Trova, A C; Paparrigopoulos, Th; Liappas, I; Ginieri-Coccossis, M
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
Osaki, Yoneatsu; Kinjo, Aya; Higuchi, Susumu; Matsumoto, Hiroshi; Yuzuriha, Takefumi; Horie, Yoshinori; Kimura, Mitsuru; Kanda, Hideyuki; Yoshimoto, Hisashi
Nationwide surveys to clarify the characteristics and trends of the drinking behavior of Japanese adults were carried out in 2003, 2008, and 2013. These were periodical cross-sectional surveys. Subjects were chosen through a stratified two-stage random sampling method. The surveys included drinking frequency and amount, ICD-10 alcoholism diagnostic standards, questionnaire for the determination of harmful alcohol use ( Alcohol Use Disorders Identification Test). In 2003, the surveys obtained responses from 2547 people (73% response rate); in 2008, 4123 people (55% response rate); and in 2013, 4153 people (59% response rate). The proportion of lifetime experience of alcohol dependence diagnosed by ICD-10 was 1.9% for male and 0.2% for female, and the estimated number of patients was 1.07 million. The declining trends were observed in the percentage of daily drinkers and the amount of alcohol consumed per week for male. The lowering of the age for consuming their first alcoholic drink and their first drunken experience was observed among female. The gender difference of prevalence of problem drinking is getting smaller. The binge drinking and heavy episodic drinking were observed especially younger generation. The only small proportion of patients with alcohol dependence had received specialized medical care, whereas the many of these visited medical institutions and health screening. The survey observed many hidden alcoholic patients, and showed the possibility that the healthcare facilities and health screening became the place of screening and intervention for alcohol dependence. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.
Khan, Sharaf; Okuda, Mayumi; Hasin, Deborah S; Secades-Villa, Roberto; Keyes, Katherine; Lin, Keng-Han; Grant, Bridget; Blanco, Carlos
An extensive clinical literature has noted gender differences in the etiology and clinical characteristics of individuals with alcohol dependence (AD). Despite this knowledge, many important questions remain. Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093), we examined differences in sociodemographic characteristics, psychiatric and medical comorbidities, clinical correlates, risk factors, and treatment-utilization patterns of men (N = 2,974) and women (N = 1,807) with lifetime AD. Men with lifetime AD were more likely than women to be diagnosed with any substance use disorder and antisocial personality disorder, whereas women were more likely to have mood and anxiety disorders. After adjusting for sociodemographic characteristics and gender differences in psychiatric comorbidity in the general population, AD was associated with externalizing disorders and any mood disorder among women only. Men with AD met more criteria, had longer episodes, and were younger at the age of first drink. There were no gender differences in remission rates. Women with AD were more likely to have a family and a spouse with history of alcohol use disorders. Treatment rates were low for both genders, and women were more likely to report social stigmatization as a treatment barrier. There are important gender differences in the psychiatric comorbidities, risk factors, clinical characteristics, and treatment-utilization patterns among individuals with lifetime AD. Copyright © 2013 by the Research Society on Alcoholism.
Marquenie, Loes A; Schadé, Annemiek; Van Balkom, Anton J L M; Koeter, Maarten; Frenken, Sipke; van den Brink, Wim; van Dyck, Richard
Despite claims that comorbid anxiety disorders tend to lead to a poor outcome in the treatment of alcohol dependence, the few studies on this topic show conflicting results. To test whether the outcome of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder is worse than that of similar patients without a comorbid phobic disorder. The probabilities of starting to drink again and of relapsing into regular heavy drinking in (i) a group of 81 alcohol-dependent patients with comorbid social phobia or agoraphobia were compared with those in (ii) a group of 88 alcohol-dependent patients without anxiety disorders in a naturalistic follow-up using Cox regression analysis. Adjusted for initial group differences, the hazard ratio for the association of phobic disorders with resumption of drinking was 1.05 (95% CI, 0.85-1.30, P = 0.66) and the adjusted hazard ratio for the association of phobic disorders with a relapse into regular heavy drinking was 1.02 (95% CI, 0.78-1.33, P = 0.89). The findings of this study do not confirm the idea that alcohol-dependent patients who have undergone alcohol-dependence treatment are at greater risk of a relapse if they have a comorbid anxiety disorder. No differences were found in abstinence duration or time to relapse into regular heavy drinking between patients with and without comorbid phobic disorders.
Pani, Pier Paolo; Trogu, Emanuela; Pacini, Matteo; Maremmani, Icro
Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Besides psychosocial interventions, different pharmacological interventions have been or currently are under investigation through Cochrane systematic reviews. The primary aim of the review is to assess the benefits/risks of anticonvulsants for the treatment of alcohol dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (October 2013), PubMed (1966 to October 2013), EMBASE (1974 to October 2013) and CINAHL (1982 to October 2013). Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing anticonvulsants alone or in association with other drugs and/or psychosocial interventions versus placebo, no treatment and other pharmacological or psychosocial interventions. We used standard methodological procedures as expected by The Cochrane Collaboration. A total of 25 studies were included in the review (2641 participants). Most participants were male, with an average age of 44 years. Anticonvulsants were compared with placebo (17 studies), other medications (seven studies) and no medication (two studies). The mean duration of the trials was 17 weeks (range four to 52 weeks). The studies took place in the USA, Europe, South America, India and Thailand. Variation was reported in the characteristics of the studies, including their design and the rating instruments used. For many key outcomes, the risk of bias associated with unclear or unconcealed allocation and lack of blinding affected the quality of the evidence.Anticonvulsants versus placebo: For dropouts (16 studies, 1675 participants, risk ratio (RR) 0.94, 95% confidence interval (Cl) 0.74 to 1.19, moderate-quality evidence) and continuous abstinence (eight studies, 634 participants, RR 1.21, 95% Cl 95% 0.97 to 1.52, moderate-quality evidence), results showed no evidence of differences. Moderate-quality evidence suggested that
Nathan, P E
Current data on efforts to prevent alcoholism indicate that we are better able to prevent some of the consequences of alcohol misuse, such as alcohol-related car crashes and fetal alcohol syndrome, than chronic alcohol dependence itself. A review of data on outcomes of treatment for long-term alcohol dependence indicates that 9 of 10 alcohol dependent persons receive no treatment for the disorder in any given year. When treatment is provided for long-term alcohol dependent persons, it has only slightly positive results. As a result, many clinicians and researchers have concluded that rather than exclusive preoccupation with long-term alcoholics, early intervention with persons who are just beginning to abuse alcohol may be a more effective use of resources. PMID:3141965
This review focuses on classical and recent research work in the field of alcohol dependence. Data from psychopathological studies trying to determine a "pre-addictive" personality are exposed. More recent studies assess personality disorders and dimensions of temperament associated to alcohol dependence. Sensation seeking, antisocial personality and novelty seeking appear as the main psychological parameters involved in dependence. Sensation seeking is a dimension of personality often associated to behavioral dependence. Sensation seeking is assessed with a five-component scale including general factor, thrill and adventure seeking, experience-seeking, disinhibition, and boredom susceptibility. Patients presenting alcohol dependence have a higher level of sensation seeking. Neurophysiological and genetic studies try to correlate these personality features to biological parameters. Preliminary results of these works are presented and discussed.
Garland, Eric L.; Gaylord, Susan A.; Boettiger, Charlotte A.; Howard, Matthew O.
Mindfulness training may disrupt the risk chain of stress-precipitated alcohol relapse. In 2008, 53 alcohol-dependent adults (mean age = 40.3) recruited from a therapeutic community located in the urban southeastern U.S. were randomized to mindfulness training or a support group. Most participants were male (79.2%), African American (60.4%), and earned < $20,000 annually (52.8%). Self-report measures, psychophysiological cue-reactivity, and alcohol attentional bias were analyzed via repeated measures ANOVA. 37 participants completed the interventions. Mindfulness training significantly reduced stress and thought suppression, increased physiological recovery from alcohol cues, and modulated alcohol attentional bias. Hence, mindfulness training appears to target key mechanisms implicated in alcohol dependence, and therefore may hold promise as an alternative treatment for stress-precipitated relapse among vulnerable members of society. PMID:20648913
Tsuchida, Hideto; Nishimura, Isao; Fukui, Kenji
In this paper, we have outlined the neurobiological basis of alcohol and drug dependence. The prevalence of drug dependence is a serious social problem in many countries, including Japan. This problem involves many background factors, including those pertaining to medical sciences, socio economics, and politics. First, we briefly describe the findings pertaining to psychotomimetic drugs as a model of schizophrenia. The biological pathogenesis of schizophrenic disorders is still unknown. The symptoms of methamphetamine (MAP) and phencyclidine (PCP) psychoses are very similar to those of schizophrenic disorders involving hallucination or delusion. PCP causes not only positive symptoms but also negative symptoms. Therefore, it has been considered as a more comprehensive model of schizophrenia than other drugs. Furthermore, amotivational syndrome, which is observed in patients with chronic cannabis and organic solvent dependence, is similar to the negative symptoms of schizophrenia. Understanding the neurobiological basis of drug dependence by using the molecular biological approach will provide an important clue for elucidating the mechanisms underlying schizophrenia and endogenous psychiatric disorders. Next, we discuss account for the neurobiological mechanisms underlying drug dependence. The reward system in the brain, which is common for all dependent drugs, has been explained, and the stages of addiction corresponding to the development of drug dependence have been discussed followed. In addition, we have discussed the epigenetics aspects of substance dependence, which is one of the hottest topics in psychiatric genetics. We expect that further studies of the mechanisms underlying drug dependence will aid in elucidating of the pathophysiology of various psychiatric diseases.
Razvodovsky, Y. E.
This study explores types of alcohol and surrogates consumed, patterns of consumption, and reasons behind noncommercial alcohol consumption among alcohol-dependent patients in Belarus. The study was conducted in the Belarusian city Grodno in 2012 with 223 alcoholics admitted to narcological clinic using structured interviews. The results suggest that at least 20.2% of alcohol dependent patients regularly consume samogon and 11.8% of patients use surrogates, the most popular among which are medications with a high percentage of ethanol and industrial spirits. The belief that, according to quality criteria, samogon exceeds licensed vodka is the main motive for its consumption. The results of this study suggest the existence of the problem of consumption of noncommercial alcohol among alcohol dependent patients in Belarus. PMID:24233448
Tambour, Sophie; Quertemont, Etienne
In recent years, advances in neuroscience led to the development of new medications to treat alcohol dependence and especially to prevent alcohol relapse after detoxification. Whereas the earliest medications against alcohol dependence were fortuitously discovered, recently developed drugs are increasingly based on alcohol's neurobiological mechanisms of action. This review discusses the most recent developments in alcohol pharmacotherapy and emphasizes the neurobiological basis of anti-alcohol medications. There are currently three approved drugs for the treatment of alcohol dependence with quite different mechanisms of action. Disulfiram is an inhibitor of the enzyme aldehyde dehydrogenase and acts as an alcohol-deterrent drug. Naltrexone, an opiate antagonist, reduces alcohol craving and relapse in heavy drinking, probably via a modulation of the mesolimbic dopamine activity. Finally, acamprosate helps maintaining alcohol abstinence, probably through a normalization of the chronic alcohol-induced hyperglutamatergic state. In addition to these approved medications, many other drugs have been suggested for preventing alcohol consumption on the basis of preclinical studies. Some of these drugs remain promising, whereas others have produced disappointing results in preliminary clinical studies. These new drugs in the field of alcohol pharmacotherapy are also discussed, together with their mechanisms of action.
Blanco, Carlos; Xu, Yang; Brady, Kathleen; Pérez-Fuentes, Gabriela; Okuda, Mayumi; Wang, Shuai
Background Despite the high rates of comorbidity of post-traumatic stress disorder (PTSD) and alcohol dependence (AD) in clinical and epidemiological samples, little is known about the prevalence, clinical presentation, course, risk factors and patterns of treatment-seeking of co-occurring PTSD-AD among the general population. Methods The sample included respondents of the Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Weighted means, frequencies and odds ratios (ORs) of sociodemographic correlates, prevalence of psychiatric disorders and rates of treatment-seeking were computed. Results: In the general population, the lifetime prevalence of PTSD only, AD only and PTSD-AD was 4.83%, 13.66% and 1.59%, respectively. Individuals with comorbid PTSD-AD were more likely than those with PTSD or AD only to have suffered childhood adversities and had higher rates of Axis I and II disorders and suicide attempts. They also met more PTSD diagnostic criteria, had earlier onset of PTSD and were more likely to use drugs and alcohol to relieve their PTSD symptoms than those with PTSD only; they also met more AD diagnostic criteria than those with AD only and had greater disability. Individuals with PTSD-AD had higher rates of treatment seeking for AD than those with AD only, but similar rates than those with PTSD only. Conclusion PTSD-AD is associated with high levels of severity across a broad range of domains even compared with individuals with PTSD or AD only, yet treatment-seeking rates are very low. There is a need to improve treatment access and outcomes for individuals with PTSD-AD. PMID:23702490
Wu, Li-Tzy; Blazer, Dan G.; Woody, George E.; Burchett, Bruce; Yang, Chongming; Pan, Jeng-Jong; Ling, Walter
Aim To address an urgent need for screening of substance use problems in medical settings, we examined substance-specific dependence criteria as potential brief screeners for the detection of patients with a substance use disorder (SUD). Methods The sample included 920 opioid-dependent adults who were recruited from outpatient treatment settings at 11 programs in 10 U.S. cities and who completed intake assessments of SUDs for a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN003). Data were analyzed by factor analysis, item response theory (IRT), sensitivity, and specificity procedures. Results Across all substances (alcohol, amphetamines, cannabis, cocaine, sedatives), withdrawal was among the least prevalent symptoms, while taking large amounts and inability to cut down were among the most prevalent symptoms. Items closely related to the latent trait of a SUD showed good-to-high values of area under the receiver operating characteristic curve in identifying cases of a SUD; IRT-defined severe and less discriminative items exhibited low sensitivity in identifying cases of a SUD (withdrawal for all substances; time using for alcohol and sedatives; giving up activities for sedatives). Conclusions Study results suggest that withdrawal and time using are much less reliable indicators for a SUD than taking larger amounts than intended and inability to cut down and should be studied further for consideration in developing a simplified tool for screening patients for SUDs in medical settings. These findings have implications for the use of common health indicators in electronic health records systems to improve patient care. PMID:22204775
Wright, Alison K.; Ashcroft, Darren M.; van Staa, Tjeerd P.; Pirmohamed, Munir
This study aims to investigate the incidence and annual presentation rates of alcohol dependence in general practice in the UK, and examine age-, gender-, socioeconomic-, and region-specific variation. We conducted a retrospective 'open' cohort study using the Clinical Practice Research Datalink (CPRD), an anonymised primary care database. Prior to data extraction, a case definition for alcohol dependence in CPRD was established using 47 Read codes, which included primary alcohol dependence and consequences of alcohol dependence. Directly standardised rates for incidence and annual presentation were calculated for each year between 1990 and 2013. Rates were compared by gender, age, UK home nation, and practice-level Index of Multiple Deprivation. The directly standardised annual incidence rates were 8.3 and 3.7 per 10,000 male and female patients, respectively. The estimated annual rates of presentation per 10,000 were 17.1 for males and 7.6 for females. Female to male rate ratios were: 0.40 (95% CI: 0.39–0.41) for incident cases; and 0.37 (95% CI: 0.36–0.39) for annual presentation. Rates were highest in those aged 35–54 for both measures and across genders, and lowest in those aged over 75 years. With England as the reference nation, Northern Ireland and Scotland had significantly higher rates for both measures. Patients from the most deprived areas had the highest incidence and annual presentation rates. There is unequal distribution of patients with severe alcohol dependence across population subgroups in general practice. Given the health and economic burden associated with dependent drinking, these data will be useful in informing future public health initiatives. PMID:28362848
Wu, Li-Tzy; Blazer, Dan G; Woody, George E; Burchett, Bruce; Yang, Chongming; Pan, Jeng-Jong; Ling, Walter
To address an urgent need for screening of substance use problems in medical settings, we examined substance-specific dependence criteria as potential brief screeners for the detection of patients with a substance use disorder (SUD). The sample included 920 opioid-dependent adults who were recruited from outpatient treatment settings at 11 programs in 10 U.S. cities and who completed intake assessments of SUDs for a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN003). Data were analyzed by factor analysis, item response theory (IRT), sensitivity, and specificity procedures. Across all substances (alcohol, amphetamines, cannabis, cocaine, sedatives), withdrawal was among the least prevalent symptoms, while taking large amounts and inability to cut down were among the most prevalent symptoms. Items closely related to the latent trait of a SUD showed good-to-high values of area under the receiver operating characteristic curve in identifying cases of a SUD; IRT-defined severe and less discriminative items exhibited low sensitivity in identifying cases of a SUD (withdrawal for all substances; time using for alcohol and sedatives; giving up activities for sedatives). Study results suggest that withdrawal and time using are much less reliable indicators for a SUD than taking larger amounts than intended and inability to cut down and that the latter two items should be studied further for consideration in developing a simplified tool for screening patients for SUDs in medical settings. These findings have implications for the use of common health indicators in electronic health records systems to improve patient care. Copyright © 2011 Elsevier Ltd. All rights reserved.
Martins, Silvia S.; Malcolm, Robert J.; Floyd, Leah; Cavanaugh, Courtenay E.; Latimer, William W.
The use of illegal drugs is common in alcohol dependence and significant psychological and social consequences are associated with the concurrent use of alcohol and illegal drugs. However, little literature has examined the patterns of concurrent drug use in alcohol dependent individuals. A latent class analysis (LCA) was used to determine whether patterns of past year illegal drug use existed in a national sample of 6,059 alcohol dependent respondents of the combined 2005, 2006 and 2007 National Survey on Drug Use and Health. Multinomial logistic regression was then used to determine whether demographic variables, mental health disturbance and social consequences were predictive of drug use classes. Results of the LCA demonstrated a five class solution with optimal fit deduced by Bayesian Information Criterion minima. The five classes included: a close to zero probability of illegal drug use (class 1: 65%), medium marijuana, medium sedatives/tranquilizers and high analgesics (class 2: 7%), high marijuana, medium cocaine use (class 3: 21%), high probabilities of marijuana, cocaine, sedatives and analgesic use (class 4: 6%) and a high concurrent drug use except other hallucinogens (class 5: 1%). Regression results suggest that younger age, comorbidity, engaging in deviant behaviors, sexually transmitted infection and incarceration are associated with concurrent illegal drug use in alcohol dependent individuals. Findings advocate that more intense psychiatric and drug dependence treatment resources may be needed for concurrent drug using alcohol dependent populations and provide evidence for targeted prevention and treatment interventions. PMID:19758770
Wetherill, Leah; Schuckit, Marc A.; Hesselbrock, Victor; Xuei, Xiaoling; Liang, Tiebing; Dick, Danielle M.; Kramer, John; Nurnberger, John I.; Tischfield, Jay A.; Porjesz, Bernice; Edenberg, Howard J.; Foroud, Tatiana
Background Several lines of evidence in both human and animal studies suggest that variation in neuropeptide Y (NPY) or its receptor genes (NPY1R, NPY2R and NPY5R) is associated with alcohol dependence as well as alcohol withdrawal symptoms. Additional studies suggest cocaine may affect NPY expression. Methods A total of 39 SNPs were genotyped across NPY and its 3 receptor genes in a sample of 1,923 subjects from 219 multiplex alcoholic families of European American descent recruited as part of the Collaborative Studies on the Genetics of Alcoholism (COGA) study. Family-based association analysis was performed to test the primary hypothesis that variation in these genes is associated with alcohol dependence. Secondary analyses evaluated whether there was an association of these SNPs with symptoms of alcohol withdrawal, cocaine dependence, or comorbid alcohol and cocaine dependence. Results Although variations in NPY itself were not associated with these phenotypes, variations in two NPY-receptor genes were. SNPs in NPY2R provided significant evidence of association with alcohol dependence, alcohol withdrawal symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence (all p<0.03). Haplotype analyses strengthened the evidence for these phenotypes (global 0.005
alcohol withdrawal characterized by seizures (p<0.05). Conclusion These results indicate that sequence variations in NPY receptor genes are associated with alcohol dependence, particularly a severe subtype of alcohol dependence characterized by withdrawal symptoms, comorbid alcohol and cocaine dependence or cocaine dependence. PMID:18828811
Gigliotti, Analice; Bessa, Marco Antonio
The Alcohol Dependence Syndrome (ADS) is a serious problem of public health. In spite of being deeply studied and having well-established diagnostic criteria, many times clinicians and even psychiatrists do not notice this disorder. The aim of this paper is to make a brief exposition on how men and society have developed their relationship with alcohol, emphasizing the development of the concept of alcoholism in medicine until the definition of ADS in ICD-10 and DSM-IV. The article explains the different ways of alcohol consume and how it influences different levels of risk and severity of its consequences, that evolves as a continuum. At last, it makes a comparison between ADS and alcohol harmful use, very important in the prevention and treatment of such disorders.
Bahlmann, M; Preuss, U W; Soyka, M
Personality disorders, and particularly antisocial personality disorder (ASPD), frequently co-occur with alcohol dependence. ASPD is considered to be an important cofactor in the pathogenesis and clinical course of alcohol dependence. The chronological relationship between the onset of symptoms of ASPD and alcohol-dependence characteristics has not yet been studied in great detail and the role of ASPD in classification schemes of alcohol dependence as suggested by Cloninger and Schuckit has yet to be determined. We studied 55 alcohol-dependent patients to assess the prevalence and age at manifestation of ASPD, conduct disorder characteristics as well as alcohol dependence by employing the Semi-Structured Assessment for the Genetics of Alcoholism and the Structured Clinical Interview for DSM-III-R. Results indicate that the onset of ASPD characteristics precede that of alcohol dependence by some 4 years. This finding suggests that in patients with ASPD, alcohol dependence might be a secondary syndrome as suggested by previous research.
Falkner, Carolyn; Christie, Grant; Zhou, Lifeng; King, Julian
To investigate the current purchasing behaviours of a group of dependent drinkers and their potential response to future increases in the price of alcohol. 115 clients undergoing medical detoxification completed an anonymous survey about their daily alcohol consumption, its cost, their response to potential price increases and strategies previously used when unable to afford alcohol. Mean and median number of standard drinks consumed per day was 24, at a median cost of $25 NZD (95%CI $22, $30). Thirty-six per cent (95%CI 26%, 46%) of the group bought alcohol at $1 or less per standard drink, and the median number of drinks consumed per day (30) by this group was significantly higher (p=0.0028) than the rest of the sample (22.5). The most common strategy used if no money was available to purchase alcohol was to forgo essentials. If facing a potential price rise, 77% (95%CI 69%, 85%) would switch wholly or partially to a cheaper product and 13% (95%CI 8%, 21%) would cut down their drinking. Although the majority of our group would be financially impacted by an increase in the minimum price per standard drink, any potential impacts would be most significant in those buying the cheapest alcohol (who also drink the most), suggesting that minimum pricing may be an important harm minimisation strategy in this group. A minimum price per standard drink would limit the possibility of switching to an alternate cheaper product and likely result in an overall reduction in alcohol consumption in this group. Stealing alcohol, or the use of non-beverage alcohol, were seldom reported as previous strategies used in response to unaffordable alcohol and fears of such are not valid reasons for rejecting minimum pricing to reduce general population consumption.
Pinto, E; Ansseau, M
Alcohol dependence is a complex and multifactorial disease resulting both from neurobiological mechanisms and environmental factors. It is frequently associated with comorbid psychiatric disorders or with specific personality or behavioral features. Although action can be taken on the environment in order to decrease the risk of the illness, current methods used to prevent or to treat this pathology show moderate efficacy: problematic consumption of ethanol in the general population as well as relapse rates under treatment in dependent patients remain indeed very high. It is therefore of major importance to broaden our knowledge of alcohol dependence and its comorbidities so as to improve both their prevention and treatment. In this perspective, recent progress in the field of neurosciences may contribute to achieve this goal. Precisely, genetics is a promising way benefiting from many advances in genetic epidemiology, cellular and molecular biology, neuroimaging and pharmacology. In parallel with a better understanding of the neurobiology of addictions and associated behaviors, these techniques led to the identification of brain mechanisms in which a genetic variation may influence the individual vulnerability towards alcohol dependence. Moreover, there is growing evidence that alcoholism results from the interaction of genetic and environmental factors influencing both its expression and its course. Given the fact that alcohol-dependence seems highly heritable (50 to 60% of the variance in both men and women), this review assesses the role of some of the genomic regions linked with the disease, as well as the principal variants of candidate genes identified as specifically involved in the predisposition. Polymorphisms of genes influencing alcohol metabolism, GABAergic, dopaminergic and serotonergic neurotransmission seem, indeed, at stake in the development of alcohol-dependence and its related features such as personality, behavior, impulse control or craving
Waszkiewicz, Napoleon; Zalewska-Szajda, Beata; Zalewska, Anna; Waszkiewicz, Magdalena; Szajda, Slawomir Dariusz; Repka, Bernadeta; Szulc, Agata; Kepka, Alina; Minarowska, Alina; Ladny, Jerzy Robert; Zwierz, Krzysztof
The purpose of this study was to evaluate the effect of chronic alcohol intoxication and smoking on the concentration and output of salivary lysozyme. Thirty seven men participated in the study, including 17 male smoking alcohol-dependent patients after chronic alcohol intoxication (AS), and 20 control non-smoking male social drinkers (CNS) with no history of alcohol abuse or smoking. The level of lysozyme was assessed by the radial immunodiffusion method. Significantly lower lysozyme output in the AS group compared to the CNS group was found. Moreover, gingival index was significantly higher in AS than in the CNS group. It appeared that the reduced salivary lysozyme output was more likely the result of ethanol action than smoking. In conclusion, persons addicted to alcohol and nicotine have a poorer periodontal status than non-smoking social drinkers, which may partially be due to the diminished protective effects of lysozyme present in the saliva.
Grant, Julia D.; Agrawal, Arpana; Bucholz, Kathleen K.; Madden, Pamela A.F.; Pergadia, Michele L.; Nelson, Elliot C.; Lynskey, Michael T.; Todd, Richard D.; Todorov, Alexandre A.; Hansell, Narelle K.; Whitfield, John B.; Martin, Nicholas G.; Heath, Andrew C.
Background Previous research has reported a significant genetic correlation between heaviness of alcohol consumption and alcohol dependence (AD), but this association might be driven by the influence of AD on consumption rather than the reverse. We test the genetic overlap between AD symptoms and a heaviness of consumption measure among individuals who do not have AD. A high genetic correlation between these measures would suggest that a continuous measure of consumption may have a useful role in the discovery of genes contributing to dependence risk. Methods Factor analysis of 5 alcohol use measures was used to create a measure of heaviness of alcohol consumption. Quantitative genetic analyses of interview data from the 1989 Australian Twin Panel (n=6257 individuals; M=29.9 years) assessed the genetic overlap between heaviness of consumption, DSM-IV AD symptoms, DSM-IV AD symptom clustering, and DSM-IV alcohol abuse. Results Genetic influences accounted for 30–51% of the variance in the alcohol measures and genetic correlations were 0.90 or higher for all measures, with the correlation between consumption and dependence symptoms among non-dependent individuals estimated at 0.97 (95% CI: 0.80–1.00). Conclusions Heaviness of consumption and AD symptoms have a high degree of genetic overlap even among non-dependent individuals in the general population, implying that genetic influences on dependence risk in the general population are acting to a considerable degree through heaviness of use, and that quantitative measures of consumption will likely have a useful role in the identification of genes contributing to AD. PMID:19576574
Mann, Karl; Lehert, Philippe; Morgan, Marsha Y
A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta-analytical techniques. All randomized, placebo-controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross-referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck-Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB). A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate-treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29-1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates
Dickie, A K; Coetzee, R H
Alcohol misuse is a significant occupational health issue in the United Kingdom Armed Forces. Dependence associated with alcohol misuse represents the severe end of the clinical and occupational consequences of sustained alcohol misuse. This article aims to explore the diagnosis, management and occupational considerations of alcohol dependence in the Naval Service environment.
Núñez-Jaramillo, Luis; Vega-Perera, Paulo; Ramírez-Lugo, Leticia; Reyes-López, Julián V; Santiago-Rodríguez, Efraín; Herrera-Morales, Wendy V
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.
Chung, Daehwan; Verbeke, Tobin J; Cross, Karissa L; Westpheling, Janet; Elkins, James G
Compounds such as furfural and 5-hydroxymethylfurfural (5-HMF) are generated through the dehydration of xylose and glucose, respectively, during dilute-acid pretreatment of lignocellulosic biomass and are also potent microbial growth and fermentation inhibitors. The enzymatic reduction of these furan aldehydes to their corresponding, and less toxic, alcohols is an engineering approach that has been successfully implemented in both Saccharomyces cerevisiae and ethanologenic Escherichia coli, but has not yet been investigated in thermophiles relevant to biofuel production through consolidated bioprocessing (CBP). Developing CBP-relevant biocatalysts that are either naturally resistant to such inhibitors, or are amenable to engineered resistance, is therefore, an important component in making biofuels production from lignocellulosic biomass feasible. A butanol dehydrogenase encoding gene from Thermoanaerobacter pseudethanolicus 39E (Teth39_1597), previously shown to have furfural and 5-HMF reducing capabilities, was cloned into a suicide plasmid, pDCW171 and transformed into a lactate dehydrogenase mutant of Caldicellulosiruptor bescii. Integration of the gene into the C. bescii chromosome was verified via PCR amplification and stable expression was observed up to 75°C. Heterologous expression of the NADPH-dependent BdhA enzyme conferred increased resistance of the engineered strain to both furfural and 5-HMF relative to the wild-type and parental strains. Further, when challenged with 15 mM concentrations of either furan aldehyde, the ability to eliminate furfural or 5-HMF from the culture medium was significantly improved in the engineered strain. A genetically engineered strain of C. bescii (JWCB044) has been constructed that shows both an improved tolerance to furan aldehydes and an improved ability to eliminate furfural and 5-HMF from the culture medium. The work presented here represents the first example of engineering furan aldehyde resistance into a CBP
Luo, Xingguang; Kranzler, Henry R; Zuo, Lingjun; Wang, Shuang; Blumberg, Hilary P; Gelernter, Joel
Cholinergic muscarinic 2 receptor (CHRM2) is implicated in memory and cognition, functions impaired in many neuropsychiatric disorders. Wang et al. [Wang, J.C., Hinrichs, A.L., Stock, H., Budde, J., Allen, R., Bertelsen, S., Kwon, J.M., Wu, W., Dick, D.M., Rice, J. et al. (2004) Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum. Mol. Genet., 13, 1903-1911] reported that variation in CHRM2 gene predisposed to alcohol dependence (AD) and major depressive syndrome. We examined the relationships between variation in CHRM2 and AD, drug dependence (DD) and affective disorders, using a novel extended case-control structured association (SA) method. Six markers at CHRM2 and 38 ancestry-informative markers (AIMs) were genotyped in a sample of 871 subjects, including 333 healthy controls [287 European-Americans (EAs) and 46 African-Americans (AAs)] and 538 AD and/or DD subjects (415 with AD and 346 with DD and 382 EAs and 156 AAs). The same CHRM2 markers were genotyped in a sample of 137 EA subjects with affective disorders. All of the six markers were in Hardy-Weinberg equilibrium in controls, but SNP3 (rs1824024) was in Hardy-Weinberg disequilibrium in the AD and DD groups. Using conventional case-control comparisons, some markers were nominally significantly or suggestively associated with phenotypes before or after controlling for population stratification and admixture effects, but these associations were not significant after multiple test correction. However, regression analysis identified specific alleles, genotypes, haplotypes and diplotypes that were significantly associated with risk for each disorder. We conclude that variation in CHRM2 predisposes to AD, DD and affective disorders. One haplotype block within the 5'-UTR of CHRM2 may be more important for the development of these disorders than other regions. Interaction between two
Heyser, Charles J.
Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence have identified specific neurotransmitter targets for the development of pharmacological treatments. Acamprosate, marketed under the brand name Campral, is an orally administered drug available by prescription in the U.S. and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in numerous clinical trials worldwide. Here we provide an overview of acamprosate in the context of the neurobiological underpinnings of alcohol dependence. We propose that unlike previously available pharmacotherapies, acamprosate represents a prototype of a neuromodulatory approach in the treatment of alcohol dependence. A neuromodulatory approach seeks to restore the disrupted changes in neurobiology resulting from chronic alcohol intake. It is our opinion that a neuromodulatory approach will provide a heuristic framework for developing more effective pharmacotherapies for alcohol dependence. PMID:20201812
Samokhvalov, Andriy V.; Popova, Svetlana; Room, Robin; Ramonas, Milita; Rehm, Jürgen
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
Shukla, Lekhansh; Shukla, Tulika; Bokka, Spandana; Kandasamy, Arun; Benegal, Vivek; Murthy, Pratima; Chand, Prabhat
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
Terranova, Claudio; Tucci, Marianna; Sartore, Daniela; Cavarzeran, Fabiano; Di Pietra, Laura; Barzon, Luisa; Palù, Giorgio; Ferrara, Santo D
The aim of this study was to analyze the connection between alcohol dependence and criminal behavior by an integrated genetic-environmental approach. The research, structured as a case-control study, examined 186 alcohol-dependent males; group 1 (N = 47 convicted subjects) was compared with group 2 (N = 139 no previous criminal records). Genetic results were innovative, highlighting differences in genotype distribution (p = 0.0067) in group 1 for single-nucleotide polymorphism rs 3780428, located in the intronic region of subunit 2 of the GABA B receptor gene (GABBR2). Some environmental factors (e.g., grade repetition) were associated with criminal behavior; others (e.g., attendance at Alcoholics Anonymous) were inversely related to convictions. The concomitant presence of the genetic and environmental factors found to be associated with the condition of alcohol-dependent inmate showed a 4-fold increase in the risk of antisocial behavior. The results need to be replicated on a larger population to develop new preventive and therapeutic proposals.
Cáceres Anillo, David; Ana Rodriguez, Yuste; Morillo Velarde, Carlos; Cabrera Gisbert, Ma Victoria
The aim is to determine the effect of the treatment with venlafaxine extended release in patients with alcohol or cocaine dependence disorder that initiate detoxification treatment. Observational, open, prospective study carried out in Spain in 2005. 55 patients older than 18 years of age with diagnosis of alcohol and/or cocaine dependence disorder, hospitalized in Specialty Care Center to initiate detoxification treatment, were included. Daily doses of 75 to 225 mg of venlafaxine extended release were administered for 6 months. Treatment was associated with significant reductions in EuropASI scores in the following areas: 3, alcohol use, baseline and final score of 8.2 +/- 0.2 and 6.4 +/- 0.4, respectively (P < 0.01); 5, family/social relations, initial score of 6.9 +/- 0.2 and of 5.2 +/- 0.5 at endpoint (P < 0.001); 1, medical status, scores of 3.7 +/- 0.4 and 0.9 +/- 0.3 (baseline and final visits, respectively) (P < 0.001); and 6, psychiatric status, with a baseline score of 7.8 +/- 0.1 and final score of 5.4 +/- 0.4 (P < 0.001). The VAS alcohol craving scores at baseline were 26.7 +/- 4.6, decreasing to 4.1 +/- 1.5 at endpoint (P < 0.001). The results of this observational study suggest that venlafaxine extended release could be effective as a coadyuvant in the treatment of alcohol dependent patients in alcohol detoxification therapy. Nevertheless, this should be confirmed with bigger placebo-controlled samples.
Crews, Fulton T; Buckley, Tracey; Dodd, Peter R; Ende, Gabriele; Foley, Nina; Harper, Clive; He, Jun; Innes, David; Loh, El-Wui; Pfefferbaum, Adolph; Zou, Jian; Sullivan, Edith V
This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of
Chung, Daehwan; Verbeke, Tobin J.; Cross, Karissa L.; ...
Compounds such as furfural and 5-hydroxymethylfurfural (5-HMF) are generated through the dehydration of xylose and glucose, respectively, during dilute-acid pretreatment of lignocellulosic biomass and are also potent microbial growth and fermentation inhibitors. The enzymatic reduction of these furan aldehydes to their corresponding, and less toxic, alcohols is an engineering approach that has been successfully implemented in both Saccharomyces cerevisiae and ethanologenicEscherichia coli, but has not yet been investigated in thermophiles relevant to biofuel production through consolidated bioprocessing (CBP). Developing CBP-relevant biocatalysts that are either naturally resistant to such inhibitors, or are amenable to engineered resistance, is therefore, an important componentmore » in making biofuels production from lignocellulosic biomass feasible.« less
Chung, Daehwan; Verbeke, Tobin J.; Cross, Karissa L.; Westpheling, Janet; Elkins, James G.
Compounds such as furfural and 5-hydroxymethylfurfural (5-HMF) are generated through the dehydration of xylose and glucose, respectively, during dilute-acid pretreatment of lignocellulosic biomass and are also potent microbial growth and fermentation inhibitors. The enzymatic reduction of these furan aldehydes to their corresponding, and less toxic, alcohols is an engineering approach that has been successfully implemented in both Saccharomyces cerevisiae and ethanologenicEscherichia coli, but has not yet been investigated in thermophiles relevant to biofuel production through consolidated bioprocessing (CBP). Developing CBP-relevant biocatalysts that are either naturally resistant to such inhibitors, or are amenable to engineered resistance, is therefore, an important component in making biofuels production from lignocellulosic biomass feasible.
McHugh, R Kathryn; Kaufman, Julia S; Frost, Katherine H; Fitzmaurice, Garrett M; Weiss, Roger D
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. 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 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. 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.
Trudell, James R.; Messing, Robert O.; Mayfield, Jody; Harris, R. Adron
Alcohol dependence is a complex condition with clear genetic factors. Some of the leading candidate genes code for subunits of the inhibitory GABAA and glycine receptors. These and related ion channels are also targets for the acute actions of alcohol, and there is considerable progress in understanding interactions of alcohol with these proteins at the molecular and even atomic levels. X-ray structures of open and closed states of ion channels combined with structural modeling and site-directed mutagenesis have elucidated direct actions of alcohol. Alcohol also alters channel function by translational and post-translational mechanisms, including phosphorylation and protein trafficking. Construction of mutant mice with either deletion of key proteins or introduction of alcohol-resistant channels has further linked specific proteins with discrete behavioral effects of alcohol. A combination of approaches, including genome wide association studies in humans, continues to advance the molecular basis of alcohol action on receptor structure and function. PMID:24865944
Thompson, A; Owens, L; Pushpakom, S P; Faizal, M; Pirmohamed, M
Alcohol dependence is a common disorder in many societies worldwide, and remains difficult to identify and treat. It is also a risk factor for many secondary non-communicable diseases. Pharmacotherapy is one available treatment option, but appears to be underutilised in practice. Major barriers to use of medications in this area include lack of clinical guidance and questionable efficacy. However, for each medication there appears to be a subpopulation that responds positively, and understanding the moderating factors to treatment efficacy is an important research goal. Thus, this review provides a narrative regarding potential stratification techniques in pharmacological treatment of alcohol dependence, with a specific focus on typologies and pharmacogenetics. In addition, we discuss the basic background of stratified medicine and recent studies on genetic predisposition to alcohol dependence. A growing repository of data exists for both approved and non-approved pharmacotherapies, but failure to replicate findings, inadequate sample sizes, and insufficient funding has resulted in a translational gap. Implementing evidence-based stratified/personalised therapy and identifying new therapeutic agents may lead to improved clinical outcomes and reduced financial burden. Despite some promising findings to date, much work is still required. Copyright © 2015 Elsevier Inc. All rights reserved.
Tikka, Deyashini Lahiri; Ram, Daya; Dubey, Indu; Tikka, Sai Krishna
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
de Timary, Philippe; Cani, Patrice D; Duchemin, Julie; Neyrinck, Audrey M; Gihousse, Dominique; Laterre, Pierre-François; Badaoui, Abdenor; Leclercq, Sophie; Delzenne, Nathalie M; Stärkel, Peter
Most physiological studies interested in alcohol-dependence examined ethanol as a pharmacological agent rather than a nutrient. We conducted two studies, which assessed the metabolic and endocrine factors involved in the regulation of alcohol and nutrient intake in alcohol-dependent (AD) subjects. We also examined the potential role of a disruption in energy balance in alcohol-dependence. In Study-1, quantitative dietetic interviews of eating and drinking habits were conducted with 97 AD subjects. The population was split around a median alcohol intake value of 12.5 kcal/kg/day. The results showed that the "low alcohol" drinking AD subjects had high Body Mass Index (BMI) and Fat Mass (FM) and alcohol intake was compensated for by a decrease in non-alcoholic intakes. "High alcohol" drinking AD subjects, on the other hand, had low BMI and FM and the total caloric intakes were largely above norms. In Study-2, 24 AD inpatients were submitted to dietetic interviews, calorimetry and blood samplings for the measurement of biomarkers of the regulation of metabolism and satiety, on day 2, 5 and 16 of abstinence. These patients were compared with 20 controls matched for age and gender. We observed in AD patients an increase in cortisol, leptin and PYY plasma levels and a decrease in ghrelin, which might explain the observed decrease in non-alcoholic intakes. However, alcoholic and non-alcoholic intakes correlated positively with basal metabolism and negatively with leptin and leptin/BMI. For individuals consuming below 12.5 kcal/kg/day of alcohol, alcohol intake is compensated for by a decrease in non-alcoholic nutrient intakes, probably due to changes in metabolic and satiety factors. For individuals consuming above 12.5 kcal/kg/day of alcohol, alcohol accelerates metabolism and decreases fat mass and leptin levels, and the total caloric intake largely exceeds norms. A dual model for regulation of energy intake in AD subjects is proposed.
Marshall, Vanessa J.; Kalu, Nnenna; Kwagyan, John; Scott, Denise M.; Cain, Gloria E.; Hill, Karen; Hesselbrock, Victor; Ferguson, Clifford L.; Taylor, Robert E.
Objective Ethnic and cultural differences in patterns of alcohol use disorders must be understood in order to address improvement in prevention of such disorders and accessibility to health care services. The purpose of this study was to evaluate factors that influence the utilization of medical and mental health services among alcohol-dependent and non alcohol–dependent African Americans. Method A cohort of 454 African Americans was evaluated. Alcohol-dependent participants were recruited from various inpatient treatment facilities in the Washington, DC, metropolitan area and through advertisement and word of mouth. Non–alcohol-dependent participants were recruited by advertisements. Each participant was administered the Semi-Structured Assessment for the Genetics of Alcoholism to assess alcohol dependency and the Family History Assessment module to access family history of alcoholism. χ2 Test and analysis of variance were used to analyze the data. Results Alcohol dependence was more prevalent among men, those with lower income, those with less education, and they utilized mental health counseling as opposed to medical-based therapy. Increased reports of medical conditions such as migraine (p < .001), loss of consciousness (p = .001), and sexually transmitted diseases (p < .001) were also associated with alcohol dependency. Other factors, including visits to inpatient treatment programs, were directly related to incidence of alcohol dependency regardless of gender status (p < .001). Conclusions This study suggests an association exists among alcohol dependence, medical conditions, health care, and mental care utilization among African Americans. Future research may benefit from investigating if an association exists between alcohol use disorders and health care utilization for other ethnic groups. PMID:23862295
Pilowsky, Daniel J; Keyes, Katherine M; Hasin, Deborah S
We sought to study the association between adverse events occurring in childhood and adolescence and lifetime alcohol dependence in a representative sample of American adults. With data from the National Epidemiologic Survey on Alcohol and Related Conditions, we conducted logistic regression multivariate analyses to examine the impact of adverse events occurring in childhood (aged < 18 years) on the lifetime prevalence of alcohol dependence. We controlled for age at drinking onset, binge drinking, alcoholism in parents and grandparents of respondents, and demographic characteristics. Adverse childhood events were associated with familial alcoholism and with early and binge drinking, and therefore, we controlled for these potential confounders. Experiencing 2 or more adverse childhood events, compared with none, significantly increased the risk for alcohol dependence, even after we controlled for sociodemographic variables and disorder-specific potential confounders not considered in the extant literature (adjusted odds ratio = 1.37; 95% confidence interval = 1.06, 1.77). Individuals who experienced 2 or more adverse childhood events are at increased risk for lifetime alcohol dependence. A better understanding of the factors underlying the risk for alcohol dependence is important for developing better prevention and early intervention measures.
Dickter, Cheryl L.; Forestell, Catherine A.; Hammett, Patrick J.; Young, Chelsie M.
Rationale Previous work has indicated that implicit attentional biases to alcohol-related cues are indicative of susceptibility to alcohol dependence and escape drinking, or drinking to avoid dysphoric mood or emotions. Objective The goal of the current study was to examine whether alcohol dependence and escape drinking were associated with early neural attentional biases to alcohol cues. Methods EEG data were recorded from 54 college students who reported that they regularly drank alcohol, while they viewed alcohol and control pictures that contained human content (active) or no human content (inactive). Results Those who were alcohol dependent showed more neural attentional bias to the active alcohol-related stimuli than to the matched control stimuli early in processing, as indicated by N1 amplitude. Escape drinkers showed greater neural attention to the active alcohol cues than non-escape drinkers, as measured by larger N2 amplitudes. Conclusions While alcohol dependence is associated with enhanced automatic attentional biases early in processing, escape drinking is associated with more controlled attentional biases to active alcohol cues during a relatively later stage in processing. These findings reveal important information about the time-course of attentional processing in problem drinkers and have important implications for addiction models and treatment. PMID:24292342
Gilpin, Nicholas W; Koob, George F
Alcoholism is a debilitating disorder for the individual and very costly for society. A major goal of alcohol research is to understand the neural underpinnings associated with the transition from alcohol use to alcohol dependence. Positive reinforcement is important in the early stages of alcohol use and abuse. Negative reinforcement can be important early in alcohol use by people self-medicating coexisting affective disorders, but its role likely increases following the transition to dependence. Chronic exposure to alcohol induces changes in neural circuits that control motivational processes, including arousal, reward, and stress. These changes affect systems utilizing the signaling molecules dopamine, opioid peptides, γ-aminobutyric acid, glutamate, and serotonin, as well as systems modulating the brain's stress response. These neuroadaptations produce changes in sensitivity to alcohol's effects following repeated exposure (i.e., sensitization and tolerance) and a withdrawal state following discontinuation of alcohol use. Chronic alcohol exposure also results in persistent neural deficits, some of which may fully recover following extended periods of abstinence. However, the organism remains susceptible to relapse, even after long periods of abstinence. Recent research focusing on brain arousal, reward, and stress systems is accelerating our understanding of the components of alcohol dependence and contributing to the development of new treatment strategies.
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
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. Published by Elsevier Inc.
Vendruscolo, Leandro F.; Barbier, Estelle; Schlosburg, Joel E.; Misra, Kaushik K.; Whitfield, Timothy W.; Logrip, Marian L.; Rivier, Catherine; Repunte-Canonigo, Vez; Zorrilla, Eric P.; Sanna, Pietro P.; Heilig, Markus; Koob, George F.
Alcoholism is characterized by a compulsion to seek and ingest alcohol, loss of control over intake, and the emergence of a negative emotional state during abstinence. We hypothesized that sustained activation of neuroendocrine stress systems (e.g., corticosteroid release via the hypothalamic-pituitary-adrenal [HPA] axis) by alcohol intoxication and withdrawal and consequent alterations in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation drive compulsive alcohol drinking. Our results showed that rats exposed to alcohol vapor to the point of dependence displayed increased alcohol intake, compulsive drinking measured by progressive-ratio responding, and persistent alcohol consumption despite punishment, assessed by adding quinine to the alcohol solution, compared with control rats that were not exposed to alcohol vapor. No group differences were observed in the self-administration of saccharin-sweetened water. Acute alcohol withdrawal was accompanied by downregulated GR mRNA in various stress/reward-related brain regions (i.e., prefrontal cortex, nucleus accumbens [NAc], and bed nucleus of the stria terminalis [BNST]), whereas protracted alcohol abstinence was accompanied by upregulated GR mRNA in the NAc core, ventral BNST, and central nucleus of the amygdala. No significant alterations in MR mRNA levels were found. Chronic GR antagonism with mifepristone (RU38486) prevented the escalation of alcohol intake and compulsive responding induced by chronic, intermittent alcohol vapor exposure. Chronic treatment with mifepristone also blocked escalated alcohol drinking and compulsive responding during protracted abstinence. Thus, the GR system appears to be involved in the development of alcohol dependence and may represent a potential pharmacological target for the treatment of alcoholism. PMID:22649234
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.
Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar
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
Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar
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.
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 nonalcoholic 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
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.
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
Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zalewska, Anna; Zwierz, Krzysztof; Szulc, Agata; Szajda, Sławomir Dariusz
Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, β-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), β-galactosidase (GAL), and β-glucuronidase (GLU), and their applicability as markers of alcohol dependence. The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence). © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.
Beck, Aaron T.; And Others
Administered the Beck Hopelessness Scale to alcoholic (N=20) and heroin-addicted (N=20) women. Results indicated that although both groups expressed comparable levels of overall hopelessness, alcoholic women anticipated more success and better lives in the next 10 years than did the heroin-dependent women. (LLL)
Beck, Aaron T.; And Others
Administered the Beck Hopelessness Scale to alcoholic (N=20) and heroin-addicted (N=20) women. Results indicated that although both groups expressed comparable levels of overall hopelessness, alcoholic women anticipated more success and better lives in the next 10 years than did the heroin-dependent women. (LLL)
Yeh, Mei-Yu; Che, Hui-Lian; Lee, Li-Wei; Horng, Fen-Fang
The purpose of this study was to explore the concepts and processes for successful abstinence from alcohol for Taiwanese Alcoholics Anonymous members. Attempting to identify the psychological and social influences upon alcohol consumption remission outside of alcoholism treatment could help professionals to engage in a broad array of community interventions in an informed fashion. Grounded theory method was utilized in this study. The study chose nine participants who had succeeded in abstinence, using theoretical sampling and conducted in-depth interviews by an open-ended questionnaire. The results of this study indicated that the core of the process during which alcoholic individuals succeeded in abstaining from further alcohol consumption was an empowerment process for the involved individual. Alcoholics felt that their family, interpersonal relationships, jobs and personal finances all had been at 'rock-bottom' level following a long period of alcohol dependence. This feeling caused the individual to experience an emotion of a loss of control and provoked the arousal of an alcoholic's inner consciousness levels, this then resulting in the generation of a driving force for abstinence from alcohol for these individuals. The expansion of an individual's internal awakening power helps the individual to obtain assistance and to resist the temptation of further alcohol consumption. Therefore, the power derived by individuals from the stages of repositioning, releasing, active sharing, resistance and assistance are the maintenance factors for an individual's empowerment process that help maintain the successful recovery from alcohol for the involved individual. A good comprehension of the recovery processes for alcoholics, we believe, will trigger clinical professionals to pay appropriate attention to the specific problems and needs of alcoholic individuals, to build an effective resource network for treatment and to help solve alcoholics' physical and psychosocial
Wall, Tamara L; Carr, Lucinda G; Ehlers, Cindy L
Two alcohol dehydrogenase genes (ADH2 and ADH3 on chromosome 4) and one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional polymorphisms. The goal of this study was to determine whether any associations exist between the ADH2, ADH3, and ALDH2 polymorphisms and alcohol dependence in a group of Native Americans. An additional goal was to determine if any associations exist between these polymorphisms and the endophenotype, maximum number of drinks ever consumed in a 24-hour period. Mission Indian adults (N=340) were recruited for participation from reservations in southern California. Each participant completed an interview with the Semi-Structured Assessment for the Genetics of Alcoholism. A blood sample was collected from each participant for genotyping at the ALDH2, ADH2, and ADH3 loci. Sixty percent of all participants (72% of men and 53% of women) met lifetime DSM-III-R criteria for alcohol dependence. A significant difference in the ADH2 allele distributions was found between alcohol-dependent and non-alcohol-dependent participants. Those with alcohol dependence were significantly less likely to have the ADH2*3 allele (odds ratio=0.28) and significantly more likely to have the ADH2*1 allele (odds ratio=2.00) than those who were not alcohol dependent. Individuals with ADH2*3 reported a lower number of maximum drinks ever consumed in a 24-hour period, compared to those without this allele. These results are consistent with genetic linkage studies showing protective associations for alcohol dependence and related behavior on chromosome 4 and suggest that ADH2 polymorphisms may account for these findings. These results also highlight the utility of evaluating protective factors in populations with high rates of alcohol dependence.
Fucito, Lisa M.; Park, Aesoon; Gulliver, Suzy Bird; Mattson, Margaret E.; Gueorguieva, Ralitza V.; O’Malley, Stephanie S.
Background Identifying factors that modify responsiveness to pharmacotherapies for alcohol dependence is important for treatment planning. Cigarette smoking predicts more severe alcohol dependence and poorer treatment response in general. Nevertheless, there is limited research on cigarette smoking as a potential predictor of differential response to pharmacological treatment of alcoholism. Methods We examined the association between cigarette smoking and drinking outcomes in the COMBINE study, a randomized, double-blind placebo-controlled 16-week trial comparing combinations of medications (i.e., acamprosate and naltrexone) and behavioral interventions (i.e., medical management (MM), combined behavioral therapy (CBI)) in 1383 alcohol dependent individuals. Results Smokers (i.e., more than half the sample) significantly differed from nonsmokers on several demographic and drinking-related variables at baseline and generally had poorer treatment outcomes than nonsmokers. However, smokers who received naltrexone had better drinking outcomes than smokers who received placebo, whereas alcohol use among nonsmokers did not vary by naltrexone assignment. This pattern of findings occurred independent of whether patients received CBI or MM and remained after controlling for alcoholism typology and baseline demographic differences. Approximately 9% of smokers quit smoking and an additional 10% reduced their cigarette intake during treatment. Reductions in smoking did not vary by treatment assignment. Conclusions These results suggest that naltrexone may be particularly beneficial for improving alcohol use outcomes in alcohol dependent smokers. Trial Registration The COMBINE Study, NCT000626, http://www.cscc.unc.edu/combine/. PMID:22541040
Leggio, Lorenzo; Zywiak, William H.; Fricchione, Samuel R.; Edwards, Steven M.; de la Monte, Suzanne M.; Swift, Robert M.; Kenna, George A.
Background There is a need to identify novel pharmacological targets to treat alcoholism. Animal and human studies suggest a role of ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving. Methods This was a double-blind placebo-controlled human laboratory proof-of-concept study. Non-treatment seeking alcohol-dependent heavy drinking individuals were randomized to receive intravenous ghrelin 1mcg/kg, 3 mcg/kg or 0 mcg/kg (placebo), followed by a cuereactivity procedure, during which participants were exposed to neutral (juice) and alcohol cues. The primary outcome variable was the increase in alcohol craving (also called “urge”) for alcohol, assessed by the Alcohol Visual Analogue Scale. Results Out of 103 screenings, 45 individuals received the study drug. Repeated measures of ANCOVA revealed a group effect across ghrelin doses in increasing alcohol craving (p < .05). A dose-specific examination revealed a significant effect of ghrelin 3 mcg/kg vs. placebo in increasing alcohol craving (p < .05) with a large effect size (d = .94). By contrast, no significant ghrelin effect was found in increasing either urge to drink juice or food craving (p: n.s.). No significant differences in side effects were found (p: n.s.). Conclusions Intravenous administration of exogenous ghrelin increased alcohol craving in alcohol-dependent heavy drinking individuals. Although the small sample requires confirmatory studies, these findings provide preliminary evidence that ghrelin may play a role in the neurobiology of alcohol craving, thus demonstrating a novel pharmacological target for treatment. PMID:24775991
Arria, Amelia M.; Caldeira, Kimberly M.; Kasperski, Sarah J.; Vincent, Kathryn B.; Griffiths, Roland R.; O'Grady, Kevin E.
Background Energy drinks are highly caffeinated beverages that are increasingly consumed by young adults. Prior research has established associations between energy drink use and heavier drinking and alcohol-related problems among college students. This study investigated the extent to which energy drink use might pose additional risk for alcohol dependence over and above that from known risk factors. Methods Data were collected via personal interview from 1,097 fourth-year college students sampled from one large public university as part of an ongoing longitudinal study. Alcohol dependence was measured with DSM-IV criteria. Results After adjustment for the sampling design, 51.3%wt of students were classified as “low-frequency” energy drink users (1 to 51 days in the past year) and 10.1%wt as “high-frequency” users (≥52 days). Typical caffeine consumption varied widely depending on the brand consumed. Compared to the low-frequency group, high-frequency users drank alcohol more frequently (141.6 vs. 103.1 days) and in higher quantities (6.15 vs. 4.64 drinks/typical drinking day). High-frequency users were at significantly greater risk for alcohol dependence relative to both non-users (AOR=2.40, 95% CI=1.27-4.56, p=.007) and low-frequency users (AOR=1.86, 95% CI=1.10, 3.14, p=.020), even after holding constant demographics, typical alcohol consumption, fraternity/sorority involvement, depressive symptoms, parental history of alcohol/drug problems, and childhood conduct problems. Low-frequency energy drink users did not differ from non-users on their risk for alcohol dependence. Conclusions Weekly or daily energy drink consumption is strongly associated with alcohol dependence. Further research is warranted to understand the possible mechanisms underlying this association. College students who frequently consume energy drinks represent an important target population for alcohol prevention. PMID:21073486
Vendruscolo, Leandro F.; Estey, David; Goodell, Vivian; Macshane, Lauren G.; Logrip, Marian L.; Schlosburg, Joel E.; McGinn, M. Adrienne; Zamora-Martinez, Eva R.; Belanoff, Joseph K.; Hunt, Hazel J.; Sanna, Pietro P.; George, Olivier; Koob, George F.; Edwards, Scott; Mason, Barbara J.
Alcoholism, or alcohol use disorder, is a major public health concern that is a considerable risk factor for morbidity and disability; therefore, effective treatments are urgently needed. Here, we demonstrated that the glucocorticoid receptor (GR) antagonist mifepristone reduces alcohol intake in alcohol-dependent rats but not in nondependent animals. Both systemic delivery and direct administration into the central nucleus of the amygdala, a critical stress-related brain region, were sufficient to reduce alcohol consumption in dependent animals. We also tested the use of mifepristone in 56 alcohol-dependent human subjects as part of a double-blind clinical and laboratory-based study. Relative to placebo, individuals who received mifepristone (600 mg daily taken orally for 1 week) exhibited a substantial reduction in alcohol-cued craving in the laboratory, and naturalistic measures revealed reduced alcohol consumption during the 1-week treatment phase and 1-week post-treatment phase in mifepristone-treated individuals. Mifepristone was well tolerated and improved liver-function markers. Together, these results support further exploration of GR antagonism via mifepristone as a therapeutic strategy for alcoholism. PMID:26121746
Farris, Sean P.; Pietrzykowski, Andrzej Z.; Miles, Michael F.; O'Brien, Megan A.; Sanna, Pietro P.; Zakhari, Samir; Mayfield, R. Dayne; Harris, R. Adron
This review summarizes the proceedings of a symposium presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference held in Volterra, Italy on May 6–9, 2014. The overall goal of the symposium titled “Applying the New Genomics to Alcohol Dependence,” chaired by Dr. Adron Harris, was to highlight recent genomic discoveries and applications for profiling alcohol use disorder (AUD). Dr. Sean Farris discussed the gene expression networks related to lifetime consumption of alcohol within human prefrontal cortex. Dr. Andrzej Pietrzykowski presented the effects of alcohol on microRNAs in humans and animal models. Alcohol-induced alterations in the synaptic transcriptome were discussed by Dr. Michael Miles. Dr. Pietro Sanna examined methods to probe the gene regulatory networks that drive excessive alcohol drinking, and Dr. Samir Zakhari served as a panel discussant and summarized the proceedings. Collectively, the presentations emphasized the power of integrating multiple levels of genetics and transcriptomics with convergent biological processes and phenotypic behaviors to determine causal factors of AUD. The combined use of diverse data types demonstrates how unique approaches and applications can help categorize genetic complexities into relevant biological networks using a systems-level model of disease. PMID:25896098
Gorini, Giorgio; Roberts, Amanda J.; Mayfield, R. Dayne
Alcohol abuse causes dramatic neuroadaptations in the brain, which contribute to tolerance, dependence, and behavioral modifications. Previous proteomic studies in human alcoholics and animal models have identified candidate alcoholism-related proteins. However, recent evidences suggest that alcohol dependence is caused by changes in co-regulation that are invisible to single protein-based analysis. Here, we analyze global proteomics data to integrate differential expression, co-expression networks, and gene annotations to unveil key neurobiological rearrangements associated with the transition to alcohol dependence modeled by a Chronic Intermittent Ethanol (CIE), two-bottle choice (2BC) paradigm. We analyzed cerebral cortices (CTX) and midbrains (MB) from male C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and represents one of the best available animal models for alcohol dependence and relapse drinking. CIE induced significant changes in protein levels in dependent mice compared with their non-dependent controls. Multiple protein isoforms showed region-specific differential regulation as a result of post-translational modifications. Our integrative analysis identified modules of co-expressed proteins that were highly correlated with CIE treatment. We found that modules most related to the effects of CIE treatment coordinate molecular imbalances in endocytic- and energy-related pathways, with specific proteins involved, such as dynamin-1. The qRT-PCR experiments validated both differential and co-expression analyses, and the correspondence among our data and previous genomic and proteomic studies in humans and rodents substantiates our findings. The changes identified above may play a key role in the escalation of ethanol consumption associated with dependence. Our approach to alcohol addiction will advance knowledge of brain remodeling mechanisms and adaptive changes in response to drug abuse, contribute to understanding of
Heberlein, Annemarie; Leggio, Lorenzo; Stichtenoth, Dirk; Hillemacher, Thomas
This article addresses the question of 'best treatment options', which clinicians face when treating pregnant women with alcohol and opioid dependence. Studies show that alcohol consumption is associated with fetal abnormalities and long-term cognitive problems depending on the amount consumed, drinking pattern, and time of gestation. Screening and evaluation of specific interventions are important to reduce alcohol consumption during pregnancy and associated problems in infants. Opioid detoxification is only recommended beyond the first trimester and only in those pregnant women who refuse opioid maintenance therapy. Methadone is the most established treatment of pregnant opioid-dependent women, though recent results indicate some advantages of buprenorphine, slow-release oral methadone and diamorphine compared with methadone. Benzodiazepines seem to be the most recommendable option for managing alcohol withdrawal, and psychosocial interventions succeed in reducing alcohol consumption or in maintaining abstinence in alcohol-dependent pregnant women. Regarding opioid dependence, current results suggest that factors like the health status of the mother, the need for additional medications (e.g. treatment for HIV), comorbid drug dependence, and concurrent drug use need to be considered in order to find the 'best opioid substitute'.
Field, Matt; Di Lemma, Lisa; Christiansen, Paul; Dickson, Joanne
Alcohol dependence is characterized by conflict between approach and avoidance motivational orientations for alcohol that operate in automatic and controlled processes. This article describes the first study to investigate the predictive validity of these motivational orientations for relapse to drinking after discharge from alcohol detoxification treatment in alcohol-dependent patients. One hundred twenty alcohol-dependent patients who were nearing the end of inpatient detoxification treatment completed measures of self-reported (Approach and Avoidance of Alcohol Questionnaire; AAAQ) and automatic (modified Stimulus-Response Compatibility task) approach and avoidance motivational orientations for alcohol. Their drinking behavior was assessed via telephone follow-ups at 2, 4, and 6 months after discharge from treatment. Results indicated that, after controlling for the severity of alcohol dependence, strong automatic avoidance tendencies for alcohol cues were predictive of higher percentage of heavy drinking days (PHDD) at 4-month (β = 0.22, 95% CI [0.07, 0.43]) and 6-month (β = 0.22, 95% CI [0.01, 0.42]) follow-ups. We failed to replicate previous demonstrations of the predictive validity of approach subscales of the AAAQ for relapse to drinking, and there were no significant predictors of PHDD at 2-month follow-up. In conclusion, strong automatic avoidance tendencies predicted relapse to drinking after inpatient detoxification treatment, but automatic approach tendencies and self-reported approach and avoidance tendencies were not predictive in this study. Our results extend previous findings and help to resolve ambiguities with earlier studies that investigated the roles of automatic and controlled cognitive processes in recovery from alcohol dependence. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Alcohol dependence is characterized by conflict between approach and avoidance motivational orientations for alcohol that operate in automatic and controlled processes. This article describes the first study to investigate the predictive validity of these motivational orientations for relapse to drinking after discharge from alcohol detoxification treatment in alcohol-dependent patients. One hundred twenty alcohol-dependent patients who were nearing the end of inpatient detoxification treatment completed measures of self-reported (Approach and Avoidance of Alcohol Questionnaire; AAAQ) and automatic (modified Stimulus-Response Compatibility task) approach and avoidance motivational orientations for alcohol. Their drinking behavior was assessed via telephone follow-ups at 2, 4, and 6 months after discharge from treatment. Results indicated that, after controlling for the severity of alcohol dependence, strong automatic avoidance tendencies for alcohol cues were predictive of higher percentage of heavy drinking days (PHDD) at 4-month (β = 0.22, 95% CI [0.07, 0.43]) and 6-month (β = 0.22, 95% CI [0.01, 0.42]) follow-ups. We failed to replicate previous demonstrations of the predictive validity of approach subscales of the AAAQ for relapse to drinking, and there were no significant predictors of PHDD at 2-month follow-up. In conclusion, strong automatic avoidance tendencies predicted relapse to drinking after inpatient detoxification treatment, but automatic approach tendencies and self-reported approach and avoidance tendencies were not predictive in this study. Our results extend previous findings and help to resolve ambiguities with earlier studies that investigated the roles of automatic and controlled cognitive processes in recovery from alcohol dependence. PMID:27935726
CENGİSİZ, Cengiz; DEVECİ, Artuner; YAPICI, Aslıhan
Introduction Treatment motivation in alcohol dependents is usually viewed as a strong predictor of seeking treatment and treatment success. The conditions affecting motivation in alcohol dependence, however, has not been clarified. In this study, it is aimed to determine the effects of depression on treatment motivation in male alcohol dependence. Methods The present study included 34 male alcohol dependents presenting to outpatient clinics in Manisa Hospital of Mental Disorders and Hospital of Celal Bayar University. The patients underwent evaluation using the socio-demographic and clinical information form, DSM-IV SCID-I Clinical Version, Treatment Motivation Questionnaire (TMQ), and Hamilton Depression Rating Scale (HDRS). Results A significant relationship was found between the total score of TMQ and HDRS (p=.039). Conclusion We believe that the present study, in which we examined the relationship between treatment motivation in male alcohol dependence and depression, would provide a significant contribution to literature. It is also important to investigate other factors that may affect treatment motivation in male alcohol dependence. Studies with larger samples are needed on this topic.
Mohagheghi, Arash; Amiri, Shahrokh; Mousavi Rizi, Seyedreza; Safikhanlou, Salman
Objective. Emotional intelligence might play an important role in the onset and persistence of different psychopathologies. This study investigated the relationship between emotional intelligence and alcohol dependence. Methods. In this case-control study, participants included alcohol dependent individuals and mentally healthy inpatients. Each group consisted of 40 individuals (male/female: 1). The diagnosis was based on the criteria of the DSM-IV-TR using the Structured Clinical Interview for DSM-IV (SCID-IV). All the participants completed Bar-On emotional intelligence test. Results. 20 males and 20 females were included in each group. Mean age of alcohol dependent participants and controls was 31.28 ± 7.82 and 34.93 ± 9.83 years in that order. The analyses showed that the alcohol dependent individuals had a significant difference compared with the control group and received lower scores in empathy, responsibility, impulse control, self-esteem, optimism, emotional consciousness, stress tolerance, autonomy, problem-solving, and total score of emotional intelligence components. Conclusion. Patients with alcohol dependence have deficits in components of emotional intelligence. Identifying and targeted training of the individuals with lower scores in components of emotional intelligence may be effective in prevention of alcohol dependence. PMID:25893214
Gilpin, Nicholas W.; Misra, Kaushik; Herman, Melissa A.; Cruz, Maureen T.; Koob, George F.; Roberto, Marisa
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
Graves, Erin; Goodwin, Lloyd R., Jr.
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…
Graves, Erin; Goodwin, Lloyd R., Jr.
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…
Terranova, Claudio; Tucci, Marianna; Sartore, Daniela; Cavarzeran, Fabiano; Barzon, Luisa; Palù, Giorgio; Ferrara, Santo D
The aim of this study is to propose an innovative approach evaluating the connection between alcohol use disorders and criminal behavior. The research, structured as a case-control study, was based on the analysis of environmental (social variables) and genetic factors (single nucleotide polymorphisms of glutamic acid decarboxylase) in a population (N = 173) of Italian alcohol-dependent men. Group 1 (N = 47, convicted subjects) was compared with Group 2 (N = 126, no previous criminal conduct). Grade repetition, work problems, and drug problems were statistically associated with criminal behavior. Having daily family meals together and having children were inversely related to convictions. The genotype distribution of the two groups was similar. The association between environmental factors and antisocial behavior confirms previous findings in the literature. The lack of genetic association does not exclude the role of the gamma-aminobutyric acid (GABA) system in determining antisocial behavior; further studies with larger samples are needed, together with investigation of other components of the GABA pathway.
Evren, Cuneyt; Sar, Vedat; Karadag, Figen; Tamar Gurol, Defne; Karagoz, Mustafa
The aim of this study was to determine the prevalence of dissociative disorders among inpatients with alcohol dependency. The Dissociative Experiences Scale was used to screen 111 alcohol-dependent patients consecutively admitted to the inpatient unit of a dependency treatment center. Subgroups of 29 patients who scored 30.0 or above and 25 patients who scored below 10.0 were then evaluated with the Dissociative Disorders Interview Schedule and the Structured Interview for DSM-IV Dissociative Disorders. The interviewers were blind to the Dissociative Experiences Scale scores. Of the 54 patients evaluated, 10 (9.0% of the original 111) patients had a dissociative disorder. A considerable number of the remaining patients reported a high level of dissociative experiences. Among the dissociative disorder group, nine patients had dissociative disorder not otherwise specified and one patient had depersonalization disorder. Female gender, younger age, history of suicide attempt, childhood emotional and sexual abuse, and neglect were more frequent in the dissociative disorder group than among non-dissociative patients. The dissociative disorder group also had somatization disorder, borderline personality disorder, and lifetime major depression more frequently. For 9 of the 10 dissociative patients, dissociative symptoms started before the onset of alcohol use. Although the probability of having a comorbid dissociative disorder was not higher among alcohol-dependent inpatients than among the general psychiatric inpatients, the dissociative subgroup had distinct features. Many patients without a dissociative disorder diagnosis (predominantly men) provided hints of subtle dissociative psychopathology. Implications of comorbid dissociative disorders and dissociative experiences on prevention and treatment of alcohol dependency and the importance of gender-specific characteristics in this relationship require further study.
de Timary, Philippe; Cani, Patrice D.; Duchemin, Julie; Neyrinck, Audrey M.; Gihousse, Dominique; Laterre, Pierre-François; Badaoui, Abdenor; Leclercq, Sophie
Background Most physiological studies interested in alcohol-dependence examined ethanol as a pharmacological agent rather than a nutrient. We conducted two studies, which assessed the metabolic and endocrine factors involved in the regulation of alcohol and nutrient intake in alcohol-dependent (AD) subjects. We also examined the potential role of a disruption in energy balance in alcohol-dependence. Methods and Results In Study-1, quantitative dietetic interviews of eating and drinking habits were conducted with 97 AD subjects. The population was split around a median alcohol intake value of 12.5 kcal/kg/day. The results showed that the “low alcohol” drinking AD subjects had high Body Mass Index (BMI) and Fat Mass (FM) and alcohol intake was compensated for by a decrease in non-alcoholic intakes. “High alcohol” drinking AD subjects, on the other hand, had low BMI and FM and the total caloric intakes were largely above norms. In Study-2, 24 AD inpatients were submitted to dietetic interviews, calorimetry and blood samplings for the measurement of biomarkers of the regulation of metabolism and satiety, on day 2, 5 and 16 of abstinence. These patients were compared with 20 controls matched for age and gender. We observed in AD patients an increase in cortisol, leptin and PYY plasma levels and a decrease in ghrelin, which might explain the observed decrease in non-alcoholic intakes. However, alcoholic and non-alcoholic intakes correlated positively with basal metabolism and negatively with leptin and leptin/BMI. Conclusion For individuals consuming below12.5 kcal/kg/day of alcohol, alcohol intake is compensated for by a decrease in non-alcoholic nutrient intakes, probably due to changes in metabolic and satiety factors. For individuals consuming above 12.5 kcal/kg/day of alcohol, alcohol accelerates metabolism and decreases fat mass and leptin levels, and the total caloric intake largely exceeds norms. A dual model for regulation of energy intake in AD subjects
Griffin, William C.
Alcohol dependence continues to be an important health concern and animal models are critical to furthering our understanding of this complex disease. A hallmark feature of alcoholism is a significant increase in alcohol drinking over time. While several different animal models of excessive alcohol (ethanol) drinking exist for mice and rats, a growing number of laboratories are using a model that combines chronic ethanol exposure procedures with voluntary ethanol drinking with mice as experimental subjects. Primarily, these studies use a chronic intermittent ethanol (CIE) exposure pattern to render mice dependent and a 2-h limited access procedure to evaluate drinking behavior. Compared to non-dependent mice that also drink ethanol, the ethanol-dependent mice demonstrate significant increases in voluntary ethanol drinking. The increased drinking significantly elevates blood and brain ethanol concentrations compared to the non-dependent control mice. Studies report that the increased drinking by dependent mice is driven by neuroadaptations in glutamatergic and corticotropin-releasing factor signaling in different brain regions known to be involved in alcohol-related behaviors. The dysregulation of these systems parallels findings in human alcoholics and treatments that demonstrate efficacy in alcoholics can also reduce drinking in this model. Moreover, preclinical findings have informed the development of human clinical trials, further highlighting the translational potential of the model. As a result of these features, the CIE exposure and free-choice drinking model is becoming more widely used and promises to provide more insight into mechanisms of excessive drinking that may be important for developing treatments for human alcoholics. The salient features and possible future considerations for CIE exposure and free-choice drinking in mice are discussed. PMID:24530006
Griffin, William C
Alcohol dependence continues to be an important health concern and animal models are critical to furthering our understanding of this complex disease. A hallmark feature of alcoholism is a significant increase in alcohol drinking over time. While several different animal models of excessive alcohol (ethanol) drinking exist for mice and rats, a growing number of laboratories are using a model that combines chronic ethanol exposure procedures with voluntary ethanol drinking with mice as experimental subjects. Primarily, these studies use a chronic intermittent ethanol (CIE) exposure pattern to render mice dependent and a 2-h limited access procedure to evaluate drinking behavior. Compared to non-dependent mice that also drink ethanol, the ethanol-dependent mice demonstrate significant increases in voluntary ethanol drinking. The increased drinking significantly elevates blood and brain ethanol concentrations compared to the non-dependent control mice. Studies report that the increased drinking by dependent mice is driven by neuroadaptations in glutamatergic and corticotropin-releasing factor signaling in different brain regions known to be involved in alcohol-related behaviors. The dysregulation of these systems parallels findings in human alcoholics and treatments that demonstrate efficacy in alcoholics can also reduce drinking in this model. Moreover, preclinical findings have informed the development of human clinical trials, further highlighting the translational potential of the model. As a result of these features, the CIE exposure and free-choice drinking model is becoming more widely used and promises to provide more insight into mechanisms of excessive drinking that may be important for developing treatments for human alcoholics. The salient features and possible future considerations for CIE exposure and free-choice drinking in mice are discussed.
Opalach, Cezary; Romaszko, Jerzy; Jaracz, Marcin; Kuchta, Robert; Borkowska, Alina; Buciński, Adam
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
Thompson, Ronald G.; Lizardi, Dana; Keyes, Katherine M.; Hasin, Deborah S.
Background This study examined whether the experiences of childhood or adolescent parental divorce/separation and parental alcohol problems affected the likelihood of offspring DSM-IV lifetime alcohol dependence, controlling for parental history of drug, depression, and antisocial behavior problems. Method Data were drawn from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a nationally representative United States survey of 43,093 civilian non-institutionalized participants aged 18 and older, interviewed in person. Logistic regression models were used to calculate the main and interaction effects of childhood or adolescent parental divorce/separation and parental history of alcohol problems on offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Results Childhood or adolescent parental divorce/separation and parental history of alcohol problems were significantly related to offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Experiencing parental divorce/separation during childhood, even in the absence of parental history of alcohol problems, remained a significant predictor of lifetime alcohol dependence. Experiencing both childhood or adolescent parental divorce/separation and parental alcohol problems had a significantly stronger impact on the risk for DSM-IV alcohol dependence than the risk incurred by either parental risk factor alone. Conclusions Further research is needed to better identify the factors that increase the risk for lifetime alcohol dependence among those who experience childhood or adolescent parental divorce/separation. PMID:18757141
Batki, Steven L.; Leontieva, Luba; Dimmock, Jacqueline A.; Ploutz-Snyder, Robert
Background Alcohol use disorders (AUDs) frequently co-occur with and exacerbate schizophrenia, yet the specific relationships between schizophrenia symptoms and alcohol use remain unclear. Methods PANSS scores were correlated with measures of alcohol and other substance use in patients with schizophrenia-spectrum disorders and AUDs entering a trial of monitored naltrexone treatment. Data were analyzed from the first 80 participants; 55% had schizophrenia and 45% had schizoaffective disorder. All had AUDs; 95% had alcohol dependence and 5% alcohol abuse; 34% also had cannabis abuse/dependence and 31% cocaine abuse/dependence. Results PANSS Negative scores were inversely correlated with Addiction Severity Index alcohol composite score, alcohol craving, quality of alcohol “high” (euphoria), and with frequency of cannabis use. An exploratory analysis indicated that the negative symptoms that may most strongly correlate with less alcohol use, craving or euphoria were passive/apathetic social withdrawal, blunted affect, difficulty in abstract thinking, and stereotyped thinking. Higher PANSS Composite scores, indicating the predominance of positive over negative PANSS symptoms, correlated with more alcohol craving and cannabis use. Higher PANSS General scores were associated with more alcohol craving. Conclusions These findings extend previous reports of the association of negative schizophrenia symptoms with less alcohol and substance use to patients with AUDs and indicate that this relationship also includes less alcohol craving and less alcohol euphoria. The findings may also provide some initial evidence that specific negative symptoms may be key to these relationships. PMID:18701256
Collier, Andrew; Watts, Maggie; Ghosh, Sujoy; Rice, Peter; Dewhurst, Neil
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.
Collier, Andrew; Watts, Maggie; Ghosh, Sujoy; Rice, Peter; Dewhurst, Neil
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
Ernst, Lena H; Plichta, Michael M; Dresler, Thomas; Zesewitz, Anna K; Tupak, Sara V; Haeussinger, Florian B; Fischer, Matthias; Polak, Thomas; Fallgatter, Andreas J; Ehlis, Ann-Christine
An approach bias for alcohol stimuli (i.e. faster approach than avoidance reactions) might facilitate relapses in alcohol dependence. Neurobiological models suggest hypersensitivity in the reward system [inter alia nucleus accumbens and orbitofrontal cortex (OFC)] to cause pathologically enhanced approach impulses towards alcohol stimuli. At the same time, in alcohol dependence, these structures are only insufficiently controlled by a hypoactive dorsolateral prefrontal cortex (DLPFC). The present study investigated the cortical aspects of this model with functional near-infrared spectroscopy in 21 alcohol-dependent in-patients and 21 healthy controls (HC; comparable in age, gender and education) during performance of the Approach-Avoidance Task (AAT) for the first time. Complementing previous findings, in reaction times (RTs), patients showed stronger approach preferences for alcohol than non-alcohol stimuli. For non-alcohol stimuli, patients even displayed avoidance preferences. The reversed pattern was found in HC. Group differences in activity of the OFC were identical to those in RTs, revealing patients to assign higher subjective value to approaching alcohol stimuli. In both groups, regulatory activity in the right DLPFC was stronger during avoiding than approaching alcohol pictures. Probable awareness of the behavioural hypotheses due to explicit task instructions and patients' deficient prefrontal function might account for this equally aligned pattern. Results are discussed with regard to recent findings revealing a reduced behavioural approach bias and risk for relapse by applying a retraining version of the AAT. Functional measurements might serve as a method for monitoring the corresponding neurobiological changes and-possibly-predicting the success of such a training.
Rozatkar, Abhijit R.; Kapoor, Abhishek; Sidana, Ajeet; Chavan, Bir Singh
Introduction: Craving is recognized as a formidable barrier in the management of patients with alcohol dependence. Among pharmacological agents that have been used in experimental studies for reduction in craving, baclofen appears to have a significant advantage over other agents. Methodology: The study is retrospective chart review of patients (n = 113) who have been treated with baclofen for alcohol dependence in a tertiary hospital of North India. Baseline assessments included sociodemography, motivation, quantity-frequency of alcohol use, and other alcohol-related clinical parameters. Weekly assessments, for a period of 4 weeks, were extracted from records which included dose of baclofen, craving intensity, and alcohol consumption. Results: The study sample was predominantly male, mean age of 41.49 (±9.75) years, most having a family history of substance use (70.97%), and many reporting binge use pattern in last year (49.46%). Baseline assessment revealed 48.7% of the sample was in precontemplation phase for alcohol use and 70% reported severe and persistent craving. This persistent craving was reported by only 15% of the sample by the end of 4 weeks treatment with baclofen (20–40 mg/day). Thirty-four percent of patients reported continued problematic use of alcohol by the end of 4 weeks. Conclusion: Our clinical experience suggests that baclofen reduces craving and alcohol consumption including in those with poor motivation. The drug causes few side effects and does not add to the intoxication effect of alcohol. Considering that baclofen is safe in those with liver cirrhosis and reduces withdrawal symptoms due to alcohol, a controlled trial comparing it with standard treatment is required. PMID:28163402
Kim, Siekyeong; Im, Sungjin; Lee, Jeonghwan; Lee, Sang-Gu
Alcohol causes damage to the brain and is associated with various functional impairments. However, much of the brain damage can be reversed by abstaining for enough time. This study aims to investigate the patterns and degrees of brain function in abstinent patients with alcohol dependence by using resting-state functional connectivity. 26 male patients with alcohol dependence (alcohol group) and 28 age-matched male healthy volunteers (control group) were recruited from a mental hospital and the community, respectively. Using 3T MRI scan data, the resting-state functional connectivity of the task-negative and task-positive networks was determined and compared between the groups. There were no significant group differences in the resting-state functional connectivity in the default mode or in the salience and sensorimotor networks. Compared with the control group, the alcohol group showed significantly lower functional connectivity in the executive control network, especially in the cingulo-opercular network and, in some regions of interest, the dorsal attention network. This finding suggests that some brain networks do not normalize their functions after abstinence from drinking, and these results may be helpful in future research to investigate the mechanisms for craving alcohol and alcohol relapse prevention.
Kreusch, Fanny; Billieux, Joël; Quertemont, Etienne
The induction of alcohol craving and the cognitive processing of alcohol-related stimuli in alcohol-dependent patients have been reported to compete with inhibitory control and contribute to alcohol relapse. The aim of the present study is to investigate whether the induction of a craving state, using an alcohol cue exposure paradigm, influences response inhibition towards both neutral stimuli and alcohol-related stimuli in alcohol-dependent patients. Thirty-one detoxified alcohol-dependent patients were exposed to either their preferred alcoholic beverage or to a glass of water. They then performed a modified stop signal task, which used alcohol-related words, neutral words and non-words, and a lexical decision as the Go response. The alcohol-cue exposure group reported significantly higher alcohol craving and showed higher percentages of commission errors towards alcohol-related words than the control group. All participants, but especially those of the alcohol-cue exposure group, showed also shorter reaction times when alcohol words were used as targets in go trials. The induction of alcohol craving in detoxified alcohol-dependent patients increases the motivational salience value of alcohol stimuli, leading them to automatically approach alcohol-related cues and therefore impairing response inhibition towards those stimuli. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Copeland, William E.; Magnusson, Åsa; Göransson, Mona; Heilig, Markus A.
Background/Objective This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that that might affect treatment planning. Methods A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. Results The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Conclusion Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. PMID:21193270
Spaeth, Michael; Bleich, Stefan; Hillemacher, Thomas
Motivational interviewing with alcohol-dependent patients Alcohol-dependent patients do not need to be motivated from the outside. They are mostly ambivalent, and the inner voice, which already speaks for change (change talk), is heard through motivational interviewing, carefully strengthened and developed together with the patient. The practitioner has to deal with the human spirit of motivational interviewing and should be able to communicate with empathy, respect, congruence, and openness. The patient's autonomy should always be maintained. Advice is only given upon request. The conversation style is directive-guiding instead of authoritariansteering. OARS and the EPE principle are the motivational interviewing basics, which are consistently applied over 4 processes of motivational interviewing: engaging, focusing, evocing, and planning. The likelihood of change talk increases as soon as discrepancies between life goals and alcohol consumption emerge. An increased rate of change talk makes a change in behavior more likely. If a patient argues against change (sustain talk), one should not confront, but should consistently work with reflections, reframing, and an emphasis on autonomy. Motivational interviewing can be applied in different settings and populations, should be learned by the entire team (best professional guidance) in teamwork, and be subjected to a critical and constant evaluation. Georg Thieme Verlag KG Stuttgart · New York.
Dickson, Joanne M; Gately, Claire; Field, Matt
Alcohol dependence is characterised by motivational conflict (or ambivalence) in controlled cognitive processes, but it is unclear if ambivalence also exists within automatic cognitive processes, and if ambivalence operates between controlled and automatic processes. To investigate ambivalence operating within and between controlled and automatic processes in alcohol dependence. Alcohol-dependent patients who had recently completed inpatient alcohol detoxification (N = 47) and social drinking controls (N = 40) completed unipolar implicit association tests and self-report measures of alcohol approach and avoidance motivation and alcohol outcome expectancies. As predicted, both positive and negative alcohol outcome expectancies were stronger in alcohol-dependent patients compared to controls, indicative of ambivalence. Groups did not differ on implicit alcohol-positive associations, but alcohol-dependent participants had significantly weaker alcohol-negative associations than controls. Regression analyses revealed that implicit negative associations accounted for unique variance in group membership after controlling for alcohol outcome expectancies. Our findings demonstrate that alcohol dependent patients possess weak automatic alcohol-negative associations but not strong automatic alcohol-positive associations, and they suggest the presence of conflict between controlled and automatic processes with regard to negative alcohol cognitions.
Martins-Oliveira, Juliana Gabrielle; Jorge, Kelly Oliva; Ferreira, Raquel Conceição; Ferreira, Efigênia Ferreira E; Vale, Míriam Pimenta; Zarzar, Patrícia Maria
The present study evaluated the possible alcohol dependence and related problems among adolescents and determined possible associations with socioeconomic factors and gender. A cross-sectional study was conducted with a representative sample of 936 adolescents aged 15 to 19 years enrolled at public and private schools in the city of Belo Horizonte, Brazil. Data related to alcohol consumption and associated problems were collected using the Alcohol Use Disorder Identification Test (AUDIT). The Social Vulnerability Index (SVI), mother's schooling and type of school were used to assess socioeconomic factors. Statistical analysis involved the chi-square test (p < 0.05) and Poisson regression. The prevalence of possible dependence was 16.4%, 52.1% reported concern of a family member regarding the adolescent's alcohol consumption. Female adolescents were less likely to exhibit possible dependence in comparison to males. Participants with living in a low vulnerability area were more likely to consume alcohol in comparison to those living in underprivileged areas. The results of the present study demonstrate that possible dependence was significantly associated with the male gender and low social vulnerability.
Martinotti, Giovanni; Di Nicola, Marco; Janiri, Luigi
Dopaminergic agonists and antagonists have both been examined for the treatment of substance abuse with contrasting results. To the best of our knowledge dopamine receptor partial agonists have not been investigated in alcohol use disorders. Thirteen detoxified alcohol-dependent subjects were treated with flexible doses of aripiprazole for 16 weeks. Six patients maintained an alcohol free condition for all the study period. All the subjects experienced a reduction of craving in both OCDS (p < .05) and VAS (p < .05), and a decrease of the SCL-90 General Severity Index (GSI) (p < .05). The data of this pilot clinical study, suggest a possible role for this drug in the treatment of individuals with alcohol problems.
... 49 Transportation 3 2012-10-01 2012-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required...
... 49 Transportation 3 2014-10-01 2014-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required...
... 49 Transportation 3 2011-10-01 2011-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required...
... 49 Transportation 3 2010-10-01 2010-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required...
... 49 Transportation 3 2013-10-01 2013-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required...
Henderson, Claire; Liu, Xinhua; Diez Roux, Ana V; Link, Bruce G; Hasin, Deborah
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.
Keating, Gillian M
A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients. Sodium oxybate was generally well tolerated. The risk of sodium oxybate abuse is generally low when it is administered to alcohol-dependent patients at its approved dosage, under the supervision of a designated family member and with continuous strict medical surveillance. However, certain patient groups, such as patients with alcohol dependence and borderline personality disorder or who are in remission from heroin or cocaine addiction, may not be suitable candidates for sodium oxybate therapy because of an increased risk of abuse. In conclusion, sodium oxybate is a useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence.
Waszkiewicz, Napoleon; Jelski, Wojciech; Zalewska, Anna; Szulc, Agata; Szmitkowski, Maciej; Zwierz, Krzysztof; Szajda, Sławomir Dariusz
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. Copyright © 2014 Elsevier Inc. All rights reserved.
Sjoerds, Zsuzsika; van den Brink, Wim; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.; Veltman, Dick J.
Introduction With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity. Methods We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels. Results Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation. Conclusion Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes
Riley, A J
Negative attitudes among carers towards people with alcohol-related problems have been reported in many studies. However, few studies have examined whether these attitudes are perceived by patients during face to face contact with healthcare professionals when receiving inpatient treatment. A sample of 26 discharged patients completed a 37-item questionnaire following treatment for alcohol problems. The Likert scale was used to measure whether patients felt that the attitude under investigation existed in the caring environment. The findings indicated that negative attitudes reported in other studies were not perceived by patients during inpatient treatment. Some barriers to treatment effectiveness such as prognostic pessimism were detected by the patients. Many upheld the view that the only goal of treatment adopted by staff was that of total abstinence. There is an increasing need to obtain feedback from patients who have received inpatient care. Greater flexibility and creativity in the care of the alcohol dependent person needs to be explored rather than the maintenance of a prescriptive approach.
Kunitz, S J; Gabriel, K R; Levy, J E; Henderson, E; Lampert, K; McCloskey, J; Quintero, G; Russell, S; Vince, A
The purpose of this study is to examine the association between conduct disorder before age 15 and subsequent alcohol dependence, and to describe the lifetime prevalence of alcohol dependence among Navajo Indian women and men. This was a case-control design which included both men (n = 735) and women (n = 351) and in which the Diagnostic Interview Schedule was used for the diagnosis of the lifetime history of alcohol dependence and conduct disorder. Alcohol dependent cases were selected from inpatient and outpatient treatment programs (204 men, 148 women). Whenever possible, controls were matched for age, sex and community of residence and were randomly selected and interviewed until a nonalcohol dependent individual was found. Among the men, there were 374 alcohol dependent controls and 157 nonalcohol dependent controls. Among the women, the figures were 60 and 143, respectively. When combined, the controls comprise samples of the adult male and female populations from which estimates of lifetime prevalence of alcohol dependence, and of the amount of alcohol dependence in the population attributable to conduct disorder, may be inferred. Conduct disorder is a risk factor for alcohol dependence among both men and women. Lifetime prevalence of alcohol dependence in this population is high (70.4% for men and 29.6% for women), but the amount of alcohol dependence in the population attributable to conduct disorder is low. On the other hand, among the alcohol dependent, those with conduct disorder had the most severe alcohol- and nonalcohol-related problems. The potential limitations of the study are those common to case-control designs, especially biased recall by cases. There are also potential sampling biases among the controls. It is shown that none of the potential biases invalidate the findings, which support the hypothesis that in this population conduct disorder is a risk for alcohol dependence. The implications for primary prevention of alcohol dependence are
Kim, Sun -Ki; Groom, Joseph; Chung, Daehwan; ...
Resistance to deconstruction is a major limitation to the use of lignocellulosic biomass as a substrate for the production of fuels and chemicals. Consolidated bioprocessing (CBP), the use of microbes for the simultaneous hydrolysis of lignocellulose into soluble sugars and fermentation of the resulting sugars to products of interest, is a potential solution to this obstacle. The pretreatment of plant biomass, however, releases compounds that are inhibitory to the growth of microbes used for CBP. Heterologous expression of the Thermoanaerobacter pseudethanolicus 39E bdhA gene, that encodes an alcohol dehydrogenase, in Clostridium thermocellum significantly increased resistance to furan derivatives at concentrationsmore » found in acid-pretreated biomass. The mechanism of detoxification of hydroxymethylfurfural was shown to be primarily reduction using NADPH as the cofactor. In addition, we report the construction of new expression vectors for homologous and heterologous expression in C. thermocellum. These vectors use regulatory signals from both C. bescii (the S-layer promoter) and C. thermocellum (the enolase promoter) shown to efficiently drive expression of the BdhA enzyme. Toxic compounds present in lignocellulose hydrolysates that inhibit cell growth and product formation are obstacles to the commercialization of fuels and chemicals from biomass. Lastly, expression of genes that reduce the effect of these inhibitors, such as furan derivatives, will serve to enable commercial processes using plant biomass for the production of fuels and chemicals.« less
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
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.
Rehm, Jürgen; Rehm, Maximilien X; Shield, Kevin D; Gmel, Gerrit; Gual, Antoni
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.
Le Strat, Yann; Grant, Bridget F.; Ramoz, Nicolas; Gorwood, Philip
Objective The accurate cut-off of an early onset of alcohol dependence is unknown. The objectives of this analysis are (1) to confirm that ages at onset variability in alcohol dependence is best described as a two sub-groups entity, (2) to define the most appropriate cut-off, and (3) to test the relevancy of such distinction. Method Data were drawn the Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This study focused on the 4,782 adults with lifetime alcohol dependence. Results The best-fit model distinguished two subgroups of age at onset of alcohol dependence, with a cut-off point at 22 years. Subjects with an earlier onset of alcohol dependence (≤22 years old) reported higher lifetime rates of specific phobia, antisocial behaviors and nearly all addictive disorders. Conclusions The early onset of alcohol dependence is best defined as beginning before the age of 22 years. PMID:20018459
Reich, T; Edenberg, H J; Goate, A; Williams, J T; Rice, J P; Van Eerdewegh, P; Foroud, T; Hesselbrock, V; Schuckit, M A; Bucholz, K; Porjesz, B; Li, T K; Conneally, P M; Nurnberger, J I; Tischfield, J A; Crowe, R R; Cloninger, C R; Wu, W; Shears, S; Carr, K; Crose, C; Willig, C; Begleiter, H
Alcohol dependence is a leading cause of morbidity and premature death. Several lines of evidence suggest a substantial genetic component to the risk for alcoholism: sibs of alcoholic probands have a 3-8 fold increased risk of also developing alcoholism, and twin heritability estimates of 50-60% are reported by contemporary studies of twins. We report on the results of a six-center collaborative study to identify susceptibility loci for alcohol dependence. A genome-wide screen examined 291 markers in 987 individuals from 105 families. Two-point and multipoint nonparametric linkage analyses were performed to detect susceptibility loci for alcohol dependence. Multipoint methods provided the strongest suggestions of linkage with susceptibility loci for alcohol dependence on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In addition, there was suggestive evidence for a protective locus on chromosome 4 near the alcohol dehydrogenase genes, for which protective effects have been reported in Asian populations.
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
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
Leksowski, W; Kawalaski, H; Czuba, Z; Krol, W; Gorczyca, P; Dworniczak, S; Rajca, M; Shani, J
Alcohol abuse is a major cause of abnormal liver development and activity. In addition to enzymatic malfunction, alcohol and its metabolites induce changes in the levels of some liver antigens, resulting in immunological disturbance. The purpose of the present study is to correlate the severity of liver function impairment with the length of alcohol abuse, in order to be able to use such tests as indicative of the severity of Alcohol Dependence Syndrome. Thirty-one alcohol abusers were allocated to three groups on the basis of the levels of their liver enzymes, and were tested for a variety of immunological parameters and skin reactions. The data indicate that even though not all immunological values measured differed significantly from the control values, in those that did (granulocytes, lymphocytes, CD4/CD8 ratio, C3, IgG, IgM and some skin positive reactions), the biggest difference was between the healthy volunteers and the group with the longest abuse period. It is suggested that changes in selected immunological parameters in alcohol abusers may indicate the severity of their liver dysfunction.
Spagnolo, Primavera A.; Ramchandani, Vijay A.; Schwandt, Melanie L.; Zhang, Lishu; Blaine, Sara K.; Usala, Julie M.; Diamond, Kristie A.; Phillips, Monte J.; George, David T.; Momenan, Reza; Heilig, Markus
Rationale Positively reinforcing properties of alcohol are in part mediated by activation of the ventral striatum (VS). Alcohol-induced release of endogenous opioids is thought to contribute to this response. Preclinical studies show that the opioid antagonist naltrexone (NTX) can block this cascade, but its ability to do so in treatment seeking alcoholics has not been examined. Objectives To study the effects of NTX on alcohol-induced VS activation and on amygdala response to affective stimuli in treatment seeking alcohol dependent inpatients. Methods Sixty-three treatment seeking alcoholics were randomized to receive NTX (50 mg) or placebo (PLC) daily. On day 7, participants underwent an alcohol cue reactivity session, and craving was measured using the Penn Alcohol Craving Scale. On day 9, participants received a saline infusion followed by an alcohol infusion and also viewed affective stimuli in an MR scanner. Results Irrespective of medication treatment condition, the alcohol infusion did not activate the VS in the alcohol dependent patients. Unexpectedly, VS activation was greater in NTX treated patients than in the PLC group. NTX treated patients also reported increased craving in response to alcohol cue exposure, and increased subjective response to alcohol (‘high’ and ‘intoxicated’) compared to PLC subjects. No significant effects of alcohol infusion on brain response to affective stimuli were in the NTX or placebo groups. Conclusions Unlike previous findings in social drinkers, a moderate level of intoxication did not activate the VS in treatment seeking alcoholics. This is likely to reflect tolerance to the positively reinforcing properties of alcohol in this clinical population. Our findings may help explain the efficacy of NTX to reduce heavy drinking, but not to maintain abstinence. PMID:25581657
Shmulewitz, Dvora; Keyes, Katherine; Beseler, Cheryl; Aharonovich, Efrat; Aivadyan, Christina; Spivak, Baruch; Hasin, Deborah
Aims To prepare for DSM-V, the structure of DSM-IV alcohol dependence and abuse criteria and a proposed additional criterion, at-risk drinking, require study in countries with low per-capita consumption, and comparison of current and lifetime results within the same sample. We investigated DSM-IV Alcohol Use Disorder (AUD) criteria in Israel, where per-capita alcohol consumption is low. Methods Household residents selected from the Israeli population register (N=1,338) were interviewed with the AUDADIS. Item Response Theory analyses were conducted using MPlus, and diagnostic thresholds examined with the kappa statistic. Results Dependence and abuse criteria fit a unidimensional model interspersed across the severity continuum, for both current and lifetime timeframes. Legal problems were rare and did not improve model fit. Weekly at-risk drinking reflected greater severity than in U.S. samples. When dependence and abuse criteria were combined, a diagnostic threshold of ≥3 criteria produced the best agreement with DSM-IV diagnoses (kappa>0.80). Conclusion Consistent with other studies, alcohol dependence and abuse criteria reflected a latent variable representing a single AUD. Results suggested little effect in removing legal problems and little gained by adding weekly at-risk drinking. Results contribute to knowledge about AUD criteria by examining them in a low-consumption country. PMID:20537809
Shortt, Niamk K; Rhynas, Sarah J; Holloway, Aisha
It has been suggested that place, and interaction with the environment, may play a role in recovery from alcohol dependence. In this paper we report findings from a project that used an adapted photovoice methodology to better understand individuals' experience and perceptions of the role of place in recovery from alcohol dependence. Individuals attending a recovery café in central Scotland documented their environment and, in focus group settings, the individuals discussed and analysed their photographs. Here we report aspects of the environment, both therapeutic and risky, experienced by individuals negotiating the journey of dependence recovery. Elements of the natural environment were largely referred to as supportive and therapeutic, as were other more quotidian spaces, such as the home and café. The largest place-based risk faced by participants was the persistent availability and marketing of alcohol. The results demonstrate that the journey of recovery from alcohol dependence is contextually shaped, with place both supporting and hindering this journey. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
Odlaug, B.L.; Gual, A.; DeCourcy, J.; Perry, R.; Pike, J.; Heron, L.; Rehm, J.
Aims Alcohol dependence is associated with high rates of co-occurring disorders which impact health-related quality of life (HRQoL) and add to the cost-of-illness. This study investigated the burden of alcohol dependence and associated co-occurring conditions on health and productivity. Methods A cross-sectional survey was conducted in eight European countries. Physicians (Psychiatrists and General Practitioners) completed patient record forms, which included assessment of co-occurring conditions, and patients completed matching self-completion forms. Drinking risk level (DRL) was calculated and the relationship between DRL, co-occurring conditions, work productivity, hospitalisations and rehabilitation stays was explored. Results Data were collected for 2979 alcohol-dependent patients (mean age 48.8 ± 13.6 years; 70% male). In total, 77% of patients suffered from moderate-to-severe co-occurring psychiatric and/or somatic conditions. High DRL was significantly associated with depression, greater work productivity losses, increased hospitalisations and rehabilitation stays. Co-occurring conditions were significantly associated with poorer HRQoL and decreased work productivity, with a statistical trend towards an increased frequency of rehabilitation stays. Conclusions Alcohol-dependent patients manifest high rates of co-occurring psychiatric and somatic conditions, which are associated with impaired work productivity and HRQoL. The continued burden of illness observed in these already-diagnosed patients suggests an unmet need in both primary and secondary care. PMID:26246514
Testino, G; Leone, S; Borro, P
Alcohol dependence (AD) is a major public health problem. Currently, three drugs for the treatment of AD have been approved by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA): acamprosate, disulfiram, and oral naltrexone. The FDA also approved the use of long-acting injectable naltrexone. In Austria and in Italy sodium oxybate is also approved. The EMA's Committee for Medicinal Products for Human Use has recently granted marketing authorization for nalmefene for the reduction of alcohol consumption. Many patients, while accepting the problem, are unable or unwilling to completely stop consuming alcohol, leading to an inevitable deterioration over time of their psycho-physical state, and social and family relationships. It is appropriate to offer these patients the opportunity to significantly reduce their consumption of alcohol. The reduction may be an opportunity to prepare the individual for achieving complete abstinence. Abstinence should always be the main goal. Currently, nalmefene is the only drug that has been authorized for the reduction of alcohol consumption. Its association with psycho-social support is mandatory; it is taken on an "as-needed" basis, which should preferably be 1-2 hours before the possible intake of alcohol. The trials showed a significant reduction in alcohol consumption, which resulted in a significant reduction in morbidity and mortality. Reducing consumption allows a decrease in the progression of numerous alcohol-induced chronic diseases, as well as a reduction in psycho-physical damage, acts of violence, motor vehicle accidents, and accidents at work, which in turn means fewer healthcare costs.
Hingson, Ralph W.; Heeren, Timothy; Winter, Michael R.
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…
McClain, Justin A; Morris, Stephanie A; Marshall, S Alexander; Nixon, Kimberly
The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence. Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence. Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively. The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence. Although these results mirror the magnitude of reactive neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults. The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats. Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.
Sugawara, Tazuko; Morita, Noriaki; Nakatani, Youji
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.
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
Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C
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
Woerle, Sandra; Roeber, Jim; Landen, Michael G
Excessive alcohol consumption claims more than 75,000 lives in the United States each year. The prevalence of alcohol dependence among excessive drinkers is not well known. Data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS) in New Mexico were used to assess the prevalence of excessive drinking, including binge drinking, heavy drinking, alcohol-impaired driving, and alcohol dependence. Of 4,761 respondents, 16.5% were excessive drinkers; 14.4% binge drank and 1.8% were alcohol dependent. While the rates of alcohol dependence were higher among the youngest age group, males, those with some college education, and those of race/ethnicity other than White, non-Hispanic, only differences by age were statistically significant. The prevalence of alcohol dependence was the highest among those who reported alcohol-impaired driving in the past 30 days (15.9%), and was lower among those who reported heavy drinking (13.4%) and binge drinking (8.1%). Although 16.5% of New Mexico adults had at least 1 type of excessive drinking, only 1.8% of all adults met the criteria for alcohol dependence. Furthermore, only a minority of those who reported binge drinking, heavy drinking, or alcohol-impaired driving met the criteria for alcohol dependence. This suggests that most alcohol problems in New Mexico are likely due to excessive drinking among persons who are not alcohol dependent. The adverse health and social consequences associated with excessive drinking are not limited to those who are alcohol dependent, but extend to a broader range of problem drinkers across the population.
Kovatchev, Boris; Breton, Marc; Johnson, Bankole
In this paper we view alcohol dependence and the response to treatment as a recurrent bio-behavioral process developing in time and propose formal models of this process combining behavior and biology in silico. The behavioral components of alcohol dependence and treatment are formally described by a stochastic process of human behavior, which serves as an event generator challenging the metabolic system. The biological component is driven by the biochemistry of alcohol intoxication described by deterministic models of ethanol pharmacodynamics and pharmacokinetics to enable simulation of drinking addiction in humans. Derived from the known physiology of ethanol and the literature of both ethanol intoxication and ethanol absorption, the different models are distilled into a minimal model (as simple as the complexity of the data allows) that can represent any specific patient. We use these modeling and simulation techniques to explain responses to placebo and ondansetron treatment observed in clinical studies. Specifically, the response to placebo was explained by a reduction of the probability of environmental reinforcement, while the effect of ondansetron was explained by a gradual decline in the degree of ethanol-induced neuromodulation. Further, we use in silico experiments to study critical transitions in blood alcohol levels after specific average number of drinks per day, and propose the existence of two critical thresholds in the human – one at 5 and another at 11 drinks/day – at which the system shifts from stable to critical and to super critical state indicating a state of alcohol addiction. The advantages of such a model-based investigation are that (1) the process of instigation of alcohol dependence and its treatment can be deconstructed into meaningful steps, which allow for individualized treatment tailoring, and (2) physiology and behavior can be quantified in different (animal or human) studies and then the results can be integrated in silico
Background Research investigating the differential effectiveness of Brief Motivational Interventions (BMI) among alcohol dependent and non-dependent patients in the medical setting is limited. Clinical guidelines suggest that BMI is most appropriate for patients with less severe alcohol problems. As a result, most studies evaluating the effectiveness of BMI have excluded patients with an indication of alcohol dependence. Methods A randomized controlled trial of brief intervention in the trauma care setting comparing BMI to treatment as usual plus assessment (TAU+) was conducted. Alcohol dependence status was determined for 1336 patients using DSM-IV diagnostic criteria. The differential effectiveness of BMI among alcohol dependent and non-dependent patients was determined with regard to volume per week, maximum amount consumed, percent days abstinent, alcohol problems at six and 12 month follow up. In addition, the effect of BMI on dependence status at six and 12 months was determined. Results There was a consistent interaction between BMI and alcohol dependence status, which indicated significantly higher reductions in volume per week at six and twelve month follow up (β=−.56, p=.03, β=−.63, p=.02, respectively), maximum amount at six months (β=−.31, p=.04), and significant decreases in percent days abstinent at twelve months (β=.11, p=.007) and alcohol problems at twelve months (β=−2.7, p12=.04) among patients with alcohol dependence receiving BMI. In addition, patients with alcohol dependence at baseline that received BMI were .59 (95% CI=.39–.91) times less likely to meet criteria for alcohol dependence at six months. Conclusions These findings suggest that BMI is more beneficial among patients with alcohol dependence who screen positive for an alcohol related injury. PMID:20493644
There is a high rate of comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of PTSD among individuals with...AD are at least twice as high as those in the general population. In addition, alcohol dependence is the most common comorbid condition in men with...sleep disturbance in combat veterans with PTSD and alcohol dependence . The objective of this study is to evaluate the efficacy of prazosis (16mg
Field, Craig A; Caetano, Raul
Research investigating the differential effectiveness of Brief Motivational Interventions (BMIs) among alcohol-dependent and non-dependent patients in the medical setting is limited. Clinical guidelines suggest that BMI is most appropriate for patients with less severe alcohol problems. As a result, most studies evaluating the effectiveness of BMI have excluded patients with an indication of alcohol dependence. A randomized controlled trial of brief intervention in the trauma care setting comparing BMI to treatment as usual plus assessment (TAU+) was conducted. Alcohol dependence status was determined for 1336 patients using DSM-IV diagnostic criteria. The differential effectiveness of BMI among alcohol-dependent and non-dependent patients was determined with regard to volume per week, maximum amount consumed, percent days abstinent, alcohol problems at 6 and 12 months follow-up. In addition, the effect of BMI on dependence status at 6 and 12 months was determined. There was a consistent interaction between BMI and alcohol dependence status, which indicated significantly higher reductions in volume per week at 6 and 12 months follow-up (beta=-.56, p=.03, beta=-.63, p=.02, respectively), maximum amount at 6 months (beta=-.31, p=.04), and significant decreases in percent days abstinent at 12 months (beta=.11, p=.007) and alcohol problems at 12 months (beta=-2.7, p(12)=.04) among patients with alcohol dependence receiving BMI. In addition, patients with alcohol dependence at baseline that received BMI were .59 (95% CI=.39-.91) times less likely to meet criteria for alcohol dependence at six months. These findings suggest that BMI is more beneficial among patients with alcohol dependence who screen positive for an alcohol-related injury. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Yoshimura, Atsushi; Maesato, Hitoshi; Hisatomi, Nobuko; Higuchi, Susumu
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.
Addolorato, Giovanni; Mirijello, Antonio; Leggio, Lorenzo; Ferrulli, Anna; Landolfi, Raffaele
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
Barkby, Helen; Dickson, Joanne M; Roper, Louise; Field, Matt
Motivational conflict is central to alcohol dependence, with patients reporting motivation to limit their drinking at the same time as urges to drink alcohol. In addition, dual process models of addiction emphasise the power of automatic cognitive processes, particularly automatic approach responses elicited by alcohol-related cues, as determinants of drinking behavior. We aimed to examine the strength of automatic and self-reported alcohol approach and avoidance tendencies among alcohol-dependent inpatients relative to matched controls. A total of 63 alcohol-dependent patients undergoing detoxification and 64 light-drinking controls completed a stimulus-response compatibility (SRC) task, which assesses the speed of categorization of alcohol-related pictures by making symbolic approach and avoidance movements. We also included modified versions of the SRC task to assess automatic motivational conflict, that is, strong approach and avoidance tendencies elicited simultaneously by alcohol-related cues. There were no differences between alcohol-dependent patients and controls on the SRC task, although individual differences in the quantity of alcohol consumed before entering treatment were significantly positively correlated with the strength of approach (but not avoidance) tendencies elicited by alcohol-related cues. Automatic approach tendencies were also positively correlated with self-reported "approach" inclinations and negatively correlated with self-reported "avoidance" inclinations. Although alcohol-dependent patients and matched controls did not differ on automatic approach and avoidance tendencies elicited by alcohol-related cues, individual differences in the quantity of alcohol consumed before entering treatment were associated with the strength of automatic approach tendencies elicited by alcohol cues. Copyright © 2011 by the Research Society on Alcoholism.
Aragues, M; Jurado, R; Quinto, R; Rubio, G
Impulsivity can be defined as choosing a smaller, immediate reward over a larger, delayed reward. From this perspective, addictive behaviors such as substance abuse and pathological gambling reflect a series of impulsive choices. However, impulsivity is not a homogeneous construct. Laboratory measures of impulsivity reflect two types of processes. The first is related to behavioral inhibition and refers to an individual's ability to appropriately inhibit thoughts or actions. The second is the delay of reward dimension, namely the degree to which immediate (rewarding) consequences have more control over an individual's behavior than consequences that are delayed. In this review, we describe how alcohol is associated with significant impairments in these paradigms. We also suggest that they may have a role in the development of alcohol dependence. These results are in agreement with a model in which delay of gratification might be a marker for early use and/or abuse of alcohol, whereas impairment in behavioral inhibition might be a marker for maintained use in time and, therefore, for progression towards alcohol dependence. Copyright © 2010 S. Karger AG, Basel.
Cabé, N; Laniepce, A; Ritz, L; Lannuzel, C; Boudehent, C; Vabret, F; Eustache, F; Beaunieux, H; Pitel, A-L
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
Jones, Gail Yvonne; Hoffmann, Norman G
Background In light of the emphasis on drug abuse, this study explored the relative prevalence of substance use disorders among United Kingdom (UK) prison inmates in the context of findings from a general inmate population in the United States (US). The lead author of the report conducted a structured diagnostic interview with 155 new admissions to one of two prisons in the UK using the CAAPE (Comprehensive Addiction And Psychological Evaluation), a structured diagnostic interview, to ensure consistent assessments. The US sample consisted of 6,881 male inmates in a state prison system evaluated with an automated version of the SUDDS-IV (Substance Use Disorder Diagnostic Schedule-IV) interview. Results Alcohol dependence emerged as the most prevalent substance use disorder in both UK prisons and in the US sample. Relative frequencies of abuse and dependence for alcohol and other drugs revealed that dependence on a given substance was more prevalent than abuse ad defined by the current diagnostic criteria. Conclusion Despite the emphasis on drugs in correctional populations, alcohol dependence appears to be the most prominent substance use disorder among the incarcerated in both the US and UK and must be considered in developing treatment programs and policy priorities. PMID:17092339
Walt, Lisa C.; Kinoti, Elias; Jason, Leonard A.
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
Ulmer, Albrecht; Müller, Markus; Frietsch, Bernhard
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
Chartier, Karen G.; Dick, Danielle M.; Almasy, Laura; Chan, Grace; Aliev, Fazil; Schuckit, Marc A.; Scott, Denise M.; Kramer, John; Bucholz, Kathleen K.; Bierut, Laura J.; Nurnberger, John; Porjesz, Bernice; Hesselbrock, Victor M.
Objective: Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption–related phenotypes. Method: Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism. Genetic markers included ADH1B-rs1229984, ADH1B-rs2066702, ADH1C-rs698, ADH4-rs1042364, and ADH4-rs1800759. Phenotypes were maximum drinks consumed in a 24-hour period and total number of alcohol dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Religious involvement was defined by self-reported religious services attendance. Results: Both religious involvement and ADH1B-rs1229984 were negatively associated with the number of maximum drinks consumed and the number of lifetime alcohol dependence symptoms endorsed. The interactions of religious involvement with ADH1B-rs2066702, ADH1C-rs698, and ADH4-rs1042364 were significantly associated with maximum drinks and alcohol dependence symptoms. Risk variants had weaker associations with maximum drinks and alcohol dependence symptoms as a function of increasing religious involvement. Conclusions: This study provided initial evidence of a modifying effect for religious involvement on relationships between ADH variants and maximum drinks and alcohol dependence symptoms. PMID:27172571
Kawamura, Tomoya; Kranzler, Henry R.; Sherva, Richard; Gelernter, Joel; Farrer, Lindsay A.; Roberto, Marisa; Sanna, Pietro Paolo
Background The neurofibromatosis type 1 (Nf1) gene encodes a GTPase activating protein that negatively regulates small GTPases of the Ras family. Methods We assessed alcohol-related behaviors including alcohol sensitivity, dependent and non-dependent drinking, and basal and alcohol-induced GABA release in the central nucleus of the amygdala (CeA) in Nf1 heterozygous null mice (Nf1+/−). We also investigated the associations of Nf1 polymorphisms with alcohol dependence risk and severity in humans. Results Nf1+/− mice do not differ from wild-type (WT) mice in non-dependent drinking, such as 24-hr, 2-bottle choice (2BC), drinking in the dark binge drinking, or limited access 2BC. However, Nf1+/− mice failed to escalate alcohol drinking following chronic intermittent ethanol vapor exposure (CIE) to induce dependence. Alcohol acutely increases GABA release in the CeA and alcohol dependence is characterized by increased baseline GABA release in CeA. Interestingly, GABA release in Nf1+/− mice is greater at baseline than WT mice, is not elevated by induction of dependence by CIE, and failed to show alcohol-induced facilitation both before and after CIE. Additionally, we observed that multiple variants in the human NF1 gene are associated with a quantitative measure of alcohol dependence in both African Americans and European Americans. Conclusions In this translational investigation, we found that Nf1 activity regulates excessive drinking and basal and ethanol-stimulated GABA release in the mouse central amygdala. We also found that genetic variation in NF1 may confer an inherent susceptibility to the transition from non-dependent to dependent drinking in humans. PMID:25483400
Lown, E. Anne; Nayak, Madhabika B.; Korcha, Rachael A.; Greenfield, Thomas. K.
Background Previous research has documented a relationship between child sexual abuse and alcohol dependence. This paper extends that work by providing a comprehensive description of past year and lifetime alcohol consumption patterns, consequences and dependence among women reporting either child physical and sexual abuse in a national sample of women. Methods This study used survey data from 3,680 women who participated in the 2005 U.S. National Alcohol Survey. Information on physical and sexual child abuse and its characteristics were assessed in relation to 8 past year and lifetime alcohol consumption measures. Results Child physical or sexual abuse was significantly associated with past year and lifetime alcohol consumption measures. In multivariate analyses, controlling for age, marital status, employment status, education, ethnicity and parental alcoholism or problem drinking, women reporting child sexual abuse vs. no abuse were more likely to report past year heavy episodic drinking (ORadj=1.7; 95% CI 1.0–2.9), alcohol dependence (ORadj=7.2; 95% CI 3.2–16.5), and alcohol consequences (ORadj=3.6; 95% CI 1.8–7.3). Sexual abuse (vs. no abuse) was associated with a greater number of past year drinks (124 vs. 74 drinks respectively, p=.002). Sexual child abuse was also associated with lifetime alcohol related consequences (ORadj=3.5; 95% CI 2.6–4.8), and dependence (ORadj=3.7; 95% CI 2.6–5.3). Physical child abuse was associated with 4 of 8 alcohol measures in multivariate models. Both physical and sexual child abuse were associated with getting into fights, health, legal, work and family alcohol related consequences. Alcohol related consequences and dependence were more common for women reporting sexual abuse compared to physical abuse, 2 or more physical abuse perpetrators, non-parental and non-family physical abuse perpetrators and women reporting injury related to the abuse. Conclusion Both child physical and sexual abuse were associated with many
Coffey, Scott F; Schumacher, Julie A; Stasiewicz, Paul R; Henslee, Amber M; Baillie, Lauren E; Landy, Noah
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. PsycINFO Database Record 2010 APA, all rights reserved.
Kwako, L. E.; Schwandt, M. L.; Sells, J. R.; Ramchandani, V. A.; George, D. T.; Sinha, R.; Heilig, M.
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
de Vargas, Divane
This study aimed to analyze the items of the Scale of Attitudes toward Alcohol, alcoholism and alcoholics in order to prepare a reduced version keeping the instrument's psychometric properties. The preliminary version of the Scale composed by 165 items was tested in a sample with 144 nursing student. The evaluation process of the items consisted of the total-item coefficient correlation and reliability of the instrument was estimated by Cronbach's alpha coefficient. Results indicate the permanence of 83 items, divided into five factors that showed satisfactory values in the different coefficients of internal consistency. Further studies are needed with larger samples in order to give continuity to the process of scale validation among health professionals.
Sivolap, Iu P
Treatment of alcohol dependence consist of alcohol detoxification with withdrawal alleviation and relapse prevention or maintenance therapy. Drugs of choice for alcohol withdrawal cure are benzodiazepines and anticonvulsants are an alternative for them. Relapse prevention and alcohol abuse alleviation are carried out using disulfiram, acamprosate, naltrexone and nalmefene. Moreover, therapeutic possibilities of memantine, gabapentine, pregabalin, baclofen, modafinil, ondansetron D-cycloserine and aripiprazole are studying nowadays. Use of selective serotonin reuptake inhibitors including fluvoxamine for alcohol patients is of great importance due to frequent comorbidity of alcoholism, depression and anxiety. There are some doubtful methods of alcoholism treatment accepted in Russian addictive medicine such as clearance detoxification and use of antipsychotics for craving elimination.
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
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
Roltsch Hellard, Emily A; Impastato, Renata A; Gilpin, Nicholas W
Humans diagnosed with alcohol use disorder are more sensitive to painful stimuli during withdrawal, which suggests that excessive alcohol drinking worsens pain outcomes. Alcohol-dependent rats exhibit increases in nociceptive sensitivity during withdrawal. Data from animal models suggest that brain melanocortin-4 receptors (MC4Rs) mediate alcohol drinking and nociception. Here we tested: (1) the effect of alcohol dependence on thermal nociception in rats, and (2) the ability of acute alcohol and (3) MC4R antagonists to reverse hyperalgesia during withdrawal in alcohol-dependent rats. Rats were trained to self-administer operant alcohol and were tested for baseline thermal nociception. Half of the rats were made dependent on alcohol, then all rats were cannulated in the lateral ventricle. We tested the effects of acute alcohol drinking, acute fixed-dose alcohol, intra-ventricular agouti-related protein (endogenous MC4R antagonist), intra-ventricular HS014 (synthetic MC4R antagonist) and intra-nasal HS014 on hyperalgesia during withdrawal in alcohol-dependent rats, relative to non-dependent drinkers and alcohol-naïve controls. Alcohol-dependent rats exhibit thermal hyperalgesia that is abolished by alcohol drinking, bolus alcohol and intra-ventricular and intra-nasal MC4R antagonists. These manipulations did not affect thermal nociception in non-dependent drinkers and alcohol-naïve controls, suggesting that alcohol dependence produces neuroadaptations in brain MC4R systems. These results suggest that brain MC4R systems may be an effective therapeutic target for reducing nociception in the alcohol-dependent organism.
Witt, Ellen D
Sex differences in patterns of drinking and rates of alcohol abuse and dependence begin to emerge during the transition from late puberty to young adulthood. Increases in pubertal hormones, including gonadal and stress hormones, are a prominent developmental feature of adolescence and could contribute to the progression of sex differences in alcohol drinking patterns during puberty. This paper reviews experimental and correlational studies of gonadal and stress-related hormone changes and their effects on alcohol drinking and other associated actions of alcohol. Mechanisms are suggested by which reproductive hormones and stress-related hormones may modulate neural circuits within the brain reward system to produce sex differences in alcohol drinking patterns and vulnerability to alcohol abuse and dependence which become apparent during the late pubertal period.
Miller, N S; Dackis, C A; Gold, M S
Alcohol and drug addiction are defined in behavioral terms as the preoccupation with, compulsive use of, and relapse to drugs that are descriptive and confirmatory. The basis of addiction may involve neurochemical changes in the brain that distort and redirect the drive states (instincts). Tolerance and dependence may only be incidentally associated with addiction as a result of a nonspecific adaptation by the body to the presence of a drug. The cellular adaptation may be the same in all organs. Addiction to alcohol and drugs may have no specific relationship to tolerance and dependence. Addiction occurs in the absence of observable tolerance and dependence to alcohol and drugs. Alcohol and drug addiction is probably more complex than tolerance and dependence. Addiction is difficult to study because of the variability of behavioral phenomena and the underlying intricacies of the neurosubstrates. Tolerance and dependence are still useful as they are indicators of drug use. It is a misconception that long term chronic use is necessary for tolerance and dependence to develop. Some studies have shown that tolerance can develop within hours and days to a single dose of alcohol or other drugs. Anxiety, depression and insomnia can occur after a single dose of ethanol in humans. These symptoms of withdrawal from the alcohol or drug constitute dependence. Redefining the criteria for addiction tolerance and dependence to alcohol and other drugs may be in order. A neurochemical model may provide a more definitive and uniform basis for considering addiction, tolerance, and dependence to alcohol and drugs.
ZUO, Lingjun; ZHANG, Clarence K.; SAYWARD, Frederick G.; CHEUNG, Kei-Hoi; WANG, Kesheng; KRYSTAL, John H.; ZHAO, Hongyu; LUO, Xingguang
Background The organization of risk genes within signaling pathways may provide clues about the converging neurobiological effects of risk genes for alcohol dependence. Aim Identify risk genes and risk gene pathways for alcohol dependence. Methods We conducted a pathway-based genome-wide association study (GWAS) of alcohol dependence using a gene-set-rich analytic approach. Approximately one million genetic markers were tested in the discovery sample which included 1409 European-American (EA) alcohol dependent individuals and 1518 EA healthy comparison subjects. An additional 681 African-American (AA) cases and 508 AA healthy subjects served as the replication sample. Results We identified several genome-wide replicable risk genes and risk pathways that were significantly associated with alcohol dependence. After applying the Bonferroni correction for multiple testing, the ‘cellextracellular matrix interactions’ pathway (p<2.0E-4 in EAs) and the PXN gene (which encodes paxillin) (p=3.9E-7 in EAs) within this pathway were the most promising risk factors for alcohol dependence. There were also two nominally replicable pathways enriched in alcohol dependence-related genes in both EAs (0.015≤p≤0.035) and AAs (0.025≤p≤0.050): the ‘Na+/Cl- dependent neurotransmitter transporters’ pathway and the ‘other glycan degradation’ pathway. Conclusion These findings provide new evidence highlighting several genes and biological signaling processes that may be related to the risk for alcohol dependence. PMID:26120261
Ponomarev, Igor; Wang, Shi; Zhang, Lingling; Harris, R Adron; Mayfield, R Dayne
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 coexpression 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 trimethylation, 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.
Abraham, John; Chandrasekaran, R.
With introduction of the concept of alcohol dependence syndrome, scales specifically to measure dependence were developed and used in clinical and research settings. 12 questions from The Severity of Alcohol Dependence Data Questionnaire were translated into the Iccal language and was administered to 70 patients referred to the deaddiction centre. The translated version showed good evidence of internal validity, criterion validity and external validity. PMID:21584036
Jayawickreme, Nuwan; Yasinski, Carly; Williams, Monnica; Foa, Edna B.
The current study examined gender-specific associations between trauma cognitions, alcohol cravings and alcohol-related consequences in individuals with dually diagnosed PTSD and alcohol dependence (AD). Participants (N = 167) had entered a treatment study for concurrent PTSD and AD; baseline information was collected from participants about PTSD-related cognitions in three areas: negative cognitions about self, negative cognitions about the world, and self-blame; and two aspects of AD, alcohol cravings and consequences of AD. Gender differences were examined while controlling for PTSD severity. The results indicate that negative cognitions about the self are significantly related to alcohol cravings in men but not women, and that interpersonal consequences of AD are significantly related to self-blame in women but not in men. These findings suggest that for individuals with comorbid PTSD and AD, psychotherapeutic interventions that focus on reducing trauma-related cognitions are likely to reduce alcohol cravings in men and relational problems in women. PMID:21480680
Salujha, S. K.; Chaudhury, S.; Menon, P. K.; Srivastava, K.; Gupta, A.
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
Lewis, Michael J
Alcohol is not only a drug of abuse but is also a food. This combination has a significant impact on the development and consequences of alcohol abuse and dependence. Understanding the neurobiological and behavioral processes that mediate them is perhaps best approached from the perspective of ingestive behavior. Research from the Hoebel laboratory has provided innovation and leadership in understanding that feeding neuropeptides plays a significant role in alcohol intake. The research reviewed here shows that galanin and other feeding peptides increase intake and also motivate abuse and the development of dependence. In addition, the consequences of long term alcohol abuse and dependence alter nutritional systems and drinking behavior. A major challenge is understanding the role of alcohol's dual properties and feeding neuropeptide in the motivation to drink.
Schuckit, Marc A; Danko, George P; Smith, Tom L; Buckman, Kelly R
Information about the prognostic implications of a DSM-IV diagnosis of alcohol dependence is important to both clinicians and researchers. In this regard, only limited data are available on the performance of specific diagnostic items. This study reports data gathered with a structured, validated interview with 642 alcohol-dependent men and women from the Collaborative Study of the Genetics of Alcoholism (COGA). The goals were to evaluate the ability of each of the DSM-IV dependence items to predict the occurrence over the next 5 years of a broad pattern of 27 alcohol-related problems. For comparison, similar data are reported regarding the performance of abuse criteria for 516 additional subjects. The results revealed that dependence item 3 (use of alcohol in larger amounts) was the only criterion that did not relate significantly to outcome, and indicated that the dependence criteria related relatively similarly to different types of outcomes among alcoholics. No specific combination of diagnostic items stood out in predicting outcome but, rather, the span of items generally performed well. These data support the potential usefulness of the DSM-IV dependence criteria.
Kittles, R A; Long, J C; Bergen, A W; Eggert, M; Virkkunen, M; Linnoila, M; Goldman, D
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.
Alcohol dependence is characterized by frequent, compulsive and uncontrolled consumption of alcohol associated with behavior of maladaption and destruction. It is an etiologically and clinically heterogeneous syndrome, moderately to highly heritable, and caused by interaction of genes and environment. Alcohol dependence is related to other psychiatric diseases by common neurobiological pathways, including those that modulate reward, behavioral control as well as anxiety and stress response. Alcohol induces adaptive changes in brain function providing the basis for tolerance, craving, withdrawal, and emotional disturbance. The differentiation of psychobiological traits of addictive behavior reflecting neurobiological processes is therefore of particular importance for the dissection of the complex genetic susceptibility to alcohol dependence. A central serotonin (5-HT) deficit is thought to be involved in the pathogenesis of alcohol dependence by modulating motivational behavior, neuroadaptive processes, and resulting emotional disturbance. 5-HT-related impulsive, aggressive, and suicidal behavior has been linked to a primordial personality that is susceptible to alcohol dependence. Although variations in many of the genes that encode receptors, enzymes, and transporters of the 5-HT system have been tested as risk factors for alcohol dependence, genetic analyses of 5-HT signaling in alcohol dependence have mainly been focused on the 5-HT transporter (5-HTT) gene. Due to its central role in the fine-tuning serotonergic neurotransmission, a regulatory variant of the 5-HTT, which is associated with anxiety related traits, is not only a key player in the neurobiological mechanism of gene x environment interaction in the etiology of depression, but also contributes to the risk to develop alcohol dependence with antisocial behavior and suicidality. Evidence for a modulatory effect of allelic variation of 5-HTT function on limbic circuit responses to emotional stimuli
Wiers, Corinde E; Stelzel, Christine; Gladwin, Thomas E; Park, Soyoung Q; Pawelczack, Steffen; Gawron, Christiane K; Stuke, Heiner; Heinz, Andreas; Wiers, Reinout W; Rinck, Mike; Lindenmeyer, Johannes; Walter, Henrik; Bermpohl, Felix
In alcohol-dependent patients, alcohol cues evoke increased activation in mesolimbic brain areas, such as the nucleus accumbens and the amygdala. Moreover, patients show an alcohol approach bias, a tendency to more quickly approach than avoid alcohol cues. Cognitive bias modification training, which aims to retrain approach biases, has been shown to reduce alcohol craving and relapse rates. The authors investigated effects of this training on cue reactivity in alcohol-dependent patients. In a double-blind randomized design, 32 abstinent alcohol-dependent patients received either bias modification training or sham training. Both trainings consisted of six sessions of the joystick approach-avoidance task; the bias modification training entailed pushing away 90% of alcohol cues and 10% of soft drink cues, whereas this ratio was 50/50 in the sham training. Alcohol cue reactivity was measured with functional MRI before and after training. Before training, alcohol cue-evoked activation was observed in the amygdala bilaterally, as well as in the right nucleus accumbens, although here it fell short of significance. Activation in the amygdala correlated with craving and arousal ratings of alcohol stimuli; correlations in the nucleus accumbens again fell short of significance. After training, the bias modification group showed greater reductions in cue-evoked activation in the amygdala bilaterally and in behavioral arousal ratings of alcohol pictures, compared with the sham training group. Decreases in right amygdala activity correlated with decreases in craving in the bias modification but not the sham training group. These findings provide evidence that cognitive bias modification affects alcohol cue-induced mesolimbic brain activity. Reductions in neural reactivity may be a key underlying mechanism of the therapeutic effectiveness of this training.
Vignesh, B. T.; Singh, Awnish K.; Mohan, S. K.; Murthy, Shruti; Joshi, Ashish
Background: Alcohol use is on the rise worldwide and urgent steps are required to curb this growing burden of alcohol consumption. Alcohol drinking leads to serious social, physical and mental consequences. Objective: The objective of this pilot study is to examine association between socio-demographics and severity of alcohol dependence among individuals obtaining treatment at alcohol de-addiction center. Methods: This pilot cross sectional study was conducted in September 2013 in South India. A convenient sample of 100 participants was enrolled. Individuals aged 30 years and above, receiving treatment from de-addiction center and providing written informed consent were eligible for the study. A modified version of previously validated questionnaires was used for gathering information on socio-demographic characteristics, severity of alcohol dependence (using Alcohol Dependent Scale [ADS] and Short Alcohol Dependence Data questionnaire [SADD]), motivational incentives for alcohol quitting and challenges faced while quitting alcohol. Results: All participants were males with mean age of 43 years (SD = 6.5 years). Significant association was seen between ADS and annual income (p = 0.001), education (p = 0.001), occupation (p < 0.0001) and work timing (p < 0.0001). Similar results were seen with SADD scores. Family support (100%) and health (60%) were reported to be the most important motivating factors for quitting alcohol. Discussion: Results showed an urgent need of interventions that are family centered and focus on unskilled, less educated individuals having high work stress. Public health interventions should not only be home based, but should also include worksite awareness initiatives. A national policy is needed to promote alcohol quitting and to bring awareness regarding the consequences of alcohol consumption on individual’s life. PMID:24762342
Dierker, Lisa; Selya, Arielle; Rose, Jennifer; Hedeker, Donald; Mermelstein, Robin
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
Bae, Sujin; Kang, Ilhyang; Lee, Boung Chul; Jeon, Yujin; Cho, Han Byul; Yoon, Sujung; Lim, Soo Mee; Kim, Jungyoon; Lyoo, In Kyoon
Alcohol dependence is a serious disorder that can be related with a number of potential health-related and social consequences. Cortical thickness measurements would provide important information on the cortical structural alterations in patients with alcohol dependence. Twenty-one patients with alcohol dependence and 22 healthy comparison subjects have been recruited and underwent high-resolution brain magnetic resonance (MR) imaging and clinical assessments. T1-weighted MR images were analyzed using the cortical thickness analysis program. Significantly thinner cortical thickness in patients with alcohol dependence than healthy comparison subjects was noted in the left superior frontal cortical region, correcting for multiple comparisons and adjusting with age and hemispheric average cortical thickness. There was a significant association between thickness in the cluster of the left superior frontal cortex and the duration of alcohol use. The prefrontal cortical region may particularly be vulnerable to chronic alcohol exposure. It is also possible that the pre-existing deficit in this region may have rendered individuals more susceptible to alcohol dependence. PMID:28035184
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
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.
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.
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
Mares, Suzanne H. W.; van der Vorst, Haske; Vermeulen-Smit, Evelien; Lichtwarck-Aschoff, Anna; Verdurmen, Jacqueline E. E.; Engels, Rutger C. M. E.
More than 50% of Dutch 12-year olds already started drinking. Since it is known that delaying the onset of alcohol use results in a lower risk of alcohol-related problems, the recently developed "In control: No alcohol!" prevention program is targeted at elementary school children and their mothers. In this pilot study, the success of…
Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R
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
Halsted, Charles H
Convincing evidence links aberrant B-vitamin dependent hepatic methionine metabolism to the pathogenesis of alcoholic liver disease (ALD). This review focuses on the essential roles of folate and vitamins B6 and B12 in hepatic methionine metabolism, the causes of their deficiencies among chronic alcoholic persons, and how their deficiencies together with chronic alcohol exposure impact on aberrant methionine metabolism in the pathogenesis of ALD. Folate is the dietary transmethylation donor for the production of S-adenosylmethionine (SAM), which is the substrate for all methyltransferases that regulate gene expressions in pathways of liver injury, as well as a regulator of the transsulfuration pathway that is essential for production of glutathione (GSH), the principal antioxidant for defense against oxidative liver injury. Vitamin B12 regulates transmethylation reactions for SAM production and vitamin B6 regulates transsulfuration reactions for GSH production. Folate deficiency accelerates the experimental development of ALD in ethanol-fed animals while reducing liver SAM levels with resultant abnormal gene expression and decreased production of antioxidant GSH. Through its effects on folate metabolism, reduced SAM also impairs nucleotide balance with resultant increased DNA strand breaks, oxidation, hepatocellular apoptosis, and risk of carcinogenesis. The review encompasses referenced studies on mechanisms for perturbations of methionine metabolism in ALD, evidence for altered gene expressions and their epigenetic regulation in the pathogenesis of ALD, and clinical studies on potential prevention and treatment of ALD by correction of methionine metabolism with SAM.
de Timary, Philippe; Leclercq, Sophie; Stärkel, Peter; Delzenne, Nathalie
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.
de Timary, Philippe; Leclercq, Sophie; Stärkel, Peter; Delzenne, Nathalie
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
Staples, Miranda C.; Mandyam, Chitra D.
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
Simons, Jeffrey S.; Wills, Thomas A.; Emery, Noah N.; Marks, Russell M.
Research on alcohol use depends heavily on the validity of self-reported drinking. The present paper presents data from 647 days of self-monitoring with a transdermal alcohol sensor by 60 young adults. We utilized a bio chemical measure, transdermal alcohol assessment with the WrisTAS, to examine the convergent validity of three approaches to collecting daily self-report drinking data: experience sampling, daily morning reports of the previous night, and 1-week timeline follow-back (TLFB) assessments. We tested associations between three pharmacokinetic indices (peak concentration, area under the curve (AUC), and time to reach peak concentration) derived from the transdermal alcohol signal and within- and between-person variation in alcohol dependence symptoms. The WrisTAS data corroborated 85.74% of self-reported drinking days based on the experience sampling data. The TLFB assessment and combined experience sampling and morning reports agreed on 87.27% of drinking days. Drinks per drinking day did not vary as a function of wearing or not wearing the sensor; this indicates that participants provided consistent reports of their drinking regardless of biochemical verification. In respect to self-reported alcohol dependence symptoms, the AUC of the WrisTAS alcohol signal was associated with dependence symptoms at both the within- and between-person level. Furthermore, alcohol dependence symptoms at baseline predicted drinking episodes characterized in biochemical data by both higher peak alcohol concentration and faster time to reach peak concentration. The results support the validity of self-report alcohol data, provide empirical data useful for optimal design of daily process sampling, and provide an initial demon stration of the use of transdermal alcohol assessment to characterize drinking dynamics associated with risk for alcohol dependence. PMID:26160523
Quinn, Amity E.; Rosen, Rochelle K.; McGeary, John E.; Amoa, Francine; Kranzler, Henry R.; Francazio, Sarah; McGarvey, Stephen T.; Swift, Robert M.
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
Borges, J.M.M. )
The Brazilian alcohol program, Proalcool, is discussed. It was developed as a strategic answer to the high dependence on imported oil and sharp increases in oil prices that adversely affected the Brazilian balance of payments. The program is intended to replace part of the gasoline consumption with ethanol. The availability of resources, including fertile land and unskilled labor, made possible its implementation. As a result of these measures, there were changes in the Brazilian energy matrix. The most important were the substitution between gasoline and fuel alcohol and also between fuel oil and electricity. Other benefits with Proalcool include environmental gains, employment creation, increase in rural area income, and technological improvements in the sugarcane sector. These have allowed an ethanol cost reduction from US$70/bbl at the beginning the program (1976) to US$45/bbl in 1989.
Manzardo, Ann M.; He, Jianghua; Poje, Albert; Penick, Elizabeth C.; Campbell, Jan; Butler, Merlin G.
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
O’Brien, Jessica W.; Hill, Shirley Y.
Background Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. Methods A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-Risk families were selected based on the presence of two alcohol dependent sisters. Low-Risk families were selected on the basis of minimal first and second degree relatives with AD. High-Risk (HR=99) and Low-Risk offspring (LR=110) were assessed annually during childhood and biennially in young-adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit mothers were interviewed concerning their prenatal use of substances. Results High-Risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than Low-Risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. Conclusions
Morris, Laurel S; Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J; Orban, Csaba; Passetti, Filippo; Paterson, Louise M; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M; Bullmore, Edward T; Lingford-Hughes, Anne R; Deakin, Bill; Nutt, David J; Sahakian, Barbara J; Robbins, Trevor W; Voon, Valerie
Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.
Mohagheghi, Arash; Amiri, Shahrokh; Mousavi Rizi, Seyedreza; Safikhanlou, Salman
Emotional intelligence might play an important role in the onset and persistence of different psychopathologies. This study investigated the relationship between emotional intelligence and alcohol dependence. In this case-control study, participants included alcohol dependent individuals and mentally healthy inpatients. Each group consisted of 40 individuals (male/female: 1). The diagnosis was based on the criteria of the DSM-IV-TR using the Structured Clinical Interview for DSM-IV (SCID-IV). All the participants completed Bar-On emotional intelligence test. 20 males and 20 females were included in each group. Mean age of alcohol dependent participants and controls was 31.28±7.82 and 34.93±9.83 years in that order. The analyses showed that the alcohol dependent individuals had a significant difference compared with the control group and received lower scores in empathy, responsibility, impulse control, self-esteem, optimism, emotional consciousness, stress tolerance, autonomy, problem-solving, and total score of emotional intelligence components. Patients with alcohol dependence have deficits in components of emotional intelligence. Identifying and targeted training of the individuals with lower scores in components of emotional intelligence may be effective in prevention of alcohol dependence.
Hasking, Penelope A; Oei, Tian P S
This study expanded earlier work conducted by this laboratory by examining the independent and interactive effects of avoidant coping strategies, positive and negative alcohol expectancies and self-efficacy, in predicting volume and frequency of alcohol consumption in a sample dependent on alcohol (n=296). Coping strategies were found to be salient predictors of frequency of drinking, while venting emotion interacted with negative expectancies to predict both volume and frequency of drinking. Venting emotion was also found to interact with drinking refusal self-efficacy in predicting volume of alcohol consumed. These interactions are discussed in terms of the cognitive and behavioural mechanisms thought to underlie drinking behaviour.
Momeni, Shima; Roman, Erika
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.
Quintana, M. I.; Bressan, R. A.; Mello, M. F.; Andreoli, S. B.
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
Bernardin, Florent; Maheut-Bosser, Anne; Paille, François
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
Evren, Cuneyt; Dalbudak, Ercan; Evren, Bilge; Cetin, Rabia; Durkaya, Mine
The aim of this study was to investigate the relationship between self-mutilation (SM) and posttraumatic stress disorder (PTSD) in male alcohol-dependent inpatients, and to examine whether there is something unique about self-mutilaters with the PTSD/alcohol-dependence co-morbidity, compared with self-mutilaters without PTSD in this population. Participants were 156 consecutively admitted male alcohol-dependent inpatients. Patients were investigated with the Self-mutilative Behaviour Questionnaire (SMBQ), the Traumatic Experiences Checklist (TEC), the Clinician Administered PTSD Scale (CAPS), the Symptom Checklist-Revised (SCL-90-R) and the Michigan Alcoholism Screening Test (MAST). Among alcohol-dependent inpatients, 34.0% (n=53) were considered as group with SM. Rate of being unemployed, history of any trauma, history of suicide attempt and lifetime PTSD diagnosis were higher, whereas being married, current age, age at onset of regular alcohol use and duration of education were lower in the group with SM. Mean scores of SCL-90 subscales, TEC and MAST were higher in the SM group. Although SM might be related with PTSD among male alcohol-dependent inpatients, predictors of SM were age at onset of regular alcohol use, history of suicide attempt, anxiety, depression and hostility. Age at onset of regular alcohol use, history of suicide attempt, anxiety, depression and somatisation predicted SM in the subgroup of patients without PTSD, whereas hostility predicted SM alone in the subgroup of patients with PTSD. Results support the anti-suicide and the affect-regulation models of SM in the non-PTSD group, whereas they support the hostility model of SM in the subgroup with PTSD in alcohol-dependent inpatients. Thus, to reduce self-mutilative behaviour (SMB)among alcohol-dependent patients, clinicians must address different subjects in different subgroup patients; that is, focussing hostility in those with PTSD co-morbidity.
Jarmolowicz, David P.; Bickel, Warren K.; Gatchalian, Kirstin M.
Background Research on delay discounting has expanded our understanding of substance dependence in many ways. Recently, orderly discounting of sexual rewards has been demonstrated in both substance-dependent individuals, and healthy controls. Less clear, however, is if rates of sexual discounting are higher than controls in alcohol-dependent-individuals. Methods 20 Alcohol-dependent individuals and 21 healthy control participants completed two delay-discounting tasks. One task involved monetary rewards, whereas the other involved the discounting of sexual rewards (i.e., number of sex acts). Results Alcohol dependent individuals discounted sexual rewards at significantly higher rates than did controls. There was a trend towards, but not a similarly significant relation for the discounting of monetary rewards. Conclusions Rates of sexual discounting are elevated in alcohol dependent individuals. If this relation is replicated in other at risk populations, the rapid devaluation of sexual rewards may be a behavioral marker of impulsive sexual choices. PMID:23312341
Berking, Matthias; Margraf, Matthias; Ebert, David; Wupperman, Peggilee; Hofmann, Stefan G.; Junghanns, Klaus
Objective As emotion regulation is widely considered to be a primary motive in the misuse of alcohol, the aim of 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 skills predicted alcohol use during and after treatment for AD. Participants were 116 individuals treated for AD with cognitive behavioral therapy. Emotion regulation and severity of AD symptoms were assessed by self-report. Alcohol use during treatment was assessed by breathalyzer and urine analysis for ethyl glucuronid; alcohol use during the 3-month follow-up interval was assessed by self-report. Results Pretreatment emotion-regulation skills predicted alcohol use during treatment, and posttreatment emotion-regulation skills predicted alcohol use at follow-up, even when controlling for other predictors potentially related to emotion regulation. Among a broad range of specific emotion-regulation skills, the ability to tolerate negative emotions was the only skill that negatively predicted subsequent alcohol consumption when controlling for the other skills. Individuals in the AD sample reported significantly more deficits in emotion-regulation skills than did those in a non-clinical control sample, but significantly less than did those in a sample of individuals exclusively meeting criteria for major depressive disorder. Conclusions Enhancement of general emotion-regulation skills, especially the ability to tolerate negative emotions, appears to be an important target in the treatment of AD. PMID:21534653
Sarid-Segal, Ofra; Piechniczek-Buczek, Joanna; Knapp, Clifford; Afshar, Maryam; Devine, Eric; Sickles, Laurie; Uwodukunda, Emma; Richambault, Courtney; Koplow, Jillian; Ciraulo, Domenic
The aim of this open-label pilot study was to assess the efficacy and safety of the novel anticonvulsant agent, levetiracetam, for the treatment of alcohol dependence. A maximal dose of 2000 mg was administered daily for 10 weeks to alcohol dependent subjects (n = 20). Mean reported ethanol intake declined significantly from 5.3 to 1.7 standard drinks per day. Levetiracetam was well tolerated by most subjects. PMID:18584574
Berglund, Kristina J; Balldin, Jan; Berggren, Ulf; Gerdner, Arne; Fahlke, Claudia
Reduced central serotonergic neurotransmission has been demonstrated in individuals with excessive alcohol consumption and/or alcohol dependence. Childhood maltreatment has also been found to have a negative impact on central serotonergic neurotransmission. The aim of this study was to evaluate the impact of childhood maltreatment on central serotonergic dysfunction in alcohol-dependent individuals. Adult men with a diagnosis of alcohol dependence (n = 18) were recruited from outpatient treatment units for alcoholism. Central serotonergic neurotransmission was assessed by a neuroendocrine method, that is, the prolactin (PRL) response to the selective 5-HT reuptake inhibitor citalopram. Childhood maltreatment was assessed retrospectively by the Childhood Trauma Questionnaire. Alcohol-dependent individuals with childhood experience of emotional abuse had significantly lower PRL response compared with those without such abuse (3 ± 5 and 64 ± 24 mU/l, respectively; t = 6.51, p < 0.001). Among those who reported childhood emotional abuse, 4 of 7 individuals had flat PRL responses in comparison with none in those with no report of such abuse (p < 0.01). This is the first study to show that self-reported childhood maltreatment, in particular emotional abuse, in male alcohol-dependent individuals is associated with a quite dramatic (more than 90%) reduction in central serotonergic neurotransmission. It should, however, be noted that the number of individuals is relatively small, and the results should therefore be considered as preliminary. Copyright © 2013 by the Research Society on Alcoholism.
Talley, Amelia E; Brown, Jennifer L; Stevens, Angela K; Littlefield, Andrew K
Objective: The current study examines the relation between peer descriptive norms for alcohol involvement and alcohol-dependence symptomatology and whether this relation differs as a function of sexual self-concept ambiguity (SSA). This study also examines the associations among peer descriptive norms for alcohol involvement, alcohol-dependence symptomatology, and lifetime HIV risk-taking behavior and how these relations are influenced by SSA. Method: Women between ages 18 and 30 years (N = 351; M = 20.96, SD = 2.92) completed an online survey assessing sexual self-concept, peer descriptive norms, alcohol-dependence symptomatology, and HIV risk-taking behaviors. Structural equation modeling was used to test hypotheses of interest. Results: There was a significant latent variable interaction between SSA and descriptive norms for peer alcohol use. There was a stronger positive relationship between peer descriptive norms for alcohol and alcohol-dependence symptomatology when SSA was higher compared with when SSA was lower. Both latent variables exhibited positive simple associations with alcohol-dependence symptoms. Peer descriptive norms for alcohol involvement directly and indirectly influenced HIV risk-taking behaviors, and the indirect influence was conditional based on SSA. Conclusions: The current findings illustrate complex, nuanced associations between perceived norms, identity-related self-concepts, and risky health behaviors from various domains. Future intervention efforts may be warranted to address both problem alcohol use and HIV-risk engagement among individuals with greater sexual self-concept ambiguity. PMID:25343661
Bagga, D; Singh, N; Modi, S; Kumar, P; Bhattacharya, D; Garg, M L; Khushu, S
Neuropsychological studies have shown that alcohol dependence is associated with neurocognitive deficits in tasks requiring memory, perceptual motor skills, abstraction and problem solving, whereas language skills are relatively spared in alcoholics despite structural abnormalities in the language-related brain regions. To investigate the preserved mechanisms of language processing in alcohol-dependents, functional brain imaging was undertaken in healthy controls (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took more time than controls for performing the task but there was no significant difference in their response accuracy. fMRI data analysis revealed that while performing the task, the alcoholics showed enhanced activations in left supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle temporal gyrus as compared to control subjects. The extensive activations observed in alcoholics as compared to controls suggest that alcoholics recruit additional brain areas to meet the behavioural demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting compensatory mechanisms for the execution of task for showing an equivalent performance or decreased neural efficiency of relevant brain networks. However, on direct comparison of the two groups, the results did not survive correction for multiple comparisons; therefore, the present findings need further exploration.
Sjoerds, Zsuzsika; Stufflebeam, Steven M; Veltman, Dick J; Van den Brink, Wim; Penninx, Brenda W J H; Douw, Linda
Alcohol dependence (AD) is characterized by corticostriatal impairments in individual brain areas such as the striatum. As yet however, complex brain network topology in AD and its association with disease progression are unknown. We applied graph theory to resting-state functional magnetic resonance imaging (RS-fMRI) to examine weighted global efficiency and local (clustering coefficient, degree and eigenvector centrality) network topology and the functional role of the striatum in 24 AD patients compared with 20 matched healthy controls (HCs), and their association with dependence characteristics. Graph analyses were performed based on Pearson's correlations between RS-fMRI time series, while correcting for age, gender and head motion. We found no significant group differences between AD patients and HCs in network topology. Notably, within the patient group, but not in HCs, the whole-brain network showed reduced average cluster coefficient with more severe alcohol use, whereas longer AD duration within the patient group was associated with a global decrease in efficiency, degree and clustering coefficient. Additionally, within four a-priori chosen bilateral striatal nodes, alcohol use severity was associated with lower clustering coefficient in the left caudate. Longer AD duration was associated with reduced clustering coefficient in caudate and putamen, and reduced degree in bilateral caudate, but with increased eigenvector centrality in left posterior putamen. Especially changes in global network topology and clustering coefficient in anterior striatum remained strikingly robust after exploratory variations in network weight. Our results show adverse effects of AD on overall network integration and possibly on striatal efficiency, putatively contributing to the increasing behavioral impairments seen in chronically addicted patients.
Mainz, Verena; Drüke, Barbara; Boecker, Maren; Kessel, Ramona; Gauggel, Siegfried; Forkmann, Thomas
Alcohol dependence is a serious condition characterized by persistent desires to drink and unsuccessful efforts to control alcohol consumption despite the knowledge of dysfunction through the usage. The study at hand examined the influence of an alcohol exposure on inhibitory processes. Research provides evidence that trying to resist the temptation to drink exerts self-control, a limited resource which is used during all acts of inhibition. In line with this, studies demonstrate an impaired ability to regulate an already initiated response in alcohol-dependent and healthy subjects when confronted with alcohol-related stimuli. The related neuronal correlates in alcohol-dependent patients remain to be elucidated. The inhibition performance of 11 male alcohol-dependent patients during an alcohol exposure was compared with the task performance during a control condition. Behavioral data and neural brain activation during task performance were acquired by means of functional magnetic resonance imaging. The alcohol cue exposure led to subjectively stronger urges to drink which was accompanied by differential neural activation in amygdala and hippocampus. Moreover, the results revealed typical neural activation during inhibition performance across both conditions. Anyhow, we could not detect any behavioral deficits and only subtle neural differences between induction conditions during the performance of the inhibition task within the inferior frontal cortex. The results suggest that although the sample reports a subjectively stronger urge to drink after the alcohol cue exposure this effect was not strong enough to significantly impair task performance. Coherently, we discover only subtle differential brain activation between conditions during the inhibition task. In opposition to findings in literature our data do not reveal that an exposure to alcohol-related cues and thereby elicited cue reactivity results in impaired inhibition abilities. PMID:22557953
Miller, Peter M; Book, Sarah W; Stewart, Scott H
To summarize published data on pharmacologic treatments for alcohol dependence alone and in combination with brief psychosocial therapies that may be feasible for primary care and specialty medical settings. We conducted electronic searches of published original research articles and reviews in MEDLINE, SCOPUS, CINAHL, Embase, and PsychINFO. In addition, hand searches of reference lists of review articles, supplemental searches of internet references and contacts with experts in the field were conducted. Randomized controlled studies published between January 1960 and August 2010 that met our inclusion/exclusion criteria were included. A total of 85 studies, representing 18,937 subjects, met our criteria for inclusion. The evidence base for oral naltrexone (6% more days abstinent than placebo in the largest study) and topiramate (prescribed off-label) (e.g., 26.2% more days abstinent than placebo in a recent study) is positive but modest. Acamprosate shows modest efficacy with recently abstinent patients, with European studies showing better results than U.S. ones. The evidence-base for disulfiram is equivocal. Depot naltrexone shows efficacy (25% greater reduction in rate of heavy drinking vs. placebo, in one of the largest studies) in a limited number of studies. Some studies suggest that patients do better with extensive psychosocial treatments added to medications while others show that brief support can be equally effective. Although treatment effects are modest, medications for alcohol dependence, in conjunction with either brief support or more extensive psychosocial therapy, can be effective in primary and specialty care medical settings.
Beghè, F; Carpanini, M T
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.
Littlewood, Rae A.; Claus, Eric D.; Arenella, Pamela; Bogenschutz, Michael; Karoly, Hollis; Feldstein Ewing, Sarah W.; Bryan, Angela D.; Hutchison, Kent E.
Rationale It is well-established that the rewarding effects of alcohol are modulated by the mesolimbic dopaminergic system. Olanzapine, a D2 dopamine antagonist, has been shown to reduce alcohol craving and consumption. Objective To clarify whether olanzapine has clinical utility in the treatment of alcohol dependence, a 12-week, double-blind, randomized clinical trial was conducted. Methods One-hundred twenty-nine treatment-seeking alcohol dependent adults were randomly assigned to 12-weeks of olanzapine (5mg vs. 2.5mg) or placebo. Outcomes examined were average drinks per drinking day (DDD), proportion of drinking days to total days in treatment (PDD), alcohol craving, and impaired control over alcohol use. Mixed models were used to examine medication effects during the course of treatment on specified outcomes. Results All of the analyses indicated a main effect for time, such that there were reductions in alcohol use and craving and an increase in control over alcohol use across treatment conditions. Dose-response analyses indicated that, in comparison to placebo, participants in the 5mg group experienced reduced craving for alcohol and participants in the 2.5mg group decreased in PDD and increased in their control over alcohol use. Better control over alcohol use remained significant 6 months post-treatment for the 2.5mg group. Subjective experiences of the medication suggest that 2.5mg and 5mg were equally well-tolerated. Conclusions Results provide some support for the notion that dosage is an important consideration in relation to effectiveness; however, the cost-benefit balance does not support the clinical utility of olanzapine in treating alcohol dependence. PMID:25304864
Wu, Ping; Liu, Xinhua; Fang, Yunyun; Fan, Bin; Fuller, Cordelia J.; Guan, Zhiqiang; Yao, Zhongling; Kong, Junhui; Lu, Jin; Litvak, Iva J.
Aims: The aim of this study was to examine alcohol abuse/dependence symptoms among hospital employees exposed to a severe acute respiratory syndrome (SARS) outbreak, and the relationship between types of exposure to the SARS outbreak and subsequent alcohol abuse/dependence symptoms. Methods: A survey was conducted among 549 randomly selected hospital employees in Beijing, China, concerning the psychological impact of the 2003 SARS outbreak. Subjects were assessed on sociodemographic factors and types of exposure to the outbreak, and on symptoms of post-traumatic stress (PTS), alcohol abuse/dependence and depression. Results: Current alcohol abuse/dependence symptom counts 3 years after the outbreak were positively associated with having been quarantined, or worked in high-risk locations such as SARS wards, during the outbreak. However, having had family members or friends contract, SARS was not related to alcohol abuse/dependence symptom count. Symptoms of PTS and of depression, and having used drinking as a coping method, were also significantly associated with increased alcohol abuse/dependence symptoms. The relationship between outbreak exposure and alcohol abuse/dependence symptom count remained significant even when sociodemographic and other factors were controlled for. When the intrusion, avoidance and hyperarousal PTS symptom clusters were entered into the model, hyperarousal was found to be significantly associated with alcohol abuse/dependence symptoms. Conclusions: Exposure to an outbreak of a severe infectious disease can, like other disaster exposures, lead not only to PTSD but also to other psychiatric conditions, such as alcohol abuse/dependence. The findings will help policy makers and health professionals to better prepare for potential outbreaks of diseases such as SARS or avian flu. PMID:18790829
Fenton, M. C.; Geier, T.; Keyes, K.; Skodol, A. E.; Grant, B. F.; Hasin, D. S.
Background Studies of the relationship between childhood maltreatment and alcohol dependence have not controlled comprehensively for potential confounding by co-occurring maltreatments and other childhood trauma, or determined whether parental history of alcohol disorders operates synergistically with gender and maltreatment to produce alcohol dependence. We addressed these issues using national data. Method Face-to-face surveys of 27 712 adult participants in a national survey. Results Childhood physical, emotional and sexual abuse, and physical neglect were associated with alcohol dependence (p<0.001), controlling for demographics, co-occurring maltreatments and other childhood trauma. Attributable proportions (APs) due to interaction between each maltreatment and parental history revealed significant synergistic relationships for physical abuse in the entire sample, and for sexual abuse and emotional neglect in women (APs, 0.21, 0.31, 0.26 respectively), indicating that the odds of alcohol dependence given both parental history and these maltreatments were significantly higher than the additive effect of each alone (p<0.05). Conclusions Childhood maltreatments independently increased the risk of alcohol dependence. Importantly, results suggest a synergistic role of parental alcoholism: the effect of physical abuse on alcohol dependence may depend on parental history, while the effects of sexual abuse and emotional neglect may depend on parental history among women. Findings underscore the importance of early identification and prevention, particularly among those with a family history, and could guide genetic research and intervention development, e.g. programs to reduce the burden of childhood maltreatment may benefit from addressing the negative long-term effects of maltreatments, including potential alcohol problems, across a broad range of childhood environments. PMID:22883538
McPherson, Andrew; Martin, Colin R
To investigate gender differences in locus of control in an alcohol-dependent population. Locus of control helps to explain behaviour in terms of internal (the individual is responsible) or external (outside forces, such as significant other people or chance, are responsible) elements. Past research on gender differences in locus of control in relation to alcohol dependence has shown mixed results. There is a need then to examine gender and locus of control in relation to alcohol dependence to ascertain the veracity of any locus of control differences as a function of gender. The Multidimensional Health Locus of Control form-C was administered to clients from alcohol dependence treatment centres in the West of Scotland. Independent t-tests were carried out to assess gender differences in alcohol dependence severity and internal/external aspects of locus of control. One hundred and eighty-eight (53% females) participants were recruited from a variety of alcohol dependence treatment centres. The majority of participants (72%) came from Alcoholics Anonymous groups. Women revealed a greater internal locus of control compared with men. Women also had a greater 'significant others' locus of control score than men. Men were more reliant on 'chance' and 'doctors' than women. All these trends were not, however, statistically significant. Gender differences in relation to locus of control and alcohol dependence from past studies are ambiguous. This study also found no clear statistically significant differences in locus of control orientation as a function of gender. This article helps nurses to contextualise health behaviours as a result of internal or external forces. It also helps nursing staff to better understand alcohol dependence treatment in relation to self-efficacy and control. Moreover, it highlights an important concept in health education theory. © 2016 John Wiley & Sons Ltd.
Pettinati, H M; Volpicelli, J R; Luck, G; Kranzler, H R; Rukstalis, M R; Cnaan, A
Clinical studies that have evaluated serotonergic medications to reduce alcohol consumption have yielded conflicting results. These studies primarily treated patients with alcohol dependence, excluding those with a current depressive disorder, in an effort to differentiate any medication effects directly on drinking from those on mood. Yet despite the exclusion of current depression, a group of alcohol-dependent patients who are not depressed can be highly heterogeneous. For example, this subgroup can include those with a lifetime depressive disorder. If these patients were more sensitive to serotonergic medications than patients without a lifetime depressive disorder, medication effects in a subgroup of patients who were not depressed could be obscured. Thus, the purpose of this study was to examine the efficacy of sertraline for treating alcohol dependence in patient groups that were differentiated by the presence or absence of lifetime depression. This study examined the effectiveness of sertraline (200 mg/day) or placebo for 14 weeks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a lifetime diagnosis of comorbid depression. Sertraline treatment seemed to provide an advantage in reducing drinking in alcohol-dependent patients without lifetime depression, illustrated best with a measure of drinking frequency during treatment. However, sertraline was no better than placebo in patients with a diagnosis of lifetime comorbid depression, and current depression did not change the results. Treatment with selective serotonin reuptake inhibitors may be useful in alcohol-dependent patients who are not depressed. Subtyping those with alcohol dependence on the basis of the absence versus the presence of a lifetime depressive disorder may help to resolve conflicting findings in the literature on the treatment of alcohol dependence with serotonergic medications.
Szalontay, Andreea Silvana
No doubt, alcoholism represents nowadays the toxicomany with the highest expansion rate among all population groups, being recognized by the specialists from the medical, social, economic and legal field as a true "toxic pandemy". Researchers consider ethanol, this small but highly aggressive molecule, to have supremacy if we were to consider the number of pages dedicated to it worldwide on daily bases, in the medical or any other specialty literature. Nonetheless, the large volume of data regarding ethanol toxicity does not seen to simplify things, on the contrary it points out new information about the its negative effects on human body. Ethanol represents a toxic that is rapidly and completely absorbed in the intestinal tract being distributed to most tissues and organs; ethanol is recognized as an enzymatic inductor of its own metabolization but also of the metabolization of numerous therapeutic agents.
Lister, Jamey J; Milosevic, Aleks; Ledgerwood, David M
A large proportion of individuals with gambling disorder also present with a history of alcohol dependence, but few studies have directly examined the relationship between these two conditions. This study's primary and secondary aims were to 1) examine the relationship of personality traits to co-occurring lifetime (current/past) alcohol dependence status, while 2) accounting for differences in gambling characteristics and co-occurring psychiatric disorders among problem/pathological gamblers recruited from the community. Problem/pathological gamblers (N=150) completed measures of personality traits and gambling characteristics (e.g., gambling severity, gambling involvement, delayed discounting of monetary rewards), and were clinically interviewed for co-occurring psychiatric disorders. A co-occurring lifetime diagnosis of alcohol dependence (n=61, 40.7%) was associated with lower personality scores for Control, Well-Being, Achievement, Traditionalism, and Harm Avoidance, as well as higher scores for Alienation (Tellegen & Waller, 1994) in bivariate analyses. Problem/pathological gamblers with lifetime alcohol dependence reported greater lifetime gambling severity, greater past-year gambling involvement, steeper delayed discounting, and a greater likelihood of current and lifetime substance dependence, lifetime antisocial personality disorder, and current unipolar mood disorders. Multivariate analyses indicated that lower Control, Traditionalism, and Well-Being and a co-occurring lifetime substance dependence diagnosis best accounted for a co-occurring lifetime alcohol dependence diagnosis in problem/pathological gamblers. Problem/pathological gamblers with co-occurring lifetime alcohol dependence demonstrate addictive behavior across multiple domains and report a personality style characterized by hopelessness, impaired control, and resistance to externally-motivated treatment approaches. Implications for the treatment of these complex cases are discussed
de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F.; Hope, Bruce T.; Brennan, Molly; Cole, Maury; Koob, George F.
Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. SIGNIFICANCE STATEMENT Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These
Hufnagel, Anna; Frick, Ulrich; Ridinger, Monika; Wodarz, Norbert
There is inconsistent evidence about the potential influence of smoking on recovery from alcohol dependence. Our study aimed at assessing the impact of smoking-behavior on relapse during a 12 months follow-up period following a detoxification in patients with Alcohol Use Disorder (AUD). Three hundred Patients with AUD (74.9% smoking) were recruited from two inpatient detoxification units in psychiatric hospitals in Germany and their alcohol consumption was prospectively followed for 1 year. Data on different indicators of smoking behavior was gathered. Cox regression model was used to evaluate potential risk factors on time to relapse of alcohol consumption. Two hundred seventy-nine participants (n = 279) were included in the final analysis. Smoking increased the risk for alcohol relapse (hazard ratio = 3.962, 95% CI 1.582-9.921). However, this increased risk is slightly reduced with higher numbers of daily consumed cigarettes (hazard ratio per cigarette = .986, 95% CI .976-.995). Smoking reduced the probability of maintaining alcohol abstinence significantly, whereas higher number of cigarettes smoked daily diminished the increased risk of alcohol relapse in alcohol-dependent patients. Coordinated psychiatric and substance abuse interventions for different subgroups of patients with AUD in the post-acute treatment phase are necessary. Individualized treatment planning is especially important in smoking patients with AUD who are vulnerable for a relapse to alcohol drinking and for somatic complications. Our findings might support individualized treatment plans. (Am J Addict 2017;26:366-373). © 2017 American Academy of Addiction Psychiatry.
Rhodes, Sharyn S.; Jasinski, Donald R.
The study found that 40 percent of 25 adult alcoholics were found to have had special education, remedial services, or repeated grade failure concurrent with a familial history of alcoholism and current discrepancies indicative of learning disabilities. Results suggest that childhood learning disorders may be related to the development of…
Wu, Jie; Gao, Ming; Taylor, Devin H
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.
Grynberg, Delphine; de Timary, Philippe; Philippot, Pierre; D'Hondt, Fabien; Briane, Yasmine; Devynck, Faustine; Douilliez, Céline; Billieux, Joël; Heeren, Alexandre; Maurage, Pierre
Emotional and interpersonal deficits play a crucial role in alcohol-related disorders as they predict alcohol consumption and relapse. Recent models of emotion regulation in psychopathology postulate that these deficits are centrally related to increased abstract/analytic repetitive thinking, combined with reduced concrete/experiential repetitive thinking. As this assumption has not been tested in addictions, this study aimed at investigating repetitive thinking modes in a large sample of alcohol-dependent individuals. One hundred recently detoxified alcohol-dependent individuals (29 females; mean age = 49.51-years-old) recruited during the 3rd week of their treatment in a detoxification center were compared to 100 healthy controls (29 females; mean age = 48.51-years-old) recruited in the experimenters' social network, matched at the group level for age, gender, and educational level. All participants completed the Mini Cambridge Exeter Repetitive Thought Scale measuring abstract/analytic and concrete/experiential repetitive thinking modes as well as complementary psychopathological measures (Beck Depression Inventory and State/Trait Anxiety Inventory). Alcohol-dependent individuals have similar levels of concrete repetitive thinking as controls but report significantly higher levels of abstract repetitive thinking (p < 0.001; d = 1.28). This effect remains significant after controlling for depression and anxiety. Relative to healthy controls, alcohol-dependent patients report more frequent use of abstract/analytic repetitive thinking, with preserved concrete/experiential thinking. Despite the cross-sectional nature of the study, the frequent use of abstract repetitive thinking thus appears to constitute a main feature of alcohol-dependence.
Gizer, Ian R.; Ehlers, Cindy L.; Vietan, Cassandra; Seaton-Smith, Kimberly L.; Feiler, Heidi S.; Lee, James V.; Segall, Samantha K.; Gilder, David A.; Wilhelmsen, Kirk C.
Ample data suggest alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31–p36.22, 2q37.3, 8q24.3, and 18p11.21–p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31–p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3–p24.1, 9p24.1–p23, and 22q12.3–q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence. PMID:20817416
Kopera, Maciej; Jakubczyk, Andrzej; Suszek, Hubert; Glass, Jennifer M.; Klimkiewicz, Anna; Wnorowska, Anna; Brower, Kirk J.; Wojnar, Marcin
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
Kissler, Jessica L; Walker, Brendan M
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. PMID:26105136
Kissler, Jessica L; Walker, Brendan M
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.
Witteman, Jurriaan; Post, Hans; Tarvainen, Mika; de Bruijn, Avalon; Perna, Elizabeth De Sousa Fernandes; Ramaekers, Johannes G; Wiers, Reinout W
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.
Plebani, Jennifer G; Oslin, David W; Lynch, Kevin G
Prior clinical findings have indicated a potential lack of naltrexone efficacy among African Americans with alcohol dependence. However, no definitive conclusions have been drawn due to the relatively small numbers of African Americans in most alcohol treatment trials. The purpose of this study was to examine alcohol and naltrexone effects on healthy African-American individuals in a laboratory environment. Nonalcohol-dependent social drinking adults of African descent (n = 43) were recruited for participation. After consenting and completing the baseline assessment, they participated in four separate alcohol challenge sessions each separated by at least 10 days. During each of the sessions, subjects were administered alcohol or sham drinks, after pretreatment with either naltrexone (50 mg/day) or placebo in a double-blind fashion. The order of the four sessions was randomly assigned. During each session, breath alcohol levels and subjective responses were measured. Results indicate an alcohol effect among these subjects for subjective responses, but no naltrexone effect. Similar to the apparent lack of clinical efficacy findings, naltrexone does not appear to impact alcohol effects in African-American social drinkers. Future studies should investigate African-American populations with heavy drinking as well as alcohol-dependent subjects in order to strengthen the parallels to clinical findings.
Evren, Cuneyt; Sar, Vedat; Dalbudak, Ercan; Oncu, Fatih; Cakmak, Duran
The aim of this study was to investigate the relationship between social anxiety and dissociation among male patients with alcohol dependency. Participants were 176 male patients consecutively admitted to an alcohol dependency treatment unit. The Liebowitz Social Anxiety Scale, the Dissociative Experiences Scale, the Beck Depression Inventory, the Spielberger State and Trait Anxiety Inventory, the Michigan Alcoholism Screening Test, and the Symptom Checklist-90-Revised were administered to all participants. The dissociative (N=58, 33.0%) group had significantly higher social anxiety scores than the non-dissociative participants. Patients with a history of suicide attempt or childhood abuse had elevated social anxiety scores compared to those without. In multivariate analysis, dissociative taxon membership predicted both of the two social anxiety subscale scores consisting of fear/anxiety and avoidance in a highly significant level while trait anxiety was a significant covariant for these subscales. Among dissociative symptoms, only depersonalization and amnesia/fugue were predictors of social anxiety. Dissociation and social anxiety are interrelated among alcohol-dependent men. This relationship may have implications for prevention and treatment of alcohol dependency among men with a childhood trauma history in particular.
de Bruin, Eveline A; Hulshoff Pol, Hilleke E; Schnack, Hugo G; Janssen, Joost; Bijl, Suzanne; Evans, Alan C; Kenemans, J Leon; Kahn, René S; Verbaten, Marinus N
The purpose of this study was to investigate whether current or lifetime alcohol intake is related to focal gray and white matter in healthy non-alcohol-dependent drinkers, and, if so, whether these densities are related to functional brain activity associated with visual attention. Voxel-based morphometric analyses of gray- and white-matter densities, and event-related potentials in response to a visual-attention task were determined in 47 male drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg). All participants had a negative personal and family history of alcohol dependence to reduce possible confounding by genetic factors related to alcohol dependence. In males, mean lifetime alcohol intake was negatively associated with gray-matter density and positively associated with white-matter density in the right frontal gyrus (BA 6) and the right parietal region (BA 40). Right frontal (but not right parietal) gray and white matter in males correlated with the P3 amplitude of the event-related potentials elicited in a visual-attention task. In females, mean lifetime alcohol intake was not associated with gray- or white-matter density. Current alcohol intake was unrelated to gray or white matter in both males and females. In conclusion, lifetime alcohol intake is associated with focal gray-matter decreases and white-matter increases in the right frontal and right parietal brain regions in non-alcohol-dependent males, but not in females. These alcohol-related differences in focal brain matter in males are associated with differences in brain function related to visual attention. As the confounding effects of genetic factors were reduced, the present results may selectively relate to the effects of alcohol intake on focal brain matter.
Mon, Anderson; Durazzo, Timothy C.; Abe, Christoph; Gazdzinski, Stefan; Pennington, David; Schmidt, Thomas; Meyerhoff, Dieter J.
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
Leggio, L.; Ferrulli, A.; Zambon, A.; Caputo, F.; Kenna, G.A.; Swift, R.M.; Addolorato, G.
Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABAB receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some LFTs (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients. PMID:22244707
Young-Wolff, Kelly C.; Kendler, Kenneth S.; Sintov, Nicole D.; Prescott, Carol A.
Background Major depression and alcohol dependence co-occur within individuals and families to a higher than expected degree. This study investigated whether mood-related drinking motives mediate the association between major depression and alcohol dependence, and what the genetic and environmental bases are for this relationship. Methods The sample included 5,181 individuals from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, aged 30 and older. Participants completed a clinical interview which assessed lifetime major depression, alcohol dependence, and mood-related drinking motives. Results Mood-related drinking motives significantly explained the depression-alcohol dependence relationship at both the phenotypic and familial levels. Results from twin analyses indicated that for both males and females, the familial factors underlying mood-related drinking motives accounted for virtually all of the familial variance that overlaps between depression and alcohol dependence. Conclusions The results are consistent with an indirect role for mood-related drinking motives in the etiology of depression and alcohol dependence, and suggest that mood-related drinking motives may be a useful index of vulnerability for these conditions. PMID:19426164
Sreekumar, Sreeja; Subhalakshmi, T. P.; Varghese, P. Joseph
Background and Objectives: Mental health and resilience of family members of individuals with alcohol dependence affect their ability to cope with stress, maintain emotional well-being, and to positively adapt to their difficult life circumstances. This study attempted to study resilience among wives of men with alcohol dependence syndrome. Materials and Methods: Consecutive patients with a diagnosis of alcohol dependence and their wives attending the Department of Psychiatry, MOSC Medical College, Kolenchery, Kerala, over a 1-year period were recruited. The wives were assessed using the Resilience Scale for Adults and the Hamilton Depressive Rating Scale, whereas their spouses were evaluated using severity of alcohol dependence questionnaire and a proforma to collect sociodemographic and clinical characteristics. Women with good resilience were compared to those with low scores using a case–control framework to evaluate factors associated with resilience. Multivariable analysis to adjust for common confounders was done using multiple linear regression. Results: Eighty patients and their spouses were recruited and evaluated. Resilience was inversely related to the severity of alcohol dependence, years of drinking in dependence pattern, history of domestic violence, and severity of depression in wives. Involvement in support groups was protective. Conclusion: Assessment of resilience in wives of individuals with alcohol dependence and identification and management of those with poor resilience should go hand in hand with their husband's treatment program. PMID:28066009
... distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that ... alcohol to feel the same effect With alcohol abuse, you are not physically dependent, but you still ...
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
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
Donadon, M.F.; Osório, F.L.
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
Chassin, Laurie; Fora, David B; King, Kevin M
This study describes trajectories of substance use and dependence from adolescence to adulthood. Identified consumption groups include heavy drinking/heavy drug use, moderate drinking/experimental drug use, and light drinking/rare drug use. Dependence groups include alcohol only, drug only, and comorbid groups. The heavy drinking/heavy drug use group was at risk for alcohol and drug dependence and persistent dependence and showed more familial alcoholism, negative emotionality, and low constraint. The moderate drinking/experimental drug use group was at risk for alcohol dependence but not comorbid or persistent dependence and showed less negative emotionality and higher constraint. Familial alcoholism raised risk for alcohol and drug use and dependence in part because children from alcoholic families were more impulsive and lower in agreeableness.
Rouvinen-Lagerström, Noora; Lahti, Jari; Alho, Hannu; Kovanen, Leena; Aalto, Mauri; Partonen, Timo; Silander, Kaisa; Sinclair, David; Räikkönen, Katri; Eriksson, Johan G.; Palotie, Aarno; Koskinen, Seppo; Saarikoski, Sirkku T.
Aims: The molecular epidemiological studies on the association of the opioid receptor µ-1 (OPRM1) polymorphism A118G (Asn40Asp, rs1799971) and alcohol use disorders have given conflicting results. The aim of this study was to test the possible association of A118G polymorphism and alcohol use disorders and alcohol consumption in three large cohort-based study samples. Methods: The association between the OPRM1 A118G (Asn40Asp, rs1799971) polymorphism and alcohol use disorders and alcohol consumption was analyzed using three different population-based samples: (a) a Finnish cohort study, Health 2000, with 503 participants having a DSM-IV diagnosis for alcohol dependence and/or alcohol abuse and 506 age- and sex-matched controls; (b) a Finnish cohort study, FINRISK (n = 2360) and (c) the Helsinki Birth Cohort Study (n = 1384). The latter two populations lacked diagnosis-based phenotypes, but included detailed information on alcohol consumption. Results: We found no statistically significant differences in genotypic or allelic distribution between controls and subjects with alcohol dependence or abuse diagnoses. Likewise no significant effects were observed between the A118G genotype and alcohol consumption. Conclusion: These results suggest that A118G (Asn40Asp) polymorphism may not have a major effect on the development of alcohol use disorders at least in the Finnish population. PMID:23729673
Hiltunen, A J; Koechling, U M; Voltaire-Carlsson, A; Borg, S
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.
van den Brink, Wim; Aubin, Henri-Jean; Bladström, Anna; Torup, Lars; Gual, Antoni; Mann, Karl
Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461). Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study. Results: The pooled population consisted of 667 patients: placebo n = 332; nalmefene n = 335. There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [treatment difference: −3.2 days (95% CI: −4.8; −1.6); P < 0.0001] and total alcohol consumption [treatment difference: −14.3 g/day (−20.8; −7.8); P < 0.0001] at Month 6. Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group. Adverse events and adverse events leading to dropout were more common with nalmefene than placebo. Conclusion: As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and randomization, and the effect in this subgroup was larger than in the total population. PMID:23873853
Rolland, Benjamin; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Gautier, Sophie; Auffret, Marine; Pignon, Baptiste; Valin, Thomas; Bordet, Régis; Cottencin, Olivier
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.
Higley, Amanda E.; Crane, Natania A.; Spadoni, Andrea D.; Quello, Susan B.; Goodell, Vivian
Rationale Alcohol dependence is associated with high rates of recidivism. Stress has been shown to increase alcohol craving in alcohol-dependent individuals, but the association between stress-induced craving and alcoholism treatment outcome is not well understood. Objective The aim of the present study was to examine the relationship between strength of stress-induced alcohol craving in the human laboratory and subsequent drinking in a cohort of treatment-seeking, alcohol-dependent adults. Materials and methods This is a prospective study assessing stress-induced craving in the lab and subsequent treatment outcomes in alcohol-dependent subjects enrolled in a 12-week outpatient study. Stress was induced using a previously developed, individualized, audio recorded stress script and validated with objective (salivary cortisol) and subjective measures of distress. In vivo craving for alcohol was measured pre- and post-challenge using VAS. Results Subjects were 28 (16 male, 12 female) alcohol-dependent outpatients. Greater stress-induced craving was associated with a blunted salivary cortisol response, significantly shorter time to alcohol relapse, higher mean drinks per week, fewer percent days abstinent, and lower rates of complete abstinence over the study duration (all p's<0.05). Conversely, no demographic or baseline variables were significant predictors of any outcome variable. Conclusions These results suggest that greater stress-related increases in alcohol craving are associated with poorer alcohol treatment outcomes. The findings support the use of stress-induced craving as a predictor of alcohol relapse propensity. Furthermore, treatments that address high stress levels and the associated high levels of alcohol craving are likely to improve treatment outcomes in alcohol dependence. PMID:21607563
Walsh, Kate; Elliott, Jennifer C.; Shmulewitz, Dvora; Aharonovich, Efrat; Strous, Rael; Frisch, Amos; Weizman, Abraham; Spivak, Baruch; Grant, Bridget F.; Hasin, Deborah
Background Substance dependence is more common among trauma-exposed individuals; however, most studies suggest that Posttraumatic Stress Disorder (PTSD) accounts for the link between trauma exposure (TE) and substance dependence. Objectives This study examined associations between TE and substance dependence (alcohol, nicotine, and marijuana), and whether PTSD accounted for this association. Method 1,317 Jewish Israeli household residents completed in-person structured interviews assessing TE, PTSD, and substance (alcohol, nicotine, marijuana) dependence between 2007–2009. Regression analyses examined associations among TE, PTSD, and substance dependence. Results In the full sample, mean number of traumatic events was 2.7 (sd=2.2), with 83.7% experiencing at least one event. In the full sample, mean number of PTSD symptoms was 2.5 (sd=3.4), with 13.5% meeting PTSD diagnostic criteria. Prevalence of alcohol dependence was 13.4%; nicotine dependence 52.8%; and marijuana dependence 12.1%. Number of traumatic events was associated with increased odds of alcohol (OR=1.3; 95% CI=1.2–1.4) and nicotine (OR=1.2; 95% CI=1.1–1.3) dependence. Similarly, any traumatic event exposure was associated with increased odds of alcohol (OR= 3.1; 95% CI= 1.6–6.0) and nicotine (OR=1.9; 95% CI=1.2–2.9) dependence. PTSD symptoms were associated with increased odds of alcohol (OR=1.2; 95% CI=1.1–1.3), nicotine (OR=1.1; 95% CI=1.1–1.2), and marijuana (OR=1.1; 95% CI=1.04–1.2) dependence; similarly, a PTSD diagnosis was associated with increased odds of alcohol (OR=3.4; 95% CI=2.1–5.5), nicotine (OR=2.2; 95% CI = 1.4–3.4), and marijuana (OR=2.6; 95% CI=1.2–5.9) dependence. PTSD symptoms accounted for a sizeable proportion of the TE effect on alcohol (46%) and nicotine dependence (31%). Conclusion Individuals with more traumatic events had heightened risk for alcohol and nicotine dependence, and PTSD symptoms partially accounted for this risk. However, marijuana
Figlie, Neliana Buzi; Laranjeira, Ronaldo
This article aims is to conceptualize and describe the main steps in case management applied to the treatment of alcohol dependence. It is important to note the case manager functions, the importance of the first appointment, check the motivation to the treatment, some goals and activities suggestions for adherence reinforcement.
Grzywacz, Anna; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy
The aim of this study was to evaluate the role of dopamine D4 receptor (DRD4) exon 3 polymorphisms (48 bp VNTR) in the pathogenesis of alcoholism. This polymorphism was investigated in the association study in a whole group of alcoholics (n = 122) and in homogenous overlapping subgroups: 1) with early age of onset of alcoholism (AOO < or = 26 years) (n = 65) and 2) with a co-occurrence of dissocial personality disorder (n = 38), and 3) in patients with a history of delirium tremens and/or alcohol seizures (n = 41). The control group consisted of healthy volunteers, gender and age matched, with excluded psychiatric disorders (n = 399). The history of alcoholism was investigated using SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism - Polish version). The DRD4 receptor exon 3 polymorphism was determined using PCR. We found significant differences in the short alleles (2-5 VNTR) frequencies between controls and patients with a history of delirium tremens and/or alcohol seizures (p = 0.043). A trend was also observed in the higher frequency of short alleles amongst individuals with an early age of onset of alcoholism (p = 0.063). The results of this study suggest that inherited short variants of DRD4 alleles may play role in pathogenesis of alcohol dependence.
Franzos, M Alaric; Franzos, Tracy L; Woolford, Jeffrey S; McDonald, William A
Alcohol is tightly interwoven with the image and culture of aviation. When alcohol is combined with aviation, the result can be fatal to aircrew, passengers, and bystanders. Alcohol has been implicated in 8 to 12% of fatal general aviation accidents. With approximately 10% of the general population estimated to have alcohol abuse or dependence, alcohol issues are similarly common among aviators. Clear and concise guidelines exist to address alcohol disorders in both civilian and military aviation. However, few health care providers outside the aviation community are aware of these guidelines. When an aviator presents with an alcohol disorder, the well-intentioned provider may be reluctant to address the issue because of poor understanding of the occupational implications or a misplaced effort to preserve the aviator's career. However, proper therapy often permits the aviator to continue flying duties without adverse career impact. This review will discuss the implications, guidelines, and prognosis for the alcohol-dependent aviator and provide resources to enable the responsible health care provider to return the pilot to flight status as soon as practicable. Knowledge of these civilian and military guidelines will help close the treatment and communication gaps between aeromedical specialists and other medical professionals.
Han, Changwoo; Bae, Hwallip; Lee, Yu-Sang; Won, Sung-Doo; Kim, Dai Jin
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
Miquel, Laia; Gual, Antoni; Vela, Emili; Lligoña, Anna; Bustins, Montserrat; Colom, Joan; Rehm, Jürgen
To examine the association between drinking levels and inpatient health service utilization in people with a lifetime diagnosis of alcohol dependence. A longitudinal prospective study was conducted in a cohort of patients with alcohol dependence who had undergone treatment in 1987. Current results refer to the association between drinking patterns at 20-year follow-up and subsequent inpatient health service utilization. At 20 years after baseline, 530 of 850 patients were alive with administrative data available. Follow-up interview was conducted on 378 patients. There were 88 refusals and 64 could not be traced. Three categories of alcohol consumption were established (abstainers, moderate drinkers and heavy drinkers) depending on the pattern of alcohol use during the last year prior to the evaluation. Health service utilization was based on official statistics, including admissions to general, rehabilitation and psychiatric hospitals. The time period analysed was 5 years after the assessment of drinking patterns. Admission rates were lowest for abstainers compared to people with moderate and heavy drinking. With respect to hospital days, heavy drinking was associated with significantly higher adjusted rates than both abstainers and moderate drinkers. Alcohol-related diagnoses in hospital admissions were more frequent for both moderate and heavy drinkers. Abstinence and moderate alcohol consumption were both associated with lower hospitalization in people with a lifetime diagnosis of alcohol dependence. Thus, not only abstinence-oriented treatment strategies but also those to reduce alcohol intake would reduce inpatient hospitalizations. Abstention and reduced drinking in lifetime alcohol-dependent patients were associated with lower health care utilization compared to heavy drinking. Alcohol treatment strategies for alcohol-dependent patients have a positive impact on the reduction in health care utilization. An increase in treatment rate for alcohol use
Thompson, Ronald G; Lizardi, Dana; Keyes, Katherine M; Hasin, Deborah S
This study examined whether the experiences of childhood or adolescent parental divorce/separation and parental alcohol problems affected the likelihood of offspring DSM-IV lifetime alcohol dependence, controlling for parental history of drug, depression, and antisocial behavior problems. Data were drawn from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a nationally representative United States survey of 43,093 civilian non-institutionalized participants aged 18 and older, interviewed in person. Logistic regression models were used to calculate the main and interaction effects of childhood or adolescent parental divorce/separation and parental history of alcohol problems on offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Childhood or adolescent parental divorce/separation and parental history of alcohol problems were significantly related to offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Experiencing parental divorce/separation during childhood, even in the absence of parental history of alcohol problems, remained a significant predictor of lifetime alcohol dependence. Experiencing both childhood or adolescent parental divorce/separation and parental alcohol problems had a significantly stronger impact on the risk for DSM-IV alcohol dependence than the risk incurred by either parental risk factor alone. Further research is needed to better identify the factors that increase the risk for lifetime alcohol dependence among those who experience childhood or adolescent parental divorce/separation.
Raman, Vijaya; Prasad, Suveera; Appaya, M. Prakash
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
Farokhnia, M; Schwandt, M L; Lee, M R; Bollinger, J W; Farinelli, L A; Amodio, J P; Sewell, L; Lionetti, T A; Spero, D E; Leggio, L
Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction, P=0.03). Ratings of feeling intoxicated were significantly higher in the baclofen group after consuming the priming drink (P=0.006). During the self-administration session, baclofen significantly increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A significant reduction in heart rate (P<0.001) and a trend-level increase in diastolic blood pressure (P=0.06) were also detected in the baclofen group during the alcohol laboratory session. In conclusion, baclofen was shown to affect subjective and physiological responses to alcohol drinking in anxious alcohol-dependent individuals. These results do not support an anti-craving or anti-reinforcing effect of baclofen, but rather suggest that baclofen may act as a substitution medication for alcohol use disorder. PMID:28440812
Mason, Barbara J; Light, John M; Williams, Lauren D; Drobes, David J
There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence that may precipitate relapse in alcoholics, e.g. craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non-treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence and a strength of craving rating 1 SD or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1 week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral and unpleasant visual stimuli followed by alcohol or water cues. Gabapentin was associated with significantly greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoked craving. Gabapentin was also associated with significant improvement on several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue-reactivity studies as proof-of-concept screens for potential antirelapse drugs.
Boschloo, L; Vogelzangs, N; van den Brink, W; Smit, J H; Beekman, A T F; Penninx, B W J H
Much is still unclear about the role of personality in the structure of common psychiatric disorders such as depressive/anxiety disorders and alcohol dependence. This study will therefore examine whether various traits of negative emotionality and impulsivity showed shared or specific associations with these disorders. Method Cross-sectional data were used from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with no DSM-IV psychiatric disorder (n = 460), depressive/anxiety disorder only (i.e. depressive and/or anxiety disorder; n = 1398), alcohol dependence only (n = 32) and co-morbid depressive/anxiety disorder plus alcohol dependence (n = 358). Aspects of negative emotionality were neuroticism, hopelessness, rumination, worry and anxiety sensitivity, whereas aspects of impulsivity included disinhibition, thrill/adventure seeking, experience seeking and boredom susceptibility. Aspects of negative emotionality formed a homogeneous dimension, which was unrelated to the more heterogeneous construct of impulsivity. Although all aspects of negative emotionality were associated with alcohol dependence only, associations were much stronger for depressive/anxiety disorder only and co-morbid depressive/anxiety disorder with alcohol dependence. The results for impulsivity traits were less profound and more variable, with disinhibition and boredom susceptibility showing modest associations with both depressive/anxiety disorder and alcohol dependence, whereas low thrill/adventure seeking and high disinhibition were more strongly related with the first and the latter, respectively. Our results suggest that depressive/anxiety disorder and alcohol dependence result from shared as well as specific aetiological pathways as they showed the same associations with all aspects of negative emotionality, disinhibition and boredom susceptibility as well as specific associations with thrill/adventure seeking and disinhibition.
Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian
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
De Sousa, Avinash
Alcohol dependence is a major health problem worldwide. Various pharmacological agents have been used in the management of alcohol dependence. This review looks at the role of topiramate and other anticonvulsants in the management of alcohol dependence. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence. The literature on topiramate is reviewed and critically analyzed, along with its proposed mechanism of action in alcohol dependence. A review of data available on other anticonvulsants like carbamazepine, oxcarbazepine, sodium valproate, gabapentin and levetiracetam are presented and their potential in the treatment of alcohol dependence is considered, together with future research directions.
Brevers, Damien; Bechara, Antoine; Cleeremans, Axel; Kornreich, Charles; Verbanck, Paul; Noël, Xavier
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
Vendruscolo, Leandro F.; Roberts, Amanda J.
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
Vendruscolo, Leandro F; Roberts, Amanda J
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. Copyright © 2014 Elsevier Inc. All rights reserved.
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
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.
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.
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
de Zambotti, Massimiliano; Baker, Fiona C.; Sugarbaker, David S.; Nicholas, Christian L.; Trinder, John; Colrain, Ian M.
Background Alcoholism is considered an important risk factor for cardiovascular disease. Autonomic nervous system (ANS) function is a major indicator of cardiovascular health. Sleep is a suitable model to investigate ANS activity free from wake-related confounders. We investigated night-time ANS functioning, and the relationship between ANS activity and severity of alcohol dependence in chronic alcoholism. Methods Fourteen recently abstaining alcoholics (Age: 42.0±9.0y, 7 women) and sixteen age- and sex-matched controls (Age: 45.2±9.1y, 8 women) underwent a night of standard clinical polysomnography, including electrocardiographic recording. Time- and frequency-domain spectral analysis of heart rate variability (HRV) was performed across hours of the night and during artifact-free epochs of stable sleep and wakefulness (pre-sleep wakefulness, rapid-eye-movement (REM) and non-REM sleep). Results Alcoholics had a poorer subjective and objective sleep quality compared to controls. Across the night, alcoholic men and women had elevated heart rate, reduced total HRV, i.e. lower standard deviation of normal-to-normal inter-beat-intervals, and reduced high frequency activity (assessed by the high frequency power and by the square root of the mean squared of successive heart period differences). This ANS pattern was most apparent at the beginning of the night. None of the ANS measures was associated with lifetime alcohol consumption or duration of alcohol dependence. Conclusions Our results show that ANS functioning is disrupted during the night, even in undisturbed sleep periods, indicating poor cardiovascular functioning in recently detoxified alcohol-dependent men and women. PMID:24575956
Hoggatt, Katherine J; Jamison, Andrea L; Lehavot, Keren; Cucciare, Michael A; Timko, Christine; Simpson, Tracy L
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.
Rozeboom, Henriëtte J; Yu, Shukun; Mikkelsen, Rene; Nikolaev, Igor; Mulder, Harm J; Dijkstra, Bauke W
The quinone-dependent alcohol dehydrogenase (PQQ-ADH, E.C. 184.108.40.206) 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. © 2015 The Protein Society.
Chauhan, Vinay Singh; Azad, Sudip
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
O’Connell, Rebecca; Chishinga, Nathaniel; Kinyanda, Eugene; Patel, Vikram; Ayles, Helen; Weiss, Helen A.; Seedat, Soraya
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
Heavy drinking contributes to involuntary body movements such as akathisia. Quetiapine has been shown to alleviate symptoms of akathisia; however, its efficacy in the alcohol dependent population is not well established. Thus, we aimed to identify efficacy of Quetiapine in treating akathisia in very heavy drinking alcohol dependent patients. 108 male and female heavy alcohol consuming study participants received 13 weeks of Quetiapine XR. Drinking history (Timeline Followback, TLFB), depression (Montgomery-Asberg Depression Rating Scale, MADRS), and movement (Barnes Akathisia Scale, BARS) measures were collected at baseline (0 W), week 6 (6 W), and week 12 (12 W). The role of drinking, symptoms of depression, and efficacy of Quetiapine for treating akathisia were assessed. In patients with no symptoms of depression (low MADRS), Quetiapine treatment decreased symptoms of akathisia. Patients with clinically significant depression (high MADRS) reported a significant increase in akathisia measures at 6 W which eventually decreased at 12 W to below baseline levels. The increase in akathisia at 6 W corresponded with a significant increase in the patients' total drinks and heavy drinking pattern. Treatment with Quetiapine progressively lowered the occurrence of akathisia in alcohol dependent patients who do not show symptoms of depression. Quetiapine treatment lowered akathisia over time in heavy drinkers who had clinically significant symptoms of depression. PMID:27847671
Booth, Brenda M.; Curran, Geoffrey M.; Han, Xiaotong; Edlund, Mark J.
This study investigates the associations of recent criminal justice involvement with perceived need for alcohol treatment and alcohol treatment utilization, adjusting for demographic and clinical characteristics. We examined a national sample of adults with alcohol use disorders (AUD, N=4,390) from the 2006 National Survey on Drug Use and Health (NSDUH). Almost 15% reported criminal justice involvement in the past year. Generalized logit models regressed perceived need for alcohol or drug treatment and past year treatment utilization (versus neither) on past year legal involvement, demographic, and clinical information. In general, results found stronger associations between frequency of criminal justice involvement for treatment utilization compared to perceived need for treatment alone. Treatment utilization was also associated with being on probation, arrests for drug possession/sale and DUI but perceived need was not. Study results suggest opportunities for interventions to increase treatment rates or treatment need, a major correlate of treatment utilization. PMID:22954511
Ide, Jaime S.; Zhang, Sheng; Hu, Sien; Matuskey, David; Bednarski, Sarah R.; Erdman, Emily; Farr, Olivia M.; Li, Chiang-shan R.
Alcohol use and misuse is known to involve structural brain changes. Numerous imaging studies have examined changes in gray matter (GM) volumes in dependent drinkers, but there is little information on whether non-dependent drinking is associated with structural changes and whether these changes are related to psychological factors – such as alcohol expectancy – that influence drinking behavior. We used voxel based morphometry (VBM) to examine whether the global positive scale of alcohol expectancy, as measured by the Alcohol Expectancy Questionnaire AEQ-3, is associated with specific structural markers and whether such markers are associated with drinking behavior in 113 adult non-dependent drinkers (66 women). Alcohol expectancy is positively correlated with GM volume of left precentrral gyrus (PCG) in men and women combined and bilateral superior frontal gyri (SFG) in women, and negatively correlated with GM volume of the right ventral putamen in men. Furthermore, mediation analyses showed that the GM volume of PCG mediate the correlation of alcohol expectancy and the average number of drinks consumed per occasion and monthly total number of drinks in the past year. When recent drinking was directly accounted for in multiple regressions, GM volume of bilateral dorsolateral prefrontal cortices (DLPFC) correlated positively with alcohol expectancy in the combined sample. To our knowledge, these results are the first to identify the structural brain correlates of alcohol expectancy and its mediation of drinking behaviors. These findings suggest that more studies are needed to investigate increased GM volume in the frontal cortices as a neural correlate of alcohol expectancy. PMID:23461484
Leggio, Lorenzo; Kenna, George A; Fenton, Miriam; Bonenfant, Erica; Swift, Robert M
The goal of typology research is to identify subtypes of alcohol dependent (AD) patients sharing fundamental characteristics and try to match each subtype, with the most precise treatment strategy. This review provides a comprehensive history of the literature on alcohol dependent subtypes starting from the earliest attempt made by Jellinek. The binary models identified most closely with Cloninger and Babor as well as the successively more complex classifications are discussed. Typology classification potentially useful in guiding the treatment of AD patients, especially in the case of the serotonergic medications. Contrasting data suggests that other factors could influence the response to a medication and/or that more complex typologies should be identified. In summary, typology models may assist in the ascertainment criteria for clinical trials performed in behavioral and pharmacotherapeutic interventions. Greater emphasis, however, must be made to more clearly delineate this field of research, while moving toward more standardized typologies.
Szücs, Attila; Berton, Fulvia; Sanna, Pietro Paolo; Francesconi, Walter
Alcohol dependence and withdrawal has been shown to cause neuroadaptive changes at multiple levels of the nervous system. At the neuron level, adaptations of synaptic connections have been extensively studied in a number of brain areas and accumulating evidence also shows the importance of alcohol dependence-related changes in the intrinsic cellular properties of neurons. At the same time, it is still largely unknown how such neural adaptations impact the firing and integrative properties of neurons. To address these problems, here, we analyze physiological properties of neurons in the bed nucleus of stria terminalis (jcBNST) in animals with a history of alcohol dependence. As a comprehensive approach, first we measure passive and active membrane properties of neurons using conventional current clamp protocols and then analyze their firing responses under the action of simulated synaptic bombardment via dynamic clamp. We find that most physiological properties as measured by DC current injection are barely affected during protracted withdrawal. However, neuronal excitability as measured from firing responses under simulated synaptic inputs with the dynamic clamp is markedly reduced in all 3 types of jcBNST neurons. These results support the importance of studying the effects of alcohol and drugs of abuse on the firing properties of neurons with dynamic clamp protocols designed to bring the neurons into a high conductance state. Since the jcBNST integrates excitatory inputs from the basolateral amygdala (BLA) and cortical inputs from the infralimbic and the insular cortices and in turn is believed to contribute to the inhibitory input to the central nucleus of the amygdala (CeA) the reduced excitability of the jcBNST during protracted withdrawal in alcohol-dependent animals will likely affect ability of the jcBNST to shape the activity and output of the CeA.
Kratz, Ewa M; Waszkiewicz, Napoleon; Kaluza, Anna; Szajda, Sławomir D; Zalewska-Szajda, Beata; Szulc, Agata; Zwierz, Krzysztof; Ferens-Sieczkowska, Miroslawa
Glycosylation of serum proteins is affected with prolonged heavy drinking, and carbohydrate deficient transferrin (CDT) is well established and highly specific biomarker of sustained alcohol consumption. However, total amount of sialic acid is not the only glycoepitope that may be altered as a result of the disease. This work is focused on glycan structures altered in salivary glycoproteins of alcoholics, indicating the most efficient carriers of such marker glycoepitopes. Salivary glycoproteins of 31 alcohol-dependent patients and 21 healthy controls were studied by means of lectin ELISA and lectin blotting with the lectins specific for core and antennary fucose, α2,3-bound sialic acid as well as T and Tn antigens in O-glycans. In direct lectin ELISA, core fucosylation, α2,3 sialylation and expression of T-antigen were significantly lowered in the saliva of alcohol-dependent patients. In lectin blotting ten glycoprotein bands were analyzed. The profile of disease-related alterations was found to be complex, but all six lectins studied here were able to detect altered glycan structures. In some glycoproteins the tendency to correct the glycosylation profile was observed after 7 weeks of abstinence. Alterations in the glycosylation profiles in the salivary glycoproteins of alcohol-dependent people were found. Some of salivary glycoproteins, such as α-amylase, clusterin, haptoglobin, heavy and light chains of immunoglobulins, and transferrin, seem to be worthy of detailed glycosylation analysis in the detection of alcohol dependence. Further studies may allow one to estimate if such glycomarkers may also reflect the amount of alcohol intake or the duration of alcohol intake.
Chaudhary, Ninad S.; Kampman, Kyle M.; Kranzler, Henry R.; Grandner, Michael A.; Debbarma, Swarnalata; Chakravorty, Subhajit
Introduction Although psychosocial problems are commonly associated with both alcohol misuse and insomnia, very little is known about the combined effects of insomnia and current alcohol dependence on the severity of psychosocial problems. The present study evaluates whether the co-occurrence of insomnia and alcohol dependence is associated with greater psychosocial problem severity. Methods Alcohol dependent individuals (N=123) were evaluated prior to participation in a placebo-controlled medication trial. The Short Index of Problems (SIP), Addiction Severity Index (ASI), Insomnia Severity Index (ISI), and Time Line Follow Back (TLFB), were used to assess psychosocial, employment, and legal problems; insomnia symptoms; and alcohol consumption, respectively. Bivariate and multivariate analyses were used to evaluate the relations between insomnia and psychosocial problems. Results Subjects’ mean age was 44 years (SD=10.3), 83% were male, and their SIP sub-scale scores approximated the median for normative data. A quarter of subjects reported no insomnia; 29% reported mild insomnia; and 45% reported moderate-severe insomnia. The insomnia groups did not differ on alcohol consumption measures. The ISI total score was associated with the SIP total scale score (β=0.23, p=0.008). Subjects with moderate-severe insomnia had significantly higher scores on the SIP total score, and on the social and impulse control sub-scales, and more ASI employment problems and conflicts with their spouses than others on the ASI. Conclusion In treatment-seeking alcohol dependent subjects, insomnia may increase alcohol-related adverse psychosocial consequences. Longitudinal studies are needed to clarify the relations between insomnia and psychosocial problems in these subjects. PMID:26151580
Chartier, Karen G; Dick, Danielle M; Almasy, Laura; Chan, Grace; Aliev, Fazil; Schuckit, Marc A; Scott, Denise M; Kramer, John; Bucholz, Kathleen K; Bierut, Laura J; Nurnberger, John; Porjesz, Bernice; Hesselbrock, Victor M
Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption-related phenotypes. Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism. Genetic markers included ADH1Brs1229984, ADH1B-rs2066702, ADH1C-rs698, ADH4-rs1042364, and ADH4-rs1800759. Phenotypes were maximum drinks consumed in a 24-hour period and total number of alcohol dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Religious involvement was defined by self-reported religious services attendance. Both religious involvement and ADH1B-rs1229984 were negatively associated with the number of maximum drinks consumed and the number of lifetime alcohol dependence symptoms endorsed. The interactions of religious involvement with ADH1B-rs2066702, ADH1C-rs698, and ADH4-rs1042364 were significantly associated with maximum drinks and alcohol dependence symptoms. Risk variants had weaker associations with maximum drinks and alcohol dependence symptoms as a function of increasing religious involvement. This study provided initial evidence of a modifying effect for religious involvement on relationships between ADH variants and maximum drinks and alcohol dependence symptoms.
Vélez-Moreno, Antonio; Lozano, Óscar M; Fernández-Calderón, Fermín; Rojas, Antonio J; Sayans-Jiménez, Pablo; González-Saiz, Francisco; Ramírez López, Juan
Therapeutic success in the treatment of alcohol use disorders highly depends on an appropriate diagnosis. The Substance Dependence Severity Scale –SDSS- is a scale that assesses substance dependence in dimensional terms and that follows the diagnostic criteria established by the international classification systems. The aim of this study is to provide validity evidence for the severity dimension of the alcohol dependence scale of the SDSS comparing it with the Mini International Neuropsychiatric Interview –MINI-, and others variables related to substance use included in the EuropASI. A total of 109 patients admitted for treatment in the Drug Abuse Center Services of Huelva who had used alcohol in the month previous to the interview participated. The SDSS, MINI and EuropASI were administered. The diagnostic capacity of the SDSS was assessed by Receiver Operating Characteristic (ROC) curve analysis, taking the MINI dependence diagnosis as standard. The area under the ROC curve (AUC) was 0.917 (CI=0.867-0.968). The trade-off between parameters was detected for a score of 9, with suitable values of sensitivity and specificity (83.58% and 83.72%). The results support the use of the SDSS for the diagnosis of alcohol dependence and for assessment the severity of dependence. Administration of this scale makes it possible to obtain information, with a single score, on how severe the disorder is and whether the dependence criteria have been met.
Quiñones-Laveriano, Dante Manuel; Espinoza-Chiong, César; Scarsi-Mejia, Ottavia; Rojas-Camayo, José; Mejia, Christian Richard
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.
Koopmann, Anne; Leménager, Tagrid; Wolf, Nadine Donata; Reinhard, Iris; Hermann, Derik; Koch, Jan; Wiedemann, Klaus; Kiefer, Falk
Atrial natriuretic peptide (ANP) is well known to modulate fluid and electrolyte homeostasis but also to counter-regulate hypothalamic-pituitary-adrenal (HPA) axis activity. Correspondingly, recent studies suggest an important role of ANP in the neurobiology of anxiety. Preclinical and clinical data now provide evidence for an involvement of ANP in the pathophysiology of addictive behavior. The present study aims to elucidate the effects of ANP on alcohol-dependent patients' anxiety, perceived stress and craving during alcohol withdrawal. A sample of 59 alcohol-dependent inpatients was included in the analysis. A blood sample was taken at day 14 of detoxification in order to assess the concentrations of ANP and cortisol in plasma. In parallel, we assessed patients' alcohol craving, using the Obsessive Compulsive Drinking Scale, as well as anxiety (State-Trait Anxiety Inventory). Patients' stress levels were assessed using the Perceived Stress Scale. We found a significant negative association between patients' ANP plasma concentrations and anxiety, craving for alcohol and perceived stress. Regression analyses suggest that ANP is a significant predictor both for patients' perceived stress and for the severity of anxiety during early abstinence. The association of patients' ANP plasma levels and craving is suggested to be mediated by perceived stress. Our results suggest that the association of patients' ANP plasma levels and craving is mediated by their perceived stress. For this reason, intranasal application of ANP may prove to be a new avenue for the treatment of alcohol dependence in patients exhibiting high levels of perceived stress.
Edwards, Scott; Little, Hilary J.; Richardson, Heather N.; Vendruscolo, Leandro F.
Chronic alcohol consumption disrupts glucocorticoid signaling at multiple physiological levels to interact with several disease-related processes associated with neuroendocrine and psychiatric disorders. Excessive alcohol use produces stress-related neuroadaptations at the level of the hypothalamic-pituitary-adrenal (HPA) axis as well as within central (extra-hypothalamic) neural circuitry, including the central amygdala (CeA) and prefrontal cortex (PFC). Altered glucocorticoid receptor (GR) signaling in these areas following excessive alcohol exposure is postulated to mediate the transition from recreational drinking to dependence, as well as the manifestation of a host of cognitive and neurological deficits. Specifically, a bidirectional regulation of stress systems by glucocorticoids leads to the development of an HPA axis tolerance and a concomitant sensitization of cortical and subcortical circuitries. A greater understanding of how hypothalamic and extra-hypothalamic glucocorticoid systems interact to mediate excessive drinking and related pathologies will lead to more effective therapeutic strategies for alcohol use disorder (AUD) and closely related comorbidities. PMID:26003866
Ostlund, Anette; Hensing, Gunnel; Sundh, Valter; Spak, Fredrik
The aim of this study was to analyse stability of and change in personality traits in a general population sample of women over 5 years. Specific questions were how personality traits changed after a first episode of alcohol dependence/abuse (ADA), anxiety or depression disorders and after remission of an episode. The study was based on data from a longitudinal general population-based survey titled, "Women and alcohol in Göteborg (WAG)". A total of 641 women were interviewed in 1990 or 1995 and re-interviewed after 5 years. Personality traits were assessed with the Karolinska Scales of Personality (KSP) and lifetime psychiatric diagnoses given according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd revised edition (DSM-III-R). Mean T-scores (KSP) for the general population sample were stable between initial assessment and follow-up 5 years later. Correlations between assessments were high for most KSP scores, indicating high individual stability. For women with resolved ADA, KSP scores were normalized to five scales at the follow-up assessment: somatic anxiety, muscular tension, monotony avoidance, social desirability and irritability. Women who recovered from anxiety disorders during the follow-up had decreased scores in somatic anxiety and muscular tension and increased scores in verbal aggression. Women who developed ADA during follow-up had increased scores on the scales impulsiveness and verbal aggression. Women who developed depression during follow-up had increased monotony avoidance. Personality traits were generally stable in this adult female population but some personality traits changed in association with changes in psychiatric disorders. This knowledge could be useful in evaluation of treatment needs and treatment outcome.
Gullo, Matthew J; St John, Nathan; McD Young, Ross; Saunders, John B; Noble, Ernest P; Connor, Jason P
Perceived impaired control over alcohol use is a key cognitive construct in alcohol dependence that has been related prospectively to treatment outcome and may mediate the risk for problem drinking conveyed by impulsivity in non-dependent drinkers. The aim of the current study was to investigate whether perceived impaired control may mediate the association between impulsivity-related measures (derived from the Short-form Eysenck Personality Questionnaire-Revised) and alcohol-dependence severity in alcohol-dependent drinkers. Furthermore, the extent to which this hypothesized relationship was moderated by genetic risk (Taq1A polymorphism in the DRD2/ANKK1 gene cluster) and verbal fluency as an indicator of executive cognitive ability (Controlled Oral Word Association Test) was also examined. A sample of 143 alcohol-dependent inpatients provided an extensive clinical history of their alcohol use, gave 10ml of blood for DNA analysis, and completed self-report measures relating to impulsivity, impaired control and severity of dependence. As hypothesized, perceived impaired control (partially) mediated the association between impulsivity-related measures and alcohol-dependence severity. This relationship was not moderated by the DRD2/ANKK1 polymorphism or verbal fluency. These results suggest that, in alcohol dependence, perceived impaired control is a cognitive mediator of impulsivity-related constructs that may be unaffected by DRD2/ANKK1 and neurocognitive processes underlying the retrieval of verbal information.
Waszkiewicz, Napoleon; Zalewska-Szajda, Beata; Zalewska, Anna; Waszkiewicz, Magdalena; Szajda, Sławomir Dariusz; Repka, Bernadeta; Szulc, Agata; Kępka, Alina; Minarowska, Alina; Chojnowska, Sylwia; Konarzewska, Beata; Ładny, Jerzy Robert; Kowzan, Urszula; Zwierz, Krzysztof
Salivary lactoferrin is a glycoprotein involved in the elimination of pathogens and the prevention of massive overgrowth of microorganisms that affect oral and general health. A high concentration of lactoferrin in saliva is often considered to be a marker of damage to the salivary glands, gingivitis, or leakage through inflamed or damaged oral mucosa, infiltrated particularly by neutrophils. We conducted a study to determine the effect of chronic alcohol intoxication on salivary lactoferrin concentration and output. The study included 30 volunteers consisting of ten non-smoking male patients after chronic alcohol intoxication (group A), and 20 control nonsmoking male social drinkers (group C) with no history of alcohol abuse. Resting whole saliva was collected 24 to 48 hours after a chronic alcohol intoxication period. Lactoferrin was assessed by enzyme-linked immunosorbent assay. For all participants, the DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. The differences between groups were evaluated using the Mann-Whitney U test. We noticed significantly decreased salivary flow (SF) in alcohol dependent patients after chronic alcohol intoxication (A), compared to the control group (C). Although there was no significant difference in salivary lactoferrin concentration between the alcohol dependent group A and the control group C, we found significantly decreased lactoferrin output in group A compared to group C. We found a significant correlation between the amount of daily alcohol use and a decrease in lactoferrin output. There was a significant increase in GI and a tendency of PBI to increase in group A compared to group C. We demonstrated that chronic alcohol intoxication decreases SF and lactoferrin output. The decreased lactoferrin output in persons chronically intoxicated by alcohol may be the result of lactoferrin exhaustion during drinking (due to its alcohol-related lower biosynthesis or
Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Owusu-Duku, Beverly; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A.; Miguel-Hidalgo, Jose J.
Background Alcohol-dependent (ALC) subjects exhibit glial and neuronal pathology in the prefrontal cortex (PFC). However, in many patients, neurophysiological disturbances are not associated with catastrophic cell depletion despite prolonged alcohol abuse. It is still unclear how some relevant markers of a cell’s propensity to degenerate or proliferate are changed in the PFC of ALC subjects without major neurological disorders. Methods Levels of pro-apoptotic caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 non-psychiatric comparison subjects. Results ALC subjects had significantly higher levels of the 14kDa C8 fragment (C8-14), an indicator of C8 activation. However, there was no change in the levels of DIABLO, XIAP or in the DIABLO/XIAP ratio. PCNA protein level and density of Ki-67-IR cells were not significantly changed in alcoholics, although PCNA levels were increased in older ALC subjects as compared to controls. Conclusions Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in XIAP level, DIABLO/XIAP ratio, or Ki-67 labeling. These results would help to explain the absence of catastrophic cell loss in the PFC of many alcohol dependent subjects, while still being consistent with an alcoholism-related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics. PMID:25421516
Morris, S A; Kelso, M L; Liput, D J; Marshall, S A; Nixon, K
Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on
Bob, Petr; Jasova, Denisa; Bizik, Gustav; Raboch, Jiri
Background Alcohol dependence during withdrawal and also in abstinent period in many cases is related to reduced inhibitory functions and kindling that may appear in the form of psychosensory symptoms similar to temporal lobe epilepsy frequently in conditions of normal EEG and without seizures. Because temporal lobe epileptic activity tend to spread between hemispheres, it is possible to suppose that measures reflecting interhemispheric information transfer such as electrodermal activity (EDA) might be related to the psychosensory symptoms. Methods and Findings We have performed measurement of bilateral EDA, psychosensory symptoms (LSCL-33) and alcohol craving (ACQ) in 34 alcohol dependent patients and 32 healthy controls. The results in alcohol dependent patients show that during rest conditions the psychosensory symptoms (LSCL-33) are related to EDA transinformation (PTI) between left and right EDA records (Spearman r = 0.44, p<0.01). Conclusions The result may present potentially useful clinical finding suggesting a possibility to indirectly assess epileptiform changes in alcohol dependent patients. PMID:21541318
O'Neil, Carol; Maranda, Michael
The purpose of this research was to develop the Identification of Alcohol Dependence in Women (IADW) Scale, which is a 51-question instrument, designed to discriminate between alcohol and non-alcohol dependent women. Questions focus on physical, psychological, family and home life, and use of alcohol. Initial testing of the IADW Scale provides preliminary evidence that it is reliable, has content validity, and is capable of correctly classifying group membership with accuracy. Eighty-six percent of the cases in the alcohol dependent group and 98% of the non-alcohol dependent group were correctly classified using direct and stepwise methods of discriminant analysis.
Copeland, William E; Magnusson, Asa; Göransson, Mona; Heilig, Markus A
This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that might affect treatment planning. A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Gilpin, Nicholas W; Misra, Kaushik; Koob, George F
The anxiolytic effects of neuropeptide Y (NPY) are mediated in part by the central nucleus of the amygdala (CeA), a brain region involved in the regulation of alcohol-drinking behaviors. Centrally administered NPY suppresses alcohol drinking in subpopulations of rats vulnerable to the development of high alcohol-drinking behavior. The purpose of the current study was to determine the role of NPY in the CeA on elevated alcohol drinking produced by alcohol dependence. Adult male Wistar rats were trained to respond for 10% w/v alcohol in an operant situation with the use of a supersaccharin fading procedure. Following stabilization of responding, rats were divided into two groups matched for intake and given daily access to either alcohol-containing (9.2% v/v) liquid diet or an isocaloric control diet. Following extended access to the diet and reliable separation of operant responding between dependent and non-dependent rats during 6-h withdrawal tests, all rats were implanted bilaterally with cannulae aimed at the CeA. Rats were then infused with 4 NPY doses (0.0, 0.25, 0.5, 1.0 microg/0.5 microl aCSF) in a within-subjects Latin-square design during acute withdrawal and tested for operant alcohol responding 30 min later. Alcohol-dependent rats exhibited higher operant alcohol responding than non-dependent rats when infused with vehicle, but responding was similar in the two groups following infusion of all doses of NPY. These results indicate that NPY abolishes dependence-induced elevations in alcohol drinking and implicate the recruitment of limbic NPY systems in the motivational drive to consume alcohol following the transition to dependence.
Vargas, Wanette M.; Bengston, Lynn; Gilpin, Nicholas W.; Whitcomb, Brian W.
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. PMID:25355229
Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N
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. Copyright © 2014 the authors 0270-6474/14/3414777-06$15.00/0.
Chiang, T; Sansuk, K
Background and Purpose δ Opioid receptor agonists are being developed as potential treatments for depression and alcohol use disorders. This is particularly interesting as depression is frequently co‐morbid with alcohol use disorders. Yet we have previously shown that δ receptor agonists range widely in their ability to modulate alcohol intake; certain δ receptor agonists actually increase alcohol consumption in mice. We propose that variations in β‐arrestin 2 recruitment contribute to the differential behavioural profile of δ receptor agonists. Experimental Approach We used three diarylmethylpiperazine‐based non‐peptidic δ receptor selective agonists (SNC80, SNC162 and ARM390) and three structurally diverse δ receptor agonists (TAN‐67, KNT127 and NIH11082). We tested these agonists in cAMP and β‐arrestin 2 recruitment assays and a behavioural assay of alcohol intake in male C57BL/6 mice. We used β‐arrestin 2 knockout mice and a model of depression‐like behaviour to further study the role of β‐arrestin 2 in δ receptor pharmacology. Key Results All six tested δ receptor agonists were full agonists in the cAMP assay but displayed distinct β‐arrestin 2 recruitment efficacy. The efficacy of δ receptor agonists to recruit β‐arrestin 2 positively correlated with their ability to increase alcohol intake (P < 0.01). The effects of the very efficacious recruiter SNC80 on alcohol intake, alcohol place preference and depression‐like behaviour were β‐arrestin 2‐dependent. Conclusions and Implications Our finding that δ receptor agonists that strongly recruit β‐arrestin 2 can increase alcohol intake carries important ramifications for drug development of δ receptor agonists for treatment of alcohol use disorders and depressive disorders. © 2015 The British Pharmacological Society PMID:26507558
Anton, Raymond F; Myrick, Hugh; Baros, Alicia M; Latham, Patricia K; Randall, Patrick K; Wright, Tara M; Stewart, Scott H; Waid, Randy; Malcolm, Robert
Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.
Burnett, Elizabeth J; Chandler, L Judson; Trantham-Davidson, Heather
Introduction Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. Objective To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Results Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure and up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, changes in NMDA receptors and additional glutamatergic neuroadaptations are often circuit and cell-type specific. Discussion Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. Conclusion While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover
Meszaros, K; Lenzinger, E; Hornik, K; Füreder, T; Willinger, U; Fischer, G; Schönbeck, G; Aschauer, H N
Personality traits have been found as strong predictors for treatment response in different psychiatric disorders. We administered the Tridimensional Personality Questionnaire, which measures the three personality dimensions: novelty seeking, harm avoidance (HA), and reward dependence, as introduced by Cloninger in a multicenter study (11 centers in the United Kingdom, Eire, Switzerland, and Austria) with detoxified alcohol-dependent patients (n = 521). The objective of this study was to evaluate a possible predictive value of these three dimensions on relapse over 1 -year follow up. A logistic regression analysis showed that novelty seeking is a strong predictor for relapse in detoxified male alcoholics (p = 0.0007; p values adjusted for treatment), but not in females. In both sexes, HA and reward dependence were of no predictive value. However, we found a trend for significance of HA for predicting "early" relapse (4 weeks) in females (p = 0.074). Our results show that Tridimensional Personality Questionnaire personality traits have direct clinical applications for prediction of relapse in detoxified alcohol dependents and indicate the necessity of additional therapeutic treatment in risk groups.
Orr, Mark G; Prescott, Marta R; Cohen, Gregory H; Calabrese, Joseph R; Tamburrino, Marijo B; Liberzon, Israel; Galea, Sandro
There is a limited amount of data examining the relation between the onset of alcohol abuse/dependence and the experiences of soldiers prior to (pre), during (peri) and after (post) military deployment. Some deployment characteristics, e.g., military unit cohesion, are potentially modifiable in the context of reducing alcohol abuse/dependence peri-/post deployment. We investigated the associations between potentially modifiable deployment characteristics and peri-/post (incident) alcohol abuse/dependence among deployed Ohio Army National Guard (OHARNG) soldiers. Using a sample of OHARNG (June, 2008 to February, 2009), eligible participants were ever been deployed and did not report alcohol abuse/dependence prior to deployment (final sample size=963). Interviews assessed soldiers' alcohol abuse/dependence, depression, PTSD, deployment related factors (e.g., exposure to warzone stressors) and three deployment characteristics (pre-deployment preparedness, unit support during deployment, and post-deployment social support). Associations between the three deployment characteristics and incident alcohol abuse/dependence (defined as abuse or dependence at any point during or after deployment) were estimated using logistic regression. Only pre-deployment preparedness was associated with incident alcohol abuse/dependence (a non-linear inverted-u shaped relation) when controlling for demographics, deployment related factors (e.g., exposure to warzone stressors), and the presence of psychopathology that exhibited peri-/post-deployment. We present these results graphically, plotting incident alcohol abuse/dependence over the levels of pre-deployment preparedness. The association between pre-deployment preparedness and alcohol abuse/dependence may be characterized as an inverted-U shaped function. Suggestions for how and whether to modify pre-deployment preparedness in an effort to reduce peri-/post-deployment alcohol abuse or dependence should await further research. Copyright
Marshall, E Jane
In 1976 Edwards & Gross proposed the concept of the alcohol dependence syndrome, based on the clinical observation that heavy drinkers manifested an inter-related clustering of signs and symptoms. That this modest 'provisional description' turned out to be so significant and influential is perhaps unsurprising when the context in which it was made is appreciated. Griffith Edwards and his colleagues at the Maudsley Hospital had undergone a rigorous 3-year training in clinical psychiatry, during which they had been taught to think critically and were grounded in the art of clinical observation. As he assessed patients for various alcohol research studies he realized that there was a clustering of certain elements. Thus clinical observation and an appreciation of the patient's drinking history contributed to the genesis of the concept. This paper reflects on the integration of his rigorous training at the Maudsley, his enquiring mind and encyclopaedic knowledge of the historical and research literature which enabled him to formulate a testable hypothesis about the alcohol dependence syndrome.
Halsted, Charles H; Medici, Valentina
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.
Halsted, Charles H.; Medici, Valentina
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
Morley, K.C.; Baillie, A.; Leung, S.; Addolorato, G.; Leggio, L.; Haber, P.S.
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
Crunelle, Cleo L; Cappelle, Delphine; Covaci, Adrian; van Nuijs, Alexander L N; Maudens, Kristof E; Sabbe, Bernard; Dom, Geert; Michielsen, Peter; Yegles, Michel; Neels, Hugo
Ethyl glucuronide (EtG) is a minor alcohol metabolite that accumulates in hair and is proposed as a stable marker for the detection of chronic and excessive alcohol consumption above a cut-off level of 30pg/mg hair. A correlation between drinking behavior and EtG hair concentrations is observed, but large variability exists. To investigate the correlation between alcohol consumption and hair EtG concentrations in alcohol dependent patients, and the effect of gender differences as a factor for the variability on this correlation. EtG was measured by gas chromatography coupled to mass spectrometry in the hairs (first 3cm) of 36 alcohol dependent patients (25 males/11 females) starting and alcohol detoxification program. Factors that possibly influence EtG content in hair (except age and gender) were excluded. Detailed retrospective alcohol consumption was obtained over the last 3 months using the Timeline Follow Back interview. Median total alcohol consumption over 3 months was 13,050g pure alcohol (range 60-650g/day). Hair EtG concentrations varied between 32 and 662pg/mg. There was a statistically significant linear and positive correlation between hair EtG and amounts of alcohol consumed (Pearson r=0.83; p<0.001), in both males (Pearson r=0.83; p<0.001) and females (Pearson r=0.76; p=0.007). There is a linear correlation, with no significant effect of gender, between hair EtG concentrations and amounts of alcohol consumed in alcohol-dependent individuals. Analysis of EtG in hair can be applied to estimate retrospective alcohol consumption in both male and female alcohol dependent subjects using the same cut-off. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Henricks, Angela M; Berger, Anthony L; Lugo, Janelle M; Baxter-Potter, Lydia N; Bieniasz, Kennedy V; Craft, Rebecca M; McLaughlin, Ryan J
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. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Lehavot, Keren; Stappenbeck, Cynthia A; Luterek, Jane A; Kaysen, Debra; Simpson, Tracy L
Alcohol dependence (AD) and posttraumatic stress disorder (PTSD) are highly prevalent and comorbid conditions associated with a significant level of impairment. Little systematic study has focused on gender differences specific to individuals with both AD and PTSD. The current study examined gender-specific associations between PTSD symptom severity, drinking to cope (i.e., reduce negative affect), drinking for enhancement (i.e., increase positive affect), and average alcohol use in a clinical sample of men (n = 46) and women (n = 46) with comorbid AD and PTSD. Results indicated that PTSD symptoms were highly associated with drinking-to-cope motives for both men and women, but with greater drinking for enhancement motives for men only. Enhancement motives were positively associated with average alcohol quantity for both men and women, but coping motives were significantly associated with average alcohol quantity for women only. These findings suggest that for individuals with comorbid AD and PTSD, interventions that focus on reducing PTSD symptoms are likely to lower coping motives for both genders, and targeting coping motives is likely to result in decreased drinking for women but not for men, whereas targeting enhancement motives is likely to lead to reduced drinking for both genders.
McHugh, R Kathryn; Hofmann, Stefan G; Asnaani, Anu; Sawyer, Alice T; Otto, Michael W
Previous studies have implicated a relationship between particular allelic variations of the serotonin transporter gene (5HTTLPR) and alcohol dependence. To provide a current estimate of the strength of this association, particularly in light of inconsistent results for 5HTTLPR, we conducted a meta-analytic review of the association between 5HTTLPR and a clinical diagnosis of alcohol dependence. Of 145 studies initially identified, 22 (including 8050 participants) met inclusion criteria. Results indicated that there was a significant albeit modest association between alcohol dependence diagnosis and the presence of at least 1 short allele (OR=1.15, 95% CI=1.01, 1.30, p<.05). Slightly more robust results were observed for participants who were homogeneous for the short allele (OR=1.21, 95% CI=1.02, 1.44, p<.05). These results were unrelated to sex and race/ethnicity of participants; however, the effect size was moderated by study sample size and publication year. Additionally, the fail-safe N analysis indicated potential publication bias. Therefore, although our review indicates that there is a significant association between 5HTTLPR and alcohol dependence diagnosis, this result should be interpreted with caution. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Bozkurt, Muge; Evren, Cuneyt; Can, Yesim; Evren, Bilge; Cetingok, Sera; Yilmaz, Alkin
Impulsivity is closely related to substance use and abuse, both as a contributor to use and as a consequence of use. Particular dimensions of temperament and character were reported to be associated with trait impulsivity in different populations. The aim of the present study was to evaluate the relationship of personality dimensions with impulsivity among men with alcohol dependence. Also we wanted to control the effect of depression and anxiety symptoms on this relationship. Participants were consecutively admitted male alcohol-dependent inpatients (n = 94) and healthy controls (n = 63). Patients were investigated with the Barratt Impulsiveness Scale, version 11 (BIS-11), the Temperament and Character Inventory (TCI) and the Symptom Checklist-Revised (SCL-90-R). Severity of impulsivity and dimensions of impulsivity were higher in alcohol-dependent inpatients than in healthy controls. Impulsivity was negatively correlated with reward dependence, persistence, self-directedness and cooperativeness, but positively correlated with novelty seeking, harm avoidance, depression and anxiety. Although high depression and temperament dimensions (high novelty seeking, harm avoidance and low reward dependence) predicted impulsivity, combinations of personality dimensions that predict dimensions of impulsivity differed. RESULTS may suggest that together with depression when impulsivity is the problem, both dimensions of impulsivity and personality must be evaluated and the treatment should be shaped accordingly for alcohol-dependent inpatients.
Caetano, Raul; Caetano Vaeth, Patrice A.; Mills, Britain A.; Rodriguez, Lori A.
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
French, Samuel W.
Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165
French, Samuel W
Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD.
Momeni, Shima; Segerström, Lova; Roman, Erika
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
Momeni, Shima; Segerström, Lova; Roman, Erika
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
Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard
This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.
Franck, Johan; Jayaram-Lindström, Nitya
The efficacy of medications for alcohol dependence remains modest, and there are no strong clinical predictors of treatment response. Approved medications include acamprosate (an N-methyl-d-aspartate receptor (NMDA) modulator), disulfiram (an acetaldehyde dehydrogenase inhibitor) and naltrexone (an opioid antagonist) while nalmefene (an opioid antagonist) is currently under review for approval in Europe. Clinical trials suggest that baclofen (a GABA-B agonist) and topiramate (an anticonvulsant) may be promising candidates, while several other drug candidates are currently evaluated at early clinical stages.
Heilig, Markus; Egli, Mark
Alcoholism is a major public health problem and resembles, in many ways, other chronic relapsing medical conditions. At least 2 separate dimensions of its symptomatology offer targetable pathophysiological mechanisms. Systems that mediate positive reinforcement by alcohol are likely important targets in early stages of the disease, particularly in genetically susceptible individuals. In contrast, long term neuroadaptive changes caused by chronic alcohol use primarily appear to affect systems mediating negative affective states, and gain importance following a prolonged history of dependence. Feasibility of pharmacological treatment in alcoholism has been demonstrated by a first wave of drugs which consists of 3 currently approved medications, the aldehyde dehydrogenase blocker disulfiram, the opioid antagonist naltrexone (NTX) and the functional glutamate antagonist acamprosate (ACM). The treatment toolkit is likely to be expanded in the near future. This will improve overall efficacy and allow individualized treatment, ultimately taking in account the patient's genetic makeup. In a second wave, early human efficacy data are available for the 5HT3 antagonist ondansetron, the GABA-B agonist baclofen and the anticonvulsant topiramate. The third wave is comprised of compounds predicted to be effective based on a battery of animal models. Using such models, a short list of additional targets has accumulated sufficient preclinical validation to merit clinical development. These include the cannabinoid CB1 receptor, receptors modulating glutamatergic transmission (mGluR2, 3 and 5), and receptors for stress-related neuropeptides corticotropin releasing factor (CRF), neuropeptide Y (NPY) and nociceptin. Once novel treatments are developed, the field faces a major challenge to assure their delivery to patients.
Williams, Robert J.; Connor, Jason P.; Ricciardelli, Lina A.
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…
Evren, Cuneyt; Evren, Bilge; Dalbudak, Ercan
Objective. The aim of this study was to determine the relationship of alexithymia and temperament and character model of personality with depression and anxiety symptoms in detoxified male alcohol-dependent inpatients. Method. The subjects consisted of 176 male alcohol-dependent inpatients according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Patients were investigated with the Beck Depression Inventory, Beck Anxiety Inventory, State and Trait Anxiety Inventory, Michigan Alcoholism Screening Test (MAST), Toronto Alexithymia Scale (TAS-20) and Temperament and Character Inventory (TCI). Results. MAST score and scores of all three factors of the TAS-20 significantly predicted depression scale and anxiety scales. Difficulty in identifying feelings and difficulty in describing feelings factors were particularly effective, relative to the externally orientated thinking factor of the TAS-20 for prediction depression and anxiety. The TCI dimensions emerged as distinct and conceptually meaningful predictors for the depression scale and anxiety scales. Conclusion. Depression and anxiety symptoms among detoxified male alcohol dependents are associated with alexithymia, a broad range of personality dimensions and higher severity of alcohol-related problems, which make these related factors highly relevant for clinical practice.
Leggio, Lorenzo; Ferrulli, Anna; Cardone, Silvia; Nesci, Antonio; Miceli, Antonio; Malandrino, Noemi; Capristo, Esmeralda; Canestrelli, Benedetta; Monteleone, Palmiero; Kenna, George A.; Swift, Robert M.; Addolorato, Giovanni
Animal studies suggest that the gut-brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics. This investigation consisted of two studies. Study 1 was a 12-week study with alcohol-dependent subjects, where plasma ghrelin determinations were assessed four times (T0-T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone (GH) levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case-control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol-dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non-abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol-dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant. This investigation suggests that ghrelin is potentially able to affect alcohol-seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD. PMID:21392177
Petit, Géraldine; Luminet, Olivier; Cordovil de Sousa Uva, Mariana; Monhonval, Pauline; Leclercq, Sophie; Spilliaert, Quentin; Zammit, François; Maurage, Pierre; de Timary, Philippe
Alcohol craving is a major cause of relapse in alcohol-dependent (AD) patients. It is closely related to the high depression and anxiety symptoms that are frequently observed at the early stages of abstinence, and these comorbid symptoms might thus constitute a relapse factor when they persist after detoxification. As these negative affects are known to evolve during the detoxification process, the aim of this study was to investigate the course of the relation between affects and craving during detoxification, with a particular attention given to gender in light of the known differences in affects between AD men and women. AD patients (n = 256) undergoing a detoxification program were evaluated for positive (PA) and negative affectivity (NA), depression and anxiety symptoms, and craving, twice within a 3-week interval (on the first [T1] and the eighteenth day [T2] of abstinence). Detoxification course was associated with improvements regarding NA, depression and anxiety symptoms, and craving. Moreover, these negative affects were related to craving intensity. However, for men, the relation was only present at the beginning of detoxification, while, for women, it persisted at the end of detoxification as did high levels of depression. Furthermore, only with women was the level of craving at T2 proportional to negative affects reported at T1, and depression symptoms experienced at T1 were reliable predictors of craving at T2. Given the importance of craving in relapse, special care should be given to improve depressive symptoms in AD women to promote long-term abstinence. Also, the remaining portion of AD women who still exhibit substantial symptoms of anxiety and depression at the end of detoxification could benefit from an integrated treatment simultaneously tackling mood and alcohol-dependence disorders. Copyright © 2017 by the Research Society on Alcoholism.
Lovi, Renee; Barr, Jennieffer
Alcohol and drug dependency is a widespread health and social issue encountered by registered nurses in contemporary practice. A study aiming to describe the experiences of registered nurses working in an alcohol and drug unit in South East Queensland was implemented. Data were analysed via Giorgi's phenomenological method and an unexpected but significant finding highlighted the frustration felt by registered nurses regarding experiences of stigma they identified in their daily work encounters. Secondary analysis confirmed the phenomenon of stigma with three themes: (1) inappropriate judgement; (2) advocacy; and (3) education. Resultantly, findings concluded registered nurses' working in this field need to become advocates for their clients, ensuring professional conduct is upheld at all times. This paper recommends that stigma could be addressed by incorporating alcohol and other drug dependency subjects and clinical placements into the curriculum of the Bachelor of Nursing degrees, and in-services for all practising registered nurses.
Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the Collaborative Study on the Genetics of Alcoholism
Johnson, Catherine; Drgon, Tomas; Liu, Qing-Rong; Walther, Donna; Edenberg, Howard; Rice, John; Foroud, Tatiana; Uhl, George R
Association genome scanning can identify markers for the allelic variants that contribute to vulnerability to complex disorders, including alcohol dependence. To improve the power and feasibility of this approach, we report validation of “100k” microarray-based allelic frequency assessments in pooled DNA samples. We then use this approach with unrelated alcohol dependent vs control individuals sampled from pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA). Allele frequency differences between alcohol-dependent and control individuals are assessed in quadruplicate at 104,268 autosomal SNPs in pooled samples. One hundred eighty eight SNPs provide 1) the largest allele frequency differences between dependent vs control individuals, 2) t values ≥ 3 for these differences and 3) clustering, so that 51 relatively small chromosomal regions contain at least three SNPs that satisfy criteria 1 and 2 above (Monte Carlo p=0.00034). These positive SNP clusters nominate interesting genes whose products are implicated in cellular signaling, gene regulation, development, “cell adhesion” and Mendelian disorders. The results converge with linkage and association results for alcohol and other addictive phenotypes. The data support polygenic contributions to vulnerability to alcohol dependence These SNPs provide new tools to aid the understanding, prevention and treatment of alcohol abuse and dependence. PMID:16894614
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.
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
Schadé, Annemiek; Marquenie, Loes A; Van Balkom, Anton J L M; Koeter, Maarten W J; De Beurs, Edwin; Van Den Brink, Wim; Van Dyck, Richard
Patients with a double diagnosis of alcohol dependence and phobic disorders are a common phenomenon in both alcohol and anxiety disorder clinics. If we are to provide optimum treatment we need to know more about the clinical characteristics of this group of comorbid patients. To answer the following questions. (1). What are the clinical characteristics of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder? (2). Are alcohol dependence and other clinical characteristics of comorbid patients different from those of 'pure' alcohol-dependent patients? (3). Are the anxiety symptoms and other clinical characteristics of comorbid patients different from those of 'pure' phobic patients? Three groups of treatment-seeking patients were compared on demographic and clinical characteristics: alcohol dependent patients with a comorbid phobic disorder (n = 110), alcohol-dependent patients (n = 148) and patients with social phobia or agoraphobia (n = 106). In order to diagnose the comorbid disorders validly, the assessment took place at least 6 weeks after detoxification. Comorbid patients have high scores on depressive symptoms and general psychopathology: 25% of patients have a current and 52% a lifetime depressive disorder. The majority have no partner and are unemployed, they have a high incidence of other substance use (benzodiazepine, cocaine, cannabis) and a substantial proportion of comorbid patients have been emotionally, physically and sexually abused. They do not have a more severe, or different type of alcohol dependence or anxiety disorder than 'pure' alcohol-dependent patients and phobic patients respectively. Comorbid patients constitute a complex part of the treatment-seeking population in alcohol clinics and psychiatric hospitals. These findings should be taken into account when diagnosing and treating alcohol-dependent patients with a comorbid phobic disorder.
Chartier, Karen G; Hesselbrock, Michie N; Hesselbrock, Victor M
The moderating effects of ethnicity and gender on factors associated with physical health consequences in adults manifesting alcohol dependence were examined using data from the 2001-2002 US National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Black and white respondents with a lifetime diagnosis of DSM-IV alcohol dependence were selected for the study (n = 3,852). A multiple-group structural equation model tested ethnicity, gender, and intervening variables as predictors of physical health status in alcohol-dependent men and women. Study findings offer implications for clinical practice with alcohol-dependent individuals by identifying likely target groups and problems for intervention.
Chartier, Karen G.; Hesselbrock, Michie N.; Hesselbrock, Victor M.
The moderating effects of ethnicity and gender on factors associated with physical health consequences in adults with alcohol dependence was examined using data from the 2001–2002 U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Black and White respondents with a lifetime diagnosis of DSM-IV alcohol dependence were selected for the study (n = 3,852). A multiple-group structural equation model tested ethnicity, gender, and intervening variables as predictors of physical health status in alcohol dependent men and women. Study findings offer implications for clinical practice with alcohol dependent individuals by identifying likely target groups and problems for intervention. PMID:23302062
Cardenas, VA; Durazzo, TC; Gazdzinski, S; Mon, A; Studholme, C; Meyerhoff, DJ
Background We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers. Methods Individuals in alcohol dependence treatment (N=75) underwent magnetic resonance imaging approximately 6 ± 4 days after their last alcoholic drink, and 40 age-matched non-smoking light drinkers were studied as controls. At follow-up 7.8 ± 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and light drinkers. Results Compared to light drinkers, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex, and bilaterally in the thalamus and adjacent subcortical white matter (WM), and had larger volume in the left lateral orbitofrontal region. Compared to light drinkers, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared to future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities. Conclusion At entry into alcohol dependence treatment, the brain structure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry may confer greater risk for resumption of hazardous drinking after treatment and may contribute to the definition of a neurobiological relapse risk profile in alcohol dependence. PMID:21601177
Beckley, Jacob T; Laguesse, Sophie; Phamluong, Khanhky; Morisot, Nadege; Wegner, Scott A; Ron, Dorit
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
Beckley, Jacob T.; Laguesse, Sophie; Phamluong, Khanhky; Morisot, Nadege; Wegner, Scott A.
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
Le Strat, Yann; Grant, Bridget F; Ramoz, Nicolas; Gorwood, Philip
The accurate cut-off of an early onset of alcohol dependence is unknown. The objectives of this analysis are (1) to confirm that ages at onset variability in alcohol dependence is best described as a two subgroups entity, (2) to define the most appropriate cut-off, and (3) to test the relevancy of such distinction. Data were drawn the Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This study focused on the 4782 adults with lifetime alcohol dependence. The best-fit model distinguished two subgroups of age at onset of alcohol dependence, with a cut-off point at 22 years. Subjects with an earlier onset of alcohol dependence (< or = 22 years old) reported higher lifetime rates of specific phobia, antisocial behaviors and nearly all addictive disorders. The early onset of alcohol dependence is best defined as beginning before the age of 22 years. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Garcia-Marchena, Nuria; Pavon, Francisco J; Pastor, Antoni; Araos, Pedro; Pedraz, Maria; Romero-Sanchiz, Pablo; Calado, Montserrat; Suarez, Juan; Castilla-Ortega, Estela; Orio, Laura; Boronat, Anna; Torrens, Marta; Rubio, Gabriel; de la Torre, Rafael; Rodriguez de Fonseca, Fernando; Serrano, Antonia
Acylethanolamides are a family of endogenous lipid mediators that are involved in physiological and behavioral processes associated with addiction. Recently, oleoylethanolamide (OEA) has been reported to reduce alcohol intake and relapse in rodents but the contribution of OEA and other acylethanolamides in alcohol addiction in humans is unknown. The present study is aimed to characterize the plasma acylethanolamides in alcohol dependence. Seventy-nine abstinent alcohol-dependent subjects (27 women) recruited from outpatient treatment programs and age-/sex-/body mass-matched healthy volunteers (28 women) were clinically assessed with the diagnostic interview PRISM according to the DSM-IV-TR after blood extraction for quantification of acylethanolamide concentrations in the plasma. Our results indicate that all acylethanolamides were significantly increased in alcohol-dependent patients compared with control subjects (p < 0.001). A logistic model based on these acylethanolamides was developed to distinguish alcohol-dependent patients from controls and included OEA, arachidonoylethanolamide (AEA) and docosatetraenoylethanolamide (DEA), providing a high discriminatory power according to area under the curve [AUC = 0.92 (95%CI: 0.87-0.96), p < 0.001]. Additionally, we found a significant effect of the duration of alcohol abstinence on the concentrations of OEA, AEA and DEA using a regression model (p < 0.05, p < 0.01 and p < 0.001, respectively), which was confirmed by a negative correlation (rho = -0.31, -0.40 and -0.44, respectively). However, acylethanolamides were not influenced by the addiction alcohol severity, duration of problematic alcohol use or diagnosis of psychiatric comorbidity. Our results support the preclinical studies and suggest that OEA, AEA and DEA are altered in alcohol-dependence during abstinence and that might act as potential markers for predicting length of alcohol abstinence.
Rationale Genetic and environmental influences on the development of alcohol and drug dependence are equally important. Exposure to early life stress, that is unfortunately common in the general population, has been shown to predict a wide range of psychopathology, including addiction. Objective This review will look at the characteristics of early life stress that may be specific predictors for adolescent and adult alcohol and drug dependence and will focus on studies in humans, non-human primates and rodents. Results Experiencing maltreatment and cumulative stressful life events prior to puberty and particularly in the first few years of life is associated with early onset of problem drinking in adolescence and alcohol and drug dependence in early adulthood. Early life stress can result in permanent neurohormonal and hypothalamic-pituitary-adrenal axis changes, morphological changes in the brain and gene expression changes in the mesolimbic dopamine reward pathway, all of which are implicated in the development of addiction. However, a large proportion of children who have experienced even severe early life stress do not develop psychopathology indicating that mediating factors such as gene-environment interactions and family and peer relationships are important for resilience. Conclusions There appears to be a direct pathway from chronic stress exposure in pre-pubertal children via adolescent problem drinking to alcohol and drug dependence in early adulthood. However, this route can be moderated by genetic and environmental factors. The role that gene-environment interactions play in the risk-resilience balance is being increasingly recognized. PMID:20596857
Armitage, Roseanne; Hoffmann, Robert; Conroy, Deirdre A.; Arnedt, J. Todd; Brower, Kirk J.
Objectives: This study evaluated slow wave activity homeostatic response to a mild sleep challenge in alcohol-dependent adults compared to healthy controls. Design: Participants maintained a 23:00-06:00 schedule for 5 days verified by actigraphy and diary, followed by 3 nights in the lab: adaptation, baseline, and a sleep delay night with an 02:00-09:00 schedule. Setting: Sleep ' Chronophysiology laboratory. Participants: 48 alcohol-dependent adults (39 men, 9 women) who were abstinent for at least 3 weeks and 16 healthy control adults (13 men, 3 women), 21-55 years of age participated in study. Interventions: N/A. Measurements and Results: Slow wave EEG activity (SWA) in consecutive NREM periods was compared between baseline and sleep delay nights and between AD and HC groups, using age and sex as statistical covariates. The AD group showed a blunted SWA response to sleep delay with significantly lower SWA power than the HC group. Exponential regression analyses confirmed lower asymptotic SWA with a slower decay rate over NREM sleep time in the AD group. Results were similar for raw SWA and %SWA on the delay night expressed relative to baseline SWA. Conclusions: Alcohol dependence is associated with impaired SWA regulation and a blunted response to a mild homeostatic sleep challenge. Citation: Armitage R; Hoffmann R; Conroy DA; Arnedt JT; Brower KJ. Effects of a 3-hour sleep delay on sleep homeostasis in alcohol dependent adults. SLEEP 2012;35(2):273-278. PMID:22294818
DEMİRBAŞ, Hatice; ÖZGÜR İLHAN, İnci; DOĞAN, Yıldırım Beyatlı; CANATAN, Ayşe
Introduction We aimed to evaluate the psychometric characteristics of the Turkish translation of the Addiction Severity Index (ASI) in 115 male alcohol-dependent patients. Method The reliability of the instrument was assessed by measuring test-retest, interrater and internal reliabilities. In the validity analysis, the correlation coefficients between corresponding severity ratings and composite scores of each subscale and concurrent validity were assessed. Moreover, the discriminant validity and concurrent validity scores were calculated. Results The test-retest reliability of the ASI scores ranged from .79 to .91. The interrater reliability assigned by three raters was high (.74 to .99). Cronbach’s alpha coefficient for internal consistency was .85 for all scales, and it varied between .64 and .77 for the subscales. The Beck Depression Inventory moderately correlated with the Psychatric status, and the MacAndrew Alcoholism Scale correlated with the Alcohol and Drug Use subscales of the Addiction Severity Index (ASI). The correlation coefficient was .91 for the alcohol use subscale. Conclusion The results obtained in this study suggest that the Turkish version of the ASI could be used as a reliable and valid instrument in alcohol-dependent patients.
Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel
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.
Schepis, Ty S.; Cavallo, Dana A.; McFetridge, Amanda K.; Liss, Thomas B.; Krishnan-Sarin, Suchitra
Introduction: Given the prevalence of alcohol use among adolescents and its negative consequences, it is important to learn more about correlates of alcohol-related problems in this population. Cigarette smoking appears to be associated with alcohol-related problems in adolescents. The purpose of this study was to assess cigarettes smoked per day and nicotine dependence (ND) severity as predictors of alcohol-related problems in cross-sectional models, using data from a smoking cessation clinical trial for adolescents. Method: Data obtained at intake were used to assess smoking-related variables as cross-sectional predictors of alcohol-related problems in models along with drinks per week and key demographics, using hierarchical multiple regression. Results: ND severity, as measured using the modified Fagerström Tolerance Questionnaire, significantly predicted alcohol-related problems, both when this score included and did not include an item concerning cigarettes smoked per day. A separate continuous item capturing cigarettes per day did not predict alcohol-related problems. Discussion: ND severity predicted alcohol-related problems in cross-sectional regression models, holding constant alcohol consumption and key demographics. This suggests that ND severity may be a clinical indicator of alcohol-related problems among adolescent smokers. To our knowledge, this is the first analysis of associations between smoking and alcohol involvement in a sample of adolescent smokers participating in a clinical trial. PMID:20231243
Feige, Bernd; Scaal, Susanne; Hornyak, Magdolna; Gann, Horst; Riemann, Dieter
Dysfunctional hyperarousal is suspected to be a neurophysiological determinant of relapse in abstinent alcohol-dependent patients. In the present study, we used spectral power analysis of the sleep electroencephalographic (EEG) to quantify brain activity during sleep in patients during subacute withdrawal as well as in control subjects. Our hypothesis was that the subgroup of patients who relapsed within the 3 months to follow-up would exhibit-increased dysfunctional arousal manifested by higher-frequency (beta) EEG power during sleep. Twenty-six alcohol-dependent in-patients were examined with polysomnography over 2 nights 2 to 3 weeks after withdrawal. At the 3-month clinical follow-up assessment, 12 of them had relapsed and 14 abstained. The control group consisted of 23 healthy subjects similar to the patients with alcohol dependence in age and gender distribution. Spectral sleep EEG analysis was performed on both nights (adaptation and baseline) of all subjects. Logarithmic artifact-controlled spectral band power of sleep stage 2 and rapid eye movement (REM) sleep was analyzed for Group, Gender, and Age effects using multiple analyses of covariance. Three groups were compared with the Group factor: relapsers, abstainers, and controls. Generally, both Group and Age effects were significant for the second, baseline night for the visually scored sleep parameters, while spectral EEG parameters showed significant differences in the adaptation night. In the adaptation night, a significant enhancement in the beta2 band (24-32 Hz) was seen in REM sleep in relapsers relative to both abstainers and controls. The beta2 increase could be interpreted as a sign of dysfunctional arousal during REM sleep "unmasked" by the additional stressor of sleep environment adaptation. Its determinants are likely to be both premorbid and drinking history related.
Lachenmeier, D W
The etiopathology of absinthe dependence was previously attributed to the effects of the wormwood constituent thujone. Current research proves otherwise. Foremost, it must be considered that the wormwood plant shows a very large variance in quantity of thujone (0 - 70 % in essential oil) dependent on chemo type and cultivation area. Thus, absinthe does not contain thujone in general. Experimental production of absinthes and analyses of vintage absinthes (1900 - 1930) consistently showed that they contained only relatively low concentrations of thujone below today's maximum limits. Scientific literature contains no proof that historic absinthes may have contained thujone in concentrations able to produce toxic effects. The current state of research considers absinthism to be a type of alcoholism with thujone playing none or only a secondary role.
Pendharkar, Shreyas; Mattoo, Surendra K.; Grover, Sandeep
Background & objectives: Sexual dysfunctions have been reported in alcohol-dependent men. Most of the studies conducted had limitation of using non-validated measures of sexual dysfunction and sampling design. This study was, therefore, conducted to determine the typology, demographic and clinical correlates of sexual dysfunction in alcohol-dependent men. Methods: One hundred and one patients with alcohol dependence (AD) attending the Drug De-addiction and Treatment Centre and 50 healthy controls were evaluated in this cross-sectional study. Participants in both the groups were assessed on Arizona Sexual experience scale (ASEX), Dyadic Adjustment Scale (DAS), Hamilton Depression Rating Scale (HDRS) and State-Trait Anxiety Inventory (STAI). In addition, patients with AD were assessed on Severity of Alcohol Dependence Questionnaire (SADQ) for severity of AD and revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) to ensure that no participant was in active alcohol withdrawal state. Results: Overall, 58.4 per cent of patients in the AD group had sexual dysfunction. Among the domains, the highest frequency was seen for dysfunction for arousal (57.4%), followed by problems in desire (54.4%), erection (36.6%), satisfaction with orgasm (34.6%) and ability to reach orgasm was least affected (12.87%). The patient and control groups differed significantly in overall dyadic adjustment, in the domains of dyadic satisfaction and affective expression. Interpretation & conclusions: The finding of this study showed that a significant proportion of patients with AD has sexual dysfunction. Longitudinal studies using validated assessment tools should be done to confirm these findings. PMID:28139538
Samek, Diana R; Keyes, Margaret A; Hicks, Brian M; Bailey, Jennifer; McGue, Matt; Iacono, William G
Objective: This study builds on previous work delineating a hierarchical model of family environmental risk in relation to a hierarchical model of externalizing disorders (EXTs) by evaluating for gene–environment interplay in these relationships. The associations between parent–child relationship quality (conflict, bonding, and management) and substance-specific adolescent family environments (parental/sibling tobacco/alcohol use) in relation to young adult EXTs (age ∼22 years nicotine, alcohol, and other drug dependence; antisocial and risky sexual behavior) were evaluated. Method: The sample included 533 adopted offspring and 323 biological offspring. Because adopted youth do not share genes with their parents, a significant association between parent–child relationship quality and EXTs would provide evidence against passive gene–environment correlation (rGE). Significant associations between parental tobacco/alcohol use in relation to offspring nicotine/alcohol dependence in the adopted offspring support common environmental influence. Significant associations detected for the biological offspring only suggest common genetic influence. Results: For both adoptive and biological offspring, there was a significant association between parent–child relationship quality and EXTs. Parental tobacco/alcohol use was unrelated to EXTs. Sibling tobacco/alcohol use was related to EXTs, but only for the biological siblings. Parental tobacco use was associated with the residual variance in nicotine dependence in adopted offspring. Conclusions: Findings replicate a long-term influence of adolescent parent–child relationship quality on adult EXTs. Findings extend previous research by providing evidence against passive rGE in this association. The association between parental tobacco use and adult nicotine dependence appears to be environmentally mediated, but caution is warranted as we found this relationship only for adopted youth. PMID:24988261
Arcury, Thomas A.; Talton, Jennifer W.; Summers, Phillip; Chen, Haiying; Laurienti, Paul J.; Quandt, Sara A.
Aims To describe alcohol consumption behavior of male Latino migrant farmworkers, compare their alcohol consumption behavior with that of other male Latino immigrants, and determine factors associated with risk for alcohol dependence among Latino immigrant workers. Methods Cross-sectional data were drawn from baseline interviews conducted as part of a larger community-based participatory research project examining the cognitive and neurological outcomes of pesticide exposure. A total of 235 farmworkers and 212 non-farmworkers completed interviews between May and August, 2012. Results Although 17.5% of the North Carolina Latino farmworkers report never having drunk alcohol, and a total of 34.5% report not having drunk alcohol in the previous three months, 48.5% engaged in heavy episodic drinking (HED) in the previous 3 months, and 23.8% frequently engaged in HED during this period. Farmworkers and non-farmworkers did not differ significantly in alcohol consumption behavior. Farmworkers and non-farmworkers did differ significantly in each component of the CAGE scale, with 37.9% of farmworkers and 16.0% of non-farmworkers being at risk for alcohol dependence (p<0.0001). Significant factors for being at risk for alcohol dependence were stress (Odds Ratio 1.06, 95% Confidence Interval 1.03, 1.09) and being a farmworker (Odds Ratio 3.58, 95% Confidence Interval 2.12, 6.06). Being married reduced the risk of alcohol dependence (Odds Ratio 0.45, 95% Confidence Interval 0.39, 0.87). Conclusions Latino farmworkers and non-farmworkers consume relatively large amounts of alcohol and engage in heavy episodic drinking at relatively high rates. Latino farmworkers have very high rates of risk for alcohol dependence. Policy changes and public health interventions are needed to address these concerns for a population that is vital to the agricultural economy. PMID:26842256
Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka
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.
Buck, Cara L; Malavar, Jordan C; George, Olivier; Koob, George F; Vendruscolo, Leandro F
Rats emit 50kHz 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 50kHz 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 50kHz 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 50kHz 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 50kHz USVs were specific for the anticipation of alcohol self-administration and did not generalize to a novel environment. These findings suggest that anticipatory 50kHz USVs may be an indicator of context-elicited negative reinforcement learning.
Mosquera Nogueira, Jacinto; Rodríguez-Míguez, Eva
Alcohol dependence causes multiple problems not only for the person suffering dependence but also for others. In this study, the contingent valuation method is proposed to measure the intangible effects of alcohol dependence from the perspective of the persons directly involved: the patients and their relatives. Interviews were conducted with 145 patients and 61 relatives. Intangible effects of alcohol dependence were determined based on willingness to pay for a hypothetical treatment for dependence, with different success scenarios (100% and 50%). The mean monthly willingness to pay among the alcohol-dependent population was €129 and €168, respectively, for the treatments with 100% and 50% success. The willingness to pay of relatives was greater in both scenarios (€307 and €420, respectively), which could be explained by their greater perception of the family, labour, and health problems resulting from alcohol dependence. Regression analysis showed that patients' willingness to pay is positively related to treatment efficacy, personal income and moderate health deterioration, and negatively related to feeling discouraged and depressed. The results from this study can be applied to economic valuation studies that aim to measure the benefits of programs intended to reduce the prevalence of alcohol dependence. The intangible costs estimated can be added to the direct and indirect costs commonly used.
Berking, Matthias; Margraf, Matthias; Ebert, David; Wupperman, Peggilee; Hofmann, Stefan G.; Junghanns, Klaus
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…
Berking, Matthias; Margraf, Matthias; Ebert, David; Wupperman, Peggilee; Hofmann, Stefan G.; Junghanns, Klaus
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…
Genetic and environmental influences on the development of alcohol and drug dependence are equally important. Exposure to early life stress, that is unfortunately common in the general population, has been shown to predict a wide range of psychopathology, including addiction. This review will look at the characteristics of early life stress that may be specific predictors for adolescent and adult alcohol and drug dependence and will focus on studies in humans, non-human primates and rodents. Experiencing maltreatment and cumulative stressful life events prior to puberty and particularly in the first few years of life is associated with early onset of problem drinking in adolescence and alcohol and drug dependence in early adulthood. Early life stress can result in permanent neurohormonal and hypothalamic-pituitary-adrenal axis changes, morphological changes in the brain, and gene expression changes in the mesolimbic dopamine reward pathway, all of which are implicated in the development of addiction. However, a large proportion of children who have experienced even severe early life stress do not develop psychopathology indicating that mediating factors such as gene-environment interactions and family and peer relationships are important for resilience. There appears to be a direct pathway from chronic stress exposure in pre-pubertal children via adolescent problem drinking to alcohol and drug dependence in early adulthood. However, this route can be moderated by genetic and environmental factors. The role that gene-environment interactions play in the risk-resilience balance is being increasingly recognized.
Rose, Gail L.; Skelly, Joan M.; Badger, Gary J.; Ferraro, Tonya A.; Helzer, John E.
Background Relapse rates following cognitive behavioral therapy (CBT) for alcohol dependence are high. Continuing care programs can prolong therapeutic effects but are underutilized. Thus there is need to explore options having greater accessibility. Methods This randomized controlled trial tested the efficacy of a novel, fully automated continuing care program, Alcohol Therapeutic Interactive Voice Response (ATIVR). ATIVR enables daily monitoring of alcohol consumption and associated variables, offers targeted feedback, and facilitates use of coping skills. Upon completing 12 weeks of group CBT for alcohol dependence, participants were randomly assigned to either four months of ATIVR (n=81) or usual care (n=77). Drinking behavior was assessed pre- and post-CBT, then at 2 weeks, 2 months, 4 months, and 12 months post-randomization. Results Drinking days per week increased over time for the control group but not the intervention group. There were no significant differences between groups on the other alcohol-related outcome measures. Comparisons on the subset of participants abstinent at the end of CBT (n=72) showed higher rates of continuous abstinence in the experimental group. Effect sizes for the other outcome variables were moderate but not significant in this subgroup. Conclusions For continuing care, ATIVR shows some promise as a tool that may help clients maintain gains achieved during outpatient treatment. However, ATIVR may not be adequate for clients who have not achieved treatment goals at the time of discharge. PMID:25452069
Strang, Nicole M; Claus, Eric D; Ramchandani, Vijay A; Graff-Guerrero, Ariel; Boileau, Isabelle; Hendershot, Christian S
Functional magnetic resonance imaging (fMRI) studies involving alcohol challenge are important for identifying neural correlates of alcohol's psychopharmacological effects. However, evaluating acute alcohol effects on blood oxygen level-dependent (BOLD) signal change is complicated by alcohol-related increases in cerebral blood flow (CBF). The present study aimed to further characterize acute alcohol effects on CBF using intravenous alcohol administration to maximize control over brain alcohol exposure. Twenty heavy-drinking young adults (M = 19.95 years old, SD = 0.76) completed alcohol and placebo imaging sessions in a within-subject, counter-balanced, placebo-controlled design. Arterial spin labeling (ASL) provided estimates of perfusion change at two target blood alcohol concentrations (40 and 80 mg%) relative to baseline and relative to a saline control infusion. Voxel-wise analyses showed widespread and dose-dependent effects of alcohol on CBF increase. Region-of-interest analyses confirmed these findings, also indicating regional variation in the magnitude of perfusion change. Additional findings indicated that lower self-reported sensitivity to alcohol corresponded with reduced perfusion change during alcohol administration. This study provides further evidence for widespread effects of acute alcohol on cerebral perfusion, also demonstrating regional, dose-dependent, and inter-individual variation. Further research is needed to evaluate implications of these effects for the design and interpretation of pharmacological fMRI studies involving alcohol challenge.
McKellar, John; Stewart, Eric; Humphreys, Keith
A positive corelation between Alcoholics Anonymous (AA) involvement and better alcohol-related outcomes has been identified in research studies, but whether this correlation reflects a causal relationship remains a subject of meaningful debate. The present study evaluated the question of whether AA affiliation appears causally related to positive alcohol-related outcomes in a sample of 2,319 male alcohol-dependent patients. An initial structural equation model indicated that 1-year posttreatment levels of AA affiliation predicted lower alcohol-related problems at 2-year follow-up, whereas level of alcohol-related problems at 1-year did not predict AA affiliation at 2-year follow-up. Additional models found that these effects were not attributable to motivation or psychopathology. The findings are consistent with the hypothesis that AA participation has a positive effect on alcohol-related outcomes.
Martinez, Diana; Slifstein, Mark; Gil, Roberto; Hwang, Dah-Ren; Huang, Yiyun; Perez, Audrey; Frankle, W. Gordon; Laruelle, Marc; Krystal, John; Abi-Dargham, Anissa
Background Rodent models as well as studies in humans have suggested alterations in serotonin (5HT) innervation and transmission in early onset genetically determined or type II alcoholism. This study examines two indices of serotonergic transmission, 5HT transporter levels and 5-HT1A availability, in vivo, in type II alcoholism. This is the first report of combined tracers for pre and post-synaptic serotonergic transmission in the same alcoholic subjects and the first study of 5HT1A receptors in alcoholism. Method Fourteen alcohol dependent subjects were scanned (11 with both tracers, 1 with [11C]DASB only and two with [11C]WAY100635 only). Twelve healthy controls (HC) subjects were scanned with [11C]DASB and another 13 were scanned with [11C]WAY100635. Binding Potential (BPp, mL/cm3) and the specific to nonspecific partition coefficient (BPND, unitless) were derived for both tracers using 2 tissue compartment model and compared to HC across different brain regions. Relationships to severity of alcoholism were assessed. Results No significant differences were observed in regional BPp or BPND between patients and controls in any of the regions examined. No significant relationships were observed between regional 5HT transporter availability, 5-HT1A availability, and disease severity with the exception of a significant negative correlation between SERT and years of dependence in amygdala and insula. Conclusion This study did not find alterations in measures of 5-HT1A or 5HT transporter levels in patients with type II alcoholism. PMID:18962444
Vélez-Moreno, Antonio; González-Saiz, Francisco; Ramírez López, Juan; Torrico Linares, Esperanza; Fernández-Calderón, Fermín; Rojas, Antonio J; Lozano, Óscar M
The Substance Dependence Severity Scale -SDSS- is one of the few scales that assesses substance dependence and abuse according DSM criteria in dimensional terms. Several studies have provided evidence of psychometric validity and reliability in its English version, but there is no Spanish version available. The aim of this work was to describe the adaptation process of the English version of the SDSS into Spanish, and provide preliminary results on its reliability and validity evidence. Participants were 146 patients (79.6% male), consumers of alcohol, cocaine, heroin and cannabis admitted to treatment in the Drug Abuse Centre Services of Huelva. Besides the SDSS, the EUROPASI and the Health Related Quality of Life for Drug Abusers test -HRQOLDA- were also administered. The Substance Dependence Severity Scale -SDSS- has shown adequate psychometric properties in terms of the rates of discrimination and internal consistency (α=0.881 for alcohol; α=0.814 for cocaine; α=0.531 for cannabis; α=0.785 for heroin). However, the scale assessing abuse showed poorer results. Concerning the validity evidence, the evidence based on internal structure showed a unidimensional structure. Furthermore, the evidence based from the relationships with other variables empirically support the theoretical relationships postulated. Preliminary results support the use of the Substance Dependence Severity Scale. The severity scale, which evaluates abuse criteria, needs further empirical evidence to assess its utility. Therefore, its current version is not recommended for use.
Karadag, Figen; Sar, Vedat; Tamar-Gurol, Defne; Evren, Cuneyt; Karagoz, Mustafa; Erkiran, Murat
To determine the prevalence of dissociative disorders among inpatients with alcohol or drug dependency. The Dissociative Experiences Scale was used to screen 215 consecutive inpatients admitted to the dependency treatment center of a large mental hospital over a 1-year period (March 1, 2003, to March 31, 2004). Patients who had scores of 30.0 or above were compared with patients who scored below 10.0 on the scale. The patients in both groups were then evaluated using the Dissociative Disorders Interview Schedule and the Structured Clinical Interview for DSM-IV Dissociative Disorders. The interviewers were blind to the Dissociative Experiences Scale scores. Of the patients, 36.7% had a Dissociative Experiences Scale score of 30.0 or above. The prevalence of DSM-IV dissociative disorders was 17.2% (N = 37). On average, 64.9% of these patients' dissociative experiences had started 3.6 years (SD = 2.9; range, 1.0-11.0 years) before onset of the substance use. Patients with dissociative disorders were younger, and the mean duration of their remission periods was shorter. Dissociative disorder patients tended to use more than 1 substance, and drugs were used more frequently than alcohol in this group. The frequency of borderline personality disorder, somatization disorder, history of suicide attempt, and childhood abuse and neglect occurred more frequently in the dissociative disorder group than in the nondissociative disorder group. History of suicide attempt (p = .005), female sex (p = .050), and childhood emotional abuse (p = .010) were significant predictors of a dissociative disorder diagnosis. Significantly more patients with dissociative disorders stopped their treatment prematurely (p < .001). Impact of dissociative disorders on development and treatment of substance dependency requires further study.
Sun, Yan; Zhang, Yan; Wang, Fan; Sun, Yankun; Shi, Jie; Lu, Lin
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.
Seo, Sambu; Mohr, Johannes; Beck, Anne; Wüstenberg, Torsten; Heinz, Andreas; Obermayer, Klaus
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.
Background Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls. While all subjects were recruited to be free of alcohol dependence, structured clinical interviews revealed significant patterns of alcohol use in the patients. Structural magnetic resonance brain images were obtained from the subjects using a 1.5 Tesla GE Signa machine. Brain cortical thickness was measured with submillimeter precision at multiple finely spaced cortical locations using semi-automated post-processing (FreeSurfer). Contrast analysis of a general linear model was used to test for differences between the two groups at each cortical location. In addition to contrasting patients with controls, a number of analyses sought to identify possible confounding effects from alcohol. Results No significant cortical thickness differences were observed between the full patient group and controls, nor between non-drinking patients and controls. Patients with a history of co-morbid heavy alcohol use (n = 29) showed reductions in the superior-frontal right hemisphere and pre-central left hemisphere when compared to healthy controls (n = 40). Conclusions Amphetamine usage was associated with reduced cortical thickness only in patients co-morbid for heavy alcohol use. Since cortical thickness is but one measure of brain structure and does not capture brain function, further studies of brain structure and function in amphetamine dependence are warranted. PMID:20487539
Walitzer, Kimberly S.; Deffenbacher, Jerry L.; Shyhalla, Kathleen
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 six-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 six months after treatment end. Both AM and AAF treatments were followed by significant reductions in heavy drinking days, alcohol consequences, anger, and maladaptive anger-related thoughts and increases in abstinence and self-confidence regarding not drinking to anger-related triggers. Treatment with AAF was associated with greater AA involvement relative to treatment with AM. Changes in anger and AA involvement were predictive of posttreatment alcohol outcomes for both treatments. Change in trait anger was a stronger predictor of posttreatment alcohol consequences for AM than for AAF clients; during-treatment AA meeting attendance was a stronger predictor of posttreatment heavy drinking and alcohol consequences for AAF than for AM clients. Anger-related constructs and drinking triggers should be foci in treatment of alcohol dependence for anger-involved clients. PMID:26387049
Simons, Jeffrey S; Carey, Kate B; Wills, Thomas A
This study tested a theoretical model hypothesizing differential pathways from 5 predictors to alcohol abuse and dependence symptoms. The participants were college students (N = 2,270) surveyed on 2 occasions in a 6-month prospective design. Social norms, perceived utility of alcohol use, and family history of alcohol problems were indirectly associated with Time 2 abuse and dependence symptoms through influencing level of alcohol consumption. Poor behavioral control had a direct effect on alcohol abuse but not on dependence symptoms at Time 2, whereas affective lability exhibited a direct prospective effect on alcohol dependence but not on abuse symptoms. A multigroup analysis showed that high levels of poor control increased the strength of paths from both consumption level and affective lability to abuse symptoms. Implications for prevention of alcohol problems among college students are discussed. 2009 APA, all rights reserved.
Buck, Cara L.; Malavar, Jordan C.; George, Olivier; Koob, George F.; Vendruscolo, Leandro F.
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
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.
Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C
Prazosin (PRZ; an α1 -adrenergic receptor antagonist) and naltrexone (NTX; a nonspecific 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. As 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. Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/d 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: (i) daily alcohol access with daily drug treatment, (ii) intermittent alcohol access with daily drug treatment, (iii) intermittent alcohol access with occasional drug treatment, and (iv) postdeprivation reinstatement of alcohol access. 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. Both daily and "as-needed" treatment with PRZ + NTX are highly effective in suppressing daily, intermittent, and postdeprivation 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 repeated relapse, as commonly
Clarke, Toni-Kim; Smith, Andrew H; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Hall, Lynsey S; Fernandez-Pujals, Ana M; MacIntyre, Donald J; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; Thomson, Pippa A; Porteous, David J; Deary, Ian J; McIntosh, Andrew M
Alcohol dependence is frequently co-morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome-wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n = 2750; Yale-Penn GWAS: n = 2377) in a population-based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P = 0.009, β = -0.027; Yale-Penn: P = 0.001, β = -0.034) and VF (SAGE: P = 0.0008, β = -0.036; Yale-Penn: P = 0.00005, β = -0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P = 5.2 × 10(-7) , β = -0.054; Yale-Penn: P = 0.000012, β = -0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders.
Maurage, Pierre; Grynberg, Delphine; Noël, Xavier; Joassin, Frédéric; Hanak, Catherine; Verbanck, Paul; Luminet, Olivier; de Timary, Philippe; Campanella, Salvatore; Philippot, Pierre
It has been repeatedly shown that alcohol dependence is associated with emotional impairments, particularly for emotional facial expression decoding. Nevertheless, most earlier studies focused on basic emotions and did not explore more subtle affective states. In order to obtain a more accurate evaluation, and in view of earlier results showing impaired performance for this task among high-risk children of alcohol-dependent participants, the "Reading the Mind in the Eyes" test was used here to explore emotional recognition in alcohol dependence. We showed that the deficit described earlier for basic negative emotions is (1) generalizable to complex and positive emotions; and (2) specific for emotional features. This strengthens the proposition of a general face recognition impairment in alcohol dependence.
Bobova, Lyuba; Finn, Peter R; Rickert, Martin E; Lucas, Jesolyn
Increased discounting of delayed rewards may reflect a decision bias that contributes to excessive use of alcohol and more generally, to an impulsive, disinhibitory predisposition that is characterized by a preference for immediate over long-term rewards. The current study examined the association between delay discounting of rewards and the covariation among several types of disinhibitory problems that are often comorbid with alcohol dependence (AD). Lifetime problems with alcohol, marijuana, other drugs, childhood conduct disorder, and adult antisocial behavior were assessed in a sample of 426 young adults, 257 of whom had a lifetime diagnosis of AD. Higher delay discounting rates were associated with the covariation among all domains of disinhibitory problems and were not uniquely associated with any one domain. Higher delay discounting rates also were associated with lower intelligence, lower working memory capacity, and higher trait impulsivity. The results suggest that increased delay discounting of rewards may reflect aspects of a general vulnerability to externalizing, disinhibitory disorders.
Shorey, Ryan C.; Stuart, Gregory L.; Anderson, Scott
Research suggests that there may be differences between individuals diagnosed with alcohol dependence and individuals diagnosed with opioid dependence on co-morbid mental health problems (e.g., personality disorders, mood disorders, etc.). The current study examined whether there were differences in early maladaptive schemas, which are theorized to underlie mental health problems, among women diagnosed with alcohol dependence or opioid dependence who were seeking treatment for their substance use (N = 420). Results showed that opioid dependent women scored higher on 2 of the 18 early maladaptive schemas, particularly the schemas of dependence and punitiveness. Overall, these findings suggest that early maladaptive schemas may be largely consistent across women diagnosed with alcohol or opioid dependence. Implications of these findings for future research and treatment are discussed. PMID:23494129
van Gorp, W G; Altshuler, L; Theberge, D C; Wilkins, J; Dixon, W
Few studies of the neurocognitive performance of patients with bipolar disorder have been performed while patients are in the euthymic state. Twenty-five euthymic bipolar patients (12 with and 13 without a history of alcohol dependence) were compared with 22 normal control subjects on a neuropsychological test battery assessing a range of cognitive domains. The relationship between subjects' neurocognitive performance and the course-of-illness variables (lifetime episodes and duration of mania, depression, or both), as well as current lithium level, was determined. The results indicated differences across the groups, with the bipolar patients with and without alcohol dependence performing more poorly than controls on tests of verbal memory. Furthermore, bipolar subjects with a history of alcohol dependence had additional decrements in executive (i.e., frontal lobe) functions when compared with controls. For subjects in the bipolar group, lifetime months of mania and depression were negatively correlated with performance in verbal memory and several executive function measures. Our findings support the presence of persistent neurocognitive difficulties in patients with long-standing bipolar disorder who are not in the psychiatrically acute state or who are suffering the effects of alcohol abuse and suggest that there may be an aggregate negative effect of lifetime duration of bipolar illness on memory and frontal or executive systems.
Cornelius, Jack R.; Douaihy, Antoine B.; Clark, Duncan B.; Chung, Tammy; Wood, D. Scott; Daley, Dennis
Objective This was a first pilot study evaluating the acute phase (8-week) efficacy of the antidepressant medication mirtazapine for the treatment of depressive symptoms and drinking of subjects with comorbid major depressive disorder and alcohol dependence (MDD/AD). We hypothesized that mirtazapine would demonstrate within-group efficacy for the treatment of both depressive symptoms and drinking in these subjects. Methods We conducted a first open label study of the second generation antidepressant mirtazapine in 12 adult outpatient subjects with comorbid major depressive disorder/alcohol dependence. The pharmacological profile of that medication is unique among antidepressants, unrelated to tricyclics or selective serotonin reuptake inhibitors. Results Mirtazapine was well tolerated in this treatment population. Self-reported depressive symptoms decreased from 31.8 to 8.3 on the Beck Depression Inventory, a 74.0% decrease (p<0.001), and drinking decreased from 33.9 to 13.3 drinks per week, a 60.8% decrease (p<0.05). None of the subjects were employed full-time at baseline, but 9 of the 12 (75%) were employed full-time at end-of-study. Conclusions These preliminary findings suggest efficacy for mirtazapine for treating both the depressive symptoms and excessive alcohol use of comorbid major depressive disorder and alcohol dependence. Double-blind studies are warranted to further clarify the efficacy of mirtazapine in this population. PMID:23230395
Ipek, Okan Ufuk; Yavuz, Kaasim Fatih; Ulusoy, Sevinc; Sahin, Oktay; Kurt, Erhan
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
O'Brien, Jessica W; Hill, Shirley Y
Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. Women with a family history of
Quinn, Amity E; Rosen, Rochelle K; McGeary, John E; Amoa, Francine; Kranzler, Henry R; Francazio, Sarah; McGarvey, Stephen T; Swift, Robert M
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. 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. 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. 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. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.
Sari, Youssef; Johnson, Verity R.; Weedman, Jason M.
Alcohol dependence remains among the most common substance abuse problems worldwide, and compulsive alcohol consumption is a significant public health concern. Alcohol is an addictive drug that alters brain function through interactions with multiple neurotransmitter systems. These neurotransmitter systems mediate the reinforcing effects of alcohol. Specifically, the serotonergic system is important in mediating alcohol reward, preference, dependence, and craving. In this review chapter, we first discuss the serotonin system as it relates to alcoholism, and then outline interactions between this system and other neurotransmitter systems. We emphasize the serotonin transporter and its possible role in alcoholism, then present several serotonergic receptors and discuss their contribution to alcoholism, and finally assess the serotonin system as a target for pharmacotherapy, with an emphasis on current and potential treatments. PMID:21199778
Van Horn, Deborah H A; Rennert, Lior; Lynch, Kevin G; McKay, James R
Research on face-to-face treatment for substance misuse suggests that patients' social networks may impact treatment entry and participation, but there has been no similar research on entry and participation in telephone-based continuing care. We examined whether alcohol-specific social support predicted engagement and participation in telephone continuing care for alcohol dependence, and whether treatment participation resulted in beneficial changes in participants' social networks. Participants were 252 adults (162 male) enrolled in a randomized clinical trial testing the effectiveness of telephone continuing care for alcohol dependence. Participants who completed 3 weeks of intensive outpatient treatment were randomly assigned to treatment as usual, telephone monitoring (TM; N = 83), or telephone monitoring and brief counseling (TMC; N = 83). TM and TMC included 18 months of telephone treatment. Alcohol-specific social support was measured with the Important People Inventory at baseline and 6, 12, 18, and 24-month follow-up. Alcohol-specific social support did not predict entry into TM or TMC. Among those who entered telephone treatment (N = 127), participants with higher network percentage of daily drinkers, higher percentage of network members who accept drinking, and lower percentage of network members who do not accept drinking completed more continuing care calls. There was no effect of continuing care participation on alcohol-specific social support over 24 months of follow-up. Participants with more problematic social networks may self-select additional support in the form of telephone continuing care. Telephone continuing care does not appear to result in social network change. © American Academy of Addiction Psychiatry.
Bierut, Laura Jean; Rice, John P; Goate, Alison; Hinrichs, Anthony L; Saccone, Nancy L; Foroud, Tatiana; Edenberg, Howard J; Cloninger, C Robert; Begleiter, Henri; Conneally, P Michael; Crowe, Raymond R; Hesselbrock, Victor; Li, Ting-Kai; Nurnberger, John I; Porjesz, Bernice; Schuckit, Marc A; Reich, Theodore
Smoking is a highly heritable, addictive disorder that commonly co-occurs with alcohol dependence. The purpose of this study is to perform a genomic screen for habitual smoking and comorbid habitual smoking and alcohol dependence in families from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per day or more for at least 6 months). Sixty seven multi-generational families with 154 independent sibling pairs affected with habitual smoking were genotyped in a screening sample. Analyses on 79 multi-generational families with 173 independent sibling pairs were repeated in a replication sample. Sibpair analyses were performed using ASPEX. Four chromosomal regions in the screening sample had increased allele sharing among sibling pairs for habitual smoking with a LOD score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on chromosome 9 (LOD = 2.02; allele sharing 58.9%). Four chromosomal regions also had modest evidence for linkage to the comorbid phenotype habitual smoking and alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on chromosome 2 (LOD = 3.30; allele sharing 69.1%). Previously identified areas (chromosomes 1 and 7) implicated in the development of alcohol dependence in this same data set did not provide evidence for linkage to habitual smoking in the screening sample. In the replication data set, there continued to be increased allele sharing near peaks identified in the screening sample on chromosomes 2 and 9, but the results were modest. An area on chromosome 7, approximately 60 cM from a location previously identified in linkage analysis with alcohol dependence, had increased allele sharing for the comorbid habitual smoking and alcohol dependence. These data provide evidence of specific genetic regions involved in the
Steinig, Jana; Foraita, Ronja; Happe, Svenja; Heinze, Martin
This study aims to investigate sleep quality and the subjective dream experience in alcohol-dependent patients during withdrawal and abstinence compared with healthy controls. Thirty-seven patients with alcohol dependency and 35 healthy control subjects were asked to fill in several questionnaires and to give information about their subjective sleep and dream experiences. Twelve patients participated in a follow-up interview 4 weeks later. Sleep quality is impaired in alcohol-dependent patients during detoxication, and the subjective dream experience is more negatively toned compared with healthy controls. Both sleep quality and dream experience improves slightly after 4 weeks of abstinence. Patients with alcohol dependency during withdrawal and abstinence dream significantly more often about alcohol. However, none of the abstinent alcohol-dependent patients dreamed about alcohol during withdrawal. This study shows that the subjective sleep and dream quality is strongly impaired in patients with alcohol dependency. Differences in the dream experience between alcohol-dependent patients and healthy controls are in accordance with the continuity hypotheses of dreaming. The hypothesis of dreaming about alcohol as a compensatory effect, however, could not be confirmed.
Hallgren, Mats; Romberg, Karin; Bakshi, Ann-Sofie; Andréasson, Sven
This pilot study explores the feasibility of yoga as part of a treatment program for alcohol dependence. Eighteen alcohol dependent patients were randomized to receive either treatment as usual or treatment as usual plus yoga. Assessments were taken at baseline and six month follow-up. 'Riddargatan 1': an outpatient alcohol treatment clinic located in Stockholm, Sweden. Treatment as usual consisted of psychological and pharmacological interventions for alcohol dependence. The 10-week yoga intervention included a weekly group yoga session. Participants were encouraged to practice the yoga movements at home once per day. Alcohol consumption (timeline follow-back method, DSM-IV criteria for alcohol dependence, and the Short Alcohol Dependence Data questionnaire), affective symptoms (the Hospital Anxiety and Depression Scale), quality of life (Sheehan Disability Scale) and stress (the Perceived Stress Scale and saliva cortisol). Yoga was found to be a feasible and well accepted adjunct treatment for alcohol dependence. Alcohol consumption reduced more in the treatment as usual plus yoga group (from 6.32 to 3.36 drinks per day) compared to the treatment as usual only group (from 3.42 to 3.08 drinks per day). The difference was, however, not statistically significant (p = 0.17). Larger studies are needed to adequately assess the efficacy and long-term effectiveness of yoga as an adjunct treatment for alcohol dependence. Copyright © 2014 Elsevier Ltd. All rights reserved.
Wiers, Corinde E; Ludwig, Vera U; Gladwin, Thomas E; Park, Soyoung Q; Heinz, Andreas; Wiers, Reinout W; Rinck, Mike; Lindenmeyer, Johannes; Walter, Henrik; Bermpohl, Felix
Alcohol-dependent patients have been shown to faster approach than avoid alcohol stimuli on the Approach Avoidance Task (AAT). This so-called alcohol approach bias has been associated with increased brain activation in the medial prefrontal cortex and nucleus accumbens. Cognitive bias modification (CBM) has been used to retrain the approach bias with the clinically relevant effect of decreasing relapse rates one year later. The effects of CBM on neural signatures of approach/avoidance tendencies remain hitherto unknown. In a double-blind placebo-controlled design, 26 alcohol-dependent in-patients were assigned to a CBM or a placebo training group. Both groups performed the AAT for three weeks: in CBM training, patients pushed away 90 percent of alcohol cues; this rate was 50 percent in placebo training. Before and after training, patients performed the AAT offline, and in a 3 T magnetic resonance imaging scanner. The relevant neuroimaging contrast for the alcohol approach bias was the difference between approaching versus avoiding alcohol cues relative to soft drink cues: [(alcohol pull > alcohol push) > (soft drink pull > soft drink push)]. Before training, both groups showed significant alcohol approach bias-related activation in the medial prefrontal cortex. After training, patients in the CBM group showed stronger reductions in medial prefrontal cortex activation compared with the placebo group. Moreover, these reductions correlated with reductions in approach bias scores in the CBM group only. This suggests that CBM affects neural mechanisms involved in the automatic alcohol approach bias, which may be important for the clinical effectiveness of CBM. © 2015 Society for the Study of Addiction.
Czapla, Marta; Baeuchl, Christian; Simon, Joe J; Richter, Barbara; Kluge, Matthias; Friederich, Hans-Christoph; Mann, Karl; Herpertz, Sabine C; Loeber, Sabine
Alcohol dependence is associated with impaired response inhibition and heightened cue reactivity towards alcohol-related stimuli. Several brain areas, but mainly prefrontal structures, have been linked to response inhibition in addiction. This study aimed at combining both aspects: salience of drug-associated cues and response inhibition using a go/no-go task with alcohol-associated stimuli during functional magnetic resonance imaging (fMRI). Nineteen abstinent alcohol-dependent patients (ADP) and 21 healthy control subjects (HC) were compared on blood oxygen level-dependent (BOLD) responses during successful inhibition of no-go stimuli and successful reactions to go stimuli. ADP and HC did not significantly differ in their behavioural performance in the task. However, both groups performed worse during the inhibition of alcoholic-associated stimuli compared to neutral stimuli. On the neural level, ADP displayed enhanced BOLD activity relative to HC during successful response inhibition in several areas involved in visual processing, cognitive and impulse control, including occipital structures, anterior cingulate gyrus, medial frontal gyrus and medial orbitofrontal cortex. We interpret these findings as a possible compensation strategy for impaired cognitive processing. Furthermore, the results underline the impact of salience of alcohol-related stimuli on response inhibition, which seems to affect both ADP and HC.
Hillmer, Ansel T.; Mason, Graeme F.; Fucito, Lisa M.; O’Malley, Stephanie S.; Cosgrove, Kelly P.
Neuroimaging studies have dramatically advanced our understanding of the neurochemical basis of alcohol dependence, a major public health issue. In this paper we review the research generated from neurochemical-specific imaging modalities including magnetic resonance spectrometry (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in studies of alcohol dependence and withdrawal. We focus on studies interrogating γ-aminobutryic acid (GABA), glutamate, and dopamine, as these are prominent neurotransmitter systems implicated in alcohol dependence. Highlighted findings include diminished dopaminergic functioning and modulation of the GABA system by tobacco smoking during alcohol withdrawal. Then, we consider how these findings impact the clinical treatment of alcohol dependence and discuss directions for future experiments to address existing gaps in the literature, e.g., sex differences and smoking comorbidity. These and other considerations provide opportunities to build upon the current neurochemistry imaging literature of alcohol dependence and withdrawal, which may usher in improved therapeutic and relapse prevention strategies. PMID:26510169
Danielsson, O; Jörnvall, H
Analysis of the activity and structure of lower vertebrate alcohol dehydrogenases reveals that relationships between the classical liver and yeast enzymes need not be continuous. Both the ethanol activity of class I-type alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 220.127.116.11) and the glutathione-dependent formaldehyde activity of the class III-type enzyme [formaldehyde:NAD+ oxidoreductase (glutathione-formylating), EC 18.104.22.168] are present in liver down to at least the stage of bony fishes (cod liver: ethanol activity, 3.4 units/mg of protein in one enzyme; formaldehyde activity, 4.5 units/mg in the major form of another enzyme). Structural analysis of the latter protein reveals it to be a typical class III enzyme, with limited variation from the mammalian form and therefore with stable activity and structure throughout much of the vertebrate lineage. In contrast, the classical alcohol dehydrogenase (the class I enzyme) appears to be the emerging form, first in activity and later also in structure. The class I activity is present already in the piscine line, whereas the overall structural-type enzyme is not observed until amphibians and still more recent vertebrates. Consequently, the class I/III duplicatory origin appears to have arisen from a functional class III form, not a class I form. Therefore, ethanol dehydrogenases from organisms existing before this duplication have origins separate from those leading to the "classical" liver alcohol dehydrogenases. The latter now often occur in isozyme forms from further gene duplications and have a high rate of evolutionary change. The pattern is, however, not simple and we presently find in cod the first evidence for isozymes also within a class III alcohol dehydrogenase. Overall, the results indicate that both of these classes of vertebrate alcohol dehydrogenase are important and suggest a protective metabolic function for the whole enzyme system. Images PMID:1409630
Le Strat, Yann; Ramoz, Nicolas; Gorwood, Philip
To examine the pattern of psychiatric comorbidity associated with nicotine dependence among alcohol-dependent respondents in the general population. Drawn from a US national survey of 43,000 adults The (National Epidemiologic Survey on Alcohol and Related Conditions) who took part in a face-to-face interview, data were examined on the 4782 subjects with lifetime alcohol dependence, and comparisons were made between those with and those without nicotine dependence. Nicotine dependence was reported by 48% of the alcohol-dependent respondents. They reported higher lifetime rates of panic disorder, specific and social phobia, generalized anxiety disorder, major depressive episode, manic disorder, suicide attempt, antisocial personality disorder and all addictive disorders than those without nicotine dependence. After controlling for the effects of any psychiatric and addictive disorder, alcohol-dependent subjects with nicotine dependence were more than twice as likely as non-nicotine-dependent, alcohol-dependent subjects to have at least one other lifetime addiction diagnosis (adjusted odds ratio 2.36; 95% confidence interval 2.07-2.68). Nicotine dependence represents a general marker of psychiatric comorbidity, particularly of addictive comorbidity. It may be used as a screening measure for psychiatric diagnoses in clinical practice as well as in future trials.
Richardson, Heather N.; Chan, Stephanie H.; Crawford, Elena F.; Lee, Youn Kyung; Funk, Cindy K.; Koob, George F.; Mandyam, Chitra D.
Experimenter-delivered alcohol decreases adult hippocampal neurogenesis, and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis was observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggests a loss in neuronal turnover and indicates that the hippocampal neurogenic niche is highly vulnerable to alcohol. PMID:19501165
Springer, Sandra A.; Azar, Marwan M.; Altice, Frederick L.
People with both HIV and alcohol use disorders are disproportionately concentrated within the U.S. criminal justice system; approximately one-quarter of all people with HIV cycle through the system each year. HIV-infected prisoners with alcohol problems face many obstacles as they transition back to the community. Specifically, although they have impressive HIV treatment outcomes during the period of incarceration while they are free from alcohol, upon release, however, they face inordinate challenges including relapse to alcohol use resulting in significant morbidity and mortality. Randomized controlled trials affirm the role of pharmacotherapy using naltrexone (NTX) as the therapeutic option conferring the best treatment outcome for alcohol use disorders within the community. Absent from these trials were inclusion of prisoners or HIV-infected individuals. Relapse to alcohol use among HIV-infected prisoners is associated with reduced retention in care, poor adherence to antiretroviral therapy with consequential poor HIV treatment outcomes and higher levels of HIV risk behaviors. Untreated alcohol dependence, particularly for released HIV-infected prisoners, has both negative consequences for the individual and society and requires a concentrated effort and rethinking of our existing approaches for this vulnerable population. The specific aim of this manuscript is to review the existing literature regarding the relationship of HIV and treatment for alcohol use disorders in criminal justice populations in an effort to determine “best practices” that might effectively result in improved treatment of HIV and alcohol disorders for released prisoners. PMID:21171933
Racz, Ildiko; Schürmann, Britta; Karpushova, Anna; Reuter, Martin; Cichon, Sven; Montag, Christian; Fürst, Robert; Schütz, Christian; Franke, Petra E; Strohmaier, Jana; Wienker, Thomas F; Terenius, Lars; Osby, Urban; Gunnar, Agneta; Maier, Wolfgang; Bilkei-Gorzó, Andras; Nöthen, Markus; Zimmer, Andreas
Experimental evidence indicates that the endogenous opioid system influences stress responses as well as reinforces effects of addictive drugs. Because stress is an important factor contributing to drug dependence and relapse, we have now studied ethanol preference in enkephalin- and beta-endorphin-deficient mice under baseline conditions and after stress exposure. In the present study we used a two-bottle choice paradigm to study ethanol consumption and stress-induced ethanol preference. To examine alcohol withdrawal symptoms the forced drinking procedure was employed. We performed an association analysis in two case-control samples of alcohol addicts to determine whether these opioid peptides also contribute to ethanol dependence in humans. Ethanol consumption was significantly reduced in the absence of beta-endorphins, particularly in female knockout animals. Stress exposure results in an increased ethanol consumption in wild-type mice but did not influence ethanol-drinking in beta-endorphin knockouts. Enkephalin-deficient mice showed no difference from wild-type mice in baseline ethanol preference but also showed no stress-induced elevation of ethanol consumption. Interestingly, we found a two-marker haplotype in the POMC gene that was associated with alcohol dependence in females in both cohorts. Together these results indicate a contribution of beta-endorphin to ethanol consumption and dependence.
Myerson, Joel; Green, Leonard; van den Berk-Clark, Carissa; Grucza, Richard A.
Rationale Alcohol dependence is known to be associated with steep discounting of delayed rewards, but its relation to the discounting of delayed losses and probabilistic rewards is unclear. Moreover, patterns of alcohol consumption vary considerably between communities, but previous research has not examined the relation between discounting and alcohol dependence in low-income African Americans. Objectives The goal of the present study was to determine whether low-income, alcohol-dependent African Americans differ from controls in the degree to which they discount delayed rewards, delayed losses, or probabilistic rewards. Methods African American participants, both cases and controls, were recruited from the same low-income neighborhoods, and propensity-score matching was used to further control for demographic differences. Participants performed three tasks that assessed their discounting of hypothetical monetary outcomes: delayed rewards, delayed losses, and probabilistic rewards. Results Alcohol-dependent cases discounted delayed gains, but not delayed losses or probabilistic gains, more steeply than their matched controls. The difference in discounting of delayed gains was localized to the male cases, whose discounting was steeper than either the male controls or the female cases; no gender difference was observed between male and female controls. Conclusions The present results extend findings regarding discounting by substance abusers to a previously unstudied group, low-income African Americans, and suggest that in this group at least, alcohol dependence, particularly in males, may be more a reflection of choosing immediate rewards than of ignoring their delayed negative consequences. PMID:26387518
Crum, R M; Helzer, J E; Anthony, J C
OBJECTIVES. Prospectively gathered data were used to reexamine and to strengthen previously described observations about education and the risk of alcohol abuse and dependence. The hypothesis was that individuals who dropped out of high school and those who entered college but failed to get a college degree might be at increased risk for an alcohol disorder. METHODS. Study subjects were selected between 1980 and 1984 by taking probability samples of roughly 3000 adult household residents at each of the five Epidemiologic Catchment Area Program survey sites. To assess the occurrence of psychiatric conditions, staff administered the Diagnostic Interview Schedule soon after sampling and again at follow-up, roughly 1 year later. RESULTS. Individuals who had dropped out of high school were 6.34 times more likely to develop alcohol abuse or dependence than were individuals with a college degree. For those who had entered college but failed to achieve a degree, the estimated relative risk was 3.01. To extend these analyses, estimates for annual incidence were calculated, and an exploratory evaluation of interaction is presented. CONCLUSIONS. If these findings can be replicated, they should help identify subgroups at higher risk for the development of alcohol disorders. PMID:8498620
Rehm, Jürgen; Allamani, Allaman; Della Vedova, Roberto; 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
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. 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. 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. 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. © 2015 Annals of Family Medicine, Inc.
Zhu, Guanshan; Pollak, Lotta; Mottagui-Tabar, Salim; Wahlestedt, Claes; Taubman, Julie; Virkkunen, Matti; Goldman, David; Heilig, Markus
Neuropeptide Y (NPY) is a modulator of alcohol intake in animal models of alcoholism, and is potentially involved in alcohol dependence. A coding Leu7Pro polymorphism in the signal peptide of preproNPY has been described, and the Pro7 allele has been reported to correlate with increased alcohol consumption in non-dependent Finnish males. Recently, this polymorphism was also reported to be associated with an actual diagnosis of alcohol dependence. We compared Pro7 allele frequencies in one Finnish (n = 135) and one Swedish (n = 472) population of alcohol dependent individuals, and ethnically matched controls (Finns: n = 213; Swedes: n = 177) in whom alcohol dependence was established, or any diagnosis of substance disorder was excluded, respectively, through the use of structured face-to-face interviews. Pro7 frequencies in alcoholics were 5.2 and 4.1% in Finns and Swedes, respectively, similar to the 5.0-5.5% recently reported in European Americans in a Yale study. However, corresponding frequencies in the control populations were similar, at 6.1 and 5.9% in Finns and Swedes, respectively, yielding no association, in contrast with the Yale study, where an association was reported based on a 2.0% Pro7 frequency in European American controls. A meta-analysis of available data yields Pro7 frequencies of 4.7% both in Caucasian alcoholics and Caucasian controls. Pro7 does not seem to be associated with a diagnosis of alcoholism in Caucasian populations.
Gilburt, Helen; Burns, Tom; Copello, Alex; Crawford, Michael; Day, Ed; Deluca, Paolo; Godfrey, Christine; Parrott, Steve; Rose, Abigail; Sinclair, Julia; Coulton, Simon
Abstract Aims A pilot randomized controlled trial (RCT) to assess the feasibility and potential efficacy of assertive community treatment (ACT) in adults with alcohol dependence. Methods Single blind, individually randomized, pilot RCT of 12 months of ACT plus treatment as usual (TAU) versus TAU alone in adults (age 18+ years) with alcohol dependence and a history of previous unsuccessful alcohol treatment attending specialist community alcohol treatment services. ACT aimed to actively engage participants for 12 months with assertive, regular, minimum weekly contact. ACT was combined with TAU. TAU comprised access to the full range of services provided by the community teams. Primary outcome is mean drinks per drinking day and percent days abstinent at 12 months follow up. Analysis of covariance was conducted using 80% confidence intervals, appropriate in the context of a pilot trial. Results A total of 94 participants were randomized, 45 in ACT and 49 in TAU. Follow-up was achieved with 98 and 88%, respectively at 12 months. Those in ACT had better treatment engagement, and were more often seen in their homes or local community than TAU participants. At 12 months the ACT group had more problems related to drinking and lower quality of life than TAU but no differences in drinking measures. The ACT group had a higher percentage of days abstinent but lower quality of life at 6 months. The ACT group had less unplanned healthcare use than TAU. Conclusions An trial of ACT was feasible to implement in an alcohol dependent treatment population. Trial registration ISRCTN22775534 PMID:27940571
Gongvatana, Assawin; Morgan, Erin E.; Iudicello, Jennifer E.; Letendre, Scott L.; Grant, Igor; Woods, Steven Paul
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
Rumpf, H J; Bischof, G; Hapke, U; Meyer, C; John, U
To assess the selection bias of recruiting participants in studies on natural recovery from alcohol dependence through media solicitation. Two samples with different recruitment strategies are compared. Media solicitation and general population. Sample 1 consists of 176 alcohol-dependent individuals remitted without formal help and recruited through media solicitation, sample 2 consists of 32 natural remitters derived from a representative general population study with a sample size of 4075 respondents and a response rate of 70.2%. Several triggering mechanisms and maintenance factors of remission were assessed in a personal interview using standardized questionnaires. Results of logistic regression analyses show that media-solicited subjects were more often abstinent in the last 12 months, were more severely dependent, were less satisfied with eight life domains prior to remission and showed higher scores in a coping behaviour measure. Besides these major differences from the multivariate analysis, media subjects revealed more health problems prior to remission, experienced more social pressure to change drinking behaviour, and showed differences in reasons for not seeking help. Media solicitation leads to a sample selection bias in research on natural recovery from alcohol dependence. When measures to foster self-change are derived from such studies, findings from representative samples have to be considered.
Ghosh, Abhishek; Malhotra, Savita; Basu, Debasish
Background & objectives: The subtyping of alcohol dependence (AD) into early-onset (EO) and late-onset (LO) subgroups has been shown to have clinical and biological validity. As externalizing disorders (EDs) predate AD, the link of ED with age of onset of alcohol dependence needs to be investigated. The aim of this study was to examine the relationship of EDs such as disruptive behaviour disorder (DBD) and attention deficit hyperactivity disorder (ADHD) with age at onset of AD in a sample of male subjects. Methods: One hundred consecutive male subjects with AD presenting to the De-Addiction Services and an equal number of biologically unrelated non-substance-dependent control subjects were included in the study. The AD subjects were divided into EO (age of onset of AD ≤25 yr; n = 21) and LO (age of onset of AD >25 yr; n = 79). Subjects were examined for evidence of DBD and ADHD in childhood, and current ADHD using structured instruments such as Semi-Structured Assessment for the Genetic of Alcoholism-IV (SSAGA-IV) and Kiddie – SADS – Present and Lifetime Version (K-SADS-PL). The odds ratio of association of EDs with EO and LO AD was calculated by comparing these subgroups with the biologically unrelated control group. Later, both the subgroups of alcohol dependence were compared for the presence of EDs. Results: All EDs (DBDs/childhood or adult ADHD) were more common in AD individuals as compared to the controls. However, when AD subgroups were compared with controls, the association of DBDs and ADHD reached a significant level only in the EO subgroup. A comparison of EO and LO AD showed that more EO individuals had history of both childhood disruptive disorder and ADHD compared to LO subgroup. Adult ADHD was also over-represented in EO subgroup. Interpretation & conclusions: Our study showed more EDs in alcohol dependent individuals compared to controls. Further, the association observed between EDs and EO alcohol dependence points towards a developmental
Butterworth, R F; Kril, J J; Harper, C G
Chronic alcoholism results in thiamine deficiency as a consequence of poor nutrition, impaired absorption, and decreased phosphorylation to the enzyme cofactor form of the vitamin, thiamine pyrophosphate (TPP). Results of this study demonstrate significant reductions of TPP-dependent enzymes [pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH), and transketolase] in autopsied cerebellar vermis samples from alcoholic patients with the clinical and neuropathologically confirmed diagnosis of Wernicke-Korsakoff Syndrome (WKS). Enzyme activities in brain samples from alcoholics without WKS were within normal limits and activities of a nonthiamine-dependent enzyme, glutamate dehydrogenase, were not significantly different from control values in brain samples from alcoholics with or without WKS. These findings provide evidence, for the first time, of a direct implication of TPP-related metabolic processes in the pathogenesis of WKS. Decreased activities of alpha KGDH could be the trigger for a sequence of metabolic events resulting in energy compromise, and ultimately neuronal death in this syndrome.
Mann, K; Mundle, G; Strayle, M; Wakat, P
For more than a century we have known the deleterious effects of alcohol on the brain regions surrounding the third ventricle and on the cerebellum. But it was only recently that we gained clearer evidence that the cortex is affected as well. Our imaging studies show that brain shrinkage is at least partially reversible once abstinence is maintained. They confirm results obtained in different laboratories from all over the world. Although our data contradict the rehydration hypothesis and thus lend credence to the idea of regeneration and neuroplasticity, the nature of reversibility is still a matter of debate.
Marcos, Miguel; Pastor, Isabel; González-Sarmiento, Rogelio; Laso, Francisco Javier
The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)-kappaB, the NF-kappaB inhibitor alpha (NFKBIA), and the peroxisome proliferator-activated receptor (PPAR)-gamma in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC. The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC. A total of 258 male alcoholics (161 without liver disease and 97 with ALC) and 101 healthy controls were genotyped for the -94ins/delATTG NFKB1, 3'-UTR+126G>A NFKBIA, and 34C>G PPARG2 polymorphisms. The association of these genetic variants with ALC was tested in alcoholic patients with alcohol abuse and alcohol dependence. A logistic regression analysis was further performed to analyze the model of inheritance. We found an association between the presence of the deletion allele in NFKB1 polymorphism and ALC in patients with alcohol dependence. We found no association between NFKBIA and PPARG2 polymorphisms and the presence of ALC. The deletion allele of the -94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data.
Howard, M O
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.
Giorgi, Ines; Ottonello, Marcella; Vittadini, Giovanni; Bertolotti, Giorgio
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
Hauser, Sheketha R; Getachew, Bruk; Oster, Scott M; Dhaher, Ronnie; Ding, Zheng-Ming; Bell, Richard L; McBride, William J; Rodd, Zachary A
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 2 different time points. Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% ethanol (EtOH) (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hour sessions. Following 10 weeks of daily 1-hour 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 subcutaneously immediately or 4 hours prior to PSR or relapse testing. Injections of nicotine immediately prior to testing reduced (5 to 10 responses PSR; 50 to 60 responses relapse), whereas injections of nicotine 4 hours 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. 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 hours, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine's metabolites (i.e., cotinine and nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors. Copyright © 2011 by the Research Society on Alcoholism.
Goldstein, Brittany; Bradley, Bekh; Ressler, Kerry J.
Objective The purpose of this study was to examine how emotion dysregulation (ED) might help explain the relationship between posttraumatic stress disorder (PTSD) and alcohol dependence (AD) symptoms in females. Method Participants included 260 women from primary, diabetes, and gynecological clinics of an urban public hospital. This is a primarily African American sample (96.9%), including individuals reporting exposure to at least 1 traumatic event. We examined the associations and predictability patterns between severity of PTSD symptoms, ED, and AD symptoms. Results Using linear regression analyses, PTSD avoidance and numbing symptoms and ED were significant predictors of AD symptoms. When looking at specific dimensions of ED, one's inability to engage in goal‐directed behavior under strong emotional influences showed a full indirect effect on the relationship between PTSD avoidance and numbing symptoms and AD symptoms. Conclusion Our findings suggest that having poor emotion regulation skills may help explain why females with PTSD become dependent on alcohol. PMID:27467499
Walker, Brendan M; Valdez, Glenn R; McLaughlin, Jay P; Bakalkin, Georgy
This review represents the focus of a symposium that was presented at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference in Volterra, Italy on May 3-6, 2011 and organized/chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN/KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders.
Walker, Brendan M.; Valdez, Glenn R.; McLaughlin, Jay P.; Bakalkin, Georgy
This review represents the focus of a symposium that was presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 and organized / chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN / KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders. PMID:22459870
Aertgeerts, B; Buntinx, F; Vandermeulen, C; Roelants, M; Fevery, J; Ansoms, S
To determine the prevalence of alcohol problems in first-year college students. Cross-sectional. Data on the prevalence of alcohol abuse or dependence according to DSM-IV criteria were collected in the period November 1995-April 1996 among college freshmen at the Catholic University of Louvain (Belgium). 3564 consecutive students completed a questionnaire which assessed drinking behaviour (Composite International Diagnostic Interview CIDI, Section J) and identified students at risk as defined by DSM-IV criteria. Our study included a large number of college freshmen, so we were able to perform our analyses with a large statistical power. All students had the opportunity to refuse their co-operation, but there were no non-responders, so selection bias was absent. The medical ethical committee of the KU Leuven approved this study. Of all 3564 consecutive students 501 (14.1%; 95% confidence interval (95% CI): 12.9-15.3) met DSM-IV criteria of alcohol abuse (n = 373; 10.5%; 9.5-11.5) or of alcohol dependence (n = 128; 3.6%; 3.0-4.2). Of the male students 301 (18.5%; 16.7-20.5) met the criteria of alcohol abuse and 96 (5.9%; 4.8-7.1) of alcohol dependence, of the female students 72 (3.7%; 2.9-4.6) and 32 (1.6%; 1.2-2.3) respectively. More than 10% (12.2%; 11.1-13.3) of these freshmen operated a vehicle under influence. This contributed in a major way to the DSM-IV conclusion. In this, one of the first studies among college freshmen using DSM-IV criteria the prevalence of alcohol abuse was in excess of 10%. In addition a substantial proportion of college freshman appeared to be alcohol dependent according to DSM-IV criteria.
Gulliver, Suzy Bird; Longabaugh, Richard; Davidson, Dena; Swift, Robert
Estimates of the prevalence of alcohol dependence among Americans approach 14% (Read, Kahler, & Stevenson, 2001). Alcohol dependence was once considered among the most recalcitrant of problem behaviors, with only 20% to 30% attaining sustained abstinence (Hunt Barnett & Branch 1971). Although current definitions of treatment success now consider…
Luczak, Susan E.; Glatt, Stephen J.; Wall, Tamara J.
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…
Rubio, Gabriel; Borrell, José; Jiménez, Mónica; Jurado, Rosa; Grüsser, Sabine M; Heinz, Andreas
Cue modulation of the startle reflex is a paradigm that has been used to understand the emotional mechanisms involved in alcohol dependence. Attenuation of the startle reflex has been demonstrated when alcohol-dependent subjects are exposed to alcohol-related stimuli. However, the role of clinical variables on the magnitude of this response is unknown. The objective of this study was to determine the relationship between a number of clinical variables-severity of alcoholism, family history of alcoholism (FHA+), personality traits related to the sensitivity to reward-and the startle reflex response when subjects with alcohol dependence were viewing alcohol-related cues. After detoxification, 98 participants completed self-report instruments and had eye blink electromyograms measured to acoustic startle probes [100-millisecond burst of white noise at 95 dB(A)] while viewing alcohol-related pictures, and standardised appetitive, aversive and neutral control scenes. Ninety-eight healthy controls were also assessed with the same instruments. There were significant differences on alcohol-startle magnitude between patients and controls. Comparisons by gender showed that women perceived alcohol cues and appetitive cues more appetitive than men. Male and female patients showed more appetitive responses to alcohol cues when compared with their respective controls. Our patients showed an appetitive effect of alcohol cues that was positively related to severity of alcohol dependence, sensitivity to reward and a FHA+. The data confirmed that the pattern of the modulation of the acoustic startle reflex reveals appetitive effects of the alcohol cues and extended it to a variety of clinical variables.
Ribadier, A; Varescon, I
Style Questionnaire-40 translated into French, but not validated, assessed defenses and defense style. Descriptive, comparative and correlational analysis was carried out using Statistica software - version 10. The alcohol-dependent people preferentially use emotion focused coping blame and less the problem focused coping humor. The highest immature defense is acting out. Correlational analyses confirm the presence of some significant relationships between defense style and some coping strategies. Thus, the mature style is the only defense style, which is linked with the problem focused strategy humor, and another one coping called distraction. Some singular relationships were found with these two dimensions of coping. Alcohol and drug disengagement show particularly strong relationships with immature defenses such as projection and somatization. Another singular result is indicated by a negative relationship between immature defenses autistic fantasy with the strategy expression of feelings. This study found a significant number of relationships between defensive styles, defenses and coping strategies. This research also highlights the value of an integrative approach of defense mechanisms for the analysis of defensive functioning of people with alcohol dependence. Indeed, the relationships between these elements are consistent and allow understanding the defensive operation as a whole to promote a new adapted means of support. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.
Elliott, Jennifer C.; Stohl, Malka; Wall, Melanie M.; Keyes, Katherine M.; Goodwin, Renee D.; Skodol, Andrew E.; Krueger, Robert F.; Grant, Bridget F.; Hasin, Deborah
Background and aims Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. Design Physical, sexual, and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over three years of follow-up, with and without control for other childhood adversities. Setting National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Participants NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n=1,172) and nicotine dependence (n=4,017). Measurements Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment, and other adverse childhood experiences (e.g., parental divorce). Findings Controlling for demographics only, physical, sexual, and emotional abuse, and physical neglect, predicted three-year persistence of alcohol dependence (adjusted odds ratios [AORs]: 1.50–2.99, 95% CIs 1.04–4.68) and nicotine dependence (AORs: 1.37–1.74, 95% CIs 1.13–2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AORs: 1.53–3.02, 95% CIs 1.07–4.71) and nicotine persistence (AORs: 1.35–1.72, 95% CIs 1.11–2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AORs: 1.19–1.36, 95% CIs 1.11–1.56). Conclusions A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of
Giorgi, Ines; Ottonello, Marcella; Vittadini, Giovanni; Bertolotti, Giorgio
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. 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. 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. This study shows the changes in psychological profile in subjects undergoing residential rehabilitation from alcohol and how this profile may permit identification of subjects requiring more
Keller, Thomas E.; Blakeslee, Jennifer E.; Lemon, Stephenie C.; Courtney, Mark E.
Objective: Distinctive combinations of factors are likely to be associated with serious alcohol problems among adolescents about to emancipate from the foster care system and face the difficult transition to independent adulthood. This study identifies particular subpopulations of older foster youths that differ markedly in the probability of a lifetime diagnosis for alcohol abuse or dependence. Method: Classification and regression tree (CART) analysis was applied to a large, representative sample (N = 732) of individuals, 17 years of age or older, placed in the child welfare system for more than 1 year. CART evaluated two exploratory sets of variables for optimal splits into groups distinguished from each other on the criterion of lifetime alcohol-use disorder diagnosis. Results: Each classification tree yielded four terminal groups with different rates of lifetime alcohol-use disorder diagnosis. Notable groups in the first tree included one characterized by high levels of both delinquency and violence exposure (53% diagnosed) and another that featured lower delinquency but an independent-living placement (21% diagnosed). Notable groups in the second tree included African American adolescents (only 8% diagnosed), White adolescents not close to caregivers (40% diagnosed), and White adolescents closer to caregivers but with a history of psychological abuse (36% diagnosed). Conclusions: Analyses incorporating variables that could be comorbid with or symptomatic of alcohol problems, such as delinquency, yielded classifications potentially useful for assessment and service planning. Analyses without such variables identified other factors, such as quality of caregiving relationships and maltreatment, associated with serious alcohol problems, suggesting opportunities for prevention or intervention. PMID:20946738
Palmer, R H C; McGeary, J E; Francazio, S; Raphael, B J; Lander, A D; Heath, A C; Knopik, V S
Personalized treatment for psychopathologies, in particular alcoholism, is highly dependent upon our ability to identify patterns of genetic and environmental effects that influence a person's risk. Unfortunately, array-based whole genome investigations into heritable factors that explain why one person becomes dependent upon alcohol and another does not, have indicated that alcohol's genetic architecture is highly complex. That said, uncovering and interpreting the missing heritability in alcohol genetics research has become all the more important, especially since the problem may extend to our inability to model the cumulative and combinatorial relationships between common and rare genetic variants. As numerous studies begin to illustrate the dependency of alcohol pharmacotherapies on an individual's genotype, the field is further challenged to identify new ways to transcend agnostic genomewide association approaches. We discuss insights from genetic studies of alcohol related diseases, as well as issues surrounding alcohol's genetic complexity and etiological heterogeneity. Finally, we describe the need for innovative systems-based approaches (systems genetics) that can provide additional statistical power that can enhance future gene-finding strategies and help to identify heretofore-unrealized mechanisms that may provide new targets for prevention/treatments efforts. Emerging evidence from early studies suggest that systems genetics has the potential to organize our neurological, pharmacological, and genetic understanding of alcohol dependence into a biologically plausible framework that represents how perturbations across evolutionarily robust biological systems determine susceptibility to alcohol dependence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Müller, Christian A; Geisel, Olga; Pelz, Patricia; Higl, Verena; Krüger, Josephine; Stickel, Anna; Beck, Anne; Wernecke, Klaus-Dieter; Hellweg, Rainer; Heinz, Andreas
Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence.
Background Heavy drinking jeopardizes the health of patients in HIV primary care. In alcohol dependent patients in HIV primary care, a technological enhancement of brief intervention, HealthCall administered via interactive voice response (HealthCall-IVR) was effective at reducing heavy drinking. The smartphone offered a technology platform to improve HealthCall. Methods Working with input from patients, technology experts, and HIV clinic personnel, we further developed HealthCall, harnessing smartphone technological capacities (HealthCall-S). In a pilot study, we compared rates of HealthCall-S daily use and drinking outcomes in 41 alcohol dependent HIV-infected patients with the 43 alcohol dependent HIV-infected patients who used HealthCall-IVR in our previous efficacy study. Procedures, clinic, personnel, and measures were largely the same in the two studies, and the two groups of patients were demographically similar (~90% minority). Results Pilot patients used HealthCall-S a median of 85.0% of the 60 days of treatment, significantly greater than the corresponding rate (63.8%) among comparison patients using HealthCall-IVR (p < .001). Mean end-of-treatment drinks per drinking day was similar in the two groups. Patients were highly satisfied with HealthCall-S (i.e., 92% reported that they liked using HealthCall-S). Conclusions Among alcohol dependent patients in HIV primary care, HealthCall delivered via smartphone is feasible, obtains better patient engagement than HealthCall-IVR, and is associated with decreased drinking. In HIV primary care settings, HealthCall-S may offer a way to improve drinking outcomes after brief intervention by extending patient engagement with little additional demands on staff time. PMID:24533631
Reis, Alessandra Diehl; Laranjeira, Ronaldo
The purpose of this paper is to supply a narrative review of the concepts, history, functions, methods, development and theoretical bases for the use of halfway houses for patients with mental disorders, and their correlations, for the net construction of chemical dependence model. This theme, in spite of its relevance, is still infrequently explored in the national literature. The authors report international and national uses of this model and discuss its applicability for the continuity of services for alcohol dependents. The results suggest that this area is in need of more attention and interest for future research. PMID:19061008
Máttyássy, Adrienne; Kéri, Szabolcs; Myers, Catherine E; Levy-Gigi, Einat; Gluck, Mark A; Kelemen, Oguz
We used an associative learning task in order to investigate cognitive dysfunctions in alcohol dependence. This test is suitable for the assessment of stimulus-response learning and memory generalization (acquired equivalence), which is related to medial temporal lobe functioning. Twenty patients with alcohol dependence (abstinence: >6 months) and 20 matched healthy controls participated in the study. In the task, antecedent stimuli were cartoon faces (girl, boy, man and woman) and consequent stimuli were color cartoon fishes. The task was to learn face-fish associations using feedback. In the transfer phase, the fish-face pairs were generalized to new associations. There was no significant difference between patients and controls during the acquisition phase of fish-face associations. In the transfer phase, patients were impaired relative to controls. We found no association between task performance and intelligence quotient. These results suggest that abstinent patients with alcohol dependence show marked dysfunctions in the generalization of associations, which may indicate the dysfunction of the medial temporal lobe.
Morley, Kirsten C; Teesson, Maree; Sannibale, Claudia; Haber, Paul S
Participants may be recruited from diverse sources for randomised controlled trials (RCT) of treatments for alcohol dependence. A mixed recruitment strategy might facilitate recruitment and increase generalisability at the expense of introducing systematic selection bias. The current study aims to compare the effects of recruitment method on socio-demographics, baseline illness characteristics, treatment retention and treatment outcome measures. A secondary analysis from a previous 12 week RCT of naltrexone, acamprosate and placebo for alcohol dependence was conducted. Participants (n = 169) were obtained via four channels of recruitment including in-patient and outpatient referral, live media and print media solicitation. Baseline parameters, retention in treatment and treatment outcomes were compared in these groups. Relative to in-patient subjects, those recruited via live and print media had significantly lower scores on taking steps, less in-patient rehabilitation admissions and less previous abstinence before entering the trial. Subjects recruited via print media had significantly lower scores of alcohol dependence relative to all other modes recruitment. There were no differences between recruitment strategies on treatment retention or compliance. At outcome, no significant effect of recruitment method was detected. These results suggest that different recruitment methods may be sourcing subjects with different baseline characteristics of illness. Nonetheless, these differences did not significantly impact on treatment retention or outcome, suggesting that in this population it was appropriate to recruit subjects from mixed sources.
Gilpin, Nicholas W.; Roberto, Marisa
Alcohol use disorders are characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and withdrawal syndrome in the absence of drug. The central amygdala (CeA) and neighboring regions (extended amygdala) mediate alcohol-related behaviors and chronic alcohol-induced plasticity. Acute alcohol suppresses excitatory (glutamatergic) transmission whereas chronic alcohol enhances glutamatergic transmission in CeA. Acute alcohol facilitates inhibitory (GABAergic) transmission in CeA, and chronic alcohol increases GABAergic transmission. Electrophysiology techniques are used to explore the effects of neuropeptides/neuromodulators (CRF, NPY, nociceptin, dynorphin, endocannabinoids, galanin) on inhibitory transmission in CeA. In general, pro-anxiety peptides increase, and anti-anxiety peptides decrease CeA GABAergic transmission. These neuropeptides facilitate or block the action of acute alcohol in CeA, and chronic alcohol produces plasticity in neuropeptide systems, possibly reflecting recruitment of negative reinforcement mechanisms during the transition to alcohol dependence. A disinhibition model of CeA output is discussed in the context of alcohol dependence- and anxiety-related behaviors. PMID:22101113
Gilpin, Nicholas W; Roberto, Marisa
Alcohol use disorders are characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and withdrawal syndrome in the absence of drug. The central amygdala (CeA) and neighboring regions (extended amygdala) mediate alcohol-related behaviors and chronic alcohol-induced plasticity. Acute alcohol suppresses excitatory (glutamatergic) transmission whereas chronic alcohol enhances glutamatergic transmission in CeA. Acute alcohol facilitates inhibitory (GABAergic) transmission in CeA, and chronic alcohol increases GABAergic transmission. Electrophysiology techniques are used to explore the effects of neuropeptides/neuromodulators (CRF, NPY, nociceptin, dynorphin, endocannabinoids, galanin) on inhibitory transmission in CeA. In general, pro-anxiety peptides increase, and anti-anxiety peptides decrease CeA GABAergic transmission. These neuropeptides facilitate or block the action of acute alcohol in CeA, and chronic alcohol produces plasticity in neuropeptide systems, possibly reflecting recruitment of negative reinforcement mechanisms during the transition to alcohol dependence. A disinhibition model of CeA output is discussed in the context of alcohol dependence- and anxiety-related behaviors.
Chester, Julia A; Coon, Laran E
The purpose of this study was to determine if aversive effects of alcohol withdrawal could be detected in mice using the place conditioning procedure and whether the GABA(A) receptor antagonist, pentylenetetrazol (PTZ), would increase the aversive effects of alcohol withdrawal and increase the probability of detecting conditioned place aversion. Subjects were alcohol-naïve mice from a specific line selectively bred for low alcohol preference (LAP1; n=91) and were assigned to three groups: alcohol withdrawal, PTZ alone, and PTZ+alcohol withdrawal. On four trials, mice received either a 4.0 g/kg intraperitoneal (i.p.) injection of alcohol (alcohol withdrawal, PTZ+alcohol withdrawal groups) or saline (PTZ group) 8 h prior to being placed on a distinctive floor texture for a 30-min conditioning session. Five minutes before these sessions, mice in the PTZ and PTZ+alcohol withdrawal groups received PTZ (5.0 mg/kg; i.p.) and the alcohol withdrawal group received saline. On intervening days mice received two saline injections at the same time points prior to being placed on a different floor texture. Post-conditioning floor preference was assessed in two 60-min tests; the first test was drug-free and the second test was state-dependent. Neither alcohol withdrawal nor PTZ produced significant place conditioning. The PTZ+alcohol withdrawal group showed a significant place aversion during the state-dependent test. These data suggest that the combined stimulus properties of PTZ and alcohol withdrawal facilitated the expression of conditioned place aversion to alcohol withdrawal. 2010 Elsevier Inc. All rights reserved.
Hack, Laura M; Kalsi, Gursharan; Aliev, Fazil; Kuo, Po-Hsiu; Prescott, Carol A; Patterson, Diana G; Walsh, Dermot; Dick, Danielle M; Riley, Brien P; Kendler, Kenneth S
Over 50 years of evidence from research has established that the central dopaminergic reward pathway is likely involved in alcohol dependence (AD). Additional evidence supports a role for dopamine (DA) in other disinhibitory psychopathology, which is often comorbid with AD. Family and twin studies demonstrate that a common genetic component accounts for most of the genetic variance in these traits. Thus, DA-related genes represent putative candidates for the genetic risk that underlies not only AD but also behavioral disinhibition. Many linkage and association studies have examined these relationships with inconsistent results, possibly because of low power, poor marker coverage, and/or an inappropriate correction for multiple testing. We conducted an association study on the products encoded by 10 DA-related genes (DRD1-D5, SLC18A2, SLC6A3, DDC, TH, COMT) using a large, ethnically homogeneous sample with severe AD (n = 545) and screened controls (n = 509). We collected genotypes from linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (SNPs) and employed a gene-based method of correction. We tested for association with AD diagnosis in cases and controls and with a variety of alcohol-related traits (including age-at-onset, initial sensitivity, tolerance, maximum daily drinks, and a withdrawal factor score), disinhibitory symptoms, and a disinhibitory factor score in cases only. A total of 135 SNPs were genotyped using the Illumina GoldenGate and Taqman Assays-on-Demand protocols. Of the 101 SNPs entered into standard analysis, 6 independent SNPs from 5 DA genes were associated with AD or a quantitative alcohol-related trait. Two SNPs across 2 genes were associated with a disinhibitory symptom count, while 1 SNP in DRD5 was positive for association with the general disinhibitory factor score. Our study provides evidence of modest associations between a small number of DA-related genes and AD as well as a range of alcohol-related traits and measures
Naim-Feil, Jodie; Fitzgerald, Paul B; Bradshaw, John L; Lubman, Dan I; Sheppard, Dianne
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.
not so far treat enough patients with trazodone so that our results would be statistically proven. "Acute" and long term treatment of dependency is not sufficiently effective with a substantial relapse rate, which is in part related to the lack of specific medication also for long term treatment. Among the available psychopharmacons, trazodone is a possible choice, since, as based on patients' reports and clinical observations, improvement of their depressive conditions and sleep problems potentially decreases the risk of relapse of drug and alcohol dependence.
Smith, Andrew H.; Gelernter, Joel; Kranzler, Henry R.; Farrer, Lindsay A.; Hall, Lynsey S.; Fernandez‐Pujals, Ana M.; MacIntyre, Donald J.; Smith, Blair H.; Hocking, Lynne J.; Padmanabhan, Sandosh; Hayward, Caroline; Thomson, Pippa A.; Porteous, David J.; Deary, Ian J.; McIntosh, Andrew M.
Abstract Alcohol dependence is frequently co‐morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome‐wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n = 2750; Yale‐Penn GWAS: n = 2377) in a population‐based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P = 0.009, β = −0.027; Yale‐Penn: P = 0.001, β = −0.034) and VF (SAGE: P = 0.0008, β = −0.036; Yale‐Penn: P = 0.00005, β = −0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P = 5.2 × 10−7, β = −0.054; Yale‐Penn: P = 0.000012, β = −0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders. PMID:25865819
Eckstrand, Kristen L; Ding, Zhaohua; Dodge, Neil C; Cowan, Ronald L; Jacobson, Joseph L; Jacobson, Sandra W; Avison, Malcolm J
Many children with heavy exposure to alcohol in utero display characteristic alterations in brain size and structure. However, the long-term effects of low-to-moderate alcohol exposure on these outcomes are unknown. Using voxel-based morphometry and region-of-interest analyses, we examined the influence of lower doses of alcohol on gray and white matter composition in a prospectively recruited, homogeneous, well-characterized cohort of alcohol-exposed (n = 11, age 19.5 ± 0.3 years) and control (n = 9, age 19.6 ± 0.5 years) young adults. A large proportion of the exposed individuals were born to mothers whose alcohol consumption during pregnancy was in the low-to-moderate range. There were no differences in total brain volume or total gray or white matter volume between the exposed and control groups. However, gray matter volume was reduced in alcohol-exposed individuals in several areas previously reported to be affected by high levels of exposure, including the left cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and right caudate nucleus. Notably, this gray matter loss was dose dependent, with higher exposure producing more substantial losses. These results indicate that even at low doses, alcohol exposure during pregnancy impacts brain development and that these effects persist into young adulthood. Copyright © 2012 by the Research Society on Alcoholism.
Camart, N; Cotte, M; Leignel, S; Bouvet, C; Limosin, F
Literature reports particularities in certain psychological dimensions, such as personality traits, early maladaptive schemas and attachment styles among patients dependent on alcohol. Several international studies have also emphasized significant gender differences in psychological profiles. However, in France, only a few studies have dealt with this subject. Our aim was on the one hand to study the characteristics of alcohol-dependent patients in these variables, and on the other hand to search for gender differences. The personality dimensions were assessed with the French Big Five Inventory (Fr-BFI), the attachment style with Bartholomew's Relationship Scales Questionnaire (RSQ), and early maladaptive schemas with the short version of Young's questionnaire (YSQ-S1). Seventy-three subjects were included: 39 alcohol-dependent patients (19 men and 20 women) and 34 healthy control subjects (17 men and 17 women). The scores of alcohol-dependent patients were compared with those of a healthy control group (n=34, 17 men, 17 women) and available standards. We also compared the scores of men and women with alcohol dependence between them, and we compared the scores of men and women to those of the control group and those of the reference sample of the same sex. This is an ongoing study and we publish here the first results. Compared with control subjects, and the reference sample, alcohol-dependent patients showed significantly higher levels of neuroticism and lower levels of extraversion. Furthermore, differences in attachment styles were observed compared to the control group: alcohol-dependent patients presented a less secure attachment, seemed more fearful and detached, but the results remained within the normal standards. Compared to the control subjects, alcohol-dependent patients showed a significant increase in scores regarding many schemas: emotional deprivation, abandonment, abuse/mistrust, isolation, imperfection, dependence, symbiotic relationship
Martinotti, G; Di Nicola, M; Di Giannantonio, M; Janiri, L
Substantial evidence suggests that both partial dopamine agents and mixed 5-HT1A/2A receptor drugs independently show significant efficacy in reducing alcohol use in both animals and humans. Aripiprazole, which acts as a dopamine/5-HT system stabilizer, approaches the optimal characteristics sought in medication to be considered for testing in the treatment of alcohol dependence. In this randomised, double-blind, confrontation trial with naltrexone, we aimed to investigate the efficacy of aripiprazole on alcohol-drinking indices. Craving and psychiatric symptom improvements were the secondary end points. Seventy-five alcohol dependent subjects were detoxified and were subsequently randomised into two groups, receiving 50 mg of naltrexone and 5-15 mg of aripiprazole, respectively. Craving (Visual Analogue Scale; Obsessive and Compulsive Drinking Scale) and withdrawal (Clinical Institute Withdrawal Assessment) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List 90-Revised. The number of subjects remained alcohol free for the entire study period (16 weeks) and the number of subjects relapsed were not significantly different in the two groups. The survival function showed that patients treated with aripiprazole remained abstinent from any alcohol amount for a longer time with respect to those treated with naltrexone. As for craving scores, patients treated with naltrexone showed a better outcome. Results from this study globally place aripiprazole at the same range of efficacy of naltrexone, one of the approved drugs used in alcohol relapse prevention. If it could be demonstrated in placebo-controlled trials that aripiprazole is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a powerful agent for the treatment of alcohol-dependent subjects.
Glahn, Alexander; Rhein, Mathias; Heberlein, Annemarie; Muschler, Marc; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas
Natriuretic peptides participate in the collection of metabolic effects during alcohol withdrawal. Having witnessed modulation of other natriuretic peptides in alcohol-dependent patients during alcohol withdrawal, we were interested in the relation of brain natriuretic peptide (BNP) methylation with protein expression and craving in this longitudinal study. Ninety-nine male patients were compared to 101 healthy controls concerning epigenetic regulation and protein expression during detoxification treatment. With BNP expression being GATA4 dependent, we observed a correlation of GATA4 binding site methylation and protein expression. BNP serum levels and Obsessive Compulsive Drinking Scale scores are significantly decreased during withdrawal. Focusing on the two CpGs that are between GATA transcription factor binding sites, statistical analysis revealed a reversely proportional methylation pattern, significantly increasing with ongoing detoxification and thereby supporting the observed serum level changes. Without the functional knowledge about regulation of BNP expression via the GATA transcription factor, it would have been easy to take the mean results of the global CpG data and propose a direct relationship between methylation and expression. Thus, these findings are a voice for functionally and mechanistically approved results. There was no causal relationship between protein expression levels and epigenetic changes. Further research is needed which includes protein expression and other approaches. © 2017 S. Karger AG, Basel.
Fein, George; Shimotsu, Ryan; Barakos, Jerome
Background We previously demonstrated, in a small sample, steeper age-related gray matter shrinkage in treatment naïve alcohol dependent (TxN) men compared to non-alcoholic controls, but could not separate out the contributions of age and lifetime duration of alcohol use (which were highly correlated) to this effect. In the current study, we have quadrupled the sample size and expanded it to include both men and women to try to replicate and extend the previous findings and to separate the contributions of age and alcohol use to the phenomenon. Methods In the current study, we examine cortical gray matter volumes in 18-50 year old TxN (n = 84) vs. age and gender comparable controls (n = 67). We used a new Region of Interest Analysis method which accounts for differences in sulcal and gyral enfolding between individuals (Fein et al., In Press). Results We found greater age-related gray matter shrinkage in TxN than in controls. Partial correlation analysis showed that the effect was a function of age and not lifetime alcohol burden. Conclusions Implications of the findings are discussed in terms of their contribution toward our knowledge of differences between different subpopulations of alcoholics and in terms of their implications for the morbidity of alcohol dependence in an aging national population. PMID:19860794
Henry, Stuart; Robinson, David
A national survey of Alcoholics Anonymous (AA) produced data on the way AA members talk about their experiences and the role this plays in achieving and maintaining sobriety. The survey was based on self-completion questionnaires given to one in four members attending meetings of a one in ten random sample of AA groups operating in England and Wales. Only 1·8 per cent of current members had never spoken at a meeting, while 62·5 per cent spoke regularly. Hearing other people's personal stories was felt by members to be the most useful part of AA meetings. At some time 81·9 per cent of members had told their own story and there was some relationship between dropping out and not telling personal stories. The great majority of those who had told stories reported changes in their content over time; 58·0 per cent of these changes involved a shift of emphasis from drinking to recovery. The results suggest that AA enables people to change the way they perceive and evaluate themselves. It enables them to talk themselves out of alcoholism. PMID:702456
Brown-Rice, Kathleen A; Scholl, Jamie L; Fercho, Kelene A; Pearson, Kami; Kallsen, Noah A; Davies, Gareth E; Ehli, Erik A; Olson, Seth; Schweinle, Amy; Baugh, Lee A; Forster, Gina L
A significant proportion of college students are adult children of an alcoholic parent (ACoA), which can confer greater risk of depression, poor self-esteem, alcohol and drug problems, and greater levels of college attrition. However, some ACoA are resilient to these negative outcomes. The goal of this study was to better understand the psychobiological factors that distinguish resilient and vulnerable college-aged ACoAs. To do so, scholastic performance and psychological health were measured in ACoA college students not engaged in hazardous alcohol use (resilient) and those currently engaged in hazardous alcohol use (vulnerable). Neural activity (as measured by functional magnetic resonance imaging) in response to performing working memory and emotion-based tasks were assessed. Furthermore, the frequency of polymorphisms in candidate genes associated with substance use, risk taking and stress reactivity were compared between the two ACoA groups. College ACoAs currently engaged in hazardous alcohol use reported more anxiety, depression and posttraumatic stress symptoms, and increased risky nicotine and marijuana use as compared to ACoAs resistant to problem alcohol use. ACoA college students with current problem alcohol showed greater activity of the middle frontal gyrus and reduced activation of the posterior cingulate in response to visual working memory and emotional processing tasks, which may relate to increased anxiety and problem alcohol and drug behaviors. Furthermore, polymorphisms of cholinergic receptor and the serotonin transporter genes also appear to contribute a role in problem alcohol use in ACoAs. Overall, findings point to several important psychobiological variables that distinguish ACoAs based on their current alcohol use that may be used in the future for early intervention. Copyright © 2017 Elsevier Inc. All rights reserved.
Brion, Mélanie; D'Hondt, Fabien; Pitel, Anne-Lise; Lecomte, Benoît; Ferauge, Marc; de Timary, Philippe; Maurage, Pierre
Alcohol-dependence is related to large-scale cognitive impairments, particularly for executive functions (EF). These deficits persist even after long-term abstinence and have a major impact on patients' everyday life and relapse risk. Earlier studies, based on multi-determined tasks, mostly focused on inhibition and did not offer a theoretically-grounded and exhaustive view of the differential deficit across EF. The present paper proposes a model-based exploration of EF in alcohol-dependent individuals (ALC), to precisely compare the specific deficit related to each executive subcomponent. Forty-seven recently detoxified ALC were compared to 47 matched healthy participants on a nine-tasks validated neuropsychological battery, simultaneously exploring and comparing the three main executive subcomponents (shifting, updating, and inhibition). Psychopathological comorbidities were also controlled for. Reaction time indexes revealed a global slowing down among ALC, whatever the EF explored. Accuracy indexes revealed a moderate deficit for inhibition tasks but a massive impairment for shifting and updating ones. Complementary analyses indicated that the executive deficits observed were centrally related to alcohol-dependence, while comorbid depressive symptoms appeared to intensify the deficits observed. By offering a direct comparison between the three major EF, these results showed that alcohol-related executive deficits extend beyond the classically described inhibition impairment. This impairment encompasses each EF subcomponent, as ALC actually presented stronger deficits for updating and shifting abilities. This first observation of a multifaceted EF deficit stresses the need for an individualized evaluation and rehabilitation of EF during and/or after the detoxification process. Copyright © 2017 Elsevier B.V. All rights reserved.
Marmorstein, N R; Iacono, W G; McGue, M
Previous research indicates that alcohol and drug dependence constitute aspects of a general vulnerability to externalizing disorders that accounts for much of the parent-offspring resemblance for these and related disorders. This study examined how adolescent offspring risk for externalizing psychopathology varies with respect to parental alcoholism and illicit drug dependence. Data from the Minnesota Twin Family Study, a community-based investigation of adolescents (age 17 years, n=1252) and their parents, were used. Lif