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

PubMed Central

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

2014-01-01

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

Serum Proteomic Profiles In Subjects with Heavy Alcohol Abuse

PubMed Central

Liangpunsakul, Suthat; Lai, Xianyin; Ringham, Heather N.; Crabb, David W.; Witzmann, Frank A.

2009-01-01

Objectives The abuse of alcohol is a major public health problem, and the diagnosis and care of patients with alcohol abuse and dependence is hindered by the lack of tests that can detect dangerous levels of drinking or relapse during therapy. Gastroenterologists and other healthcare providers find it very challenging to obtain an accurate alcohol drinking history. We hypothesized that the effects of ethanol on numerous systems may well be reflected in changes in quantity or qualities of constituent or novel plasma proteins or protein fragments. Organ/tissue-specific proteins may be released into the blood stream when cells are injured by alcohol, or when systemic changes are induced by alcohol, and such proteins would be detected using a proteomic approach. The objective of this pilot study was to determine if there are plasma proteome profiles that correlate with heavy alcohol use. Methods Paired serum samples, before and after intensive alcohol treatment, were obtained from subjects who attended an outpatient alcohol treatment program. Serum proteomic profiles using MALDI –OTOF Mass Spectrometry were compared between pre- and post treatment samples. Results Of 16 subjects who enrolled in the study, 8 were females. The mean age of the study subjects was 49 yrs. The baseline laboratory data showed elevated AST (54 ± 37 IU/L), ALT (37 ± 19 IU/L), and MCV (99 ± 5 fl). Self-reported pre-treatment drinking levels for these subjects averaged 17 ± 7drinks/day and 103 ± 37 drinks/week. Mass spectrometry analyses showed a novel 5.9 kDa protein, a fragment of alpha fibrinogen, isoform 1, that might be might be a new novel marker for abusive alcohol drinking. Conclusions We have shown in this pilot study that several potential protein markers have appeared in mass spectral profiles and that they may be useful clinically to determine the status of alcohol drinking by MALDI –OTOF mass spectrometry, especially a fragment of alpha fibrinogen, isoform 1. However, a

Psychopathological symptoms, defense mechanisms and time perspectives among subjects with alcohol dependence (AD) presenting different patterns of coping with stress.

PubMed

Iwanicka, Katarzyna; Gerhant, Aneta; Olajossy, Marcin

2017-01-01

The problem of coping with stress is an important one in the context of development and persistence of alcohol dependence. In the literature to date very little attention has been paid to coping patterns construed as a configuration of specific coping styles, particularly as regards the functioning of addicted individuals. The aim of the study was to verify whether individuals with alcohol dependence characterized by different coping patterns differ with respect to the severity of psychopathological symptoms, defense mechanisms and time perspectives. Participants were given a battery of psychological tests-Coping Inventory for Stresfull Situations (CISS), Defense Style Questionnaire (DSQ 40), Syndrom Checklist (SCL-90) and Short Zimbardo Time Perspective Inventory (SZPTI-PL). The sample comprised 112 individuals with alcohol dependence, aged 20 to 63 years old, the average age was 37.86; 78 percent were men. There were identified three sub-groups of individuals characterized by a distinctive patterns of coping with stress -"emotional-avoidant", "task oriented" and a "mixed one". Individuals with the predominant emotional-avoidant coping pattern are characterized by significantly higher severity of psychopathological symptoms, less mature defense mechanisms and past time perspectives. Subjects reliant on task-oriented coping pattern were characterized by the highest level of adaptation and the most constructive way of functioning in the face of difficulties. It is worth regarding the examination of patterns of coping as an indispensable element of collecting medical history from alcohol dependent individuals.

Interrelationship between family history of alcoholism and generational status in the prediction of alcohol dependence in US Hispanics.

PubMed

Chartier, K G; Thomas, N S; Kendler, K S

2017-01-01

Both a family history of alcoholism and migration-related factors like US v. foreign nativity increase the risk for developing alcohol use disorders in Hispanic Americans. For this study, we integrated these two lines of research to test whether the relationship between familial alcoholism and alcohol dependence changes with successive generations in the United States. Data were from the waves 1 and 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Subjects self-identified Hispanic ethnicity (N = 4122; n = 1784 first, n = 1169 second, and n = 1169 third or later generation) and reported ever consuming ⩾12 drinks in a 1-year period. A family history of alcoholism was assessed in first- and second-degree relatives. Analyses predicting the number of alcohol dependence symptoms were path models. Alcohol dependence symptoms were associated with a stronger family history of alcoholism and later generational status. There was a significant interaction effect between familial alcoholism and generational status; the relationship of familial alcoholism with alcohol dependence symptoms increased significantly with successive generations in the United States, more strongly in women than men. Acculturation partially mediated the interaction effect between familial alcoholism and generational status on alcohol dependence, although not in the expected direction. Familial alcoholism interacted with generational status in predicting alcohol dependence symptoms in US Hispanic drinkers. This relationship suggests that heritability for alcoholism is influenced by a higher-order environmental factor, likely characterized by a relaxing of social restrictions on drinking.

Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

PubMed Central

Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

2015-01-01

Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

Randomized open-label trial of baclofen for relapse prevention in alcohol dependence.

PubMed

Gupta, Manushree; Verma, Pankaj; Rastogi, Rajesh; Arora, Sheetal; Elwadhi, Deeksha

2017-05-01

Alcohol dependence is a progressive chronic disorder characterized by narrowing of the drinking repertoire, salience of drinking, tolerance and withdrawal phenomenon, compulsion to drink, and frequent relapses. Baclofen has been shown to promote abstinence, to reduce craving, and to reduce anxiety in alcohol-dependent individuals, and it promises to be a useful agent, although clinical data are limited at present. The current study aimed to test the utility of baclofen, a GABA agonist, in improving the relapse rates in alcohol-dependent subjects. A total of 122 alcohol-dependent subjects were randomized into two groups. Groups were administered baclofen (30 mg/day) or benfothiamine (a nutritional supplement) using an open label design. Both groups received brief motivational intervention. Subjects were assessed at 0, 2, 4, 8, and 12 weeks for the primary outcome measures: time to first relapse, heavy drinking days, cumulative abstinence duration, and craving (measured by the Obsessive Compulsive Drinking Scale (OCDS)). Seventy-two participants received baclofen, and 50 received benfothiamine. Participants receiving baclofen remained abstinent for significantly more days than the benfothiamine group (p < 0.05). The percentage of heavy drinking days was significantly lower in the baclofen group (p = 0.001). Craving and anxiety scores (Hamilton Anxiety Rating Scale) were also significantly decreased in the baclofen group relative to the control group (p = 0.001). Time to first relapse was similar in both groups. In this open-label trial, alcohol-dependent participants receiving baclofen showed significant improvements in drinking outcomes compared with participants receiving benfothiamine. This study provides further evidence that baclofen is useful for the treatment of alcohol dependence.

Is dependence on one drug associated with dependence on other drugs? The cases of alcohol, caffeine and nicotine.

PubMed

Hughes, J R; Oliveto, A H; MacLaughlin, M

2000-01-01

Several studies have correlated the use of one drug with that of another drug; however, whether dependence on one drug is associated with dependence on another drug, independent of any use/use association, is unclear. We asked 196 randomly-selected subjects the DSM-IV criteria for dependence as applied to alcohol, caffeine, and nicotine. Among ever users, the severity of alcohol vs nicotine dependence and alcohol vs caffeine dependence was related, but this relationship was weak (r = .22 & .31). Nicotine and caffeine dependence were not correlated. These results fail to confirm theories of commonality that hypothesize dependence on one drug predisposes to dependence on another drug.

Benzodiazepine dependence in subjects with alcohol use disorders: what prevalence?

PubMed

Morel, A; Grall-Bronnec, M; Bulteau, S; Chauvin-Grelier, P; Gailledrat, L; Pinot, M L; Jolliet, P; Victorri-Vigneau, C

2016-10-01

To our knowledge, no studies have been conducted in France on benzodiazepine (BZD) dependence among outpatients with alcohol use disorders (AUD). Some international studies have been conducted on the consumption of BZD in this specific population, but the comparisons among them are difficult. We aimed to assess the current prevalence of probable benzodiazepine and BZD-like hypnotics (Z-drugs) dependence among outpatients seeking treatment for AUD. Participants were patients seeking treatment for AUD for the first time or repeating treatment after more than twelve months. Recruitment took place in seven addiction centres between January and December 2013 in the Nantes region (France). BZD/Z-drug dependence was assessed according to the DSM-IV diagnostic criteria for dependence. This information was gathered through a self-report questionnaire. Among the 1005 patients included in this study, 413 were BZD/Z-drug users (41.1%). Among the 413 patients, 217 were probably dependent on at least one substance, which represents 21.6% of the total population and 52.5% of BZD/Z-drug users. BZD/Z-drug dependence represents a public health concern. Prescribers should take the risks into account and keep treatment courses to a minimum.

Anterior Cingulate Glutamate Is Reduced by Acamprosate Treatment in Patients With Alcohol Dependence.

PubMed

Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Feeder, Scott E; Choi, Doo-Sup; Port, John D

2016-12-01

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.

Mood disorder, anxiety, and suicide risk among subjects with alcohol abuse and/or dependence: a population-based study.

PubMed

Wiener, Carolina D; Moreira, Fernanda P; Zago, Alethea; Souza, Luciano M; Branco, Jeronimo C; Oliveira, Jacqueline F de; Silva, Ricardo A da; Portela, Luis V; Lara, Diogo R; Jansen, Karen; Oses, Jean P

2018-01-01

To evaluate the prevalence of alcohol abuse and/or dependence in a population-based sample of young adults and assess the prevalence of comorbid mood disorders, anxiety, and suicide risk in this population. This cross-sectional, population-based study enrolled 1,953 young adults aged 18-35 years. The CAGE questionnaire was used to screen for alcohol abuse and/or dependence, with CAGE scores ≥ 2 considered positive. Psychiatric disorders were investigated through the structured Mini International Neuropsychiatric Interview (MINI). Alcohol abuse and/or dependence was identified in 187 (9.60%) individuals (5.10% among women and 15.20% among men). Alcohol abuse and/or dependence were more prevalent among men than women, as well as among those who used tobacco, illicit drugs or presented with anxiety disorder, mood disorder, and suicide risk. These findings suggest that alcohol abuse and/or dependence are consistently associated with a higher prevalence of psychiatric comorbidities, could be considered important predictors of other psychiatric disorders, and deserve greater public heath attention, pointing to the need for alcohol abuse prevention programs.

[Alcohol dependence in homeless men. Incidence, development and determinants].

PubMed

Dufeu, P; Podschus, J; Schmidt, L G

1996-11-01

Against the background of the complex relationship of alcoholism and homelessness, we investigated the question of whether homeless alcoholics and those with homes differed regarding biographical and clinical variables. Therefore, 49 of 72 (68.1%) homeless male visitors to a city kitchen in the center of Berlin, who had fulfilled the ICD-10 criteria for the alcohol-dependence syndrome, were compared with 141 outpatients of the addiction research unit of the Department of Psychiatry of the Free University of Berlin. It was found that homeless alcoholics had more psychosocial disadvantages than other alcoholics. They had been raised more frequently in families with an alcoholic father or mother and a higher number of children. The level of education and job qualification was lower in the homeless alcoholics. Early homelessness was predicted by a lack of sexual behavior (no partnership experienced) and a family history of alcoholism. In the interview, homeless alcoholics reported fewer symptoms of alcohol-dependence syndrome than other alcoholics; however, the first symptoms had been experienced earlier. Alcohol-related somatic and psychological consequences were reported more frequently in alcoholics with homes, whereas social problems were more common in the homeless subjects. The results are discussed in the light of methodological limitations and other reports on the topic.

Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease.

PubMed

Dubinkina, Veronika B; Tyakht, Alexander V; Odintsova, Vera Y; Yarygin, Konstantin S; Kovarsky, Boris A; Pavlenko, Alexander V; Ischenko, Dmitry S; Popenko, Anna S; Alexeev, Dmitry G; Taraskina, Anastasiya Y; Nasyrova, Regina F; Krupitsky, Evgeny M; Shalikiani, Nino V; Bakulin, Igor G; Shcherbakov, Petr L; Skorodumova, Lyubov O; Larin, Andrei K; Kostryukova, Elena S; Abdulkhakov, Rustam A; Abdulkhakov, Sayar R; Malanin, Sergey Y; Ismagilova, Ruzilya K; Grigoryeva, Tatiana V; Ilina, Elena N; Govorun, Vadim M

2017-10-17

Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative "shotgun" metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts-with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group. Alcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis-with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus-but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of

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

PubMed Central

2010-01-01

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

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

PubMed Central

Bjurstrom, Martin F.; Olmstead, Richard

2016-01-01

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

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

PubMed

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

2015-10-01

High-dose baclofen, i.e., 300 mg/d or more, has recently emerged as a strategy for treating alcohol dependence. The impact that the co-exposure of large amounts of alcohol and baclofen has on sedation is unclear. In a prospective cohort of 253 subjects with alcohol dependence, we collected daily alcohol and baclofen doses across the first year of baclofen treatment and the monthly maximum subjective sedation experienced by each patient (0-10 visual analog scale). For each patient-month, we determined the average weekly alcohol consumption (AWAC; standard-drinks/week) and the maximum daily dose of baclofen (DDB; mg/d). The occurrence of an episode of major sedation (EMS) during a patient-month was defined as a sedation score ≥7. The relationship between the EMS occurrence and the concurrent AWAC and DDB was investigated using a generalized estimating equation model. In total, 1528 patient-months were compiled (70 with an EMS). Univariate analyses demonstrated that the rate of patient-month to EMS increased gradually with AWAC (p<0.001), from 0.9% for AWAC=0 to 9.4% for AWAC >35. There was also a significant gradual risk for EMS associated with DDB (<0.001). Multivariate analysis demonstrated a significant interaction between DDB and AWAC on EMS risk (p=0.047). Each 20mg/d increase in DDB was associated with an OR of EMS in AWAC >35 of 1.22 (95%CI, 1.08-1.38) versus 1.11 (95%CI, 0.96-1.29) in AWAC=1-35, and 0.95 (95%CI, 0.76-1.19) in AWAC=0. The level of sedation observed in patients using baclofen for alcohol dependence appears to directly depend on the immediate doses of both the baclofen and the alcohol. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

INTERRELATIONSHIP BETWEEN FAMILY HISTORY OF ALCOHOLISM AND GENERATIONAL STATUS IN THE PREDICTION OF ALCOHOL DEPENDENCE IN U.S. HISPANICS

PubMed Central

Chartier, Karen G.; Thomas, Nathaniel S.; Kendler, Kenneth S.

2017-01-01

Background Both a family history of alcoholism and migration-related factors like U.S. versus foreign nativity increase the risk for developing alcohol use disorders in Hispanic Americans. For this study, we integrated these two lines of research to test whether the relationship between familial alcoholism and alcohol dependence changes with successive generations in the U.S. Methods Data were from the wave 1 and wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Subjects self-identified Hispanic ethnicity (N = 4,122; n = 1,784 first, n = 1,169 second, and n = 1,169 third or later generation) and reported ever consuming 12 or more drinks in a one-year period. A family history of alcoholism was assessed in first and second degree relatives. Analyses predicting the number of alcohol dependence symptoms were path models. Results Alcohol dependence symptoms were associated with a stronger family history of alcoholism and later generational status. There was a significant interaction effect between familial alcoholism and generational status; the relationship of familial alcoholism with alcohol dependence symptoms increased significantly with successive generations in the U.S., more strongly in women than men. Acculturation partially mediated the interaction effect between familial alcoholism and generational status on alcohol dependence, although not in the expected direction. Conclusions Familial alcoholism interacted with generational status in predicting alcohol dependence symptoms in U.S. Hispanic drinkers. This relationship suggests that heritability for alcoholism is influenced by a higher order environmental factor, likely characterized by a relaxing of social restrictions on drinking. PMID:27681653

Interactions Between Alcohol Metabolism Genes and Religious Involvement in Association With Maximum Drinks and Alcohol Dependence Symptoms

PubMed Central

Chartier, Karen G.; Dick, Danielle M.; Almasy, Laura; Chan, Grace; Aliev, Fazil; Schuckit, Marc A.; Scott, Denise M.; Kramer, John; Bucholz, Kathleen K.; Bierut, Laura J.; Nurnberger, John; Porjesz, Bernice; Hesselbrock, Victor M.

2016-01-01

Objective: Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption–related phenotypes. Method: Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism. Genetic markers included ADH1B-rs1229984, ADH1B-rs2066702, ADH1C-rs698, ADH4-rs1042364, and ADH4-rs1800759. Phenotypes were maximum drinks consumed in a 24-hour period and total number of alcohol dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Religious involvement was defined by self-reported religious services attendance. Results: Both religious involvement and ADH1B-rs1229984 were negatively associated with the number of maximum drinks consumed and the number of lifetime alcohol dependence symptoms endorsed. The interactions of religious involvement with ADH1B-rs2066702, ADH1C-rs698, and ADH4-rs1042364 were significantly associated with maximum drinks and alcohol dependence symptoms. Risk variants had weaker associations with maximum drinks and alcohol dependence symptoms as a function of increasing religious involvement. Conclusions: This study provided initial evidence of a modifying effect for religious involvement on relationships between ADH variants and maximum drinks and alcohol dependence symptoms. PMID:27172571

Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence.

PubMed

Thompson, Ronald G; Alonzo, Dana; Hasin, Deborah S

2013-01-01

This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce and history of alcohol problems for both parents tripled the likelihood. Offspring of parental divorce may be more vulnerable to developing alcohol dependence, particularly when one or both parents have alcohol problems.

Neurobiological Signatures of Alcohol Dependence Revealed by Protein Profiling

PubMed Central

Gorini, Giorgio; Roberts, Amanda J.; Mayfield, R. Dayne

2013-01-01

Alcohol abuse causes dramatic neuroadaptations in the brain, which contribute to tolerance, dependence, and behavioral modifications. Previous proteomic studies in human alcoholics and animal models have identified candidate alcoholism-related proteins. However, recent evidences suggest that alcohol dependence is caused by changes in co-regulation that are invisible to single protein-based analysis. Here, we analyze global proteomics data to integrate differential expression, co-expression networks, and gene annotations to unveil key neurobiological rearrangements associated with the transition to alcohol dependence modeled by a Chronic Intermittent Ethanol (CIE), two-bottle choice (2BC) paradigm. We analyzed cerebral cortices (CTX) and midbrains (MB) from male C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and represents one of the best available animal models for alcohol dependence and relapse drinking. CIE induced significant changes in protein levels in dependent mice compared with their non-dependent controls. Multiple protein isoforms showed region-specific differential regulation as a result of post-translational modifications. Our integrative analysis identified modules of co-expressed proteins that were highly correlated with CIE treatment. We found that modules most related to the effects of CIE treatment coordinate molecular imbalances in endocytic- and energy-related pathways, with specific proteins involved, such as dynamin-1. The qRT-PCR experiments validated both differential and co-expression analyses, and the correspondence among our data and previous genomic and proteomic studies in humans and rodents substantiates our findings. The changes identified above may play a key role in the escalation of ethanol consumption associated with dependence. Our approach to alcohol addiction will advance knowledge of brain remodeling mechanisms and adaptive changes in response to drug abuse, contribute to understanding of

Subjective Effects of Thiopental in Young Adults with and without a Family History of Alcoholism

PubMed Central

Petrakis, Ismene L; Kerfoot, Karin; Pittman, Brian; Perrino, Albert; Koretski, Julia; Newcomb, Jenelle; Limoncelli, Diana; Acampora, Gregory; Ralevski, Elizabeth

2013-01-01

Background The development of alcohol use disorders is genetically influenced, and may be mediated through differences in the subjective response to alcohol. There is some evidence to suggest that response differences to alcohol could be conveyed by heritable differences in GABAA receptors. The purpose of this study was to investigate whether individuals with a family history positive (FHP) for alcohol dependence would experience alterations in response to the GABAA receptor agonist thiopental, in comparison to family history negative (FHN) subjects. Methods 73 subjects (24 FHP and 49 FHN) between the ages of 21 and 30 years were administered sub-anesthetic doses of the GABAA receptor agonist thiopental and placebo on two separate test days. Various alcohol-related measures were administered, including those examining subjective effects, coordination, and cognition. Results Sub-anesthetic doses of thiopental produced alcohol-like subjective effects, as well as alcohol-like impaired coordination and cognition in healthy subjects. While there were no significant main effects in subjective, coordination, or cognitive effects between FHP and FHN individuals, analysis of peak effects suggested FHP had blunted sedative, but not stimulant effects compared to FHN. Conclusion Thiopental produced alcohol-like effects and perceived similarities to alcohol in healthy individuals. Subtle differences in sedative effects are consistent with reports of blunted FHP response to the negative but not stimulant effects of alcohol. Future studies are needed to better understand how this insight informs our understanding of the heritable risk for alcoholism and the treatment of alcohol use disorders. PMID:24273687

Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence

PubMed Central

THOMPSON, RONALD G.; ALONZO, DANA; HASIN, DEBORAH S.

2014-01-01

This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce and history of alcohol problems for both parents tripled the likelihood. Offspring of parental divorce may be more vulnerable to developing alcohol dependence, particularly when one or both parents have alcohol problems. PMID:24678271

Abnormal intrinsic functional hubs in alcohol dependence: evidence from a voxelwise degree centrality analysis.

PubMed

Luo, Xiaoping; Guo, Linghong; Dai, Xi-Jian; Wang, Qinglai; Zhu, Wenzhong; Miao, Xinjun; Gong, Honghan

2017-01-01

To explore the abnormal intrinsic functional hubs in alcohol dependence using voxelwise degree centrality analysis approach, and their relationships with clinical features. Twenty-four male alcohol dependence subjects free of medicine (mean age, 50.21±9.62 years) and 24 age- and education-matched male healthy controls (mean age, 50.29±8.92 years) were recruited. The alcohol use disorders identification test and the severity of alcohol dependence questionnaire (SADQ) were administered to assess the severity of alcohol craving. Voxelwise degree centrality approach was used to assess the abnormal intrinsic functional hubs features in alcohol dependence. Simple linear regression analysis was performed to investigate the relationships between the clinical features and abnormal intrinsic functional hubs. Compared with healthy controls, alcohol dependence subjects exhibited significantly different degree centrality values in widespread left lateralization brain areas, including higher degree centrality values in the left precentral gyrus (BA 6), right hippocampus (BA 35, 36), and left orbitofrontal cortex (BA 11) and lower degree centrality values in the left cerebellum posterior lobe, bilateral secondary visual network (BA 18), and left precuneus (BA 7, 19). SADQ revealed a negative linear correlation with the degree centrality value in the left precentral gyrus ( R 2 =0.296, P =0.006). The specific abnormal intrinsic functional hubs appear to be disrupted by alcohol intoxication, which implicates at least three principal neural systems: including cerebellar, executive control, and visual cortex, which may further affect the normal motor behavior such as an explicit type of impaired driving behavior. These findings expand our understanding of the functional characteristics of alcohol dependence and may provide a new insight into the understanding of the dysfunction and pathophysiology of alcohol dependence.

Nicotine Dependence and Alcohol Problems from Adolescence to Young Adulthood.

PubMed

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

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. 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. 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. 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.

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

PubMed Central

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

2015-01-01

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

Rare ADH Variant Constellations are Specific for Alcohol Dependence

PubMed Central

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

2013-01-01

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

Effects of alcohol mixed with energy drink and alcohol alone on subjective intoxication.

PubMed

Ulbrich, Andrea; Hemberger, Sophie Helene; Loidl, Alexandra; Dufek, Stephanie; Pablik, Eleonore; Fodor, Sugarka; Herle, Marion; Aufricht, Christoph

2013-12-01

Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol.

Traumas and other adverse life events in adolescents with alcohol abuse and dependence.

PubMed

Clark, D B; Lesnick, L; Hegedus, A M

1997-12-01

Clinical observation suggests that adolescents with alcohol use disorders often have complex histories that include childhood maltreatment and other traumas. The aim of this study was to determine the relationships among adolescent alcohol use disorders and a broad range of traumas and adverse life events. The subjects were 132 adolescents with alcohol dependence, 51 adolescents with alcohol abuse, and 73 adolescents recruited from the community as a control group. Trauma history was assessed by a semistructured interview and other adverse life events by questionnaire. Traumatic events reflecting interpersonal violence had occurred in many of the adolescents with alcohol dependence and abuse and few of the control adolescents. Adolescents with alcohol abuse or dependence, compared with control subjects, were 6 to 12 times more likely to have a physical abuse history and 18 to 21 times more likely to have a sexual abuse history. Sexual abuse was more common in females, and victimization by other violent acts was more common in males. Many other adverse life events were also significantly more common in the alcohol use disorder groups than in the control group, including having a close friend die, arguments within the family, and legal difficulties. These results demonstrate that trauma and other adverse life events are strongly associated with alcohol use disorders in adolescents. Clinical screening of adolescents with alcohol use disorders for a range of traumatic events is recommended.

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

PubMed Central

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

2016-01-01

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

Association and family studies of DRD2 gene polymorphisms in alcohol dependence syndrome.

PubMed

Małecka, Iwona; Jasiewicz, Andrzej; Suchanecka, Aleksandra; Samochowiec, Jerzy; Grzywacz, Anna

2014-11-06

The human dopamine receptor 2 gene DRD2 plays a central role in susceptibility to Alcohol Dependence Syndrome (ADS). The aim of this study was to evaluate 3 single nucleotide polymorphisms: D2 (rs1076560), Tag1D (rs1800498), Tag1B (rs1079597) located in dopamine receptor 2 DRD2 gene and its role in alcohol dependence. DNA was provided from alcohol dependent (AD) patients (n=171) and healthy control subjects (n=160) all of Polish descent. The history of alcoholism was obtained using the Polish version of the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). We conducted case-control association study and transmission disequilibrium test (TDT). Samples were genotyped using real-time PCR method. We did not confirm the association between studied polymorphisms and alcohol dependence syndrome. TDT reveled an adequate transmission of both alleles in the group of alcohol families. The lack of association of studied polymorphisms and ADS does not preclude its participation in the pathogenesis. Further research is needed to determine the actual contribution of DRD2 gene in the pathogenesis of alcoholism.

Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking.

PubMed

Kosobud, Ann E K; Wetherill, Leah; Plawecki, Martin H; Kareken, David A; Liang, Tiebing; Nurnberger, John L; Windisch, Kyle; Xuei, Xiaoling; Edenberg, Howard J; Foroud, Tatiana M; O'Connor, Sean J

2015-07-01

Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABAA receptor genes GABRG1 and GABRA2 and recent drinking history on the acute adaptation of subjective responses to alcohol. One hundred and thirty-two nondependent moderate to heavy drinkers, aged 21 to 27, participated in 2 single-blind, counterbalanced sessions, approximately 1 week apart. One session was an intravenous alcohol "clamp," during which breath alcohol concentration was held steady at 60 mg/dl (60 mg%) for 3 hours, and the other an identical session using saline infusion. Subjective perceptions of Intoxication, Enjoyment, Stimulation, Relaxation, Anxiety, Tiredness, and Estimated Number of Drinks were acquired before (baseline), and during the first and final 45 minutes of the clamp. A placebo-adjusted index of the subject's acute adaptation to alcohol was calculated for each of the 7 subjective measures and used in a principal component analysis to create a single aggregate estimate for each subject's adaptive response to alcohol. Analysis of covariance tested whether GABRA2 and GABRG1 single nucleotide polymorphism (SNP) genotypes, gender, placebo session, family history of alcoholism, recent drinking history, and the genotype × recent drinking history interaction significantly predicted the adaptive response. Recent drinking history (p = 0.01), and recent drinking history × genotype interaction (p = 0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the GABRA2 SNP rs279858. Higher recent drinking was found to be associated with reduced acute tolerance to positive, stimulating effects of alcohol in carriers of the rs279858 risk allele. We postulate that the GABRA2 effect on

[Motivational interviewing with alcohol-dependent patients].

PubMed

Spaeth, Michael; Bleich, Stefan; Hillemacher, Thomas

2017-09-01

Motivational interviewing with alcohol-dependent patients Alcohol-dependent patients do not need to be motivated from the outside. They are mostly ambivalent, and the inner voice, which already speaks for change (change talk), is heard through motivational interviewing, carefully strengthened and developed together with the patient. The practitioner has to deal with the human spirit of motivational interviewing and should be able to communicate with empathy, respect, congruence, and openness. The patient's autonomy should always be maintained. Advice is only given upon request. The conversation style is directive-guiding instead of authoritariansteering. OARS and the EPE principle are the motivational interviewing basics, which are consistently applied over 4 processes of motivational interviewing: engaging, focusing, evocing, and planning. The likelihood of change talk increases as soon as discrepancies between life goals and alcohol consumption emerge. An increased rate of change talk makes a change in behavior more likely. If a patient argues against change (sustain talk), one should not confront, but should consistently work with reflections, reframing, and an emphasis on autonomy. Motivational interviewing can be applied in different settings and populations, should be learned by the entire team (best professional guidance) in teamwork, and be subjected to a critical and constant evaluation. Georg Thieme Verlag KG Stuttgart · New York.

Brain alcohol detectability in human subjects with and without a paternal history of alcoholism.

PubMed

Chiu, Tak-Ming; Mendelson, Jack H; Sholar, Michelle B; Mutschler, Nicole H; Wines, James D; Hesselbrock, Victor M; Mello, Nancy K

2004-01-01

This study examined the putative effects of a paternal history of alcoholism on the apparent detectability of brain alcohol in human subjects. Brain to blood ethanol ratios in two cohorts of men were determined, using proton magnetic resonance spectroscopic imaging in a brain voxel (2 x 2 x 2 cm) containing the putamen. The men were light drinkers with a positive (n = 8) or a negative (n = 8) paternal history of alcoholism and were given an alcohol dose of 0.8 g/kg body weight. In both groups, brain alcohol detectability was less than 100%. No significant difference (p = .37) was found in the brain/blood ethanol ratios of the two groups. However, subjective assessments of feeling the extreme effects of alcohol and the extent of intoxication ("how drunk") were highly correlated with a paternal history of alcoholism, with the paternal history negative group reporting significantly more intense feelings of intoxication. A review of existing literature evidence and data obtained in this study indicate that brain alcohol detectability via magnetic resonance spectroscopic imaging is less than 100%. There were no significant differences in brain alcohol detectability between paternal history positive and paternal history negative men. Differences in the Subjective High Assessment Scale ratings between the two groups, however, indicate the importance of a genetic influence on the subjective response to alcohol.

Sequence variations of the human MPDZ gene and association with alcoholism in subjects with European ancestry.

PubMed

Karpyak, Victor M; Kim, Jeong-Hyun; Biernacka, Joanna M; Wieben, Eric D; Mrazek, David A; Black, John L; Choi, Doo-Sup

2009-04-01

Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice. To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon-intron boundaries, and 2 kilobases in the 5' region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To explore potential associations of the human MPDZ gene with alcoholism and AWS, single SNP and haplotype analyses were performed using 13 common variants. Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019). Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS. Further functional genomic analysis of MPDZ

Varenicline for treatment of alcohol dependence: a randomized, placebo-controlled trial.

PubMed

de Bejczy, Andrea; Löf, Elin; Walther, Lisa; Guterstam, Joar; Hammarberg, Anders; Asanovska, Gulber; Franck, Johan; Isaksson, Anders; Söderpalm, Bo

2015-11-01

Alcohol dependence is a devastating illness affecting a large population, and new pharmacological treatments with good efficacy are greatly needed. One potential candidate is varenicline, a smoking cessation agent with partial agonist action at α4 β2 nicotinic acetylcholine receptors. A total of 160 subjects, 30 to 70 years of age, fulfilling DSM-IV criteria for alcohol dependence without any serious physical or mental disorders, were recruited through advertisement at 3 university clinics in Sweden during March 2009 to January 2011. After a 2-week placebo run-in period, subjects received 2 mg varenicline daily (titrated from 0.5 mg during first week) or placebo for 12 weeks in a double-blind manner. The primary outcome was the proportion of heavy drinking days, measured by self-reported alcohol consumption. Primary and secondary outcomes were calculated as a mean over the 10-week steady-state active treatment period. In the primary outcome analysis, no effect of varenicline over placebo was found (p = 0.73 for the intention to treat [ITT] and 0.92 for per protocol [PP]). Secondary outcome analysis found a significant reduction of specific alcohol marker phosphatidylethanol (PEth) in the blood in the varenicline group compared to placebo (p = 0.02 ITT). Craving (p = 0.048 PP) and Alcohol Use Disorders Identification Test (AUDIT) scores (p = 0.015 ITT) were also reduced in the active treatment group. PEth more strongly correlated with self-reported alcohol consumption than carbohydrate-deficient ttransferrin and γ-glutamyl transferase, and correlation coefficients were higher in the varenicline group than in the placebo group for all markers. Although the results of the main outcome of this study did not support an effect of varenicline in alcohol-dependent individuals, the secondary analyses of PEth, craving and AUDIT score support an effect of varenicline on alcohol consumption. The disclosure of a treatment effect and the lack of a clear placebo effect when

Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence.

PubMed

Huang, San-Yuan; Lin, Wei-Wen; Wan, Fang-Jung; Chang, Ai-Ju; Ko, Huei-Chen; Wang, Tso-Jen; Wu, Pei-Lin; Lu, Ru-Band

2007-05-01

Low monoamine oxidase (MAO) activity and the neurotransmitter dopamine are 2 important factors in the development of alcohol dependence. MAO is an important enzyme associated with the metabolism of biogenic amines. Therefore, the present study investigates whether the association between the dopamine D2 receptor (DRD2) gene and alcoholism is affected by different polymorphisms of the MAO type A (MAOA) gene. A total of 427 Han Chinese men in Taiwan (201 control subjects and 226 with alcoholism) were recruited for the study. Of the subjects with alcoholism, 108 had pure alcohol dependence (ALC) and 118 had both alcohol dependence and anxiety, depression or both (ANX/DEP ALC). All subjects were assessed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime. Alcohol dependence, anxiety and major depressive disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. The genetic variant of the DRD2 gene was only associated with the ANX/DEP ALC phenotype, and the genetic variant of the MAOA gene was associated with pure ALC. Subjects carrying the MAOA 3-repeat allele and genotype A1/A1 of the DRD2 were 3.48 times (95% confidence interval = 1.47-8.25) more likely to be ANX/DEP ALC than the subjects carrying the MAOA 3-repeat allele and DRD2 A2/A2 genotype. The MAOA gene may modify the association between the DRD2 gene and ANX/DEP ALC phenotype.

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence.

PubMed

Yates, W R; Cadoret, R J; Troughton, E P; Stewart, M; Giunta, T S

1998-06-01

The objective of this study is to examine the effect of fetal alcohol exposure on later substance dependence using an adoption study method. One hundred ninety-seven adoptees were interviewed for substance abuse disorders, including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers who drank during pregnancy. Adoptees with fetal alcohol exposure were compared with those without fetal alcohol exposure for symptoms of adult nicotine, alcohol, and drug dependence. Adoptee symptom counts for alcohol, drug, and nicotine dependence were higher for those exposed to alcohol in utero. The effect of fetal alcohol exposure remained after controlling for gender, biological parent alcohol dependence diagnosis, birth weight, gestational age and other environmental variables. Fetal alcohol exposure may produce increased risk for later nicotine, alcohol, and drug dependence. Possible effects of fetal alcohol exposure on development of adult substance use patterns needs attention in genetic studies of substance abuse.

Alcohol-dependent patients with comorbid phobic disorders: a comparison between comorbid patients, pure alcohol-dependent and pure phobic patients.

PubMed

Schadé, Annemiek; Marquenie, Loes A; Van Balkom, Anton J L M; Koeter, Maarten W J; De Beurs, Edwin; Van Den Brink, Wim; Van Dyck, Richard

2004-01-01

Patients with a double diagnosis of alcohol dependence and phobic disorders are a common phenomenon in both alcohol and anxiety disorder clinics. If we are to provide optimum treatment we need to know more about the clinical characteristics of this group of comorbid patients. To answer the following questions. (1). What are the clinical characteristics of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder? (2). Are alcohol dependence and other clinical characteristics of comorbid patients different from those of 'pure' alcohol-dependent patients? (3). Are the anxiety symptoms and other clinical characteristics of comorbid patients different from those of 'pure' phobic patients? Three groups of treatment-seeking patients were compared on demographic and clinical characteristics: alcohol dependent patients with a comorbid phobic disorder (n = 110), alcohol-dependent patients (n = 148) and patients with social phobia or agoraphobia (n = 106). In order to diagnose the comorbid disorders validly, the assessment took place at least 6 weeks after detoxification. Comorbid patients have high scores on depressive symptoms and general psychopathology: 25% of patients have a current and 52% a lifetime depressive disorder. The majority have no partner and are unemployed, they have a high incidence of other substance use (benzodiazepine, cocaine, cannabis) and a substantial proportion of comorbid patients have been emotionally, physically and sexually abused. They do not have a more severe, or different type of alcohol dependence or anxiety disorder than 'pure' alcohol-dependent patients and phobic patients respectively. Comorbid patients constitute a complex part of the treatment-seeking population in alcohol clinics and psychiatric hospitals. These findings should be taken into account when diagnosing and treating alcohol-dependent patients with a comorbid phobic disorder.

Personality traits in alcohol-dependent individuals in the context of childhood abuse.

PubMed

Gerhant, Aneta; Olajossy, Marcin

2016-10-31

The aim of this study was to identify groups of alcohol-dependent individuals differing in the severity of childhood physical, emotional and sexual abuse and to find the personality variables that discriminate between those groups. The study included 90 individuals dependent on alcohol. The following questionnaires were used: the Temperament and Character Inventory (TCI), the Coping Inventory (COPE), the Buss and Perry Aggression Questionnaire (BPAQ), Cattell's IPAT Anxiety Scale, and the Early Trauma Inventory (ETI). Two groups of subjects addicted to alcohol were identified: group 1 with high and group 2 with low childhood physical, emotional and sexual abuse indices. The subjects in Group 1 had significantly higher scores than the subjects in Group 2 on the TCI Temperament scales of NS and HA and lower scores on the TCI character scales of SD, C2 and C4. Group 1 subjects were significantly more likely than those from Group 2 to use avoidant coping strategies; they were also less likely to use problem-focused strategies and had significantly higher scores on general anxiety, overt anxiety, latent anxiety, level of aggression, physical aggression, hostility and anger. The higher severity of childhood physical, emotional and sexual abuse in alcoholics is associated with those personality traits that seem to be crucial for maintaining abstinence and the quality of cooperation in therapy.

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

PubMed

Marczinski, Cecile A

2014-07-01

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

A New Genomewide Association Meta-Analysis of Alcohol Dependence.

PubMed

Zuo, Lingjun; Tan, Yunlong; Zhang, Xiangyang; Wang, Xiaoping; Krystal, John; Tabakoff, Boris; Zhong, Chunlong; Luo, Xingguang

2015-08-01

Conventional meta-analysis based on genetic markers may be less powerful for heterogeneous samples. In this study, we introduced a new meta-analysis for 4 genomewide association studies on alcohol dependence that integrated the information of putative causal variants. A total of 12,481 subjects in 4 independent cohorts were analyzed, including 1 European American cohort (1,409 cases with alcohol dependence and 1,518 controls), 1 European Australian cohort (a total of 6,438 family subjects with 1,645 probands), 1 African American cohort from SAGE + COGA (681 cases and 508 controls), and 1 African American cohort from Yale (1,429 cases and 498 controls). The genomewide association analysis was conducted for each cohort, and then, a new meta-analysis was performed to derive the combined p-values. cis-Acting expression of quantitative locus (cis-eQTL) analysis of each risk variant in human tissues and RNA expression analysis of each risk gene in rat brain served as functional validation. In meta-analysis of European American and European Australian cohorts, we found 10 top-ranked single nucleotide polymorphisms (SNPs) (p < 10(-6) ) that were associated with alcohol dependence. They included 6 at SERINC2 (3.1 × 10(-8) ≤ p ≤ 9.6 × 10(-8) ), 1 at STK40 (p = 1.3 × 10(-7) ), 2 at KIAA0040 (3.3 × 10(-7) ≤ p ≤ 5.2 × 10(-7) ), and 1 at IPO11 (p = 6.9 × 10(-7) ). In meta-analysis of 2 African American cohorts, we found 2 top-ranked SNPs including 1 at SLC6A11 (p = 2.7 × 10(-7) ) and 1 at CBLN2 (p = 7.4 × 10(-7) ). In meta-analysis of all 4 cohorts, we found 2 top-ranked SNPs in PTP4A1-PHF3 locus (6.0 × 10(-7) ≤ p ≤ 7.2 × 10(-7) ). In an African American cohort only, we found 1 top-ranked SNP at PLD1 (p = 8.3 × 10(-7) ; OR = 1.56). Many risk SNPs had positive cis-eQTL signals, and all these risk genes except KIAA0040 were found to express in both rat and mouse brains. We found multiple genes that were significantly or suggestively associated with alcohol

Alcohol dependence as a chronic pain disorder

PubMed Central

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

2013-01-01

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

Lifetime posttraumatic stress disorder in Turkish alcohol-dependent inpatients: relationship with depression, anxiety and erectile dysfunction.

PubMed

Evren, Cuneyt; Can, Suat; Evren, Bilge; Saatcioglu, Omer; Cakmak, Duran

2006-02-01

The aim of the present study was to evaluate the prevalence of lifetime posttraumatic stress disorder (PTSD) in Turkish male alcohol-dependent inpatients, and to investigate the relationship of lifetime PTSD diagnosis with anxiety, depression, hopelessness, erectile dysfunction and psychosocial problems related with alcohol dependency. Eighty-two male inpatients who met DSM-IV criteria for alcohol dependence and 48 subjects without substance use disorder as a control group were included in the study. Subjects were applied the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), the Michigan Alcoholism Screening Test (MAST), the Beck Hopelessness Scale (BHS) and the International Index of Erectile Function (IIEF). Rate of lifetime PTSD diagnosis was found to be 26.8% among alcohol-dependent inpatients. The mean age of patients with lifetime PTSD was lower than in patients without this diagnosis, while there were no significant differences between these two groups in terms of age of first alcohol use, lifetime major depression, current depression, presence and severity of erectile dysfunction. Mean scores of HAM-D, HAM-A, BHS and MAST in the group with lifetime PTSD were significantly higher than the group without this diagnosis. There was a positive relationship between lifetime PTSD diagnosis and depression, anxiety, hopelessness and severity of psychosocial problems related to alcohol dependency, while there was no relationship between lifetime PTSD comorbidity and erectile dysfunction in alcohol-dependent patients.

Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity.

PubMed

Hogarth, Lee; Hardy, Lorna; Mathew, Amanda R; Hitsman, Brian

2018-04-01

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18-25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Negative Mood-Induced Alcohol-Seeking Is Greater in Young Adults Who Report Depression Symptoms, Drinking to Cope, and Subjective Reactivity

PubMed Central

2018-01-01

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18–25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. PMID:29389212

High-dose naltrexone therapy for cocaine-alcohol dependence.

PubMed

Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard

2009-01-01

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.

Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.

PubMed

Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L

2006-04-01

Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.

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

PubMed

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

2015-07-08

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

Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial.

PubMed

Morley, Kirsten C; Teesson, Maree; Reid, Sophie C; Sannibale, Claudia; Thomson, Clare; Phung, Nghi; Weltman, Martin; Bell, James R; Richardson, Kylie; Haber, Paul S

2006-10-01

To compare the efficacy of acamprosate and naltrexone in the treatment of alcohol dependence. A double-blind, placebo-controlled trial. Three treatment centres in Australia. A total of 169 alcohol dependent subjects were given naltrexone (50 mg/day), acamprosate (1998 mg/day) or placebo for 12 weeks. All subjects were offered manualized compliance therapy, a brief intervention that targets problems that may affect treatment compliance such as ambivalence and misperceptions about medication. Time to the first drink, time to first relapse, drinks per drinking day and cumulative abstinence. In intention-to-treat analyses, there were no differences between groups on outcome measures of drinking, craving or biochemical markers. Similarly, analyses of the 94 subjects that completed the study in full and demonstrated 80% compliance, revealed no significant treatment effects. Differential treatment effects were identified after stratification according to scores on the Alcohol Dependence Scale (ADS) and Depression Anxiety and Stress Scale (DASS). A significant beneficial treatment effect on time to first relapse was revealed for subjects with 'no depression' allocated to naltrexone (n = 56; P < 0.01). In addition, a significant beneficial treatment effect was revealed in subjects with 'low dependence' allocated to naltrexone (n = 34; P < 0.05). The results of this study support the efficacy of naltrexone in the relapse prevention of alcoholism amongst those with low levels of clinical depression and alcohol dependence severity. No effect of acamprosate was found in our sample.

Avoidance of alcohol-related stimuli in alcohol-dependent inpatients.

PubMed

Townshend, J M; Duka, T

2007-08-01

Previous research has shown an attentional bias toward drug-related stimuli in heavy social drinkers. Attentional orientation to drug-related cues may lead to increased craving and preoccupation with the drug and impaired ability to focus attention on nondrug-related activities, resulting in renewed drug taking or relapse from drug abstinence. The aim of this study was to investigate whether alcohol-dependent inpatients would differ in their selective attention toward alcohol-related stimuli in comparison with a group of social drinking controls. Thirty-five alcohol-dependent inpatients were compared with a group of 39 social drinking controls matched for age, sex, and verbal IQ. Attentional bias was assessed using alcohol-related pictures in a dot probe detection task. Questionnaires were used to examine outcome expectancies after alcohol consumption, anxiety, mood, and craving. The alcoholic inpatients showed a bias away from the alcohol-related stimuli, scored higher on alcohol outcome expectancies, and on anxiety measures (both state and trait). They also presented with more negative mood compared with the control group. Craving was higher in the alcoholic group for the factor "loss of control over drinking." Alcoholic inpatients undergoing treatment based on the 12-step treatment of Alcoholics Anonymous (Minnesota model), which includes counseling, and intensive group, individual, and family psychotherapy, show an avoidance for drug-related stimuli and a perception of loss of control over drinking. We suggest that their increased perception of loss of control over drinking produces the avoidance from the drug-related stimuli.

Prevalence and Trends in Alcohol Dependence and Alcohol Use Disorders in Japanese Adults; Results from Periodical Nationwide Surveys.

PubMed

Osaki, Yoneatsu; Kinjo, Aya; Higuchi, Susumu; Matsumoto, Hiroshi; Yuzuriha, Takefumi; Horie, Yoshinori; Kimura, Mitsuru; Kanda, Hideyuki; Yoshimoto, Hisashi

2016-07-01

Nationwide surveys to clarify the characteristics and trends of the drinking behavior of Japanese adults were carried out in 2003, 2008, and 2013. These were periodical cross-sectional surveys. Subjects were chosen through a stratified two-stage random sampling method. The surveys included drinking frequency and amount, ICD-10 alcoholism diagnostic standards, questionnaire for the determination of harmful alcohol use ( Alcohol Use Disorders Identification Test). In 2003, the surveys obtained responses from 2547 people (73% response rate); in 2008, 4123 people (55% response rate); and in 2013, 4153 people (59% response rate). The proportion of lifetime experience of alcohol dependence diagnosed by ICD-10 was 1.9% for male and 0.2% for female, and the estimated number of patients was 1.07 million. The declining trends were observed in the percentage of daily drinkers and the amount of alcohol consumed per week for male. The lowering of the age for consuming their first alcoholic drink and their first drunken experience was observed among female. The gender difference of prevalence of problem drinking is getting smaller. The binge drinking and heavy episodic drinking were observed especially younger generation. The only small proportion of patients with alcohol dependence had received specialized medical care, whereas the many of these visited medical institutions and health screening. The survey observed many hidden alcoholic patients, and showed the possibility that the healthcare facilities and health screening became the place of screening and intervention for alcohol dependence. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

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

PubMed

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

2009-05-01

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

Subjective response as a consideration in the pharmacogenetics of alcoholism treatment.

PubMed

Roche, Daniel Jo; Ray, Lara A

2015-01-01

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.

Subjective Responses to Alcohol Consumption as Endophenotypes: Advancing Behavioral Genetics in Etiological and Treatment Models of Alcoholism

PubMed Central

Ray, Lara A.; MacKillop, James; Monti, Peter M.

2015-01-01

Individual differences in subjective responses to alcohol consumption represent genetically-mediated biobehavioral mechanisms of alcoholism risk (i.e., endophenotype). The objective of this review is three-fold: (1) to provide a critical review the literature on subjective response to alcohol and to discuss the rationale for its conceptualization as an endophenotype for alcoholism; (2) to examine the literature on the neurobiological substrates and associated genetic factors subserving individual differences in subjective response to alcohol; and (3) to discuss the treatment implications of this approach and to propose a framework for conceptualizing, and systematically integrating, endophenotypes into alcoholism treatment. PMID:20590398

Race-Specific Associations Between Trauma Cognitions and Symptoms of Alcohol Dependence in Individuals with Comorbid PTSD and Alcohol Dependence

PubMed Central

Williams, Monnica; Jayawickreme, Nuwan; Sposato, Rosanna; Foa, Edna B.

2011-01-01

Posttraumatic Stress Disorder (PTSD) changes the way people think about themselves, others, and the safety of the world. These cognitions may play a role in alcohol dependence, where alcohol dependence is maintained as an attempt to manage posttraumatic anxiety. The current study examined black-white differences in various PTSD cognitions and their relationship to symptoms of alcohol dependence in a dually diagnosed sample (N=167). Analyses revealed racial differences in trauma cognitions and their impact on symptoms of alcohol dependence, suggesting that trauma cognitions are more strongly associated with adverse consequences of drinking and alcohol craving severity among African Americans than European Americans. Additional relationships between ethnic identification and trauma-related cognitions are described and theoretical and clinical implications of these findings are discussed. PMID:21930346

Cognitive remediation therapy during treatment for alcohol dependence.

PubMed

Rupp, Claudia I; Kemmler, Georg; Kurz, Martin; Hinterhuber, Hartmann; Fleischhacker, W Wolfgang

2012-07-01

Cognitive impairments in individuals with alcohol dependence may interfere with the progress of treatment and contribute to the progression of the disease. This study aimed to determine whether cognitive remediation (CR) therapy applied during treatment for alcohol dependence improves cognitive functioning in alcohol-dependent inpatients. A secondary aim was to evaluate whether the benefits of CR generalize to noncognitive clinically meaningful outcomes at the end of inpatient treatment. Forty-one alcohol-dependent patients entering inpatient treatment for alcohol dependence were randomly assigned to receive conventional treatment (n = 21) or an additional 12 sessions of computer-assisted CR focusing on cognitive enhancement in attention/executive function and memory domains (n = 20). Assessments of cognitive abilities in these domains as well as of psychological well-being and alcohol craving were conducted at baseline (at the beginning of inpatient treatment) and after CR (at the end of treatment). Results indicated that, relative to patients completing conventional treatment, those who received supplemental CR showed significant improvement in attention/executive function and memory domains, particularly in attention (alertness, divided attention), working memory, and delayed memory (recall). In addition, patients receiving CR during alcohol-dependence treatment showed significantly greater improvements in psychological well-being (Symptom Checklist-90-Revised) and in the compulsion aspect of craving (Obsessive Compulsive Drinking Scale-German version). CR during inpatient treatment for alcohol dependence is effective in improving cognitive impairments in alcohol-dependent patients. The benefits generalize to noncognitive outcomes, demonstrating that CR may be an efficacious adjunctive intervention for the treatment of alcohol dependence.

Alcohol attentional bias is associated with autonomic indices of stress-primed alcohol cue-reactivity in alcohol-dependent patients.

PubMed

Garland, Eric L; Franken, Ingmar H; Sheetz, John J; Howard, Matthew O

2012-06-01

When alcohol-dependent individuals are exposed to drinking-related cues, they exhibit psychophysiological reactivity such as changes in heart rate variability (HRV) and skin temperature. Moreover, such alcohol cue-reactivity may co-occur with attentional bias (AB) toward alcohol cues. In turn, stress may promote appetitive responses by exacerbating these autonomic and attentional factors. Although cue-reactivity paradigms have been used for decades to probe such automatic appetitive processes in persons with alcohol-use disorders, less is known about the attentional correlates of alcohol cue-reactivity. In this study, alcohol-dependent adults (N = 58) recruited from a residential treatment facility completed a spatial cueing task as a measure of alcohol AB and affect-modulated cue-reactivity protocol. Multiple linear regression analyses revealed that alcohol AB was significantly positively associated with parasympathetically mediated HRV and finger temperature slope and inversely associated with sympathetically mediated HRV during stress-primed alcohol cue-exposure, independent of alcohol dependence severity, time in treatment, alcohol craving, and perceived stress. Study findings suggest that alcohol AB is linked with physiological cue-reactivity and that different attentional strategies are associated with distinct profiles of autonomic responses that may ultimately index or confer additional risk for alcohol dependence.

[Dimensions of personality, attachment style and early maladaptive schemas in alcohol-dependent patients: Are there gender-specific differences?

PubMed

Camart, N; Cotte, M; Leignel, S; Bouvet, C; Limosin, F

2016-12-01

Literature reports particularities in certain psychological dimensions, such as personality traits, early maladaptive schemas and attachment styles among patients dependent on alcohol. Several international studies have also emphasized significant gender differences in psychological profiles. However, in France, only a few studies have dealt with this subject. Our aim was on the one hand to study the characteristics of alcohol-dependent patients in these variables, and on the other hand to search for gender differences. The personality dimensions were assessed with the French Big Five Inventory (Fr-BFI), the attachment style with Bartholomew's Relationship Scales Questionnaire (RSQ), and early maladaptive schemas with the short version of Young's questionnaire (YSQ-S1). Seventy-three subjects were included: 39 alcohol-dependent patients (19 men and 20 women) and 34 healthy control subjects (17 men and 17 women). The scores of alcohol-dependent patients were compared with those of a healthy control group (n=34, 17 men, 17 women) and available standards. We also compared the scores of men and women with alcohol dependence between them, and we compared the scores of men and women to those of the control group and those of the reference sample of the same sex. This is an ongoing study and we publish here the first results. Compared with control subjects, and the reference sample, alcohol-dependent patients showed significantly higher levels of neuroticism and lower levels of extraversion. Furthermore, differences in attachment styles were observed compared to the control group: alcohol-dependent patients presented a less secure attachment, seemed more fearful and detached, but the results remained within the normal standards. Compared to the control subjects, alcohol-dependent patients showed a significant increase in scores regarding many schemas: emotional deprivation, abandonment, abuse/mistrust, isolation, imperfection, dependence, symbiotic relationship

Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure.

PubMed

De Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Toennes, S W; Ramaekers, J G

2016-09-01

Alcohol and cannabis use have been implicated in aggression. Alcohol consumption is known to facilitate aggression, whereas a causal link between cannabis and aggression has not been clearly demonstrated. This study investigated the acute effects of alcohol and cannabis on subjective aggression in alcohol and cannabis users, respectively, following aggression exposure. Drug-free controls served as a reference. It was hypothesized that aggression exposure would increase subjective aggression in alcohol users during alcohol intoxication, whereas it was expected to decrease subjective aggression in cannabis users during cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21), and controls (n = 20) were included in a mixed factorial study. Alcohol and cannabis users received single doses of alcohol and placebo or cannabis and placebo, respectively. Subjective aggression was assessed before and after aggression exposure consisting of administrations of the point-subtraction aggression paradigm (PSAP) and the single category implicit association test (SC-IAT). Testosterone and cortisol levels in response to alcohol/cannabis treatment and aggression exposure were recorded as secondary outcome measures. Subjective aggression significantly increased following aggression exposure in all groups while being sober. Alcohol intoxication increased subjective aggression whereas cannabis decreased the subjective aggression following aggression exposure. Aggressive responses during the PSAP increased following alcohol and decreased following cannabis relative to placebo. Changes in aggressive feeling or response were not correlated to the neuroendocrine response to treatments. It is concluded that alcohol facilitates feelings of aggression whereas cannabis diminishes aggressive feelings in heavy alcohol and regular cannabis users, respectively.

Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

PubMed Central

Irwin, Michael R.; Olmstead, Richard; Valladares, Edwin M.; Breen, Elizabeth Crabb; Ehlers, Cindy L.

2009-01-01

Background In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo. Results Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep. Conclusions Pharmacologic neutralization of TNF-α activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-α may have a physiologic role in the regulation of REM sleep in humans. PMID:19185287

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

PubMed Central

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

2009-01-01

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

Virtual Reality Therapy for the Treatment of Alcohol Dependence: A Preliminary Investigation With Positron Emission Tomography/Computerized Tomography.

PubMed

Son, Ji Hyun; Lee, Sang Hoon; Seok, Ju Won; Kee, Baik Seok; Lee, Hyun Woong; Kim, Hyung Joon; Lee, Tae Kyung; Han, Doug Hyun

2015-07-01

Virtual reality therapy (VRT) uses multimodal stimulation that includes visual, auditory, olfactory, and gustatory stimuli. The aim of this study was to assess the effectiveness of VRT in treating subjects with alcohol dependence (AD) by evaluating changes in brain metabolism. The VRT protocol consisted of three steps: relaxation, presentation of a high-risk situation, and presentation of an aversive situation. Twelve alcohol-dependent subjects underwent 10 sessions of VRT. The alcohol-dependent subjects were assessed with 18F-fluorodeoxyglucose positron emission tomography images before and after VRT, whereas the control group underwent imaging according to the same protocol only at baseline. Compared with the healthy control group, AD subjects showed higher metabolism in the right lentiform nucleus and right temporal lobe (BA20) at baseline (P(FDR < .05) = .026). In addition, the metabolism in the left anterior cingulate was lower in subjects with AD (P(uncorr) = .001). After VRT, alcohol-dependent subjects showed decreased brain metabolism in the right lentiform nucleus (P(FDR < .05) = .026) and right temporal lobe (BA38, P(FDR < .05) = .032) relative to that at baseline. Our results suggest a neurobiological imbalance, notably, a high sensitivity to stimuli, in the limbic system in subjects with AD. Furthermore, we determined that metabolism decreased in the basal ganglia after VRT, which may explain the limbic-regulated responses of reward and regulation. Therefore, we tentatively recommend VRT to treat AD through its regulating effect on limbic circuits.

Alcohol dependence and health care utilization in African Americans.

PubMed

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

2013-01-01

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

Prenatal and adult androgen activities in alcohol dependence.

PubMed

Lenz, B; Mühle, C; Braun, B; Weinland, C; Bouna-Pyrrou, P; Behrens, J; Kubis, S; Mikolaiczik, K; Muschler, M-R; Saigali, S; Sibach, M; Tanovska, P; Huber, S E; Hoppe, U; Eichler, A; Heinrich, H; Moll, G H; Engel, A; Goecke, T W; Beckmann, M W; Fasching, P A; Müller, C P; Kornhuber, J

2017-07-01

Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy and Safety of Baclofen for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Garbutt, James C; Kampov-Polevoy, Alexei B; Gallop, Robert; Kalka-Juhl, Linda; Flannery, Barbara A.

2010-01-01

Background Recent clinical trials and case-reports indicate that baclofen, a GABAB agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol dependent individuals in two placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States. Methods The study was a double-blind, placebo-controlled, randomized study comparing 30 mg per day of baclofen to placebo over 12 weeks of treatment and utilizing eight sessions of BRENDA, a low-intensity psychosocial intervention. 121 subjects were screened to yield 80 randomized subjects (44 male) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined. Results 76% of subjects completed the study. No difference by drug condition was seen in % heavy drinking days where on-average rates were 25.5% (± 23.6%) for placebo and 25.9% (± 23.2%) for baclofen during treatment (t(73)=0.59, p=0.56). Similarly, no differences were seen by drug condition in % days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F(1,73)=5.39, p=0.02). Baclofen was well tolerated with only two individuals stopping baclofen because of adverse events. There were no serious adverse events. Conclusions Baclofen, a GABAB agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is

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

PubMed Central

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

2016-01-01

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

Alcohol Dependence and Health Care Utilization in African Americans

PubMed Central

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

2013-01-01

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

Abnormal Metabolite in Alcoholic Subjects,

DTIC Science & Technology

1982-01-01

this study included alcoholic hepatitis or cirrhosis of the liver in 29. of the alcoholic subjects; diabetes mellitus in 8 and Korsakoff’s syndrome in 6...evidence of -7- Korsakoff’s syndrome and the presence or absence of 2,3-butanediol. There was, however, a suggestive correlation with independently...Gamma GT 193, SGPT 29 b 0 0.023 0.05 51a F.B. 22 M 28 0.029 0.14 b 0 ɘ.01 0.12 77 J.N.S. 52 M 0 0.027 0.11 57 JJ.S 45 m 4. 0.25 .35 Korsakoff ’s

The link between inflammation, bugs, the intestine and the brain in alcohol dependence

PubMed Central

Leclercq, S; de Timary, P; Delzenne, N M; Stärkel, P

2017-01-01

In recent years, some new processes have been proposed to explain how alcohol may influence behavior, psychological symptoms and alcohol seeking in alcohol-dependent subjects. In addition to its important effect on brain and neurotransmitters equilibrium, alcohol abuse also affects peripheral organs including the gut. By yet incompletely understood mechanisms, chronic alcohol abuse increases intestinal permeability and alters the composition of the gut microbiota, allowing bacterial components from the gut lumen to reach the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in target organs, which consequently synthesize and release pro-inflammatory cytokines. Circulating cytokines are considered important mediators of the gut–brain communication, as they can reach the central nervous system and induce neuroinflammation that is associated with change in mood, cognition and drinking behavior. These observations support the possibility that targeting the gut microbiota, by the use of probiotics or prebiotics, could restore the gut barrier function, reduce systemic inflammation and may have beneficial effect in treating alcohol dependence and in reducing alcohol relapse. PMID:28244981

The link between inflammation, bugs, the intestine and the brain in alcohol dependence.

PubMed

Leclercq, S; de Timary, P; Delzenne, N M; Stärkel, P

2017-02-28

In recent years, some new processes have been proposed to explain how alcohol may influence behavior, psychological symptoms and alcohol seeking in alcohol-dependent subjects. In addition to its important effect on brain and neurotransmitters equilibrium, alcohol abuse also affects peripheral organs including the gut. By yet incompletely understood mechanisms, chronic alcohol abuse increases intestinal permeability and alters the composition of the gut microbiota, allowing bacterial components from the gut lumen to reach the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in target organs, which consequently synthesize and release pro-inflammatory cytokines. Circulating cytokines are considered important mediators of the gut-brain communication, as they can reach the central nervous system and induce neuroinflammation that is associated with change in mood, cognition and drinking behavior. These observations support the possibility that targeting the gut microbiota, by the use of probiotics or prebiotics, could restore the gut barrier function, reduce systemic inflammation and may have beneficial effect in treating alcohol dependence and in reducing alcohol relapse.

Aversion to injection limits acceptability of extended-release naltrexone among homeless, alcohol-dependent patients.

PubMed

Friedmann, Peter D; Mello, Dawn; Lonergan, Sean; Bourgault, Claire; O'Toole, Thomas P

2013-01-01

Ending homelessness is a major priority of the Department of Veteran Affairs (VA), and alcohol use can be a barrier to stable housing. Clinical trials suggest that depot extended-release naltrexone (XR-NTX) is efficacious in reducing alcohol consumption among alcohol-dependent subjects. An open-label, randomized pilot study sought to examine the feasibility and effectiveness of XR-NTX versus oral naltrexone to improve alcohol consumption and housing stability among homeless, alcohol-dependent veterans at the Providence Veteran Affairs Medical Center. Of 215 potential candidates approached over a 16-month recruitment period, only 15 agreed to consider study entry and 7 were randomized. The primary reasons given for refusal were not wanting an injection; fear of needles; and not wanting to change drinking habits. Only 1 participant in the XR-NTX group returned after the first injection. Three participants in the oral naltrexone group attended all 7 visits and had good outcomes. Although XR-NTX has demonstrated efficacy in reducing heavy drinking, limited acceptance of the injection might reduce its effectiveness among homeless, alcohol-dependent patients.

Brain pathways to recovery from alcohol dependence.

PubMed

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

2015-08-01

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

Test-retest reliability of the underlying latent factor structure of alcohol subjective response.

PubMed

Lutz, Joseph A; Childs, Emma

2017-04-01

Alcohol subjective experiences are multi-dimensional and demonstrate wide inter-individual variability. Recent efforts have sought to establish a clearer understanding of subjective alcohol responses by identifying core constructs derived from multiple measurement instruments. The aim of this study was to evaluate the temporal stability of this approach to conceptualizing alcohol subjective experiences across successive alcohol administrations in the same individuals. Healthy moderate alcohol drinkers (n = 104) completed six experimental sessions each, three with alcohol (0.8 g/kg), and three with a non-alcoholic control beverage. Participants reported subjective mood and drug effects using standardized questionnaires before and at repeated times after beverage consumption. We explored the underlying latent structure of subjective responses for all alcohol administrations using exploratory factor analysis and then tested measurement invariance over the three successive administrations using multi-group confirmatory factor analyses. Exploratory factor analyses on responses to alcohol across all administrations yielded four factors representing "Positive mood," "Sedation," "Stimulation/Euphoria," and "Drug effects and Urges." A confirmatory factor analysis on the separate administrations indicated acceptable configural and metric invariance and moderate scalar invariance. In this study, we demonstrate temporal stability of the underlying constructs of subjective alcohol responses derived from factor analysis. These findings strengthen the utility of this approach to conceptualizing subjective alcohol responses especially for use in prospective and longitudinal alcohol challenge studies relating subjective response to alcohol use disorder risk.

Salivary exoglycosidases as markers of alcohol dependence.

PubMed

Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zalewska, Anna; Zwierz, Krzysztof; Szulc, Agata; Szajda, Sławomir Dariusz

2014-01-01

Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, β-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), β-galactosidase (GAL), and β-glucuronidase (GLU), and their applicability as markers of alcohol dependence. The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence). © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

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

ERIC Educational Resources Information Center

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

2007-01-01

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

Using the Theory of Planned Behaviour to examine enrolled nursing students' intention to care for patients with alcohol dependence: A survey study.

PubMed

Talbot, Anna-Lisa; Dorrian, Jillian; Chapman, Janine

2015-11-01

Nurses are often the first point of contact for patients hospitalized due to alcohol-related causes. Alcohol dependence is highly stigmatized and as a result healthcare professionals often have low behavioural intentions, meaning low willingness to care for these patients. This can have a direct influence on quality of care. The purpose of this study was to explore enrolled nursing students' intention to care for patients with alcohol dependence and the antecedents, preliminary factors, that predict this within the Theory of Planned Behaviour; specifically attitudes, subjective norms, self-efficacy and controllability. The study was a cross-sectional survey using the Theory of Planned Behaviour. Two Technical and Further Education South Australia campuses across metropolitan Adelaide. n=86 enrolled nursing students completed the survey (62% response rate). Enrolled nursing students' intention, attitudes, subjective norms, self-efficacy and controllability were measured using a Theory of Planned Behaviour Questionnaire. The Short Alcohol and Alcohol Problems Perception Questionnaire investigated attitudes in more detail and a short knowledge scale assessed alcohol-related knowledge. Subjective norms and attitudes had a significant, positive effect on intention to care within the final model, accounting for 22.6% of the variance, F2,83=12.12, p<0.001. Subjective norms were the strongest predictor. External factors such as age, previous alcohol training and alcohol-related knowledge held direct paths to antecedents of intention. Subjective norms were the strongest predictor of intention to care for patients with alcohol dependence, followed by attitudes. The study provides an understanding of enrolled nursing students' intention to care for alcohol dependent patients. These findings can assist in developing tailored alcohol training for students, to increase attitudes and foster behavioural change, in order to improve the quality of care for these patients. Copyright

Experiences of alcohol dependence: a qualitative study.

PubMed

Dyson, Jane

2007-01-01

Despite the increasing incidence of alcohol misuse and the costs it incurs, British society continues to hold equivocal and ambiguous attitudes towards drinking, and understanding of the nature of alcohol dependence and related issues is limited. This qualitative study aimed to investigate the experiences of individuals with alcohol dependence to enhance understanding of the illness, identify key issues and common themes and provide insight into the experiences of the participants during their alcohol dependent period and recovery. A qualitative approach, using narrative method, was used. Eight participants, all members of Alcoholics Anonymous (AA), were interviewed by the researchers. Using a grounded theory approach and content analysis, the in-depth narratives of the eight participants were systematically analysed. While participants continued to deny the existence of a problem to those around them, their behaviours indicated that they were aware of the problem but were afraid to admit it openly through fear of other people's reactions. Participants generally regarded GPs as helpful but other health professionals less so, especially nurses and Accident and Emergency staff. Participants considered that the success of treatment depended on their own motivation and willingness to engage in radical behaviour change. They considered that reaching this stage represented a turning point in their illness. The point at which this stage was reached appeared to be different for each participant. This systematic analysis of a small sample of alcohol dependent individuals gives insight into their experiences during alcohol dependency and the journey to recovery. The findings suggest that denial of the problem to the outside world occurs simultaneously with individuals being aware of their problem. Participants felt the illness carries a stigma and their negative experiences of health professionals other than GPs suggests that nurses and other health workers need to revise

Importance of alcohol-related expectations and emotional expressivity for prediction of motivation to refuse alcohol in alcohol-dependent patients.

PubMed

Slavinskienė, Justina; Žardeckaitė-Matulaitienė, Kristina

2014-01-01

The aim of this study was to evaluate the importance of alcohol-dependent patients' emotional expressivity, alcohol-related expectations and socio-demographic factors for prediction of motivation to refuse alcohol consumption. The study sample consisted of 136 alcohol-dependent patients (100 men and 36 women) undergoing treatment in Kaunas center for addictive disorders. Only higher expression of negative alcohol-related expectations (std. beta=0.192, P=0.023), higher emotional impulse intensity (std. beta=0.229, P=0.021) and higher expression of positive emotional expressiveness (std. beta=0.021, P=0.020) as well as gender (std. beta=0.180, P=0.049), education (std. beta=-0.137, P=0.038) and alcohol dependency treatment conditions (members of support group after rehabilitation program) (std. beta=0.288, P=0.001; std. beta=0.608, P=0.001) were significant factors for predicting the different level of alcohol-dependent patients motivation to refuse alcohol consumption. Negative alcohol-related expectations, emotional impulse intensity and positive emotional expressiveness were significant even though quite weak triggers for alcohol-dependent patients' different level of motivation to refuse alcohol consumption. An assumption could be made that by changing these triggers it is possible to change addictive behavior. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The effects of energy drink in combination with alcohol on performance and subjective awareness.

PubMed

Alford, Chris; Hamilton-Morris, Jennifer; Verster, Joris C

2012-08-01

This study investigated the coadministration of an energy drink with alcohol to study the effects on subjective intoxication and objective performance. This study aims to evaluate the objective and subjective effects of alcohol versus placebo at two alcohol doses, alone and in combination with an energy drink, in a balanced order, placebo-controlled, double-blind design. Two groups of ten healthy volunteers, mean (SD) age of 24 (6.5), participated in the study. One group consumed energy drink containing 80 mg of caffeine and the other consumed a placebo drink, with both receiving two alcohol doses (0.046 and 0.087% breathalyser alcohol concentration). Tests included breath alcohol assessment, objective measures of performance (reaction time, word memory and Stroop task) and subjective visual analogue mood scales. Participants showed significantly impaired reaction time and memory after alcohol compared to the no alcohol condition and had poorer memory after the higher alcohol dose. Stroop performance was improved with the energy drink plus alcohol combination compared to the placebo drink plus alcohol combination. Participants felt significant subjective dose-related impairment after alcohol compared to no alcohol. Neither breath alcohol concentration nor the subjective measures showed a significant difference between the energy drink and the placebo energy drink when combined with alcohol. Subjective effects reflected awareness of alcohol intoxication and sensitivity to increasing alcohol dose. There were no overall significant group differences for subjective measures between energy drink and placebo groups in the presence of alcohol and no evidence that the energy drink masked the subjective effects of alcohol at either dose.

Alcohol dependence, consumption of alcoholic energy drinks and associated work characteristics in the Taiwan working population.

PubMed

Cheng, Wan-Ju; Cheng, Yawen; Huang, Ming-Chyi; Chen, Chiou-Jong

2012-01-01

To examine the association between work characteristics and the risk of alcohol dependence across different employment types and occupations, including the pattern of alcohol consumption in the form of energy drinks and its association with alcohol dependence. A total of 13,501 men and 8584 women participated in a national survey in Taiwan. Alcohol dependence was defined as ≥2 points in the CAGE questionnaire. A self-administered questionnaire recorded drinking behaviors, consumption of alcoholic energy drinks, employment type, occupation and a number of psychosocial work stressors, namely job demands, job control, employment security and workplace justice. Of the total, 9.4% of men and 0.8% of women were CAGE-positive, and 6.0% of men and 0.7% of women regularly consumed alcoholic energy drinks. In male and female regular consumers of alcoholic energy drinks, 38.7 and 23.3%, respectively, were alcohol-dependent. Multivariate regression analyses showed that male employees in manual skilled occupations, with lower workplace justice, having weekly working hours <40 h and on piece-rated or time-based pay systems were at higher risks of alcohol dependence. Certain occupational groups and workers with adverse psychosocial work characteristics should be targets for prevention of alcohol dependence. Alcoholic energy drink consumption should be taken into consideration while studying alcohol dependence in the work population in Taiwan.

Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study

PubMed Central

Farokhnia, M; Schwandt, M L; Lee, M R; Bollinger, J W; Farinelli, L A; Amodio, J P; Sewell, L; Lionetti, T A; Spero, D E; Leggio, L

2017-01-01

Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction, P=0.03). Ratings of feeling intoxicated were significantly higher in the baclofen group after consuming the priming drink (P=0.006). During the self-administration session, baclofen significantly increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A significant reduction in heart rate (P<0.001) and a trend-level increase in diastolic blood pressure (P=0.06) were also detected in the baclofen group during the alcohol laboratory session. In conclusion, baclofen was shown to affect subjective and physiological responses to alcohol drinking in anxious alcohol-dependent individuals. These results do not support an anti-craving or anti-reinforcing effect of baclofen, but rather suggest that baclofen may act as a substitution medication for alcohol use disorder. PMID:28440812

Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study.

PubMed

Farokhnia, M; Schwandt, M L; Lee, M R; Bollinger, J W; Farinelli, L A; Amodio, J P; Sewell, L; Lionetti, T A; Spero, D E; Leggio, L

2017-04-25

Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction, P=0.03). Ratings of feeling intoxicated were significantly higher in the baclofen group after consuming the priming drink (P=0.006). During the self-administration session, baclofen significantly increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A significant reduction in heart rate (P<0.001) and a trend-level increase in diastolic blood pressure (P=0.06) were also detected in the baclofen group during the alcohol laboratory session. In conclusion, baclofen was shown to affect subjective and physiological responses to alcohol drinking in anxious alcohol-dependent individuals. These results do not support an anti-craving or anti-reinforcing effect of baclofen, but rather suggest that baclofen may act as a substitution medication for alcohol use disorder.

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

PubMed Central

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

2014-01-01

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

Plasma concentrations of oleoylethanolamide and other acylethanolamides are altered in alcohol-dependent patients: effect of length of abstinence.

PubMed

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

2017-09-01

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. © 2016 Society for the Study of

Serotonin receptor, SERT mRNA and correlations with symptoms in males with alcohol dependence and suicide.

PubMed

Thompson, P M; Cruz, D A; Olukotun, D Y; Delgado, P L

2012-09-01

This study tested the hypothesis that abnormalities in components of the serotonin (5HT) system in the prefrontal cortex are associated with suicide in alcohol-dependent subjects. Second, we assessed the relationship of lifetime impulsivity and mood symptoms with prefrontal cortex 5-HT measures. Tissue was obtained from Brodmann's areas (BA) 9 and 24 in postmortem samples of individuals who were alcohol dependent with suicide (n = 5), alcohol dependent without suicide (n = 9) and normal controls (n = 5). Serotonin receptor (5HT) and serotonin reuptake transporter (SERT) mRNA were measured. Interviews with next of kin estimated lifetime impulsivity and mood symptoms in the last week of life. Serotonin receptor 1A (5HT1A) mRNA in BA 9 was elevated in the alcohol dependence without suicide group compared with controls. In the alcohol dependence with suicide group, anxiety symptoms were associated with decreased BA 24 SERT mRNA and depressive symptoms with BA 9 5HT1A mRNA expression. In the alcohol dependent only group impulsivity is correlated with increased BA 9, and BA 24 serotonin receptor 2A mRNA. Our data suggest region-specific change, rather than global serotonin blunting is involved in alcohol dependence and suicide. It also suggests that symptoms are differentially influenced by prefrontal cortex serotonin receptor mRNA levels. © 2011 John Wiley & Sons A/S.

The role of multifamily therapy in promoting retention in treatment of alcohol and cocaine dependence.

PubMed

Conner, K R; Shea, R R; McDermott, M P; Grolling, R; Tocco, R V; Baciewicz, G

1998-01-01

The authors present a model for incorporating multifamily therapy in the treatment of chemical dependency and investigate the association of family participation in multifamily therapy group with treatment retention in a sample of 164 alcohol- and/or cocaine-dependent outpatients. Results indicate that level of family attendance at a multifamily group strongly predicted completion of short-term and long-term out-patient treatment. Effects were greater for cocaine-dependent than for alcohol-dependent subjects in analyses of short-term treatment retention. Multifamily therapy may be a powerful method to engage patients families in treatment and promote treatment retention, especially in the early, intensive phases of treatment for cocaine dependency.

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

PubMed Central

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

2014-01-01

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

Emotion Regulation in Alcohol Dependence.

PubMed

Petit, Géraldine; Luminet, Olivier; Maurage, François; Tecco, Juan; Lechantre, Stéphane; Ferauge, Marc; Gross, James J; de Timary, Philippe

2015-12-01

The main aim of this study was to investigate, in alcohol-dependent (AD) patients, the use of the 5 emotion regulation strategies specified in Gross's (1998, Rev Gen Psychol, 2, 271) process model of emotion regulation with the use of a semi-structured interview allowing a detailed and high-quality assessment of emotion regulation strategies. A secondary aim was to examine the possible influence of protracted abstinence and detoxification on emotion dysregulation. Finally, the association between the level of craving and the types of regulation strategies was investigated. Forty-four treatment-seeking AD patients with varying time spent in rehabilitation, and 26 healthy controls were interviewed using a version of the Emotion Regulation Interview (Werner et al., 2011, J Psychopathol Behav Assess, 33, 346) adapted to alcohol dependence. Compared to controls, AD patients reported significantly greater use of response modulation and attentional deployment, but lesser use of cognitive change. Among patients, (1) rehabilitation duration was positively correlated with the use of cognitive change and (2) the use of response modulation was positively associated with the level of craving. These findings clarify the specific pattern of emotion dysregulation associated with alcohol dependence. They also suggest that (1) abstinence is associated with a shift toward more adaptive emotion regulation patterns and that (2) inefficient regulation strategies may lead to craving and the maintenance of alcohol use. If these findings are confirmed through longitudinal and mediation designs, they will have important clinical implications. Copyright © 2015 by the Research Society on Alcoholism.

Automatic Avoidance Tendencies for Alcohol Cues Predict Drinking After Detoxification Treatment in Alcohol Dependence

PubMed Central

2016-01-01

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

Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.

PubMed

Spreckelmeyer, Katja N; Paulzen, Michael; Raptis, Mardjan; Baltus, Thomas; Schaffrath, Sabrina; Van Waesberghe, Julia; Zalewski, Magdalena M; Rösch, Frank; Vernaleken, Ingo; Schäfer, Wolfgang M; Gründer, Gerhard

2011-10-15

Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system. Availability of D(2/3) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride. Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding (Δ%BP(ND)). The [(18)F]fallypride binding potentials (BP(ND)s) were significantly reduced in the ventral striatum, dorsal putamen, and amygdala after remifentanil application in both patients and control subjects. In the patient group, ventral striatum Δ%BP(ND) was correlated with the Alcohol Use Disorders Identification Test score. The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system, supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway. No difference in dopamine release was found between patients and control subjects, but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence

Aggression among male alcohol-dependent inpatients who smoke cigarettes.

PubMed

Saatcioglu, Omer; Erim, Rahsan

2009-12-01

The authors aimed to explore the relation between nicotine dependence and the severity of aggression among Turkish male alcohol-dependent inpatients who smoked cigarettes, as well as the effect of aggression in these groups. Participants were 126 male alcohol-dependent inpatients who were given the Structured Clinical Interview for DSM-IV, Substance Use Disorder Module (A. Corapcioglu, O. Aydemir, & M. Yildiz, 1999; M. B. First, R. L. Spitzer, & J. B. W. Williams, 1997), the Fagerstrom Test for Nicotine Dependence (K. O. Fagerstrom, 1978), and the Overt Aggression Scale (OAS; S. C. Yudofsky, J. M. Silver, W. Jackson, J. Endicott, & D. Williams, 1986). The authors found differences between male alcohol-dependent inpatients with nicotine dependence (n = 94) and those with nondependence (n = 32) in OAS subtypes. The authors' findings showed that smoking cigarettes-an addiction frequently observed with alcoholism-was positively correlated with aggressive behaviors. The authors suggest that smoking cigarettes may cause aggression or aggression may cause smoking. Observing and evaluating how aggression and smoking cigarettes are associated with alcohol dependence may help relapse prevention and improve effectiveness of treatment interventions in alcoholism.

Depression and social phobia secondary to alcohol dependence.

PubMed

Olgiati, Paolo; Liappas, Ioannis; Malitas, Petros; Piperi, Christina; Politis, Antonis; Tzavellas, Elias O; Zisaki, Aikaterini; Ferrari, Barbara; De Ronchi, Diana; Kalofoutis, Anastasios; Serretti, Alessandro

2007-01-01

According to the self-medication hypothesis, individuals with depression and anxiety disorders use alcohol to control their symptoms and subsequently become dependent. Conversely, alcohol dependence disorder (ADD) can cause or exacerbate psychiatric disorders. This study analyzed the characteristics of depression and social phobia secondary to ADD. (1) What is their functional impact? (2) Are they independent or associated conditions? (3) Do they completely remit in abstinent individuals? (4) Is the remission of one disorder associated with the remission of the other disorder? Sixty-four inpatients with ADD were evaluated with depression and anxiety disorder scales upon admission to hospital and after 5 weeks of detoxification. Baseline comparisons differentiated patients with a Hamilton Rating Scale for Depression (HDRS) score > 35 (n = 50; 78%) from those with an HDRS score < or = 35 by higher levels of generalized anxiety and lower global functioning. Patients with generalized social phobia [Leibowitz Social Anxiety Scale (LSAS) score > 60: n = 20; 31.2%] were not distinguishable from those with an LSAS score < or = 60 by depressive and anxiety disorder symptoms. In postdetoxification assessment, patients who remitted from depression (HDRS score < 7: n = 35; 54.6%) had a lower generalized anxiety and marginally higher levels of hypochondriasis compared to nonremitter subjects (HDRS score > or = 7). Patients who remitted from social phobia (LSAS score < 30: n = 32; 50%) did not significantly differ from nonremitter subjects in depressive and anxiety disorder symptoms. Generalized anxiety (Hamilton Rating Scale for Anxiety) and hypochondriasis (Whiteley Index) were the significant predictors of global functioning (Global Assessment Scale). Depression and social phobia secondary to ADD are independent conditions that do not completely remit after cessation of drinking. Specific treatments are needed to reduce residual depressive and anxiety symptoms in abstinent

Shared additive genetic influences on DSM-IV criteria for alcohol dependence in subjects of European ancestry.

PubMed

Palmer, Rohan H C; McGeary, John E; Heath, Andrew C; Keller, Matthew C; Brick, Leslie A; Knopik, Valerie S

2015-12-01

Genetic studies of alcohol dependence (AD) have identified several candidate loci and genes, but most observed effects are small and difficult to reproduce. A plausible explanation for inconsistent findings may be a violation of the assumption that genetic factors contributing to each of the seven DSM-IV criteria point to a single underlying dimension of risk. Given that recent twin studies suggest that the genetic architecture of AD is complex and probably involves multiple discrete genetic factors, the current study employed common single nucleotide polymorphisms in two multivariate genetic models to examine the assumption that the genetic risk underlying DSM-IV AD is unitary. AD symptoms and genome-wide single nucleotide polymorphism (SNP) data from 2596 individuals of European descent from the Study of Addiction: Genetics and Environment were analyzed using genomic-relatedness-matrix restricted maximum likelihood. DSM-IV AD symptom covariance was described using two multivariate genetic factor models. Common SNPs explained 30% (standard error=0.136, P=0.012) of the variance in AD diagnosis. Additive genetic effects varied across AD symptoms. The common pathway model approach suggested that symptoms could be described by a single latent variable that had a SNP heritability of 31% (0.130, P=0.008). Similarly, the exploratory genetic factor model approach suggested that the genetic variance/covariance across symptoms could be represented by a single genetic factor that accounted for at least 60% of the genetic variance in any one symptom. Additive genetic effects on DSM-IV alcohol dependence criteria overlap. The assumption of common genetic effects across alcohol dependence symptoms appears to be a valid assumption. © 2015 Society for the Study of Addiction.

Childhood or adolescent parental divorce/separation, parental history of alcohol problems, and offspring lifetime alcohol dependence.

PubMed

Thompson, Ronald G; Lizardi, Dana; Keyes, Katherine M; Hasin, Deborah S

2008-12-01

This study examined whether the experiences of childhood or adolescent parental divorce/separation and parental alcohol problems affected the likelihood of offspring DSM-IV lifetime alcohol dependence, controlling for parental history of drug, depression, and antisocial behavior problems. Data were drawn from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a nationally representative United States survey of 43,093 civilian non-institutionalized participants aged 18 and older, interviewed in person. Logistic regression models were used to calculate the main and interaction effects of childhood or adolescent parental divorce/separation and parental history of alcohol problems on offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Childhood or adolescent parental divorce/separation and parental history of alcohol problems were significantly related to offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Experiencing parental divorce/separation during childhood, even in the absence of parental history of alcohol problems, remained a significant predictor of lifetime alcohol dependence. Experiencing both childhood or adolescent parental divorce/separation and parental alcohol problems had a significantly stronger impact on the risk for DSM-IV alcohol dependence than the risk incurred by either parental risk factor alone. Further research is needed to better identify the factors that increase the risk for lifetime alcohol dependence among those who experience childhood or adolescent parental divorce/separation.

Childhood or Adolescent Parental Divorce/Separation, Parental History of Alcohol Problems, and Offspring Lifetime Alcohol Dependence

PubMed Central

Thompson, Ronald G.; Lizardi, Dana; Keyes, Katherine M.; Hasin, Deborah S.

2013-01-01

Background This study examined whether the experiences of childhood or adolescent parental divorce/separation and parental alcohol problems affected the likelihood of offspring DSM-IV lifetime alcohol dependence, controlling for parental history of drug, depression, and antisocial behavior problems. Method Data were drawn from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a nationally representative United States survey of 43,093 civilian non-institutionalized participants aged 18 and older, interviewed in person. Logistic regression models were used to calculate the main and interaction effects of childhood or adolescent parental divorce/separation and parental history of alcohol problems on offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Results Childhood or adolescent parental divorce/separation and parental history of alcohol problems were significantly related to offspring lifetime alcohol dependence, after adjusting for parental history of drug, depression, and antisocial behavior problems. Experiencing parental divorce/separation during childhood, even in the absence of parental history of alcohol problems, remained a significant predictor of lifetime alcohol dependence. Experiencing both childhood or adolescent parental divorce/separation and parental alcohol problems had a significantly stronger impact on the risk for DSM-IV alcohol dependence than the risk incurred by either parental risk factor alone. Conclusions Further research is needed to better identify the factors that increase the risk for lifetime alcohol dependence among those who experience childhood or adolescent parental divorce/separation. PMID:18757141

Automatic avoidance tendencies for alcohol cues predict drinking after detoxification treatment in alcohol dependence.

PubMed

Field, Matt; Di Lemma, Lisa; Christiansen, Paul; Dickson, Joanne

2017-03-01

Alcohol dependence is characterized by conflict between approach and avoidance motivational orientations for alcohol that operate in automatic and controlled processes. This article describes the first study to investigate the predictive validity of these motivational orientations for relapse to drinking after discharge from alcohol detoxification treatment in alcohol-dependent patients. One hundred twenty alcohol-dependent patients who were nearing the end of inpatient detoxification treatment completed measures of self-reported (Approach and Avoidance of Alcohol Questionnaire; AAAQ) and automatic (modified Stimulus-Response Compatibility task) approach and avoidance motivational orientations for alcohol. Their drinking behavior was assessed via telephone follow-ups at 2, 4, and 6 months after discharge from treatment. Results indicated that, after controlling for the severity of alcohol dependence, strong automatic avoidance tendencies for alcohol cues were predictive of higher percentage of heavy drinking days (PHDD) at 4-month (β = 0.22, 95% CI [0.07, 0.43]) and 6-month (β = 0.22, 95% CI [0.01, 0.42]) follow-ups. We failed to replicate previous demonstrations of the predictive validity of approach subscales of the AAAQ for relapse to drinking, and there were no significant predictors of PHDD at 2-month follow-up. In conclusion, strong automatic avoidance tendencies predicted relapse to drinking after inpatient detoxification treatment, but automatic approach tendencies and self-reported approach and avoidance tendencies were not predictive in this study. Our results extend previous findings and help to resolve ambiguities with earlier studies that investigated the roles of automatic and controlled cognitive processes in recovery from alcohol dependence. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Impulsivity, risky behaviors and accidents in alcohol-dependent patients

PubMed Central

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

2013-01-01

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

Brain Pathways to Recovery from Alcohol Dependence

PubMed Central

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

2015-01-01

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

The Role of GABRA2 in Alcohol Dependence, Smoking and Illicit Drug Use in an Australian Population Sample

PubMed Central

Lind, Penelope A; Macgregor, Stuart; Agrawal, Arpana; Montgomery, Grant W; Heath, Andrew C; Martin, Nicholas G; Whitfield, John B

2008-01-01

Background Multiple studies have shown that genetic variation in the α-2 subunit of the GABA-A receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol's intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking and illicit drug use within the Australian population. Methods We genotyped 11 single nucleotide polymorphisms within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs and 627 twins whose co-twin did not participate. Family-based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, cannabis and other illicit drug use. Results We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM-IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence, nor with smoking, cannabis or illicit drug use. Conclusions The GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required. PMID:18727688

Effect of community nurse follow-up when treating alcohol dependence with acamprosate.

PubMed

Pelc, I; Hanak, C; Baert, I; Houtain, C; Lehert, P; Landron, F; Verbanck, P

2005-01-01

To measure the effect of community nurse follow-up on abstinence and retention rates in the outpatient treatment of alcohol-dependent patients treated with acamprosate. Recently detoxified alcohol-dependent patients were prescribed acamprosate for 26 weeks and randomized to either physician-only follow-up, or physician plus regular visits from a community nurse. Drinking behaviour in the next 26 weeks was assessed at monthly visits to non-blind clinicians. The cumulative abstinence duration proportion (CADP) was significantly longer in (P=0.03) the subjects who had received community nurse support (0.57) than in those who had not (0.39). This might, in part, be an artefact of the higher retention rate among those followed up by the nurse, in that, the method of calculating CADP allocates 100% days of drinking for the month before a failed attendance. Differences favouring nurse in the follow-up were seen for time to first drink, and clinical global impression. For recently detoxified alcohol-dependent patients treated with acamprosate, follow-up by a community nurse improves patient retention and probably also improves the 6-month drinking outcome.

Stimulus augmenting and field dependence in children of alcoholic fathers.

PubMed

Hennecke, L

1984-11-01

The relationship between paternal alcoholism and two perceptual characteristics, stimulus augmenting and field dependence, was tested in boys and girls aged 10-12. Thirty children of alcoholic fathers, presumed at high risk for the disease because of its familial-genetic component, were compared with 30 children of nonalcoholic parents. Stimulus augmenting was measured by the Kinesthetic Figural After-Effect (KFA) test and field dependence by the Embedded Figures Test (EFT). It was reasoned that the consistent findings of field dependence in alcoholics could be a manifestation of brain damage and the consequent cognitive deficits often found in alcoholics. Thus it was proposed that field dependence would not differentiate the children of alcoholic fathers from those of nonalcoholics. No difference in field dependence was found between the groups, which supports other evidence that alcoholism can lead to field dependence. Since KFA scores revealed a significantly higher incidence of stimulus augmenters in the children of alcoholic fathers, it is proposed that stimulus augmenting is premorbid to alcoholism. It remains unclear, however, whether this phenomenon is due to an environmental or genetic factor.

Psychiatric Comorbidity and Physical Correlates in Alcohol-dependent Patients.

PubMed

Gauba, Deepak; Thomas, Pramod; Balhara, Yatan P S; Deshpande, Smita N

2016-01-01

To examine the prevalence and pattern of comorbidity in alcohol dependence and its relationship with physical and laboratory findings. Eighty males with alcohol dependence were examined using the Hindi version of Diagnostic Interview for Genetic Studies, the International Classification of Disease-10 th Edition Personality Disorder Examination, Alcohol Use Disorder Identification Test for alcohol use, global assessment of functioning, blood sampling electrocardiogram, and ultrasonogram. Eighty-seven percent had a comorbid Axis I or an Axis II psychiatric disorder, over 78% had nicotine dependence, and 56% had comorbid Axis II disorder, antisocial personality being the most common. Gamma glutamyl transpeptidase levels were significantly associated with comorbidity. High comorbidity of Axis I psychiatric disorders was found among persons with alcohol dependence. Axis II disorders were also present.

Acamprosate: A prototypic neuromodulator in the treatment of alcohol dependence

PubMed Central

Heyser, Charles J.

2010-01-01

Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence have identified specific neurotransmitter targets for the development of pharmacological treatments. Acamprosate, marketed under the brand name Campral, is an orally administered drug available by prescription in the U.S. and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in numerous clinical trials worldwide. Here we provide an overview of acamprosate in the context of the neurobiological underpinnings of alcohol dependence. We propose that unlike previously available pharmacotherapies, acamprosate represents a 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

Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

PubMed

Quelch, Darren R; Mick, Inge; McGonigle, John; Ramos, Anna C; Flechais, Remy S A; Bolstridge, Mark; Rabiner, Eugenii; Wall, Matthew B; Newbould, Rexford D; Steiniger-Brach, Björn; van den Berg, Franz; Boyce, Malcolm; Østergaard Nilausen, Dorrit; Breuning Sluth, Lasse; Meulien, Didier; von der Goltz, Christoph; Nutt, David; Lingford-Hughes, Anne

2017-06-01

Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion. Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Energy drink consumption and increased risk for alcohol dependence.

PubMed

Arria, Amelia M; Caldeira, Kimberly M; Kasperski, Sarah J; Vincent, Kathryn B; Griffiths, Roland R; O'Grady, Kevin E

2011-02-01

Energy drinks are highly caffeinated beverages that are increasingly consumed by young adults. Prior research has established associations between energy drink use and heavier drinking and alcohol-related problems among college students. This study investigated the extent to which energy drink use might pose additional risk for alcohol dependence over and above that from known risk factors. Data were collected via personal interview from 1,097 fourth-year college students sampled from 1 large public university as part of an ongoing longitudinal study. Alcohol dependence was assessed according to DSM-IV criteria. After adjustment for the sampling design, 51.3%(wt) of students were classified as "low-frequency" energy drink users (1 to 51 days in the past year) and 10.1%(wt) as "high-frequency" users (≥52 days). Typical caffeine consumption varied widely depending on the brand consumed. Compared to the low-frequency group, high-frequency users drank alcohol more frequently (141.6 vs. 103.1 days) and in higher quantities (6.15 vs. 4.64 drinks/typical drinking day). High-frequency users were at significantly greater risk for alcohol dependence relative to both nonusers (AOR = 2.40, 95% CI = 1.27 to 4.56, p = 0.007) and low-frequency users (AOR = 1.86, 95% CI = 1.10, 3.14, p = 0.020), even after holding constant demographics, typical alcohol consumption, fraternity/sorority involvement, depressive symptoms, parental history of alcohol/drug problems, and childhood conduct problems. Low-frequency energy drink users did not differ from nonusers on their risk for alcohol dependence. Weekly or daily energy drink consumption is strongly associated with alcohol dependence. Further research is warranted to understand the possible mechanisms underlying this association. College students who frequently consume energy drinks represent an important target population for alcohol prevention. Copyright © 2010 by the Research Society on Alcoholism.

Separating intentional inhibition of prepotent responses and resistance to proactive interference in alcohol-dependent individuals.

PubMed

Noël, Xavier; Van der Linden, Martial; Brevers, Damien; Campanella, Salvatore; Verbanck, Paul; Hanak, Catherine; Kornreich, Charles; Verbruggen, Frederick

2013-03-01

Impulsivity is a hallmark of addictive behaviors. Addicts' weakened inhibition of irrelevant prepotent responses is commonly thought to explain this association. However, inhibition is not a unitary mechanism. This study investigated the efficiency of overcoming competition due to irrelevant responses (i.e., inhibition of a prepotent response) and overcoming competition in memory (i.e., resistance to proactive interference) in sober and recently detoxified alcohol-dependent individuals. Three cognitive tasks assessing the inhibition of a prepotent response (Hayling task, anti-saccade task and Stroop task) and two tasks tapping into the capacity to resist proactive interference (cued recall, Brown-Peterson variant) were administered to 30 non-amnesic recently detoxified alcohol-dependent individuals and 30 matched healthy participants without alcohol dependency. In addition, possible confounds such as verbal updating in working memory was assessed. Alcohol-dependent subjects performed worse than healthy participants on the three cognitive tasks assessing the inhibition of irrelevant prepotent responses but group performance was similar in the tasks assessing overcoming proactive interference in memory, updating of working memory and abstract reasoning. These findings suggest that alcohol-dependence is mainly associated with impaired capacity to intentionally suppress irrelevant prepotent response information. Control of proactive interference from memory is preserved. Theoretical and clinical implications are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2011-01-01

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

Translating the semi-structured assessment for drug dependence and alcoholism in the Western Pacific: rationale, study design and reliability of alcohol dependence.

PubMed

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

2014-01-01

The aims of this study were to develop a bilingual version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) in English and Samoan and determine the reliability of assessments of alcohol dependence in American Samoa. The study consisted of development and reliability-testing phases. In the development phase, the SSADDA alcohol module was translated and the translation was evaluated through cognitive interviews. In the reliability-testing phase, the bilingual SSADDA was administered to 40 ethnic Samoans, including a sub-sample of 26 individuals who were retested. Cognitive interviews indicated the initial translation was culturally and linguistically appropriate except items pertaining to alcohol tolerance, which were modified to reflect Samoan concepts. SSADDA reliability testing indicated diagnoses of DSM-III-R and DSM-IV alcohol dependence were reliable. Reliability varied by language of administration. The English/Samoan version of the SSADDA is appropriate for the diagnosis of DSM-III-R alcohol dependence, which may be useful in advancing research and public health efforts to address alcohol problems in American Samoa and the Western Pacific. The translation methods may inform researchers translating diagnostic and assessment tools into different languages and cultures. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Gender differences in trait aggression in young adults with drug and alcohol dependence compared to the general population.

PubMed

Bácskai, Erika; Czobor, Pál; Gerevich, József

2011-07-01

Data in gender differences in aggression among alcohol and drug dependent subjects are lacking, and no published data are available about gender differences among various subtypes of substance using populations. The goal of this cross-sectional study was to investigate gender differences with regard to types of trait aggression in substance dependent young populations (age: 20-35 years) compared to the general population. Subjects were selected from two clinical samples with a diagnosis of alcohol and drug dependence as well as from a representative sample of the general population. Trait aggression was measured by the four individual subscales of the Buss Perry Aggression Questionnaire (physical-PA, verbal aggression-VA, hostility-H and anger AN) whereas alcohol and drug use were characterized by the AUDIT and EuroADAD scales, respectively. Alcohol and drug dependent subjects showed higher severity on all four subscales of trait aggression compared to the general population. The male-female difference was the highest in the cannabis group. General Linear Model analysis for PA indicated a significant main effect of gender (higher PA for males, p=0.034) with no interaction between substance dependence and gender. For VA, no main effect or interaction for gender was found. Effect sizes for gender difference indicated that while males and females were similar in the control group in the severity in H and A, the level of H and AN was substantially higher in females than in males in the clinical group. These differences between the two genders reached statistical significance in the marijuana group, where female subjects showed a significantly higher severity in these two domains. Compared to the normal sample chronic substance use is associated with higher scores on certain factors of trait aggression, including hostility and anger, in females than in males. Our data suggest that aggression in substance dependent females is more provocable by chronic use of alcohol and

Energy drink consumption and increased risk for alcohol dependence

PubMed Central

Arria, Amelia M.; Caldeira, Kimberly M.; Kasperski, Sarah J.; Vincent, Kathryn B.; Griffiths, Roland R.; O'Grady, Kevin E.

2010-01-01

Background Energy drinks are highly caffeinated beverages that are increasingly consumed by young adults. Prior research has established associations between energy drink use and heavier drinking and alcohol-related problems among college students. This study investigated the extent to which energy drink use might pose additional risk for alcohol dependence over and above that from known risk factors. Methods Data were collected via personal interview from 1,097 fourth-year college students sampled from one large public university as part of an ongoing longitudinal study. Alcohol dependence was measured with DSM-IV criteria. Results After adjustment for the sampling design, 51.3%wt of students were classified as “low-frequency” energy drink users (1 to 51 days in the past year) and 10.1%wt as “high-frequency” users (≥52 days). Typical caffeine consumption varied widely depending on the brand consumed. Compared to the low-frequency group, high-frequency users drank alcohol more frequently (141.6 vs. 103.1 days) and in higher quantities (6.15 vs. 4.64 drinks/typical drinking day). High-frequency users were at significantly greater risk for alcohol dependence relative to both non-users (AOR=2.40, 95% CI=1.27-4.56, p=.007) and low-frequency users (AOR=1.86, 95% CI=1.10, 3.14, p=.020), even after holding constant demographics, typical alcohol consumption, fraternity/sorority involvement, depressive symptoms, parental history of alcohol/drug problems, and childhood conduct problems. Low-frequency energy drink users did not differ from non-users on their risk for alcohol dependence. Conclusions Weekly or daily energy drink consumption is strongly associated with alcohol dependence. Further research is warranted to understand the possible mechanisms underlying this association. College students who frequently consume energy drinks represent an important target population for alcohol prevention. PMID:21073486

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

PubMed Central

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

2014-01-01

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

Emotional traits and affective temperaments in alcohol users, abusers and dependents in a national sample.

PubMed

Leite, Leticia; Machado, Leonardo N; Lara, Diogo R

2014-07-01

It is unclear how temperament is related to alcohol-related behavior in large population studies. We have used the Affective and Emotional Composite Temperament Scale (AFECTS) model to evaluate how emotional traits and affective temperaments are associated with alcohol use, abuse, and dependence in the general population. Data from 10,603 subjects (mean age=28.0±7.8 years, 70.3% females) was collected anonymously by the Internet in Brazil using the AFECTS model and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Alcohol use was stratified into control, low use, abuse, and dependence groups. The analysis of dimensional traits showed that Volition and Coping were lower, and Sensitivity was higher, in the abuse and dependence groups, with no differences between the Control and the Low Use groups. Alcohol consumption was also associated with lower Control, Stability, and Caution, and higher with Anger, Anxiety, and Desire, with significant differences between all groups. Regarding affective temperament types, alcohol abuse and dependence were associated with euphoric and cyclothymic temperaments in both genders, which was mirrored by a lower frequency of both euthymic and hyperthymic types. Only hyperthymics were overrepresented in the Control group for both genders. Data was collected by Internet only. A global dysfunction of emotional traits and a predominance of cyclothymic and euphoric temperaments were associated with alcohol-related behavior. Prevention and treatment strategies may be developed more effectively if these traits are taken into account. Copyright © 2014 Elsevier B.V. All rights reserved.

FRONTO-STRIATAL FUNCTIONAL CONNECTIVITY DURING RESPONSE INHIBITION IN ALCOHOL DEPENDENCE

PubMed Central

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

2013-01-01

Poor response inhibition has been implicated in the development of alcohol dependence, yet little is known about how neural pathways underlying cognitive control are affected in this disorder. Moreover, endogenous opioid levels may impact the functionality of inhibitory control pathways. This study investigated the relationship between alcohol dependence severity and functional connectivity of fronto-striatal networks during response inhibition in an alcohol dependent sample. A secondary aim of this study was to test the moderating effect of a functional polymorphism (A118G) of the µ-opioid receptor (OPRM1) gene. Twenty individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) who were prospectively genotyped on the OPRM1 gene underwent blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) while performing a Stop Signal Task (SST). The relationship between alcohol dependence severity and functional connectivity within fronto-striatal networks important for response inhibition was assessed using psychophysiological interaction (PPI) analyses. Analyses revealed greater alcohol dependence severity associated with weaker functional connectivity between the putamen and prefrontal regions (e.g., the anterior insula, anterior cingulate, and medial prefrontal cortex) during response inhibition. Further, the OPRM1 genotype was associated with differential response inhibition-related functional connectivity. This study demonstrates that individuals with more severe alcohol dependence exhibit less frontal connectivity with the striatum, a component of cognitive control networks important for response inhibition. These findings suggest that the fronto-striatal pathway underlying response inhibition is weakened as alcoholism progresses. PMID:23240858

Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm.

PubMed

Bujarski, Spencer; Jentsch, J David; Roche, Daniel J O; Ramchandani, Vijay A; Miotto, Karen; Ray, Lara A

2018-05-08

The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use severity was associated with greater baseline negative affect, sedation, and craving but did not predict changes in any SR domain during the alcohol challenge. Alcohol use severity also predicted greater self-administration. Craving during the alcohol challenge strongly predicted self-administration and sedation predicted lower self-administration. Neither stimulation, nor negative affect predicted self-administration. This study represents a novel approach to translating preclinical neuroscientific theories to the human laboratory. As expected, craving predicted self-administration and sedation was protective. Contrary to the predictions of the Allostatic Model, however, these results were inconsistent with a transition from positively to negatively reinforced alcohol consumption in severe AUD. Future studies that assess negative reinforcement in the context of an acute stressor are warranted.

Imaging resilience and recovery in alcohol dependence.

PubMed

Charlet, Katrin; Rosenthal, Annika; Lohoff, Falk W; Heinz, Andreas; Beck, Anne

2018-05-09

Resilience and recovery are of increasing importance in the field of alcohol dependence (AD). This paper describes how imaging studies in man can be used to assess the neurobiological correlates of resilience and, if longitudinal, of disease trajectories, progression rates and markers for recovery to inform treatment and prevention options. Original articles on recovery and resilience in alcohol addiction and its neurobiological correlates were identified from 'PubMed' and have been analyzed and condensed within a systematic literature review. Findings deriving from (f)MRI and PET studies have identified links between increased resilience and less task-elicited neural activation within the basal ganglia, and benefits of heightened neural prefrontal cortex (PFC) engagement regarding resilience in a broader sense, namely resilience against relapse in early abstinence of AD. Furthermore, findings consistently propose at least partial recovery of brain glucose metabolism and executive and general cognitive functioning, as well as structural plasticity effects throughout the brain of alcohol-dependent patients during the course of short, medium and long-term abstinence, even when patients only lowered their alcohol consumption to a moderate level. Additionally, specific factors were found that appear to influence these observed brain recovery processes in AD, e.g. genotype-dependent neuronal (re)growth, gender-specific neural recovery effects, critical interfering effects of psychiatric comorbidities, additional smoking or marijuana influences, or adolescent alcohol abuse. Neuroimaging research has uncovered neurobiological markers that appear to be linked to resilience and improved recovery capacities that are furthermore influenced by various factors such as gender or genetics. Consequently, future system-oriented approaches may help to establish a broad neuroscience-based research framework for alcohol dependence. This article is protected by copyright. All rights

Nicotine dependence syndrome scale and craving: comparing nicotine-dependent individuals with and without comorbid alcohol dependence.

PubMed

Choi, Sam-Wook; Chon, Younghoon; Bhang, Soo-Young; Jang, Yong Lee; Won, Wang-Youn; Choi, Jin Tae; Kim, Dai-Jin

2014-06-01

Although several studies have explored craving for certain drugs, there is limited data describing the relationship between alcohol and nicotine craving from a multidimensional perspective among individuals with comorbid nicotine dependence (ND) and alcohol dependence (AD). We compared a group of male patients diagnosed with ND and AD (n = 160) to a group of male patients diagnosed with ND only (n = 235). Smoking- and drinking-related clinical features were measured, including craving levels and the Nicotine Dependence Syndrome Scale (NDSS), which is a multidimensional questionnaire measuring ND. Subsequently, we studied factors that influenced smoking and alcohol craving in the ND and AD group. Regarding the NDSS, the sum, priority and tolerance scores were significantly higher in the ND and AD group compared with the ND only group (P < 0.000, P < 0.000 and P = 0.001, respectively). In the comorbid group, regression analyses revealed that alcohol craving and Fagerstrom Test for Nicotine Dependence (FTND) scores contributed to nicotine craving (beta coefficient = 0.37, P = 0.005 and beta coefficient = 0.35, P = 0.026, respectively) and these two factors explained 36% of the variance). Nicotine craving appeared to be the only factor that contributed to alcohol craving (beta coefficient = 0.35, P = 0.002), and nicotine craving explained 16% of the variance. This study may help clarify the clinical relationship between comorbid alcohol and nicotine dependence and help guide the development of effective treatment strategies for ND and AD patients. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Consistency of field dependence in treated alcoholics.

PubMed

Danahy, S; Kahn, M W

1981-10-01

In accounting for the consistent finding that alcoholics are more field dependent than other groups, research generally supports the predisposition rather than the consequence hypothesis. In this study 32 alcoholics were tested for field dependence with Embedded Figures on admission to and at discharge from a 60-d treatment program. A large and significant drop in the field dependence measure was found, supporting the consequence hypothesis. The pre-posttime period not controlled in other studies, allowing for clearing acute effects and improved nutrition, health, and test motivation, amy account for this change.

Impairments in learning by monetary rewards and alcohol-associated rewards in detoxified alcoholic patients.

PubMed

Jokisch, Daniel; Roser, Patrik; Juckel, Georg; Daum, Irene; Bellebaum, Christian

2014-07-01

Excessive alcohol consumption has been linked to structural and functional brain changes associated with cognitive, emotional, and behavioral impairments. It has been suggested that neural processing in the reward system is also affected by alcoholism. The present study aimed at further investigating reward-based associative learning and reversal learning in detoxified alcohol-dependent patients. Twenty-one detoxified alcohol-dependent patients and 26 healthy control subjects participated in a probabilistic learning task using monetary and alcohol-associated rewards as feedback stimuli indicating correct responses. Performance during acquisition and reversal learning in the different feedback conditions was analyzed. Alcohol-dependent patients and healthy control subjects showed an increase in learning performance over learning blocks during acquisition, with learning performance being significantly lower in alcohol-dependent patients. After changing the contingencies, alcohol-dependent patients exhibited impaired reversal learning and showed, in contrast to healthy controls, different learning curves for different types of rewards with no increase in performance for high monetary and alcohol-associated feedback. The present findings provide evidence that dysfunctional processing in the reward system in alcohol-dependent patients leads to alterations in reward-based learning resulting in a generally reduced performance. In addition, the results suggest that alcohol-dependent patients are, in particular, more impaired in changing an established behavior originally reinforced by high rewards. Copyright © 2014 by the Research Society on Alcoholism.

Diagnosed alcohol dependence and criminal sentencing among British Columbian Aboriginal offenders.

PubMed

Rempel, Emily S; Somers, Julian M; Calvert, John R; McCandless, Lawrence C

2015-09-01

Alcohol use is commonly reported as a short-term criminal risk factor; however there is minimal research on the effects of alcohol dependence on crime. Canadian Aboriginal offenders exhibit both disproportionate crime and alcohol disorder prevalence. This study aims to examine the impact of diagnosed alcohol dependence on Aboriginal ethnicity and criminal sentencing in British Columbia. We used an administrative linkage database of social, health and justice system variables to develop a retrospective cohort of 70,035 offenders sentenced through courts in British Columbia from 2001-2010. We used a coefficient difference mediation analysis to evaluate the mediating effect of alcohol dependence on the association between self-reported Aboriginal status and sentencing rate. Aboriginal offenders had 1.92 (95% C.I.: 1.79,2.06) times higher odds of alcohol dependence than Caucasian offenders. Adjustment for health, social and demographic factors resulted in a 27% (95% Confidence Interval (CI): 15%, 33%) reduction in the association of Aboriginal ethnicity on sentencing. Adjustment for alcohol dependence resulted in only a further reduction of 2% (95% CI: -12%, 15%). Although alcohol dependence was associated both with Aboriginal ethnicity and sentencing, it did not have a significant mediating impact on sentencing rate. Alcohol dependence was not a mediator for the relationship between sentencing rate and Aboriginal ethnicity. However, due to the proportion of offenders diagnosed with alcohol dependence, these results support alcohol misuse as an important public health policy target in this population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

Sugawara, Tazuko; Morita, Noriaki; Nakatani, Youji

2013-12-01

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

Applicability of Type A/B alcohol dependence in the general population.

PubMed

Tam, Tammy W; Mulia, Nina; Schmidt, Laura A

2014-05-01

This study examined the concurrent and predictive validity of Type A/B alcohol dependence in the general population-a typology developed in clinical populations to gauge severity of dependence. Data were drawn from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The sample included 1,172 alcohol-dependent drinkers at baseline who were reinterviewed three years later. Latent class analysis was used to derive Type A/B classification using variables replicating the original Type A/B typology. Predictive validity of the Type A/B classification was assessed by multivariable linear and logistic regressions. A two-class solution consistent with Babor's original Type A/B typology adequately fit the data. Type B alcoholics in the general population, compared to Type As, had higher alcohol severity and more co-occurring drug, mental, and physical health problems. In the absence of treatment services utilization, Type B drinkers had two times the odds of being alcohol dependent three years later. Among those who utilized alcohol treatment services, Type B membership was predictive of heavy drinking and drug dependence, but not alcohol dependence, three years later. Findings suggest that Type A/B classification is both generalizable to, and valid within, the US general population of alcohol dependent drinkers. Results highlight the value of treatment for mitigating the persistence of dependence among Type B alcoholics in the general population. Screening for markers of vulnerability to Type B dependence could be of clinical value for health care providers to determine appropriate intervention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Alcohol-related diseases and alcohol dependence syndrome is associated with increased gout risk: A nationwide population-based cohort study.

PubMed

Tu, Hung-Pin; Tung, Yi-Ching; Tsai, Wen-Chan; Lin, Gau-Tyan; Ko, Ying-Chin; Lee, Su-Shin

2017-03-01

Alcohol intake is strongly associated with hyperuricemia, which may cause gout. This study evaluated the risk of gout in patients with alcohol-related diseases and alcohol dependence syndrome. We used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a nationwide population-based cohort study to assess the risk of gout and gout incidence in patients with alcohol-related diseases and alcohol dependence syndrome (as defined by the International Classification of Diseases, Ninth Revision). In the NHIRD records from 1998 to 2008, we identified 11,675 cases of alcohol-related diseases. The control group comprised 23,350 cases without alcohol-related diseases propensity score-matched (1 case: 2 controls) for age, age group, and sex. The results revealed that alcohol-related diseases were significantly associated with gout risk (adjusted hazard ratio 1.88; P<0.0001). Of the alcohol-related disease cases, 34.1% of the patients had alcohol dependence syndrome (males 34.8%; females 32.4%), and alcohol dependence was independently associated with gout occurrence (relative risk [RR] 2.01; P<0.0001). Severe alcohol-dependent patients (who were also the heavy benzodiazepines users), were associated with an increased risk of gout (RR 1.71 to 4.21, P≤0.0182). Physicians should be aware of the association between alcohol dependence syndrome and gout occurrence, and alcohol use assessment and measures to prevent alcohol dependence should be implemented in the integrative care for patients with gout. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns.

PubMed

Gilman, Jodi M; Ramchandani, Vijay A; Crouss, Tess; Hommer, Daniel W

2012-01-01

Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We performed a double-blind, placebo-controlled, randomized crossover alcohol challenge study comparing functional magnetic resonance imaging and subjective response to intravenously administered 6% v/v ethanol to a target blood alcohol concentration of 0.08% or placebo between HDs and social drinkers (SDs). During the imaging, we presented emotional cues in order to measure how emotion modulated the effects of alcohol on the brain's reward circuitry. We found that, at equivalent blood alcohol concentrations, HDs reported lower subjective alcohol effects than SDs. Alcohol significantly activated the nucleus accumbens in SDs, but not in HDs. Self-reported ratings of intoxication correlated with striatal activation, suggesting that activation may reflect subjective experience of intoxication. Fearful faces significantly activated the amygdala in the SDs only, and this activation was attenuated by alcohol. This study shows that HDs not only experience reduced subjective effects of alcohol, but also demonstrate a blunted response to alcohol in the brain's reward system. Our findings indicate that reduced subjective and neural response to alcohol in HDs may be suggestive of either the development of tolerance to alcohol, or of pre-existing decreased sensitivity to alcohol's effects.

Abstract and concrete repetitive thinking modes in alcohol-dependence.

PubMed

Grynberg, Delphine; de Timary, Philippe; Philippot, Pierre; D'Hondt, Fabien; Briane, Yasmine; Devynck, Faustine; Douilliez, Céline; Billieux, Joël; Heeren, Alexandre; Maurage, Pierre

2016-01-01

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.

Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families.

PubMed

O'Brien, Jessica W; Hill, Shirley Y

2014-12-01

Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. Women with a family history of

Emotional intelligence components in alcohol dependent and mentally healthy individuals.

PubMed

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

2015-01-01

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

An intensive assessment of alcohol use and emergency department utilization in homeless alcohol-dependent adults.

PubMed

Holtyn, August F; Jarvis, Brantley P; Subramaniam, Shrinidhi; Wong, Conrad J; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

2017-09-01

Excessive alcohol use among the homeless may contribute to their high rates of emergency department use. Survey-based studies have provided some information on the relation between alcohol and emergency department use among the homeless. This study used an intensive schedule of random breath collections and self-report assessments to examine the relation between emergency department utilization and alcohol use in homeless alcohol-dependent adults. Data were from homeless alcohol-dependent adults (N=116) who were participating in a therapeutic workplace that provided job-skills training every weekday for 26 weeks. Breath-sample collections and assessments of self-reported alcohol use were scheduled each week, an average of twice per week per participant, at random times between 9:00 A.M. and 5:00 P.M. Participants received $35 for each breath sample collected. Self-reports of emergency department use were assessed throughout the study. Thirty-four percent of participants reported attending an emergency department and reported an average of 2.2 emergency department visits (range 1-10 visits). Alcohol intoxication was the most common reason for emergency department use. Participants who used the emergency department had significantly more alcohol-positive breath samples and more self-reported heavy alcohol use than participants who did not use the emergency department. This study provided a rare intensive assessment of alcohol and emergency department use in homeless alcohol-dependent adults over an extended period. Emergency department use was high and was significantly related to indices of alcohol use. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolomics biomarkers to predict acamprosate treatment response in alcohol-dependent subjects.

PubMed

Hinton, David J; Vázquez, Marely Santiago; Geske, Jennifer R; Hitschfeld, Mario J; Ho, Ada M C; Karpyak, Victor M; Biernacka, Joanna M; Choi, Doo-Sup

2017-05-31

Precision medicine for alcohol use disorder (AUD) allows optimal treatment of the right patient with the right drug at the right time. Here, we generated multivariable models incorporating clinical information and serum metabolite levels to predict acamprosate treatment response. The sample of 120 patients was randomly split into a training set (n = 80) and test set (n = 40) five independent times. Treatment response was defined as complete abstinence (no alcohol consumption during 3 months of acamprosate treatment) while nonresponse was defined as any alcohol consumption during this period. In each of the five training sets, we built a predictive model using a least absolute shrinkage and section operator (LASSO) penalized selection method and then evaluated the predictive performance of each model in the corresponding test set. The models predicted acamprosate treatment response with a mean sensitivity and specificity in the test sets of 0.83 and 0.31, respectively, suggesting our model performed well at predicting responders, but not non-responders (i.e. many non-responders were predicted to respond). Studies with larger sample sizes and additional biomarkers will expand the clinical utility of predictive algorithms for pharmaceutical response in AUD.

Quantitative determination of caffeine and alcohol in energy drinks and the potential to produce positive transdermal alcohol concentrations in human subjects.

PubMed

Ayala, Jessica; Simons, Kelsie; Kerrigan, Sarah

2009-01-01

The purpose of this study was to determine whether non-alcoholic energy drinks could result in positive "alcohol alerts" based on transdermal alcohol concentration (TAC) using a commercially available electrochemical monitoring device. Eleven energy drinks were quantitatively assayed for both ethanol and caffeine. Ethanol concentrations for all of the non-alcoholic energy drinks ranged in concentration from 0.03 to 0.230% (w/v) and caffeine content per 8-oz serving ranged from 65 to 126 mg. A total of 15 human subjects participated in the study. Subjects consumed between 6 and 8 energy drinks over an 8-h period. The SCRAM II monitoring device was used to determine TACs every 30 min before, during, and after the study. None of the subjects produced TAC readings that resulted in positive "alcohol alerts". TAC measurements for all subjects before, during and after the energy drink study period (16 h total) were <0.02% (w/v). Subjects in the study consumed a quantity of non-alcoholic energy drink that greatly exceeds what would be considered typical. Based on these results, it appears that energy drink consumption is an unlikely explanation for elevated TACs that might be identified as potential drinking episodes or "alcohol alerts" using this device.

Alcohol dependence and opiate dependence: lack of relationship in mice.

PubMed

Goldstein, A; Judson, B A

1971-04-16

According to a recently proposed hypothesis, physical dependence upon alcohol is due to the formation of an endogenous opiate. We tested the hypothesis by determining whether or not ethanol-dependent mice would show typical opiate-dependent behavior (withdrawal jumping syndrome) when challenged with the opiate antagonist naloxone. Our results do not support the hypothesis.

Hopelessness in Alcohol- and Heroin-Dependent Women.

ERIC Educational Resources Information Center

Beck, Aaron T.; And Others

1984-01-01

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)

Burnout and Alcohol Abuse/Dependence Among U.S. Medical Students.

PubMed

Jackson, Eric R; Shanafelt, Tait D; Hasan, Omar; Satele, Daniel V; Dyrbye, Liselotte N

2016-09-01

To explore the relationship between alcohol abuse/dependence with burnout and other forms of distress among a national cohort of medical students. In 2012, the authors completed a national survey of medical students from the American Medical Association's Physician Masterfile containing validated items assessing alcohol abuse/dependence, burnout, depression, suicidality, quality of life (QOL), and fatigue. Descriptive and comparative statistical analyses were computed, including chi-square and multivariate logistic regression, to determine relationships between variables. Of the 12,500 students, 4,402 (35.2%) responded. Of these, 1,411 (32.4%) met diagnostic criteria for alcohol abuse/dependence. Students who were burned out (P = .01), depressed (P = .01), or reported low mental (P =.03) or emotional (P = .016) QOL were more likely to have alcohol abuse/dependence. Emotional exhaustion and depersonalization domains of burnout were strongly associated with alcohol abuse/dependence. On multivariate analysis, burnout (OR 1.20; 95% CI 1.05-1.37; P < .01), having $50,000 to $100,000 (OR 1.21 versus < $50,000; CI 1.02-1.44; P < .05) or > $100,000 (OR 1.27 versus < $50,000; CI 1.08-1.48; P < .01) of educational debt, being unmarried (OR 1.89; CI 1.57-2.27; P < .001), and being younger (for every five years, OR 1.15; CI 1.02-1.28; P = .01) were independently associated with increased risk for alcohol abuse/dependence. Burnout was strongly related to alcohol abuse/dependence among sampled medical students and increased educational debt predicted a higher risk. A multifaceted approach addressing burnout, medical education costs, and alcohol use is needed.

Effects of caffeine on alcohol reinforcement: beverage choice, self-administration, and subjective ratings.

PubMed

Sweeney, Mary M; Meredith, Steven E; Evatt, Daniel P; Griffiths, Roland R

2017-03-01

Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., beverage A) and three sessions with alcohol and caffeine (e.g., beverage B). Participants chose which beverage to consume on a subsequent session (e.g., beverage A or B). The effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings and reported greater drinking behavior prior to the study. Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest that decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine.

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

PubMed

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

2015-10-01

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

Emotional Intelligence Components in Alcohol Dependent and Mentally Healthy Individuals

PubMed Central

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

2015-01-01

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

The effects of gender and a co-occurring depressive disorder on neurocognitive functioning in patients with alcohol dependence.

PubMed

Liu, I-Chao; Chiu, Chen-Huan; Yang, Tsung-Tsair

2010-01-01

The present study aims to examine neuropsychological impairments by comorbidity and gender among patients with alcohol dependence. The study sample is comprised of 123 subjects who fulfilled a Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV) diagnosis of alcohol dependence from January 2006 to December 2007. Subjects were asked to complete the following psychological tests: the Barratt Impulsivity Scale (BIS), Wechsler Adult Intelligence Scale, Wechsler Memory Scale and Color Trails Test. We compared the results of neuropsychological assessments based on two types of classifications: people with comorbid depression and people without comorbidity; females and males. The immediate visual memory and the BIS scores in patients with comorbid depression were significantly different from the scores in patients without comorbidity. In addition, females performed significantly poorer on the Working Memory Index than males and had a later age of regular drinking. Further investigation of the mechanism associated with the gender difference on cognition and exploration of the temporal relationship between alcohol dependence and depressive disorder on the cognitive aspect is needed.

Psychosocial functioning, quality of life and clinical correlates of comorbid alcohol and drug dependence syndromes in people with schizophrenia across Europe.

PubMed

Carrà, Giuseppe; Johnson, Sonia; Crocamo, Cristina; Angermeyer, Matthias C; Brugha, Traolach; Azorin, Jean-Michel; Toumi, Mondher; Bebbington, Paul E

2016-05-30

Little is known about the correlates of comorbid drug and alcohol dependence in people with schizophrenia outside the USA. We tested hypotheses that dependence on alcohol/drugs would be associated with more severe symptoms, and poorer psychosocial functioning and quality of life. The EuroSC Cohort study (N=1204), based in France, Germany and the UK, used semi-structured clinical interviews for diagnoses, and standardized tools to assess correlates. We used mixed models to compare outcomes between past-year comorbid dependence on alcohol/drugs, controlling for covariates and modelling both subject and country-level effects. Participants dependent on alcohol or drugs had fewer negative symptoms on PANSS than their non-dependent counterparts. However, those dependent on alcohol scored higher on PANSS general psychopathology than those who were not, or dependent only on drugs. People with schizophrenia dependent on drugs had poorer quality of life, more extrapyramidal side effects, and scored worse on Global Assessment of Functioning (GAF) than those without dependence. People with alcohol dependence reported more reasons for non-compliance with medication, and poorer functioning on GAF, though not on Global Assessment of Relational Functioning. In people with schizophrenia, comorbid dependence on alcohol or drugs is associated with impaired clinical and psychosocial adjustment, and poorer quality of life. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impaired decision-making under risk in individuals with alcohol dependence

PubMed Central

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

2014-01-01

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

Pavlovian-to-instrumental transfer in alcohol dependence: a pilot study.

PubMed

Garbusow, Maria; Schad, Daniel J; Sommer, Christian; Jünger, Elisabeth; Sebold, Miriam; Friedel, Eva; Wendt, Jean; Kathmann, Norbert; Schlagenhauf, Florian; Zimmermann, Ulrich S; Heinz, Andreas; Huys, Quentin J M; Rapp, Michael A

2014-01-01

Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT. © 2014 S. Karger AG, Basel.

Callosal involvement in a lateralized stroop task in alcoholic and healthy subjects.

PubMed

Schulte, T; Müller-Oehring, E M; Salo, R; Pfefferbaum, A; Sullivan, E V

2006-11-01

To investigate the role of interhemispheric attentional processes, 25 alcoholic and 28 control subjects were tested with a Stroop match-to-sample task and callosal areas were measured with magnetic resonance imaging. Stroop color-word stimuli were presented to the left or right visual field (VF) and were preceded by a color cue that did or did not match the word's color. For matching colors, both groups showed a right VF advantage; for nonmatching colors, controls showed a left VF advantage, whereas alcoholic subjects showed no VF advantage. For nonmatch trials, VF advantage correlated with callosal splenium area in controls but not alcoholic subjects, supporting the position that information presented to the nonpreferred hemisphere is transmitted via the splenium to the hemisphere specialized for efficient processing. The authors speculate that alcoholism-associated callosal thinning disrupts this processing route.

Effects of caffeine on alcohol reinforcement: Beverage choice, self-administration, and subjective ratings

PubMed Central

Sweeney, Mary M.; Meredith, Steven E.; Evatt, Daniel P.; Griffiths, Roland R.

2017-01-01

Rationale Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. Objectives This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Methods Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., Beverage A) and three sessions with alcohol and caffeine (e.g., Beverage B). Participants chose which beverage to consume on a subsequent session (e.g., Beverage A or B). Effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. Results A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings, and reported greater drinking behavior prior to the study. Conclusions Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine. PMID:28108773

A Multilevel Structural Equation Model of Within- and Between-Person Associations among Subjective Responses to Alcohol, Craving, and Laboratory Alcohol Self-Administration

PubMed Central

Wardell, Jeffrey D.; Ramchandani, Vijay A.; Hendershot, Christian S.

2017-01-01

Subjective responses to alcohol are important determinants of drinking behavior and have been linked with risk for alcohol use disorders. However, few attempts have been made to examine proximal within-person associations among state changes in subjective responses and ongoing alcohol self-administration in the laboratory. This study disaggregated within- and between-person associations among subjective responses and alcohol self-administration, while also examining the mediating role of craving and the moderating role of trait impaired control over alcohol. Sixty young heavy drinkers (mean age=19.90, SD=0.86) completed self-report measures including the Impaired Control Scale, then participated in a 2-hour intravenous alcohol self-administration session using the Computer-Assisted Self-infusion of Ethanol (CASE) paradigm. Repeated assessments of subjective stimulation, subjective sedation, and craving were examined in relation to ongoing in-session self-administration, as indexed by breath alcohol concentration (BrAC) assessed 15 minutes later. Multilevel structural equation modeling was used to disentangle within-person and between-person associations. The results showed few significant associations at the between-person level, except for a direct negative association between sedation and BrAC. At the within-person level, state fluctuations in stimulation were positively associated with both craving and subsequent BrAC, whereas state changes in sedation were negatively associated with craving and positively associated with BrAC. Within-person indirect associations from subjective stimulation and sedation to subsequent BrAC mediated via craving were statistically significant. Also, participants higher on impaired control showed stronger within-person associations between craving and greater subsequent BrAC. The results suggest that subjective responses to alcohol and craving have proximal associations with self-administration behavior, the strength of which is

The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings.

PubMed

Suchankova, Petra; Yan, Jia; Schwandt, Melanie L; Stangl, Bethany L; Jerlhag, Elisabet; Engel, Jörgen A; Hodgkinson, Colin A; Ramchandani, Vijay A; Leggio, Lorenzo

2017-07-01

The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol. Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase). The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, β = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, β = -12.00, 95% CI = -19.10 to -4.89, P < 0.001). The IV-ASA study further revealed that 72Met carriers had greater subjective responses to alcohol (P < 0.05) when compared to Leu72Leu both at priming and during ad lib self-administration. Although preliminary, these findings suggest that the Leu72Leu genotype may lead to increased risk of AUD possibly via mechanisms involving a lower response to alcohol resulting in excessive alcohol consumption. Further investigations are warranted. We investigated whether a Leu72Met missense polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary

Craving for alcohol and food during treatment for alcohol dependence: modulation by T allele of 1519T>C GABAAalpha6.

PubMed

Han, Doug Hyun; Bolo, Nicholas; Daniels, Melissa A; Lyoo, In Kyoon; Min, Kyung Joon; Kim, Chang Hyun; Renshaw, Perry F

2008-09-01

Craving for alcohol and food has been studied in association with alcohol dependence and eating disorders, respectively. One subclass of the gamma-aminobutyric acid (GABA) receptor, 1519T>C GABA(A)alpha6 has been reported to be associated with both alcohol dependence and weight gain. In this study, we hypothesized that patients being treated for alcohol dependence would report decreased craving for alcohol, but an increased craving for food during a 4-week treatment period. We further hypothesized that the T allele of the 1519T>C GABA(A)alpha6 gene would modulate the extent of changes in craving for alcohol and food. This study included 98 male inpatients being treated for alcohol dependence. A 7-point visual analog scale was applied to evaluate relative levels of alcohol and food craving at baseline and again 4 weeks later. Body weight was also checked at the same periods. Genotyping of the 1519T>C SNP in GABA(A)alpha6 was carried out by restriction fragment length polymorphism. There were significant changes in craving for alcohol and food in all patients with alcohol dependence. During the treatment period, body weight increased in all patients with alcohol dependence. Changes in alcohol and food craving in T-allele carriers (CT + TT) of 1519T>C GABA(A)alpha6 were greater than those observed in CC homozygotes. In T-allele carriers, body weight significantly increased and the changes in weight showed a negative correlation with the change in the craving for alcohol and a positive correlation with the changes in craving for food. The current results suggest that in T-allele carriers the change in craving for alcohol during treatment for alcohol dependence is negatively associated with changes in craving for food. The T allele of the 1519T>C GABA(A)alpha6 gene may be one of the modulating factors associated with changes in craving for alcohol and food during treatment of patients with alcohol dependence.

Prone to feel guilty: Self-evaluative emotions in alcohol-dependence.

PubMed

Grynberg, Delphine; de Timary, Philippe; Van Heuverswijn, Aude; Maurage, Pierre

2017-10-01

Prior research has repeatedly shown that alcohol-dependence is associated with interpersonal difficulties. However, guilt and shame, two crucial self-evaluative emotions triggered by the transgression of social norms, have not been explored among alcohol-dependent individuals despite their important role in psychiatric disorders. The present study thus aimed to investigate whether alcohol-dependence is associated with greater proneness to negatively evaluate one's own behaviors (guilt) or the entire self (shame). 25 alcohol-dependent individuals (ADI) and 25 matched healthy individuals completed a scenario-based inventory (TOSCA-3), requiring from participants to rate the extent they will react to each scenario in terms of (contextualized) guilt and shame. Participants also completed a list of adjectives related to the frequency at which they generally experience (uncontextualized) guilt and shame (PFQ-2). When controlling for possible confounds (i.e., depression and anxiety), ADI reported greater proneness to experience guilt at the TOSCA-3 (η 2 =.22) compared to healthy individuals. This study is the first to show that alcohol-dependence is associated with greater contextualized guilt-proneness, i.e., negative evaluation of one's own behaviors that transgress social norms. Therefore, these results reinforce the relevance of social disorders in alcohol-dependence and indicate that ADI may benefit of therapeutic programs to avoid a generalization of guilt towards shame. Copyright © 2017 Elsevier B.V. All rights reserved.

Social cost of heavy drinking and alcohol dependence in high-income countries.

PubMed

Mohapatra, Satya; Patra, Jayadeep; Popova, Svetlana; Duhig, Amy; Rehm, Jürgen

2010-06-01

A comprehensive review of cost drivers associated with alcohol abuse, heavy drinking, and alcohol dependence for high-income countries was conducted. The data from 14 identified cost studies were tabulated according to the potential direct and indirect cost drivers. The costs associated with alcohol abuse, alcohol dependence, and heavy drinking were calculated. The weighted average of the total societal cost due to alcohol abuse as percent gross domestic product (GDP)--purchasing power parity (PPP)--was 1.58%. The cost due to heavy drinking and/or alcohol dependence as percent GDP (PPP) was estimated to be 0.96%. On average, the alcohol-attributable indirect cost due to loss of productivity is more than the alcohol-attributable direct cost. Most of the countries seem to incur 1% or more of their GDP (PPP) as alcohol-attributable costs, which is a high toll for a single factor and an enormous burden on public health. The majority of alcohol-attributable costs incurred as a consequence of heavy drinking and/or alcohol dependence. Effective prevention and treatment measures should be implemented to reduce these costs.

Use of AUDIT-based measures to identify unhealthy alcohol use and alcohol dependence in primary care: a validation study.

PubMed

Johnson, J Aaron; Lee, Anna; Vinson, Daniel; Seale, J Paul

2013-01-01

As programs for screening, brief intervention, and referral to treatment (SBIRT) for unhealthy alcohol use disseminate, evidence-based approaches for identifying patients with unhealthy alcohol use and alcohol dependence (AD) are needed. While the National Institute on Alcohol Abuse and Alcoholism Clinician Guide suggests use of a single alcohol screening question (SASQ) for screening and Diagnostic and Statistical Manual checklists for assessment, many SBIRT programs use alcohol use disorders identification test (AUDIT) "zones" for screening and assessment. Validation data for these zones are limited. This study used primary care data from a bi-ethnic southern U.S. population to examine the ability of the AUDIT zones and other AUDIT-based approaches to identify unhealthy alcohol use and dependence. Existing data were analyzed from interviews with 625 female and male adult drinkers presenting to 5 southeastern primary care practices. Timeline follow-back was used to identify at-risk drinking, and diagnostic interview schedule was used to identify alcohol abuse and dependence. Validity measures compared performance of AUDIT, AUDIT-C, and AUDIT dependence domains scores, with and without a 30-day binge drinking measure, for detecting unhealthy alcohol use and dependence. Optimal AUDIT scores for detecting unhealthy alcohol use were lower than current commonly used cutoffs (5 for men, 3 for women). Improved performance was obtained by combining AUDIT cutoffs of 6 for men and 4 for women with a 30-day binge drinking measure. AUDIT scores of 15 for men and 13 for women detected AD with 100% specificity but low sensitivity (20 and 18%, respectively). AUDIT dependence subscale scores of 2 or more showed similar specificity (99%) and slightly higher sensitivity (31% for men, 24% for women). Combining lower AUDIT cutoff scores and binge drinking measures may increase the detection of unhealthy alcohol use in primary care. Use of lower cutoff scores and dependence subscale

Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence

PubMed Central

Uhrig, Stefanie; Vandael, David; Marcantoni, Andrea; Dedic, Nina; Bilbao, Ainhoa; Vogt, Miriam A; Hirth, Natalie; Broccoli, Laura; Bernardi, Rick E; Schönig, Kai; Gass, Peter; Bartsch, Dusan; Spanagel, Rainer; Deussing, Jan M; Sommer, Wolfgang H; Carbone, Emilio; Hansson, Anita C

2017-01-01

It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol-dependent rats during protracted abstinence and naive controls using in situ hybridization and western blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons. We then measured alcohol self-administration and cue-induced reinstatement of alcohol seeking in dependent and nondependent rats after intracerebroventricular (i.c.v.) injection of the LTCC antagonist verapamil, as well as in mice with an inducible knockout (KO) of Cav1.2 in Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα)-expressing neurons. Our results show that Cacna1c mRNA concentration was increased in the amygdala and hippocampus of alcohol-dependent rats after 21 days of abstinence, with no changes in Cacna1d mRNA. This was associated with increased Cav1.2 protein concentration and L-type calcium current amplitudes. Further analysis of Cacna1c mRNA in the CA1, basolateral amygdala (BLA), and central amygdala (CeA) revealed a dynamic regulation over time during the development of alcohol dependence. The inhibition of central LTCCs via i.c.v. administration of verapamil prevented cue-induced reinstatement of alcohol seeking in alcohol-dependent rats. Further studies in conditional Cav1.2-KO mice showed a lack of dependence-induced increase of alcohol-seeking behavior. Together, our data indicate that central Cav1.2 channels, rather than Cav1.3, mediate alcohol-seeking behavior. This finding may be of interest for the development of new antirelapse medications. PMID:27905406

The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings

PubMed Central

Suchankova, Petra; Yan, Jia; Schwandt, Melanie L.; Stangl, Bethany L.; Jerlhag, Elisabet; Engel, Jörgen A.; Hodgkinson, Colin A.; Ramchandani, Vijay A.; Leggio, Lorenzo

2017-01-01

Abstract Aims The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol. Method Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase). Results The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44–1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, β = −2.49, 95% CI = −4.34 to −0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, β = −12.00, 95% CI = −19.10 to −4.89, P < 0.001). The IV-ASA study further revealed that 72Met carriers had greater subjective responses to alcohol (P < 0.05) when compared to Leu72Leu both at priming and during ad lib self-administration. Conclusion Although preliminary, these findings suggest that the Leu72Leu genotype may lead to increased risk of AUD possibly via mechanisms involving a lower response to alcohol resulting in excessive alcohol consumption. Further investigations are warranted. Short Summary We investigated whether a Leu72Met missense polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol

GABA-benzodiazepine receptor function in alcohol dependence: a combined 11C-flumazenil PET and pharmacodynamic study.

PubMed

Lingford-Hughes, A R; Wilson, S J; Cunningham, V J; Feeney, A; Stevenson, B; Brooks, D J; Nutt, D J

2005-08-01

Gamma-aminobutyric acid (GABA)-benzodiazepine receptor function is hypothesised to be reduced in alcohol dependence. We used positron emission tomography (PET) with [11C]flumazenil, a non-selective tracer for brain GABA-benzodiazepine (GABA-BDZ) receptor binding, to determine in vivo the relationship between BDZ receptor occupancy by an agonist, midazolam, and its functional effects. Abstinent male alcohol dependent subjects underwent [11C]flumazenil PET to measure occupancy of BDZ receptors by midazolam whilst recording its pharmacodynamic effects on behavioural and physiological measures. Rate constants describing the exchange of [11C]flumazenil between the plasma and brain compartments were derived from time activity curves. A 50% reduction in electroencephalography (EEG)-measured sleep time was seen in the alcohol dependent group despite the same degree of occupancy by midazolam as seen in the control group. The effects of midazolam on other measures of benzodiazepine receptor function, increasing EEG beta1 power and slowing of saccadic eye movements, were similar in the two groups. No differences in midazolam or flumazenil metabolism were found between the groups. In summary, our study suggests that alcohol dependence in man is associated with a reduced EEG sleep response to the benzodiazepine agonist, midazolam, which is not explained by reduced BDZ receptor occupancy, and is consistent with reduced sensitivity in this measure of GABA-BDZ receptor function in alcohol dependence. The lack of change in other functional measures may reflect a differential involvement of particular subtypes of the GABA-BDZ receptor.

Ionized magnesium in plasma and erythrocytes for the assessment of low magnesium status in alcohol dependent patients.

PubMed

Ordak, Michal; Maj-Zurawska, Magdalena; Matsumoto, Halina; Bujalska-Zadrozny, Magdalena; Kieres-Salomonski, Ilona; Nasierowski, Tadeusz; Muszynska, Elzbieta; Wojnar, Marcin

2017-09-01

Studies on the homeostasis of magnesium in alcohol-dependent patients have often been characterized by low hypomagnesemia detection rates. This may be due to the fact that the content of magnesium in blood serum constitutes only 1% of the average magnesium level within the human body. However, the concentration of ionized magnesium is more physiologically important and makes up 67% of the total magnesium within a human organism. There are no data concerning the determination of the ionized fraction of magnesium in patients addicted to alcohol and its influence on mental health status. This study included 100 alcohol-dependent patients and 50 healthy subjects. The free magnesium fraction was determined using the potentiometric method by means of using ion-selective electrodes. The total magnesium level was determined by using a biochemical Indiko Plus analyzer. In this study, different psychometric scales were applied. Our results confirm the usefulness of ionized magnesium concentrations in erythrocytes and plasma as a diagnostic parameter of low magnesium status in alcohol-dependent patients. The lower the concentration of ionized magnesium, the worse the quality of life an alcohol-dependent person might experience. In the case of total magnesium, no such correlation was determined. Copyright © 2017 Elsevier B.V. All rights reserved.

Longitudinal Associations of Alcohol Involvement with Subjective Well-Being in Adolescence and Prediction to Alcohol Problems in Early Adulthood

ERIC Educational Resources Information Center

Mason, W. Alex; Spoth, Richard L.

2011-01-01

Adolescent alcohol involvement is associated with numerous negative outcomes, but also appears to have positive correlates, including subjective well-being. Additional research is needed to understand these paradoxical findings. The current study examines alcohol use, adverse alcohol-related (and other substance-related) consequences, and…

Alcohol and aldehyde dehydrogenase polymorphisms in Chinese and Indian populations.

PubMed

Tan, Ene-Choo; Lim, Leslie; Leong, Jern-Yi; Lim, Jing-Yan; Lee, Arthur; Yang, Jun; Tan, Chay-Hoon; Winslow, Munidasa

2010-01-01

The association between two functional polymorphisms in alcohol dehydrogenase (ADH2/ADH1B) and aldehyde dehydrogenase (ALDH2) genes and alcohol dependence was examined in 182 Chinese and Indian patients undergoing treatment for alcohol dependence and 184 screened control subjects from Singapore. All subjects were screened by the Alcohol Use Disorders Identification Test (AUDIT). Patients were also administered the Severity of Alcohol Dependence Questionnaire (SADQ). Polymorphisms were genotyped by allele-specific polymerase chain reaction and selected genotypes confirmed by DNA sequencing or restriction fragment length polymorphism. Our results showed that frequencies of ADH1B*2 and ALDH2*2 were higher in controls compared to alcohol-dependent subjects for both Chinese and Indians. Frequencies of these two alleles were also higher in the 104 Chinese controls compared to the 80 Indian controls. None of the eight Chinese who were homozygous for both protective alleles was alcohol dependent. The higher frequencies of the protective alleles could explain the lower rate of alcohol dependence in Chinese.

Genetic markers of comorbid depression and alcoholism in women.

PubMed

Procopio, Daniela O; Saba, Laura M; Walter, Henriette; Lesch, Otto; Skala, Katrin; Schlaff, Golda; Vanderlinden, Lauren; Clapp, Peter; Hoffman, Paula L; Tabakoff, Boris

2013-06-01

Alcohol dependence (AD) is often accompanied by comorbid depression. Recent clinical evidence supports the benefit of subtype-specific pharmacotherapy in treating the population of alcohol-dependent subjects with comorbid major depressive disorder (MDD). However, in many alcohol-dependent subjects, depression is a reactive response to chronic alcohol use and withdrawal and abates with a period of abstinence. Genetic markers may distinguish alcohol-dependent subjects with MDD not tied chronologically and etiologically to their alcohol consumption. In this work, we investigated the association of adenylyl cyclase genes (ADCY1-9), which are implicated in both AD and mood disorders, with alcoholism and comorbid depression. Subjects from Vienna, Austria (n = 323) were genotyped, and single nucleotide polymorphisms (1,152) encompassing the genetic locations of the 9 ADCY genes were examined. The Vienna cohort contained alcohol-dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology, subjects are segregated into 4 types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females. We identified 4 haplotypes associated with the phenotype of Type III alcoholism in females. One haplotype was in a genomic area in proximity to ADCY2, but actually within a lincRNA gene, 2 haplotypes were within ADCY5, and 1 haplotype was within the coding region of ADCY8. Three of the 4 haplotypes contributed independently to Type III alcoholism and together generated a positive predictive value of 72% and a negative predictive value of 78% for distinguishing women with a Lesch Type III diagnosis versus women designated as Type I or II alcoholics. Polymorphisms in ADCY8 and ADCY5 and within a lincRNA are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. Each of these genetic locations can rationally contribute to the polygenic etiology of

Alcohol Dependence, Mortality, and Chronic Health Conditions in a Rural Population in Korea

PubMed Central

Noh, Samuel; Shin, Jongho; Ahn, Joung-Sook; Kim, Tae-Hui

2008-01-01

To determine the effects of excessive drinking and alcohol dependency on mortality and chronic health problems in a rural community in South Korea, this study represents a nested case-control study. In 1998, we conducted the Alcohol Dependence Survey (ADS), a population survey of a village in Korea. To measure the effects of alcohol on chronic health conditions and mortality over time, in 2004, we identified 290 adults from the ADS sample (N=1,058) for follow-up. Of those selected, 145 were adults who had alcohol problems, either alcohol dependence as assessed in the ADS by the Severity of Alcohol Dependence Questionnaire (N=59), or excessive drinking without dependency (N=86). Further 145 nondrinkers were identified, matching those with alcohol problems in age and sex. We revisited the village in 2004 and completed personal interviews with them. In multivariate logistic regressions, the rates of mortality and morbidity of chronic health conditions were three times greater for alcohol dependents compared with the rate for nondrinkers. Importantly, however, excessive drinking without dependency was not associated with the rates of either mortality or morbidity. Future investigations would benefit by attending more specifically to measures for alcohol dependence as well as measures for alcohol consumption. PMID:18303191

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

PubMed

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

2015-12-01

A randomized controlled trial for an innovative alcohol-adapted anger management treatment (AM) for outpatient alcohol dependent individuals scoring moderate or above on anger is described. AM treatment outcomes were compared to those of an empirically-supported intervention, Alcoholics Anonymous Facilitation treatment (AAF). Clients in AM, relative to clients in AAF, were hypothesized to have greater improvement in anger and anger-related cognitions and lesser AA involvement during the 6-month follow-up. Anger-related variables were hypothesized to be stronger predictors of improved alcohol outcomes in the AM treatment condition and AA involvement was hypothesized to be a stronger predictor of alcohol outcomes in the AAF treatment group. Seventy-six alcohol dependent men and women were randomly assigned to treatment condition and followed for 6 months after treatment end. Both AM and AAF treatments were followed by significant reductions in heavy drinking days, alcohol consequences, anger, and maladaptive anger-related thoughts and increases in abstinence and self-confidence regarding not drinking to anger-related triggers. Treatment with AAF was associated with greater AA involvement relative to treatment with AM. Changes in anger and AA involvement were predictive of posttreatment alcohol outcomes for both treatments. Change in trait anger was a stronger predictor of posttreatment alcohol consequences for AM than for AAF clients; during-treatment AA meeting attendance was a stronger predictor of posttreatment heavy drinking and alcohol consequences for AAF than for AM clients. Anger-related constructs and drinking triggers should be foci in treatment of alcohol dependence for anger-involved clients. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

A randomized controlled trial for an innovative alcohol-adapted anger management treatment (AM) for outpatient alcohol dependent individuals scoring moderate or above on anger is described. AM treatment outcomes were compared to those of an empirically-supported intervention, Alcoholics Anonymous Facilitation treatment (AAF). Clients in AM, relative to clients in AAF, were hypothesized to have greater improvement in anger and anger-related cognitions and lesser AA involvement during the 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

Alcohol consumption, hazardous drinking, and alcohol dependency among the population of Andaman and Nicobar Islands, India.

PubMed

Manimunda, Sathya Prakash; Sugunan, Attayuru Purushottaman; Thennarasu, Kandavelu; Pandian, Dhanasekara; Pesala, Kasturi S; Benegal, Vivek

2017-01-01

Harmful use of alcohol is one of the globally recognized causes of health hazards. There are no data on alcohol consumption from Andaman and Nicobar Islands. The objective of the study was to assess the prevalence and pattern of alcohol use among the population of Andaman and Nicobar Islands, India. A representative sample of 18,018 individuals aged ≥14 years were chosen by multistage random sampling and administered a structured instrument, a modified version of the Gender, Alcohol, and Culture: An International Study (GENACIS) which included sociodemographic details and Alcohol Use Disorders Identification Test (AUDIT). The overall prevalence of alcohol consumption was 35% among males and over 6.0% in females, aged 14 and above. Two out of every five alcohol users fit into a category of hazardous drinkers. One-fourth of the total users (23%) are alcohol dependents. Both the hazardous drinking and dependent use are high among males compared to females. Almost 18.0% of male drinkers and 12.0% of female drinkers reported heavy drinking on typical drinking occasions. The predominant beverages consumed were in the category of homebrews such as toddy and handia. The present study highlights the magnitude of hazardous drinking and alcohol dependence in Andaman and Nicobar Islands, India and the complex sociocultural differences in the pattern of alcohol use. Based on the AUDIT data, among the population of Andaman and Nicobar Islands (aged 14 and above), one out of ten requires active interventions to manage the harmful impact of alcohol misuse.

The effect of alcohol price on dependent drinkers' alcohol consumption.

PubMed

Falkner, Carolyn; Christie, Grant; Zhou, Lifeng; King, Julian

2015-12-18

To investigate the current purchasing behaviours of a group of dependent drinkers and their potential response to future increases in the price of alcohol. 115 clients undergoing medical detoxification completed an anonymous survey about their daily alcohol consumption, its cost, their response to potential price increases and strategies previously used when unable to afford alcohol. Mean and median number of standard drinks consumed per day was 24, at a median cost of $25 NZD (95%CI $22, $30). Thirty-six per cent (95%CI 26%, 46%) of the group bought alcohol at $1 or less per standard drink, and the median number of drinks consumed per day (30) by this group was significantly higher (p=0.0028) than the rest of the sample (22.5). The most common strategy used if no money was available to purchase alcohol was to forgo essentials. If facing a potential price rise, 77% (95%CI 69%, 85%) would switch wholly or partially to a cheaper product and 13% (95%CI 8%, 21%) would cut down their drinking. Although the majority of our group would be financially impacted by an increase in the minimum price per standard drink, any potential impacts would be most significant in those buying the cheapest alcohol (who also drink the most), suggesting that minimum pricing may be an important harm minimisation strategy in this group. A minimum price per standard drink would limit the possibility of switching to an alternate cheaper product and likely result in an overall reduction in alcohol consumption in this group. Stealing alcohol, or the use of non-beverage alcohol, were seldom reported as previous strategies used in response to unaffordable alcohol and fears of such are not valid reasons for rejecting minimum pricing to reduce general population consumption.

Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.

PubMed

Beck, Anne; Wüstenberg, Torsten; Genauck, Alexander; Wrase, Jana; Schlagenhauf, Florian; Smolka, Michael N; Mann, Karl; Heinz, Andreas

2012-08-01

In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. Subsequent relapsers displayed increased brain atrophy in brain areas associated with

Empathy, and its relationship with cognitive and emotional functions in alcohol dependency.

PubMed

Erol, Almila; Akyalcin Kirdok, Asusinem; Zorlu, Nabi; Polat, Serap; Mete, Levent

2017-04-01

Empathy can be defined as the ability to understand the other's thoughts and feelings. It contains both cognitive and emotional components. The aim of this study was to investigate the empathy ability of patients with alcohol dependency in association with cognitive and emotional functions, after acute detoxification and during long-term abstinence. Thirty-three alcohol dependent inpatients that completed a detoxification process and stayed abstinent throughout the study, and 33 healthy comparison subjects that matched the patients for age, gender, and education level were included in the study. All the participants were administered the Facial Emotion Identification Test (FEIT), Facial Emotion Discrimination Test (FEDT), Trail Making Test (TMT), Digit Span Test (DST), Auditory Consonant Trigram Test (ACT), and Empathy Quotient Scale (EQS). All the tests were repeated after 3 months of abstinence. At the first evaluation conducted after detoxification, patients performed significantly worse than healthy comparisons in almost all tests. At the second evaluation, which was conducted after 3 months of abstinence, the patients improved significantly in all measures, and no significant differences were detected between the patient and comparison groups. There were significant correlations between the test scores and EQS score. Alcohol dependency has deleterious effects on empathy ability, and cognitive and emotional functions. Those impairments can improve with abstinence. Empathy ability has strong relationships with cognitive and emotional functions.

Cigarette Smoking Predicts Differential Benefit from Naltrexone for Alcohol Dependence

PubMed Central

Fucito, Lisa M.; Park, Aesoon; Gulliver, Suzy Bird; Mattson, Margaret E.; Gueorguieva, Ralitza V.; O’Malley, Stephanie S.

2012-01-01

Background Identifying factors that modify responsiveness to pharmacotherapies for alcohol dependence is important for treatment planning. Cigarette smoking predicts more severe alcohol dependence and poorer treatment response in general. Nevertheless, there is limited research on cigarette smoking as a potential predictor of differential response to pharmacological treatment of alcoholism. Methods We examined the association between cigarette smoking and drinking outcomes in the COMBINE study, a randomized, double-blind placebo-controlled 16-week trial comparing combinations of medications (i.e., acamprosate and naltrexone) and behavioral interventions (i.e., medical management (MM), combined behavioral therapy (CBI)) in 1383 alcohol dependent individuals. Results Smokers (i.e., more than half the sample) significantly differed from nonsmokers on several demographic and drinking-related variables at baseline and generally had poorer treatment outcomes than nonsmokers. However, smokers who received naltrexone had better drinking outcomes than smokers who received placebo, whereas alcohol use among nonsmokers did not vary by naltrexone assignment. This pattern of findings occurred independent of whether patients received CBI or MM and remained after controlling for alcoholism typology and baseline demographic differences. Approximately 9% of smokers quit smoking and an additional 10% reduced their cigarette intake during treatment. Reductions in smoking did not vary by treatment assignment. Conclusions These results suggest that naltrexone may be particularly beneficial for improving alcohol use outcomes in alcohol dependent smokers. Trial Registration The COMBINE Study, NCT000626, http://www.cscc.unc.edu/combine/. PMID:22541040

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

PubMed

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

2016-01-01

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

Genetic moderators and psychiatric mediators of the link between sexual abuse and alcohol dependence.

PubMed

Copeland, William E; Magnusson, Asa; Göransson, Mona; Heilig, Markus A

2011-06-01

This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that might affect treatment planning. A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2011-01-01

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

Low μ-Opioid Receptor Status in Alcohol Dependence Identified by Combined Positron Emission Tomography and Post-Mortem Brain Analysis

PubMed Central

Hermann, Derik; Hirth, Natalie; Reimold, Matthias; Batra, Anil; Smolka, Michael N; Hoffmann, Sabine; Kiefer, Falk; Noori, Hamid R; Sommer, Wolfgang H; Reischl, Gerald; la Fougère, Christian; Mann, Karl; Spanagel, Rainer; Hansson, Anita C

2017-01-01

Blockade of the μ-opioid receptor (MOR) by naltrexone reduces relapse risk in a subpopulation of alcohol-dependent patients. Previous positron-emission-tomography (PET) studies using the MOR ligand [11C]carfentanil have found increased MOR availability in abstinent alcoholics, which may reflect either increased MOR expression or lower endogenous ligand concentration. To differentiate between both effects, we investigated two cohorts of alcoholic subjects using either post-mortem or clinical PET analysis. Post-mortem brain tissue of alcohol-dependent subjects and controls (N=43/group) was quantitatively analyzed for MOR ([3H]DAMGO)-binding sites and OPRM1 mRNA in striatal regions. [11C]carfentanil PET was performed in detoxified, medication free alcohol-dependent patients (N=38), followed by a randomized controlled study of naltrexone versus placebo and follow-up for 1 year (clinical trial number: NCT00317031). Because the functional OPRM1 variant rs1799971:A>G affects the ligand binding, allele carrier status was considered in the analyses. MOR-binding sites were reduced by 23–51% in post-mortem striatal tissue of alcoholics. In the PET study, a significant interaction of OPRM1 genotype, binding potential (BPND) for [11C]carfentanil in the ventral striatum, and relapse risk was found. Particularly in G-allele carriers, lower striatal BPND was associated with a higher relapse risk. Interestingly, this effect was more pronounced in the naltrexone treatment group. Reduced MOR is interpreted as a neuroadaptation to an alcohol-induced release of endogenous ligands in patients with severe alcoholism. Low MOR availability may explain the ineffectiveness of naltrexone treatment in this subpopulation. Finally, low MOR-binding sites are proposed as a molecular marker for a negative disease course. PMID:27510425

Attention and recognition memory bias for alcohol-related stimuli among alcohol-dependent patients attending residential treatment.

PubMed

Klein, Audrey A; Nelson, Lindsay M; Anker, Justin J

2013-03-01

Though studies have examined attentional bias for alcohol-related information among alcohol-dependent individuals, few have examined memory bias. This study examined attention and recognition memory biases for alcohol-related information among patients recently admitted to residential alcohol treatment (n=100; 40% female). Participants completed a computerized attentional task wherein they classified a centrally-presented digit as odd or even. On some trials, an alcohol word, neutral word, or anagram was presented along with the digit. On these dual trials participants first classified the digit and then classified the other stimulus as a word or nonword. Participants took longer to classify digits that appeared with alcohol words compared to neutral words; suggesting the alcohol words distracted them from processing the digit. In a subsequent recognition memory test, participants showed significantly higher hit rates (i.e., correctly classifying an old item as old) and false alarm rates (i.e., incorrectly classifying a new item as old) to the alcohol words compared to the neutral words, and they also showed a more liberal response bias to alcohol words. The findings suggest that alcohol-dependent individuals exhibit both attention and memory bias for alcohol-related information. Copyright © 2012 Elsevier Ltd. All rights reserved.

Alcohol Dependence, Co-occurring Conditions and Attributable Burden

PubMed Central

Odlaug, B.L.; Gual, A.; DeCourcy, J.; Perry, R.; Pike, J.; Heron, L.; Rehm, J.

2016-01-01

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

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis

PubMed Central

Treutlein, Jens; Streit, Fabian; Juraeva, Dilafruz; Degenhardt, Franziska; Rietschel, Liz; Forstner, Andreas J.; Ridinger, Monika; Dukal, Helene; Foo, Jerome C.; Soyka, Michael; Maier, Wolfgang; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Müller-Myhsok, Bertram; Lucae, Susanne; Ising, Marcus; Stickel, Felix; Berg, Thomas; Roggenbuck, Ulla; Jöckel, Karl-Heinz; Scholz, Henrike; Zimmermann, Ulrich S.; Buch, Stephan; Sommer, Wolfgang H.; Spanagel, Rainer; Brors, Benedikt; Cichon, Sven; Mann, Karl; Kiefer, Falk; Hampe, Jochen; Rosendahl, Jonas; Nöthen, Markus M.; Rietschel, Marcella

2017-01-01

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10−6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed. PMID:28714907

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

PubMed

Treutlein, Jens; Frank, Josef; Streit, Fabian; Reinbold, Céline S; Juraeva, Dilafruz; Degenhardt, Franziska; Rietschel, Liz; Witt, Stephanie H; Forstner, Andreas J; Ridinger, Monika; Strohmaier, Jana; Wodarz, Norbert; Dukal, Helene; Foo, Jerome C; Hoffmann, Per; Herms, Stefan; Heilmann-Heimbach, Stefanie; Soyka, Michael; Maier, Wolfgang; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Müller-Myhsok, Bertram; Lucae, Susanne; Ising, Marcus; Stickel, Felix; Berg, Thomas; Roggenbuck, Ulla; Jöckel, Karl-Heinz; Scholz, Henrike; Zimmermann, Ulrich S; Buch, Stephan; Sommer, Wolfgang H; Spanagel, Rainer; Brors, Benedikt; Cichon, Sven; Mann, Karl; Kiefer, Falk; Hampe, Jochen; Rosendahl, Jonas; Nöthen, Markus M; Rietschel, Marcella

2017-07-17

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach ( p uncorrected = 1.2 × 10 -6 ; p corrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.

Alcohol's effects on emotionally motivated attention, defensive reactivity and subjective anxiety during uncertain threats.

PubMed

Bradford, Daniel E; Motschman, Courtney A; Starr, Mark J; Curtin, John J

2017-11-01

Developing a better understanding of how and under what circumstances alcohol affects the emotions, cognitions and neural functions that precede and contribute to dangerous behaviors during intoxication may help to reduce their occurrence. Alcohol intoxication has recently been shown to reduce defensive reactivity and anxiety more during uncertain vs certain threat. However, alcohol's effects on emotionally motivated attention to these threats are unknown. Alcohol may disrupt both affective response to and attentional processing of uncertain threats making intoxicated individuals less able to avoid dangerous and costly behaviors. To test this possibility, we examined the effects of a broad range of blood alcohol concentrations on 96 participants' sub-cortically mediated defensive reactivity (startle potentiation), retrospective subjective anxiety (self-report) and cortically assessed emotionally motivated attention (probe P3 event related potential) while they experienced visually cued uncertain and certain location electric shock threat. As predicted, alcohol decreased defensive reactivity and subjective anxiety more during uncertain vs certain threat. In a novel finding, alcohol dampened emotionally motivated attention during uncertain but not certain threat. This effect appeared independent of alcohol's effects on defensive reactivity and subjective anxiety. These results suggest that alcohol intoxication dampens processing of uncertain threats while leaving processing of certain threats intact. © The Author (2017). Published by Oxford University Press.

Childhood and Adolescent Predictors of Alcohol Abuse and Dependence in Young Adulthood*

PubMed Central

Guo, Jie; Hawkins, J. David; Hill, Karl G.; Abbott, Robert D

2007-01-01

Objective To provide a comprehensive examination of childhood and adolescent predictors of alcohol abuse and dependence at age 21, theoretically guided by the social development model. Method Data were taken from an ethnically diverse urban sample of 808 students [51% male), surveyed at age 10 and followed prospectively to age 21 in 1996. Potential predictors of alcohol abuse and dependence at age 21 were measured at ages 10, 14 and 16. Relationships between these predictors and alcohol abuse and dependence were examined at each age, to assess changes in their patterns of prediction over time. Results Strong bonding to school, close parental monitoring of children and clearly defined family rules for behavior, appropriate parental rewards for good behaviors, high level of refusal skills and strong belief in the moral order predicted a lower risk for alcohol abuse and dependence at age 21. Of these, strong bonding to school consistently predicted lower alcohol abuse and dependence from all three ages (10, 14 and 16). By contrast, youths who had a higher risk of alcohol abuse and dependence at age 21 engaged in more problem behaviors, had more opportunities to be involved with antisocial individuals and spent more time with and were more bonded to those individuals, viewed fewer negative consequences from antisocial behaviors and held more favorable views on alcohol use. Of these, prior problem behaviors and antisocial opportunities and involvements at ages 10, 14 and 16 consistently predicted alcohol abuse and dependence at age 21. Conclusions These important malleable predictors, identifiable as early as age 10, provide potential intervention targets for the prevention of alcohol abuse and dependence in early adulthood. PMID:11838912

Heart rate variability predicts alcohol craving in alcohol dependent outpatients: further evidence for HRV as a psychophysiological marker of self-regulation.

PubMed

Quintana, Daniel S; Guastella, Adam J; McGregor, Iain S; Hickie, Ian B; Kemp, Andrew H

2013-09-01

Past research has highlighted an important role of the autonomic nervous system in alcohol dependence and capacity for self-regulation. While previous studies have examined alcohol dependent inpatients, it remains unclear whether resting-state HRV, a potential psychophysiological marker of ones capacity for self-regulation, is related to craving in patients who currently consume alcohol. Thus, the aim of the present study was to determine whether HRV predicts alcohol craving in dependent individuals in the community. Resting-state HRV and alcohol craving, as indexed by the obsessive compulsive drinking scale, were assessed in 26 alcohol dependent outpatients. Results supported hypotheses indicating that HRV accounts for an additional 12.1% of the variance in craving after controlling for age, anxiety and levels of alcohol consumption. Here we show for the first time that resting-state HRV predicts craving in alcohol dependent outpatients. Results provide important new evidence for a role of the autonomic nervous system in the maintenance of dependence disorders. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Quantifying alcohol consumption: Self-report, transdermal assessment, and prediction of dependence symptoms.

PubMed

Simons, Jeffrey S; Wills, Thomas A; Emery, Noah N; Marks, Russell M

2015-11-01

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 biochemical 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 demonstration of the use of transdermal alcohol assessment to characterize drinking dynamics associated with risk for alcohol dependence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantifying alcohol consumption: Self-report, transdermal assessment, and prediction of dependence symptoms☆

PubMed Central

Simons, Jeffrey S.; Wills, Thomas A.; Emery, Noah N.; Marks, Russell M.

2015-01-01

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

Targeting Cognitive-Affective Risk Mechanisms in Stress-Precipitated Alcohol Dependence: An Integrated, Biopsychosocial Model of Automaticity, Allostasis, and Addiction

PubMed Central

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

2011-01-01

This paper proposes a novel hypothetical model integrating formerly discrete theories of stress appraisal, neurobiological allostasis, automatic cognitive processing, and addictive behavior to elucidate how alcohol misuse and dependence are maintained and re-activated by stress. We outline a risk chain in which psychosocial stress initiates physiological arousal, perseverative cognition, and negative affect that, in turn, triggers automatized schema to compel alcohol consumption. This implicit cognitive process then leads to attentional biases toward alcohol, subjective experiences of craving, paradoxical increases in arousal and alcohol-related cognitions due to urge suppression, and palliative coping through drinking. When palliative coping relieves distress, it results in negative reinforcement conditioning that perpetuates the cycle by further sensitizing the system to future stressful encounters. This model has implications for development and implementation of innovative behavioral interventions (such as mindfulness training) that disrupt cognitive-affective mechanisms underpinning stress-precipitated dependence on alcohol. PMID:21354711

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

PubMed

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

2014-09-01

Increasing attention to the importance of saliva testing is not surprising because smoking and alcohol drinking act synergistically on oral tissues, and their metabolite levels, e.g., acetaldehyde, are much higher in saliva than in blood. The activity of salivary alcohol dehydrogenase (ADH) comes from oral microbiota, mucosa, and salivary glands. The purpose of this study was to investigate the involvement of ADH in the oral health pathology of smoking (AS) and non-smoking (ANS) alcohol-dependent males. The results indicated that the AS group had a more significant and longer duration (until the 30th day of alcohol abstinence) decrease in ADH activity and output than the ANS group (until the 15th day of alcohol abstinence) compared to controls (social drinkers; C). The decreased salivary flow (SF) in alcoholics was observed longer in the ANS group (until the 30th day of alcohol abstinence), whereas in the AS group SF normalized at the 15th day, probably due to the irritating effect of tobacco smoke on the oral mucosa. Because saliva was centrifuged to remove cells and debris (including microbial cells), the detected salivary ADH activity was derived from salivary glands and/or oral mucosa. A more profound and longer decrease in ADH activity/output in smoking than non-smoking alcoholics was likely due to the damaged salivary glands and/or oral mucosa, caused by the synergistic effect of alcohol drinking and smoking. The lower values of salivary ADH in smoking than non-smoking alcoholics might also be partly due to the reversed/inhibited ADH reaction by high levels of accumulated acetaldehyde. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of the therapeutic workplace and heavy alcohol use on homelessness among homeless alcohol-dependent adults.

PubMed

Carlson, Emily; Holtyn, August F; Fingerhood, Michael; Friedman-Wheeler, Dara; Leoutsakos, Jeannie-Marie S; Silverman, Kenneth

2016-11-01

A clinical trial demonstrated that a therapeutic workplace could promote alcohol abstinence in homeless, alcohol-dependent adults. This secondary-data analysis examined rates of homelessness and their relation to the therapeutic workplace intervention and alcohol use during the trial. In the trial, homeless, alcohol-dependent adults could work in a therapeutic workplace for 6 months and were randomly assigned to Unpaid Training, Paid Training, or Contingent Paid Training groups. Unpaid Training participants were not paid for working. Paid Training participants were paid for working. Contingent Paid Training participants were paid for working if they provided alcohol-negative breath samples. Rates of homelessness during the study were calculated for each participant and the three groups were compared. Mixed-effects regression models were conducted to examine the relation between alcohol use (i.e., heavy drinking, drinks per drinking day, and days of alcohol abstinence) and homelessness. Unpaid Training, Paid Training, and Contingent Paid Training participants did not differ in the percentage of study days spent homeless (31%, 28%, 17%; respectively; F(2,94)=1.732, p=0.183). However, participants with more heavy drinking days (b=0.350, p<0.001), more drinks per drinking day (b=0.267, p<0.001), and fewer days of alcohol abstinence (b=-0.285, p<0.001) spent more time homeless. Reducing heavy drinking and alcohol use may help homeless, alcohol-dependent adults transition out of homelessness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Expected Personality Characteristics of Alcohol-Dependent Individuals.

ERIC Educational Resources Information Center

Malouff, John M.; Schutte, Nicola S.

2002-01-01

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

Salivary lysozyme in smoking alcohol dependent persons.

PubMed

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

2012-01-01

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

Imbalance between cognitive systems in alcohol-dependence and Korsakoff syndrome: An exploration using the Alcohol Flanker Task.

PubMed

Brion, Mélanie; Dormal, Valérie; Lannoy, Séverine; Mertens, Serge; de Timary, Philippe; Maurage, Pierre

2018-03-06

Alcohol-dependent individuals (ALC) simultaneously present decreased inhibitory control and increased attention towards alcohol-related cues. The dual-process models have proposed that these symptoms reflect an imbalance between prefrontal/reflective and limbic/automatic systems, respectively leading to cognitive dysfunctions in executive processes and to alcohol-related bias. However, most previous research has focused on a separate exploration of these systems among ALC, and the direct measure of their interactions remains to be conducted. Moreover, no study has explored the evolution of this imbalance across the successive stages of alcohol-related disorders, and particularly in Korsakoff syndrome (KS), the most frequent neurological complication of alcohol-dependence. Ten KS, 14 ALC, and 14 matched control participants performed a modified Flanker task, the "Alcohol Flanker Task," based on congruent, incongruent, and neutral conditions with alcohol-related stimuli. This task required inhibitory processing on alcohol-related stimuli and evaluated, through a behavioral approach, the interaction between reflective and automatic systems, as well as its evolution between ALC and KS. ALC and KS both presented high reactivity towards alcohol-related stimuli, confirming the presence of alcohol-related bias. KS showed increased omission rates (related to distractor interference) while ALC showed higher false-alarm rates (related to prepotent response inhibition). These results suggest that different inhibitory subcomponents might be altered at the successive stages of the pathology, and experimentally confirms the crucial role of the interaction between reflective and automatic processes in alcohol-use disorders. The present results reinforce the proposal that alcohol-related cues significantly impact inhibitory control in alcohol-related disorders. However, ALC and KS present different patterns of deficits depending on task complexity (i.e., executive load), thus

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

PubMed

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

2015-12-01

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

Anxiety and smoking cessation outcomes in alcohol-dependent smokers.

PubMed

Kelly, Megan M; Grant, Christoffer; Cooper, Sharon; Cooney, Judith L

2013-02-01

Anxiety-related characteristics, including anxiety sensitivity and trait anxiety, are elevated in individuals with alcohol and nicotine dependence and associated with greater difficulties with quitting smoking. However, little is known about how anxiety-related characteristics are related to smoking cessation outcomes in alcohol-dependent smokers. The present study, part of a larger smoking cessation clinical trial, examined associations between anxiety sensitivity, trait anxiety, nicotine withdrawal symptoms, smoking urges, and smoking cessation outcomes in a sample of 83 alcohol-dependent smokers. Participants were enrolled in concurrent alcohol and tobacco treatment as part of a substance-abuse intensive outpatient program. Smoking cessation treatment was administered in a 3-week cognitive-behavioral format that included 8 weeks of open-label nicotine patch treatment. Information on nicotine withdrawal, smoking urges, and CO-confirmed smoking consumption rates was collected at baseline, quit date, end of behavioral treatment, and at a 1-month follow-up. Higher levels of anxiety sensitivity were associated with more smoking urges due to anticipation of negative affect relief at quit date. Higher levels of trait anxiety were associated with more smoking urges due to positive reinforcement and anticipation of relief of negative affect at quit date, as well as more severe nicotine withdrawal symptoms at the end of treatment. Levels of anxiety sensitivity and trait anxiety were not associated with Cox regression survival times to relapse. These results indicate that for alcohol-dependent smokers, levels of anxiety sensitivity and trait anxiety are important to consider in the assessment and treatment of nicotine dependence.

Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships.

PubMed

Hartman, Rebecca L; Brown, Timothy L; Milavetz, Gary; Spurgin, Andrew; Gorelick, David A; Gaffney, Gary; Huestis, Marilyn A

2016-07-01

Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Δ(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r≥0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective

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

PubMed Central

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

2013-01-01

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

Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence

PubMed Central

Blevins, Tana; Aliev, Fazil; Adkins, Amy; Hack, Laura; Bigdeli, Tim; D. van der Vaart, Andrew; Web, Bradley Todd; Bacanu, Silviu-Alin; Kalsi, Gursharan; Kendler, Kenneth S.; Miles, Michael F.; Dick, Danielle; Riley, Brien P.; Dumur, Catherine; Vladimirov, Vladimir I.

2015-01-01

Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. PMID:26381263

Does alcohol craving mediate the impulsivity-aggression relationship in recently detoxified alcohol-dependent patients?

PubMed

Roozen, H G; Wetering, B J M van de; Franken, I H A

2013-01-01

The relationship between the use of alcohol and aggression is complex and represents major public health issues. Delving into the nature of this association is vital, since various underlying factors may contribute to the expression of aggression. This study examined trait aggression by assessing correlates and, subsequently, the unique contribution of alcohol craving, and dysfunctional impulsivity, by means of correlational and mediational analyses. Forty inpatient detoxified alcohol-dependent patients were recruited. These participants completed the Desire for Alcohol Questionnaire (DAQ), Dickman Impulsivity Inventory (DII), and the Aggression Questionnaire (AQ). The findings indicated that aggression, dysfunctional impulsivity, and alcohol craving were all positively intercorrelated. The association between dysfunctional impulsivity and aggression was robust. The mediational analyses yielded that craving partially mediated this relationship, although not very substantial. It was shown that impulsivity, as a personality characteristic, is strongly associated with aggressive behaviors, whereby the impact of craving on the relationship between impulsivity and trait aggression in alcohol-dependent inpatients was weak. Since it has been posited that factors such as impulsivity and craving may contribute to the lucid association between substance use and aggression, these findings mirror previous research on stimulant users and, subsequently, substantiates that craving exerts only a minor weight on the strong impulsivity-aggression relationship.

Acute subjective response to alcohol as a function of reward and punishment sensitivity.

PubMed

Morris, David H; Treloar, Hayley; Tsai, Chia-Lin; McCarty, Kayleigh N; McCarthy, Denis M

2016-09-01

Individual differences in subjective response to alcohol play a crucial role in the development of heavy drinking and related problems. In light of this, a growing focus of research has been identifying factors that contribute to differences in response. The aim of the present study was to determine whether individual differences in the subjective experience of rewarding and aversive effects of alcohol are a specific manifestation of general differences in reward and punishment sensitivity. Eighty-nine participants (M age=22.4, SD=1.9; 47.2% women) consumed a moderate dose of alcohol, i.e., peak breath alcohol concentration (BrAC)≈0.080g%, and rated their level of stimulation and sedation at seven timepoints over the BrAC curve. Sensitivity to reward and punishment were assessed by a self-report questionnaire prior to consumption. Multilevel growth models showed that post-consumption changes in stimulation ratings varied as a function of participants' level of reward and punishment sensitivity. Drinkers more sensitive to reward reported feeling more stimulated shortly after drinking and exhibited an attenuated rate of decline in stimulation over the blood alcohol curve, relative to drinkers with less strong reward sensitivity. Reward sensitivity was not related to subjective ratings of sedation, and punishment sensitivity was not related to either stimulation or sedation ratings. Findings suggest that reward sensitivity may increase risk for alcohol misuse among young adult social drinkers by increasing their subjective feelings of stimulation while drinking. Copyright © 2016. Published by Elsevier Ltd.

Comorbid mental disorders among the patients with alcohol abuse and dependence in Korea.

PubMed Central

Cho, Maeng Je; Hahm, Bong-Jin; Suh, Tongwoo; Suh, Guk-Hee; Cho, Seong-Jin; Lee, Chung Kyoon

2002-01-01

This study investigated the patterns of alcohol disorder comorbidity with other psychiatric disorders, using Korean nationwide epidemiological data. By two-stage cluster sampling, 5,176 adult household residents of Korea were interviewed using the Korean version of the Diagnostic Interview Schedule. Psychiatric disorders strongly associated with alcohol disorders were, other drug abuse or dependence, major depression, simple phobia, antisocial personality disorder, tobacco dependence, and pathological gambling. Male alcoholics had a tendency to begin with tobacco dependence, and some male pathological gamblers first had alcohol disorders. The presence of comorbid psychiatric disorders was associated with a more severe form and the later onset of alcohol disorders, and associated with help-seeking for alcohol abuse/dependence. PMID:11961310

Heterogeneity of emotional and interpersonal difficulties in alcohol-dependence: A cluster analytic approach.

PubMed

Maurage, Pierre; Timary, Philippe de; D'Hondt, Fabien

2017-08-01

Emotional and interpersonal impairments have been largely reported in alcohol-dependence, and their role in its development and maintenance is widely established. However, earlier studies have exclusively focused on group comparisons between healthy controls and alcohol-dependent individuals, considering them as a homogeneous population. The variability of socio-emotional profiles in this disorder thus remains totally unexplored. The present study used a cluster analytic approach to explore the heterogeneity of affective and social disorders in alcohol-dependent individuals. 296 recently-detoxified alcohol-dependent patients were first compared with 246 matched healthy controls regarding self-reported emotional (i.e. alexithymia) and social (i.e. interpersonal problems) difficulties. Then, a cluster analysis was performed, focusing on the alcohol-dependent sample, to explore the presence of differential patterns of socio-emotional deficits and their links with demographic, psychopathological and alcohol-related variables. The group comparison between alcohol-dependent individuals and controls clearly confirmed that emotional and interpersonal difficulties constitute a key factor in alcohol-dependence. However, the cluster analysis identified five subgroups of alcohol-dependent individuals, presenting distinct combinations of alexithymia and interpersonal problems ranging from a total absence of reported impairment to generalized socio-emotional difficulties. Alcohol-dependent individuals should no more be considered as constituting a unitary group regarding their affective and interpersonal difficulties, but rather as a population encompassing a wide variety of socio-emotional profiles. Future experimental studies on emotional and social variables should thus go beyond mere group comparisons to explore this heterogeneity, and prevention programs proposing an individualized evaluation and rehabilitation of these deficits should be promoted. Copyright © 2017

Alcohol dependence: international policy implications for prison populations.

PubMed

Jones, Gail Yvonne; Hoffmann, Norman G

2006-11-08

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. 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. 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.

Effects of alcohol on body-sway patterns in human subjects.

PubMed

Nieschalk, M; Ortmann, C; West, A; Schmäl, F; Stoll, W; Fechner, G

1999-01-01

The vestibulospinal aspects of vestibular function are commonly neglected in the evaluation of alcohol-induced intoxication. Thus, in the present study the effect of an acute intoxication with a low or moderate quantity of alcohol was examined with respect to the equilibrium in 30 healthy subjects. The blood alcohol concentration (BAC) was measured 30 min after the ingestion of the last alcohol, ranging between 0.22 and 1.59 per thousand. Stability of stance was quantified by static platform posturography in Romberg-test conditions with eyes open and eyes closed. Among other parameters, the average body sway path (SP) and area of body sway (SA) were assessed. Posturography revealed a significant increase in body sway. There was a positive correlation between SA (or SP) and BAC both with eyes open and eyes closed. Multiple group comparisons revealed that the large-alcohol-dose group (BAC > or = 1.0 per thousand) could be clearly differentiated from test cases with BAC lower than 0.8 per thousand. Sway area was the most sensitive parameter for detecting increased body sway after alcohol ingestion. The area increase, present not only with eyes closed but with eyes open, revealed an inadequate compensation of the ethanol-induced ataxia by visual stabilization. The Romberg's quotient, which denotes eyes closed relative to eyes open, remained constant. The increase in sway path with eyes closed showed an omnidirectional sway. A comparison of the sway pattern of subjects after acute ethanol ingestion with the data of patients with permanent cerebellar lesions suggested that the acute effect of alcohol resembles that of a lesion of the spinocerebellum. This finding contrasts with earlier studies, which postulated an acute effect of ethanol resembling that in patients with an atrophy of the anterior lobe of the cerebellum due to chronic alcohol abuse. In seven cases of the lower dose group (BAC < or = 0.8 per thousand), a reduction in body sway after alcohol ingestion was

[Relationship between alcohol dependence and new detected hypertension in adult residents of Xuzhou city].

PubMed

Dong, Zongmei; Lou, Pei'an; Zhang, Pan; Chen, Peipei; Qiao, Cheng; Li, Ting

2015-12-01

To observe the relationship between alcohol dependence and new detected hypertension in adult residents of Xuzhou city. Participants were sampled by stratified multi-stage randomly cluster sampling method from February 2013 to June 2013 among permanent residents aged 18 and more in Xuzhou city. The alcohol dependence was defined with Michigan Alcoholism Screening Test (MAST). Other information was obtained by questionnaire. Spearman correlation analysis and multivariate logistic regression analysis were performed to identify the relationship between alcohol dependence and new detected hypertension. The alcohol dependence rate was 11.56% on the whole cohort (n=36 157), and 22.02%(3 854/17 501) for male and 1.74%(324/18 656) for female(P<0.01). The new detected hypertension rate was 9.46%(3 422/36 157) in the whole cohort. The new detected hypertension rate increased in proportion with the severity of alcohol dependence (P<0.01). Spearman correlation analysis showed that alcohol dependence was positively correlated with systemic blood pressure(r=0.071, P<0.01) and diastolic blood pressure (r=0.077, P<0.01). After adjusting for gender, age, marital status, body mass index, smoking status, physical activity level, educational level, income level and region, multivariate logistic regression analysis showed that alcohol dependence was an independent risk factor for hypertension (low alcohol dependence: OR=1.44, 95%CI 1.14-1.81, P<0.01; light alcohol dependence: OR=1.35, 95%CI 1.11-1.64, P<0.01; medium alcohol dependence: OR=1.83, 95%CI 1.40-2.41, P<0.01). The alcohol dependence is an independent risk factor for new detected hypertension in adult residents of Xuzhou city. Intensive hypertension prevention and treatment strategies should be performed on this population based on our results.

Ways of problem solving as predictors of relapse in alcohol dependent male inpatients.

PubMed

Demirbas, Hatice; Ilhan, Inci Ozgur; Dogan, Yildirim Beyatli

2012-01-01

The purpose of this study was to identify how remitters and relapsers view their everyday problem solving strategies. A total of 128 male alcohol dependent male inpatients who were hospitalized at the Ankara University Psychiatry Clinic, Alcohol and Substance Abuse Treatment Unit were recruited for the study. Subjects demographic status and alcohol use histories were assessed by a self-report questionnaire. Also, patients were evaluated with The Coopersmith Self-esteem Inventory (CSI), The Spielberger State-Trait Anxiety Scale (STAI-I-II), and The Problem Solving Inventory (PSI). Patients were followed for six months with monthly intervals after hospital discharge. Drinking status was assessed in terms of abstinence and relapse. Data were assessed with Student t-test, and univariate and multivariate analyses. In the logistic regression analysis, age, marital status, employment status and PSI subscores were taken as the independent variables and drinking state at the end of six months as the dependent variable. There were significant differences in reflective and avoidant styles, and monitoring style of problem solving between abstainers and relapses. It was found that subjects who perceived their problem solving style as less avoidant and less reflective were at greater risk to relapse. The findings demonstrated that active engagement in problem solving like utilizing avoidant and reflective styles of problem solving enhances abstinence. In treatment, expanding the behavior repertoire and increasing the variety of ways of problem solving ways that can be utilized in daily life should be one of the major goals of the treatment program. Copyright © 2011 Elsevier Ltd. All rights reserved.

Perceived barriers to quitting smoking among alcohol dependent patients in treatment.

PubMed

Asher, Marilyn K; Martin, Rosemarie A; Rohsenow, Damaris J; MacKinnon, Selene Varney; Traficante, Regina; Monti, Peter M

2003-03-01

Little is known about the perceived barriers to quitting smoking among alcohol abusers. In addition to the usual barriers perceived by smokers, alcohol dependent smokers may have a few barriers unique to their addictive lifestyle. The Barriers to Quitting Smoking in Substance Abuse Treatment (BQS-SAT) was administered to 96 alcohol dependent smokers in residential substance abuse treatment. The BQS-SAT is designed to assess perceived barriers to quitting smoking among alcohol abusers using eleven true-false items. One open-ended item was included to gather information about potential additional barriers. The majority of respondents reported withdrawal-related barriers such as expecting to feel irritable, anxious, restless, and about half expected intolerable urges to smoke if they were to quit smoking, as most smokers do. However, concerns about effects on sobriety and needing cigarettes to cope with feeling down were also endorsed by almost half of the patients. Total number of perceived barriers was significantly related to smoking history, expected effects from smoking, and smoking temptation but was not associated with severity of alcohol use or dependence on admission. Providing corrective feedback about these barriers could be useful when addressing smoking with patients who have alcohol abuse or dependence.

Cognitive barriers to readiness to change in alcohol-dependent patients.

PubMed

Le Berre, Anne-Pascale; Vabret, François; Cauvin, Céline; Pinon, Karine; Allain, Philippe; Pitel, Anne-Lise; Eustache, Francis; Beaunieux, Hélène

2012-09-01

Patients' personal investment and readiness to change have proved to be a prerequisite for the successful treatment of alcohol addiction. The aim of this study was to determine the contribution of cognitive functions to the motivation process to abandon maladjusted behavior in favor of a healthier lifestyle. An adapted version of the "readiness to change" questionnaire was completed by 31 alcohol-dependent patients after detoxification and at alcohol treatment entry. This tool is designed to assess the 3 main stages of motivation to change regarding alcohol consumption: precontemplation (substance abuse and no intention to stop drinking), contemplation (strong intention to change habits but ambivalent behavior), and action (cessation of excessive alcohol consumption and behavioral changes for healthier habits) stages. Patients and 37 healthy controls also underwent an extensive neuropsychological battery including episodic memory, metamemory, executive functions, and decision-making assessment. When alcohol-dependent patients were considered as a group, the mean score on the action subscale was significantly higher than the precontemplation and contemplation ones. Nevertheless, when the stage of change reached by each patient was considered individually, we found that some alcohol-dependent patients were still in the earlier precontemplation and contemplation stages. Stepwise regression analysis revealed links between impaired memory and executive functions and low motivation, and between good decision-making skills and high motivation. Our results suggest that a set of complementary cognitive abilities is needed to achieve awareness and resolve ambivalence toward alcohol addiction, which is essential for activating the desire to change problematic behavior. Copyright © 2012 by the Research Society on Alcoholism.

Elemental analysis of fingernail of alcoholic and doping subjects by laser-induced breakdown spectroscopy

NASA Astrophysics Data System (ADS)

Bahreini, M.; Ashrafkhani, B.; Tavassoli, S. H.

2014-03-01

Laser-induced breakdown spectroscopy (LIBS) is applied to investigate the effect of alcoholism and doping on elemental composition of fingernails of subjects. Measurements are made on 36 fingernail clippings including 8 doping, 8 alcoholic and 20 normal subjects. Classification of normal, alcoholic and doping subjects based on 46 atomic and ionic emission lines belonging to 13 elements of fingernail is examined using discriminant function analysis (DFA) method. The most affecting elements in classification of groups are discussed. In order to improve the repeatability of LIBS measurements, an auto-focus system has been designed and used in experiments. Results are promising and show that by improving the repeatability of experiments through improving the setup, some evidence of the impact of the alcohol and doping on elemental composition of fingernails is observed.

Safer-drinking Strategies Used by Chronically Homeless Individuals with Alcohol Dependence

PubMed Central

Grazioli, Véronique S.; Hicks, Jennifer; Kaese, Greta; Lenert, James; Collins, Susan E.

2015-01-01

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. PMID:25690515

The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity: within-family association and linkage analyses.

PubMed

Matthews, Abigail G; Hoffman, Eric K; Zezza, Nicholas; Stiffler, Scott; Hill, Shirley Y

2007-09-01

The genes encoding the gamma-aminobutyric acid(A) (GABA(A)) receptor have been the focus of several recent studies investigating the genetic etiology of alcohol dependence. Analyses of multiplex families found a particular gene, GABRA2, to be highly associated with alcohol dependence, using within-family association tests and other methods. Results were confirmed in three case-control studies. The objective of this study was to investigate the GABRA2 gene in another collection of multiplex families. Analyses were based on phenotypic and genotypic data available for 330 individuals from 65 bigenerational pedigrees with a total of 232 alcohol-dependent subjects. A proband pair of same-sex siblings meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence was required for entry of a family into the study. One member of the proband pair was identified while in treatment for alcohol dependence. Linkage and association of GABRA2 and alcohol dependence were evaluated using SIBPAL (a nonparametric linkage package) and both the Pedigree Disequilibrium Test and the Family-Based Association Test, respectively. We find no evidence of a relationship between GABRA2 and alcohol dependence. Linkage analyses exhibited no linkage using affected/affected, affected/unaffected, and unaffected/unaffected sib pairs (all p's < .13). There was no evidence of a within-family association (all p's > .39). Comorbidity may explain why our results differ from those in the literature. The presence of primary drug dependence and/or other psychiatric disorders is minimal in our pedigrees, although several of the other previously published multiplex family analyses exhibit a greater degree of comorbidity.

Obtaining the Optimal Dose in Alcohol Dependence Studies

PubMed Central

Wages, Nolan A.; Liu, Lei; O’Quigley, John; Johnson, Bankole A.

2012-01-01

In alcohol dependence studies, the treatment effect at different dose levels remains to be ascertained. Establishing this effect would aid us in identifying the best dose that has satisfactory efficacy while minimizing the rate of adverse events. We advocate the use of dose-finding methodology that has been successfully implemented in the cancer and HIV settings to identify the optimal dose in a cost-effective way. Specifically, we describe the continual reassessment method (CRM), an adaptive design proposed for cancer trials to reconcile the needs of dose-finding experiments with the ethical demands of established medical practice. We are applying adaptive designs for identifying the optimal dose of medications for the first time in the context of pharmacotherapy research in alcoholism. We provide an example of a topiramate trial as an illustration of how adaptive designs can be used to locate the optimal dose in alcohol treatment trials. It is believed that the introduction of adaptive design methods will enable the development of medications for the treatment of alcohol dependence to be accelerated. PMID:23189064

An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

PubMed Central

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

2016-01-01

Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644

Genetic overlap between impulsivity and alcohol dependence: a large-scale national twin study.

PubMed

Khemiri, L; Kuja-Halkola, R; Larsson, H; Jayaram-Lindström, N

2016-04-01

Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity. Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985. The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31-57%] for males and 62% (95% CI 52-72%) for females. For impulsivity, the heritability was 33% (95% CI 30-36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23-0.58) in males and 0.20 (95% CI 0.07-0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47-117%) for males and 53% (95% CI 19-86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors. The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour.

Gabapentin treatment for alcohol dependence: a randomized clinical trial.

PubMed

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

2014-01-01

Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics. To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner. A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital. Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling. Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study. RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups. Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia

Dissociable Patterns in the Control of Emotional Interference in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and in Adults with Alcohol Dependence

PubMed Central

Marx, Ivo; Krause, John; Berger, Christoph; Häßler, Frank

2014-01-01

Objectives To effectively manage current task demands, attention must be focused on task-relevant information while task-irrelevant information is rejected. However, in everyday life, people must cope with emotions, which may interfere with actual task demands and may challenge functional attention allocation. Control of interfering emotions has been associated with the proper functioning of the dorsolateral prefrontal cortex (DLPFC). As DLPFC dysfunction is evident in subjects with ADHD and in subjects with alcohol dependence, the current study sought to examine the bottom-up effect of emotional distraction on task performance in both disorders. Methods Male adults with ADHD (n = 22), male adults with alcohol dependence (n = 16), and healthy controls (n = 30) performed an emotional working memory task (n-back task). In the background of the task, we presented neutral and negative stimuli that varied in emotional saliency. Results In both clinical groups, a working memory deficit was evident. Moreover, both clinical groups displayed deficient emotional interference control. The n-back performance of the controls was not affected by the emotional distractors, whereas that of subjects with ADHD deteriorated in the presence of low salient distractors, and that of alcoholics did not deteriorate until high salient distractors were presented. Subsequent to task performance, subjects with ADHD accurately recognized more distractors than did alcoholics and controls. In alcoholics, picture recognition accuracy was negatively associated with n-back performance, suggesting a functional association between the ability to suppress emotional distractors and successful task performance. In subjects with ADHD, performance accuracy was negatively associated with ADHD inattentive symptoms, suggesting that inattention contributes to the performance deficit. Conclusions Subjects with ADHD and alcoholics both display an emotional interference control deficit, which is

Decreased subcortical volumes in alcohol dependent individuals: effect of polysubstance use disorder.

PubMed

Grodin, Erica N; Momenan, Reza

2017-09-01

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Cessation of Alcohol Consumption Decreases Rate of Nicotine Metabolism In Male Alcohol-Dependent Smokers#

PubMed Central

Gubner, Noah R.; Kozar-Konieczna, Aleksandra; Szoltysek-Boldys, Izabela; Slodczyk-Mankowska, Ewa; Goniewicz, Jerzy; Sobczak, Andrzej; Jacob, Peyton; Benowitz, Neal L.; Goniewicz, Maciej L.

2016-01-01

Background Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. Methods Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). Results and conclusions There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6 ± 1.3 vs. 4.1 ± 0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increases the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population. PMID:27107849

Cessation of alcohol consumption decreases rate of nicotine metabolism in male alcohol-dependent smokers.

PubMed

Gubner, Noah R; Kozar-Konieczna, Aleksandra; Szoltysek-Boldys, Izabela; Slodczyk-Mankowska, Ewa; Goniewicz, Jerzy; Sobczak, Andrzej; Jacob, Peyton; Benowitz, Neal L; Goniewicz, Maciej L

2016-06-01

Rate of nicotine metabolism is an important factor influencing cigarette smoking behavior, dependence, and efficacy of nicotine replacement therapy. The current study examined the hypothesis that chronic alcohol abuse can accelerate the rate of nicotine metabolism. Nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism) and patterns of nicotine metabolites were assessed at three time points after alcohol cessation. Participants were 22 Caucasian men randomly selected from a sample of 165 smokers entering a 7-week alcohol dependence treatment program in Poland. Data were collected at three time points: baseline (week 1, after acute alcohol detoxification), week 4, and week 7. Urine was analyzed for nicotine and metabolites and used to determine the nicotine metabolite ratio (NMR, a biomarker for rate of nicotine metabolism), and total nicotine equivalents (TNE, a biomarker for total daily nicotine exposure). There was a significant decrease in urine NMR over the 7 weeks after alcohol abstinence (F(2,42)=18.83, p<0.001), indicating a decrease in rate of nicotine metabolism. On average NMR decreased 50.0% from baseline to week 7 (9.6±1.3 vs 4.1±0.6). There was no change in urine TNE across the three sessions, indicating no change daily nicotine intake. The results support the idea that chronic alcohol abuse may increase the rate of nicotine metabolism, which then decreases over time after alcohol cessation. This information may help to inform future smoking cessation interventions in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reminiscence therapy using odor in alcohol-dependent patients--psychophysiological evaluation and psychological evaluation; power spectral analysis of heart rate variability.

PubMed

Arizono, H; Morita, N; Iizuka, S; Satoh, S; Nakatani, Y

2000-12-01

This research was based on the hypothesis that when alcohol-dependent patients describe themselves, awakening of emotion by affirmative odor stimulation may facilitate memory reframing focusing on more affirmative emotion and memories. To prove the hypothesis, physiological changes accompanied by emotional awakening were evaluated by measuring the autonomic activity. In addition, subjective evaluation by a self-report manner was examined to investigate the effectiveness of Reminiscence Therapy (RT) using odor in alcohol-dependent patients. Thirty-four patients who met the DSM-IV criteria of alcohol-related disorders and were hospitalized in a ward specialized to alcohol dependence therapy. Each patient underwent a one-to-one interview twice. For counterbalance, one interview was performed with odor stimulation using an odor with a relaxing effect that recall pleasant emotion, and the other was without odor stimulation. As the evaluation indices of physiological changes accompanied by emotional awakening, index of autonomic function (HRV; Heart rate variability) for objective evaluation and psychological indices (STAI; State-Trait Anxiety Inventory VAS; Visual Analog Scale) for subjective evaluation were measured. 1) Objective evaluation: Regarding the evaluation index of the autonomic function, the sympathetic nervous system activity (LF/HF; low frequency component/high frequency component ratio) was significantly inhibited by odor stimulation (p < 0.05). 2) Subjective evaluation: Compared to the state prior to interview, state anxiety judged by STAI was significantly decreased after interview (p < 0.01). The VAS score was significantly decreased after interview regardless of the presence or absence of odor stimulation (p < 0.0001). A reduction in state anxiety was observed. The effect of odor was not significant on the subjective evaluation, but the objective evaluation suggested that the odor inhibited the sympathetic nervous system. Thus, it was suggested that

The risk for persistent adult alcohol and nicotine dependence: the role of childhood maltreatment.

PubMed

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 S

2014-05-01

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. Physical, sexual and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over 3 years of follow-up, with and without control for other childhood adversities. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n = 1172) and nicotine dependence (n = 4017). 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). Controlling for demographics only, physical, sexual and emotional abuse and physical neglect predicted 3-year persistence of alcohol dependence [adjusted odds ratio (AOR) = 1.50-2.99; 95% CI = 1.04-4.68] and nicotine dependence (AOR = 1.37-1.74; 95% CI = 1.13-2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AOR = 1.53-3.02; 95% CI = 1.07-4.71) and nicotine persistence (AOR = 1.35-1.72; 95% CI = 1.11-2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AOR = 1.19-1.36; 95% CI = 1.11-1.56). 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 dependence. © 2014 Society for the Study of Addiction.

Adjunctive aripiprazole therapy with escitalopram in patients with co-morbid major depressive disorder and alcohol dependence: Clinical and neuroimaging evidence

PubMed Central

Han, Doug Hyun; Kim, Sun Mi; Choi, Jung Eun; Min, Kyung Joon; Renshaw, Perry F.

2015-01-01

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

Impact of Social Cognition on Alcohol Dependence Treatment Outcome: Poorer Facial Emotion Recognition Predicts Relapse/Dropout.

PubMed

Rupp, Claudia I; Derntl, Birgit; Osthaus, Friederike; Kemmler, Georg; Fleischhacker, W Wolfgang

2017-12-01

Despite growing evidence for neurobehavioral deficits in social cognition in alcohol use disorder (AUD), the clinical relevance remains unclear, and little is known about its impact on treatment outcome. This study prospectively investigated the impact of neurocognitive social abilities at treatment onset on treatment completion. Fifty-nine alcohol-dependent patients were assessed with measures of social cognition including 3 core components of empathy via paradigms measuring: (i) emotion recognition (the ability to recognize emotions via facial expression), (ii) emotional perspective taking, and (iii) affective responsiveness at the beginning of inpatient treatment for alcohol dependence. Subjective measures were also obtained, including estimates of task performance and a self-report measure of empathic abilities (Interpersonal Reactivity Index). According to treatment outcomes, patients were divided into a patient group with a regular treatment course (e.g., with planned discharge and without relapse during treatment) or an irregular treatment course (e.g., relapse and/or premature and unplanned termination of treatment, "dropout"). Compared with patients completing treatment in a regular fashion, patients with relapse and/or dropout of treatment had significantly poorer facial emotion recognition ability at treatment onset. Additional logistic regression analyses confirmed these results and identified poor emotion recognition performance as a significant predictor for relapse/dropout. Self-report (subjective) measures did not correspond with neurobehavioral social cognition measures, respectively objective task performance. Analyses of individual subtypes of facial emotions revealed poorer recognition particularly of disgust, anger, and no (neutral faces) emotion in patients with relapse/dropout. Social cognition in AUD is clinically relevant. Less successful treatment outcome was associated with poorer facial emotion recognition ability at the beginning of

Child physical and sexual abuse: a comprehensive look at alcohol consumption patterns, consequences, and dependence from the National Alcohol Survey.

PubMed

Lown, E Anne; Nayak, Madhabika B; Korcha, Rachael A; Greenfield, Thomas K

2011-02-01

Previous research has documented a relationship between child sexual abuse and alcohol dependence. This paper extends that work by providing a comprehensive description of past year and lifetime alcohol consumption patterns, consequences, and dependence among women reporting either physical and sexual abuse in a national sample. This study used survey data from 3,680 women who participated in the 2005 U.S. National Alcohol Survey. Information on physical and sexual child abuse and its characteristics were assessed in relation to 8 past year and lifetime alcohol consumption measures. Child physical or sexual abuse was significantly associated with past year and lifetime alcohol consumption measures. In multivariate analyses, controlling for age, marital status, employment status, education, ethnicity, and parental alcoholism or problem drinking, women reporting child sexual abuse vs. no abuse were more likely to report past year heavy episodic drinking (OR(adj) = 1.7; 95% CI 1.0 to 2.9), alcohol dependence (OR(adj) = 7.2; 95% CI 3.2 to 16.5), and alcohol consequences (OR(adj) = 3.6; 95% CI 1.8 to 7.3). Sexual abuse (vs. no abuse) was associated with a greater number of past year drinks (124 vs. 74 drinks, respectively, p = 0.002). Sexual child abuse was also associated with lifetime alcohol-related consequences (OR(adj) = 3.5; 95% CI 2.6 to 4.8) and dependence (OR(adj) = 3.7; 95% CI 2.6 to 5.3). Physical child abuse was associated with 4 of 8 alcohol measures in multivariate models. Both physical and sexual child abuse were associated with getting into fights, health, legal, work, and family alcohol-related consequences. Alcohol-related consequences and dependence were more common for women reporting sexual abuse compared to physical abuse, 2 or more physical abuse perpetrators, nonparental and nonfamily physical abuse perpetrators, and women reporting injury related to the abuse. Both child physical and sexual abuse were associated with many alcohol outcomes in

Does sexual self-concept ambiguity moderate relations among perceived peer norms for alcohol use, alcohol-dependence symptomatology, and HIV risk-taking behavior?

PubMed

Talley, Amelia E; Brown, Jennifer L; Stevens, Angela K; Littlefield, Andrew K

2014-11-01

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. 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. 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. 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.

The relation of autonomic function to physical fitness in patients suffering from alcohol dependence.

PubMed

Herbsleb, Marco; Schulz, Steffen; Ostermann, Stephanie; Donath, Lars; Eisenträger, Daniela; Puta, Christian; Voss, Andreas; Gabriel, Holger W; Bär, Karl-Jürgen

2013-10-01

Reduced cardio-vascular health has been found in patients suffering from alcohol dependence. Low cardio-respiratory fitness is an independent predictor of cardio-vascular disease. We investigated physical fitness in 22 alcohol-dependent patients 10 days after acute alcohol withdrawal and compared results with matched controls. The standardized 6-min walk test (6 MWT) was used to analyze the relationship of autonomic dysfunction and physical fitness. Ventilatory indices and gas exchanges were assessed using a portable spiroergometric system while heart rate recordings were obtained separately. We calculated walking distance, indices of heart rate variability and efficiency parameters of heart rate and breathing. In addition, levels of exhaled carbon monoxide were measured in all participants to account for differences in smoking behaviour. Multivariate analyses of variance (MANOVA) were performed to investigate differences between patients and controls with regard to autonomic and efficiency parameters. Patients walked a significantly shorter distance in comparison to healthy subjects during the 6 MWT. Significantly decreased heart rate variability was observed before and after the test in patients when compared to controls, while no such difference was observed during exercise. The efficiency parameters indicated significantly reduced efficiency in physiological regulation when the obtained parameters were normalized to the distance. The 6 MWT is an easily applied instrument to measure physical fitness in alcohol dependent patients. It can also be used during exercise interventions. Reduced physical fitness, as observed in our study, might partly be caused by autonomic dysfunction, leading to less efficient regulation of physiological processes during exercise. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mapping the maintenance stage of recovery: a qualitative study among treated and non-treated former alcohol dependents in Poland.

PubMed

Klingemann, Justyna Iwona

2012-01-01

The study provides an in-depth qualitative understanding of the maintenance stage when recovering from alcohol dependence with a focus on the broader social context of change of addictive behaviour. It explores the recovery as a subjective process within the abstinence-oriented Polish treatment system organized on the basis of the Minnesota model and is probes for group differences between treated and non-treated populations. The study is based on qualitative data from a media-recruited sample of 29 treated and non-treated former alcohol dependents (ICD-10) in Warsaw/Poland 2006/2007. They reported a recovery time of at least 2 years (M(recovery) = 11, SD = 9). In-depth, semi-structured interviews were analysed according to the problem-centred interview method using ATLAS.ti software. A wide range of maintenance strategies potentially contributing to the stabilization of recovery from alcohol dependence was identified. However, from the respondents' point of view, the change process is contingent upon the subjective weighing of specific maintenance factors and the importance attributed to their interplay. This includes time management as well as one's ability to invest available resources and strengths in shaping and pursuing personal goals. More commonalities than differences can be observed between groups during the maintenance stage, regardless of respondents' type of the pathway out of addiction. However, when confronting professional concepts of recovery with subjective accounts, only a subgroup conforms to the invasive, potentially normative definitions of recovery, while others do not link their recovery with identity transformation.

Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent

PubMed Central

Winham, Stacey J.; Preuss, Ulrich W.; Geske, Jennifer R.; Zill, Peter; Heit, John A.; Bakalkin, Georgy; Biernacka, Joanna M.; Karpyak, Victor M.

2015-01-01

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

Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent.

PubMed

Winham, Stacey J; Preuss, Ulrich W; Geske, Jennifer R; Zill, Peter; Heit, John A; Bakalkin, Georgy; Biernacka, Joanna M; Karpyak, Victor M

2015-10-27

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.

Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

PubMed

Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

2017-05-01

According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

Deficient inhibition in alcohol-dependence: let's consider the role of the motor system!

PubMed

Quoilin, Caroline; Wilhelm, Emmanuelle; Maurage, Pierre; de Timary, Philippe; Duque, Julie

2018-04-26

Impaired inhibitory control contributes to the development, maintenance, and relapse of alcohol-dependence, but the neural correlates of this deficit are still unclear. Because inhibitory control has been labeled as an executive function, most studies have focused on prefrontal areas, overlooking the contribution of more "primary" structures, such as the motor system. Yet, appropriate neural inhibition of the motor output pathway has emerged as a central aspect of healthy behavior. Here, we tested the hypothesis that this motor inhibition is altered in alcohol-dependence. Neural inhibitory measures of motor activity were obtained in 20 detoxified alcohol-dependent (AD) patients and 20 matched healthy subjects, using a standard transcranial magnetic stimulation procedure whereby motor-evoked potentials (MEPs) are elicited in a choice reaction time task. Moreover, behavioral inhibition and trait impulsivity were evaluated in all participants. Finally, the relapse status of patients was assessed 1 year after the experiment. As expected, AD patients displayed poorer behavioral inhibition and higher trait impulsivity than controls. More importantly, the MEP data revealed a considerable shortage of neural motor inhibition in AD patients. Interestingly, this neural defect was strongest in the patients who ended up relapsing during the year following the experiment. Our data suggest a strong motor component in the neural correlates of altered inhibitory control in AD patients. They also highlight an intriguing relationship with relapse and the perspective of a new biomarker to follow strategies aiming at reducing relapse in AD patients.

Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

PubMed

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

2008-04-01

Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (< 14 drinks per week) paid volunteers recruited through advertisements at an academic center. A taste of alcohol and a series of alcohol-related pictures, neutral beverage pictures, and visual control images were provided to volunteers after 7 days of double-blind randomly assigned daily dosing with 50 mg of naltrexone (n = 23), 0.50 mg of ondansetron hydrochloride (n = 23), the combination of the 2 medications (n = 20), or matching placebos (n = 24). Difference in brain blood oxygen level-dependent magnetic resonance when viewing alcohol pictures vs neutral beverage pictures with a particular focus on ventral striatum activity comparison across medication groups. Self-ratings of alcohol craving. The combination treatment decreased craving for alcohol. Naltrexone with (P = .02) or without (P = .049) ondansetron decreased alcohol cue-induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination

Does Sexual Self-Concept Ambiguity Moderate Relations Among Perceived Peer Norms for Alcohol Use, Alcohol-Dependence Symptomatology, and HIV Risk-Taking Behavior?

PubMed Central

Talley, Amelia E; Brown, Jennifer L; Stevens, Angela K; Littlefield, Andrew K

2014-01-01

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

Childhood trauma and dissociation in patients with alcohol dependence, drug dependence, or both-A multi-center study.

PubMed

Schäfer, Ingo; Langeland, Willemien; Hissbach, Johanna; Luedecke, Christel; Ohlmeier, Martin D; Chodzinski, Claudia; Kemper, Ulrich; Keiper, Peter; Wedekind, Dirk; Havemann-Reinecke, Ursula; Teunissen, Sybille; Weirich, Steffen; Driessen, Martin

2010-06-01

The aims of this study were to examine the level of dissociative symptoms in patients with different substance related disorders (alcohol dependence, drug dependence, and combined alcohol and drug dependence), and to investigate the influence of potentially traumatic events in childhood, age, gender, and posttraumatic stress disorder on the relationship between dissociative symptoms and type of substance abuse. Of the 459 participants (59.7% male) 182 (39.7%) were alcohol-dependent (A), 154 (33.6%) were drug-dependent (D), and 123 (26.8%) were dependent on both, alcohol and drugs (AD) based on the DSM-IV criteria for a current diagnosis. Participants completed the Childhood Trauma Questionnaire (CTQ) and the Dissociative Experiences Scale (DES). The International Diagnostics Checklist (IDCL) was administered to diagnose PTSD. Higher levels of dissociation were observed in patients with drug dependence as compared to patients with mere alcohol dependence (mean DES group A: 9.9+/-8.8; group D: 12.9+/-11.7; group AD: 15.1+/-11.3). However, when severity of potentially traumatic events in childhood, PTSD, age and gender were included in the analysis, the influence of the type of substance abuse did not prove to be statistically significant. The variable most strongly related to dissociative symptoms was severity of potentially traumatic events in childhood, in particular emotional abuse, even after controlling for PTSD and other potential confounders. It seems appropriate to screen SUD patients for dissociative symptoms, especially those with a more complex risk profile including (additional) drug abuse, female gender, younger age and most importantly a history of childhood trauma. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Targeting Dynorphin/Kappa Opioid Receptor Systems to Treat Alcohol Abuse and Dependence

PubMed Central

Walker, Brendan M.; Valdez, Glenn R.; McLaughlin, Jay P.; Bakalkin, Georgy

2012-01-01

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

An empowerment process: successful recovery from alcohol dependence.

PubMed

Yeh, Mei-Yu; Che, Hui-Lian; Lee, Li-Wei; Horng, Fen-Fang

2008-04-01

The purpose of this study was to explore the concepts and processes for successful abstinence from alcohol for Taiwanese Alcoholics Anonymous members. Attempting to identify the psychological and social influences upon alcohol consumption remission outside of alcoholism treatment could help professionals to engage in a broad array of community interventions in an informed fashion. Grounded theory method was utilized in this study. The study chose nine participants who had succeeded in abstinence, using theoretical sampling and conducted in-depth interviews by an open-ended questionnaire. The results of this study indicated that the core of the process during which alcoholic individuals succeeded in abstaining from further alcohol consumption was an empowerment process for the involved individual. Alcoholics felt that their family, interpersonal relationships, jobs and personal finances all had been at 'rock-bottom' level following a long period of alcohol dependence. This feeling caused the individual to experience an emotion of a loss of control and provoked the arousal of an alcoholic's inner consciousness levels, this then resulting in the generation of a driving force for abstinence from alcohol for these individuals. The expansion of an individual's internal awakening power helps the individual to obtain assistance and to resist the temptation of further alcohol consumption. Therefore, the power derived by individuals from the stages of repositioning, releasing, active sharing, resistance and assistance are the maintenance factors for an individual's empowerment process that help maintain the successful recovery from alcohol for the involved individual. A good comprehension of the recovery processes for alcoholics, we believe, will trigger clinical professionals to pay appropriate attention to the specific problems and needs of alcoholic individuals, to build an effective resource network for treatment and to help solve alcoholics' physical and psychosocial

Effects of alcohol and energy drink on mood and subjective intoxication: a double-blind, placebo-controlled, crossover study.

PubMed

Benson, Sarah; Scholey, Andrew

2014-07-01

There is concern that combining energy drinks with alcohol may 'mask' subjective intoxication leading to greater alcohol consumption. This study examines the effects of alcohol alone and combined with energy drink on objective and subjective intoxication and mood over the course of 3 h. Using a double-blind, placebo-controlled, balanced, crossover design, 24 participants (mean age 22.23 years) were administered with double placebo, 0.6 g/kg alcohol (mean peak blood alcohol content of 0.051%), 250 ml energy drink and alcohol/energy drink, according to a Latin square design, with a washout of >48 h. On each visit, they were breathalysed and rated themselves on a comprehensive battery of mood items at baseline and then at 45, 90 and 180 min post-drink. Blood alcohol and subjective intoxication were significantly increased following both alcohol alone and alcohol/energy drink. Both measures were statistically indistinguishable between alcohol conditions. In keeping with its (80 mg) caffeine content, the energy drink alone significantly increased self-rated 'alertness' and reduced 'depression-dejection' scores compared with the combined alcohol/energy drink. The alcohol/energy drink increased 'vigor' and 'contentment' at 45 min and decreased 'contentment' at 180 min. The co-ingestion of an energy drink with alcohol does not differently influence blood alcohol content recordings or subjective intoxication compared with alcohol alone, although some mood items are differentially affected. Copyright © 2014 John Wiley & Sons, Ltd.

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

PubMed Central

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

2015-01-01

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

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

ERIC Educational Resources Information Center

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

1998-01-01

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

Polymorphisms of the mu-opioid receptor and dopamine D4 receptor genes and subjective responses to alcohol in the natural environment.

PubMed

Ray, Lara A; Miranda, Robert; Tidey, Jennifer W; McGeary, John E; MacKillop, James; Gwaltney, Chad J; Rohsenow, Damaris J; Swift, Robert M; Monti, Peter M

2010-02-01

Polymorphisms of the mu-opioid receptor (OPRM1) and dopamine D4 receptor (DRD4) genes are associated with subjective responses to alcohol and urge to drink under laboratory conditions. This study examined these associations in the natural environment using ecological momentary assessment. Participants were non-treatment-seeking heavy drinkers (n = 112, 52% female, 61% alcohol dependent) who enrolled in a study of naltrexone effects on craving and drinking in the natural environment. Data were culled from 5 consecutive days of drinking reports prior to medication randomization. Analyses revealed that, after drinking, carriers of the Asp40 allele of the OPRM1 gene reported higher overall levels of vigor and lower levels negative mood, as compared to homozygotes for the Asn40 variant. Carriers of the long allele (i.e., >or=7 tandem repeats) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele. Effects of OPRM1 and DRD4 variable-number-of-tandem-repeats genotypes appear to be alcohol dose-dependent. Specifically, carriers of the DRD4-L allele reported slight decreases in urge to drink at higher levels of estimated blood alcohol concentration (eBAC), and Asp40 carriers reported decreases in vigor and increases in negative mood as eBAC rose, as compared to carriers of the major allele for each gene. Self-reported vigor and urge to drink were positively associated with alcohol consumption within the same drinking episode. This study extends findings on subjective intoxication, urge to drink, and their genetic bases from controlled laboratory to naturalistic settings.

Complementary medicine for alcohol dependence in Italian services: a mail questionnaire.

PubMed

Bardazzi, Gabriele; Merluzzi, Jo-Anne; Voller, Fabio; Fontana, Aldo; Abenavoli, Ludovico; Leggio, Lorenzo; Addolorato, Giovanni

2006-08-01

It is well known that Complementary Medicine (CM) is extensively used in western countries for the treatment of many afflictions. CM has been recently promoted in addiction treatment. To evaluate CM use in alcohol dependence we planned a mail questionnaire for Italian alcohol services. We sent out 612 questionnaires. Health services that were unable to respond to the questionnaire within a 20-day limit period were contacted by phone and if we obtained agreement to participate in the study the questionnaire was sent by fax. We obtained 312 (51.82%) completed questionnaires. Only 16.50% of Italian services use CM for alcohol dependence treatment and acupuncture is utilized more frequently than other methods (phytotherapy, homeopathy, etc.). In Italian alcohol services CM is identified as an instrument incorporated into traditional alcohol treatments (self-help groups, drug treatment, etc.) and not an alternative method. In fact, health services that use it as a principal method of treatment were a rare event in our study (1%). CM plays an integrated role with traditional forms of alcohol treatment in Italian alcohol services and this utilization could be useful to reduce drop-outs and improve alcohol treatment compliance.

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

PubMed

Crescentini, Cristiano; Matiz, Alessio; Fabbro, Franco

2015-01-01

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

An Event-Level Examination of Sex Differences and Subjective Intoxication in Alcohol-Related Aggression

PubMed Central

Quinn, Patrick D.; Stappenbeck, Cynthia A.; Fromme, Kim

2013-01-01

Laboratory-based experimental research has demonstrated that the pharmacological effects of alcohol can increase aggressive responding. Given mixed findings and concerns regarding task validity, however, it remains uncertain whether this effect holds constant across men and women and whether variability in subjective alcohol intoxication contributes to alcohol-related aggression. In the present investigation, we used four years of event-level data in a sample of 1,775 college students (140,618 total observations) to provide a test of laboratory-derived findings on the link between alcohol and aggression in an alternative methodology. We found support for several such findings: 1) Within-person increases in alcohol intoxication, as assessed by estimated blood alcohol concentrations (eBACs), were associated with increases in the probability of aggression at the drinking-episode level; 2) This association was significantly stronger among men than among women; and 3) Within-person variability and between-persons individual differences in levels of subjective alcohol intoxication were associated with aggression over and beyond eBACs. Cross-methodological replication can reduce the impact of constraints specific to experimental studies on conclusions regarding alcohol’s relation with aggression. PMID:23421356

Impulsive suicide attempts predict post-treatment relapse in alcohol-dependent patients.

PubMed

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

2008-10-01

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

Genetic variation of the ghrelin signaling system in females with severe alcohol dependence.

PubMed

Landgren, Sara; Jerlhag, Elisabet; Hallman, Jarmila; Oreland, Lars; Lissner, Lauren; Strandhagen, Elisabeth; Thelle, Dag S; Zetterberg, Henrik; Blennow, Kaj; Engel, Jörgen A

2010-09-01

Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.

Priming deficiency in male subjects at risk for alcoholism: the N4 during a lexical decision task.

PubMed

Roopesh, Bangalore N; Rangaswamy, Madhavi; Kamarajan, Chella; Chorlian, David B; Stimus, Arthur; Bauer, Lance O; Rohrbaugh, John; O'Connor, Sean J; Kuperman, Samuel; Schuckit, Marc; Porjesz, Bernice

2009-12-01

While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics. A semantic priming task was administered to nonalcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n = 23] and nonalcoholic fathers [low risk (LR) n = 28] to study whether the 2 groups differ in terms of the N4 component. Subjects were presented with 150 words and 150 nonwords. Among the words, 50 words (primed) were preceded by their antonyms (prime, n = 50), whereas the remaining 50 words were unprimed. For the analysis, N4 amplitude and latency as well as behavioral measures for the primed and unprimed words were considered. A significant interaction effect was observed between semantic condition and group, where HR subjects did not show N4 attenuation for primed stimuli. The lack of N4 attenuation to primed stimuli and/or inability to differentiate between primed and unprimed stimuli, without latency and reaction time being affected, suggest deficits in semantic priming, especially in semantic expectancy and/or postlexical semantic processing in HR male offspring. Further, it indicates that it might be an electrophysiological endophenotype that reflects genetic vulnerability to develop alcoholism.

Alcohol dependence and domestic violence as sequelae of abuse and conduct disorder in childhood.

PubMed

Kunitz, S J; Levy, J E; McCloskey, J; Gabriel, K R

1998-11-01

To examine in the Navajo population: (1) the importance of childhood abuse as a risk factor for conduct disorder; (2) the importance of each form of abuse and conduct disorder as risk factors for alcohol dependence; and (3) the relative importance of each form of abuse, conduct disorder, and alcohol dependence as risk factors for being a perpetrator and/or victim of domestic violence. The study is based on a case-control design. Cases (204 men and 148 women) between the ages of 21 and 65 were interviewed in alcohol treatment program and matched to community controls. There were two groups of controls: alcohol dependent (374 men, 60 women) and nonalcohol dependent (157 men, 143 women). When adjusted for stratification by age, community of residence, and sex, the combined control groups comprise a representative sample of the Navajo male and female population 21-65 years of age. The prevalence of physical and sexual abuse before age 15 is within limits observed in other populations. Each form of abuse is a risk factor for conduct disorder. Along with conduct disorder, physical abuse is a risk factor for alcohol dependence. Physical abuse and alcohol dependence are independent risk factors for being involved in domestic violence as both perpetrator and victim. There appears to have been no secular trend in the incidence of childhood abuse over the past several generations, but there is suggestive evidence that domestic violence has become more common. Physical abuse is a significant risk factor for alcohol dependence as well as for domestic violence independent of the effects of alcohol abuse. The effects of sexual abuse with regard to both domestic violence and alcohol dependence do not appear to be significant.

Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence.

PubMed

de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F; Hope, Bruce T; Brennan, Molly; Cole, Maury; Koob, George F; George, Olivier

2016-09-07

Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These results identify a

Intensive motivational interviewing for women with concurrent alcohol problems and methamphetamine dependence.

PubMed

Korcha, Rachael A; Polcin, Douglas L; Evans, Kristy; Bond, Jason C; Galloway, Gantt P

2014-02-01

Motivational interviewing (MI) for the treatment of alcohol and drug problems is typically conducted over 1 to 3 sessions. The current work evaluates an intensive 9-session version of MI (Intensive MI) compared to a standard single MI session (Standard MI) using 163 methamphetamine (MA) dependent individuals. The primary purpose of this paper is to report the unexpected finding that women with co-occurring alcohol problems in the Intensive MI condition reduced the severity of their alcohol problems significantly more than women in the Standard MI condition at the 6-month follow-up. Stronger perceived alliance with the therapist was inversely associated with alcohol problem severity scores. Findings indicate that Intensive MI is a beneficial treatment for alcohol problems among women with MA dependence. © 2013.

Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

ERIC Educational Resources Information Center

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

2008-01-01

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

Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?

PubMed

Venkataraman, Ashwin; Kalk, Nicola; Sewell, Gavin; Ritchie, Craig W; Lingford-Hughes, Anne

2017-03-09

To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). Review of the literature using searches of Medline, Pubmed, EMBASE, PsycInfo, and meeting abstracts and presentations. The role of alcohol as a risk factor and contributor for cognitive decline associated with AD has received little attention. This is despite the high prevalence of alcohol use, the potential reversibility of a degree of cognitive impairment and the global burden of AD. Until now the focus has largely been on the toxic effects of alcohol, neuronal loss and the role of thiamine. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. We describe the common underlying neurobiology in alcohol and AD, and examine ways alcohol likely contributes to neuroinflammation directly via stimulation of Toll-like receptors and indirectly from small bowel changes, hepatic changes, withdrawal and traumatic brain injury to the pathogenesis of AD. Alcohol use, misuse and dependence cause cognitive impairment. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

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

PubMed Central

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

2015-01-01

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

CORRELATES OF RECOVERY FROM ALCOHOL DEPENDENCE: A PROSPECTIVE STUDY OVER A 3-YEAR FOLLOW-UP INTERVAL

PubMed Central

Dawson, Deborah A.; Goldstein, Risë B.; Ruan, W. June; Grant, Bridget F.

2011-01-01

Background Correlates of recovery from alcohol dependence have been identified through a variety of study designs characterized by different strengths and limitations. The goal of this study was to compare correlates of recovery based on a 3-year prospective design with those based on cross-sectional analyses of data from the same source. Methods Data from the 2001-2002 Wave 1 and 2004-2005 Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to examine baseline characteristics associated with Wave 2 recovery from alcohol dependence, among those who classified with past-year DSM-IV alcohol dependence at Wave 1 (n=1,172). Results Abstinent recovery (AR) was significantly associated with Black/Asian/Hispanic race/ethnicity, children <1 year of age in the household at baseline, attending religious services ≥weekly at follow-up, and having initiated help seeking that comprised/included 12-step participation within <3 years prior to baseline. Nonabstinent recovery (NR) was positively associated with being never married at baseline, having job problems or being unemployed in the year preceding baseline, attending religious services dependent covariates but differed in many ways from cross-sectional analyses of Wave 1 NESARC. Conclusions Various aspects of study design must be considered when interpreting correlates of recovery. Cross-sectional analyses of lifetime correlates of recovery are highly subject to misinterpretation, but pseudo-prospective survival analyses with time-dependent covariates may yield results as valid as those from prospective studies. PMID:22309217

Evaluation of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in African Americans.

PubMed

Marshall, Vanessa J; Ramchandani, Vijay A; Kalu, Nnenna; Kwagyan, John; Scott, Denise M; Ferguson, Clifford L; Taylor, Robert E

2014-01-01

The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers. The sample included eighty-seven 21- to 35-year-old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates. Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA. ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration

[Use in France of Baclofen for Alcohol Dependence from 2007 to 2013: Cohort Study Based on the Databases SNIIRAM and PMSI].

PubMed

Chaignot, Christophe; Weill, Alain; Ricordeau, Philippe; Alla, François

2015-01-01

To quantify and describe the population starting treatment with baclofen for alcohol dependence during the period 2007-2013 in France. The French national health insurance (système national d'information inter-régimes de l'Assurance maladie [SNIIRAM]) and French hospital discharge (programme de médicalisation des systèmes d'information [PMSI]) databases were used to identify the population starting treatment with baclofen, determine the algorithm of baclofen use, define patient characteristics and their treatment. About 200,000 subjects initiated baclofen therapy between 2007 and 2013, for alcohol dependence in 52.0% of cases. In 2013, this population was predominantly male (62.3%), with a mean age of 50.1 years, the first prescriber was a general practitioner in 58.9% of cases, they continued their treatment 6 months after their initiation in 48.8% of cases and one half of these subjects consumed at least 57.0 mg of baclofen daily. The use of baclofen for alcohol dependence increased considerably since 2008, with more than 34,000 new users and more than 9,000 general practitioners as first prescribers in 2013. © 2015 Société Française de Pharmacologie et de Thérapeutique.

The effect of acamprosate on alcohol and food craving in patients with alcohol dependence.

PubMed

Han, Doug Hyun; Lyool, In Kyoon; Sung, Young Hoon; Lee, Sang Hoon; Renshaw, Perry F

2008-03-01

The balance between inhibitory (gamma aminobutyric acid; GABAergic) and excitatory (glutamatergic) neurotransmission is thought to be associated with craving for alcohol and food. The anticraving effect of acamprosate is thought to be mediated through modifying the balance of GABA and glutamate. Recent studies in animals have suggested that acamprosate may have non-selective effects on craving for both alcohol and food. The influence of acamprosate for reducing craving for alcohol and food was assessed in 204 in-patients with alcohol dependence (96 patients treated with acamprosate, PWA; 108 patients were not treated PNA) was assessed at baseline and following 1, 2, and 4 weeks of treatment. There was a significant reduction in craving for alcohol over 4 weeks of treatment in both PWA and PNA groups, but without significant group differences. In contrast, a reduction in food craving was observed only in the PWA group. In addition, there was a significant increase of body mass index (BMI) in the PNA group but not the PWA group over the 4-week period. These results demonstrate acamprosate nonselective effects on craving for drinking and eating in alcoholic patients.

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition.

PubMed

Burnett, Elizabeth J; Chandler, L Judson; Trantham-Davidson, Heather

2016-02-04

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. To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure. In particular, up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, this observation as well as other glutamatergic neuroadaptations are often circuit and cell-type specific. Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests that 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. 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 novel, possibly circuit

Anticonvulsants for alcohol dependence.

PubMed

Pani, Pier Paolo; Trogu, Emanuela; Pacini, Matteo; Maremmani, Icro

2014-02-13

Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Besides psychosocial interventions, different pharmacological interventions have been or currently are under investigation through Cochrane systematic reviews. The primary aim of the review is to assess the benefits/risks of anticonvulsants for the treatment of alcohol dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (October 2013), PubMed (1966 to October 2013), EMBASE (1974 to October 2013) and CINAHL (1982 to October 2013). Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing anticonvulsants alone or in association with other drugs and/or psychosocial interventions versus placebo, no treatment and other pharmacological or psychosocial interventions. We used standard methodological procedures as expected by The Cochrane Collaboration. A total of 25 studies were included in the review (2641 participants). Most participants were male, with an average age of 44 years. Anticonvulsants were compared with placebo (17 studies), other medications (seven studies) and no medication (two studies). The mean duration of the trials was 17 weeks (range four to 52 weeks). The studies took place in the USA, Europe, South America, India and Thailand. Variation was reported in the characteristics of the studies, including their design and the rating instruments used. For many key outcomes, the risk of bias associated with unclear or unconcealed allocation and lack of blinding affected the quality of the evidence.Anticonvulsants versus placebo: For dropouts (16 studies, 1675 participants, risk ratio (RR) 0.94, 95% confidence interval (Cl) 0.74 to 1.19, moderate-quality evidence) and continuous abstinence (eight studies, 634 participants, RR 1.21, 95% Cl 95% 0.97 to 1.52, moderate-quality evidence), results showed no evidence of differences. Moderate-quality evidence suggested that

A family history of Type 1 alcoholism differentiates alcohol consumption in high cortisol responders to stress.

PubMed

Brkic, Sejla; Söderpalm, Bo; Söderpalm Gordh, Anna

2015-03-01

The differentiation between high and low cortisol responders to stress is of interest in determining the risk factors which may, along with genetic vulnerability, influence alcohol intake. Thirty-two healthy volunteers, family history positive to alcoholism (FHP, n = 16) and family history negative (FHN, n = 16) attended two laboratory sessions during which alcohol or placebo was offered. There were no differences in consumption of alcohol or placebo between FHP and FHN subjects. STUDY 2: Fifty-eight healthy social drinkers, FHP (n = 27) and FHN (n = 31) attended two laboratory sessions. They were administered either alcohol or placebo in both sessions they attended. All subjects underwent either a stress task (the Trier Social Stress Test, TSST) or a stress-free period, at two separate occasions, before being offered beverage. After the salivary cortisol analysis, subjects in each group were divided into high (HCR) or low (LCR) cortisol responders. After stress, subjects who were FHP-HCR consumed more alcohol than FHN-HCR. There were no differences in the placebo intake between FHP and FHN subjects regardless of their cortisol response. This result indicates that stress promotes alcohol consumption only in subjects with a family history of Type 1 alcoholism who show an increase in cortisol response to stress. This behaviour is similar to that previously observed in alcohol dependent individuals after stress and thus could represent an endophenotype posing a risk for future development of alcohol use disorders. Copyright © 2015. Published by Elsevier Inc.

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

PubMed

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

2016-05-01

In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. © 2015 Society for the Study of Addiction.

Neuropsychological assessment of decision making in alcohol-dependent commercial pilots.

PubMed

Georgemiller, Randy; Machizawa, Sayaka; Young, Kathleen M; Martin, Cynthia N

2013-09-01

The aim of this exploratory archival study was to discern the utility of the Iowa Gambling Task (IGT) in identifying adaptive decision-making capacities among pilots with a history of alcohol dependence both with and without Cluster B personality features. Participants included 18 male airmen at the rank of captain with a history of receiving alcohol dependence treatment and subsequent referral for a fitness-for-duty evaluation. Data from prior comprehensive neuropsychological evaluations conducted in a private practice setting at the mandate of the FAA utilizing criteria outlined in the HIMS program was used. ANOVA was conducted to compare pilots with (N = 4) and without Cluster B personality features (N = 14) on measures of decisionmaking capacities, intelligence, and executive functioning. Pilots with Cluster B personality features were found to have a significantly lower Total Net T-Score on IGT (M = 35.00, SD = 9.27) than pilots without features of Cluster B (M = 56.36, SD = 9.55). Furthermore, with the exception of the first 20 cards (i.e., Net 1); the groups significantly differed in their Net scores. No statistically significant difference was found on airmen's intelligence and executive functioning. The present study found that alcohol-dependent airmen with Cluster B personality features evidenced significantly poorer decisionmaking capacities as measured by the ICT in comparison to alcohol dependent airman without Cluster B personality features. Implications and limitations of the study are discussed.

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

PubMed

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

2015-09-01

Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. © 2014 Society for the Study of Addiction.

Association between insulin and executive functioning in alcohol dependence: a pilot study.

PubMed

Han, Changwoo; Bae, Hwallip; Won, Sung-Doo; Lim, Jaeyoung; Kim, Dai-Jin

2015-01-01

Alcohol dependence is a disorder ascribable to multiple factors and leads to cognitive impairment. Given that insulin dysregulation can cause cognitive impairment, patients with alcohol dependence are likely to develop insulin dysregulation such as that in diabetes. The purposes of this study are to identify an association between cognitive functioning and insulin and to investigate insulin as the biomarker of cognitive functioning in alcohol-dependent patients. Serum insulin levels were measured and cognitive functions were assessed in 45 patients with chronic alcoholism. The Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K), a battery of cognitive function tests, was used to assess cognitive functioning. Serum insulin levels were not significantly correlated with most CERAD-K scores, but there was a significant negative correlation with scores on the Trail Making Test B, which is designed to measure executive functioning. Lower serum insulin levels were associated with slower executive functioning responses on the Trail Making Test B, suggesting that executive functioning may be in proportion to serum insulin levels. Thus, in patients with alcohol dependence, insulin level is associated with cognitive functioning. In addition, the present findings suggest that insulin level is a potential biomarker for determining cognitive functioning.

Episodic Future Thinking: Expansion of the Temporal Window in Individuals with Alcohol Dependence.

PubMed

Snider, Sarah E; LaConte, Stephen M; Bickel, Warren K

2016-07-01

Episodic future thinking (EFT) requires an individual to vividly pre-experience a realistic future event. Inspired by previous reports of reducing delay discounting following EFT in other populations, we examined the effects of engaging alcohol-dependent individuals in EFT or episodic recent thinking (ERT; control) to examine its effects on delay discounting and alcohol purchasing. Participants (n = 50) with alcohol dependence were allocated into EFT or ERT groups and asked to generate positive future or recent past events for each of 5 time points. Participants then completed a delay-discounting task, during which event cues were displayed, and a hypothetical alcohol purchase task. EFT significantly increased valuation of future monetary rewards, while decreasing initial consumption (Q0 ) of alcoholic drinks indicative of lower demand intensity. Two additional findings suggest potential moderators of this effect. EFT more readily influenced individuals with lower Alcohol Use Disorders Identification Test scores, and self-reported cue valence differed between groups. Together, these results suggest a widening of alcohol-dependent individuals' temporal window following engagement of EFT. While our data suggest that EFT may be moderated by certain susceptibility criteria, exercises such as EFT could be easily adaptable as a potential therapeutic tool for use in rehabilitation programs. Copyright © 2016 by the Research Society on Alcoholism.

The comparability of solicited versus clinic subjects in alcohol treatment research.

PubMed

Pearlman, S; Zweben, A; Li, S

1989-05-01

The increasing use of media advertisements to recruit subjects in alcohol treatment research has raised concerns about the comparability of such solicited subjects and subjects drawn from more traditional clinic populations. This paper, based on a study that involved both solicited and clinic subjects, identifies differences between the two types of subjects in terms of sociodemographic variables; pre-treatment drinking and marital adjustment; several dimensions of 'self-definition'; and three outcome measures. These findings suggest that there may be significant differences between solicited and clinic subjects and that these differences should be taken into account in the design of studies utilizing solicited subjects in order to determine the generalizability of the results.

[Nationwide survey of alcohol drinking and alcoholism among Japanese adults].

PubMed

Osaki, Yoneatsu; Matsushita, Sachio; Shirasaka, Tomonobu; Hiro, Hisanori; Higuchi, Susumu

2005-10-01

To investigate the characteristics of alcohol use among Japanese adults and prevalence of alcohol dependence in Japan, we conducted a nationwide survey on alcohol drinking behavior and alcohol dependence among Japanese adults using a representative sampling method. We sampled 3500 adults from throughout the entire country using a stratified random sampling method with two-step stratification, and carried out a home visit interview survey. A total of 2547 people (72.8%) responded to the survey. The survey period was June, 2003. The questionnaire contained questions about the frequency and quantity of alcohol use, 'hazardous use of alcohol' and 'alcohol dependence' according to the ICD-10 definition, several screening scales on problem use of alcohol (CAGE, KAST, AUDIT), life-time prevalence of 24 alcohol related diseases, smoking status, dysgryphia, and nightcap drinking. The number of respondents was, 1184 males, and 1363 females. Lifetime alcohol drinking, and weekly drinking, and daily drinking rates were 95.1%, 64.4%, and 36.2% for males, 79.0%, 27.5%, and 7.5% for females, respectively. Average daily alcohol consumption was 3.7 units for males, and 2.0 units for females (1 unit = 10 g pure alcohol). The proportion of drinkers who drank alcohol 4 units or more daily was 28.9% for males, and 7.6% for females, and that for 6 units or more was 12.7% for males, and 3.4% for females. The proportion of flasher was 41.2% for males, and 35.0% for females. Among screening questions, problem drinking was most frequently identified using AUDIT (score 12 points or more, 150 persons), followed by KAST (2 points or more, 100 persons) and CAGE (2 points or more, 98 persons). The number of subjects who met the ICD-10 criteria for alcohol dependence was 24, while the number who engaged in hazardous alcohol use was 64. This study revealed that problem drinking and alcohol dependence are a serious problem in Japanese general population. The problem of females drinking may be

A preliminary, randomized trial of aerobic exercise for alcohol dependence

PubMed Central

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

2015-01-01

Interventions targeting physical activity may be valuable as an adjunct to alcohol treatment, but have been relative untested. In the current study, alcohol dependent, physically sedentary patients were randomized to: a 12-week moderate-intensity, group aerobic exercise intervention (AE; n = 25) or a brief advice to exercise intervention (BA-E; n=23). Results showed that individuals in AE reported significantly fewer drinking and heavy drinking days, relative to BA-E during treatment. Furthermore adherence to AE strengthened the beneficial effect of intervention on alcohol use outcomes. While high levels of moderate-intensity exercise appeared to facilitate alcohol recovery regardless of intervention arm, attending the group-based AE intervention seemed to further enhance the positive effects of exercise on alcohol use. Study findings indicate that a moderate intensity, group aerobic exercise intervention is an efficacious adjunct to alcohol treatment. Improving adherence to the intervention may enhance its beneficial effects on alcohol use. PMID:24666811

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

PubMed

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

2014-07-01

Interventions targeting physical activity may be valuable as an adjunct to alcohol treatment, but have been relatively untested. In the current study, alcohol dependent, physically sedentary patients were randomized to: a 12-week moderate-intensity, group aerobic exercise intervention (AE; n=25) or a brief advice to exercise intervention (BA-E; n=23). Results showed that individuals in AE reported significantly fewer drinking and heavy drinking days, relative to BA-E during treatment. Furthermore adherence to AE strengthened the beneficial effect of intervention on alcohol use outcomes. While high levels of moderate-intensity exercise appeared to facilitate alcohol recovery regardless of intervention arm, attending the group-based AE intervention seemed to further enhance the positive effects of exercise on alcohol use. Study findings indicate that a moderate intensity, group aerobic exercise intervention is an efficacious adjunct to alcohol treatment. Improving adherence to the intervention may enhance its beneficial effects on alcohol use. Copyright © 2014 Elsevier Inc. All rights reserved.

Alcohol enhances oxysterol-induced apoptosis in human endothelial cells by a calcium-dependent mechanism.

PubMed

Spyridopoulos, I; Wischhusen, J; Rabenstein, B; Mayer, P; Axel, D I; Fröhlich, K U; Karsch, K R

2001-03-01

Controversy exists about the net effect of alcohol on atherogenesis. A protective effect is assumed, especially from the tannins and phenolic compounds in red wine, owing to their inhibition of low density lipoprotein (LDL) oxidation. However, increased atherogenesis occurs in subjects with moderate to heavy drinking habits. The purpose of this study was to investigate the influence of alcohol in combination with oxysterols on the endothelium. Cultured human arterial endothelial cells (HAECs) served as an in vitro model to test the cellular effects of various oxysterols. Oxysterols (7beta-hydroxycholesterol, 7-ketocholesterol, and cholesterol-5,6-epoxides), which are assumed to be the most toxic constituents of oxidized LDL, induced apoptosis in HAECs through calcium mobilization followed by activation of caspase-3. Ethanol, methanol, isopropanol, tert-butanol, and red wine all potentiated oxysterol-induced cell death up to 5-fold, paralleled by further induction of caspase-3. The alcohol effect occurred in a dose-dependent manner and reached a plateau at 0.05% concentration. Alcohol itself did not affect endothelial cell viability, nor did other solvents such as dimethyl sulfoxide mimic the alcohol effect. So far as the physiologically occurring oxysterols are concerned, this effect was apparent only for oxysterols oxidized at the steran ring. The possibility of alcohol facilitating the uptake of oxysterols into the cell was not supported by the data from an uptake study with radiolabeled compounds. Finally, alcohol in combination with oxysterols did cause a dramatic increase in cytosolic calcium influx. Blockage of calcium influx by the calcium channel blocker aurintricarboxylic acid or the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abrogated the alcohol-mediated enhancement of oxysterol toxicity. We describe for the first time a mechanistic concept explaining possible adverse effects of alcohol in conjunction with

Reports of alcohol-related problems and alcohol dependence for demographic subgroups using interactive voice response versus telephone surveys: the 2005 US National Alcohol Survey.

PubMed

Midanik, Lorraine T; Greenfield, Thomas K

2010-07-01

Interactive voice response (IVR), a computer-based interviewing technique, can be used within a computer-assisted telephone interview (CATI) survey to increase privacy and the accuracy of reports of sensitive attitudes and behaviours. Previous research using the 2005 National Alcohol Survey indicated no overall significant differences between IVR and CATI responses to alcohol-related problems and alcohol dependence. To determine if this result holds for demographic subgroups that could respond differently to modes of data collection, this study compares the prevalence rates of lifetime and last-year alcohol-related problems by gender, ethnicity, age and income subgroups obtained by IVR versus continuous CATI interviewing. As part of the 2005 National Alcohol Survey, subsamples of English-speaking respondents were randomly assigned to an IVR group that received an embedded IVR module on alcohol-related problems (n = 450 lifetime drinkers) and a control group that were asked identical alcohol-related problem items using continuous CATI (n = 432 lifetime drinkers). Overall, there were few significant associations. Among lifetime drinkers, higher rates of legal problems were found for white and higher income respondents in the IVR group. For last-year drinkers, a higher percentage of indicators of alcohol dependence was found for Hispanic respondents and women respondents in the CATI group. Data on alcohol problems collected by CATI provide largely comparable results to those from an embedded IVR module. Thus, incorporation of IVR technology in a CATI interview does not appear strongly indicated even for several key subgroups.

Witness memory and alcohol: The effects of state-dependent recall.

PubMed

Schreiber Compo, Nadja; Carol, Rolando N; Evans, Jacqueline R; Pimentel, Pamela; Holness, Howard; Nichols-Lopez, Kristin; Rose, Stefan; Furton, Kenneth G

2017-04-01

Many real-world eyewitnesses are under the influence of alcohol either at the time of the crime, the interview, or both. Only recently has empirical research begun to examine the effects of alcohol on witness memory, yielding mixed results. The present study tested the importance of state-dependent memory in the context of alcohol's effects on encoding versus retrieval of a witnessed event, while simultaneously informing real-world investigative practices: Should witnesses sober up before an interview? Participants (N = 249) were randomized to a control, placebo, or alcohol condition at encoding and to either an immediate retrieval condition (in the same state) or a 1-week delay control, placebo, or alcohol retrieval condition. They recalled a witnessed mock crime using open ended and cued recall formats. After a delay, witnesses intoxicated at both encoding and retrieval provided less accurate information than witnesses in sober or placebo groups at both times. There was no advantage of state-dependent memory but intoxicated witnesses were best when recalling immediately compared to 1 week later (sober, placebo, or reintoxicated). Findings have direct implications for the timing of intoxicated witnesses' interviews such that moderately intoxicated witnesses may not benefit from a sobering delay but rather, should be interviewed immediately. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

PubMed

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

2011-11-01

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

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

PubMed

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

2009-01-01

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

Preserved Affective Sharing But Impaired Decoding of Contextual Complex Emotions in Alcohol Dependence.

PubMed

Grynberg, Delphine; Maurage, Pierre; Nandrino, Jean-Louis

2017-04-01

Prior research has repeatedly shown that alcohol dependence is associated with a large range of impairments in psychological processes, which could lead to interpersonal deficits. Specifically, it has been suggested that these interpersonal difficulties are underpinned by reduced recognition and sharing of others' emotional states. However, this pattern of deficits remains to be clarified. This study thus aimed to investigate whether alcohol dependence is associated with impaired abilities in decoding contextual complex emotions and with altered sharing of others' emotions. Forty-one alcohol-dependent individuals (ADI) and 37 matched healthy individuals completed the Multifaceted Empathy Test, in which they were instructed to identify complex emotional states expressed by individuals in contextual scenes and to state to what extent they shared them. Compared to healthy individuals, ADI were impaired in identifying negative (Cohen's d = 0.75) and positive (Cohen's d = 0.46) emotional states but, conversely, presented preserved abilities in sharing others' emotional states. This study shows that alcohol dependence is characterized by an impaired ability to decode complex emotional states (both positive and negative), despite the presence of complementary contextual cues, but by preserved emotion-sharing. Therefore, these results extend earlier data describing an impaired ability to decode noncontextualized emotions toward contextualized and ecologically valid emotional states. They also indicate that some essential emotional competences such as emotion-sharing are preserved in alcohol dependence, thereby offering potential therapeutic levers. Copyright © 2017 by the Research Society on Alcoholism.

Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process

PubMed Central

Walker, Brendan M.

2013-01-01

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. PMID:22459874

MAOA expression predicts vulnerability for alcohol use.

PubMed

Cervera-Juanes, R; Wilhem, L J; Park, B; Lee, R; Locke, J; Helms, C; Gonzales, S; Wand, G; Jones, S R; Grant, K A; Ferguson, B

2016-04-01

The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.

The role of negative emotionality and impulsivity in depressive/anxiety disorders and alcohol dependence.

PubMed

Boschloo, L; Vogelzangs, N; van den Brink, W; Smit, J H; Beekman, A T F; Penninx, B W J H

2013-06-01

Much is still unclear about the role of personality in the structure of common psychiatric disorders such as depressive/anxiety disorders and alcohol dependence. This study will therefore examine whether various traits of negative emotionality and impulsivity showed shared or specific associations with these disorders. Method Cross-sectional data were used from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with no DSM-IV psychiatric disorder (n = 460), depressive/anxiety disorder only (i.e. depressive and/or anxiety disorder; n = 1398), alcohol dependence only (n = 32) and co-morbid depressive/anxiety disorder plus alcohol dependence (n = 358). Aspects of negative emotionality were neuroticism, hopelessness, rumination, worry and anxiety sensitivity, whereas aspects of impulsivity included disinhibition, thrill/adventure seeking, experience seeking and boredom susceptibility. Aspects of negative emotionality formed a homogeneous dimension, which was unrelated to the more heterogeneous construct of impulsivity. Although all aspects of negative emotionality were associated with alcohol dependence only, associations were much stronger for depressive/anxiety disorder only and co-morbid depressive/anxiety disorder with alcohol dependence. The results for impulsivity traits were less profound and more variable, with disinhibition and boredom susceptibility showing modest associations with both depressive/anxiety disorder and alcohol dependence, whereas low thrill/adventure seeking and high disinhibition were more strongly related with the first and the latter, respectively. Our results suggest that depressive/anxiety disorder and alcohol dependence result from shared as well as specific aetiological pathways as they showed the same associations with all aspects of negative emotionality, disinhibition and boredom susceptibility as well as specific associations with thrill/adventure seeking and disinhibition.

Differences in functional connectivity between alcohol dependence and internet gaming disorder

PubMed Central

Han, Ji Won; Han, Doug Hyun; Bolo, Nicolas; Kim, BoAh; Kim, Boong Nyun; Renshaw, Perry F.

2017-01-01

Introduction Internet gaming disorder (IGD) and alcohol dependence (AD) have been reported to share clinical characteristics including craving and over-engagement despite negative consequences. However, there are also clinical factors that differ between individuals with IGD and those with AD in terms of chemical intoxication, prevalence age, and visual and auditory stimulation. Methods We assessed brain functional connectivity within the prefrontal, striatum, and temporal lobe in 15 patients with IGD and in 16 patients with AD. Symptoms of depression, anxiety, and the attention deficit hyperactivity disorder were assessed in patients with IGD and in patients with AD. Results Both AD and IGD subjects have positive functional connectivity between the dorsolateral prefrontal cortex (DLPFC), cingulate, and cerebellum. In addition, both groups have negative functional connectivity between the DLPFC and the orbitofrontal cortex. However, the AD subjects have positive functional connectivity between the DLPFC, temporal lobe and striatal areas while IGD subjects have negative functional connectivity between the DLPFC, temporal lobe and striatal areas. Conclusions AD and IGD subjects may share deficits in executive function, including problems with self-control and adaptive responding. However, the negative connectivity between the DLPFC and the striatal areas in IGD subjects, different from the connectivity observed in AD subjects, may be due to the earlier prevalence age, different comorbid diseases as well as visual and auditory stimulation. PMID:25282597

Differences in functional connectivity between alcohol dependence and internet gaming disorder.

PubMed

Han, Ji Won; Han, Doug Hyun; Bolo, Nicolas; Kim, BoAh; Kim, Boong Nyun; Renshaw, Perry F

2015-02-01

Internet gaming disorder (IGD) and alcohol dependence (AD) have been reported to share clinical characteristics including craving and over-engagement despite negative consequences. However, there are also clinical factors that differ between individuals with IGD and those with AD in terms of chemical intoxication, prevalence age, and visual and auditory stimulation. We assessed brain functional connectivity within the prefrontal, striatum, and temporal lobe in 15 patients with IGD and in 16 patients with AD. Symptoms of depression, anxiety, and the attention deficit hyperactivity disorder were assessed in patients with IGD and in patients with AD. Both AD and IGD subjects have positive functional connectivity between the dorsolateral prefrontal cortex (DLPFC), cingulate, and cerebellum. In addition, both groups have negative functional connectivity between the DLPFC and the orbitofrontal cortex. However, the AD subjects have positive functional connectivity between the DLPFC, temporal lobe and striatal areas while IGD subjects have negative functional connectivity between the DLPFC, temporal lobe and striatal areas. AD and IGD subjects may share deficits in executive function, including problems with self-control and adaptive responding. However, the negative connectivity between the DLPFC and the striatal areas in IGD subjects, different from the connectivity observed in AD subjects, may be due to the earlier prevalence age, different comorbid diseases as well as visual and auditory stimulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Does retigabine affect the development of alcohol dependence?--A pharmaco-EEG study.

PubMed

Zwierzyńska, Ewa; Andrzejczak, Dariusz; Pietrzak, Bogusława

2016-01-12

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial

PubMed Central

Wardle, Margaret C.; Marcus, Benjamin A.; de Wit, Harriet

2015-01-01

Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants’ drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21–31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs’ effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants’ responses to the three drugs were unrelated. Unexpectedly, “wanting more” alcohol was inversely correlated with “wanting more” THC. Additionally, in women, but not in men, “disliking” alcohol was negatively correlated with “disliking” THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a “drug of choice” model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other

Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects.

PubMed

Truitt, E B; Gaynor, C R; Mehl, D L

1987-01-01

Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.

Association Splitting: A randomized controlled trial of a new method to reduce craving among inpatients with alcohol dependence.

PubMed

Schneider, Brooke C; Moritz, Steffen; Hottenrott, Birgit; Reimer, Jens; Andreou, Christina; Jelinek, Lena

2016-04-30

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improved synthesis of chiral alcohols with Escherichia coli cells co-expressing pyridine nucleotide transhydrogenase, NADP+-dependent alcohol dehydrogenase and NAD+-dependent formate dehydrogenase.

PubMed

Weckbecker, Andrea; Hummel, Werner

2004-11-01

Recombinant pyridine nucleotide transhydrogenase (PNT) from Escherichia coli has been used to regenerate NAD+ and NADPH. The pnta and pntb genes encoding for the alpha- and beta-subunits were cloned and co-expressed with NADP+-dependent alcohol dehydrogenase (ADH) from Lactobacillus kefir and NAD+-dependent formate dehydrogenase (FDH) from Candida boidinii. Using this whole-cell biocatalyst, efficient conversion of prochiral ketones to chiral alcohols was achieved: 66% acetophenone was reduced to (R)-phenylethanol over 12 h, whereas only 19% (R)-phenylethanol was formed under the same conditions with cells containing ADH and FDH genes but without PNT genes. Cells that were permeabilized with toluene showed ketone reduction only if both cofactors were present.

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

PubMed

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

2016-01-01

The aim of this study was to determine the association between alcohol dependence and altitude of residence in 11 villages in two high altitude areas of Peru. An analytical cross-sectional study was performed using a survey conducted by physicians in primary health care in 11 villages until 2013, that were divided into low altitude (≤2500m asl (above sea level)), and high altitude (>2500m asl) areas. The CAGE test for alcoholism (cut point, ≥2) was applied to those who responded positively when asked if they consumed alcohol. Statistical associations were obtained with generalised linear models Of the 737 participants, 51% were women and the median age was 36 years [interquartile range, 25-50], 334 (45%) lived at low altitude, and 113 (15%) had alcohol dependence. The highest frequency of alcoholism was positively associated with being a village considered extremely poor (Likelihood Ratio (LP)=2.42; 95%CI, 1.40-4.19), while being female (LP=0.44; 95%CI, 0.23-0.89) and residing at high altitude (LP=0.15; 95%CI, 0.07-0.31) were negatively associated. These were adjusted for nine socio-occupational and pathological variables. According to these data, there is a higher frequency of alcohol dependence in being, male, extremely poor, and residing at low altitude. These results should be taken into account by professionals who work in primary care and those involved in mental health care, because of their implications in society. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Encoding-Imagery Specificity in Alcohol State-Dependent Learning

ERIC Educational Resources Information Center

Weingartner, Herbert; And Others

1976-01-01

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

Decreased prefrontal cortical dopamine transmission in alcoholism.

PubMed

Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

2014-08-01

Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

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

PubMed Central

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

2015-01-01

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

Are the binary typology models of alcoholism valid in polydrug abusers?

PubMed

Pombo, Samuel; da Costa, Nuno F; Figueira, Maria L

2015-01-01

To evaluate the dichotomy of type I/II and type A/B alcoholism typologies in opiate-dependent patients with a comorbid alcohol dependence problem (ODP-AP). The validity assessment process comprised the information regarding the history of alcohol use (internal validity), cognitive-behavioral variables regarding substance use (external validity), and indicators of treatment during 6-month follow-up (predictive validity). ODP-AP subjects classified as type II/B presented an early and much more severe drinking problem and a worse clinical prognosis when considering opiate treatment variables as compared with ODP-AP subjects defined as type I/A. Furthermore, type II/B patients endorse more general positive beliefs and expectancies related to the effect of alcohol and tend to drink heavily across several intra- and interpersonal situations as compared with type I/A patients. These findings confirm two different forms of alcohol dependence, recognized as a low-severity/vulnerability subgroup and a high-severity/vulnerability subgroup, in an opiate-dependent population with a lifetime diagnosis of alcohol dependence.

QUETIAPINE IMPROVES RESPONSE INHIBITION IN ALCOHOL DEPENDENT PATIENTS: A PLACEBO-CONTROLLED PILOT STUDY

PubMed Central

Moallem, Nathasha; Ray, Lara A.

2013-01-01

Rationale Quetiapine has been shown to be a promising medication for the treatment of alcoholism. As an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT1A and 5-HT2A, H1 and α1 and α2 receptors, quetiapine has been found to decrease impulsivity in other psychiatric disorders but its effects on impulsivity have not been studied in alcohol dependent patients. Objective This study seeks to test the effects of quetiapine on a specific dimension of impulsivity, namely response inhibition. This pilot study seeks to further elucidate the mechanisms of action of quetiapine for alcohol use disorders. Method A total of 20 non-treatment seeking alcohol dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants completed two counterbalanced intravenous placebo-alcohol administration sessions as well as behavioral measure of response inhibition (i.e. stop signal task) pre and post placebo-alcohol administration sessions. Results Analyses revealed a significant effect of quetiapine in improving response inhibition as measured by the stop signal task. These results provide preliminary evidence suggesting that quetiapine improves response inhibition in alcohol dependent patients, as compared to placebo. Conclusion This pilot study contributes a novel putative mechanism of action of quetiapine in alcoholism, namely an improvement in response inhibition. PMID:22037407

Predictors of posttreatment drinking outcomes in patients with alcohol dependence.

PubMed

Flórez, Gerardo; Saiz, Pilar A; García-Portilla, Paz; De Cos, Francisco J; Dapía, Sonia; Alvarez, Sandra; Nogueiras, Luis; Bobes, Julio

2015-01-01

This cohort study examined how predictors of alcohol dependence treatment outcomes work together over time by comparing pretreatment and posttreatment predictors. A sample of 274 alcohol-dependent patients was recruited and assessed at baseline, 6 months after treatment initiation (end of the active intervention phase), and 18 months after treatment initiation (end of the 12-month research follow-up phase). At each assessment point, the participants completed a battery of standardized tests [European Addiction Severity Index (EuropASI), Obsessive Compulsive Drinking Scale (OCDS), Alcohol Timeline Followback (TLFB), Fagerström, and International Personality Disorder Examination (IPDE)] that measured symptom severity and consequences; biological markers of alcohol consumption were also tested at each assessment point. A sequential strategy with univariate and multivariate analyses was used to identify how pretreatment and posttreatment predictors influence outcomes up to 1 year after treatment. Pretreatment variables had less predictive power than posttreatment ones. OCDS scores and biological markers of alcohol consumption were the most significant variables for the prediction of posttreatment outcomes. Prior pharmacotherapy treatment and relapse prevention interventions were also associated with posttreatment outcomes. The findings highlight the positive impact of pharmacotherapy during the first 6 months after treatment initiation and of relapse prevention during the first year after treatment and how posttreatment predictors are more important than pretreatment predictors.

Polymorphisms in genes encoding dopamine signalling pathway and risk of alcohol dependence: a systematic review.

PubMed

Bhaskar, Lakkakula V K S; Kumar, Shanmugasundaram Arun

2014-04-01

Alcohol dependence (AD) is one of the major elements that significantly influence drinking pattern that provoke the alcohol-induced organ damage. The structural and neurophysiologic abnormalities in the frontal lobes of chronic alcoholics were revealed by magnetic resonance imaging scans. It is well known that candidate genes involved in dopaminergic pathway are of immense interest to the researchers engaged in a wide range of addictive disorders. Dopaminergic pathway gene polymorphisms are being extensively studied with respect to addictive and behavioral disorders. From the broad literature available, the current review summarizes the specific polymorphisms of dopaminergic genes that play a role in alcohol dependence. No evidence indicating any strong association between AD and polymorphisms of dopamine pathway genes has emerged from the literature. Further studies are warranted, considering a range of alcohol-related traits to determine the genes that influence alcohol dependence.

Efficacy of Naltrexone for the Treatment of Alcohol Dependence in Latino Populations.

PubMed

López, Cristina M; Barr, Simone C; Reid-Quiñones, Kathryn; de Arellano, Michael A

2017-05-01

Naltrexone has been identified as a promising psychopharmacological treatment for alcohol dependence. Previous studies have suggested that its efficacy may vary based on ethnic background. The current study examined the efficacy of naltrexone in the treatment of alcohol dependence in Latino adults, a previously unexplored population. This was a secondary analysis of the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study. The overall COMBINE sample consisted of 1,383 adult participants who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence, including 155 Latinos, who are the focus of this report. Consistent with the main trial, primary drinking outcomes, including percentage of days abstinent (PDA) and time to first heavy drinking day (TTHD), were examined. In addition, we examined the effects of naltrexone on a clinically relevant secondary outcome measure, global clinical outcome of alcohol consumption and alcohol-related problems. As seen with the subsample of African Americans from the COMBINE Study, results of the present analysis indicated that there were no significant effects of naltrexone on PDA and TTHD despite these significant effects in the original study. However, contrary to findings in the African American subsample, for Latino participants naltrexone was a significant predictor of a good global clinical outcome (i.e., abstinence or moderate drinking without problems). Naltrexone was not significantly associated with improvements in the primary drinking outcomes of PDA or TTHD at the end of treatment or at follow-up. However, Latinos appeared to benefit from naltrexone as demonstrated by improved ratings of global clinical outcome. These results indicate mixed findings for the efficacy of naltrexone among Latinos in the COMBINE Study.

Low levels of alcohol impair driving simulator performance and reduce perception of crash risk in partially sleep deprived subjects.

PubMed

Banks, Siobhan; Catcheside, Peter; Lack, Leon; Grunstein, Ron R; McEvoy, R Doug

2004-09-15

Partial sleep deprivation and alcohol consumption are a common combination, particularly among young drivers. We hypothesized that while low blood alcohol concentration (<0.05 g/dL) may not significantly increase crash risk, the combination of partial sleep deprivation and low blood alcohol concentration would cause significant performance impairment. Experimental Sleep Disorders Unit Laboratory 20 healthy volunteers (mean age 22.8 years; 9 men). Subjects underwent driving simulator testing at 1 am on 2 nights a week apart. On the night preceding simulator testing, subjects were partially sleep deprived (5 hours in bed). Alcohol consumption (2-3 standard alcohol drinks over 2 hours) was randomized to 1 of the 2 test nights, and blood alcohol concentrations were estimated using a calibrated Breathalyzer. During the driving task subjects were monitored continuously with electroencephalography for sleep episodes and were prompted every 4.5 minutes for answers to 2 perception scales-performance and crash risk. Mean blood alcohol concentration on the alcohol night was 0.035 +/- 0.015 g/dL. Compared with conditions during partial sleep deprivation alone, subjects had more microsleeps, impaired driving simulator performance, and poorer ability to predict crash risk in the combined partial sleep deprivation and alcohol condition. Women predicted crash risk more accurately than did men in the partial sleep deprivation condition, but neither men nor women predicted the risk accurately in the sleep deprivation plus alcohol condition. Alcohol at legal blood alcohol concentrations appears to increase sleepiness and impair performance and the detection of crash risk following partial sleep deprivation. When partially sleep deprived, women appear to be either more perceptive of increased crash risk or more willing to admit to their driving limitations than are men. Alcohol eliminated this behavioral difference.

The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort study.

PubMed

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

2017-07-01

Our aim is to study the relationship between dose of baclofen and effectiveness in alcohol dependence. Two hundred two patients with alcohol dependence, who received baclofen treatment for drinking reduction, were followed up for 1 year. For each patient-month of treatment, the maximum daily dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for at least 2 consecutive months. We divided the DDB of each patient-month into 3 categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150 mg/d) and investigated the relationship between reaching a favorable outcome and the concurrent DDB category in a time-varying Cox regression analysis. Hazard ratios (HRs) were adjusted based on age, sex, and initial AWAC. One hundred forty subjects were followed during at least 1 month. Of these patients, 58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose was associated with a decreased rate of favorable drinking outcome (HR = 0.42; 95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31; 95% CI [0.65, 2.64]). The relationship between dose of baclofen and favorable drinking outcome was U-shaped, that is, was increased at low and high doses compared to medium doses. Copyright © 2017 John Wiley & Sons, Ltd.

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

PubMed Central

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

2009-01-01

Hispanics are heterogeneous in national origin, evidenced by wide ranges of alcohol abuse and dependence rates across different Hispanic national groups. This paper examines associations between 12-month rates of DSM-IV alcohol abuse and dependence with birthplace and acculturation. The 2006 Hispanic Americans Baseline Alcohol Survey, using a multistage cluster sample design, interviewed 5,224 adults (18+ years) in five selected U.S. metropolitan areas: Miami, New York, Philadelphia, Houston, and Los Angeles. Comprehensive data on drinking behavior were collected and the analyses include bivariate and multivariate regression techniques. Alcohol abuse and dependence rates were higher among U.S.-born Puerto Ricans and South/Central Americans compared to their foreign-born counterparts, while no such differences were found for Cuban and Mexican Americans. Overall, those with higher acculturation report higher rates of abuse and dependence (statistically significant only for abuse among Puerto Ricans). Risk factors for abuse include being male and being in the high acculturation group. Risk factors for dependence include being male, being Puerto Rican or Mexican American, having less than a college education, and being U.S.-born. Hispanics were found to share several common risk factors with the larger U.S. population for abuse and dependence, such as male gender, lower education, and lower income. PMID:18945554

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

PubMed

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

2009-01-01

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

Attempts to reduce alcohol intake and treatment needs among people with probable alcohol dependence in England: a general population survey.

PubMed

Dunne, Jacklyn; Kimergård, Andreas; Brown, Jamie; Beard, Emma; Buykx, Penny; Michie, Susan; Drummond, Colin

2018-03-25

To compare the proportion of people in England with probable alcohol dependence [Alcohol Use Disorders Identification Test (AUDIT) score ≥ 20] with those with other drinking patterns (categorized by AUDIT scores) in terms of motivation to reduce drinking and use of alcohol support resources. A combination of random probability and simple quota sampling to conduct monthly cross-sectional household computer-assisted interviews between March 2014 and August 2017. The general population in all nine regions of England. Participants in the Alcohol Toolkit Study (ATS), a monthly household survey of alcohol consumption among people aged 16 years and over in England (n = 69 826). The mean age was 47 years [standard deviation (SD) = 18.78; 95% confidence interval (CI) = 46.8-47] and 51% (n = 35 560) were female. χ 2 tests were used to investigate associations with demographic variables, motivation to quit drinking, attempts to quit drinking, general practitioner (GP) engagement and types of support accessed in the last 12 months across AUDIT risk zones. A total of 0.6% were classified as people with probable alcohol dependence (95% CI = 0.5-0.7). Motivation to quit (χ 2  = 1692.27, P < 0.001), current attempts (χ 2  = 473.94, P < 0.001) and past-year attempts (χ 2  = 593.67, P < 0.001) differed by AUDIT risk zone. People with probable dependence were more likely than other ATS participants to have a past-year attempt to cut down or quit (51.8%) and have received a specialist referral from their GP about drinking (13.7%), and less likely to report no motivation to reduce their drinking (26.2%). Those with probable dependence had higher use of self-help books and mobile applications (apps) than other ATS participants; however, 27.7% did not access any resources during their most recent attempt to cut down. Adults in England with probable alcohol dependence, measured through the Alcohol Use Disorders Identification Test, demonstrate higher

Alcohol Attenuates Load-related Activation During a Working Memory Task: Relation to Level of Response to Alcohol

PubMed Central

Paulus, Martin P.; Tapert, Susan F.; Pulido, Carmen; Schuckit, Marc A.

2008-01-01

Background A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. Method Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level–dependent activation to an event-related visual working memory test was examined. Results The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load–dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. Conclusion Low-level responders relative to high-level responders exhibited an increased working memory load–dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol. PMID:16899039

Effects of mixing alcohol with energy drink on objective and subjective intoxication: results from a Dutch on-premise study.

PubMed

Verster, J C; Benjaminsen, J M E; van Lanen, J H M; van Stavel, N M D; Olivier, B

2015-03-01

The purpose of this on-premise study was to determine if alcohol mixed with energy drink (AMED) consumption masks the subjective feelings of intoxication when compared to consuming alcohol only. The study was conducted on five nights in the city center of Utrecht. N = 997 people leaving bars were interviewed about their alcohol consumption with and without energy drinks, for that particular evening and for other occasions. People reporting drug and medication use were excluded (N = 84). Subjective intoxication was rated on a 10-point scale. Objective intoxication (breath alcohol concentration, BrAC) was determined with a breath alcohol test. Three groups were identified: (1) the AMED-tonight group (N = 185, 20.2 %), (2) the AMED-other-nights group (N = 246, 27.1 %), and (3) the no-AMED group (N = 482, 52.7 %). Objective intoxication (BrAC) did not significantly differ (p = 0.94) between the AMED-tonight group (0.074 % ± 0.05), AMED-other-nights group (0.073 % ± 0.05), and the no-AMED group (0.074 % ± 0.05). In line, subjective intoxication was not significantly different (p = 0.96) between the AMED-tonight group (4.5 ± 2.2), AMED-other-nights group (4.6 ± 2.3), and no-AMED group (4.6 ± 2.2). Within-subjects comparisons revealed no significant differences in total alcohol consumption between AMED occasions and alcohol only occasions. Regression analyses showed that "gender" (beta = 0.078, p = 0.016), "time of testing" (beta = 0.085, p = 0.009,) and "BrAC" (beta = 0.574, p = 0.0001) together explained 37.7 % of variance of subjective intoxication scores (Cohen's f (2) = 0.605). Whether or not subjects consumed energy drinks did not predict subjective intoxication scores. The data suggests that mixing alcohol with energy drink does not mask subjective intoxication.

Outpatient treatment of alcohol use disorders among subjects 60+ years: design of a randomized clinical trial conducted in three countries (Elderly Study).

PubMed

Andersen, Kjeld; Bogenschutz, Michael P; Bühringer, Gerhard; Behrendt, Silke; Bilberg, Randi; Braun, Barbara; Ekstrøm, Claus Thorn; Forcehimes, Alyssa; Lizarraga, Christine; Moyers, Theresa B; Nielsen, Anette Søgaard

2015-11-14

The proportion of 60+ years with excessive alcohol intake varies in western countries between 6-16 % among men and 2-7 % among women. Specific events related to aging (e.g. loss of job, physical and mental capacity, or spouse) may contribute to onset or continuation of alcohol use disorders (AUD). We present the rationale and design of a multisite, multinational AUD treatment study for subjects aged 60+ years. 1,000 subjects seeking treatment for AUD according to DSM-5 in outpatient clinics in Denmark, Germany, and New Mexico (USA) are invited to participate in a RCT. Participants are randomly assigned to four sessions of Motivational Enhancement Treatment (MET) or to MET plus an add-on with eight sessions based on the Community Reinforcement Approach (CRA), which include a new module targeting specific problems of older adults. A series of assessment instruments is applied, including the Form-90, Alcohol Dependence Scale, Penn Alcohol Craving Scale, Brief Symptom Inventory and WHO Quality of Life. Enrolment will be completed by April 2016 and data collection by April 2017. The primary outcome is the proportion in each group who are abstinent or have a controlled use of alcohol six months after treatment initiation. Controlled use is defined as maximum blood alcohol content not exceeding 0.05 % during the last month. Total abstinence is a secondary outcome, together with quality of life andcompliance with treatment. The study will provide new knowledge about brief treatment of AUD for older subjects. As the treatment is manualized and applied in routine treatment facilities, barriers for implementation in the health care system are relatively low. Finally, as the study is being conducted in three different countries it will also provide significant insight into the possible interaction of service system differences and related patient characteristics in predictionof treatment outcome. Clinical Trials.gov NCT02084173 , March 7, 2014.

The Effect of Alcohols on Red Blood Cell Mechanical Properties and Membrane Fluidity Depends on Their Molecular Size

PubMed Central

Sonmez, Melda; Ince, Huseyin Yavuz; Yalcin, Ozlem; Ajdžanović, Vladimir; Spasojević, Ivan; Meiselman, Herbert J.; Baskurt, Oguz K.

2013-01-01

The role of membrane fluidity in determining red blood cell (RBC) deformability has been suggested by a number of studies. The present investigation evaluated alterations of RBC membrane fluidity, deformability and stability in the presence of four linear alcohols (methanol, ethanol, propanol and butanol) using ektacytometry and electron paramagnetic resonance (EPR) spectroscopy. All alcohols had a biphasic effect on deformability such that it increased then decreased with increasing concentration; the critical concentration for reversal was an inverse function of molecular size. EPR results showed biphasic changes of near-surface fluidity (i.e., increase then decrease) and a decreased fluidity of the lipid core; rank order of effectiveness was butanol > propanol > ethanol > methanol, with a significant correlation between near-surface fluidity and deformability (r = 0.697; p<0.01). The presence of alcohol enhanced the impairment of RBC deformability caused by subjecting cells to 100 Pa shear stress for 300 s, with significant differences from control being observed at higher concentrations of all four alcohols. The level of hemolysis was dependent on molecular size and concentration, whereas echinocytic shape transformation (i.e., biconcave disc to crenated morphology) was observed only for ethanol and propanol. These results are in accordance with available data obtained on model membranes. They document the presence of mechanical links between RBC deformability and near-surface membrane fluidity, chain length-dependence of the ability of alcohols to alter RBC mechanical behavior, and the biphasic response of RBC deformability and near-surface membrane fluidity to increasing alcohol concentrations. PMID:24086751

The effect of alcohols on red blood cell mechanical properties and membrane fluidity depends on their molecular size.

PubMed

Sonmez, Melda; Ince, Huseyin Yavuz; Yalcin, Ozlem; Ajdžanović, Vladimir; Spasojević, Ivan; Meiselman, Herbert J; Baskurt, Oguz K

2013-01-01

The role of membrane fluidity in determining red blood cell (RBC) deformability has been suggested by a number of studies. The present investigation evaluated alterations of RBC membrane fluidity, deformability and stability in the presence of four linear alcohols (methanol, ethanol, propanol and butanol) using ektacytometry and electron paramagnetic resonance (EPR) spectroscopy. All alcohols had a biphasic effect on deformability such that it increased then decreased with increasing concentration; the critical concentration for reversal was an inverse function of molecular size. EPR results showed biphasic changes of near-surface fluidity (i.e., increase then decrease) and a decreased fluidity of the lipid core; rank order of effectiveness was butanol > propanol > ethanol > methanol, with a significant correlation between near-surface fluidity and deformability (r = 0.697; p<0.01). The presence of alcohol enhanced the impairment of RBC deformability caused by subjecting cells to 100 Pa shear stress for 300 s, with significant differences from control being observed at higher concentrations of all four alcohols. The level of hemolysis was dependent on molecular size and concentration, whereas echinocytic shape transformation (i.e., biconcave disc to crenated morphology) was observed only for ethanol and propanol. These results are in accordance with available data obtained on model membranes. They document the presence of mechanical links between RBC deformability and near-surface membrane fluidity, chain length-dependence of the ability of alcohols to alter RBC mechanical behavior, and the biphasic response of RBC deformability and near-surface membrane fluidity to increasing alcohol concentrations.

Replication of Genome Wide Association Studies of Alcohol Dependence: Support for Association with Variation in ADH1C

PubMed Central

Biernacka, Joanna M.; Geske, Jennifer R.; Schneekloth, Terry D.; Frye, Mark A.; Cunningham, Julie M.; Choi, Doo-Sup; Tapp, Courtney L.; Lewis, Bradley R.; Drews, Maureen S.; L.Pietrzak, Tracy; Colby, Colin L.; Hall-Flavin, Daniel K.; Loukianova, Larissa L.; Heit, John A.; Mrazek, David A.; Karpyak, Victor M.

2013-01-01

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI) = 0.80 (0.66, 0.95); women: OR (95%CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes. PMID:23516558

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

PubMed

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

2015-11-01

Childhood maltreatment decreases age of first use and speeds the transition from first use to dependence (i.e., telescoping) for alcohol use, however, it is currently unknown whether this influence is the same for men and women. Analyses were conducted with the National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,653). Outcome variables included age of alcohol initiation and time to onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence. Predictor variables included gender and childhood maltreatment. Linear and Poisson regression analyses were conducted. Results demonstrated that in regard to age of drinking initiation, individuals who experienced childhood maltreatment initiated 1 year earlier than those without maltreatment, however, there was no interaction of this relationship with gender. Regarding the time to dependence, it was found that women who experienced childhood maltreatment demonstrated telescoping (shorter time between onset and dependence) compared to women without maltreatment and men (both with and without maltreatment). Women with a history of childhood maltreatment are particularly vulnerable to an accelerated time from initiation of alcohol use until dependence, a pattern indicative of increased negative alcohol-related outcomes. Findings highlight the need for development of gender-specific prevention efforts and behavioral treatments to aid in early intervention of problematic alcohol use in women. © The Author(s) 2015.

Effects of T'ai Chi on Serotonin, Nicotine Dependency, Depression, and Anger in Hospitalized Alcohol-Dependent Patients.