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…
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
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.
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.
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.
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.
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
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
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
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.
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.
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.
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
Prazosin for Treatment of Patients with PTSD and Comorbid Alcohol Dependence PRINCIPAL INVESTIGATOR...of Patients with PTSD and Comorbid Alcohol Dependence 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-2-0075 5c. PROGRAM ELEMENT NUMBER 6...comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of TSD among individuals with AD are at least twice
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…
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
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
08-2-0075 TITLE: Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence PRINCIPAL INVESTIGATOR: Ismene...page. Subject terms on next page. 6 Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence Ismene Petrakis Yale University New...PTSD. There is evidence of common neurobiological mechanisms that underlie both AD and PTSD. Prazosin is an alpha-! adrenergic •ceptor antagonist
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.
Reviews ethical and practical dilemmas associated with clients who have hidden alcohol dependencies, and proposes an approach rooted in Gestalt counseling theory which confronts these issues and is compatible with a current emerging alcohol-treatment model. Suggests specific activities for addressing client resistance to revealing a hidden alcohol…
Soyka, Michael; Rösner, Susanne
Alcohol dependence is a widespread psychiatric disorder. While relapse prevention therapy in alcoholism was exclusively dominated by social and psychological treatments for many years, in the last decades the benefits of pharmacological agents for the rehabilitation treatment in alcoholism have become increasingly evident. Naltrexone, an opiate receptor antagonist, blocks the pleasant and reinforcing effects of alcohol by preventing the stimulation of opioid receptors and the reduction of dopamine release in the ventral tegmental area (VTA). Clinical evidence about the effectiveness of the substance is not always consistent, but meta-analyses confirm naltrexone's effect on the risk of heavy drinking. Evidence about the abstinence-maintaining effects of the substance comes from a relatively small database and needs further investigation. The evaluation of differential effects of naltrexone depending on biological or psychological profiles, which could further enhance the effectiveness of treatments for alcohol dependence, remains a challenge. Nalmefene, another opioid antagonist, as well as naltrexone depot, a sustained release formulation of naltrexone, are further promising strategies for the treatment of alcohol dependence. The review at hand gives on overview of the current evidence on opioid antagonists for the treatment of alcohol dependence regarding the possible mechanism of action, the substances' safety profiles and their effectiveness. The corresponding evidence is critically reviewed taking into consideration the influence of the study design on the magnitude and consistency of effect sizes as well the impact of patient characteristics on the response to the treatment with opioid antagonists. Future studies on the role of different subtypes of alcoholics according to their genetic or psychological profile to explain or even predict the effects of opioid antagonists in the treatment of alcohol dependence are needed.
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.
Suh, Jesse J.; Pettinati, Helen M.; Kampman, Kyle M.; O’Brien, Charles P.
Recently, we reported that naltrexone at 150mg/day significantly decreased cocaine and alcohol use for men, but not women with co-occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender response to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems, or nausea while in treatment. Further research on the impact of pre-treatment and in-treatment gender differences with naltrexone is warranted. PMID:19034737
Alba-Ferrara, L.; Fernandez, F.; Salas, R.; de Erausquin, G. A.
Alcohol dependence is a major social, economic, and public health problem. Alcoholism can lead to damage of the gastrointestinal, nervous, cardiovascular, and respiratory systems and it can be lethal, costing hundreds of billions to the health care system. Despite the existence of cognitive-behavioral therapy, psychosocial interventions, and spiritually integrated treatment to treat it, alcohol dependence has a high relapse rate and poor prognosis, albeit with high interindividual variability. In this review, we discuss the use of two neuromodulation techniques, namely repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), and their advantages and disadvantages compared to first-line pharmacological treatment for alcohol dependence. We also discuss rTMS and DBS targets for alcohol dependence treatment, considering experimental animal and human evidence, with careful consideration of methodological issues preventing the identification of feasible targets for neuromodulation treatments, as well as inter-individual variability factors influencing alcoholism prognosis. Lastly, we anticipate future research aiming to tailor the treatment to each individual patient by combining neurofunctional, neuroanatomical and neurodisruptive techniques optimizing the outcome. PMID:25598743
Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Feeder, Scott E; Choi, Doo-Sup; Port, John D
Although the precise drug mechanism of action of acamprosate remains unclear, its antidipsotropic effect is mediated in part through glutamatergic neurotransmission. We evaluated the effect of 4 weeks of acamprosate treatment in a cohort of 13 subjects with alcohol dependence (confirmed by a structured interview, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) on proton magnetic resonance spectroscopy glutamate levels in the midline anterior cingulate cortex (MACC). We compared levels of metabolites with a group of 16 healthy controls. The Pennsylvania Alcohol Craving Scale was used to assess craving intensity. At baseline, before treatment, the mean cerebrospinal fluid-corrected MACC glutamate (Glu) level was significantly elevated in subjects with alcohol dependence compared with controls (P = 0.004). Four weeks of acamprosate treatment reduced glutamate levels (P = 0.025), an effect that was not observed in subjects who did not take acamprosate. At baseline, there was a significant positive correlation between cravings, measured by the Pennsylvania Alcohol Craving Scale, and MACC (Glu) levels (P = 0.019). Overall, these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence. Further research is needed to evaluate the use of these findings for clinical practice, including monitoring of craving intensity and individualized selection of treatment with antidipsotropic medications in subjects with alcohol dependence.
Lee, Jinhee; Kresina, Thomas F.; Campopiano, Melinda; Lubran, Robert; Clark, H. Westley
Substance-related and addictive disorders are chronic relapsing conditions that substantially impact public health. Effective treatments for these disorders require addressing substance use/dependence comprehensively as well as other associated comorbidities. Comprehensive addressing of substance use in a medical setting involves screening for substance use, addressing substance use directly with the patient, and formulating an appropriate intervention. For alcohol dependence and opioid dependence, pharmacotherapies are available that are safe and effective when utilized in a comprehensive treatment paradigm, such as medication assisted treatment. In primary care, substance use disorders involving alcohol, illicit opioids, and prescription opioid abuse are common among patients who seek primary care services. Primary care providers report low levels of preparedness and confidence in identifying substance-related and addictive disorders and providing appropriate care and treatment. However, new models of service delivery in primary care for individuals with substance-related and addictive disorders are being developed to promote screening, care and treatment, and relapse prevention. The education and training of primary care providers utilizing approved medications for the treatment of alcohol use disorders and opioid dependence in a primary care setting would have important public health impact and reduce the burden of alcohol abuse and opioid dependence. PMID:25629034
Trova, A C; Paparrigopoulos, Th; Liappas, I; Ginieri-Coccossis, M
context of relevant interventions, various techniques are used, such as role playing. At the level of social policy, different measures may contribute to increase the effectiveness of preventive programs (e.g. prohibition of sale of alcohol in young people). Interventions of tertiary prevention aim at the development of motivation for abstinence in alcohol dependent individuals and the prevention of relapse, as well as the acquisition of new behaviors, which support modification of the problem of alcohol dependence. These interventions can take place in the context of psychotherapeutic follow-up provided to alcohol dependent individuals, and may include various short-term interventions, such as motivational interviewing, but also alternative forms of treatment (e.g. acupuncture, meditation). Elements of prevention in combination with elements of promotion of mental health may be incorporated in the same programme for alcohol dependence, endorsing similar or different activities, which may be complementary and may reinforce the effectiveness of the prevention program. Finally, it is necessary to raise the awareness of mental health professionals regarding prevention and provide specialized education to those who work in drug addiction programmes. Mental health professionals may act as therapists and as intervention coordinators, and performing these roles, they may contribute to the effectiveness of preventive programs and more generally to the treatment of disorders connected with alcohol use.
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.
Fein, George; McGillivray, Shannon; Finn, Peter
Background Research suggests that substance abusers make more disadvantageous decisions on the simulated gambling task (SGT); such decisions are associated with deviance proneness and antisocial symptoms. This study examines decision-making on the SGT in young adults with alcohol dependence that are treatment-naïve (TxN). Methods 116 subjects (58 controls, 58 TxNs) were tested on the SGT, where participants choose cards from 4 different decks that vary in terms of the magnitude of the immediate gain (large/small) and the magnitude of long-term loss (larger/smaller). Participants also were assessed on measures of externalizing symptoms, personality traits reflecting social deviance, neuropsychological function, and the density of the family history of alcoholism. Results TxNs did not differ from controls on measures of SGT decision-making. SGT performance was not associated with externalizing symptoms, social deviance proneness, or a familial density of alcoholism. Although, TxNs had higher levels of externalizing symptoms, social deviance and familial density of alcoholism compared with controls, these variables were only modestly elevated compared with previous samples of long-term abstinent alcohol dependent individuals who showed decision-making deficits on the SGT. Conclusions The results suggest that our sample of young adult TxN adults with alcohol dependence do not have global deficits in decision-making as measured by the SGT, and that their poor decisions regarding their alcohol consumption are more specific to drinking. PMID:16737453
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
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
... dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. 17... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
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
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
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
Potthast, Nadine; Neuner, Frank; Catani, Claudia
Studies reporting a link between child maltreatment and addiction have typically focused on physical and sexual abuse. In contrast, emotional maltreatment has rarely been studied in substance-abusing samples although it is associated with a wide range of dysfunction. The current study aimed to determine the specific impact of different types of maltreatment and peer victimization on alcohol dependence and to examine the potentially mediating role of psychopathology. A sample of treatment seeking adults with alcohol dependence (N=72) underwent an extensive clinical examination including both a standardized interview and self-report measures. Child maltreatment, peer victimization, severity of alcohol dependence, and general psychopathology were assessed. Regression analyses revealed that emotional maltreatment was the strongest predictor of alcohol dependence severity whereas a unique contribution of peer victimization was not found. Our findings suggest that emotional maltreatment might have a major role in the etiology of AD that seems to exceed the contribution of other abuse and victimization experiences. Thereby, the study underscores the need for considering child maltreatment experiences in the prevention and treatment of AD.
Currently detoxification of drug and alcohol dependent patients is pharmacologically unresolved, and long-term treatment following the acute phase is also not very successful including a high number of relapses. We would need medications that on the short term cease: the severe vegetative symptoms, the pain, the extremely distressing psychosyndrome characterised by restlessness, anxiety or acute depressive symptoms, and the craving. The optimal would be if there was one medication capable of simultaneously alleviating or diminishing all the above symptoms without causing dependency and preventing relapse in the long-term. Dependency is almost all cases accompanied by primary and/or secondary mood disorder or sleep disorder which should also be treated. It should be considered, however, that following withdrawal of the agent benzodiazepine dependency often develops. The serotonin antagonist and reuptake inhibitor (SARI) trazodone is effective in the treatment of depression accompanied by sleeping disorder and it has also shown efficacy in alcohol and benzodiazepine-dependency. Its administration may improve the efficacy of detoxification and treatment of following conditions, may decrease medication load and the risk of the development of benzodiazepine dependency. In our clinical practice we frequently use this agent to treat our patients simultaneously suffering from depression and addiction problems, gaining experience comparing it to other pharmacotherapies (benzodiazepines or other antidepressants). The medication is not approved for alcohol and drug dependence, however, treatment t of comorbid conditions is not against to the official recommendations. Our aim was, in addition to reviewing the literature, to share our experience which, although cannot be considered an evidence based study, we deemed worthy of publishing. We cannot, at this point, put forward a protocol addressing all related scientific problems and problems of off-label treatment, and we could
Weinrieb, Robert M; Van Horn, Deborah H A; Lynch, Kevin G; Lucey, Michael R
Alcohol is the second most common cause of cirrhosis necessitating liver transplantation in the United States, yet rates of posttransplant drinking approach 50% and no controlled clinical trials of alcoholism treatment exist in this population. Eligible patients were randomly assigned to receive Motivational Enhancement Therapy (MET), or referral to local treatment sources ("treatment as usual" [TAU]). Addictive behavior, mood states, and general health were compared. Candor concerning alcohol use was encouraged by keeping drinking questionnaires in confidence, except in medical emergencies. Ninety-one subjects were studied; 46 received MET, 45 received TAU, 29 proceeded to transplantation (MET, n = 13; TAU, n = 16). A total of 69 subjects completed 24 weeks of observation, and 25 subjects were assessed at 96 weeks. No difference in study attendance was observed, but significantly more MET subjects attended 1 or more treatment sessions. Twenty-three subjects (25% of sample) drank after randomization but before transplant. Excluding an extreme outlier, MET drinkers had significantly fewer drinks per drinking days than TAU drinkers. Neither treatment plan resulted in significant variances in measures of psychosocial health. In conclusion, although MET afforded no significant benefit over TAU for mood or general health outcomes, this study provides some degree of support for MET to limit the quantity and frequency of pretransplant alcohol consumption among liver transplant candidates with alcohol dependence. However, because of the limited number of study subjects, these data must be interpreted cautiously. Further research to validate our findings or to identify better methods to identify and intervene with patients at risk of pretransplant and posttransplant drinking should continue.
Kiefer, Falk; Jiménez-Arriero, Miguel Angel; Klein, Oliver; Diehl, Alexander; Rubio, Gabriel
Naltrexone is an opiate receptor antagonist mainly at the micro-receptor that is thought to reduce the positively reinforcing, pleasurable effects of alcohol and to reduce craving. An increase in time to first relapse to heavy drinking has been the most consistent finding obtained with naltrexone, although not all trials including two of the largest have been positive. Inconsistent outcome data suggest that effectiveness varies among different subgroups of patients. This paper re-evaluates recent data on the effectiveness of naltrexone in subjects differentiated according to Cloninger Type I and II. Moreover, it combines and cross-validates results of two recent European studies that found naltrexone treatment more beneficial in alcohol-dependent patients with early age at onset of drinking problems (Cloninger Type II). It is discussed whether especially these subjects should be targeted for pharmacological relapse prevention treatment with naltrexone.
Andreas, Jasmina Burdzovic; O'Farrell, Timothy J
We investigated longitudinal associations between alcohol-dependent fathers' 12-step treatment involvement and their children's internalizing and externalizing problems (N = 125, M(age) = 9.8 +/- 3.1), testing the hypotheses that fathers' greater treatment involvement would benefit later child behavior and that this effect would be mediated by fathers' posttreatment behaviors. The initial association was established between fathers' treatment involvement and children's externalizing problems only, whereas Structural Equation Modeling (SEM) results supported mediating hypotheses. Fathers' greater treatment involvement predicted children's lower externalizing problems 12 months later, and fathers' posttreatment behaviors mediated this association: Greater treatment involvement predicted greater posttreatment Alcoholics Anonymous attendance, which in turn predicted greater abstinence. Finally, fathers' abstinence was associated with lower externalizing problems in children. Theoretical and practical implications of these findings are discussed.
Zandberg, Laurie J.; Rosenfield, David; McLean, Carmen P.; Powers, Mark B.; Asnaani, Anu; Foa, Edna B.
Objective The present study examined predictors and moderators of treatment response among 165 adults meeting DSM-IV criteria for comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD) who were randomized to 24 weeks of naltrexone (NAL), NAL and prolonged exposure (PE), pill placebo, or pill placebo and PE. All participants received supportive counseling for alcohol use. Method Six domains of predictors/moderators (23 variables) were evaluated using measures of PTSD (Posttraumatic Stress Symptom Scale Interview; PSS-I) and AD (percent days drinking from the Timeline Follow-Back Interview) collected every four weeks throughout treatment. Multi-level modeling using the Fournier approach was employed to evaluate predictors and moderators of rates of symptom improvement and post-treatment outcomes. Results Combat trauma, sexual assault trauma, and higher baseline anxiety sensitivity predicted slower improvement and poorer PTSD outcome. Combat trauma, white race, and higher baseline drinking severity predicted poorer drinking outcome. PTSD severity moderated the efficacy of PE on PTSD outcomes, such that the benefit of PE over no-PE was greater for participants with higher baseline PTSD severity. Baseline depressive severity moderated the efficacy of PE on drinking outcomes, whereby the benefit of PE over no-PE was greater for participants with higher depressive symptoms. NAL effects were most beneficial for those with the longest duration of alcohol dependence. Conclusions These results suggest that concurrent, trauma-focused treatment should be recommended for PTSD-AD patients who present with moderate or severe baseline PTSD and depressive symptoms. Future research should examine the mechanisms underlying poorer outcome among identified sub-groups of PTSD-AD patients. PMID:26460570
Huebner, Robert B.; Kantor, Lori Wolfgang
Researchers are working on numerous and varied approaches to improving the accessibility, quality, effectiveness, and cost-effectiveness of treatment for alcohol use disorders (AUDs). This overview article summarizes the approaches reviewed in this issue, including potential future developments for alcoholism treatment, such as medications development, behavioral therapy, advances in technology that are being used to improve treatment, integrated care of patients with AUDs and co-occurring disorders, the role of 12-step programs in the broader realm of treatment, treating patients with recurring and chronic alcohol dependence, strategies to close the gap between treatment need and treatment utilization, and how changes in the health care system may affect the delivery of treatment. This research will not only reveal new medications and behavioral therapies but also will contribute to new ways of approaching current treatment problems. PMID:23580014
Dieter J. Meyerhoff, Dr.rer.nat., UCSF Rationale and Content: Civilian and military personnel with posttraumatic stress disorder (PTSD) frequently...observed in both Alcohol Use Disorder (AUD) and Posttraumatic Stress Disorder (PTSD) and is associated with worse treatment outcome. Impairment in...CA 94121 Purpose: Cognitive dysfunction is commonly observed among individuals with Alcohol Use Disorder (AUD) and Posttraumatic Stress Disorder
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.
Disorder 3.30% Cannabis Abuse or Dependence 6.70% Cocaine Abuse or Dependence 16.70% Sedative Abuse or Dependence 6.70% Opiate Abuse or Dependence 3.30...of Cannabis Use in the Past 90 Days [n = 9] 45 (9–90, 78) No. of Days of Cocaine Use in the Past 90 Days [n = 3] 37.0 (45.9) No. of Days of Opiate Use...Dependence Yes No Lifetime alcohol dependence Yes No ______ Cannabis Abuse Yes No Cannabis Dependence Yes No Cocaine Abuse
Parks, Cheryl A.; Hesselbrock, Michie N.; Hesselbrock, Victor M.; Segal, Bernard
Investigates alcohol treatment among Alaska Natives. Time between age at diagnosis and first treatment was similar for men and women. Women were more likely to be parents and reported more contact with health and mental health providers. Among men, acting as a parent, lifetime depression, and type of professional consulted were significantly…
Margetić, Branimir; Aukst-Margetić, Branka; Zarković-Palijan, Tija
The beneficial effect of clozapine on polydipsia and water intoxication in patients with schizophrenia has been demonstrated many times. The authors report a successful clozapine treatment of polydipsia, intermittent water intoxication, and delusional jealousy of an alcoholic. This is a rare case of clozapine treatment of a non-schizophrenic patient affected by polydipsia.
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.
Schacht, Joseph P.; Anton, Raymond F.; Randall, Patrick K.; Li, Xingbao; Henderson, Scott; Myrick, Hugh
Rationale The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. Objectives This pilot study tested varenicline’s effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Methods Thirty-five such individuals (mean age = 30, 57% male, 76% heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Results Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. Conclusions These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption. PMID:24647921
Barrio, Pablo; Miquel, Laia; Moreno-España, Jose; Martínez, Alicia; Ortega, Lluisa; Teixidor, Lidia; Manthey, Jakob; Rehm, Jürgen; Gual, Antoni
primary health care services for other reasons. The aim of the present study is to describe the differential characteristics of AD patients in primary care, distinguishing between those who receive treatment and those who do not, and their reasons for not seeking it. In a cross-sectional study patients were evaluated by their general practitioner (GP) and interviewed by a member of the research team. Sociodemographic, diagnostic and clinical data were collected. From 1,372 patients interviewed in Catalonia, 118 (8.6%) were diagnosed as AD. These patients showed a lower socioeconomic status (48.3% vs 33.3%, odds ratio 2.02), higher unemployment rates (32.2% vs 19.2 %, odds ratio 2.11), and greater psychological distress and disability. Patients with AD receiving treatment (16.9%), were older (44 vs 36 years of age), reported higher unemployment rates (66% vs 25.5%, odds ratio 6.32) and higher daily alcohol consumption (61.5 vs 23.7 grams), suggesting a more advanced disease. Patients with AD in general showed a higher degree of comorbidity compared to other patients, with patients in treatment showing the most elevated level. The main reasons given for not seeking treatment were shame, fear of giving up drinking and barriers to treatment. Taken together, the data suggest the need to implement earlier strategies for the detection and treatment of AD.
Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S
Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131
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.
Eames, Sarah F.; Businelle, Michael S.; Suris, Alina; Walker, Robrina; Rao, Uma; North, Carol S.; Xiao, Hong; Adinoff, Bryon
Objective This study sought to clarify the relationship between childhood trauma and adversity with later alcohol consumption and the moderating effects of adult psychosocial stress. Method Seventy-seven recently abstinent alcohol-dependent men attending residential treatment programs were assessed. Childhood trauma/adversity was assessed with the Childhood Trauma Questionnaire (CTQ), drinks per drinking day (DDD) with the TimeLine Follow Back, and chronic psychosocial stress with the UCLA Stress Interview. Drinking and stress were retrospectively assessed for six months prior to the present treatment episode. Direct associations between childhood trauma/adversity and alcohol consumption and the moderating effects of recent psychosocial stress were assessed. All measures were considered as continuous variables. Results Pretreatment drinking severity (DDD) was associated with CTQ Total score (p = .009) and the Emotional Abuse (p < .001) and Physical Abuse (p < .01) subscales. UCLA Total Stress significantly moderated the effects of CTQ Total score on drinking severity (p = .04). Whereas higher CTQ scores were significantly associated with a greater amount of pretreatment drinking in participants with high UCLA stress scores (p = .01), CTQ scores were not associated with the amount of drinking in those with low UCLA stress scores (p = .63). Conclusions Childhood trauma predicts drinking severity in alcohol-dependent men and this effect is stronger in participants with ongoing stress in adult life. These findings suggest that early childhood trauma/adversity may sensitize stress-response systems. PMID:24635549
Falk, Daniel E.; Castle, I-Jen P.; Ryan, Megan; Fertig, Joanne; Litten, Raye Z.
Objectives To explore if varenicline (Chantix®) showed more efficacy in treating certain subgroups of patients. In a recent multi-site trial, varenicline was shown to be effective in reducing drinking in alcohol dependent patients, both smokers and nonsmokers. Given the heterogeneity among alcohol dependent patients, secondary analyses were conducted to determine if certain subgroups responded more favorably than others to treatment with varenicline. Methods Data were drawn from a Phase 2 randomized, double-blind, placebo-controlled multi-site 13-week trial of varenicline in alcohol dependent patients (Litten et al., 2013). Seventeen moderator variables were selected for exploratory testing on the basis of theoretical and scientific interest. Results Of the 17 moderator variables assessed, four were statistically significant, including cigarettes per day reduction, treatment drinking goal, years drinking regularly, and age of patient. Two other variables—the type of adverse events experienced by patients and the severity of alcohol-related consequences—appeared to moderate the varenicline treatment effect at borderline statistical significance. Individuals who reduced the number of cigarettes per day experienced a significant effect from varenicline in reducing drinking, whereas those who did not change or who increased their number of cigarettes observed no beneficial effect. Reviewing the moderators related to severity, varenicline appeared to have greater efficacy than placebo among less severely-dependent patients. Conclusions Varenicline appears to be more efficacious in certain subgroups, particularly in those who reduced their smoking and in the “less severe” patient. Additional studies are warranted to confirm the results of these exploratory analyses. PMID:26083958
Slósarska, M; Wójcik, M; Habrat, B
Heart rate, respiratory rate, postural muscle tone and tapping in 14 alcohol dependent patients (type II ac. Cloninger) during 10 days of detoxification were investigated. Despite subjective mood increased, no longer observed were tachycardia and clinical symptoms of alcohol withdrawal; increased muscle tonus and faster respiration rhythm were observed. The observed physiological changes in alcohol dependent patients after 10 days of abstinence suggest that continuation of pharmacotherapy and psychotherapy after detoxification in acute alcohol withdrawal is recommended.
Muhonen, Leea H; Lahti, Jari; Alho, Hannu; Lönnqvist, Jouko; Haukka, Jari; Saarikoski, Sirkku T
The aim of this study was to determine whether the serotonin transporter gene polymorphism (5-HTTLPR) is associated with the treatment outcomes of escitalopram for patients with comorbid major depression and alcohol dependence. Eighty treatment-seeking patients were randomly assigned to either receive 20mg of escitalopram or a control of 20mg of the non-serotonergically acting memantine. Depression was measured by the Montgomery-Asberg Depression Rating Scale (MADRS) and alcoholism by the Alcohol Use Disorders Identification Test (AUDIT). Twenty-nine participants in each treatment group completed the study, and from those DNA was given by 27 in the escitalopram group and 21 in the memantine group. In the escitalopram group linear regression showed that LL genotype predicted greater decrease in MADRS scores compared with the SS/SL genotypes (p=0.04) after a 3month treatment period. Moreover, each L allele associated with MADRS score decrease by 15% (p=0.04) in the escitalopram group. In the memantine group, however, no association between LL genotype and MADRS decrease was detected. AUDIT decrease was not associated with the 5-HTTLPR genotype for either medication. This is the first study in the treatment of depression in dual diagnosis patients to report a significant association between outcomes with escitalopram and the 5-HTTLPR gene polymorphism.
Kalman, David; Kim, Sun; DiGirolamo, Gregory; Smelson, David; Ziedonis, Douglas
Despite the declining overall rate of cigarette smoking in the general population in the United States, the prevalence of smoking is estimated to be as high as 80% among treatment-seeking alcoholics. The serious adverse health effects of tobacco and heavy alcohol use are synergistic and recent evidence suggests that smoking slows the process of cognitive recovery following alcohol abstinence. In addition, substantial evidence shows that treatment for tobacco dependence does not jeopardize alcohol abstinence. In this paper, we focus on the impact and treatment implications of tobacco dependence among treatment-seeking alcoholics through a review of five areas of research. We begin with brief reviews of two areas of research: studies investigating the genetic and neurobiological vulnerability of comorbid tobacco and alcohol dependence and studies investigating the consequences of comorbid dependence on neurobiological and cognitive functioning. We then review literature on the effects of smoking cessation on drinking urges and alcohol use and the effectiveness of smoking cessation interventions with alcoholic smokers. Finally, we offer recommendations for research with an emphasis on clinical research for enhancing smoking cessation outcomes in this population. PMID:19748166
de Beaurepaire, Renaud
Baclofen, particularly high-dose baclofen, has recently emerged as a treatment of major interest for alcohol-dependence. However, baclofen has many potentially dangerous side effects, and the maximal dose of baclofen that may be used is a matter of discussion. Here, the author analyses the medical charts of the last 100 patients seen in his clinic, 17 of whom have been taking a very high dose of baclofen, which is to say, more than 300 mg/day. The analysis of the charts shows that the very high-doses baclofen were justified in almost all the cases. Side effects are analyzed. PMID:25346700
Witkiewitz, Katie; Bowen, Sarah; Donovan, Dennis M.
Objective: Negative affect is a significant predictor of alcohol relapse, and the relation between negative affect and drinking has been shown to be strongly mediated by alcohol craving. Thus, targeting craving during treatment could potentially attenuate the relation between negative affect and drinking. Method: The current study is a secondary…
Kampman, Kyle M.; Lynch, Kevin G.; Pettinati, Helen M.; Spratt, Kelly; Wierzbicki, Michael R.; Dackis, Charles; O'Brien, Charles P.
Background Modafinil is a medication approved for narcolepsy and shift work sleep disorder. It has both dopaminergic and glutamatergic activity that could be useful for the treatment of cocaine dependence. Modafinil has reduced cocaine subjective effects and cocaine self-administration in human laboratory trials and has reduced cocaine use in cocaine dependent patients in some clinical trials. Methods This was an 8-week, double blind, placebo controlled clinical trial involving 94 cocaine dependent subjects. Subjects received 300 mg of modafinil or identical placebo daily along with weekly individual therapy. The primary outcome measure was cocaine use measured by self-report, and confirmed by twice weekly urine benzoylecgonine tests (UBT). Additional outcome measures included cocaine craving measured by the Brief Substance Craving Scale and global improvement measured by the Clinical Global Impression Scale (CGI). Results The odds ratio (OR) in favor of abstinence for modafinil vs. placebo was 2.54 (p=. 03) and modafinil-treated subjects were significantly more likely than placebo-treated subjects to be abstinent from cocaine during the last 3 weeks of the trial, 23% vs. 9%, χ2 = 3.9, p <.05. Modafinil treated subjects were more likely to report very low levels of cocaine craving intensity and duration on the Brief Substance Craving Scale (OR = 2.04 p =.03 and OR 1.06 p = .03 respectively). Modafinil–treated subjects were also more likely than placebo-treated subjects to rate themselves as “very much improved” on the CGI (OR = 2.69, p= .03). Conclusion Modafinil may be an efficacious treatment for cocaine dependence. PMID:26320827
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.
Wright, Tara M; Myrick, Hugh
Acamprosate, a medication that has been used in Europe for years, is the newest drug to be approved by the US Federal Drug Administration for the treatment of alcohol dependence. It has been shown to assist in the maintenance of abstinence in recently detoxified alcohol-dependent individuals. The following review delineates the proposed mechanism of action and pharmacokinetics of the drug. Findings of clinical trials are outlined and topics such as cost effectiveness, comparison with other medications used for the treatment of alcohol dependences as well as combination pharmacotherapy are discussed. In combination with psychosocial treatment, acamprosate is a promising tool for the maintenance of abstinence in alcohol-dependent patients after alcohol withdrawal. This review also illustrates the continued need to search for more effective treatments, as the overall effectiveness of our currently available pharmacotherapies remains limited in the long-term maintenance of recovery from alcohol dependence. PMID:19412493
McKay, James R.; Van Horn, Deborah H. A.; Oslin, David W.; Lynch, Kevin G.; Ivey, Megan; Ward, Kathleen; Drapkin, Michelle L.; Becher, Julie R.; Coviello, Donna M.
Objective: The study tested whether adding up to 18 months of telephone continuing care, either as monitoring and feedback (TM) or longer contacts that included counseling (TMC), to intensive outpatient programs (IOPs) improved outcomes for alcohol-dependent patients. Method: Participants (N = 252) who completed 3 weeks of IOP were randomized to…
Prisciandaro, James J.; Schacht, Joseph P.; Prescot, Andrew P.; Renshaw, Perry F.; Brown, Truman R.; Anton, Raymond F.
Background Proton magnetic resonance spectroscopy (1H-MRS) studies have consistently found abnormal brain concentrations of N-acetylaspartate (NAA) and glutamate in individuals with alcohol use disorders (AUD) relative to light drinkers. However, most such studies have focused on individuals in treatment for severe alcohol dependence and few studies have investigated associations between neurochemical concentrations and recent alcohol consumption. The present study focused on associations between recent drinking and prefrontal neurometabolite concentrations in non-severe, non-treatment seeking individuals with AUD. Methods Nineteen treatment naïve alcohol-dependent individuals aged 21–40 completed a 1H-MRS scan. Single-voxel 1H-MRS spectra were acquired in dorsal anterior cingulate (dACC) using a Two-dimensional J-resolved Point Resolved Spectroscopy (2D J-PRESS) sequence. Associations between recent heavy drinking, assessed using the Timeline FollowBack, and dACC metabolite concentrations were estimated via regression controlling for within-voxel tissue composition. Results Participants provided a negative breathalyzer reading and reported between 1 and 5 days (M = 2.45, SD = 1.23) since their last drink. Number of heavy drinking days in the 14 days preceding the scan (M = 4.84, SD = 3.32) was significantly inversely associated with both glutamate/water (β = −0.63, t(17) = −3.37, p = 0.004) and NAA/water concentrations (β = −0.59, t(17) = −2.98, p = 0.008). Conclusions The present study extends the literature by demonstrating inverse associations between recent heavy drinking and dACC glutamate and NAA concentrations in a sample of non-severe, non-treatment seeking individuals with AD. These findings may support the hypothesis that amount of recent alcohol consumption may account for differences in neuronal metabolism, even in non-severe, non-treatment seeking alcoholics. PMID:26853538
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.
Three drugs are currently marketed in France in the prevention of relapse in alcohol-dependent patients. Their efficacy though real remains limited and it is useful to develop other molecules. Some products are at present under evaluation, and are already or could be used in the near future in the treatment of alcohol dependence: baclofene, oxybate de sodium (GHB), nalmefene, topiramate, ondansetron and aripiprazole. The available studies on these molecules are still limited and the results sometimes clinically modest. Nevertheless, some of them open interesting future prospects. If there is no big revolution to wait in the short term in the treatment of alcohol dependence, we can consider some interesting orientations: better effectiveness on alcohol consumption, but also change of paradigm concerning the objectives and the methods of this treatment: reduction of consumption versus abstinence, treatment on request, choice of the molecule guided by objective criteria (psychosocial, biological, genetic...).
The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence.
Trovero, Fabrice; David, Sabrina; Bernard, Philippe; Puech, Alain; Bizot, Jean-Charles; Tassin, Jean-Pol
Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg) and cyproheptadine (1 mg/kg) (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively) blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v) and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France) and cyproheptadine (1 mg/kg) could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs.
The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence
Trovero, Fabrice; David, Sabrina; Bernard, Philippe; Puech, Alain; Bizot, Jean-Charles; Tassin, Jean-Pol
Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg) and cyproheptadine (1 mg/kg) (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively) blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v) and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France) and cyproheptadine (1 mg/kg) could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs. PMID:26968030
Bonnet, U; Banger, M; Leweke, F M; Maschke, M; Kowalski, T; Gastpar, M
Four in-patients with moderate alcohol-withdrawal syndromes benefited from treatment with gabapentin administered in an add-on fashion to clomethiazole. In comparison with the amount of clomethiazole required as estimated using a specially developed score during previous detoxifications of these patients at our hospital, gabapentin (400 mg q.i.d.) clearly reduced the amount of clomethiazole needed now Gabapentin, an anticonvulsant with favorable pharmacokinetic properties and tolerability, and with no known risk of dependence, may therefore be a useful new drug in the treatment of alcohol withdrawal. We believe that the potential value of gabapentin in alcohol withdrawal deserves further controlled studies.
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
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.
Niehoff, Marilee S.
Uses a hypothetical case study to examine burnout and drinking problems of alcoholic treatment counselors. Suggests ways of coping with stress and developing goals and strategies for positive change. (JAC)
Guardia, Josep; Roncero, Carlos; Galan, Jaime; Gonzalvo, Begoña; Burguete, Teresa; Casas, Miquel
The objective of this study was to determine whether quetiapine plus naltrexone is more effective than naltrexone alone for the treatment of alcohol-dependent patients. This was a double-blind, randomized clinical trial where eligible alcohol-dependent patients were randomized to receive naltrexone (50mg/day) plus quetiapine (25-200mg/day) or naltrexone (50mg/day) plus placebo for 12 weeks, and afterwards patients received naltrexone alone during 4 additional weeks. The primary efficacy measures were percent days abstinent, drinks per drinking day, and the relapse rate. Sixty-two patients received a single-blind treatment with placebo plus naltrexone, and they were thereafter randomly assigned to quetiapine plus naltrexone (n=30) or placebo plus naltrexone (n=32). Eleven (36.7%) patients in the quetiapine-treated group and 4 (12.5%) patients in the placebo-treated group withdrew before they completed 12 weeks of treatment. There were no statistically significant differences for any primary drinking outcomes between treatment groups. Both regimens were well tolerated. This study failed to demonstrate any additional benefit from the combination of quetiapine and naltrexone compared to naltrexone alone on drinking outcomes.
The DSM-V Committee plans to abolish the distinction between Alcohol Abuse and Alcohol Dependence (dsm5.org). The author presents a case report as a proof of concept that this distinction should be retained. The author has asserted that Alcohol Abuse is a purely psychological addiction, while Alcohol Dependence involves capture of the ventral tegmental dopaminergic SEEKING system (Johnson, 2003). In psychological addiction the brain can be assumed to function normally, and ordinary psychoanalytic technique can be followed. For the patient described, transference interpretation was the fundamental key to recovery. Alcoholic drinking functioned to prevent this man from remembering overwhelming childhood events; events that were also lived out in his current relationships. Murders that occurred when he was a child were hidden in a screen memory. The patient had an obsessional style of relating where almost all feeling was left out of his associations. After he stopped drinking compulsively, he continued to work compulsively. The maternal transference had to be enacted and then interpreted in order for overwhelming memories to be allowed into conscious thought. After psychoanalysis, the patient resumed drinking and worked a normal schedule that allowed more fulfilling relationships. He had no further symptoms of distress from drinking over a 9-year followup. This case illustrates that Alcohol Abuse is a purely psychological illness, that it does not have the brain changes typical of Alcohol Dependence. Combining epidemiological, neurobiological, longitudinal, and psychoanalytic observations would allow multiple sources of information to be used in creating diagnostic categories. Losing details of human behavior by relying only on epidemiological studies is likely to cause errors in categorization of disorders. In turn, having faulty categories as the basis of further research is likely to impair identification of specific effective treatments. PMID:22144975
Schumm, Jeremiah A.; O’Farrell, Timothy J.; Kahler, Christopher W.; Murphy, Marie M.; Muchowski, Patrice
Objective: Multiple studies show that behavioral couples therapy (BCT) is more efficacious than individually-based therapy (IBT) for substance use and relationship outcomes among men with alcohol use disorder (AUD). The present study compared BCT with IBT for women with AUD. Method: Participants were women with AUD (N = 105) and their male partners without SUD. Participants were mostly White and in their forties. Women were randomized to equally intensive treatments consisting of either BCT plus 12-step-oriented IBT or IBT only. Primary outcomes included: Timeline Followback Interview percentage days abstinent (PDA) and Inventory of Drug Use Consequences measure of substance-related problems. Secondary outcomes included: Dyadic Adjustment Scale (DAS), Relationship Happiness Scale (RHS), and Revised Conflict Tactics Scales measure of intimate partner violence (IPV). Outcome data were collected at baseline, post-treatment, and quarterly for 1-yr follow-up. Results: Compared to IBT only, BCT plus IBT had significantly better primary outcomes of higher PDA and fewer substance-related problems during the 1-yr follow-up period. Compared to IBT only, BCT had significantly higher male RHS during the 1-yr follow-up. Women with lower pretreatment DAS had significantly higher DAS following BCT versus IBT, and there was an increasing advantage for BCT on female DAS over the follow-up. IPV was significantly reduced from pretreatment to follow-up, with no differences between treatment conditions. Conclusion: Results showed that BCT for women with AUD was more efficacious than IBT in reducing substance use and substance-related problems and improving partner relationships. PMID:25045910
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.
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
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.
Kenna, George A; Zywiak, William H; Swift, Robert M; McGeary, John E; Clifford, James S; Shoaff, Jessica R; Fricchione, Samuel; Brickley, Michael; Beaucage, Kayla; Haass-Koffler, Carolina L; Leggio, Lorenzo
The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol-dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender-specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200 mg/day of sertraline or 0.5 mg/day of ondansetron for 3 weeks followed by an alcohol self-administration experiment (ASAE), then placebo for 3 weeks followed by a second ASAE, then receive the alternate drug, in a counterbalanced order, for 3 weeks followed by a third ASAE. Results for men were not significant. Women with the LL 5-HTTLPR genotype receiving ondansetron and SS/SL 5-HTTLPR genotype receiving sertraline (matched), drank significantly fewer drinks per drinking day (DDD) during the 7 days prior to the first and third ASAEs than women receiving the mismatched medication (i.e., sertraline to LL and ondansetron to SS/SL). In a 3-way interaction, 5-HTTLPR alleles by DRD4 alleles by medications, women with the LL genotype who received ondansetron and had DRD4≥7 exon III repeats drank significantly fewer DDD as did SS/SL women who received sertraline but conversely had DRD4<7 repeats in the 7-day period leading up to the first and third ASAEs. Consistent with these data was a significant reduction of milliliters consumed ad libitum during these same ASAEs. These exploratory findings add possible support to gender and genetic differences among AD individuals in response to serotonergic pharmacotherapies. Future trials should be powerful enough to take into account that endophenotypes and a targeting of serotonergic interactions may be
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
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
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
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.
Pruett, Dawn; Waterman, Emily Hubbard; Caughey, Aaron B
Maternal alcohol use during pregnancy is prevalent, with as many as 12% of pregnant women consuming alcohol. Alcohol intake may vary from an occasional drink, to weekly binge drinking, to chronic alcohol use throughout pregnancy. Whereas there are certain known consequences from fetal alcohol exposure, such as fetal alcohol syndrome, other effects are less well defined. Craniofacial dysmorphologies, abnormalities of organ systems, behavioral and intellectual deficits, and fetal death have all been attributed to maternal alcohol consumption. This review article considers the theoretical mechanisms of how alcohol affects the fetus, including the variable susceptibility to fetal alcohol exposure and the implications of ethanol dose and timing of exposure. Criteria for diagnosis of fetal alcohol syndrome are discussed, as well as new methods for early detection of maternal alcohol use and fetal alcohol exposure, such as the use of fatty acid ethyl esters. Finally, current and novel treatment strategies, both in utero and post utero, are reviewed.
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
Worley, Matthew J; Trim, Ryan S; Tate, Susan R; Roesch, Scott C; Myers, Mark G; Brown, Sandra A
Proximal personal and environmental factors typically predict outcomes of treatment for alcohol or drug dependence (AODD), but longitudinal treatment studies have rarely examined these factors in adults with co-occurring psychiatric disorders. In adults with AODD and major depression, the aims of this study were to: (a) disaggregate person-and time-level components of network substance use and self-efficacy, (b) examine their prospective effects on posttreatment alcohol/drug use, and (c) examine whether residential environment moderated relations between these proximal factors and substance use outcomes. Veterans (N = 201) enrolled in a trial of group psychotherapy for AODD and independent MDD completed assessments every 3 months during 1 year of posttreatment follow-up. Outcome variables were percent days drinking (PDD) and using drugs (PDDRG). Proximal variables included abstinence self-efficacy and social network drinking and drug use. Self-efficacy and network substance use at the person-level prospectively predicted PDD (ps < .05) and PDDRG (ps < .05). Within-person, time-level effects of social networks predicted future PDD (ps < .05) but not PDDRG. Controlled environments moderated person-level social network effects (ps < .05), such that greater time in controlled settings attenuated the association between a heavier drinking/using network and posttreatment drinking and drug use. Both individual differences and time-specific fluctuations in proximal targets of psychosocial interventions are related to posttreatment substance use in adults with co-occurring AODD and MDD. More structured environmental settings appear to alleviate risk associated with social network substance use, and may be especially advised for those who have greater difficulty altering social networks during outpatient treatment.
Philibert, Robert A; Penaluna, Brandan; White, Teresa; Shires, Sarah; Gunter, Tracy; Liesveld, Jill; Erwin, Cheryl; Hollenbeck, Nancy; Osborn, Terry
Alcoholism has a profound impact on millions of people throughout the world. However, the ability to determine if a patient needs treatment is hindered by reliance on self-reporting and the clinician’s capability to monitor the patient’s response to treatment is challenged by the lack of reliable biomarkers. Using a genome-wide approach, we have previously shown that chronic alcohol use is associated with methylation changes in DNA from human cell lines. In this pilot study, we now examine DNA methylation in peripheral mononuclear cell DNA gathered from subjects as they enter and leave short-term alcohol treatment. When compared with abstinent controls, subjects with heavy alcohol use show widespread changes in DNA methylation that have a tendency to reverse with abstinence. Pathway analysis demonstrates that these changes map to gene networks involved in apoptosis. There is no significant overlap of the alcohol signature with the methylation signature previously derived for smoking. We conclude that DNA methylation may have future clinical utility in assessing acute alcohol use status and monitoring treatment response. PMID:25147915
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
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.
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.
... social service. (x) Individual counseling as appropriate. (xi) Opportunities for learning/development of...-free life style). (xiii) Opportunities for learning, testing, and internalizing knowledge of illness... Veterans Affairs staff members involved with the treatment program of the veterans concerned....
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.
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.
Johnson, Bankole A.
Alcoholism remain a serious cause of morbidity and mortality, despite progress through neurobiological research in identifying new pharmacological strategies for its treatment. Drugs that affect neural pathways that modulate the activity of the cortico-mesolimbic dopamine system have been shown to alter drinking behavior, presumably because this dopaminergic system is closely associated with rewarding behavior. Ondansetron, naltrexone, topiramate, and baclofen are examples. Subtyping alcoholism in adults into an early-onset type, with chronic symptoms and a strong biological predisposition to the disease, and a late-onset type, typically brought on by psychosocial triggers and associated with mood symptoms, may help in the selection of optimal therapy. Emerging adults with binge-drinking patterns also might be aided by selective treatments. Although preliminary work on the pharmacogenetics of alcoholism and its treatment has been promising, the assignment to treatment still depends on clinical assessment. Brief behavioral interventions that encourage the patient to set goals for a reduction in heavy drinking or abstinence also are part of optimal therapy. PMID:20516163
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.
Pollock, Brianna E; Macfie, Jenny; Elledge, L Christian
We report on the treatment and successful outcome of a 58-year-old Native American male with a history of complex trauma presenting with dissociative identity disorder (DID) and major depressive disorder. The treatment included a trauma-informed phase-based psychotherapy as recommended by the International Society for the Study of Trauma and Dissociation for treating DID. We assessed symptoms at baseline and at three additional time points over the course of 14 months. We utilized the Reliable Change Index to examine statistically significant change in symptoms over the course of treatment. Significant symptom improvements were realized posttreatment across all measured domains of functioning, including dissociative symptoms, alcohol abuse, depression, anxiety, and emotion regulation skills. Moreover, the client no longer met criteria for DID, major depressive disorder, or alcohol abuse. Results are discussed in terms of the effectiveness of trauma-focused, phase-based treatment for DID for cases of complex trauma with comorbid disorders.
Beraha, Esther M; Salemink, Elske; Goudriaan, Anna E; Bakker, Abraham; de Jong, David; Smits, Natasha; Zwart, Jan Willem; Geest, Dick van; Bodewits, Pieter; Schiphof, Tom; Defourny, Harma; van Tricht, Mirjam; van den Brink, Wim; Wiers, Reinout W
Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ(2)=0.41; p=0.813) or the 16-weeks complete medication period (χ(2)=0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered.
Kern, Joseph C.; And Others
Treatment agencies that ignore needs of children of alcoholics are inadvertently breeding a second generation of alcoholics. This paper reports on an effort to mount an education/prevention effort with children of alcoholics and their mothers. Each session is described in detail and recommendations for programming offered. (Author)
Chun, Young-Min; Cho, Sung-Min; Shin, Sung-Man
The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) is an instrument used to measure the level of motivation in regards to changing drinking and other addictive behaviors. While some initial factor analysis studies on the SOCRATES described a three-factor orthogonal structure of the scale, some other studies found a two-factor correlated structure. Therefore, the primary objective of the present study was to test the validity of the Korean language version of the instrument using a Korean population. The study examined the factor structure of the Korean version of the SOCRATES with clinical samples consisting of 219 inpatients and 271 outpatients with alcohol dependency. An exploratory factor analysis with an alpha factoring method revealed a three-factor correlated structure (i.e., Taking Steps, Recognition, and Ambivalence). The factorial structure of the SOCRATES Korean version corresponded almost exactly to that of its original French version as well as the German version. Moreover, confirmatory factor analyses showed that a three-factor correlated structure provided the best fit for the data.
Many individuals wait until alcohol use becomes severe before treatment is sought. However, social networks, or the number of social groups an individual belongs to, may play a moderating role in this relationship. Logistic regression examined the interaction of alcohol consumption and social networks as a predictor of treatment utilization while adjusting for sociodemographic and clinical variables among 1,433 lifetime alcohol-dependent respondents from wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC). Results showed that social networks moderate the relationship between alcohol consumption and treatment utilization such that for individuals with few network ties, the relationship between alcohol consumption and treatment utilization was diminished, compared to the relationship between alcohol consumption and treatment utilization for individuals with many network ties. Findings offer insight into how social networks, at times, can influence individuals to pursue treatment, while at other times, influence individuals to stay out of treatment, or seek treatment substitutes.
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 Melo, Raquel Calvão; Lopes, Rui; Alves, José Carlos
Background. Disulfiram, a drug used in the treatment of alcohol dependence, is an inhibitor of dopamine-β-hydroxylase causing an increase in the concentration of dopamine in the mesolimbic system. In addition to the physical symptoms associated with concomitant use of alcohol, disulfiram may lead to adverse events, when used alone, including psychosis. Aims. To report a case of a rare complication when using disulfiram for alcoholism treatment in a patient in alcoholic abstinence. Case Report. We describe the case of a 42-year-old male patient, who developed psychotic symptoms 3 weeks after initiating treatment with disulfiram for alcohol dependency. The patient had a history of chronic alcoholism for 12 years and was under disulfiram treatment (250 mg/day) for 1 month, with no other past history of psychiatric illness. The symptoms worsened after he initiated alcohol consumption, while taking disulfiram. The patient was hospitalized and disulfiram was suspended. After 4 days he was asymptomatic and at 6-week follow-up remained asymptomatic. Conclusion. Treatment with disulfiram can lead to the appearance of psychosis in patients with increased vulnerability. In clinical practice, psychosis in the context of alcoholism with disulfiram therapy is often neglected and should be taken into account. PMID:24818034
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.
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
Delaney, Harold D; Forcehimes, Alyssa A; Campbell, William P; Smith, Bruce W
Spirituality is presumed by millions of Americans to be directly relevant to problems of alcohol abuse. We summarize findings regarding the role of religion and spirituality in the prevention and treatment of substance abuse and present a case illustration. We also consider mechanisms responsible for these effects. We offer advice about why, by whom, and how religion and spirituality should be discussed with clients with substance use disorders. In a recent clinical trial, therapists trained in a client-centered approach to facilitate exploration of spirituality fostered clients' use of spiritual practices. We suggest that the therapist's ability to skillfully engage clients in a discussion of spirituality is largely determined by how the therapist balances the dual roles of authoritative expert and evocative facilitator.
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.
Thomason, Timothy C.
Reviews the literature on the treatment of Native Americans who abuse alcohol or have dependence disorders and provides an interpretation of the research on this topic. The most common treatment modalities are described and critiqued. Recommendations are made regarding revising standard treatments to make them more culturally appropriate for this…
Kolla, Bhanu Prakash; Schneekloth, Terry D; Biernacka, Joanna M; Frye, Mark A; Mansukhani, Meghna P; Hall-Flavin, Daniel K; Karpyak, Victor M; Loukianova, Larissa L; Lesnick, Timothy G; Mrazek, David
Trazodone is one of the most commonly prescribed hypnotic medications in patients with sleep disturbances in alcohol recovery. A recent study concluded that treating insomnia with trazodone in patients with alcohol dependence might impede improvements in alcohol consumption and lead to increased drinking when trazodone is stopped. We set out to investigate the relationship between trazodone use during alcoholism treatment and relapse rates in patients who were discharged from a residential alcohol treatment program. We retrospectively reviewed records of patients with a diagnosis of alcohol dependence in a residential addiction treatment center from 2005 to 2008 and analyzed the association of trazodone use at discharge and alcohol relapse at 6 months. We also assessed the association between trazodone use and relapse at 6 months adjusting for sex, drug dependence, nonsubstance use Axis I psychiatric diagnoses, patient self-report of difficulties with sleep, and anti-dipsotropic medication use at discharge and evaluated pair-wise interactions of trazodone use with the adjustment variables. Of 283 patients eligible for inclusion, 85 (30%) were taking trazodone at discharge. Older age, self-reported sleep problems, and having a nonsubstance use Axis I psychiatric diagnosis were associated with trazodone use. After discharge, 170 (60%) subjects responded to follow-up efforts. Neither intent to treat nor responder only analysis revealed any association between trazodone use and relapse. Our retrospective study of a complex patient population discharged from a residential treatment setting did not find an association between trazodone use at discharge and relapse rates at 6 months.
Geizer, Bernard P., Ed.
The report presents the results of an evaluation of New York's 13 Alcoholism Treatment Centers (ATCs). The goals of the evaluation were to review the role of the ATCs in relation to other alcoholism treatment facilities, to assess their effectiveness and efficiency, and to determine how much money is collected for service provided to patients.…
Nace, E P
The historical role of inpatient treatment for alcoholism is reviewed in terms of its advantages and disadvantages. The factors that have forced a change in the utilization of inpatient treatment include increasing recognition of the heterogeneity of alcoholic patients, negative outcome studies, and cost-containment efforts. The clinical domains that warrant inpatient treatment are outlined, and decisions of treatment placement are necessarily guided by the factors of acuteness, ability, safety, and stabilization.
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
Shasthry, Saggere Muralikrishna; Sarin, Shiv Kumar
The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using "Omics" platforms, newer options for patients with alcoholic hepatitis are expected soon.
Schumm, Jeremiah A.; O'Farrell, Timothy J.; Murphy, Christopher M.; Fals-Stewart, William
This study examined partner violence before and in the 1st and 2nd year after behavioral couples therapy (BCT) for 103 married or cohabiting women seeking alcohol dependence treatment and their male partners; it used a demographically matched nonalcoholic comparison sample. The treatment sample received M = 16.7 BCT sessions over 5-6 months.…
López-Goñi, José J; Fernández-Montalvo, Javier; Arteaga, Alfonso
This study explored the characteristics of a representative sample of patients who were addicted to either alcohol or cocaine, comparing the profiles of both types of drug users. A sample of 234 addicted patients (109 alcoholics and 125 cocaine addicts) who sought outpatient treatment in a Spanish clinical centre was assessed. Data on socio-demographic, consumption, psychopathological and maladjustment characteristics were collected using the European Addiction Severity Index (EuropASI), the Symptom Checklist-90-Revised (SCL-90-R) and the Millon Clinical Multiaxial Inventory (MCMI-II). Demographically, differences were observed with regard to age (alcoholics were older than cocaine addicts; t = 12.2, p = .001), employment (the alcoholic group had more labor problems; χ 2 = 6.2, p = .045) and family consequences (worse in alcoholics; t = 2.3, p = .025). The EuropASI results showed statistically significant differences in addiction severity, with alcoholics showing a greater severity than cocaine addicts. In terms of psychopathology, alcoholics presented more associated symptomatology than cocaine addicts. According to these results, patients with alcohol dependence have a different profile from patients with cocaine dependence, resulting in different repercussions for important areas of their lives. These differences should be taken into account when standard treatments for addiction are implemented.
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.
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
Survey respondents' views about alcoholism as an illness, support for treatment, treatment recommendation and stigma surrounding alcoholics are examined. Subjects (N = 482) comprise a random sample of the population of Contra Costa County, California. About 91% of the respondents agree with the notion that alcoholism is an illness, but 40% also agree that alcoholics drink because they want to. More women than men support the idea that to recover alcoholics will have to quit drinking forever. The contrary is true of the idea of controlled drinking. Education and income are negatively associated with items on loss of control and controlled drinking. Respondents who have had their lives deeply affected by an alcoholic and those who report a drinking problem of their own do not differ in their opinions about alcoholism from those who do not have these characteristics. Alcoholics Anonymous is the most common form of treatment recommended by the respondents. In general, results show considerable support for treatment as well as ambivalence regarding the disease concept.
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
Arias, Albert J; Sewell, R Andrew
Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict treatment response and side-effect risk for specific medications. We review the literature on pharmacogenetics relevant to alcohol dependence treatment, and describe state-of-the-art methods of pharmacogenetic research in this area. Two main pharmacogenetic study designs predominate: challenge studies and treatment-trial analyses. Medications studied include US FDA-approved naltrexone and acamprosate, both indicated for treating alcohol dependence, as well as several investigational (and off-label) treatments such as sertraline, olanzapine and ondansetron. The best-studied functional genetic variant relevant to alcoholism treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1 gene that encodes the μ-opioid receptor. Evidence from clinical trials suggests that the presence of the variant G allele of rs1799971 may predict better treatment response to opioid receptor antagonists such as naltrexone. Evidence from clinical trials also suggests that several medications interact pharmacogenetically with variation in genes that encode proteins involved in dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene, which encodes the dopamine D(4) receptor, may predict better response to naltrexone and olanzapine. A polymorphism in the serotonin transporter gene SLC6A4 promoter region appears related to differential treatment response to sertraline depending on the subject's age of onset of alcoholism. Genetic variation in SLC6A4 may also be associated with better treatment response to ondansetron. Initial pharmacogenetic efforts in alcohol research have identified functional variants with potential clinical utility, but more research is needed to further elucidate the mechanism of these pharmacogenetic interactions and their moderators in order to translate them into clinical practice.
Zemore, Sarah E.; Mulia, Nina; Ye, Yu; Borges, Guilherme; Greenfield, Thomas K.
This study, using 3 waves of U.S. National Alcohol Surveys (1995-2005), examines lifetime alcohol treatment utilization and perceived treatment barriers among Latinos. The sample included 4204 Latinos (2178 women, 2024 men); data were weighted. Analyses were linear and logistic regressions. Controlling for survey year, severity, and other covariates, male gender and English language interview predicted higher utilization generally and AA use specifically; English interview was also associated with institutional treatment. (Effects for gender on general utilization were marginal.) Other predictors of utilization included older age, lower education, greater social pressures, greater legal consequences, greater dependence symptoms, and public insurance. Whereas men and women differed little on perceived barriers, analyses showed greater barriers among Spanish (vs. English) interviewees. Latina women's underutilization of alcohol treatment requires further research, but may be partially explained by stigma. Associations between language of interview and treatment utilization imply a need for outreach and culturally sensitive programming. PMID:19004599
Bozikas, Vasilis; Petrikis, Petros; Gamvrula, Katerina; Savvidou, Ioanna; Karavatos, Athanasios
Gabapentin is an anticonvulsant agent, also effective in the treatment of mood disorders and anxiety disorders. Three cases of alcohol withdrawal treated with gabapentin are presented. All patients received gabapentin 400 mg tid for 3 days, 400 mg bid for 1 day, and finally 400 mg for 1 day. Withdrawal symptoms subsided and no adverse effects were observed. The possible effectiveness of gabapentin in the treatment of alcohol withdrawal warrants further investigation by systematic and well-designed studies.
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
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
Palpacuer, Clément; Laviolle, Bruno; Boussageon, Rémy; Reymann, Jean Michel; Bellissant, Eric; Naudet, Florian
Background Nalmefene is a recent option in alcohol dependence treatment. Its approval was controversial. We conducted a systematic review and meta-analysis of the aggregated data (registered as PROSPERO 2014:CRD42014014853) to compare the harm/benefit of nalmefene versus placebo or active comparator in this indication. Methods and Findings Three reviewers searched for published and unpublished studies in Medline, the Cochrane Library, Embase, ClinicalTrials.gov, Current Controlled Trials, and bibliographies and by mailing pharmaceutical companies, the European Medicines Agency (EMA), and the US Food and Drug Administration. Double-blind randomized clinical trials evaluating nalmefene to treat adult alcohol dependence, irrespective of the comparator, were included if they reported (1) health outcomes (mortality, accidents/injuries, quality of life, somatic complications), (2) alcohol consumption outcomes, (3) biological outcomes, or (4) treatment safety outcomes, at 6 mo and/or 1 y. Three authors independently screened the titles and abstracts of the trials identified. Relevant trials were evaluated in full text. The reviewers independently assessed the included trials for methodological quality using the Cochrane Collaboration tool for assessing risk of bias. On the basis of the I2 index or the Cochrane’s Q test, fixed or random effect models were used to estimate risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% CIs. In sensitivity analyses, outcomes for participants who were lost to follow-up were included using baseline observation carried forward (BOCF); for binary measures, patients lost to follow-up were considered equal to failures (i.e., non-assessed patients were recorded as not having responded in both groups). Five randomized controlled trials (RCTs) versus placebo, with a total of 2,567 randomized participants, were included in the main analysis. None of these studies was performed in the specific population
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
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.
Nathan, Sally; Rawstorne, Patrick; Hayen, Andrew; Bryant, Joanne; Baldry, Eileen; Ferry, Mark; Williams, Megan; Shanahan, Marian; Jayasinha, Ranmalie
Introduction Young people with drug and alcohol problems are likely to have poorer health and other psychosocial outcomes than other young people. Residential treatment programmes have been shown to lead to improved health and related outcomes for young people in the short term. There is very little robust research showing longer term outcomes or benefits of such programmes. This paper describes an innovative protocol to examine the longer term outcomes and experiences of young people referred to a residential life management and treatment programme in Australia designed to address alcohol and drug issues in a holistic manner. Methods and analysis This is a mixed-methods study that will retrospectively and prospectively examine young people's pathways into and out of a residential life management programme. The study involves 3 components: (1) retrospective data linkage of programme data to health and criminal justice administrative data sets, (2) prospective cohort (using existing programme baseline data and a follow-up survey) and (3) qualitative in-depth interviews with a subsample of the prospective cohort. The study will compare findings among young people who are referred and (a) stay 30 days or more in the programme (including those who go on to continuing care and those who do not); (b) start, but stay fewer than 30 days in the programme; (c) are assessed, but do not start the programme. Ethics and dissemination Ethics approval has been sought from several ethics committees including a university ethics committee, state health departments and an Aboriginal-specific ethics committee. The results of the study will be published in peer-reviewed journals, presented at research conferences, disseminated via a report for the general public and through Facebook communications. The study will inform the field more broadly about the value of different methods in evaluating programmes and examining the pathways and trajectories of vulnerable young people. PMID
Hammond, Christopher J; Niciu, Mark J; Drew, Shannon; Arias, Albert J
Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.
Andó, Bálint; Rózsa, Sándor; Kurgyis, Eszter; Szkaliczki, Andrea; Demeter, Ildikó; Szikszay, Petronella; Demetrovics, Zsolt; Janka, Zoltán; Álmos, Péter Z
Temperament and character factors are strongly related to the developmental, clinical, and treatment aspects of alcohol dependence. This study had the aim of revealing the underlying personality structure and individual differences in the symptoms of alcohol dependence measured by multiple severity indicators. Patients with alcohol dependence exhibited higher levels of novelty seeking and harm avoidance, and lower levels of persistence, self-directedness, and cooperativeness. Especially novelty seeking was connected with more severe alcohol dependence. These characteristics could be useful targets of interventions and Temperament and Character Inventory is therefore a useful measurement to identify patients with more severe alcohol-related problems.
Alcoholics Anonymous (AA) self-help groups are the most commonly accessed component of the de facto system of care for alcohol problems in the United States. Further, AA's concepts and approach have strongly influenced a significant number of professional treatment programs. Nevertheless, only a modest number of longitudinal, comparative outcome studies on AA and on professional 12-step treatment programs have been conducted, which has limited both the certainty and scope of conclusions that can be drawn about these interventions. Research indicates that participation in Alcoholics Anonymous and in 12-step treatment are associated with significant reductions in substance abuse and psychiatric problems. Further, such interventions, it has been found, reduce health care costs over time in naturalistic, quasi-experimental, and experimental studies. Evaluation studies have also begun to illuminate the processes through which self-help groups and 12-step treatment programs exert their effects. To build on this knowledge base, future research should (1) be methodologically flexible and well-matched to its phenomenon of interest, (2) include evaluation of the unique features of self-help organizations, (3) increase representation of African-Americans and women in research samples, and (4) increase statistical power through larger sample sizes and more reliable measurement. Key content areas for future enquiry include further longitudinal evaluation of the outcomes of participation in AA and 12-step treatment (particularly in outpatient samples); better specification of the aspects of AA that influence outcome; and individual-, community-, and health organization-level controlled studies of the health care cost consequences of 12-step interventions.
... You are Not Alone Like any other chronic disease, addiction to alcohol and other drugs affects people of all ages regardless of income, educational background, country of origin, ethnicity, sexuality, and/or community where they live. ...
Shasthry, Saggere Muralikrishna; Sarin, Shiv Kumar
The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using “Omics” platforms, newer options for patients with alcoholic hepatitis are expected soon. PMID:27099434
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.
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.
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.
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)
Myrick, H; Brady, K T; Malcolm, R
The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group x CIWA-Ar score interaction [F(8,72) = 2.57, p < or = .01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p < or = .001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal.
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
Wackernah, Robin C; Minnick, Matthew J; Clapp, Peter
Alcohol use disorders (AUD) continue to be a concerning health issue worldwide. Harmful alcohol use leads to 2.5 million deaths annually worldwide. Multiple options exist for the management of dependence on alcohol, not all of which are approved by drug-regulating agencies. Current practice in treating AUD does not reflect the diversity of pharmacologic options that have potential to provide benefit, and guidance for clinicians is limited. Few medications are approved for treatment of AUD, and these have exhibited small and/or inconsistent effects in broad patient populations with diverse drinking patterns. The need for continued research into the treatment of this disease is evident in order to provide patients with more specific and effective options. This review describes the neurobiological mechanisms of AUD that are amenable to treatment and drug therapies that target pathophysiological conditions of AUD to reduce drinking. In addition, current literature on pharmacologic (both approved and non-approved) treatment options for AUD offered in the United States and elsewhere are reviewed. The aim is to inform clinicians regarding the options for alcohol abuse treatment, keeping in mind that not all treatments are completely successful in reducing craving or heavy drinking or increasing abstinence. PMID:24648792
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
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.
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
Vatsalya, Vatsalya; Barve, Shirish S.; McClain, Craig J.; Ramchandani, Vijay A.
HIV and HCV co-infection is a unique disease condition, and medical management of such condition is difficult due to severity and systemic complications. Added with heavy alcohol drinking, risk of liver injury increases due to several pro-inflammatory responses that subsequently get involved with alcohol metabolism. Elevated levels of fatty acids have been reported both in viral infections as well as alcoholic liver disease though such investigations have not addressed the adverse events with dual viral infection of HIV and HCV along with heavy drinking. This case report is of a patient with excessive alcohol drinking and first time diagnosis of HIV and HCV dual infection, elaborating concurrent alteration in Linoleic Acid (LA) levels and pro-inflammatory shift in ω-6/ω-3 ratio along with the elevations in liver injury markers. Elevated LA has been recently studied extensively for its role in alcoholic liver disease; and in the present case, we also found it to be clinically relevant to liver injury. PMID:27489857
Allen, J P
Alcoholism treatment research has traditionally focused on direct questions of efficacy, such as is a particular intervention better than no treatment or is one treatment more effective than another. Recent projects, however, have also attempted to identify variables explaining why treatments vary in their effects. Many of these variables relate to the process of treatment itself or changes that may occur within the patients. Clinicians also need to continuously monitor progress of patients in engaging in behaviors supportive of long-term sobriety and how well the values and behaviors fostered by the particular treatment regimen are being incorporated into daily life. Measurement of process variables may assist in both regards. In the last decade several psychometric instruments have been developed to elucidate the processes involved in Alcoholic Anonymous (AA), a key adjunct of most formal alcoholism programs in the United States. These instruments measure dimensions such as involvement in AA, completion of steps, and adoption of values encouraged by AA. Six such measures are summarized here and several fruitful topics for future research on the measures are suggested.
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
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
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
Haxby, D G
Drug and nondrug interventions used in treating nicotine dependence are reviewed. Tobacco use is the leading preventable cause of death in the United States. Risks of smoking-related disease and death decline sharply when smokers quit, but 26% of Americans continue to smoke. Most smokers find it extremely difficult to quit smoking because of their nicotine addiction. Nonpharmacologic interventions used to promote smoking cessation include behavioral therapy, setting a specific date for quitting, receiving advice to quit from a health care professional, follow-up visits to review progress, self-help approaches, group counseling, filtration devices, hypnosis, and acupuncture. The efficacy of these approaches ranges from substantial to almost nil. The only pharmacologic agent with FDA-approved labeling for use in smoking-cessation therapy is nicotine. When used in conjunction with appropriate nonpharmacologic interventions, nicotine-replacement therapy roughly doubles the rate of quitting obtained with placebo. Nicotine-replacement therapies consist of nicotine transdermal (patch) systems and nicotine chewing gum. The nicotine patch is the first-line replacement therapy because it is effective when accompanied by only minimal (as opposed to more intensive) nonpharmacologic interventions and because it is easier to use and comply with than gum. Clonidine, antidepressants, and buspirone require further study to determine what role, if any, they should play in the treatment of nicotine dependence. The stages of smoking cessation are precontemplation, contemplation, action, and maintenance; interventions are selected on the basis of the stage the smoker is in. Nicotine dependence is difficult to treat, but there are aids that boost a smoker's chances of quitting. Nicotine patches and chewing gum offer the most effective pharmacologic options, especially when combined with behavioral interventions and counseling.
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
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
de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F.; Hope, Bruce T.; Brennan, Molly; Cole, Maury; Koob, George F.
results identify a critical neurobiological mechanism that is required for alcohol dependence, suggesting that targeting dependence neuronal ensembles may lead to a better understanding of the etiology of alcohol use disorders, with implications for diagnosis, prevention, and treatment. PMID:27605618
... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82 Pensions... Agencies § 17.82 Contracts for outpatient services for veterans with alcohol or drug dependence or abuse disabilities. (a) Contracts for treatment services authorized under § 17.80 may be awarded in accordance...
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.
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
Winham, Stacey J.; Preuss, Ulrich W.; Geske, Jennifer R.; Zill, Peter; Heit, John A.; Bakalkin, Georgy; Biernacka, Joanna M.; Karpyak, Victor M.
We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states, and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p = 0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285 G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific. PMID:26502829
Evren, Cuneyt; Evren, Bilge; Yancar, Cenk; Erkiran, Murat
The aims of this study were to evaluate the differences in dimensions of temperament and character in Turkish alcohol- and drug-dependent inpatients, and to examine which dimensions would predict drug dependency. The subjects consisted of 111 alcohol-dependent and 93 drug-dependent inpatients according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Subjects were tested using Cloninger's Temperament and Character Inventory (TCI). Among the temperament dimensions, novelty seeking score was higher and reward dependency score was lower in drug-dependent patients than in alcohol-dependent patients. Among the character dimensions, self-directedness and cooperativeness scores were lower in drug-dependent patients. Low age and novelty seeking predicted drug dependency in forward logistic regression model. Subscales that predicted drug dependency other than young age were lower scores on compassion vs revengefulness (C4) and helpfulness (C3), and higher score on spiritual acceptance vs rational materialism (ST3). As in previous studies, which indicate an association between personality and substance choice, in the present study, TCI was shown to be an efficient tool in discriminating alcohol and drug dependents; thus, it seems to be important to consider TCI dimensions in planning the treatment of substance dependency.
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
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.
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.
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.
Ross, David S.; Blessing, James E.
A method for the hydroconversion of coal by solvent treatment at elevated temperatures and pressure wherein an alcohol having an .alpha.-hydrogen atom, particularly a secondary alcohol such as isopropanol, is utilized as a hydrogen donor solvent. In a particular embodiment, a base capable of providing a catalytically effective amount of the corresponding alcoholate anion under the solvent treatment conditions is added to catalyze the alcohol-coal reaction.
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.
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
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
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
Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon; Choi, Ihn-Geun
Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.
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.
Taft, Casey T.; O'Farrell, Timothy J.; Doron-Lamarca, Susan; Panuzio, Jillian; Suvak, Michael K.; Gagnon, David R.; Murphy, Christopher M.
Objective: This study examined static and time-varying risk factors for perpetration of intimate partner violence (IPV) among men in treatment for alcohol use disorders. Method: Participants were 178 men diagnosed with alcohol abuse or dependence and their partners. Most (85%) of the men were European American; their average age was 41.0 years.…
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.
Zakiniaeiz, Yasmin; Scheinost, Dustin; Seo, Dongju; Sinha, Rajita; Constable, R Todd
Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC), mid (MCC) and posterior cingulate cortex (PCC), voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome). Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC) participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.
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
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.
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
Klimas, Jan; Muench, John; Wiest, Katharina; Croff, Raina; Rieckman, Traci; McCarty, Dennis
Problem alcohol use is associated with adverse health and economic outcomes, especially among people in opioid agonist treatment. Screening, brief intervention, and referral to treatment (SBIRT) are effective in reducing alcohol use; however, issues involved in SBIRT implementation among opioid agonist patients are unknown. To assess identification and treatment of alcohol use disorders, we reviewed clinical records of opioid agonist patients screened for an alcohol use disorder in a primary care clinic (n = 208) and in an opioid treatment program (n = 204) over a two-year period. In the primary care clinic, 193 (93%) buprenorphine patients completed an annual alcohol screening and six (3%) had elevated AUDIT scores. In the opioid treatment program, an alcohol abuse or dependence diagnosis was recorded for 54 (27%) methadone patients. Practitioner focus groups were completed in the primary care (n = 4 physicians) and the opioid treatment program (n = 11 counselors) to assess experience with and attitudes towards screening opioid agonist patients for alcohol use disorders. Focus groups suggested that organizational, structural, provider, patient, and community variables hindered or fostered alcohol screening. Alcohol screening is feasible among opioid agonist patients. Effective implementation, however, requires physician training and systematic changes in workflow.
Hanpatchaiyakul, Kulnaree; Eriksson, Henrik; Kijsompon, Jureerat; Östlund, Gunnel
Background Men are overrepresented with regard to alcohol addiction and in terms of alcohol treatment worldwide. In Thailand, alcohol consumption continues to rise, but few of those afflicted with alcohol addiction attend alcohol treatment programs, even though there is universal care for all. No comprehensive studies have been done on men’s experiences with addiction and alcohol treatment programs in Thailand. Objective The aim of this study was to explore men’s experiences in terms of the ‘pros and cons of alcohol consumption’ in order to identify the barriers that exist for Thai men with regard to alcohol addiction and the decision to stop drinking. Design Purposive sampling was applied in the process of recruiting participants at an alcohol clinic in a hospital in Thailand. Thirteen men with alcohol addiction (aged 32–49 years) were willing to participate and were interviewed in thematic interviews. The analysis of the data was done with descriptive phenomenology. Results Through men’s descriptions, three clusters of experiences were found that were ‘mending the body’, ‘drinking as payoff and doping related to work’, and ‘alcohol becoming a best friend’ as ways of describing the development of addiction. Conclusions The results highlight the importance of addressing concepts of masculinity and related hegemonic ideas in order to decrease the influence of the barriers that exist for Thai men with alcohol addiction with regard to entering treatment and to stop drinking. PMID:24845212
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
Browne, Kendall C; Wray, Tyler B; Stappenbeck, Cynthia A; Krenek, Marketa; Simpson, Tracy L
Research has demonstrated the positive association between alcohol craving and alcohol use and has identified craving as a central component of alcohol use disorders (AUD). Despite potential clinical implications, few studies have examined the relationship between craving and alcohol use in individuals with AUD and common psychiatric comorbidities or explored possible moderators of the craving-alcohol use relationship. The current study used daily monitoring data to: 1) replicate previous findings detecting a positive relationship between craving and alcohol use in individuals with AUD and co-occurring posttraumatic stress disorder (PTSD) and 2) extend these findings by examining the influence of initial change motivation on the craving-use relationship and within-day associations among craving, efforts to control craving, and alcohol consumption. Participants were 84 individuals with alcohol dependence and PTSD enrolled in an intervention study. Generalized estimating equations using pre-treatment baseline daily data revealed significant main effects for craving, craving control, and motivation to change alcohol use. Daily craving was positively related to alcohol use. Greater change motivation and craving control (i.e., efforts to resist craving, avoidance of thoughts and feelings related to craving) were negatively related to alcohol use. A significant interaction was detected between baseline change motivation and daily craving indicating that the association between craving and alcohol use was significantly stronger for those with low baseline change motivation. A significant interaction was also detected between craving control and daily craving, suggesting that participants were more likely to consume alcohol when experiencing high levels of craving if they reported low levels of craving control. Findings bolster the idea that efforts to prevent or ameliorate craving are critical to treatment success for individuals with AUD and PTSD who are seeking to
Soyka, Michael; Zill, Peter; Koller, Gabi; Samochowiec, Agnieszka; Grzywacz, Anna; Preuss, Ulrich W
Aggression, violence and antisocial behavior are common in alcoholism, but their biological basis is poorly understood. Several studies and recent meta-analyses indicate that in schizophrenia the catecholamine-O-methyltransferase (COMT) Val158Met genotype may be associated with aggression, most often in methionine allele carriers. We tested this hypothesis in a sample of treatment-seeking alcohol-dependent in-patients (293 German patients and 499 controls, and additional 190 Polish patients as replication sample). As expected, patients with a history of violent or non-violent crime were more often male, had an earlier onset of alcoholism and more withdrawal seizures and delirium tremens, and were more likely to have a history of suicide attempts. COMT genotype was not associated with a history of violent or non-violent crime. More studies are needed on the neurobiological basis of aggression and violence in alcoholism.
Leeman, Robert F; McKee, Sherry A; Toll, Benjamin A; Krishnan-Sarin, Suchitra; Cooney, Judith L; Makuch, Robert W; O'Malley, Stephanie S
Little is known about the impact of alcohol involvement on smoking cessation relapse or possible mechanisms for these associations. We addressed these issues using data from a randomized clinical trial of two types of framed messages (gain vs. loss) in conjunction with open label sustained-release (SR) bupropion (Toll et al., 2007) (N = 249). Participants were categorized according to whether or not they were diagnosed with a lifetime alcohol use disorder (AUD; i.e., current or past alcohol abuse or past alcohol dependence) and according to three levels of alcohol use: abstinence, moderate, or hazardous use. Alcohol use categories were established for drinking at baseline, during the 6-week treatment period and through 12 weeks post-quit. There were few significant differences by baseline alcohol use level or AUD history for a series of predictors of smoking cessation failure (e.g., depressive symptoms). During treatment and follow-up, the probability of any smoking on heavy drinking days was significantly higher than the probability of smoking on moderate drinking or abstinent days. AUD history did not predict smoking cessation relapse in any analysis, nor were any alcohol usexAUD history interactions significant. Moderate alcohol users and, to a lesser extent, abstainers from alcohol at baseline were less likely than hazardous drinkers to have relapsed at 12 weeks post-quit. Based on these findings, it appears that risk of any smoking and of relapse was associated primarily with heavy drinking days and a hazardous pattern of use respectively, rather than with moderate drinking.
Leeman, Robert F.; McKee, Sherry A.; Toll, Benjamin A.; Krishnan-Sarin, Suchitra; Cooney, Judith L.; Makuch, Robert W.; O’Malley, Stephanie
Little is known about the impact of alcohol involvement on smoking cessation relapse or possible mechanisms for these associations. We addressed these issues using data from a randomized clinical trial of 2 types of framed messages (gain vs. loss) in conjunction with open label sustained-release (SR) bupropion (Toll et al., 2007) (N = 249). Participants were categorized according to whether or not they were diagnosed with a lifetime alcohol use disorder (AUD; i.e., current or past alcohol abuse or past alcohol dependence) and according to 3 levels of alcohol use: abstinence, moderate or hazardous use. Alcohol use categories were established for drinking at baseline, during the 6-week treatment period and through 12 weeks post-quit. There were few significant differences by baseline alcohol use level or AUD history for a series of predictors of smoking cessation failure (e.g., depressive symptoms). During treatment and follow-up, the probability of any smoking on heavy drinking days was significantly higher than the probability of smoking on moderate drinking or abstinent days. AUD history did not predict smoking cessation relapse in any analysis, nor were any alcohol use × AUD history interactions significant. Moderate alcohol users and to a lesser extent, abstainers from alcohol at baseline were less likely than hazardous drinkers to have relapsed at 12 weeks post-quit. Based on these findings, it appears that risk of any smoking and of relapse was associated primarily with heavy drinking days and a hazardous pattern of use respectively, rather than with moderate drinking. PMID:19023831
... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism
Manzardo, Ann M.; Pendleton, Tiffany; Poje, Albert; Penick, Elizabeth C.; Butler, Merlin G.
Background Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with serious illness and neurological deficits that influence mood and cognition. We previously reported reduced alcohol consumption among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). As a follow-up, we have examined the relationship between lifetime alcoholism severity and psychiatric symptoms among the alcohol dependent men from this cohort and their response to BF treatment. Methods Eighty-five adult men (mean age = 48 ± 8 yrs) meeting DSM-IV-TR criteria for current alcohol dependence participated in a randomized, double-blind, placebo-controlled trial of 600 mg BF vs placebo (PL) for 6 months. Psychometric testing included a derived Lifetime Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months with data analyzed using ANOVA and MANOVA modeling. Results Baseline SCL-90-R scale scores for men with high alcoholism severity (AS ≥ 24; N=46 HAS) were significantly greater than for men with low alcoholism severity (AS < 24; N=39 LAS), but BIS scores did not differ. MANOVA modeling identified a significant treatment effect (F=2.5, df=10, p<0.03) and treatment x alcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, p<0.03) with SCL-90-R scores showing a reduction in symptoms among BF treated, high severity males. Conclustion BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with lifetime alcohol dependence and should be considered for adjuvant therapy in alcohol rehabilitation. PMID:25908323
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
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.
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.
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.
O'Farrell, Timothy J.
Couples therapy interventions can be used with alcohol abusers and alcoholics during three broadly defined states of recovery: (1) initial commitment to change; (2) change itself; and (3) long-term maintenance of change. Intervening with the alcoholic's spouse (and/or other nonalcoholic family members) can motivate and reinforce commitment to…
McGough, Dixie P.; Hindman, Margaret H.
This guide contains information from the alcoholism literature and from interviews with people in state alcoholism agencies, major professional associations, and public and private service programs. It is designed to help readers plan and develop community alcoholism programs by providing an overview of the many considerations involved in starting…
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
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
Wietschorke, Katharina; Lippold, Julian; Jacob, Christian; Polak, Thomas; Herrmann, Martin J
Alcohol craving has been shown to be an important factor for relapses in alcohol-dependent patients. Furthermore, brain activity in reward-related areas in response to alcohol-related cues is positively related to the amount of post-relapse alcohol consumption. On the other hand, it has been shown that cue-exposure based extinction training (CET) leads to larger decrease of striatal and left dorsolateral prefrontal cortex (dLPFC) cue-induced activation compared to standard clinical day-care treatment, but the effect sizes are relatively small. The question of this study was, whether it is possible to change cue-reactivity and subjective craving by applying bilateral prefrontal transcranial direct current stimulation (tDCS). We stimulated 30 detoxified alcohol-dependent patients (50 % with a sham and 50 % with left cathodal/right anodal stimulation) and presented emotional as well as alcohol-related pictures. We measured the emotional startle modulation and found significantly increased startle amplitudes in the verum stimulation condition for alcohol-related cues, indicating a more negative processing of this cues in alcohol-dependent patients after verum tDCS stimulation. Additionally we found tendencies for stronger reduction in subjective craving in verum-stimulated patients. Therefore our study underscores the positive value of DCS in reducing craving and might help to improve the understanding and therapy of alcohol dependence.
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.
Gazdzinski, Stefan; Durazzo, Timothy C; Meyerhoff, Dieter J
Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage.
Zwierzyńska, Ewa; Andrzejczak, Dariusz; Pietrzak, Bogusława
New antiepileptic drugs have been investigated for their potential role in the treatment of alcohol dependence. One of these drugs is retigabine and this study examines the effect of retigabine co-administered with ethanol on the development of alcohol dependence and the course of acute withdrawal syndrome. A pharmaco-EEG method was used to examine this impact in selected brain structures of rabbits (midbrain reticular formation, hippocampus and frontal cortex). Retigabine was administered p.o. at a dose of 5mg/kg/day with ethanol ad libitum for 6 weeks and then alone for 2 weeks during an abstinence period. Changes in bioelectric activity, which demonstrated the inhibitory effect of alcohol on the brain structures, were already visible after 2 weeks of ethanol administration. In the abstinence period, changes were of a different nature and significant neuronal hyperactivity was observed, particularly in the midbrain reticular formation and the hippocampus. This findings reveal that retigabine decreased ethanol-induced changes during both alcohol administration and abstinence periods. In particular, the modulatory effect of retigabine on the hippocampus may be a significant element of its mechanism of action in alcohol dependence therapy.
Seward, Cynthia A.; Barber, William H.
This article discusses fetal alcohol syndrome (FAS) including causes, common characteristics, secondary characteristics, prevention, and treatment. Economic implications are noted which suggest that treatment costs are 100 times the cost of prevention programs. (DB)
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.
Jovanovic, Mirjana; Antunovic, Marko
Alcohol continues to occupy a leading position in Europe as a popular substance of abuse. According to WHO sources together with cigarette smoking and obesity, alcohol is a major cause of preventable diseases. Harmful use of alcohol is one of the main factors contributing to premature deaths and disability and has a major impact on public health. The consequences of alcohol use on human health are enormous. Additionally, alcohol use can have harmful effects that do not directly affect person who consumes alcohol (e.g., fetal alcohol syndrome violations that are related to alcohol use, etc.). It is well known that the harmful effects and consequences of alcohol use (e.g., acute and chronic illness, injuries in fights, at the workplace, in traffic, violent behavior, and death) create a great burden for the economic development of society. Persons who have been diagnosed with alcoholism and currently drinking have a less chance to achieve a life insurance cover. On the contrary, recovering alcoholic with a significant abstinent period can get a good life insurance quote. The abstinence of a year or 2 is usually enough for a person to get an average price of life insurance. Furthermore, new consequent relapses could also be considered as potential aggravating factor to accomplish this kind of financial benefits. So far, the research (and interventions) focused on the effects on the population level, such as the increase in taxes, advertising bans, and the implementation of laws that prevent the use of alcohol in traffic. However, it seems that the problem may be viewed at the individual level. The models of the treatment should be designed according to the needs of the individual. These models should incorporate not only the reduction of alcohol intake but also the path to abstinence. The plan should take into account the different (individual) needs for treatment, with regard to the degree of alcohol dependence and health status and also include the needs of the
Jovanovic, Mirjana; Antunovic, Marko
Alcohol continues to occupy a leading position in Europe as a popular substance of abuse. According to WHO sources together with cigarette smoking and obesity, alcohol is a major cause of preventable diseases. Harmful use of alcohol is one of the main factors contributing to premature deaths and disability and has a major impact on public health. The consequences of alcohol use on human health are enormous. Additionally, alcohol use can have harmful effects that do not directly affect person who consumes alcohol (e.g., fetal alcohol syndrome violations that are related to alcohol use, etc.). It is well known that the harmful effects and consequences of alcohol use (e.g., acute and chronic illness, injuries in fights, at the workplace, in traffic, violent behavior, and death) create a great burden for the economic development of society. Persons who have been diagnosed with alcoholism and currently drinking have a less chance to achieve a life insurance cover. On the contrary, recovering alcoholic with a significant abstinent period can get a good life insurance quote. The abstinence of a year or 2 is usually enough for a person to get an average price of life insurance. Furthermore, new consequent relapses could also be considered as potential aggravating factor to accomplish this kind of financial benefits. So far, the research (and interventions) focused on the effects on the population level, such as the increase in taxes, advertising bans, and the implementation of laws that prevent the use of alcohol in traffic. However, it seems that the problem may be viewed at the individual level. The models of the treatment should be designed according to the needs of the individual. These models should incorporate not only the reduction of alcohol intake but also the path to abstinence. The plan should take into account the different (individual) needs for treatment, with regard to the degree of alcohol dependence and health status and also include the needs of the
Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K
Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol.
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
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.
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
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.
Walker, Brendan M
This article represents one of five contributions focusing on the topic "Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure" that were developed by awardees participating in the Young Investigator Award Symposium at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference in Volterra, Italy on May 3-6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms.
Alén, Francisco; Orio, Laura; Gorriti, Miguel Á; de Heras, Raquel Gómez; Ramírez-López, María Teresa; Pozo, Miguel Ángel; de Fonseca, Fernando Rodríguez
The use of antidepressants for alcoholism in humans has been a matter of controversy in recent years. Despite the existence of an important co-morbidity for depression and alcoholism, some studies suggest that the use of antidepressants could worsen the prognosis of alcoholism. However, there is a lack of studies in animal models exploring this phenomenon. In the present study, we show how the 15-d treatment with fluoxetine (10 mg/kg) or venlafaxine (50 mg/kg) affected alcohol deprivation effect (ADE) and subsequent alcohol consumption. Initially, fluoxetine reduced ADE and venlafaxine did not affect it. However, in the following days, both antidepressants increased alcohol consumption, an effect that was found to last at least 5 wk. Fluoxetine treatment was shown to cause a locomotor sensitized response to a challenge dose of amphetamine (0.5 mg/kg), indicating the presence of a supersensitive dopaminergic transmission. In summary, antidepressant treatment may increase alcohol consumption in rats after a period of alcohol deprivation and this could be related to alterations in the reward circuitry. This finding confirms in an animal model previous reports in humans that may limit the use of antidepressants for alcoholism.
JOHNSON, BANKOLE A.
The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)–approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored. PMID:17880925
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
Steffenhagen, R. A.
Reviews the history and theory of alcoholism and hypnosis and proposes a theoretical model of alcholism based on self-esteem. Suggets that hypnosis may be an effective tool in the treatment of alcoholism with cure as the goal, and calls for more consistency in theory and practice. (JAC)
McCrady, Barbara S.; Hay, William
The role of the spouse in both the etiology and the maintenance of alcoholism has been focussed on by theoreticians of various persuasions, including psychoanalytic, behavioral, sociological and family systems. These models, focussing on individual and interactional components of alcoholism, have generated a variety of treatment interventions…
Demmel, Ralf; Beck, Beate; Lammers, André
Cognitive processes related to client motivation are important mediators of alcoholism treatment outcome. The present study aimed to expand previous research on client motivation and treatment outcome by establishing the predictive utility of self-efficacy, alcohol expectancies, and readiness to change in a sample of alcohol-dependent inpatients (N = 83). Treatment outcome was assessed three months following discharge. According to self-reported alcohol use, 22 clients were classified as abstainers and 41 clients as relapsers. Twenty participants were lost to follow-up. Readiness to change and anticipated reinforcement from alcohol predicted abstinence at follow-up. Client motivation was unrelated to both frequency and quantity of alcohol use. In accordance with social learning theory, self-efficacy was inversely correlated with alcohol expectancies. The results of the present study suggest that once abstinence has been violated factors other than pretreatment motivation determine drinking behavior.
Shukla, Lekhansh; Kandasamy, Arun; Kesavan, Muralidharan; Benegal, Vivek
Benzodiazepine (BZD) dependence is a significant public health problem. Apart from the long-term tapering doses of BZD, no others drugs are available for the maintenance treatment of BZD dependence. Baclofen has been used in alcohol and other drug dependence as long-term anti-craving agent. Since alcohol and BZD act through the GABA receptor, we attempted to study the effect of Baclofen as maintenance treatment in a series of five cases with BZD dependence. PMID:25540541
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.
Thoma, Patrizia; Winter, Natalia; Juckel, Georg; Roser, Patrik
Impaired social cognition has been associated with interpersonal problems and with the development of and relapse into alcohol abuse. In the present study, self-reported trait empathy, decoding of complex mental states and cognitive and affective mental state reasoning were assessed in alcohol-dependent participants, and the association with executive function and psychopathological characteristics was investigated. Twenty recently detoxified alcohol-dependent patients and 20 matched healthy controls were assessed with an abbreviated German version of the interpersonal reactivity index, the revised reading the mind in the eyes test, the faux pas story test, the trail making test and the letter-number-sequencing test. Patients were impaired relative to controls with regard to mental state decoding on the eyes test and showed reduced faux pas detection and impaired mental state reasoning reflected by lower faux pas understanding and faux pas empathy scores. There were no group differences regarding self-reported trait empathy. Performance on the sociocognitive measures was related to executive functioning and the severity of depressive symptoms. Although self-report measures might not always reliably detect impairments of social cognition, behavioural measures suggest pronounced impairments of mental state decoding and mental state reasoning in association with alcohol dependence. Findings ought to be incorporated into current treatment strategies.
Large numbers of clients entering publicly-funded substance abuse treatment facilities cite problems with alcohol as one reason for seeking treatment. This report presents the results of a secondary analysis of the National Treatment Improvement Evaluation Study (NTIES) data set. It profiles the treatment experiences of three study groups that…
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.
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.
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
Fein, George; Smith, Stan; Greenstein, David
Background Disturbed gait and balance are among the most consistent sequelae of chronic alcoholism. However, although a majority of alcoholics have never sought treatment, most investigations showing ataxia in alcohol dependent individuals have relied on samples drawn from treated populations. In addition, few studies have addressed the associations of codependence on other drugs with alcoholic gait and balance disturbance. Methods The present study employed the Walk-a-line Ataxia Battery (Fregly et al. 1972) to assess gait and balance in treatment-naive, actively drinking alcohol dependent men and women (TNA; n = 69) who were dependent on alcohol only (ALC; n = 43), or who also had a lifetime drug dependence (ALC+DRG; n = 26; i.e., methamphetamine, cocaine, opiates, and/or marijuana), compared with non-substance abusing controls (NSAC; n = 74). We also examined associations between lifetime alcohol use and age with gait and balance measures. Results Our main findings were 1) no evidence of disturbed gait and balance in ALC vs. NSAC and 2) significantly disturbed gait and balance in ALC+DRG, relative to both NSAC and ALC, along with steeper age-associated decline in gait and balance performance in ALC vs. ALC+DRG. Conclusions Our results provide evidence consistent with previous studies that TNA (without a lifetime drug codependence) may represent a population that is different and less impaired (including in gait and balance) than treated alcoholics. Additionally, we provide evidence that ALC+DRG, with greater alcohol use and family drinking density than ALC, have an accelerated effect of age on gait and balance disturbance compared to both NSAC and ALC. The ALC+DRG group likely represents a subset of TNA with different characteristics than ALC. PMID:22390787
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.
Schuler, Megan S.; Puttaiah, Savitha; Mojtabai, Ramin; Crum, Rosa M.
Objective Low rates of alcohol treatment seeking has been shown to be associated with perceived barriers to treatment, yet heterogeneity in patterns of perceived barriers have not been explored. We used data from a population-based sample of adults with alcohol abuse and dependence to: describe latent classes of perceived barriers to seeking alcohol treatment and identify characteristics associated with class membership. Methods Data are from the National Epidemiologic Survey on Alcohol and Related Conditions (2001-02). Analyses were restricted to treatment-naive adults with alcohol abuse or dependence with a perceived treatment need (N=1,053). Latent class analysis was performed to identify subgroups with respect to barriers to treatment; latent class regression was performed to identify variables associated with each subgroup. Results Two subgroups emerged: the low barriers class (87%), characterized primarily by attitudinal barriers, and the high barriers class (13%), characterized by significant attitudinal, financial, stigma and readiness for change barriers. In both classes, the most frequently endorsed barrier was the attitudinal belief that they should be “strong enough” to handle it on their own. Univariate analyses showed strong associations between membership in the high barriers class and comorbid psychiatric disorders, alcohol dependence (relative to abuse), and family history of alcohol problems; multivariate analyses found significant associations with lifetime anxiety disorder and education level. Conclusions Findings show that attitudinal barriers are most prevalent, and highlight the existence of a notable subgroup with multiple barriers, including financial and stigma-related barriers, who may require additional resources and support in order to enter treatment. PMID:26234326
Bartha, Robert; Davis, Tom
Discusses how a holistic and wellness philosophy is a viable alternative in the treatment of alcoholism. Describes five major dimensions of high-level wellness: nutritional awareness, physical fitness, stress management, environmental sensitivity, and self-responsibility. (RC)
Heyes, Cathy M.; Schofield, Toni; Gribble, Robert; Day, Carolyn A.; Haber, Paul S.
Background Liver transplantation (LT) is the optimum treatment for patients with end-stage alcoholic liver disease (ALD). However, despite a recognized risk of relapse to harmful drinking, ALD transplant patients are reluctant to use speciality alcohol treatment to support their abstinence, even when offered within the LT context. This study aimed to understand and identify factors contributing to alcohol treatment reluctance by ALD patients undergoing transplantation. Methods We conducted an in-depth qualitative study of ALD transplant patients. Minimally structured face-to-face interviews explored participants' alcohol-related experiences and their reasons for not using alcohol treatment during the course of their transplantation. Thematic analysis was used to analyze and interpret interview data to understand treatment reluctance based on participants' experiences. Results Five major themes were identified among 3 subgroups of patients (pretransplant and posttransplant abstainers and posttransplant relapsers): (i) the “contract” of mandatory abstinence, (ii) the “gap in the program” involving the lack of candour between patient and staff about alcohol-related matters and the lack of addiction services, (iii) a preference by participants to self-manage their alcohol use disorder, (iv) social support as a facilitator of abstinence and the risk of relapse when social support is diminished, and (v) the fear of stigmatization. Each of these factors were dynamically interrelated and differed slightly for each subgroup. Conclusions The LT services may benefit from the inclusion of integrated specialist addiction services in their model of care. Such an approach may enhance the acceptability of alcohol treatment and reduce the risk of relapse among ALD transplant participants, especially for those whose social supports have diminished. PMID:27795986
An extensive literature supports the role of dopamine in the development and maintenance of alcohol dependence. Yet the organization of brain dopamine is complex, with multiple dopamine receptor subtypes and distinct effects on reinforcement, craving, motivation and behavior. Several modestly effective pharmacological treatments for alcoholism, including naltrexone, baclofen and ondansetron, affect dopaminergic systems indirectly. Direct dopamine antagonists, including tiapride, quetiapine, ondansetron and clozapine have been shown to be somewhat effective in reducing alcohol consumption in controlled clinical trials. The partial dopamine agonist, aripiprazole has shown mixed efficacy. Dopaminergic medications can have significant side effects. A better understanding of how dopamine affects the various aspects of addictive behavior may lead to more effective medications.
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…
McCarty, Dennis; Gustafson, David; Capoccia, Victor A.; Cotter, Frances
The Network for the Improvement of Addiction Treatment (NIATx) teaches alcohol and drug treatment programs to apply process improvement strategies and make organizational changes that improve quality of care. Participating programs reduce days to admission, increase retention in care and spread the application of process improvement within their treatment centers. More generally, NIATx provides a framework for addressing the Institute of Medicine’s six dimensions of quality care (i.e., safe, effective, patient-centered, efficient, timely and equitable) in treatments for alcohol, drug and mental health disorders. NIATx and its extensions illustrate how the behavioral health field can respond to the demand for higher quality treatment services. PMID:18259871
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.
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.
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.
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
Caputo, Fabio; Vignoli, Teo; Leggio, Lorenzo; Addolorato, Giovanni; Zoli, Giorgio; Bernardi, Mauro
Alcohol-use-disorders (AUDs) afflict 1–3% of elderly subjects. The CAGE, SMAST-G, and AUDIT are the most common and validated questionnaires used to identify AUDs in the elderly, and some laboratory markers of alcohol abuse (AST, GGT, MCV, and CDT) may also be helpful. In particular, the sensitivity of MCV or GGT in detecting alcohol misuse is higher in older than in younger populations. The incidence of medical and neurological complications during alcohol withdrawal syndrome in elderly alcoholics is higher than in younger alcoholics. Chronic alcohol abuse is associated with tissue damage to several organs. Namely, an increased level of blood pressure is more frequent in the elderly than in younger adults, and a greater vulnerability to the onset of alcoholic liver disease, and an increasing risk of breast cancer in menopausal women have been described. In addition, the prevalence of dementia in elderly alcoholics is almost 5 times higher than in non-alcoholic elderly individuals, approximately 25% of elderly patients with dementia also present AUDs, and almost 20% of individuals aged 65 and over with a diagnosis of depression have a co-occurring AUD. Moreover, prevention of drinking relapse in older alcoholics is, in some cases, better than in younger patients; indeed, more than 20% of treated elderly alcohol-dependent patients remain abstinent after four years. Considering that the incidence of AUDs in the elderly is fairly high, and AUDs in the elderly are still underestimated, more studies in the fields of epidemiology, prevention and pharmacological and psychotherapeutic treatment of AUDs in the elderly are warranted. PMID:22575256
Chakravorty, Subhajit; Chaudhary, Ninad S; Brower, Kirk J
Sleep-related complaints are widely prevalent in those with alcohol dependence (AD). AD is associated not only with insomnia, but also with multiple sleep-related disorders as a growing body of literature has demonstrated. This article will review the various aspects of insomnia associated with AD. In addition, the association of AD with other sleep-related disorders will be briefly reviewed. The association of AD with insomnia is bidirectional in nature. The etiopathogenesis of insomnia has demonstrated multiple associations and is an active focus of research. Treatment with cognitive behavioral therapy for insomnia is showing promise as an optimal intervention. In addition, AD may be associated with circadian abnormalities, short sleep duration, obstructive sleep apnea, and sleep-related movement disorder. The burgeoning knowledge on insomnia associated with moderate-to-severe alcohol use disorder has expanded our understanding of its underlying neurobiology, clinical features, and treatment options.
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
Hartung, Daniel M; McCarty, Dennis; Fu, Rongwei; Wiest, Katharina; Chalk, Mady; Gastfriend, David R
Through improved adherence, once-monthly injectable extended-release naltrexone (XR-NTX) may provide an advantage over other oral agents approved for alcohol and opioid dependence treatment. The objective of this study was to evaluate cost and utilization outcomes between XR-NTX and other pharmacotherapies for treatment of alcohol and opioid dependence. Published studies were identified through comprehensive search of two electronic databases. Studies were included if they compared XR-NTX to other approved medicines and reported economic and healthcare utilization outcomes in patients with opioid or alcohol dependence. We identified five observational studies comparing 1,565 patients using XR-NTX to other therapies over 6 months. Alcohol dependent XR-NTX patients had longer medication refill persistence versus acamprosate and oral naltrexone. Healthcare utilization and costs was generally lower or as low for XR-NTX-treated patients relative to other alcohol dependence agents. Opioid dependent XR-NTX patients had lower inpatient substance abuse-related utilization versus other agents and $8170 lower total cost versus methadone.
Jiménez-Murcia, Susana; Del Pino-Gutiérrez, Amparo; Fernández-Aranda, Fernando; Granero, Roser; Hakänsson, Anders; Tárrega, Salomé; Valdepérez, Ana; Aymamí, Neus; Gómez-Peña, Mónica; Moragas, Laura; Baño, Marta; Sauvaget, Anne; Romeu, Maria; Steward, Trevor; Menchón, José M.
Aims: The primary objective of this study was to analyze the association between alcohol consumption and short-term response to treatment (post intervention) in male patients with gambling disorder enrolled in a group cognitive behavioral therapy (CBT) program. Methods: The sample consisted of 111 male individuals with a diagnosis of Gambling Disorder, with a mean age of 45 years (SD = 12.2). All participants were evaluated by a comprehensive assessment battery and assigned to CBT groups of 10–14 patients attending 16 weekly outpatient sessions lasting 90 min each. Results: The highest mean pre- and post-therapy differences were recorded for the alcohol risk/dependence group on the obsessive/compulsive and anxiety dimensions of the SCL-90-R. As regards the presence of relapses and dropouts over the course of the CBT sessions, the results show a significant association with moderate effect size: patients with risk consumption or alcohol dependence were more likely to present poor treatment outcomes. Conclusions: Alcohol abuse was frequent in GD, especially in patients with low family income and high accumulated debts. High levels of somatization and high overall psychopathology (measured by the SCL-90-R) were associated with increased risk of alcohol abuse. Alcohol abuse was also associated with poor response to treatment. PMID:27065113
Discusses steps that professional sports organizations are taking to identify athletes with drinking problems and help them reach full recovery. Many teams are taking preventive steps such as offering information about the dangers of alcohol, issuing new policies dealing with players' rights and providing for employee assistance programs. (SM)
Kuerbis, Alexis; Morgenstern, Jon; Hail, Lisa
Understanding for whom moderated drinking is a viable, achievable, and sustainable goal among those with a range of alcohol use disorders (AUD) remains an important public health question. Despite common acceptance as severe risk factors, there is little empirical evidence to conclude whether co-occurring mental health disorders or drug dependence contribute to an individual’s inability to successfully moderate his drinking. Utilizing secondary data analysis, the purpose of this study was to identify predictors of moderation among both treatment seeking and non-treatment seeking, primarily alcohol dependent, problem drinking men who have sex with men (MSM), with an emphasis on the high risk factors psychiatric comorbidity and drug dependence. Problem drinkers (N=187) were assessed, provided feedback about their drinking, given the option to receive brief AUD treatment or change their drinking on their own, and then followed for 15 months. Findings revealed that neither psychiatric comorbidity or drug dependence predicted ability to achieve moderation when controlling for alcohol dependence severity. Those who were younger, more highly educated, and had more mild alcohol dependence were more likely to achieve moderated drinking. Impact of treatment on predictors is explored. Limitations of this study and arenas for future research are discussed. PMID:22201219
Witkiewitz, Katie; Villarroel, Nadia Aracelliz
Clinical research has found a strong association between negative affect and returning to alcohol use after a period of abstinence. Yet little is known about the probability of a lapse given a particular level of negative affect or whether there is a reciprocal relationship between negative affect and alcohol use across time. The goal of the current study was to examine the association between negative affect and drinking behavior in the 1st year following alcohol treatment. The authors applied an associative latent transition analysis to the Project MATCH outpatient data (n = 952) and then replicated the model in the Project MATCH aftercare data (n = 774). Changes in drinking following treatment were significantly associated with current and prior changes in negative affect, and changes in negative affect were related to prior changes in drinking (effect size range = 0.13-0.33). The results supported the hypothesis that negative affect and alcohol lapses are dynamically linked and suggest that targeting the relationship between negative affect and alcohol use could greatly decrease the probability of lapses and improve alcohol treatment outcomes.
Adamson, Simon J; Sellman, J Douglas; Foulds, James A; Frampton, Christopher M A; Deering, Daryle; Dunn, Alistair; Berks, John; Nixon, Lee; Cape, Gavin
Despite the high rate of co-occurrence of major depression and alcohol dependence, the role of pharmacotherapy in their treatment remains unclear. In the new era of naltrexone for alcohol dependence, it is notable that only 1 study to date has examined the efficacy of antidepressant medication prescribed concurrently with naltrexone. We aimed to determine whether combining naltrexone with citalopram produced better treatment outcomes than naltrexone alone in patients with co-occurring alcohol dependence and depression, and to investigate whether either sex or depression type (independent or substance-induced depression) moderated treatment response. Participants were 138 depressed alcohol-dependent adults who were not required to be abstinent at the commencement of the trial. They were randomized to 12 weeks of citalopram or placebo, plus naltrexone and clinical case management. Treatment was well attended, and medications were reasonably well tolerated with high adherence rates. Substantial improvements in both mood and drinking occurred in both groups, with no significant differences between groups on any of the mood or drinking outcome measures, whether or not other variables were controlled for. No interaction effect was found for independent/substance-induced depression status, whereas there was a marginal effect found by sex, with greater improvement in 1 drinking outcome measure (percent days abstinent) in women taking citalopram. These findings suggest that citalopram is not a clinically useful addition to naltrexone and clinical case management in this treatment population. Independent/substance-induced depression status did not predict treatment response. Findings for sex were equivocal.
Zarkin, Gary A.; Bray, Jeremy W.; Aldridge, Arnie; Mitra, Debanjali; Couper, David J.; Cisler, Ron A.
Context The COMBINE clinical trial recently evaluated the efficacy of medications, behavioral therapies, and their combinations for the outpatient treatment of alcohol dependence. The costs and cost-effectiveness of these combinations are unknown and of interest to clinicians and policy makers. Objective To evaluate the costs and cost-effectiveness of the COMBINE interventions at the end of 16 weeks of treatment. Design, Setting, and Participants A prospective cost and cost-effectiveness study of patients in COMBINE, a randomized controlled clinical trial (RCT) involving 1383 patients with diagnoses of primary alcohol dependence across 11 US clinical sites. Interventions Nine treatment arms, with 4 arms receiving medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or placebo; 4 arms receiving the same options as above but delivered with combined behavioral intervention (CBI); and 1 arm receiving CBI only. Main Outcomes Measures Incremental cost per percentage point increase in percent days abstinent (PDA), incremental cost per patient of avoiding heavy drinking, and incremental cost per patient of achieving a good clinical outcome. Results Based on the mean values of cost and effectiveness, 3 interventions are cost-effective options relative to the other interventions for all three outcomes: medical management (MM) with placebo ($409 cost per patient), MM + naltrexone ($671 cost per patient), and MM + naltrexone + acamprosate ($1003 cost per patient). Conclusions This is only the second prospective RCT-designed cost-effectiveness study that has been performed for the treatment of alcohol dependence. Focusing just on effectiveness, MM + naltrexone + acamprosate is not significantly better than MM + naltrexone. However, looking at cost and effectiveness, MM + naltrexone + acamprosate may be a cost-effective choice, depending on whether the cost of the incremental increase in effectiveness is worth it to the decision maker. PMID
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
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.
Lisek, Victor J.; Coll, Kenneth M.
Investigated personality and family-of-origin differences in male and female alcoholics. Results, based on medical records (N=204) of patients admitted to a residential chemical dependency center indicate that, regarding personality disturbances, men were healthier than women. More women had psychiatric treatment, were married to an alcoholic, or…
Jhugroo, Anil; Ellayah, Darmen; Norman, Amanda; Hulse, Gary
Although substitution therapy with opiate agonist treatments such as methadone and buprenorphine has resulted in a reduction of illicit drug use related harm, such treatment has also resulted in severe problems in some countries where opioid-dependent individuals now inject illicitly sold buprenorphine or buprenorphine-naloxone instead of heroin. There is no approved treatment for buprenorphine dependence. Naltrexone is an opioid antagonist which has been used for the treatment of both alcohol and opioid dependencies. Although both buprenorphine and heroin resemble each other concerning their effects, buprenorphine has a higher affinity to opioid receptors than heroin. Therefore, it is not known if naltrexone can block the psychoactive effects of buprenorphine as it does for heroin. This paper presents observational case series data on the use of a sustained-release naltrexone implant for the treatment of buprenorphine dependence. To the authors' knowledge this is the first use of sustained-release naltrexone for this indication.
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
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
Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.
Few studies examining alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of post-treatment alcohol outcomes. The present study uses a multivariate approach based on a theoretical model to study the relationship between psychosocial factors and post treatment-initiation alcohol use. Predictors of alcohol use outcomes were examined in 278 individuals diagnosed with a current DSM-IV schizophrenia-spectrum or bipolar disorder and an alcohol use disorder (AUD). At 6-months follow-up after initiating treatment, 144 of 228 available participants (63%) had good clinical outcomes. The results of structural equation modeling indicated that type of pretreatment residential setting was directly related to treatment with participants living in supervised settings (41%) reporting significantly more days of treatment (β = .34, p < .001). In addition, participants with more psychiatric symptoms, assessed by the Brief Symptom Inventory and Structured Clinical Interview for the Positive and Negative Syndrome Scale, reported significantly fewer treatment days (β = −.20, p < .001). Number of days participants attended treatment was indirectly associated with alcohol use outcomes and was mediated by use of alcohol coping skills, such that more frequent use of alcohol-specific coping skills was associated with less post treatment-initiation alcohol use (β = −.34, p < .001). This study emphasizes the favorable prognosis for alcohol outcomes among treated individuals with a SMI and AUD and the importance of psychosocial interventions, particularly those that result in better alcohol-specific coping skills. PMID:19968390
Wolitzky-Taylor, Kate; Brown, Lily A.; Roy-Byrne, Peter; Sherbourne, Cathy; Stein, Murray B.; Sullivan, Greer; Bystritsky, Alexander; Craske, Michelle G.
Objective The presence of anxiety disorders is associated with poorer alcohol use disorder treatment outcomes, but little is known about the impact of alcohol use problems on anxiety disorder treatment outcomes despite their high comorbidity. The current study examined the impact of alcohol use symptom severity on anxiety disorder treatment outcomes in a multi-site primary care effectiveness study of anxiety disorder treatment. Method Data came from the Coordinated Anxiety Learning and Management (CALM) effectiveness trial. Participants (N = 1004) were randomized to an evidence-based anxiety intervention (including cognitive behavioral therapy and medications) or usual care in primary care. Participants completed measures of alcohol use, anxiety, and depression a baseline, 6-mo, 12-mo, and 18-mo follow-up periods. Patients with alcohol dependence were excluded. Results There were no significant moderating (Treatment Group x Alcohol Use Severity) interactions. The majority of analyses revealed no predictive effects of alcohol use severity on outcome; however, alcohol problems at baseline were associated with somewhat higher anxiety and depression symptoms at the 18-mo follow-up. Conclusions These data indicate that patients with alcohol problems in primary care can be effectively treated for anxiety disorders. Baseline alcohol problems were associated with some poorer long-term outcomes, but this was evident across CALM and usual care. These findings provide preliminary evidence that there may be no need to postpone treatment of anxiety disorders until alcohol problems are addressed, at least among those who have mild to moderate alcohol problems. Replication with more severe alcohol use disorders is needed. PMID:25615523
Zhu, Xi; Cortes, Carlos R; Mathur, Karan; Tomasi, Dardo; Momenan, Reza
Alcohol dependence is characterized by impulsiveness toward consumption despite negative consequences. Although neuro-imaging studies have implicated some regions underlying this disorder, there is little information regarding its large-scale connectivity pattern. This study investigated the within- and between-network functional connectivity (FC) in alcohol dependence and examined its relationship with clinical impulsivity measures. Using probabilistic independent component analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 alcohol-dependent (AD) and 26 healthy control (HC) participants, we compared the within- and between-network FC between AD and HC. Then, the relationship between FC and impulsiveness as measured by the Barratt Impulsiveness Scale (BIS-11), the UPPS-P Impulsive Scale and the delay discounting task (DDT), was explored. Compared with HC, AD exhibited increased within-network FC in salience (SN), default mode (DMN), orbitofrontal cortex (OFCN), left executive control (LECN) and amygdala-striatum (ASN) networks. Increased between-network FC was found among LECN, ASN and SN. Between-network FC correlations were significantly negative between Negative-Urgency and OFCN pairs with right executive control network (RECN), anterior DMN (a-DMN) and posterior DMN (p-DMN) in AD. DDT was significantly correlated with the between-network FC among the LECN, a-DMN and SN in AD. These findings add evidence to the concept of altered within-network FC and also highlight the role of between-network FC in the pathophysiology of AD. Additionally, this study suggests differential neurobiological bases for different clinical measures of impulsivity that may be used as a systems-level biomarker for alcohol dependence severity and treatment efficacy.
MANTHOU, EIRINI; GEORGAKOULI, KALLIOPI; FATOUROS, IOANNIS G.; GIANOULAKIS, CHRISTINA; THEODORAKIS, YANNIS; JAMURTAS, ATHANASIOS Z.
Excessive alcohol use can cause harmful effects on the human body, which are associated with serious health problems, and it can also lead to the development of alcohol use disorders (AUDs). There is certain evidence that physical exercise positively affects excessive alcohol use and the associated problems by leading to reduced alcohol intake. A literature search was conducted using the databases PubMed, Medline and Web of Science. The search terms used as keywords were: Addiction, abuse, alcohol use disorders, exercise training, β-endorphin, opioids, brain, ethanol and alcohol. The current study presents the studies that reported on the use of exercise in the treatment of AUDs between 1970 and 2015. The potential psychological and physiological mechanisms that contribute to the action of exercise were also reviewed, highlighting the role of β-endorphin and the hypothalamic-pituitary-adrenal axis in AUDs and the possible association among physical activity, the endogenous opioid system and the desire for alcohol. Only 11 studies were identified that refer to the effect of exercise on alcohol consumption and/or the associated outcomes. Six of those studies concluded that exercise may have a positive impact towards alcohol consumption, abstinence rates or the urge to drink. One of those studies also indicated that a bout of exercise affects the endogenous opioids, which may be associated with the urge to drink. Another 3 studies indicated that responses to acute exercise in individuals with AUDs are different compared to those in healthy ones. Generally, despite limited research data and often contradictory results, there is certain early promising evidence for the role of exercise as an adjunctive tool in the treatment of AUDs. Physiological and biochemical parameters that would confirm that exercise is safe for individuals with AUDs should be examined in future studies. PMID:27123244
Grant, Sean; Watkins, Katherine E.; Bogart, Andy; Paddock, Susan M.; Hepner, Kimberly A.
Background This study assessed patient-reported alcohol treatment offers by healthcare providers following routine annual screening for alcohol use in primary care. Methods A telephone interview within 30 days of the annual screen assessed demographics, alcohol and other drug use, mental health symptoms, and offers of formal treatment for alcohol by a VA healthcare provider. We included male patients (n = 349) at high-risk for an alcohol use disorder (AUD) who had not received alcohol treatment in the past three months. We assessed self-reported receipt of any offers of formal treatment for alcohol, and associations of offer of formal treatment for alcohol with demographic and clinical variables. Results 145 (41.5%) patients reported an offer of at least one type of formal treatment for alcohol. More severe alcohol misuse (OR 1.07, 95% CI 1.03 to 1.11) and younger age (OR 0.97, 95% CI 0.95 to 0.99) were associated with reporting an offer of formal treatment. Discussion Most primary care patients at high-risk for an AUD were not offered treatment following an annual screening. Our results highlight the importance of training primary care providers in what constitutes appropriate medical treatment for this population and the most effective ways of making a treatment offer. PMID:28076250
Resnick, Sheilagh M.; Griffiths, Mark D.
The objective of the study was to qualitatively evaluate the managerial and organisational issues associated with service quality in a privately funded alcohol treatment centre in the UK. Two different groups of participants at a private treatment clinic were interviewed. The first group comprised 25 of its patients. The second group comprised 15…
Epler, Amee J.; Sher, Kenneth J.; Loomis, Tiffany B.; O'Malley, Stephanie S.
Objective: Heavy episodic drinking remains a significant problem on college campuses. Although most interventions for college students are behavioral, pharmacological treatments, such as naltrexone, could provide additional options. Participants: The authors evaluated receptivity to various alcohol treatment options in a general population of…
Soyka, Michael; Mutschler, Jochen
Substance use disorders are common, but only a small minority of patients receive adequate treatment. Although psychosocial therapies are effective, relapse is common. This review focusses on novel pharmacological and other treatments for patients with alcohol, opioid, or cocaine use disorders who do not respond to conventional treatments. Disulfiram, acamprosate, and the opioid antagonist naltrexone have been approved for the treatment of alcoholism. A novel, "as needed" approach is the use of the mu-opioid antagonist and partial kappa agonist nalmefene to reduce alcohol consumption. Other novel pharmacological approaches include the GABA-B receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the partial nicotine receptor agonist varenicline, and other drugs. For opioid dependence, opioid agonist therapy with methadone or buprenorphine is the first-line treatment option. Other options include oral or depot naltrexone, morphine sulfate, depot or implant formulations, and heroin (diacetylmorphine) in treatment-refractory patients. To date, no pharmacological treatment has been approved for cocaine addiction; however, 3 potential pharmacological treatments are being studied, disulfiram, methylphenidate, and modafinil. Pharmacogenetic approaches may help to optimize treatment response in otherwise treatment-refractory patients and to identify which patients are more likely to respond to treatment, and neuromodulation techniques such as repeated transcranial magnetic stimulation and deep brain stimulation also may play a role in the treatment of substance use disorders. Although no magic bullet is in sight for treatment-refractory patients, some novel medications and brain stimulation techniques have the potential to enrich treatment options at least for some patients.
This paper describes the factor structure of the concept of alcohol dependence as proposed in two psychiatric classifications, the DSM-III-R and the ICD-10. Subjects are 219 men and 162 women who were interviewed while in treatment for alcohol-related problems in nine different treatment programs in Contra Costa county, California. Tests of hypotheses supporting a single factor and a dual factor structure of dependence were rejected by confirmatory factor analysis. Results from exploratory factor analysis show a four factor structure for the concept of dependence in DSM-III-R. For ICD-10 there is a four factor solution among men and a three factor solution among women. The item composition of these factors vary by gender and across the two classifications. However, there is good agreement between dependence as measured by DSM-III-R and ICD-10 criteria. Since work on DSM-IV is now under way, the present research aims to provide some empirical base for how future changes should be made.
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
Byrne, Shannon A.; Petry, Nancy M.
Concurrent alcohol dependence (AD) among polysubstance abusers has been associated with negative consequences, although it may not necessarily lead to poor treatment outcomes. One of the most efficacious treatments for cocaine abuse is contingency management (CM), but little research has explored the impact of AD on abstinence outcomes, particularly among patients in methadone maintenance. Using data from three trials of CM for cocaine use, we compared baseline characteristics and post-treatment and follow-up cocaine outcomes between methadone maintained, cocaine dependent patients (N=193) with and without concurrent AD, randomized to standard care (SC) with or without CM. Patients with and without concurrent AD had similar baseline characteristics, with the exception that AD patients reported more alcohol use. AD patients achieved longer durations of cocaine abstinence and were more likely to submit a cocaine negative sample at follow-up than non-AD patients. Patients randomized to CM achieved better outcomes than those randomized to SC, but there was no interaction between treatment condition and AD status. These findings suggest that cocaine using methadone patients with AD achieve greater cocaine abstinence than their non-AD counterparts and should not be necessarily viewed as more difficult to treat. PMID:21463068
Dupouy, Julie; Fournier, Jean-Pascal; Jouanjus, Émilie; Palmaro, Aurore; Poutrain, Jean-Christophe; Oustric, Stéphane; Lapeyre-Mestre, Maryse
Recently, baclofen has been widely promoted for treatment of alcohol dependence in France. Our aim was firstly to describe the incidence of patients newly treated with baclofen for alcohol dependence in France from 2007 to 2011, and secondly to describe baclofen prescription patterns and prescribers. A retrospective cohort study of patients newly treated with baclofen was conducted using the "Echantillon Généraliste des Bénéficiaires" database (EGB). Patients with a first dispensation of baclofen between 01/01/2007 and 31/12/2011, followed by a second in the next 120 days, were included. Patients were considered treated with baclofen for neurological conditions if at least one of the following conditions was found to be true: (1) presence of a neurological condition for which baclofen could be prescribed, (2) dispensation of dantrolene, another anti-spastic drug, or (3) hospitalization for a neurological condition for which baclofen could be prescribed. We assumed that all the remaining patients were treated for alcohol dependence. During the 5-year period, 676 patients were incident users. While the annual incidence rate of patients newly treated with baclofen for neurological conditions remained stable, the annual incidence rate of patients newly treated with baclofen for alcohol dependence increased by a factor of 2.9 between 2007 (0.09/1000 person-years) and 2011 (0.26/1000 person-years). In the alcohol dependence group, median duration of baclofen treatment was 143.5 [74.0; 377.0] days; median daily dose was 24.4 [14.8; 39.5] mg. This study demonstrated the rapidly increasing use of baclofen in France for treatment of alcohol dependence.
Avila Escribano, J J; Pérez Madruga, A; Rodríguez Treceño, M
This survey analyzes the evolution of one sample of alcoholic patients two years after finishing treatment. Its target is to determine the percentage of patients that remain abstinent, their rate of retention, and what factors can have an influence on abstinence. In 1990, 72 alcoholic patients were treated in the Alcoholism Unit, who make up our study sample. The average age was 37.9 +/- 11.47 years old; 77.8% were diagnosed as being Alcohol-dependents and 22.2% as Alcohol-abusers; 19.4% dropped out the treatment early. In 1992 our sample of study was 53 patients (2 died and 17 refused to participate), of whom 77.7% were abstinent and 28.3% continued ingesting alcohol; the average abstinence was 22.92 +/- 8.73 months. An important finding of this study was that the diagnosis, sex, and treatment with aversives had not an influence on abstinence; however the percentage of abstinent patients in those who had attended Therapeutic Discussion Groups was significantly higher than in those who had not.
Schneider, Brooke C; Moritz, Steffen; Hottenrott, Birgit; Reimer, Jens; Andreou, Christina; Jelinek, Lena
Association Splitting, a novel cognitive intervention, was tested in patients with alcohol dependence as an add-on intervention in an initial randomized controlled trial. Preliminary support for Association Splitting has been found in patients with obsessive-compulsive disorder, as well as in an online pilot study of patients with alcohol use disorders. The present variant sought to reduce craving by strengthening neutral associations with alcohol-related stimuli, thus, altering cognitive networks. Eighty-four inpatients with verified diagnoses of alcohol dependence, who were currently undergoing inpatient treatment, were randomly assigned to Association Splitting or Exercise Therapy. Craving was measured at baseline, 4-week follow-up, and six months later with the Obsessive-Compulsive Drinking Scale (primary outcome) and the Alcohol Craving Questionnaire. There was no advantage for Association Splitting after three treatment sessions relative to Exercise Therapy. Among Association Splitting participants, 51.9% endorsed a subjective decline in craving and 88.9% indicated that they would use Association Splitting in the future. Despite high acceptance, an additional benefit of Association Splitting beyond standard inpatient treatment was not found. Given that participants were concurrently undergoing inpatient treatment and Association Splitting has previously shown moderate effects, modification of the study design may improve the potential to detect significant effects in future trials.
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
McCrady, Barbara S.; Epstein, Elizabeth E.; Kahler, Christopher W.
Ninety men with alcohol problems and their female partners were randomly assigned to 1 of 3 outpatient conjoint treatments: alcohol behavioral couples therapy (ABCT), ABCT with relapse prevention techniques (RP/ABCT), or ABCT with interventions encouraging Alcoholics Anonymous (AA) involvement (AA/ABCT). Couples were followed for 18 months after…
Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.
Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of…
Awan, Saima; Samokhvalov, Andriy V; Aleem, Nadia; Hendershot, Christian S; Irving, Julie Anne; Kalvik, Anne; Lefebvre, Lisa; Le Foll, Bernard; Quilty, Lena; Voore, Peter
Integrated care pathways (ICPs) provide an approach for delivering evidence-based treatment in a hospital setting. This column describes the development and pilot implementation in a clinical setting of an ICP for patients with concurrent major depressive disorder and alcohol dependence at the Centre for Addiction and Mental Health (CAMH), an academic tertiary care hospital, in Toronto, Canada. The ICP methodology includes evidence reviews, knowledge translation, process reengineering, and change management. Pilot results indicate high patient satisfaction, evidence of symptom improvement, and excellent retention.
Heilig, Markus; Goldman, David; Berrettini, Wade; O’Brien, Charles P.
Addictive disorders are partly heritable, chronic, relapsing conditions that account for a tremendous disease burden. Currently available addiction pharmacotherapies are only moderately successful, continue to be viewed with considerable scepticism outside the scientific community and have not become widely adopted as treatments. More effective medical treatments are needed to transform addiction treatment and address currently unmet medical needs. Emerging evidence from alcoholism research suggests that no single advance can be expected to fundamentally change treatment outcomes. Rather, studies of opioid, corticotropin-releasing factor, GABA and serotonin systems suggest that incremental advances in treatment outcomes will result from an improved understanding of the genetic heterogeneity among patients with alcohol addiction, and the development of personalized treatments. PMID:22011682
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.
Agabio, Roberta; Colombo, Giancarlo
The present paper summarizes the preclinical and clinical studies conducted to define the “anti-alcohol” pharmacological profile of the prototypic GABAB receptor agonist, baclofen, and its therapeutic potential for treatment of alcohol use disorder (AUD). Numerous studies have reported baclofen-induced suppression of alcohol drinking (including relapse- and binge-like drinking) and alcohol reinforcing, motivational, stimulating, and rewarding properties in rodents and monkeys. The majority of clinical surveys conducted to date—including case reports, retrospective chart reviews, and randomized placebo-controlled studies—suggest the ability of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. The recent identification of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABAB receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABAB receptor reproduce several “anti-alcohol” effects of baclofen and display a higher therapeutic index (with larger separation—in terms of doses—between “anti-alcohol” effects and sedation). PMID:24936171
Goodwani, Sunil; Saternos, Hannah; Alasmari, Fawaz; Sari, Youssef
Emerging evidence indicates that dysfunctional glutamate neurotransmission is critical in the initiation and development of alcohol and drug dependence. Alcohol consumption induced downregulation of glutamate transporter 1 (GLT-1) as reported in previous studies from our laboratory. Glutamate is the major excitatory neurotransmitter in the brain, which acts via interactions with several glutamate receptors. Alcohol consumption interferes with the glutamatergic signal transmission by altering the functions of these receptors. Among the glutamate receptors involved in alcohol-drinking behavior are the metabotropic receptors such as mGluR1/5, mGluR2/3, and mGluR7, as well as the ionotropic receptors, NMDA and AMPA. Preclinical studies using agonists and antagonists implicate these glutamatergic receptors in the development of alcohol use disorder (AUD). Therefore, the purpose of this review is to discuss the neurocircuitry involving glutamate transmission in animals exposed to alcohol and further outline the role of metabotropic and ionotropic receptors in the regulation of alcohol-drinking behavior. This review provides ample information about the potential therapeutic role of glutamatergic receptors for the treatment of AUD.
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.
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…
Han, Doug Hyun; Kim, Sun Mi; Choi, Jung Eun; Min, Kyung Joon; Renshaw, Perry F.
The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits. We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone. Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups. At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated. During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups. In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23.3±8.4 to 14.3±4.9, compared with those of the escitalopram group of from 21.6±8.4 to 19.3±7.1 (F=13.1, p<0.01). The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group. The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol. These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder. PMID:23325372
Han, Doug Hyun; Kim, Sun Mi; Choi, Jung Eun; Min, Kyung Joon; Renshaw, Perry F
The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits. We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone. Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups. At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated. During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups. In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23.3±8.4 to 14.3±4.9, compared with those of the escitalopram group of from 21.6±8.4 to 19.3±7.1 (F=13.1, p<0.01). The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group. The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol. These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder.
Härtel, Roland; Limmer, Uwe; Schiller, Martin; Wolfersdorf, Manfred
OBJECTIVE: The study aimed at comparing burnout in staff members at residential drug and alcohol detoxification wards with and without teamsupervision. METHOD: 4 times in a period of 18 month all staff members (n = 44) were assessed for burnout using a german version (Checkliste Burnoutmerkmale) of the Maslach Burnout Inventory (MBI, Maslach u. Jackson 1986) to asses the severity and the CBE (Checkliste Burnoutentstehungsmerkmale) for associated burnout risc-factors. RESULT: There was no statistical differences between the mean scores of the 3 different wards due to extreme SDs. The interpersonal differences among staff on the 4 occasions were remarkably. On repeated measurements the intraindividual changes were high. Higher scores were correlated with high workload (seen as frequent admissions). CONCLUSION: Work-related variables (admissions) turned out to be of more importance than supervision in times of chronic staff-shortage.
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…
Fernández-Solà, Joaquim; Planavila Porta, Ana
High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use. PMID:27690014
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
Cannady, Reginald; McGonigal, Justin T; Newsom, Ryan J; Woodward, John J; Mulholland, Patrick J; Gass, Justin T
Identifying novel treatments that facilitate extinction learning could enhance cue-exposure therapy and reduce high relapse rates in alcoholics. Activation of mGlu5 receptors in the infralimbic prefrontal cortex (IL-PFC) facilitates learning during extinction of cue-conditioned alcohol-seeking behavior. Small-conductance calcium-activated potassium (KCa2) channels have also been implicated in extinction learning of fear memories, and mGlu5 receptor activation can reduce KCa2 channel function. Using a combination of electrophysiological, pharmacological, and behavioral approaches, this study examined KCa2 channels as a novel target to facilitate extinction of alcohol-seeking behavior in rats. This study also explored related neuronal and synaptic mechanisms within the IL-PFC that underlie mGlu5-dependent enhancement of extinction learning. Using whole-cell patch clamp electrophysiology, activation of mGlu5 in ex vivo slices significantly reduced KCa2 channel currents in layer V IL-PFC pyramidal neurons, confirming functional down-regulation of KCa2 channel activity by mGlu5 receptors. Additionally, positive modulation of KCa2 channels prevented mGlu5 receptor-dependent facilitation of long-term potentiation in the IL-PFC. Systemic and intra-IL-PFC treatment with apamin (KCa2 channel allosteric inhibitor) significantly enhanced extinction of alcohol-seeking behavior across multiple extinction sessions; an effect that persisted for 3 weeks, but was not observed after apamin treatment in the prelimbic PFC. Positive modulation of IL-PFC KCa2 channels significantly attenuated mGlu5-dependent facilitation of alcohol cue-conditioned extinction learning. These data suggest that mGlu5-dependent facilitation of extinction learning and synaptic plasticity in the IL-PFC involves functional inhibition of KCa2 channels. Moreover, these findings demonstrate that KCa2 channels are a novel target to facilitate long-lasting extinction of alcohol-seeking behavior
Haasen, C; Eiroa-Orosa, F J; Verthein, U; Soyka, M; Dilg, C; Schäfer, I; Reimer, J
Alcohol has been suggested to be a risk factor for opioid-dependent patients in methadone maintenance treatment (MMT). Literature shows that MMT has limited effects on alcohol use. Nevertheless, a decrease in alcohol use was detected in the Swiss heroin-assisted treatment (HAT) study. In this article, we carry out an in-depth analysis of the German HAT trial with the aim of determining whether alcohol use was affected among patients undergoing HAT and MMT. Analysis was carried out using self-reported data on consumption units of alcohol used (CU), Addiction Severity Index composite scores (ASI CSs), and carbohydrate-deficient transferrin (CDT) measures. Results suggest significant reduction of CU and CDT in both groups, yet larger effects in the HAT group. ASI CS significantly decreased in the HAT but not in the MMT group. The greater benefit of HAT in reducing alcohol use may be due to the greater daily frequency of dispensing heroin coupled with a requirement of sobriety at each dosing occasion.
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
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
Osborn, Cynthia J.
Surveyed alcoholism counselors (N=284) to determine whether the disease concept of alcoholism precludes acceptance and use of Solution-Focused Brief Therapy (SFBT) in alcoholism treatment. Results suggest that SFBT may be feasible for alcoholism treatment and that endorsement of the disease concept is compatible with the principles of SFBT. (EMK)
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.
Vernig, Peter M; Orsillo, Susan M
Drinking motivated by the desire to cope with painful emotions has been shown to be strongly related to alcohol dependence; the resulting maladaptive pattern of substance use can, therefore, be conceptualized as a form of experiential avoidance (an attempt to decrease contact with unpleasant internal states). Acceptance-based interventions, which specifically address experiential avoidance, are multifaceted, and the mechanisms of action are only beginning to be understood. Using a treatment analogue design to look at the underlying components of acceptance-based interventions, the authors tested the effects of brief mindfulness instructions on the emotional responding of alcohol-dependent college students and compared these results with those from a sample of nondependent students. Multidimensional self-reported and psychophysiological emotional responses to pleasant, unpleasant, and neutral pictorial stimuli did not differ between alcohol-dependent and nondependent participants or between the alcohol-dependent participants receiving the mindfulness versus neutral condition. Alcohol-dependent participants' severity of alcohol dependence was found to be related to both self-reported and psychophysiological responses to the unpleasant pictures; these results support the notion that alcohol-dependent participants may use alcohol to cope with unpleasant emotions.
Vaca, Federico; Winn, Diane; Anderson, Craig; Kim, Doug; Arcila, Mauricio
The purpose of this study was to assess the feasibility of utilizing a computerized alcohol screening and intervention (CASI) kiosk in an emergency department (ED). An interactive English and Spanish audiographical computer program, developed for used on a mobile computer cart, was administered to 5103 patients. Patients who screened at risk (19%) also received a fully computer-guided brief negotiated interview (BNI) and a printed personal alcohol reduction plan. A higher percentage of younger patients, and males (31% versus 16% females), screened at risk or dependent. Patient surveys indicated CASI was easy to use and over 75% did not prefer a medical professional over the computer. The ED-based bilingual computerized alcohol screening, brief intervention, and referral to treatment required little time to administer, was acceptable to patients, identified at-risk and dependent drinkers, and was able to provide personalized feedback and brief intervention.
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.
Ooteman, Wendy; Naassila, Mickaël; Koeter, Maarten W J; Verheul, Roel; Schippers, Gerard M; Houchi, Hakim; Daoust, Martine; van den Brink, Wim
Acamprosate and naltrexone are effective medications in the treatment of alcoholism. However, effect sizes are modest. Pharmacogenomics may improve patient-treatment-matching and effect sizes. It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system, whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system. Alcohol-dependent subjects were randomly assigned to either acamprosate or naltrexone. Subjects participated in a cue-exposure experiment at the day before and at the last day of medication. Reductions in cue-induced craving and physiological cue reactivity were measured. Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid, dopamine, glutamate and GABA-receptors. Significant matching effects were found for polymorphisms at the DRD2, GABRA6 and GABRB2 gene. In addition, a trend was found for the OPRM1 polymorphism. This provides evidence for the matching potential of genotypes. It is expected that more effective treatments can be offered when genetic information is used in patient-treatment-matching.
Joos, Leen; Goudriaan, Anna E; Schmaal, Lianne; van den Brink, Wim; Sabbe, Bernard G C; Dom, Geert
Cognitive deficits are highly prevalent in alcohol-dependent (AD) patients and may have a detrimental impact on treatment response and treatment outcome. Enhancing cognitive functions may improve treatment success. Modafinil is a promising compound in this respect. Therefore, a randomized double-blind placebo-controlled trial was conducted with modafinil (300 mg/d) or placebo in 83 AD patients for 10 weeks. Various cognitive functions (digit span task, Tower of London task, Stroop task) were measured at baseline, during and after treatment. Compared to placebo, modafinil improved verbal short-term memory (number of forward digit spans) (p=0.030), but modafinil exerted a negative effect on the working memory score of the digit span task (p=0.003). However, subgroup analyses revealed that modafinil did improve both working memory and verbal short-term memory in AD patients with a poor working memory ability at baseline (25% worst performers), whereas no significant treatment effect of modafinil was found on these two dependent variables in patients with good working memory skills at baseline (25% best performers). No effect of modafinil was found on measures of planning (Tower of London task) and selective attention (Stroop task). Further research is needed to better understand the relationship between cognitive remediation and treatment outcome in order to design targeted treatments.
Bujarski, Spencer; O'Malley, Stephanie S.; Lunny, Katy; Ray, Lara A.
Objective: It is well known to clinicians and researchers in the field of alcoholism that patients vary with respect to drinking goal. The objective in this study was to elucidate the contribution of drinking goal to treatment outcome in the context of specific behavioral and pharmacological interventions. Method: Participants were 1,226…
Chan, James G.
Introduces the development and theoretical underpinnings of family-involved treatment for alcoholism. Describes several interventions from the family therapy literature with an emphasis on behavioral techniques. Outlines efficacy research and considers some problems with the family approach. (Contains 42 references.) (GCP)
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
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
... that early intervention treatment services can improve a child's development. Early intervention services help children from birth to ... wait for a formal diagnosis. Learn more about child development, milestones, and delays » Learn more about early intervention ...
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
Brower, Kirk J
Insomnia in patients with alcohol dependence has increasingly become a target of treatment due to its prevalence, persistence, and associations with relapse and suicidal thoughts, as well as randomized controlled studies demonstrating efficacy with behavior therapies and non-addictive medications. This article focuses on assessing and treating insomnia that persists despite 4 or more weeks of sobriety in alcohol-dependent adults. Selecting among the various options for treatment follows a comprehensive assessment of insomnia and its multifactorial causes. In addition to chronic, heavy alcohol consumption and its effects on sleep regulatory systems, contributing factors include premorbid insomnia; co-occurring medical, psychiatric, and other sleep disorders; use of other substances and medications; stress; environmental factors; and inadequate sleep hygiene. The assessment makes use of history, rating scales, and sleep diaries as well as physical, mental status, and laboratory examinations to rule out these factors. Polysomnography is indicated when another sleep disorder is suspected, such as sleep apnea or periodic limb movement disorder, or when insomnia is resistant to treatment. Sobriety remains a necessary, first-line treatment for insomnia, and most patients will have some improvement. If insomnia-specific treatment is needed, then brief behavioral therapies are the treatment of choice, because they have shown long-lasting benefit without worsening of drinking outcomes. Medications work faster, but they generally work only as long as they are taken. Melatonin agonists; sedating antidepressants, anticonvulsants, and antipsychotics; and benzodiazepine receptor agonists each have their benefits and risks, which must be weighed and monitored to optimize outcomes. Some relapse prevention medications may also have sleep-promoting activity. Although it is assumed that treatment for insomnia will help prevent relapse, this has not been firmly established. Therefore
Fein, G.; Allen, J.
Background The present study examines the EEG spectra of actively drinking treatment naïve alcoholics (TxNA). Methods EEGs were gathered on 51 TxNA’s and age and sex-matched controls during eyes-closed conditions. Participants were excluded for lifetime diagnoses of psychiatric or substance abuse disorders. Power for the theta to high beta bands was examined across midline electrodes. Results The TxNA sample exhibited a nexus of disinhibited traits associated with the vulnerability to alcoholism, and had developed alcohol dependence, but no other diagnosable psychiatric or substance abuse disorders. The TxNA subjects evidenced higher power for all EEG bands compared to controls. The magnitude and anterior-posterior extent of the group differences varied across bands. Within the TxNA group, EEG power was negatively correlated with average and peak alcohol drinking duration and average and peak alcohol dose. Conclusions Increased EEG power across the theta to high beta bands distinguishes TxNAs without comorbid diagnoses from controls. These effects varied across bands in their magnitude and spatial extent, suggesting that there are different effects for the different EEG spectral generators. We hypothesize the increased power in these individuals is a trait difference associated with the inherited nexus of disinhibited traits and its manifestation in alcoholism. Based on the strong negative correlations with alcohol use variables, we speculate that decreases in EEG power are a morbid effect of long-term alcohol abuse. We acknowledge that this hypothesized effect of alcohol abuse on EEG power is opposite to the increased EEG power we hypothesize is associated with alcoholism and its inherited nexus of disinhibited traits. An implication of this model is that with continuing alcohol abuse, the increased EEG power in TxNAs will eventually be overpowered by the effects of long-term severe alcohol abuse. This model predicts that in very long-term alcoholics EEG power
Brückmann, Christof; Di Santo, Adriana; Karle, Kathrin Nora; Batra, Anil; Nieratschker, Vanessa
Alcohol dependence is a severe disorder contributing substantially to the global burden of disease. Despite the detrimental consequences of chronic alcohol abuse and dependence, effective prevention strategies as well as treatment options are largely missing to date. Accumulating evidence suggests that gene-environment interactions, including epigenetic mechanisms, play a role in the etiology of alcohol dependence. A recent epigenome-wide study reported widespread alterations of DNA methylation patterns in alcohol dependent patients compared to control individuals. In the present study, we validate and replicate one of the top findings from this previous investigation in an independent cohort: the hypomethylation of GDAP1 in patients. To our knowledge, this is the first independent replication of an epigenome-wide finding in alcohol dependence. Furthermore, the AUDIT as well as the GSI score were negatively associated with GDAP1 methylation and we found a trend toward a negative association between GDAP1 methylation and the years of alcohol dependency, pointing toward a potential role of GDAP1 hypomethylation as biomarker for disease severity. In addition, we show that the hypomethylation of GDAP1 in patients reverses during a short-term alcohol treatment program, suggesting that GDAP1 DNA methylation could also serve as a potential biomarker for treatment outcome. Our data add to the growing body of knowledge on epigenetic effects in alcohol dependence and support GDAP1 as a novel candidate gene implicated in this disorder. As the role of GDAP1 in alcohol dependence is unknown, this novel candidate gene should be followed up in future studies.
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
Zywiak, William H.; Neighbors, Charles J.; Martin, Rosemarie A.; Johnson, Jennifer E.; Eaton, Cheryl A.; Rohsenow, Damaris J.
Research with the Important People instrument has demonstrated that social support for abstinence is related to alcohol treatment outcomes but less work has been done on the role of network support in drug treatment outcomes. A drug and alcohol version of the Important People instrument (IPDA) was developed and administered to 141 patients in residential treatment for cocaine dependence. Three components were found, all with acceptable internal consistency: (1) substance involvement of the network, (2) general/treatment support, and (3) support for abstinence. These components and three fundamental network characteristics (size of daily network, size of network, and importance of the most important people) were investigated as correlates of pretreatment and posttreatment alcohol and drug use. The general/treatment support component and network size were inversely related to pretreatment days using drugs while network substance involvement positively correlated with pretreatment drinking frequency. Size of the daily network predicted less drinking, less drug use, and less problem severity during the 6 months after treatment whereas general/treatment support and support for abstinence did not predict outcome. Network substance involvement decreased for patients who stayed abstinent but not for those who later relapsed. Results suggest that increasing the number of people the patient sees daily while replacing substance-involved with abstinent-supportive people may improve treatment outcomes. Treatment programs may use the IPDA to identify clients most likely to benefit from changes in their social networks. PMID:18835677
Zywiak, William H; Neighbors, Charles J; Martin, Rosemarie A; Johnson, Jennifer E; Eaton, Cheryl A; Rohsenow, Damaris J
Research with the Important People instrument has shown that social support for abstinence is related to alcohol treatment outcomes, but less work has been done on the role of network support in drug treatment outcomes. A drug and alcohol version of the Important People instrument (IPDA) was developed and administered to 141 patients in residential treatment for cocaine dependence. Three components were found, all with acceptable internal consistency: (a) substance involvement of the network, (b) general/treatment support, and (c) support for abstinence. These components and three fundamental network characteristics (size of daily network, size of network, and importance of the most important people) were investigated as correlates of pretreatment and posttreatment alcohol and drug use. The general/treatment support component and network size were inversely related to pretreatment days using drugs, whereas network substance involvement positively correlated with pretreatment drinking frequency. Size of the daily network predicted less drinking, less drug use, and less problem severity during the 6 months after treatment, whereas general/treatment support and support for abstinence did not predict outcome. Network substance involvement decreased for patients who stayed abstinent but not for those who later relapsed. Results suggest that increasing the number of people the patient sees daily while replacing substance-involved with abstinent-supportive people may improve treatment outcomes. Treatment programs may use the IPDA to identify clients most likely to benefit from changes in their social networks.
Roche, Daniel Jo; Ray, Lara A
Currently available pharmacological treatments for alcoholism have modest efficacy and high individual variability in treatment outcomes, both of which have been partially attributed to genetic factors. One path to reducing the variability and improving the efficacy associated with these pharmacotherapies may be to identify overlapping genetic contributions to individual differences in both subjective responses to alcohol and alcoholism pharmacotherapy outcomes. As acute subjective response to alcohol is highly predictive of future alcohol related problems, identifying such shared genetic mechanisms may inform the development of personalized treatments that can effectively target converging pathophysiological mechanisms that convey risk for alcoholism. The focus of this review is to revisit the association between subjective response to alcohol and the etiology of alcoholism while also describing genetic contributions to this relationship, discuss potential pharmacogenetic approaches to target subjective response to alcohol in order to improve the treatment of alcoholism and examine conceptual and methodological issues associated with these topics, and outline future approaches to overcome these challenges.
Lenz, Bernd; Kraus, Thomas; Sperling, Wolfgang; Bayerlein, Kristina; Biermann, Teresa; Stoessel, Christina
The ratio of the lengths of the second and fourth finger (2D∶4D) has been described as reflecting the degree of prenatal androgen exposure in humans. 2D∶4D is smaller for males than females and is associated with traits such as left-handedness, physical aggression, attention-deficit-hyperactivity disorder and a genetic polymorphism of the androgen receptor. All of these traits are known to be correlated to the vulnerability for alcohol dependency. We therefore hypothesized low 2D∶4D in patients with alcohol dependency. In the present study on 131 patients suffering from alcohol dependency and 185 healthy volunteers, we found that alcohol dependent patients had smaller 2D∶4D ratios compared to controls with preserved sexual dimorphism but with reduced right-left differences. The detection of alcohol dependency based on 2D∶4D ratios was most accurate using the right hand of males (ROC-analysis: AUC 0.725, sensitivity 0.667, specificity 0.723). These findings provide novel insights into the role of prenatal androgen exposure in the development of alcohol dependency and for the use of 2D∶4D as a possible trait marker in identifying patients with alcohol dependency. PMID:21547078
Gilpin, Nicholas W
Neuropeptide Y (NPY) is abundant in the extended amygdala, a conceptual macrostructure in the basal forebrain important for regulation of negative affective states. NPY has been attributed a central role in anxiety-like behavior, fear, nociception, and reward in rodents. Deletion of the NPY gene in mice produces a high-anxiety high-alcohol-drinking phenotype. NPY infused into the brains of rats selectively bred to consume high quantities of alcohol suppresses alcohol drinking by those animals, an effect that is mediated by central amygdala (CeA). Likewise, alcohol-preferring rats exhibit basal NPY deficits in CeA. NPY infused into the brains of alcohol-dependent rats blocks excessive alcohol drinking by those animals, an effect that also has been localized to the CeA. NPY in CeA may rescue dependence-induced increases in anxiety and alcohol drinking via inhibition of downstream effector regions that receive GABAergic inputs from CeA. It is hypothesized here that NPY modulates anxiety-like behavior via Y2R regulation of NPY release, whereas NPY modulation of alcohol-drinking behavior in alcohol-dependent animals occurs via Y2R regulation of GABA release.
Cooper, Louis F.; Wilson, Earl D.
Determined effects on sobriety of two follow-up treatments, self-management and letter and telephone, for alcoholics (N=60) who had completed an alcohol treatment program. Results showed significant difference for the letter and telephone group after one month in comparison to the self-management and the control groups, but no significant…
Conde López, V; Pacheco Yáñez, L; Pérez Puente, C
The authors refer on introduction to a former research where they describe results from 150 inpatients diagnosed of "Alcohol Dependence" and "Alcohol Abuse Syndromes" admitted during 1980-1984 at the Psychiatry Department of University Hospital of Valladolid. A comparison of epidemiologic, clinic, diagnostic and care patients patterns is made versus three other studies , where similar groups of alcoholic patients are studied through 47 variables. The first investigation reports findings from 613 alcoholic out patients demanding psychiatric care at University Hospital in Valladolid. The second one study 134 alcoholic patients (70% outpatients and 30% inpatients) at the Hospital General in Burgos. The last one reports finding from 403 alcoholic inpatients at the Psychiatric Service of "Ramón y Cajal" Hospital of Madrid. A group of 130 patients are studied as a whole, 1,127 males (86.89%) and 173 females (13.3%). Fifty per cent of the sample (n = 653) were inpatients and the remainder were outpatients; 28.30% (n = 368) were diagnosed by means of CIE-8a; 61.38% (n = 798) by means of CIE-9a; and 10.30 by DSM-III diagnostic criteria. The variables evaluated were population, age, sex, civil state, place of birth, place of living, level of education, profession, work capability, economical status and current social class, working and marriage adaptation, place composition, first work age, emigration, family psychiatric problems, affective deprivation, personal background, former treatment for drinking problems, start of drinking average age, abuse average time, kind of drinking, drinking day average amount, motive of abuse increments, consultation motive, somatic and psychiatric diagnoses, others drugs consultations, TAC and EEG results, first pharmacologic treatment, inpatient average time, and later hospitalizations. A table, a graphic and 83 bibliographic quotations, part of which belong to a former work, are included.
Conde López, V; Pacheco Yáñez, L; Pérez Puente, C
The authors refer on introduction to a former research where they describe results from 150 inpatients diagnosed of "Alcohol Dependence" and "Alcohol Abuse Syndromes" admitted during 1980-1984 at the Psychiatry Department of University Hospital of Valladolid. A comparison of epidemiologic, clinic, diagnostic and care patients patterns is made versus three others researches, where similar groups of alcoholic patients are studied through 47 variables. The first ++ investigation reports findings from 613 alcoholic out patients demanding psychiatric care at University Hospital in Valladolid. The second one study 134 alcoholic patients (70% out patients and 30% in patients) at the Hospital General in Burgos. The last one reports finding from 403 alcoholic in patients at the Psychiatric Service of "Ramon y Cajal" Hospital of Madrid. A group of 130 patients are studied as a whole, 1127 males (86.89%) and 173 females (13.3%). Fifty per cent of the simple (n = 653) were in-patient and the remainder were out-patients; 28.30% (n = 368) were diagnosed by means of CIE-8 , 61.38% (n = 798) by means of CIE-9 and 10.30 by DSM-III diagnostic criteria. The variables evaluated were population, age, sex, civil state, place of birth, place of living, level of education, profession, work capability, economical status and current social class, working and marriage adaptation, place composition, first work age, emigration, family psychiatric problems, affective deprivation, personal background, former treatment for drinking problems, start of drinking average age, abuse average time, kind of drinking, drinking day average amount, motive of abuse increments, consultation motive, somatic and psychiatric diagnoses, other drug consumptions, TAC and EEG results, first pharmacologic treatment, in-patient average time, and later hospitalisations. A table, a graphic, and 83 bibliographic quotations, part of which belong to a former work, are included.
Evren, Cuneyt; Sar, Vedat; Dalbudak, Ercan; Cetin, Rabia; Durkaya, Mine; Evren, Bilge; Celik, Selime
The aim of this study was to investigate the impact of lifetime posttraumatic stress disorder (PTSD), dissociation and a history of childhood trauma on quality of life (QoL) among men with alcohol dependency. A consecutive series of alcohol-dependent men (N=156) admitted to an inpatient treatment unit were screened using the Michigan Alcoholism Screening Test, the Clinician Administered PTSD Scale, the Dissociative Experiences Scale, and the Childhood Trauma Questionnaire. QoL was assessed using the Medical Outcomes Study Short-Form 36-item health survey. Fifty (32.1%) patients had lifetime diagnosis of PTSD. Besides problems related to severity of alcohol use, the lifetime PTSD group was impaired on several physical and mental components of QoL. While the lifetime PTSD group and remaining patients did not differ on reports of childhood trauma and dissociation, in lifetime PTSD group, dissociative patients had higher scores of childhood emotional abuse than those of the non-dissociative patients. In multivariate covariance analysis, both dissociation and lifetime PTSD predicted impairment in physical functioning, general health, vitality, and mental health components of QoL. Among alcohol-dependent men with lifetime PTSD, a history of childhood emotional abuse contributes to impairment of QoL through its relationship with dissociation.
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
Orwat, John; Saitz, Richard; Tompkins, Christopher P; Cheng, Debbie M; Dentato, Michael P; Samet, Jeffrey H
This is a prospective cohort study to identify factors associated with receipt of substance abuse treatment (SAT) among adults with alcohol problems and HIV/AIDS. Data from the HIV Longitudinal Interrelationships of Viruses and Ethanol study were analyzed. Generalized estimating equation logistic regression models were fit to identify factors associated with any service utilization. An alcohol dependence diagnosis had a negative association with SAT (adjusted odds ratio [AOR] = 0.36, 95% confidence interval [95% CI] = 0.19-0.67), as did identifying sexual orientation other than heterosexual (AOR = 0.46, CI = 0.29-0.72) and having social supports that use alcohol/drugs (AOR = 0.62, CI = 0.45-0.83). Positive associations with SAT include presence of hepatitis C antibody (AOR = 3.37, CI = 2.24-5.06), physical or sexual abuse (AOR = 2.12, CI = 1.22-3.69), social supports that help with sobriety (AOR = 1.92, CI = 1.28-2.87), homelessness (AOR = 2.40, CI = 1.60-3.62), drug dependence diagnosis (AOR = 2.64, CI = 1.88-3.70), and clinically important depressive symptoms (AOR = 1.52, CI = 1.08-2.15). While reassuring that factors indicating need for SAT among people with HIV and alcohol problems (e.g., drug dependence) are associated with receipt, nonneed factors (e.g., sexual orientation, age) that should not decrease likelihood of receipt of treatment were identified.
Ellis, A; Schoenfeld, E
Alcoholics Anonymous and related 12-step programs are the predominant influence on chemical dependency treatment programs in the United States today. 12-step programs have a strong religious orientation, despite rationalizations that Higher Power need not mean the traditional definition of God. The teaching of religious beliefs is not a proper function of therapists treating addictions in a general population. Moreover, teaching patients they can only recover through the intervention of a Higher Power locks them into a pattern of dependence on something outside themselves in order to function. 12-step programs have helped millions of people. Even more could be helped were they to eliminate the concept of needing a Higher Power.
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.
Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida
Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644
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…
... Age 12 and Older Dependent on or Abusing Alcohol and Illicit Drugs Alcohol / 17,876 Marijuana / 4,476 Pain Relievers / 1,921 Sedatives / 162 Tranquilizers / 521 Stimulants / 357 Heroin / ... Health Services Administration, 2005 National Survey on Drug Use and Health
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.
Emery, Clifton R; Wu, Shali; Yang, Hyerin; Lee, Hotaek; Kim, Junpyo; Chan, Ko Ling
Although previous research documents a reliable relationship between physical intimate partner violence (IPV) victimization and alcoholism, relatively little research has examined new theoretical constructs in IPV research that may increase risk for or help buffer women from alcohol abuse/dependence. The purpose of the present study was to examine informal social control of IPV by family members as a protective factor against and coercive control as a risk factor for alcohol abuse/dependence in a small population sample of married women in Seoul, South Korea. We hypothesized that (a) informal social control by family members would be negatively associated with victim alcohol abuse/dependence and (b) husband's coercive control would be positively associated with victim alcohol abuse/dependence. We measured alcohol abuse/dependence (CAGE scale), IPV and coercive control by husbands, and informal social control of IPV (ISC_IPV) by extended family members in a three-stage random cluster sample of 462 married women in Seoul, South Korea. Both random effects regression and zero-inflated Poisson regression models found that ISC_IPV by extended family members was associated with a significantly lower CAGE scores, and coercive control was associated with significantly higher CAGE scores. Interventions to boost ISC_IPV by extended family members may mitigate some of the risk of alcohol abuse/dependence by victims.
Garbusow, Maria; Schad, Daniel J; Sebold, Miriam; Friedel, Eva; Bernhardt, Nadine; Koch, Stefan P; Steinacher, Bruno; Kathmann, Norbert; Geurts, Dirk E M; Sommer, Christian; Müller, Dirk K; Nebe, Stephan; Paul, Sören; Wittchen, Hans-Ulrich; Zimmermann, Ulrich S; Walter, Henrik; Smolka, Michael N; Sterzer, Philipp; Rapp, Michael A; Huys, Quentin J M; Schlagenhauf, Florian; Heinz, Andreas
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Prince, Mark A.; Connors, Gerard J.; Maisto, Stephen A.; Dearing, Ronda L.
While past research has demonstrated a positive relationship between the therapeutic alliance (TA) and improved drinking outcomes, specific aspects of the alliance have received less attention. In this study, we examined the association between alliance characteristics during treatment and 4-month follow-up drinking reports. 65 treatment-seeking alcohol dependent clients who participated in 12 weeks of individual outpatient treatment provided weekly TA ratings during treatment and reported on pre-treatment, during treatment, and post-treatment alcohol use. Latent profile analysis was conducted to discern distinct profiles of client and therapist ratings of therapeutic alliance with similar alliance characteristics. TA profiles were based on clients’ and therapists’ mean alliance rating, minimum alliance rating, maximum alliance rating, the range of alliance ratings, and the difference in session number between maximum and minimum alliance ratings. 1- through 4- class models were fit to the data. Model fit was judged by comparative fit indices, substantive interpretability, and parsimony. Wald tests of mean equality determined whether classes differed on follow-up percentage of days abstinent (PDA) at 4 months posttreatment. 3-profile solutions provided the best fit for both client and therapist ratings of the therapeutic alliance. Client alliance rating profiles predicted drinking in the follow-up period, but therapist rating profiles did not. These results suggest that distinct profiles of the therapeutic alliance can be identified and that client alliance rating profiles are associated with frequency of alcohol use following outpatient treatment. PMID:26999350
Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae
Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD. PMID:27547010
Udemgba, Chinelo; Johnson, Shakevia; Stockmeier, Craig A.; Luo, Jia; Albert, Paul R.; Wang, Junming; May, Warren L.; Harris, Sharonda; Sittman, Donald B.; Ou, Xiao-Ming
Background The biochemical pathways underlying alcohol abuse and dependence are not well understood, although brain cell loss and neurotoxicity have been reported in subjects with alcohol dependence. Monoamine oxidase B (MAO B, which catabolizes neurotransmitters such as dopamine) is consistently increased in this psychiatric illness. MAO B has been implicated in the pathogenesis of alcohol dependence, neurodegenerative diseases and alcohol-induced brain neurotoxicity. Recently, the cell growth-inhibitor protein, Kruppel-like factor 11 (KLF11), has been reported to be an MAO-transcriptional activator. KLF11 is also known as TIEG2 (transforming growth factor-beta-inducible early gene 2) and mediates apoptotic cell death. This study investigates the protein expression of KLF11 and its relationship with MAO B using human postmortem prefrontal cortex from subjects with alcohol dependence. Methods Twelve subjects with alcohol dependence and the respective psychiatrically-normal control subjects were investigated. Expression of KLF11 and MAO B proteins in the prefrontal cortex were measured by Western blot analysis. A correlation study between KLF11 and MAO B protein expression was also performed. Results Levels of KLF11 protein were significantly increased by 44 percent (p<0.03) in the postmortem prefrontal cortex of subjects with alcohol dependence as compared to age- and gender-matched, psychiatrically-normal control subjects. In addition, KLF11 levels were significantly and positively correlated with the increased MAO B protein levels associated with alcohol dependence. Conclusions This novel study shows the important role of KLF11, an MAO-transcriptional activator, in human alcohol dependence. It further supports that the KLF11-MAO B cell death cascade may contribute to chronic alcohol-induced brain damage. This argues a case for KLF11-MAO B inhibition as a novel therapeutic strategy that may impact this highly prevalent, often treatment resistant, illness. PMID
Cerdá, Magdalena; Moffitt, Terrie E; Meier, Madeline H; Harrington, HonaLee; Houts, Renate; Ramrakha, Sandhya; Hogan, Sean; Poulton, Richie; Caspi, Avshalom
With the increasing legalization of cannabis, understanding the consequences of cannabis use is particularly timely. We examined the association between cannabis use and dependence, prospectively assessed between ages 18-38, and economic and social problems at age 38. We studied participants in the Dunedin Longitudinal Study, a cohort (n=1,037) followed from birth to age 38. Study members with regular cannabis use and persistent dependence experienced downward socioeconomic mobility, more financial difficulties, workplace problems, and relationship conflict in early midlife. Cannabis dependence was not linked to traffic-related convictions. Associations were not explained by socioeconomic adversity, childhood psychopathology, achievement orientation, or family structure; cannabis-related criminal convictions; early onset of cannabis dependence; or comorbid substance dependence. Cannabis dependence was associated with more financial difficulties than alcohol dependence; no difference was found in risks for other economic or social problems. Cannabis dependence is not associated with fewer harmful economic and social problems than alcohol dependence.
... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...
If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...
Brower, Kirk J; Krentzman, Amy; Robinson, Elizabeth A R
Insomnia is common, persistent, and increases the risk for relapse in alcohol-dependent (AD) patients. Abstinence has long been considered the best strategy for allowing sleep to normalize, although how many and which patients respond to abstinence is unknown. The aims of this study were to investigate the prevalence and correlates of both baseline and persistent insomnia in AD patients. The course of sleep problems in response to abstinence, moderate drinking, or relapse following treatment was also examined. A naturalistic longitudinal outcomes study interviewed 267 patients (69% male; mean age of 44 years) with DSM-IV alcohol dependence at baseline and 6 months later (84% follow-up rate) . The Sleep Problems Questionnaire, Time-Line Follow-Back Interview, and Brief Symptom Inventory measured insomnia, drinking, and psychiatric symptoms, respectively. Simple correlations, logistic regression, and repeated measures analysis of variance were used to analyze the data. At baseline, 47% of patients were classified with insomnia, which was independently predicted by female gender and psychiatric severity. Both abstinence and moderate drinking outcomes significantly predicted a reduction of insomnia symptoms after controlling for gender and psychiatric severity. Among patients with baseline insomnia, however, insomnia persisted in over 60% of cases, which was predicted by baseline insomnia severity. Moreover, insomnia persisted in one-quarter of patients despite abstinence. Treatment aimed at preventing relapse to heavy drinking provides good first-line therapy for insomnia in AD patients, but some may require insomnia-specific evaluation and treatment in addition to substance-focused treatment and psychiatric care.
Conroy, Deirdre A.; Arnedt, J. Todd; Brower, Kirk J.; Strobbe, Stephen; Consens, Flavia; Hoffmann, Robert; Armitage, Roseanne
Background Subjective and objective measures of poor sleep in alcoholic insomniacs predict relapse to drinking. Non-alcoholic insomniacs underestimate their total sleep time (TST), and overestimate their sleep onset latency (SOL) and wake time after sleep onset (WASO) compared to polysomnography (PSG). This study evaluated three hypotheses: (1) subjective SOL would predict frequency of drinking during and after treatment; (2) participants would overestimate SOL and WASO and underestimate TST; and (3) higher amounts of over- and underestimates of sleep at baseline would predict worse drinking outcomes during and after treatment. Methods Participants (N=18), mean age 44.6 years (±13.2) underwent an adaptation night and two nights of PSG. They provided morning estimates of SOL, WASO, TST, and sleep efficiency (SE). Following PSG, participants were randomized to 6 weeks of placebo or gabapentin as part of a separate study. After 6 weeks, participants discontinued medication and were followed to week 12. A two-way ANOVA (night x method of measuring sleep) compared results and regression analyses predicted drinking. Drinking outcomes were defined as number of days drinking (DD) and number of heavy drinking days (HDD) during two consecutive 6-week periods. Results Most participants (72%) overestimated SOL by a mean of 21.3 (±36) minutes compared to PSG, F (1, 14) =7.1, p<.03. Unexpectedly, 89% underestimated WASO by a mean difference of 48.7 (±49) minutes, F (1, 14) =15.6, p<.01. Drinking during the 6-week study period was predicted by both subjective estimates of WASO and their accuracy. Post-treatment drinking was also predicted by subjective estimations of sleep and REM sleep latency. Conclusion Greater subjective accuracy of wakefulness at night provided by the patient predicted drinking during treatment. Unlike non-alcoholic insomniacs, this alcoholic sample significantly underestimated WASO compared to PSG values. The predictive ability of sleep parameters
Rozeboom, Henriëtte J; Yu, Shukun; Mikkelsen, Rene; Nikolaev, Igor; Mulder, Harm J; Dijkstra, Bauke W
The quinone-dependent alcohol dehydrogenase (PQQ-ADH, E.C. 188.8.131.52) 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.
Gilburt, Helen; Drummond, Colin; Sinclair, Julia
Aims Provision of effective treatment for dependent drinkers has been identified as a priority in England yet evidence suggests that access is problematic and there are low levels of retention. This qualitative study explores how the alcohol treatment system is experienced by service users, identifying barriers and facilitators that influence treatment outcomes. Methods A total of 20 semi-structured face-to-face interviews were conducted with patients from community alcohol treatment services in three London boroughs in 2012. Interviews were undertaken one year after initially entering treatment. A thematic analysis was conducted, with the results further abstracted to relate them to specific aspects of the treatment journey. Results Patients journeys were characterized by a perceived lack of control leading to help-seeking, with treatment outcomes influenced by an individuals' self-efficacy and the capabilities and skills of staff in actively engaging and supporting patients on the journey. A focus of services on the detoxification process and fragmented care pathways impacted negatively on engagement. Conclusions Current alcohol care pathways require significant levels of motivation and self-efficacy to navigate that few patients possess. Pathways need to better reflect the capacity and capabilities of patients to be successful in supporting recovery. PMID:25825267
Nuutinen, Saara; Vanhanen, Jenni; Mäki, Tiia; Panula, Pertti
The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders. PMID:22629238
Nuutinen, Saara; Vanhanen, Jenni; Mäki, Tiia; Panula, Pertti
The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders.
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
Fein, George; Landman, Bennett
Most research on alcoholism uses convenience samples of individuals who have been in some type of treatment; Berkson’s fallacy results when the associations found in studies of select samples are incorrectly presumed to apply to all alcoholics (i.e. including untreated alcoholics in the general population). This study examines whether treated and untreated alcoholics have similar early alcohol use histories by comparing abstinent alcoholics (treated and sober at least 6 months) to treatment-naïve alcoholics (active drinkers). We studied fourteen pairs of women and twenty-five pairs of men matched on the age at which they first met criteria for heavy alcohol use (80 drinks/month for women and 100 drinks/month for men). The timeline follow-back interview methodology was used to gather retrospective alcohol use information. Alcohol dose and duration was then computed for two intervals: the time between the person’s first drink and the date at which they met criteria for heavy drinking, and the period between meeting criteria for heavy drinking and the current age of the treatment-naïve person from each pair. During the period prior to meeting the matching ‘heavy drinking’ criteria, alcohol dose did not differ between groups. In the period after meeting criteria for heavy alcohol use, the treated alcoholics had higher average and peak alcohol doses than the treatment naïve alcoholics. We rejected the hypothesis that the treatment naïve alcoholics and the treated alcoholics have similar alcohol use trajectories over time, with the treatment naïve sample simply being observed earlier in their alcohol use histories. Instead we concluded that the two groups come from different populations with regard to alcohol use (in fact, the treated alcoholics had alcohol doses over 50% higher than treatment-naïve alcoholics in the years just after they began drinking heavily). This suggests that results from studies of alcoholics in treatment or post-treatment (i
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.
McMartin, K E
Translational toxicology can be defined as the movement of potential antidotes for the treatment of poisonings from basic mechanistic research to the marketplace. Because poisonings are infrequent, the clinical development of antidotes is fraught with trials and tribulations. Academic scientists often conduct basic mechanistic work with antidotes but are infrequently involved in further drug development. This article presents the development of 4-methylpyrazole (4MP) (fomepizole) as an antidote against toxic alcohol poisonings, particularly by methanol and ethylene glycol (EG).
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
Sofin, Yvonne; Danker-Hopfe, Heidi; Gooren, Tina; Neu, Peter
Aims. This prospective study aims to identify patient characteristics as predictors for treatment outcome during inpatient detoxification treatment for drug and alcohol dependent patients. Methods. A mixed gender sample of 832 consecutively admitted drug and alcohol dependent patients were interviewed by an experienced physician. The impact of a variety of factors concerning social environment, therapy motivation, impulsivity related variables, medical history, and addiction severity on treatment outcome was examined. Results. 525 (63.1%) of the patients completed detoxification treatment whereas 307 (36.9%) dropped out prematurely. Being female, living in a partnership, having children, being employed, and having good education were predictive for a positive outcome. Family, health, the fear of losing the job, prosecution, and emergency admission were significant motivational predictors for treatment outcome. Being younger, history of imprisonment, and the number of previous drop-outs were predictive for a negative outcome. Conclusions. Variables concerning social environment and the number of previous drop-outs have been identified as best predictors for treatment outcome. Socially stable patients benefit from the current treatment setting and treatment shall be adapted for patients with negative predictors. Treatment may consequently be tailored with respect to intervention type, duration, and intensity to improve the outcome for those patients that fulfil criteria with negative impact on treatment retention.
Danker-Hopfe, Heidi; Gooren, Tina
Aims. This prospective study aims to identify patient characteristics as predictors for treatment outcome during inpatient detoxification treatment for drug and alcohol dependent patients. Methods. A mixed gender sample of 832 consecutively admitted drug and alcohol dependent patients were interviewed by an experienced physician. The impact of a variety of factors concerning social environment, therapy motivation, impulsivity related variables, medical history, and addiction severity on treatment outcome was examined. Results. 525 (63.1%) of the patients completed detoxification treatment whereas 307 (36.9%) dropped out prematurely. Being female, living in a partnership, having children, being employed, and having good education were predictive for a positive outcome. Family, health, the fear of losing the job, prosecution, and emergency admission were significant motivational predictors for treatment outcome. Being younger, history of imprisonment, and the number of previous drop-outs were predictive for a negative outcome. Conclusions. Variables concerning social environment and the number of previous drop-outs have been identified as best predictors for treatment outcome. Socially stable patients benefit from the current treatment setting and treatment shall be adapted for patients with negative predictors. Treatment may consequently be tailored with respect to intervention type, duration, and intensity to improve the outcome for those patients that fulfil criteria with negative impact on treatment retention. PMID:28367351
Hingson, R; Zakocs, R; Heeren, T; Winter, M; Rosenbloom, D; DeJong, W
Objective: This analysis tested whether comprehensive community interventions that focus on reducing alcohol availability and increasing substance abuse treatment can reduce alcohol related fatal traffic crashes. Intervention: Five of 14 communities awarded Fighting Back grants by The Robert Wood Johnson Foundation to reduce substance abuse and related problems attempted to reduce availability of alcohol and expand substance abuse treatment programs (FBAT communities). Program implementation began on 1 January 1992. Design: A quasi-experimental design matched each program community to two or three other communities of similar demographic composition in the same state. Main outcome measures: The ratio of fatal crashes involving a driver or pedestrian with a blood alcohol concentration of 0.01% or higher, 0.08% or higher, or 0.15% or higher were examined relative to fatal crashes where no alcohol was involved for 10 years preceding and 10 years following program initiation. Results: Relative to their comparison communities, the five FBAT communities experienced significant declines of 22% in alcohol related fatal crashes at 0.01% BAC or higher, 20% at 0.08% or higher, and 17% at 0.15% or higher relative to fatal crashes not involving alcohol. Conclusions: Community interventions to reduce alcohol availability and increase substance abuse treatment can reduce alcohol related fatal traffic crashes. PMID:15805436
In 1979, "Alcoholism Diagnosis Committee, the Ministry of Health and Welfare" established the diagnostic criteria for alcohol dependence syndrome, which included "the resistance to negative reinforcement". The author raises a question about this criterion which indicates the condition that "an individual continues to drink despite alcohol-related physical diseases, rejection by his/her family or economic poverty and drinking-related criminal problem." The author defines this condition not as "resistance to negative reinforcement" but as "resistance to punishment." Furthermore, the author can not find the data supporting that "the resistance to negative reinforcement" in the correct sense exists in the individuals with alcohol dependence syndrome. In a theoretical sense, an opposite idea seems to exist. There is an observed fact that can be regarded as a phenomenon that explains the involvement of "negative reinforcement" in enhancement of psychological dependence as in the case of the secondary development of psychological dependence. Consequently, the author would have to say that defining "the resistance to negative reinforcement" as one of common features of alcohol dependence syndrome or one of diagnostic criteria for alcohol dependence syndrome is inappropriate.
Stuewig, Jeffrey; Tangney, June Price; Mashek, Debra; Forkner, Peter; Dearing, Ronda
This article examines the relationship of shame, guilt, and symptoms of alcohol dependence to pre-incarceration HIV risk behaviors in an ongoing study in a metropolitan jail. Between 2002 and 2004 an ethnically diverse sample of 368 male inmates (mean age = 31, SD = 9.7), were interviewed on a variety of constructs including shame- and guilt-proneness (TOSCA-SD; Hanson and Tangney, 1996), alcohol dependence (TCU-CRTF; Simpson and Knight, 1998), and HIV risk behavior (TCU-ARA; Simpson, 1997). Symptoms of alcohol dependence were associated with elevated levels of HIV risk behavior (risky needle use and unprotected sex) prior to incarceration. Guilt-proneness was negatively related to risky sexual behavior. In addition, there was an interaction between shame and symptoms of alcohol dependence. Specifically, among those who were low on alcohol dependence, shame-proneness was negatively related to risky sexual behavior. The study's limitations are noted and findings are discussed in the context of the importance of considering moral emotions and alcohol dependence when designing programs to reduce HIV risk.
... de los dientes Video: Getting an X-ray Alcohol KidsHealth > For Kids > Alcohol Print A A A What's in this article? ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...
Prince, Mark A; Connors, Gerard J; Maisto, Stephen A; Dearing, Ronda L
Although past research has demonstrated a positive relationship between the therapeutic alliance (TA) and improved drinking outcomes, specific aspects of the alliance have received less attention. In this study, we examined the association between alliance characteristics during treatment and 4-month follow-up drinking reports. Sixty-five treatment-seeking alcohol dependent clients who participated in 12 weeks of individual outpatient treatment provided weekly TA ratings during treatment and reported on pretreatment, during treatment, and posttreatment alcohol use. Latent profile analysis was conducted to discern distinct profiles of client and therapist ratings of therapeutic alliance with similar alliance characteristics. TA profiles were based on clients' and therapists' mean alliance rating, minimum alliance rating, maximum alliance rating, the range of alliance ratings, and the difference in session number between maximum and minimum alliance ratings. One- through 4-class models were fit to the data. Model fit was judged by comparative fit indices, substantive interpretability, and parsimony. Wald tests of mean equality determined whether classes differed on follow-up percentage of days abstinent (PDA) at 4-months posttreatment. Three-profile solutions provided the best fit for both client and therapist ratings of the therapeutic alliance. Client alliance rating profiles predicted drinking in the follow-up period, but therapist rating profiles did not. These results suggest that distinct profiles of the therapeutic alliance can be identified and that client alliance rating profiles are associated with frequency of alcohol use following outpatient treatment.
Kampman, Kyle M
Cocaine dependence continues to be a significant public health problem in the United States. Although some cocaine- dependent patients will respond well to drug counseling, for many, standard psychosocial treatment is inadequate. Therefore, the development of an effective medication for the treatment of cocaine dependence is a research priority. However, despite many years of research, no medication has emerged as consistently effective for the treatment of cocaine dependence. Progress in the understanding of the neurobiology of cocaine dependence has led to the discovery of several promising medications that have already shown encouraging results in controlled clinical trials. Among more severely addicted patients, propranolol may be helpful in promoting an initial period of stable abstinence. For the prevention of relapse, medications that block cocaine euphoria or reduce cocaine craving have shown promise. Potential relapse-prevention medications include GABAergic medications, such as baclofen, tiagabine, and topiramate, and the glutamatergic medication, modafinil. Surprisingly, an old treatment for alcohol dependence, disulfiram, may also have efficacy for cocaine relapse prevention. Finally, a vaccine capable of stimulating the production of cocaine specific antibodies has shown promise in preliminary studies for the prevention of relapse to cocaine use.
Meszaros, K; Willinger, U; Fischer, G; Schönbeck, G; Aschauer, H N
C.R. Cloninger proposed a biosocial model for personality, linking personality traits to patterns of responses to various external stimuli, including alcohol. The Tridimensional Personality Questionnaire (TPQ) was administered in a multicenter study to detoxified alcohol-dependent patients (N = 521). The objectives of the study were to evaluate (1) the expression of the three personality dimensions, novelty-seeking (NS), harm avoidance (HA), and reward dependence (RD), of the TPQ in this sample, and (2) the influence of different variables on these personality dimensions. The following variables were selected for a multiple and a stepwise regression analysis: sex, family history for major psychiatric disorders, marital status, occupation, age at study enrollment, age of onset of alcoholism, serum cholesterol level, intake of neuroleptics or benzodiazepines for detoxification, and severity of depression and anxiety. In comparison to Austrian normative data, both sexes of detoxified alcohol addicts scored higher in HA. The variables examined explain 23% of the variance of NS and 35% of HA. Only one variable, namely age of onset, is significantly influencing NS (19% explained variance). HA is significantly influenced by three variables: anxiety state, anxiety trait, and sex (32% explained variance). RD is not influenced by any of the variables examined.
Capusan, Andrea J; Bendtsen, Preben; Marteinsdottir, Ina; Kuja-Halkola, Ralf; Larsson, Henrik
Previous research indicates that attention deficit hyperactivity disorder (ADHD) frequently co-occurs with alcohol dependence; however, the extent to which shared genetic risk factors underpin this association remains unclear. The aim of this study is to investigate the relative importance of genetic, shared, and nonshared environmental factors for the overlap between ADHD and alcohol dependence in adults. Almost 18,000 adult twins aged 20-45 years, from more than 12,000 twin pairs (5,420 complete pairs), from the population-representative Swedish Twin Registry, were included. Self-ratings were used to assess symptoms of ADHD and alcohol dependence. Twin analysis was used to determine the role of additive genetic (A), shared (C), and nonshared environmental (E) factors. As a result, we found a significant association between ADHD and alcohol dependence (odds ratio 3.58; 95% confidence interval, 2.85-4.49). Twin analysis suggested that shared genetic risk factors explained 64% of the overlap between ADHD and alcohol dependence. Nonshared environmental factors accounted for the remaining 36%, whereas the contribution of shared environmental factors was minimal. We found no support for statistically significant sex differences in the overlap between ADHD and alcohol dependence. In conclusion the overlap between ADHD and alcohol dependence in adulthood was largely explained by shared genetic risk factors. This is an important step toward understanding the underlying nature of the risk of alcohol dependence in patients with ADHD and suggests that individuals with ADHD and their family members are important targets for alcohol prevention and treatment. © 2015 Wiley Periodicals, Inc.
Adams, Zachary W.; Schacht, Joseph P.; Randall, Patrick; Anton, Raymond F.
Objective: People consume alcohol at problematic levels for many reasons. These different motivational pathways may have different biological underpinnings. Valid, brief measures that discriminate individuals’ reasons for drinking could facilitate inquiry into whether varied drinking motivations account for differential response to pharmacotherapies for alcohol use disorders. The current study evaluated the factor structure and predictive validity of a brief measure of alcohol use motivations developed for use in randomized clinical trials, the Reasons for Heavy Drinking Questionnaire (RHDQ). Method: The RHDQ was administered before treatment to 265 participants (70% male) with alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, in three pharmacotherapy randomized clinical trials. Principal components analysis was used in half the sample to determine the RHDQ factor structure. This structure was verified with confirmatory factor analysis in the second half of the sample. The factors derived from this analysis were evaluated with respect to alcohol dependence severity indices. Results: A two-factor solution was identified. Factors were interpreted as Reinforcement and Normalizing. Reinforcement scores were weakly to moderately associated with severity, whereas normalizing scores were moderately to strongly associated with severity. In all cases in which significant associations between RHDQ scores and severity indices were observed, the relationship was significantly stronger for normalizing than for reinforcing. Conclusions: The RHDQ is a promising brief assessment of motivations for heavy alcohol use, particularly in the context of randomized clinical trials. Additional research should address factor structure stability in non–treatment-seeking individuals and the RHDQ’s utility in detecting and accounting for changes in drinking behavior, including in response to intervention. PMID:26997195
Grosso, Justine A; Epstein, Elizabeth E; McCrady, Barbara S; Gaba, Ayorkor; Cook, Sharon; Backer-Fulghum, Lindsey M; Graff, Fiona S
This study examined types of internal and external motivations for seeking treatment and the predictive utility of different types of motivation among 180 women with an alcohol use disorder (AUD) participating in a two-armed trial testing different individual and couple therapies for AUDs. Reasons for seeking treatment were coded for type of internal or external motivation. Most women (97%) cited internal reasons for seeking help, including: concern about progression of AUD (61.1%), health (43.3%), mental health (38.9%), and family (38.3%). Occupational concerns, an internal motivator cited by 6% of women, were associated with better drinking outcomes; interpersonal-family concerns were associated with poorer outcomes. Some motivators for seeking treatment may not be related to sustained changes in drinking, suggesting that understanding motivators for treatment may be inadequate to maintain change. Reasons for help-seeking may need to be addressed in treatment to produce long-lasting change.
Charlet, Katrin; Schlagenhauf, Florian; Richter, Anne; Naundorf, Karina; Dornhof, Lina; Weinfurtner, Christopher E J; König, Friederike; Walaszek, Bernadeta; Schubert, Florian; Müller, Christian A; Gutwinski, Stefan; Seissinger, Annette; Schmitz, Lioba; Walter, Henrik; Beck, Anne; Gallinat, Jürgen; Kiefer, Falk; Heinz, Andreas
Neuropsychological studies reported decoding deficits of emotional facial expressions in alcohol-dependent patients, and imaging studies revealed reduced prefrontal and limbic activation during emotional face processing. However, it remains unclear whether this reduced neural activation is mediated by alcohol-associated volume reductions and whether it interacts with treatment outcome. We combined analyses of neural activation during an aversive face-cue-comparison task and local gray matter volumes (GM) using Biological Parametric Mapping in 33 detoxified alcohol-dependent patients and 33 matched healthy controls. Alcoholics displayed reduced activation toward aversive faces-neutral shapes in bilateral fusiform gyrus [FG; Brodmann areas (BA) 18/19], right middle frontal gyrus (BA46/47), right inferior parietal gyrus (BA7) and left cerebellum compared with controls, which were explained by GM differences (except for cerebellum). Enhanced functional activation in patients versus controls was found in left rostral anterior cingulate cortex (ACC) and medial frontal gyrus (BA10/11), even after GM reduction control. Increased ACC activation correlated significantly with less (previous) lifetime alcohol intake [Lifetime Drinking History (LDH)], longer abstinence and less subsequent binge drinking in patients. High LDH appear to impair treatment outcome via its neurotoxicity on ACC integrity. Thus, high activation of the rostral ACC elicited by affective faces appears to be a resilience factor predicting better treatment outcome. Although no group differences were found, increased FG activation correlated with patients' higher LDH. Because high LDH correlated with worse task performance for facial stimuli in patients, elevated activation in the fusiform 'face' area may reflect inefficient compensatory activation. Therapeutic interventions (e.g. emotion evaluation training) may enable patients to cope with social stress and to decrease relapses after detoxification.
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
Fortuna, Jeffrey L
Contemporary research has shown that a high number of alcohol-dependent and other drug-dependent individuals have a sweet preference, specifically for foods with a high sucrose concentration. Moreover, both human and animal studies have demonstrated that in some brains the consumption of sugar-rich foods or drinks primes the release of euphoric endorphins and dopamine within the nucleus accumbens, in a manner similar to some drugs of abuse. The neurobiological pathways of drug and "sugar addiction" involve similar neural receptors, neurotransmitters, and hedonic regions in the brain. Craving, tolerance, withdrawal and sensitization have been documented in both human and animal studies. In addition, there appears to be cross sensitization between sugar addiction and narcotic dependence in some individuals. It has also been observed that the biological children of alcoholic parents, particularly alcoholic fathers, are at greater risk to have a strong sweet preference, and this may manifest in some with an eating disorder. In the last two decades research has noted that specific genes may underlie the sweet preference in alcohol- and drug-dependent individuals, as well as in biological children of paternal alcoholics. There also appears to be some common genetic markers between alcohol dependence, bulimia, and obesity, such as the A1 allele gene and the dopamine 2 receptor gene.
Padma, Lakshminarayana; Swaminath, Gopalrao; Thimmaiah, Rohini S.
Background: Currently, benzodiazepines are the preferred drugs in the management of alcohol withdrawal symptoms. Chlordiazepoxide and diazepam, the most frequently used drugs have a long duration of action and are converted to active metabolites in the liver, while lorazepam is shorter acting, with no active metabolites. Objective: To compare and evaluate the safety and efficacy of lorazepam and chlordiazepoxide in patients with alcohol dependence syndrome with symptoms of alcohol withdrawal. Materials and Methods: This was a prospective, randomized, double-blind, study carried out at a teaching hospital in Bangalore. Sixty patients aged ≥18 y with alcohol dependence syndrome with mild-to-moderate withdrawal symptoms were allocated at a ratio of 1:1 to either lorazepam or chlordiazepoxide, by means of a computer-generated randomization chart. Thirty patients each were started with lorazepam tablets 8 mg/day and chlordiazepoxide 80 mg/day. For both treatment groups, the dose was tapered and at the end of 8 days, the patients were drug-free. The severity of alcohol dependence was assessed using the Severity of Alcohol Dependence Questionnaire (SADQ). The CIWA-Ar was used for quantification of withdrawal symptoms. Liver function tests were performed at baseline and at the end of the study. Results: Of the 60 patients included in the study, 15 patients each had mild and moderate withdrawal symptoms in the chlordiazepoxide group and 17 and 13 patients respectively in the lorazepam group, based on the SADQ score. At baseline, the mean CIWA-Ar scores were similar in both the treatment groups: 24.77±5.98 in the chlordiazepoxide group and 24.90±6.12 in the lorazepam group. There was a significant intragroup decrease in the CIWA-Ar scores measured from baseline to the end of 8 days (p<0.0001) and 12 days (p<0.0001) in both treatment groups; however, there was no significant difference between the two groups. There was no significant difference observed in the liver
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
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
... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82 Pensions... Agencies § 17.82 Contracts for outpatient services for veterans with alcohol or drug dependence or abuse... requirements of the “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR part 2) and...
... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82 Pensions... Agencies § 17.82 Contracts for outpatient services for veterans with alcohol or drug dependence or abuse... requirements of the “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR part 2) and...
Grazioli, Véronique S; Hicks, Jennifer; Kaese, Greta; Lenert, James; Collins, Susan E
Chronically homeless individuals with alcohol dependence experience severe alcohol-related consequences. It is therefore important to identify factors that might be associated with reduced alcohol-related harm, such as the use of safer-drinking strategies. Whereas effectiveness of safer-drinking strategies has been well-documented among young adults, no studies have explored this topic among more severely affected populations, such as chronically homeless individuals with alcohol dependence. The aims of this study were thus to qualitatively and quantitatively document safer-drinking strategies used in this population. Participants (N=31) were currently or formerly chronically homeless individuals with alcohol dependence participating in a pilot study of extended-release naltrexone and harm-reduction counseling. At weeks 0 and 8, research staff provided a list of safer-drinking strategies for participants to endorse. Implementation of endorsed safer-drinking strategies was recorded at the next appointment. At both time points, strategies to buffer the effects of alcohol on the body (e.g., eating prior to and during drinking) were most highly endorsed, followed by changing the manner in which one drinks (e.g., spacing drinks), and reducing alcohol consumption. Quantitative analyses indicated that all participants endorsed safer-drinking strategies, and nearly all strategies were implemented (80-90% at weeks 0 and 8, respectively). These preliminary findings indicate that chronically homeless people with alcohol dependence use strategies to reduce harm associated with their drinking. Larger randomized controlled trials are needed to test whether interventions that teach safer-drinking strategies may reduce overall alcohol-related harm in this population.
Li, Fengyuan; Duan, Kangmin; Wang, Cuiling; McClain, Craig; Feng, Wenke
Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration) approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed. PMID:26839540
Zhou, Qing; King, Kevin M; Chassin, Laurie
This study examined the prospective relations among family history density of alcoholism (FHD), adolescent family harmony, and young adults' alcohol and drug dependence. Family harmony was rated by mothers and fathers in adolescence, and young adults' substance dependence diagnoses were obtained through structured interviews. Higher FHD predicted lower adolescent family harmony, which in turn increased young adults' odds of being diagnosed with drug dependence (with and without alcohol dependence) compared to no diagnoses or to alcohol dependence only. Family harmony also interacted with FHD such that the protective effect of family harmony on young adults' drug dependence with or without alcohol dependence decreased as FHD rose, and was nonsignificant at high levels of FHD. The findings suggest the importance of distinguishing among alcohol and drug dependence disorders and examining their differential etiological pathways, and also suggest that the protective effects of harmonious family environments on substance dependence may be limited at high levels of FHD.
Freynhagen, Rainer; Backonja, Miroslav; Schug, Stephan; Lyndon, Gavin; Parsons, Bruce; Watt, Stephen; Behar, Regina
Treatments for physical dependence and associated withdrawal symptoms following the abrupt discontinuation of prescription drugs (such as opioids and benzodiazepines), nicotine, alcohol, and cannabinoids are available, but there is still a need for new and more effective therapies. This review examines evidence supporting the potential use of pregabalin, an α2δ voltage-gated calcium channel subunit ligand, for the treatment of physical dependence and associated withdrawal symptoms. A literature search of the MEDLINE and Cochrane Library databases up to and including 11 December 2015 was conducted. The search term used was '(dependence OR withdrawal) AND pregabalin'. No other date limits were set and no language restrictions were applied. Works cited in identified articles were cross-referenced and personal archives of references also searched. Articles were included based on the expert opinions of the authors. There is limited evidence supporting the role of pregabalin for the treatment of physical dependence and accompanying withdrawal symptoms associated with opioids, benzodiazepines, nicotine, cannabinoids, and alcohol, although data from randomized controlled studies are sparse. However, the current evidence is promising and provides a platform for future studies, including appropriate randomized, placebo- and/or comparator-controlled studies, to further explore the efficacy and safety of pregabalin for the treatment of withdrawal symptoms. Given the potential for pregabalin misuse or abuse, particularly in individuals with a previous history of substance abuse, clinicians should exercise caution when using pregabalin in this patient population.
Ubaldi, Massimo; Del Bello, Fabio; Domi, Esi; Pigini, Maria; Nasuti, Cinzia
We have recently demonstrated that allyphenyline, behaving as α2C-adrenoceptor/serotonin 5-HT1A receptor agonist and α2A-adrenoceptor antagonist, in mice enhanced morphine analgesia, attenuated morphine withdrawal symptoms, showed significant antidepressant-like activity and was devoid of sedative side effects. Opioid and alcohol withdrawal shares several common neurobiological and molecular mechanisms. Therefore, in this study we expanded our analysis of the pharmacological properties of allyphenyline by investigating its ability to prevent the expression of somatic withdrawal signs, anxiety-like behavior and hyperlocomotion associated with chronic ethanol intoxication. Rats were subjected to induction of ethanol dependence via repeated daily intragastric ethanol (20%) administration for 4 consecutive days. Twelve hours after the last alcohol administration, somatic alcohol withdrawal signs were scored. Results revealed a significant expression of physical withdrawal signs that were not affected by intraperitoneal (i.p.) administration of allyphenyline at the doses of 0.05, 0.275 and 0.5 mg/kg. In contrast, allyphenyline (0.05 and 0.275 mg/kg i.p.) significantly reduced hyperanxiety-like behavior observed 6 days after alcohol intoxication as measured using the defensive burying test. Allyphenyline also reduced open field hyperlocomotor activity associated with alcohol withdrawal. Notably, the anxiolytic effect of the compound, as well as the already reported antidepressant action, was observed at very low doses, suggesting the involvement of its α2C-adrenoceptor/serotonin 5-HT1A receptor agonism. Therefore, the present investigation suggests that allyphenyline might represent an interesting pharmacological tool to investigate the potential of compounds exhibiting α2C-adrenoceptor/serotonin 5-HT1A receptor agonism and α2A-adrenoceptor antagonism in the treatment of hyperanxiety and hyperlocomotion occurring during alcohol withdrawal in dependent subjects.
McDonell, Michael G.; Skalisky, Jordan; Leickly, Emily; McPherson, Sterling; Battalio, Samuel; Nepom, Jenny R.; Srebnik, Debra; Roll, John; Ries, Richard K.
Aims This study investigated which ethyl glucuronide immunoassay (EtG-I) cutoff best detects heavy versus light drinking over five days in alcohol dependent outpatients. Methods A total of 121 adults with alcohol use disorders and co-occurring psychiatric disorders taking part in an alcohol treatment study. Participants provided self-reported drinking data and urine samples three time per week for 16-weeks (total samples = 2761). Agreement between low (100 ng/mL, 200 ng/mL), and moderate (500 ng/mL) EtG-I cutoffs and light (women ≤3 standard drinks, men ≤ 4 standard drinks) and heavy drinking (women >3, men >4 standard drinks) were calculated over one to five days. Results The 100 ng/mL cutoff detected >76% of light drinking for two days, and 66% at five days. The 100 ng/mL cutoff detected 84% (1 day) to 79% (5 days) of heavy drinking. The 200 ng/mL cutoff detected >55% of light drinking across five days and >66% of heavy drinking across five days. A 500 ng/mL cutoff identified 68% of light drinking and 78% of heavy drinking for one day, with detection of light (2–5 days <58%) and heavy drinking (2–5 days <71%) decreasing thereafter. Relative to 100 ng/mL, the 200 ng/mL and 500 ng/mL cutoffs were less likely to result in false positives. Conclusions An EtG-I cutoff of 100 ng/mL is most likely to detect heavy drinking for up to five days and any drinking during the previous two days. Cutoffs of ≥ 500 ng/mL are likely to only detect heavy drinking during the previous day. PMID:26475403
Hoeppner, Bettina B.; Kahler, Christopher W.; Jackson, Kristina M.
Background Current initiatives to update diagnostic criteria for alcohol use disorders (AUDs) have stimulated dialogue about the usefulness of indicators of alcohol consumption in the diagnosis of AUDs. Methods This study used Rasch model analyses to examine the properties of alcohol consumption descriptors and AUD symptoms among 3,382 treatment-seeking adolescents, aged 12–18 years, in the DATOS-A (USDHHS, 1993–1995) baseline assessment, and evaluated the predictive validity of different scoring methods (with and without alcohol consumption) for 12-month alcohol involvement. Results Rasch model analyses supported the unidimensionality of indices of alcohol consumption and AUD symptoms. Test information functions showed that adding consumption items provides further information at all points of the alcohol involvement severity spectrum. Combining AUD symptoms with indices of alcohol consumption provided better prediction of alcohol involvement after treatment than either AUD symptoms counts or DSM-IV dependence diagnosis alone. Differential item functioning (DIF), however, was observed for select items. Generally, indices of drinking “too much too fast” were more severe for females, African Americans and Hispanics, while the opposite was true for items measuring “too much too often”. For age, “too much too often” items were more severe for the younger (12–14yrs) age group, and AUD symptoms were more severe for the older (15–18yrs) age group. Conclusions Indices of alcohol consumption can be validly scaled along with AUD symptoms in this population, and their inclusion provides statistical measurement advantages. Nevertheless, caution is necessary in using consumption items in measuring alcohol involvement due to DIF observed across sex, race and age. PMID:21146941
Reimer, J; Cimander, K F; Reimer, C
Subjects with alcohol dependence or alcohol-related health problems frequently use the primary care system without receiving the correct diagnosis or specific interventions. Stigma, lack of knowledge and know-how with regards to diagnosis and treatment of alcohol-related disorders on the site of the health care professionals may contribute to the treatment gap. General anamnesis, clinical evaluation, and laboratory parameters can serve as indicators, and validated screening tests can further corroborate the hypothesis. However, a diagnosis should only be made according to ICD-10 criteria. Adequate counselling techniques substantially contribute to successful physician-patient interaction. Motivational Interviewing combines a positive, appreciative attitude with communicative techniques to create a motivation to change. It includes general approaches as open questions, appreciation of the patient, active listening, summarizing results as well as specific approaches such as change and confidence talk and dealing with resistance. Within a positive relationship, the conversation can lead to change. Brief interventions cover four to five sessions with a duration between five and sixty minutes. Brief interventions based on an empathic attitude und reflection of findings, a brief advice leaving the responsibility on the patient's side and supporting self-efficacy can improve alcohol-related disorders. The transtheoretical model of change may help the health care provider to adapt intervention strategies to the patient's state. Primary health care provides an adequate framework for screening, diagnosis and intervention for alcohol-related disorders with the aim of reduction or abstinence. Further institutions in addiction treatment such as self-help and clinical institutions may complement the treatment system.
Brown, E. Sherwood; Domingo Davila, S.; Nakamura, Alyson; Carmody, Thomas J.; Rush, A. John; Lo, Alexander; Holmes, Traci; Adinoff, Bryon; Caetano, Raul; Swann, Alan C; Sunderajan, Prabha; Bret, Mary E.
Background Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment non-adherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study. Methods Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/day) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression (HRSD17), Inventory of Depressive Symptomatology–Self-Report (IDS-SR30), Young Mania Rating Scale (YMRS), Penn Alcohol Craving Scale (PACS), liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model. Results Baseline and demographic characteristics in the two groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks/day or other alcohol-related or mood measures (p>.05). Overall side effect burden, glucose and cholesterol were similar in the two groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. −2.0 lbs [SE 1.4], p=.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p=.04) with quetiapine (+0.40 (SE 0.3)) than placebo (−0.52 (SE 0.3)) at week 6 but not week 12. Retention (survival) in the study was similar in the groups. Conclusions Findings suggest that
Karlsson, Oskar; Roman, Erika
The acute effects of alcohol administration are age-, dose-, time- and task-dependent. Although generally considered to be a sedative drug, alcohol has both stimulatory and depressant effects on behavior, depending on dose and time. Alcohol-induced motor activating effects are consistently shown in mice but rarely demonstrated in adult, outbred rats using conventional behavioral tests. The aim of the present experiment was to study acute alcohol-induced effects on behavioral profiles in a more complex environment using the novel multivariate concentric square field™ (MCSF) test, designed for assessing different behaviors in the same trial including locomotor activity. Adult male Wistar rats (Sca:WI) were administered one intraperitoneal (i.p.) injection of alcohol (0.0 g/kg, 0.5 g/kg, 1.0 g/kg, or 1.5 g/kg) 5 min prior to the 30-min MCSF test. The two highest doses induced marked motor-suppressing effects. A significant interaction between group and time was found in general activity when comparing rats exposed to alcohol at 0.0 g/kg and 0.5 g/kg. In contrast to the 0.0 g/kg dose that increased the activity over time, animals administered the low dose (0.5 g/kg) demonstrated an initial high activity followed by a decline over time. No indications for acute alcohol-induced anxiolytic-like effects were found. The multivariate setting in the MCSF test appears to be sensitive for detecting motor-activating effects of low doses of alcohol as well as reduced locomotion at doses lower than in other behavioral tasks. The detection of subtle changes in behavior across time and dose is important for understanding alcohol-induced effects. This approach may be useful in evaluating alcohol doses that correspond to different degrees of intoxication in humans.
Nosen, Elizabeth; Nillni, Yael I.; Berenz, Erin C.; Schumacher, Julie A.; Stasiewicz, Paul R.; Coffey, Scott F.
Posttraumatic stress disorder (PTSD) commonly co-occurs with alcohol dependence (AD) and negatively affects treatment outcomes. Trauma-related negative affect enhances substance craving in laboratory cue-reactivity studies of AD individuals, but the role of positive affect has not been established. In this study, 108 AD treatment-seeking adults…
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
Schumacher, Julie A; Coffey, Scott F; Leonard, Kenneth E; O'Jile, Judith R; Landy, Noah C
This study builds on research identifying deficits in behavioral self-regulation as risk factors for intimate partner violence (IPV). It also builds on alcohol administration research identifying these deficits as moderators of the association between acute alcohol consumption and aggression in laboratory paradigms. Participants analyzed were 97 men seeking residential treatment for alcohol dependence who were involved in a current or recent heterosexual relationship of at least 1 year. Participants completed a self-report measure of impulsivity, neuropsychological tests of executive function, and computerized delay discounting and behavioral inhibition tasks. With the exception of the self-report measure of impulsivity, performance on measures of behavioral self-regulation was not associated with the occurrence or frequency of past year IPV in this sample. Similarly, self-reported impulsivity moderated the association between daily drinking and IPV in multivariate models controlling for daily drug use, but deficits in performance on other measures did not. Performance on a tower task moderated the association between daily drinking and the occurrence of IPV, but contrary to hypotheses, better task performance was associated with greater likelihood of IPV on drinking days. These results suggest that self-perceived impulsivity is a better predictor of IPV in alcohol treatment seeking men than deficits in performance on behavioral measures of delay discounting, behavioral inhibition, and executive function.
Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L; Musselman, Samuel C; Forbes, Erika E
Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.
Podschus, J; Dufeu, P; Schmidt, L G; Sallstrom-Baum, S; Rommelspacher, H
Plasma dopamine, β-carbolines (norharman, harman) and isoquinolines ((R)- and (S)-salsolinol) were examined for their relationship to antisocial tendencies in 138 drinking men with an alcohol dependence syndrome according to ICD-10 criteria. Antisociality was assessed according to the following criteria: delinquency, involvement in fist-fights and homelessness. The personality structure was documented by the Tridimensional Personality Questionnaire of Cloninger. An early age of onset of alcohol dependence and a high degree of 'novelty seeking' were associated with antisocial tendencies. Of the β-carbolines and isoquinolines, harman and (S)-salsolinol were significantly decreased among antisocial alcoholics. Norharman, (R)-salsolinol and dopamine were not associated with antisocial personality. The contribution of endogenous alkaloids to the biological characterization of antisocial tendencies in alcoholics is described.
... parents and other adults use alcohol socially — having beer or wine with dinner, for example — alcohol seems ... besides just hanging out in someone's basement drinking beer all night. Plan a trip to the movies, ...
Quanbeck, Andrew; Chih, Ming-Yuan; Isham, Andrew; Johnson, Roberta; Gustafson, David
Several systems for treating alcohol-use disorders (AUDs) exist that operate on mobile phones. These systems are categorized into four groups: text-messaging monitoring and reminder systems, text-messaging intervention systems, comprehensive recovery management systems, and game-based systems. Text-messaging monitoring and reminder systems deliver reminders and prompt reporting of alcohol consumption, enabling continuous monitoring of alcohol use. Text-messaging intervention systems additionally deliver text messages designed to promote abstinence and recovery. Comprehensive recovery management systems use the capabilities of smart-phones to provide a variety of tools and services that can be tailored to individuals, including in-the-moment assessments and access to peer discussion groups. Game-based systems engage the user using video games. Although many commercial applications for treatment of AUDs exist, few (if any) have empirical evidence of effectiveness. The available evidence suggests that although texting-based applications may have beneficial effects, they are probably insufficient as interventions for AUDs. Comprehensive recovery management systems have the strongest theoretical base and have yielded the strongest and longest-lasting effects, but challenges remain, including cost, understanding which features account for effects, and keeping up with technological advances. PMID:26259005
Schellekens, Arnt F A; Franke, Barbara; Ellenbroek, Bart; Cools, Alexander; de Jong, Cor A J; Buitelaar, Jan K; Verkes, Robbert-Jan
Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene-environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene-environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.
Caliguri, Joseph P., Ed.
This extensive annotated bibliography provides a compilation of documents retreived from a computerized search of the ERIC, Social Science Citation Index, and Med-Line databases on the topic of alcoholism. The materials address the following areas of concern: (1) attitudes toward alcohol users and abusers; (2) characteristics of alcoholics and…
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
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.
The treatment of alcoholism still presents great problems because a number of factors have to be taken into consideration. Tranquilizers and chlormethiazol are only justified in the detoxication phase. For the subsequent after-care, depot neuroleptics are recommended because of the uniformly high plasma level. We gave clopentixol decanoate - 100 mg i.m. - in two-weekly intervals. The symptoms caused by ethylism were adequately overcome without side effects. Clopentixol decanoate creates the basis for successful psychotherapy: only when the mood situation is compensated and the internal unrest overcome can verbal therapy be successful.
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
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
Ashcroft, Darren M.; Owens, Lynn; van Staa, Tjeerd P.; Pirmohamed, Munir
Aim To evaluate drug therapy for alcohol dependence in the 12 months after first diagnosis in UK primary care. Design Open cohort study. Setting General practices contributing data to the UK Clinical Practice Research Database. Participants 39,980 people with an incident diagnosis of alcohol dependence aged 16 years or older between 1 January 1990 and 31 December 2013. Main outcome measure Use of pharmacotherapy (acamprosate, disulfiram, naltrexone, baclofen and topiramate) to promote abstinence from alcohol or reduce drinking to safe levels in the first 12 months after a recorded diagnosis of alcohol dependence. Findings Only 4,677 (11.7%) of the cohort received relevant pharmacotherapy in the 12 months following diagnosis. Of the 35,303 that did not receive pharmacotherapy, 3,255 (9.2%) received psychosocial support. The remaining 32,048 (80.2%) did not receive either mode of treatment in the first 12 months. Factors that independently reduced the likelihood of receiving pharmacotherapy included: being male (Odds Ratio [OR] 0.74; 95% CI 0.69 to 0.78); older (65-74 years: OR 0.61; 95% CI 0.49 to 0.77); being from a practice based in the most deprived quintile (OR 0.58; 95% CI 0.53 to 0.64); and being located in Northern Ireland (OR 0.78; 95% CI 0.67 to 0.91). The median duration to initiation of pharmacotherapy was 0.80 months (95% CI 0.70 to 1.00) for acamprosate and 0.60 months (95% CI 0.43 to 0.73) for disulfiram. Persistence analysis for those receiving acamprosate and disulfiram revealed that many patients never received a repeat prescription; persistence at 6 months was 27.7% for acomprosate and 33.2% for disulfiram. The median duration of therapy was 2.10 months (95% CI 1.87 to 2.53) for acamprosate and 3.13 months (95% CI 2.77 to 3.36) for disulfiram. Conclusion Drug therapy to promote abstinence in alcohol dependent patients was low, with the majority of patients receiving no therapy, either psychological or pharmacological. When drug therapy was
Thurang, Anna Maria; Palmstierna, Tom; Tops, Anita Bengtsson
The aim of the present study is to describe and understand the meaning of living with alcohol dependency (AD) as a man. Studies point out a high prevalence of AD in men and the reasons for, and consequences of, that are complex. However, today there is a lack of knowledge about men's lived experiences of having AD. In-depth interviews were conducted with 15 alcohol dependent men and analyzed using a phenomenological-hermeneutic approach. In the comprehensive understanding, findings from the naïve understanding and the structural analysis were interpreted with help from both gender and caring theoretical perspectives. "A Fallible Man" and "A Man with Powerfulness" were disclosed as two main gender formations influencing senses of well-being. A Fallible Man involved varying experiences of restrictions, being in control, and meaninglessness. Being in control promoted a sense of well-being. A Man with Powerfulness involved energetic activity, and the development and maintaining of interests as well as risk-taking. Being powerful diminished feelings of meaninglessness, cravings, and social alienation. The results show, among other things, that the men live an incompatible life and, because of that, need support and guidance to find a more meaningful life. This can be accomplished if caregivers allow men to be in focus and involved in planning their own care. To avoid limiting the men while they are in treatment, the health care professionals also need to focus on the men's everyday life. This focus involves acknowledging the men's individual experiences of what enriches and limits their everyday lives.
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
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
Miguel-Hidalgo, José Javier; Wilson, Barbara A; Hussain, Syed; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A
Reduced density of glial cells and low levels of some astrocyte proteins have been described in the orbitofrontal cortex (OFC) in depression and alcoholism, two disorders often comorbid. These regressive changes may also involve the communication between astrocytes via gap junctions and hemichannels, which play important regulatory roles in neurotransmission. We determined levels and morphological immunostaining parameters of connexin 43 (Cx43), the main protein subunit of astrocyte gap junctions/hemichannels, in the OFC of subjects with depression, alcoholism or comorbid depression/alcoholism as compared to non-psychiatric subjects. Postmortem brain samples from 23 subjects with major depressive disorder (MDD), 16 with alcohol dependence, 13 with comorbid MDD and alcohol dependence, and 20 psychiatrically-normal comparison subjects were processed for western blots to determine Cx43 levels. Area fraction of Cx43 immunoreactivity, and density and average size of immunoreactive puncta were measured in histological sections. There was a significant, larger than 60 percent decrease in Cx43 level in the three psychiatric groups as compared to controls. Area fraction of immunoreactivity and immunoreactive punctum size were reduced in all psychiatric groups, but Cx43-immunoreactive puncta density was reduced only in alcohol-dependent subjects. Among psychiatric subjects, no difference in Cx43 levels or immunostaining was found between suicides and non-suicides. The present data suggest that dysfunction of the OFC is accompanied by reduction in the levels of gap junction protein Cx43 in depression and alcoholism, and reduction in density of Cx43 immunoreactive puncta only in alcoholism, pointing to altered gap junction or hemichannel-based communication in the pathophysiology of those disorders.
Miguel-Hidalgo, José Javier; Wilson, Barbara A.; Hussain, Syed; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A.
Reduced density of glial cells and low levels of some astrocyte proteins have been described in the orbitofrontal cortex (OFC) in depression and alcoholism, two disorders often comorbid. These regressive changes may also involve the communication between astrocytes via gap junctions and hemichannels, which play important regulatory roles in neurotransmission. We determined levels and morphological immunostaining parameters of connexin 43 (Cx43), the main protein subunit of astrocyte gap junctions/hemichannels, in the OFC of subjects with depression, alcoholism or comorbid depression/alcoholism as compared to non-psychiatric subjects. Postmortem brain samples from 23 subjects with major depressive disorder (MDD), 16 with alcohol dependence, 13 with comorbid MDD and alcohol dependence, and 20 psychiatrically-normal comparison subjects were processed for western blots to determine Cx43 levels. Area fraction of Cx43 immunoreactivity, and density and average size of immunoreactive puncta were measured in histological sections. There was a significant, larger than 60 percent decrease in Cx43 level in the three psychiatric groups as compared to controls. Area fraction of immunoreactivity and immunoreactive punctum size were reduced in all psychiatric groups, but Cx43-immunoreactive puncta density was reduced only in alcohol-dependent subjects. Among psychiatric subjects, no difference in Cx43 levels or immunostaining was found between suicides and non-suicides. The present data suggest that dysfunction of the OFC is accompanied by reduction in the levels of gap junction protein Cx43 in depression and alcoholism, and reduction in density of Cx43 immunoreactive puncta only in alcoholism, pointing to altered gap junction or hemichannel-based communication in the pathophysiology of those disorders. PMID:24774648
Clarke, Toni-Kim; Laucht, Manfred; Ridinger, Monika; Wodarz, Norbert; Rietschel, Marcella; Maier, Wolfgang; Lathrop, Mark; Lourdusamy, Anbarasu; Zimmermann, Ulrich S; Desrivieres, Sylvane; Schumann, Gunter
Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p=0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p=0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.
Lang, J-P; Bonnewitz, M-L; Kusterer, M; Lalanne-Tongio, L
Alcohol consumption in France exceeds the European average (12.7L of pure alcohol/habitant/year in 2009 for an average of 12.5 L). This consumption has a major professional, social and health impact on the individuals and their families. The cost of such, estimated in Europe to be of 155.8 billion Euros in 2010, is the highest among the central nervous system diseases in Europe, far higher than that of depression or dementia. Patients suffering from psychiatric disorders are more frequently affected by problems related to alcohol use than the general population. They are also more vulnerable to the immediate and subsequent consequences of their consumption. The alcohol related disorders that are often accompanied by risk taking and other addictive behaviour require a global assessment of the addiction, with and without substance, and of the complications. These have a strong impact on risk taking, compliance with care, and the morbidity of somatic and psychiatric disorders, as well as access to optimal care and the life span of patients suffering from psychiatric disorders. The development of addictology care, with integrative treatment programs, is recommended in response to these public health issues. Nevertheless, specific addictology practices and partners with addictology care structures are still scarcely developed in psychiatry. Firstly, it would be necessary to set up such integrated treatments through the systematisation of an "addictology" checkup on admission, a global assessment of addictive behaviour and cognitive disorders, using pragmatic tools that are user-friendly for the care teams, maintain the reduction in risk taking, and apply prescriptions for addiction to psychotropic treatments, in liaison with the referring general practitioner. As early as possible, accompanied by specific training in addictology for the psychiatrists and the mental health nursing teams, such care could be enhanced by the development of liaison and advanced psychiatric
Bell, Richard L.; Franklin, Kelle M.; Hauser, Sheketha R.; Zhou, Feng C.
This paper introduces the Special Section: Pharmacotherapies for the Treatment of Alcohol Abuse and Dependence and provides a summary of patents targeting neurotransmitter systems not covered in the other four chapters. The World Health Organization notes that alcoholic-type drinking results in 2.5 million deaths per year, and these deaths occur to a disproportionately greater extent among adolescents and young adults. Developing a pharmacological treatment targeting alcohol abuse and dependence is complicated by (a) the heterogeneous nature of the disease(s), (b) alcohol affecting multiple neurotransmitter and neuromodulator systems, and (c) alcohol affecting multiple organ systems which in turn influence the function of the central nervous system. Presently, the USA Federal Drug Administration has approved three pharmacotherapies for alcoholism: disulfiram, naltrexone, and acamprosate. This chapter provides a summary of the following systems, which are not covered in the accompanying chapters; alcohol and acetaldehyde metabolism, opioid, glycinergic, GABA-A, neurosteroid, dopaminergic, serotonergic, and endocannabinoid, as well as patents targeting these systems for the treatment of alcoholism. Finally, an overview is presented on the use of pharmacogenetics and pharmacogenomics in tailoring treatments for certain subpopulations of alcoholics, which is expected to continue in the future. PMID:22574678
Mensinger, Janell Lynn; Lynch, Kevin G.; Tenhave, Thomas R.; McKay, James R.
A previous randomized trial with 224 alcohol and/or cocaine addicts who had completed an initial phase of treatment indicated that 12 weeks of telephone-based continuing care yielded higher abstinence rates over 24 months than did group counseling continuing care. The current study examined mediators of this treatment effect. Results suggested…
Mccrady, Barbara S.; Epstein, Elizabeth E.; Cook, Sharon; Jensen, Noelle; Hildebrandt, Thomas
Although alcohol use disorders (AUDs) adversely affect women, research on efficacious treatments for women is limited. In this randomized efficacy trial of 102 heterosexual women with AUDs, the authors compared alcohol behavioral couple therapy (ABCT) and alcohol behavioral individual therapy (ABIT) on percentage of days abstinent (PDA) and…
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
Denaës, Timothé; Lodder, Jasper; Chobert, Marie-Noële; Ruiz, Isaac; Pawlotsky, Jean-Michel; Lotersztajn, Sophie; Teixeira-Clerc, Fatima
Kupffer cells, the resident macrophages of the liver, play a major role in the pathogenesis of alcoholic liver disease. We have previously demonstrated that CB2 receptor protects against alcoholic liver disease by inhibiting alcohol-induced inflammation and steatosis via the regulation of Kupffer cell activation. Here, we explored the mechanism underlying these effects and hypothesized that the anti-inflammatory properties of CB2 receptor in Kupffer cells rely on activation of autophagy. For this purpose, mice invalidated for CB2 receptor (CB2(Mye-/-) mice) or for the autophagy gene ATG5 (ATG5(Mye-/-) mice) in the myeloid lineage, and their littermate wild-type mice were subjected to chronic-plus-binge ethanol feeding. CB2(Mye-/-) mice showed exacerbated alcohol-induced pro-inflammatory gene expression and steatosis. Studies in cultured macrophages demonstrated that CB2 receptor activation by JWH-133 stimulated autophagy via a heme oxygenase-1 dependent pathway. Moreover, JWH-133 reduced the induction of inflammatory genes by lipopolysaccharide in wild-type macrophages, but not in ATG5-deficient cells. The CB2 agonist also protected from alcohol-induced liver inflammation and steatosis in wild-type mice, but not in ATG5(Mye-/-) mice demonstrating that macrophage autophagy mediates the anti-inflammatory and anti-steatogenic effects of CB2 receptor. Altogether these results demonstrate that CB2 receptor activation in macrophages protects from alcohol-induced steatosis by inhibiting hepatic inflammation through an autophagy-dependent pathway.
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
... Alcohol Awareness Month April is Alcohol Awareness Month Biosensor Challenge Learn more College Drinking Learn More Alcohol Dependence Get the facts Alcohol Awareness Month Biosensor Challenge College Drinking Alcohol Dependence Latest News New & ...
Baird, Francis X.; Frankel, Arthur J.
Reviews the history of community-based treatment for offenders with drug and alcohol addiction. Describes the treatment regimen in two residential programs for offenders with drug and alcohol problems, including a description of the components of the residential treatment model utilized in these two programs. Findings support the efficacy of…
Loas, G; Otmani, O; Lecercle, C; Jouvent, R
Several authors have shown that alexithymia, emotional and perceptual dependency characterize patients suffering from substance abuse. The aim of the study is to test the hypothesis that the emotional and cognitive components of alexithymia are associated with dependency in alcoholics. Three groups were investigated: 60 inpatients meeting the DSM-IV criteria for alcohol dependence, 57 healthy subjects, 144 university students. All subjects completed the following rating scales: The 20-item Toronto Alexithymia Scale (TAS-20), the Interpersonal Dependency Inventory (IDI), the Beck Depression Inventory (BDI), and the Embedded Figures Test (EFT). Partial correlations, using the BDI score as constant, were calculated. In normal subjects, the 'Emotion' subscale of the TAS-20 correlated with the 'Lack of social self-confidence' subscale of the IDI and the 'Cognitive' subscale of the TAS-20 did not correlate with the EFT score. In alcoholics, the 'Cognitive' subscale of the TAS-20 correlated with the 'Lack of social self-confidence' subscale, with the EFT score and with the 'Affirmation of autonomy' subscale. A particular cognitive style characterized by externally oriented thinking, affirmation of autonomy as denial of emotional dependency and field dependence could characterize alcoholics.
Merinov, A V; Shustov, D I
The effect of the suicidal activity in men with alcohol dependence on suicidal indexes, personal-codependency and psychological specifics of their wives has been studied. It has been found that women married to suicidal men with alcohol dependence significantly more frequently demonstrate suicidal activity (a phenomenon of suicidal matrimonial comorbidity) compared to wives of "non-suicidal" men. They also reveal non-suicidal behavioral patterns more frequently and prosuicidal predictors are quite common in them. This contingent of women has high suicidal potential that needs special attention during the therapeutic work.
Geisel, Olga; Hellweg, Rainer; Müller, Christian A
The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders.
Penzlin, Ana Isabel; Siepmann, Timo; Illigens, Ben Min-Woo; Weidner, Kerstin; Siepmann, Martin
Background and objective In patients with alcohol dependence, ethyl-toxic damage of vasomotor and cardiac autonomic nerve fibers leads to autonomic imbalance with neurovascular and cardiac dysfunction, the latter resulting in reduced heart rate variability (HRV). Autonomic imbalance is linked to increased craving and cardiovascular mortality. In this study, we sought to assess the effects of HRV biofeedback training on HRV, vasomotor function, craving, and anxiety. Methods We conducted a randomized controlled study in 48 patients (14 females, ages 25–59 years) undergoing inpatient rehabilitation treatment. In the treatment group, patients (n=24) attended six sessions of HRV biofeedback over 2 weeks in addition to standard rehabilitative care, whereas, in the control group, subjects received standard care only. Psychometric testing for craving (Obsessive Compulsive Drinking Scale), anxiety (Symptom Checklist-90-Revised), HRV assessment using coefficient of variation of R-R intervals (CVNN) analysis, and vasomotor function assessment using laser Doppler flowmetry were performed at baseline, immediately after completion of treatment or control period, and 3 and 6 weeks afterward (follow-ups 1 and 2). Results Psychometric testing showed decreased craving in the biofeedback group immediately postintervention (OCDS scores: 8.6±7.9 post-biofeedback versus 13.7±11.0 baseline [mean ± standard deviation], P<0.05), whereas craving was unchanged at this time point in the control group. Anxiety was reduced at follow-ups 1 and 2 post-biofeedback, but was unchanged in the control group (P<0.05). Following biofeedback, CVNN tended to be increased (10.3%±2.8% post-biofeedback, 10.1%±3.5% follow-up 1, 10.1%±2.9% follow-up 2 versus 9.7%±3.6% baseline; P=not significant). There was no such trend in the control group. Vasomotor function assessed using the mean duration to 50% vasoconstriction of cutaneous vessels after deep inspiration was improved following biofeedback
Joos, Leen; Goudriaan, Anna E; Schmaal, Lianne; Fransen, Erik; van den Brink, Wim; Sabbe, Bernard G C; Dom, Geert
Poor impulse control plays an important role in the development, course and relapse of substance use disorders. Therefore, improving impulse control may represent a promising approach in the treatment of alcohol dependence. This study aimed to test the effect of modafinil on impulse control and alcohol use in alcohol dependent patients (ADP) in a randomized, double-blind, placebo-controlled trial. Eighty-three abstinent ADP were randomized to 10 weeks modafinil (300 mg/d) or placebo. Alcohol use was quantified using the timeline follow-back method and was assessed until 6 months after treatment discontinuation. Impulsivity was assessed using self-report questionnaires (Barratt Impulsiveness Scale; State Impulsivity questionnaire) and neurocognitive tasks (Stop Signal Task; Delay Discounting Task) administered before, during and after treatment. Modafinil significantly improved self-report measures of state impulsivity, but had no effect on percentage of abstinent days or percentage of heavy drinking days, nor on the behavioral measures of impulsivity. However, subgroup analysis revealed that modafinil prolonged the time to relapse (p=.022) and tended to increase the percentage of abstinent days (p=.066) in ADP with poor response inhibition at baseline, whereas modafinil increased the percentage of heavy drinking days (p=.003) and reduced the percentage of abstinent days (p=.002) in patients with better baseline response inhibition. Overall results do not favor the use of modafinil in order to reduce relapse or relapse severity in ADP, and caution is required in prescribing modafinil to a non-selected sample of ADP. Further research on the effect of modafinil in ADP with poor baseline response inhibition is warranted.
Zaniewska, Agnieszka; Borzym-Kluczyk, Malgorzata; Szajda, Slawomir D; Romatowski, Jacek; Gil, Andrzej; Knas, Malgorzata; Dobryniewski, Jacek; Zwierz, Krzysztof
The aim of this study was to determine the activity of the lysosomal exoglycosidases: alpha-mannosidase (MAN), alpha-fucosidase (FUC), and beta-glucuronidase (GLUCUR) in serum of alcohol-dependent men supplemented and not supplemented with borage oil enriched with vitamin E. Serum was collected from eight social drinkers and 16 alcohol-dependent men after a drinking period. The activity of exoglycosidases and the concentration of protein in serum were determined. The increase in specific activity of MAN and GLUCUR was significant in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E, in comparison with the specific activity in serum of social drinkers. In serum of alcohol-dependent men treated with borage oil enriched with vitamin E, specific activity of MAN and GLUCUR fluctuated in comparison with alcohol-dependent men not supplemented. Specific activity of FUC in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E showed a tendency to increase, in comparison with social drinkers. Specific activity of FUC had a tendency to decrease in serum of alcohol-dependent men supplemented with borage oil enriched with vitamin E, in comparison with alcohol-dependent men not supplemented. Thus, supplementation of alcohol-dependent men after a long-lasting drinking period with borage oil and vitamin E did not change the rate of catabolism of the oligosaccharide chains of glycoconjugates, as evaluated by serum activity of exoglycosidases.
Pettinati, Helen M.; Oslin, David W.; Kampman, Kyle M.; Dundon, William D.; Xie, Hu; Gallis, Thea L.; Dackis, Charles A.; O’Brien, Charles P.
BACKGROUND Empirical evidence has only weakly supported antidepressant treatment for patients with co-occurring depression and alcohol dependence. While some studies have demonstrated that antidepressants reduce these patients’ depressive symptoms, most studies have not found antidepressants helpful in reducing excessive drinking in these patients. We provide results from a double blind, placebo-controlled trial that evaluated the efficacy of combining approved medications for depression (sertraline) and alcohol dependence (naltrexone) for treating patients with both disorders. METHODS 170 depressed, alcohol-dependent patients were randomized for 14 weeks to sertraline (200mg/day), naltrexone (100mg/day), the combination, or placebo, while receiving weekly cognitive behavioral therapy. RESULTS The sertraline + naltrexone combination produced a higher alcohol abstinence rate (53.7%; p = .001; odds ratio = 3.7), and a longer delay before relapse to heavy drinking (98 median days; p = .003; d = .54), than the other treatments: naltrexone (21.3% abstinent, 29 days), sertraline (27.5% abstinent, 23 days), or placebo (23.1% abstinent, 26 days). There also was a trend for more patients in the medication combination group not to be depressed by the end of treatment (83.3%; p = .014; odds ratio = 3.6), compared to the other treatments. The serious adverse event rate was 25.9%, with fewer reported by the medication combination group (11.9%; p < .02) than the other treatments. CONCLUSION More depressed, alcohol-dependent patients taking the sertraline + naltrexone combination achieved abstinence from alcohol, delayed relapse to heavy drinking, reported fewer serious adverse events, and tended not to be depressed by the end of treatment. PMID:20231324
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.
Mathies, Laura D; Blackwell, GinaMari G; Austin, Makeda K; Edwards, Alexis C; Riley, Brien P; Davies, Andrew G; Bettinger, Jill C
Alcohol abuse is a widespread and serious problem. Understanding the factors that influence the likelihood of abuse is important for the development of effective therapies. There are both genetic and environmental influences on the development of abuse, but it has been difficult to identify specific liability factors, in part because of both the complex genetic architecture of liability and the influences of environmental stimuli on the expression of that genetic liability. Epigenetic modification of gene expression can underlie both genetic and environmentally sensitive variation in expression, and epigenetic regulation has been implicated in the progression to addiction. Here, we identify a role for the switching defective/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in regulating the behavioral response to alcohol in the nematode Caenorhabditis elegans. We found that SWI/SNF components are required in adults for the normal behavioral response to ethanol and that different SWI/SNF complexes regulate different aspects of the acute response to ethanol. We showed that the SWI/SNF subunits SWSN-9 and SWSN-7 are required in neurons and muscle for the development of acute functional tolerance to ethanol. Examination of the members of the SWI/SNF complex for association with a diagnosis of alcohol dependence in a human population identified allelic variation in a member of the SWI/SNF complex, suggesting that variation in the regulation of SWI/SNF targets may influence the propensity to develop abuse disorders. Together, these data strongly implicate the chromatin remodeling associated with SWI/SNF complex members in the behavioral responses to alcohol across phyla.
Kallupi, Marsida; Vendruscolo, Leandro F; Carmichael, Casey Y; George, Olivier; Koob, George F; Gilpin, Nicholas W
Electrophysiological data suggest a dual role of Y2 receptors (Y2 Rs) as autoreceptors regulating neuropeptide Y release and heteroceptors regulating gamma-aminobutyric acid release in the central amygdala (CeA). Here, we report that neither systemic (JNJ-31020028) nor intra-CeA (BIIE0246) Y2 R antagonism altered operant alcohol responding by alcohol-dependent or non-dependent rats. Conversely, BIIE0246 in the CeA reduced anxiety-like behavior in alcohol-dependent and alcohol-naïve rats. The finding that Y2 R antagonism reduces anxiety-like behavior but not alcohol drinking suggests that these two effects may occur via different functions of the Y2 R (e.g. autoreceptor versus heteroceptor function).
Peters, Erica N.; Petry, Nancy M.; LaPaglia, Donna M.; Reynolds, Brady; Carroll, Kathleen M.
Delay discounting is an index of impulsive decision-making and reflects an individual’s preference for smaller immediate rewards relative to larger delayed rewards. Multiple studies have indicated comparatively high rates of discounting among tobacco, alcohol, cocaine, and other types of drug users, but few studies have examined discounting among marijuana users. This report is a secondary analysis of data from a clinical trial that randomized adults with marijuana dependence to receive one of four treatments that involved contingency management (CM) and cognitive–behavioral therapy interventions. Delay discounting was assessed with the Experiential Discounting Task (Reynolds & Schiffbauer, 2004) at pretreatment in 93 participants and at 12 weeks posttreatment in 61 participants. Results indicated that higher pretreatment delay discounting (i.e., more impulsive decision-making) significantly correlated with lower readiness to change marijuana use (r = − 0.22, p = .03) and greater number of days of cigarette use (r = .21, p = .04). Pretreatment discounting was not associated with any marijuana treatment outcomes. CM treatment significantly interacted with time to predict change in delay discounting from pre- to posttreatment; participants who received CM did not change their discounting over time, whereas those who did not receive CM significantly increased their discounting from pre- to posttreatment. In this sample of court-referred young adults receiving treatment for marijuana dependence, delay discounting was not strongly related to treatment outcomes, but there was some evidence that CM may protect against time-related increases in discounting. PMID:23245197
Paulus, Daniel J; Vujanovic, Anka A; Schuhmann, Bailee B; Smith, Lia J; Tran, Jana
Depression, posttraumatic stress, and alcohol use are highly prevalent among firefighters. However, no study has evaluated the interactive effects of depression and posttraumatic stress with regard to alcohol use among firefighters. The current study examined main and interactive effects of depression and posttraumatic stress in terms of alcohol dependence symptoms, positive alcohol dependence screen, and drinks per occasion. Participants included 2707 male urban firefighters. There was a main effect of posttraumatic stress in relation to all alcohol-related outcomes and a main effect of depression only for alcohol dependence symptoms. There was a significant interaction of depression and posttraumatic stress with regard to symptoms of alcohol dependence, positive screen for alcohol dependence, and number of drinks per occasion. Interactions were evident above main effects and covariates (age, presence of a spouse/partner, tenure in the fire department, history of active duty in the U.S. armed forces, and racial/ethnic minority status). Overall, heightened depression was positively associated with alcohol-related outcomes for those with lower but not higher levels of posttraumatic stress in all models. Posttraumatic stress and depression may pose unique interactive risks for alcohol dependence in urban male firefighters. Implications for clinical intervention in firefighters are discussed.
Strac, Dubravka Svob; Erjavec, Gordana Nedic; Perkovic, Matea Nikolac; Sviglin, Korona Nenadic; Borovecki, Fran; Pivac, Nela
Alcohol dependence is a common chronic disorder precipitated by the complex interaction between biological, genetic and environmental risk factors. Recent studies have demonstrated that polymorphisms of the gene encoding the GABAA receptor α2 subunit (GABRA2) are associated with alcohol dependence in different populations of European ancestry. As aggression often occurs in the context of alcohol dependence, the aim of this study was to examine the allelic and haplotypic association of GABRA2 gene with alcohol dependence and related aggressive behavior in subjects of Eastern European (Croatian) origin. Genotyping of the 3 single nucleotide polymorphisms (SNPs) across the GABRA2 gene (rs567926, rs279858 and rs9291283) was performed in patients with alcohol dependence (N=654) and healthy control subjects (N=574). Alcohol-dependent participants were additionally subdivided according to the presence/absence of aggressive behavior and type of alcohol dependence according to the Cloninger's classification. The association of rs279858 with alcohol dependence yielded nominal significance level. Haplotype analysis revealed a high degree of linkage disequilibrium (LD) for rs567926 and rs279858, but not for rs9291283 polymorphism in the GABRA2 gene. In patients with alcohol dependence, the A-C (rs567926 and rs279858) haplotype carriers were more likely to demonstrate aggressive behavior. The same haplotype (present only in 1.6% of all subjects) was significantly more often present in patients with a combination of early onset alcohol abuse and aggression, corresponding to the Cloninger's type II alcoholism subgroup. These findings support the involvement of GABRA2 gene in alcohol dependence-related aggressive behavior.
Simon O'Brien, Emmanuelle; Legastelois, Rémi; Houchi, Hakim; Vilpoux, Catherine; Alaux-Cantin, Stéphanie; Pierrefiche, Olivier; André, Etienne; Naassila, Mickaël
A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5-40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment.
Wezeman, Frederick H; Juknelis, Dainius; Himes, Ryan; Callaci, John J
Decreased bone mass and bone strength can result from excess alcohol consumption in humans and alcohol treatment in the rat. Although the specific mechanism is unknown, the damaging effects of alcohol abuse modulate the bone remodeling cycle and increase bone turnover. Chronic alcohol consumption models have shown an inhibition of bone formation. We previously reported that binge alcohol treatment increases bone resorption and that alcohol-induced damage can be prevented by treatments with intermittent parathyroid hormone and bisphosphonates. In this study, we hypothesized that an effective dose of vitamin D (cholecalciferol) or a single dose of ibandronate would prevent bone loss caused by binge alcohol treatment in male rats. Forty-eight adult (450 gram) male Sprague-Dawley rats were randomly assigned to 6 treatment groups (n=8): (a) saline i.p., 3 days/week (C); (b) binge alcohol, 3 g/kg i.p., 3 days/week (A); (c) vitamin D, 5,000 IU/kg daily s.c. (D); (d) binge alcohol and vitamin D (AD); (e) ibandronate (120 microg, given as a single i.p. injection (I)); and (f) alcohol and ibandronate (AI) . After 4 weeks of treatment, proximal tibia and L3 and L4 vertebrae were analyzed for bone mineral density (BMD) by quantitative computerized tomography and compressive strength-to-failure using an Instron materials testing machine. Type I collagen cross-linked c-telopeptide, calcium, and 25-OH vitamin D levels were measured in serum collected at the time of sacrifice. Binge alcohol significantly decreased cancellous BMD by 58% in tibia and 23% in lumbar spine (p<0.05). Binge alcohol treatment decreased L3 and L4 compressive strength-to-failure by 21% (p<.05). Treatment with vitamin D at 5,000 IU/kg/day prevented alcohol-induced bone loss, significantly increasing both tibial and vertebral cancellous BMD values (161% increase in tibia and 40% increase in vertebra, respectively, p<0.05) compared to alcohol alone groups. Pre-treatment with the single dose of 120 microg
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
King, Serena M.; Keyes, Margaret; Malone, Stephen M.; Elkins, Irene; Legrand, Lisa N.; Iacono, William G.; McGue, Matt
Aim To examine the genetic and environmental influences of parental alcoholism on offspring disinhibited behavior. Design We compared the effect of parental alcoholism history on offspring in adoptive and non-adoptive families. In families with a history of parental alcohol dependence, we examined the effect of exposure to parental alcoholism symptoms during the lifetime of the adolescent. Setting Assessments occurred at the University of Minnesota from 1998-2004. Participants Adolescents adopted in infancy were systematically ascertained from records of three private Minnesota adoption agencies; non-adopted adolescents were ascertained from Minnesota birth records. Adolescents and their rearing parents participated in in-person assessments. Measurements For adolescents, measures included self- reports of delinquency, deviant peers, substance use, antisocial attitudes, and personality. For parents, we conducted DSM-IV clinical assessments of alcohol abuse and dependence. Findings A history of parental alcohol dependence was associated with higher levels of disinhibition only when adolescents were biologically related to their rearing parents. Within families with a history of parental alcoholism, exposure to parental alcohol misuse during the lifetime of the adolescent was associated with increased odds of using alcohol in adopted adolescents only. Conclusions These findings suggest that the association between a history of parental alcohol dependence and adolescent offspring behavioral disinhibition is largely attributable to genetic rather than environmental transmission. We also obtained some evidence for parental alcohol misuse as a shared environmental risk factor in adoptive families. PMID:19215604
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
Nelson, Elliot C.; Agrawal, Arpana; Pergadia, Michele L.; Wang, Jen C.; Whitfield, John B.; Saccone, F. Scott; Kern, Jason; Grant, Julia D.; Schrage, Andrew J.; Rice, John P.; Montgomery, Grant W.; Heath, Andrew C.; Goate, Alison M.; Martin, Nicholas G.; Madden, Pamela A.F.
Animal research supports a central role for corticotropin releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a CRHR1 polymorphism, and negative events. CRHR1 and at least 4 other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (N=1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from 4 indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA (p<0.017). A similar G × E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95%CI 0.20 – 0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence. PMID:19878140
Stotts, Angela L.; Dodrill, Carrie L.; Kosten, Thomas R.
The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed. PMID:19538000
Bonnet, Udo; Banger, Markus; Leweke, F Markus; Specka, Michael; Müller, Bernhard W; Hashemi, Thilo; Nyhuis, Peter W; Kutscher, Sven; Burtscheidt, Wilhelm; Gastpar, Markus
A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 +/- 5.4/GP = 6.2 +/- 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe.
Bayer, Gregory A.; Bayer, Marilyn A.
A family system is intimately affected by the presence of an alcoholic within the system. One symptom of alcoholism is the development of elaborate defenses. In response to the defense of the alcoholic, each family member develops individual well established and unique defenses. The diagnosis of the defenses is essential in determining the nature…
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
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
The aim of the study was to examine the relationship between neuropsychological impairment in severe alcohol dependence and relapse. This was assessed following inpatient detoxification over a period of three months. Participants were tested on measures of neuropsychological functioning at the end of a seven to ten day stay in an inpatient alcohol…
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.
Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth
Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented.
Kresina, Thomas F
Clinical trials and clinical studies, using patented drugs and drugs off patent, provide data that impact the best treatment practices for substance abuse and dependence. In the United States, medications have been approved for use in the treatment of both alcohol and opioid dependence. Medications are used in the detoxification from drug abuse and dependence in the symptomatic relief of withdrawal. For long term treatment or medical maintenance treatment, medications eliminate the physiological effects of drug use by blocking drug-receptor binding in the brain. Therefore, patented drugs showing interactions with neurotransmitters in the brain, are attractive candidates for treatment efficacy trials. An effective long term treatment paradigm for reducing drug dependence is the combinatorial use of medications that block the effects of drug use with behavior change counseling and psychotherapy. Medications used for the long term treatment of opioid dependence are methadone, buprenorphine, and naltrexone. Pharmacotherapies used in the treatment of alcohol dependence include acamprosate, antabuse and naltrexone. A reliable indicator for successful treatment of drug dependence is time in treatment. Patients remain in long term treatment when they perceive that their health care environment is supportive and non-stigmatizing and with a good patient-provider relationship where their needs are identified and met. Additional medications are needed for individual comprehensive substance abuse treatment plans, particularly for individuals who abuse stimulants. Patented drugs remain an important source of candidate pharmacotherapies comprising medication assistant treatment, part of a comprehensive treatment plan for drug dependence that addresses the medical, social, and psychological needs of the patient. Adapting this drug treatment paradigm globally requires identifying and testing new drug candidates while building and changing programs to patient centered treatment
Crews, Fulton T.; Qin, Liya; Sheedy, Donna; Vetreno, Ryan P.; Zou, Jian
Background Innate immune gene expression is regulated in part through high mobility group box 1(HMGB1), an endogenous proinflammatory cytokine, that activates multiple members of the interleukin-1/Toll-like receptor (IL-1/TLR) family associated with danger signaling. We investigated expression of HMGB1, TLR2, TLR3 and TLR4 in chronic ethanol treated mouse brain, post-mortem human alcoholic brain, and rat brain slice culture to test the hypothesis that neuroimmune activation in alcoholic brain involves ethanol activation of HMGB1/TLR danger signaling. Methods Protein levels were assessed using Western blot, ELISA, immunohistochemical immunoreactivity (+IR), and mRNA levels were measured by real time PCR in ethanol-treated mice (5 g/kg/day, i.g., 10 days + 24 hr), rat brain slice culture, and post-mortem human alcoholic brain. Results Ethanol treatment of mice increased brain mRNA and +IR protein expression of HMGB1, TLR2, TLR3, and TLR4. Post-mortem human alcoholic brain also showed increased HMGB1, TLR2, TLR3, and TLR4+IR cells that correlated with lifetime alcohol consumption as well as each other. Ethanol treatment of brain slice culture released HMGB1 into the media and induced the proinflammatory cytokine, IL-1β. Neutralizing antibodies to HMGB1 and small inhibitory mRNA to HMGB1 or TLR4 blunted ethanol induction of IL-1β. Conclusions Ethanol-induced HMGB1/TLR signaling contributes to induction of the proinflammatory cytokine, IL-1β. Increased expression of HMGB1, TLR2, TLR3, and TLR4 in alcoholic brain and in mice treated with ethanol suggests that chronic alcohol-induced brain neuroimmune activation occurs through HMGB1/TLR signaling. PMID:23206318
Kalapatapu, Raj K.; Chambers, R.
Alcohol use disorders are highly prevalent conditions that generate a large fraction of the total public health burden. These disorders are concentrated in mentally ill populations, in which reliability of self-reporting of alcohol consumption may be especially compromised. The application of objective biomarkers for alcohol use may therefore play an important role in these patients. This article provides a description and comparative overview of traditional versus novel biomarkers of alcohol consumption. Greater professional familiarity with and use of novel biomarkers as diagnostic and treatment management tools may enhance clinical standards and research on alcohol use in patients with a dual diagnosis. PMID:20582236
One out of 2 Americans report drinking on a routine basis, making the excessive consumption of alcohol the third leading cause of preventable death in America (). Alcoholism and depression are common comorbidities that home healthcare professionals frequently encounter. To achieve the best patient outcomes, alcoholism should be addressed initially. Although all age groups are at risk, alcoholism and depression occur in more than 8 percent of older adults. Prevention through identifying alcohol use early in adolescence is vital to reduce the likelihood of alcohol dependence. This article provides an overview of the long-term effects of alcohol abuse, including alcoholic cirrhosis and hepatic encephalopathy. The diagnostic criteria for substance dependence and ideas for nonthreatening screening questions to use with patients who are adolescent or older are discussed. While providing patient care, home healthcare nurses share the patient's intimate home environment. This environment is perceived as a safe haven by the patient and home care nurses can take advantage of counseling and treatment opportunities in this nonthreatening environment.
Pérez Gómez, Augusto; Sierra Acuña, Diana Raquel
This study examines the concept of natural recovery (without formal treatment) from problems associated with alcohol, marijuana, cocaine and heroin abuse, each one alone or in any combination. Two groups of males (40 Ss between 18 and 60 years of age) and two groups of females (19 Ss between 18 and 55 years of age) with at least one year of abstinence were studied. The main issues considered were: reason for attending treatment or ceasing the use of substances, factors related to maintenance of abstinence, and difficulties and threats associated with abstinence. Several significant differences were found between groups with and without treatment, as well as between males and females, particularly regarding factors related to the maintenance of abstinence. In both cases family and affective links appear as the most relevant factors in the decision to stop using substances. On the other hand, commitment to one's goals and life project are the principal motives for maintaining abstinence or moderate consumption. This reflects the progressive transition from cognitive and emotional processes with external referents to processes with internal referents, associated with personal achievement.
Moncrieff, J; Drummond, D C
This review considers the novel drug treatments that have been suggested to help prevent relapse or attenuate drinking in people with alcohol problems. The evidence from randomized controlled trials for the efficacy of some of the main candidates: acamprosate, naltrexone, bromocriptine, selective serotonin re-uptake inhibitors and buspirone, was examined. Important methodological problems which may have introduced bias were detected in many of the trials. These included failure to test the integrity of the double blind, excluding or estimating outcome in early withdrawals and the comparison of groups on multiple outcome measures with selective reporting of results. In addition, the generalizability of some studies was limited by the procedures used for sample selection. In view of the potential adverse effects of drug treatment it is concluded that the evidence is not strong enough to support the introduction of any of these substances into routine clinical practice at present. The review also emphasizes the importance of methodological rigour to maximize objectivity in treatment evaluation research.
O'Malley, Stephanie S; Krishnan-Sarin, Suchitra; McKee, Sherry A; Leeman, Robert F; Cooney, Ned L; Meandzija, Boris; Wu, Ran; Makuch, Robert W
The opiate antagonist naltrexone (Ntx) has demonstrated efficacy in the treatment of alcohol dependence and as a component of treatment to reduce heavy drinking. At present, there are no published dose-ranging clinical trials of the oral preparation for treatment of problem drinking. The present study evaluated the effects of Ntx on alcohol use among the subset of hazardous drinkers (n=102) who participated in a placebo-controlled, dose-ranging trial of oral Ntx (25-mg, 50-mg and 100-mg doses) combined with open-label transdermal nicotine patch for enhancing smoking cessation. On the primary outcome--no hazardous drinking (drinking that exceeded weekly or daily limits) during treatment--25 mg and 50 mg Ntx were superior to placebo (each p<0.05). These findings remained after controlling for baseline predictors or smoking abstinence during treatment. Time to remission of hazardous drinking was examined as a secondary outcome with definitions of hazardous drinking based on weekly limits, daily limits and the combination of weekly and daily limits and the results were consistent with the primary findings. In conclusion, the findings suggest that Ntx can reduce the risk of hazardous drinking in smokers who are not seeking or receiving alcohol treatment, providing strong evidence for the pharmacological effects of Ntx on drinking. This effect appears to favour lower doses that may be better tolerated and less expensive than the higher 100-mg dose. Given its efficacy and favourable side-effect profile, the 25-mg dose should be considered for future studies of combination therapy.
Andreas, Jasmina Burdzovic; O'Farrell, Timothy J.; Fals-Stewart, William
Psychosocial adjustment in children of alcoholics (COAs; N = 125) was examined before and at 3 follow-ups in the 15 months after their fathers entered alcoholism treatment. Before their fathers' treatment, COAs exhibited greater overall and clinical-level symptomatology than children from the demographically matched comparison sample, but they…
McGovern, Mark P.
Compared medical and social setting detoxification treatments of alcohol withdrawal syndrome regarding the degree to which each involved alcoholics (N=200) in ongoing rehabilitative efforts. Results showed highly significant differences between treatment models, with the social setting model showing significantly greater rates of commitment to…
Park, Aesoon; Sher, Kenneth J.; Todorov, Alexandre A.; Heath, Andrew C.
The manifestation of alcohol dependence at different developmental stages may be associated with different genetic and environmental factors. Taking a developmental approach, the current study characterized interaction between the dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism and developmentally specific environmental factors (childhood adversity, college/Greek involvement, and delayed adult role transition) on alcohol dependence during emerging and young adulthood. Prospective data were obtained from a cohort of 234 Caucasian individuals (56% female) followed up at ages 18 through 34. A longitudinal hierarchical factor model was estimated to model a trait-like persistent alcohol dependence factor throughout emerging and young adulthood and two residual state-like alcohol dependence factors limited to emerging adulthood and young adulthood, respectively. To account for those alcohol dependence factors, three two-way interaction effects between the DRD4 VNTR polymorphism and the three developmentally specific environment factors were modeled. Carriers of the DRD4 long allele showed greater susceptibility to environmental effects; they showed more persistent alcohol dependence symptoms as childhood adversity increased and more alcohol dependence symptoms limited to emerging adulthood as college/Greek involvement increased. Alcohol dependence among non-carriers of the long allele, however, did not differ as a function of those environments. Although replication is necessary, these findings highlight the importance of repeated phenotypic assessments across development and modeling both distal and proximal environments and their interaction with genetic susceptibility at specific developmental stages. PMID:21381802
Brickham, Dana M.
People with alcohol abuse/dependence disabilities are often faced with a complex recovery process due to the exacerbating and chronic aspects of their condition. Vocational rehabilitation for people with alcohol abuse/dependence can help individuals access and maintain employment, and through employment can enhance physical and psychological…
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
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.
... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria ... change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...
Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)
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.
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 184.108.40.206) and the glutathione-dependent formaldehyde activity of the class III-type enzyme [formaldehyde:NAD+ oxidoreductase (glutathione-formylating), EC 220.127.116.11] 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
Kresina, Thomas F; Bruce, R Douglas; McCance-Katz, Elinore F
Drug use and HIV/AIDS are global public health issues. The World Health Organization (WHO) estimates that up to 30% of HIV infections are related to drug use and associated behaviors. The intersection, of the twin epidemics of HIV and drug/alcohol use, results in difficult medical management issues for the health care providers and researchers who work in the expanding global HIV prevention and treatment fields. Access to care and treatment, medication adherence to multiple therapeutic regimens, and concomitant drug -drug interactions of prescribed treatments are difficult barriers for drug users to overcome without directed interventions. Injection drug users are frequently disenfranchised from medical care and suffer sigma and discrimination creating additional barriers to care and treatment for their drug abuse and dependence as well as HIV infection. In an increasing number of studies, medication assisted treatment of drug abuse and dependence has been shown to be an important HIV prevention intervention. Controlling the global transmission of HIV will require further investment in evidence-based interventions and programs to enhance access to care and treatment of individuals who abuse illicit drugs and alcohol. In this review, we present the cumulative evidence of the importance of medication assisted treatment in the prevention, care, and treatment of HIV infected individuals who also abuse drugs and alcohol.
Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya
Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730