unknown, background NADPH-oxidising activity in absence of any added substrate was observed when the recombinant enzyme or T. vaginalis extract were used. This activity was strongly enhanced at low oxygen concentrations. Unexpectedly, all functions of ADH-1 were efficiently inhibited by coenzyme A which is a cofactor of a number of key enzymes in T. vaginalis metabolism, i.e. pyruvate:ferredoxin oxidoreductase (PFOR). These observations could be extended to Entamoeba histolytica and Tritrichomonas foetus, both of which have a homologue of ADH-1, but not to Giardia lamblia which lacks an NADP-dependent secondary alcohol dehydrogenase. Although we could not identify the substrate of the observed background activity, we propose that ADH-1 functions as a major sink for NADPH in microaerophilic parasites at low oxygen tension.

  20. Unexpected properties of NADP-dependent secondary alcohol dehydrogenase (ADH-1) in Trichomonas vaginalis and other microaerophilic parasites.

    PubMed

    Leitsch, David; Williams, Catrin F; Lloyd, David; Duchêne, Michael

    2013-07-01

    Our previous observation that NADP-dependent secondary alcohol dehydrogenase (ADH-1) is down-regulated in metronidazole-resistant Trichomonas vaginalis isolates prompted us to further characterise the enzyme. In addition to its canonical enzyme activity as a secondary alcohol dehydrogenase, a pronounced, so far unknown, background NADPH-oxidising activity in absence of any added substrate was observed when the recombinant enzyme or T. vaginalis extract were used. This activity was strongly enhanced at low oxygen concentrations. Unexpectedly, all functions of ADH-1 were efficiently inhibited by coenzyme A which is a cofactor of a number of key enzymes in T. vaginalis metabolism, i.e. pyruvate:ferredoxin oxidoreductase (PFOR). These observations could be extended to Entamoeba histolytica and Tritrichomonas foetus, both of which have a homologue of ADH-1, but not to Giardia lamblia which lacks an NADP-dependent secondary alcohol dehydrogenase. Although we could not identify the substrate of the observed background activity, we propose that ADH-1 functions as a major sink for NADPH in microaerophilic parasites at low oxygen tension. PMID:23578856

  1. Gender-specific gene-environment interaction in alcohol dependence: the impact of daily life events and GABRA2.

    PubMed

    Perry, Brea L; Pescosolido, Bernice A; Bucholz, Kathleen; Edenberg, Howard; Kramer, John; Kuperman, Samuel; Schuckit, Marc Alan; Nurnberger, John I

    2013-09-01

    Gender-moderated gene-environment interactions are rarely explored, raising concerns about inaccurate specification of etiological models and inferential errors. The current study examined the influence of gender, negative and positive daily life events, and GABRA2 genotype (SNP rs279871) on alcohol dependence, testing two- and three-way interactions between these variables using multi-level regression models fit to data from 2,281 White participants in the Collaborative Study on the Genetics of Alcoholism. Significant direct effects of variables of interest were identified, as well as gender-specific moderation of genetic risk on this SNP by social experiences. Higher levels of positive life events were protective for men with the high-risk genotype, but not among men with the low-risk genotype or women, regardless of genotype. Our findings support the disinhibition theory of alcohol dependence, suggesting that gender differences in social norms, constraints and opportunities, and behavioral undercontrol may explain men and women's distinct patterns of association.

  2. Unexpected properties of NADP-dependent secondary alcohol dehydrogenase (ADH-1) in Trichomonas vaginalis and other microaerophilic parasites

    PubMed Central

    Leitsch, David; Williams, Catrin F.; Lloyd, David; Duchêne, Michael

    2013-01-01

    Our previous observation that NADP-dependent secondary alcohol dehydrogenase (ADH-1) is down-regulated in metronidazole-resistant Trichomonas vaginalis isolates prompted us to further characterise the enzyme. In addition to its canonical enzyme activity as a secondary alcohol dehydrogenase, a pronounced, so far unknown, background NADPH-oxidising activity in absence of any added substrate was observed when the recombinant enzyme or T. vaginalis extract were used. This activity was strongly enhanced at low oxygen concentrations. Unexpectedly, all functions of ADH-1 were efficiently inhibited by coenzyme A which is a cofactor of a number of key enzymes in T. vaginalis metabolism, i.e. pyruvate:ferredoxin oxidoreductase (PFOR). These observations could be extended to Entamoeba histolytica and Tritrichomonas foetus, both of which have a homologue of ADH-1, but not to Giardia lamblia which lacks an NADP-dependent secondary alcohol dehydrogenase. Although we could not identify the substrate of the observed background activity, we propose that ADH-1 functions as a major sink for NADPH in microaerophilic parasites at low oxygen tension. PMID:23578856

  3. Pharmacological Correction of Alcohol Motivation Depends on the Phenotype of the Response to Emotional Stress.

    PubMed

    Kolik, L G; Gudasheva, T A; Martyanov, V A; Seredenin, S B

    2016-08-01

    The specific features of alcohol behavior were studied in MR and MNRA rats that exhibit an opposite reaction to emotional stress. We evaluated the effect of a dipeptide anxiolytic GB-115 (N-phenyl-hexanoyl-glycyl-L-tryptophan amide, neuropeptide cholecystokinin-4 analogue with antagonistic activity) on alcohol motivation in rats, which was formed over 12 months. High-emotionality MR rats were more sensitive to the anxiolytic effect of ethanol in the conflict situation test than low-emotionality MNRA rats. MNRA rats consumed a greater amount of ethanol under a free-choice condition with 15% ethanol solution and water (as in comparison with MR rats). However, the behavior of MR rats was transformed due to a significant increase in alcohol motivation from the 5th month of long-term free access to ethanol. An anxiolytic GB-115 (0.025 mg/kg intraperitoneally for 14 days) with selective activity in high-emotionality rats was shown to reduce significantly the average daily consumption and alcohol-deprivation effect in MR rats, but did not modulate ethanol addiction in MNRA rats. PMID:27590755

  4. Mediators of Telephone-Based Continuing Care for Alcohol and Cocaine Dependence

    ERIC Educational Resources Information Center

    Mensinger, Janell Lynn; Lynch, Kevin G.; Tenhave, Thomas R.; McKay, James R.

    2007-01-01

    A previous randomized trial with 224 alcohol and/or cocaine addicts who had completed an initial phase of treatment indicated that 12 weeks of telephone-based continuing care yielded higher abstinence rates over 24 months than did group counseling continuing care. The current study examined mediators of this treatment effect. Results suggested…

  5. The Alcohol-Affected Student: Co-Dependency in the College Classroom.

    ERIC Educational Resources Information Center

    Szymanski, Theodore J.

    1992-01-01

    Describes the characteristics of Adult Children of Alcoholics (ACOAs), indicating that they are an increasing part of the college campus population. Discusses nine steps that instructors may take to assist the academic success of ACOAs. Indicates that college staff must recognize the syndrome and provide a therapeutic environment for students. (14…

  6. Cortical Thickness, Surface Area and Volume of the Brain Reward System in Alcohol Dependence: Relationships to Relapse and Extended Abstinence

    PubMed Central

    Durazzo, Timothy C.; Tosun, Duygu; Buckley, Shannon; Gazdzinski, Stefan; Mon, Anderson; Fryer, Susanna L.; Meyerhoff, Dieter J.

    2011-01-01

    BACKGROUND At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area and volume in neocortical components of the BRS among non-smoking light drinking controls (Controls), individuals who remained abstinent and those who relapsed after treatment. ME