Sjoerds, Zsuzsika; van den Brink, Wim; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.; Veltman, Dick J.
Introduction With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity. Methods We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels. Results Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation. Conclusion Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes
Manzardo, Ann M.; He, Jianghua; Poje, Albert; Penick, Elizabeth C.; Campbell, Jan; Butler, Merlin G.
Background Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analogue, benfotiamine (BF), and BF’s effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. Methods A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Results Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, −611±380 Std Dev; PL: N=11, −159±562 Std Dev, p-value=0.02). Conclusions BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism. PMID:23992649
Chaudhary, Ninad S.; Kampman, Kyle M.; Kranzler, Henry R.; Grandner, Michael A.; Debbarma, Swarnalata; Chakravorty, Subhajit
Introduction Although psychosocial problems are commonly associated with both alcohol misuse and insomnia, very little is known about the combined effects of insomnia and current alcohol dependence on the severity of psychosocial problems. The present study evaluates whether the co-occurrence of insomnia and alcohol dependence is associated with greater psychosocial problem severity. Methods Alcohol dependent individuals (N=123) were evaluated prior to participation in a placebo-controlled medication trial. The Short Index of Problems (SIP), Addiction Severity Index (ASI), Insomnia Severity Index (ISI), and Time Line Follow Back (TLFB), were used to assess psychosocial, employment, and legal problems; insomnia symptoms; and alcohol consumption, respectively. Bivariate and multivariate analyses were used to evaluate the relations between insomnia and psychosocial problems. Results Subjects’ mean age was 44 years (SD=10.3), 83% were male, and their SIP sub-scale scores approximated the median for normative data. A quarter of subjects reported no insomnia; 29% reported mild insomnia; and 45% reported moderate-severe insomnia. The insomnia groups did not differ on alcohol consumption measures. The ISI total score was associated with the SIP total scale score (β=0.23, p=0.008). Subjects with moderate-severe insomnia had significantly higher scores on the SIP total score, and on the social and impulse control sub-scales, and more ASI employment problems and conflicts with their spouses than others on the ASI. Conclusion In treatment-seeking alcohol dependent subjects, insomnia may increase alcohol-related adverse psychosocial consequences. Longitudinal studies are needed to clarify the relations between insomnia and psychosocial problems in these subjects. PMID:26151580
Morris, S A; Kelso, M L; Liput, D J; Marshall, S A; Nixon, K
Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on
Andó, Bálint; Rózsa, Sándor; Kurgyis, Eszter; Szkaliczki, Andrea; Demeter, Ildikó; Szikszay, Petronella; Demetrovics, Zsolt; Janka, Zoltán; Álmos, Péter Z
Temperament and character factors are strongly related to the developmental, clinical, and treatment aspects of alcohol dependence. This study had the aim of revealing the underlying personality structure and individual differences in the symptoms of alcohol dependence measured by multiple severity indicators. Patients with alcohol dependence exhibited higher levels of novelty seeking and harm avoidance, and lower levels of persistence, self-directedness, and cooperativeness. Especially novelty seeking was connected with more severe alcohol dependence. These characteristics could be useful targets of interventions and Temperament and Character Inventory is therefore a useful measurement to identify patients with more severe alcohol-related problems.
The aim of the study was to examine the relationship between neuropsychological impairment in severe alcohol dependence and relapse. This was assessed following inpatient detoxification over a period of three months. Participants were tested on measures of neuropsychological functioning at the end of a seven to ten day stay in an inpatient alcohol…
DEMİRBAŞ, Hatice; ÖZGÜR İLHAN, İnci; DOĞAN, Yıldırım Beyatlı; CANATAN, Ayşe
Introduction We aimed to evaluate the psychometric characteristics of the Turkish translation of the Addiction Severity Index (ASI) in 115 male alcohol-dependent patients. Method The reliability of the instrument was assessed by measuring test-retest, interrater and internal reliabilities. In the validity analysis, the correlation coefficients between corresponding severity ratings and composite scores of each subscale and concurrent validity were assessed. Moreover, the discriminant validity and concurrent validity scores were calculated. Results The test-retest reliability of the ASI scores ranged from .79 to .91. The interrater reliability assigned by three raters was high (.74 to .99). Cronbach’s alpha coefficient for internal consistency was .85 for all scales, and it varied between .64 and .77 for the subscales. The Beck Depression Inventory moderately correlated with the Psychatric status, and the MacAndrew Alcoholism Scale correlated with the Alcohol and Drug Use subscales of the Addiction Severity Index (ASI). The correlation coefficient was .91 for the alcohol use subscale. Conclusion The results obtained in this study suggest that the Turkish version of the ASI could be used as a reliable and valid instrument in alcohol-dependent patients.
Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka
We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.
Leclercq, Sophie; Matamoros, Sébastien; Cani, Patrice D; Neyrinck, Audrey M; Jamar, François; Stärkel, Peter; Windey, Karen; Tremaroli, Valentina; Bäckhed, Fredrik; Verbeke, Kristin; de Timary, Philippe; Delzenne, Nathalie M
Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.
Leclercq, Sophie; Matamoros, Sébastien; Cani, Patrice D.; Neyrinck, Audrey M.; Jamar, François; Stärkel, Peter; Windey, Karen; Tremaroli, Valentina; Bäckhed, Fredrik; Verbeke, Kristin; de Timary, Philippe; Delzenne, Nathalie M.
Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut–brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence. PMID:25288760
Wetherill, Leah; Kapoor, Manav; Agrawal, Arpana; Bucholz, Kathleen; Koller, Daniel; Bertelsen, Sarah E.; Le, Nhung; Wang, Jen-Chyong; Almasy, Laura; Hesselbrock, Victor; Kramer, John; Nurnberger, John I.; Schuckit, Marc; Tischfield, Jay A.; Xuei, Xiaoling; Porjesz, Bernice; Edenberg, Howard J.; Goate, Alison M.; Foroud, Tatiana
Background Despite the high heritability of alcohol dependence (AD), the genes found to be associated with it account for only a small proportion of its total variability. The goal of this study was to identify and analyze phenotypes based on homogeneous classes of individuals to increase the power to detect genetic risk factors contributing to the risk of AD. Methods The 7 individual DSM-IV criteria for AD were analyzed using latent class analysis (LCA) to identify classes defined by the pattern of endorsement of the criteria. A genome-wide association study was performed in 118 extended European American families (n = 2,322 individuals) densely affected with AD to identify genes associated with AD, with each of the seven DSM-IV criteria, and with the probability of belonging to two of three latent classes. Results Heritability for DSM-IV AD was 61%, and ranged from 17-60% for the other phenotypes. A SNP in the olfactory receptor OR51L1 was significantly associated (7.3 × 10−8) with the DSM-IV criterion of persistent desire to, or inability to, cut down on drinking. LCA revealed a three-class model: the “low risk” class (50%) rarely endorsed any criteria, and none met criteria for AD; the “moderate risk” class (33) endorsed primarily 4 DSM-IV criteria, and 48% met criteria for AD; the “high risk” class (17%) manifested high endorsement probabilities for most criteria and nearly all (99%) met criteria for AD One single nucleotide polymorphism (SNP) in a sodium leak channel NALCN demonstrated genome-wide significance with the high risk class (p=4.1 × 10−8). Analyses in an independent sample did not replicate these associations. Conclusion We explored the genetic contribution to several phenotypes derived from the DSM-IV alcohol dependence criteria. The strongest evidence of association was with SNPs in NALCN and OR51L1. PMID:24015780
Sloan, Matthew E; Gowin, Joshua L; Yan, Jia; Schwandt, Melanie L; Spagnolo, Primavera A; Sun, Hui; Hodgkinson, Colin A; Goldman, David; Ramchandani, Vijay A
The endocannabinoid system plays an important role in reward and addiction. One of the two main endocannabinoid neurotransmitters, anandamide, is metabolized by fatty acid amide hydrolase, an enzyme with a functional genetic polymorphism (FAAH Pro129Thr, rs324420). The Thr129 allele has been linked to problem drug and alcohol use, but the association has not been widely replicated and may be stronger for clinical measures of severity rather than categorical diagnosis. In the present study, we sought to determine whether the Thr129 allele was associated with both alcohol dependence (AD) diagnosis and severity in a sample of 1434 European American and African American individuals, 952 of whom were diagnosed with lifetime AD. Participants were genotyped for FAAH rs324420, and ancestry was determined via a genome-wide panel of ancestry informative markers. Subjects participated in Structured Clinical Interviews for psychiatric disorders and 90-day Timeline Followback interviews to assess recent alcohol use. European American participants with current AD had a higher Thr129 allele frequency than non-dependent controls. In European Americans with lifetime AD, there were significantly different distributions of drinking days and binge drinking days between the two genotype groups, with Thr129 carriers reporting a median of 10 fewer abstinent days and 13 more binge drinking days than Pro129/Pro129 homozygotes. In African American participants, there were no significant differences between Thr129 allele frequency in cases and controls and no significant differences in measures of AD severity by genotype. These findings provide evidence that the Pro129Thr missense variant is associated with AD severity in European Americans.
Brückmann, Christof; Di Santo, Adriana; Karle, Kathrin Nora; Batra, Anil; Nieratschker, Vanessa
Alcohol dependence is a severe disorder contributing substantially to the global burden of disease. Despite the detrimental consequences of chronic alcohol abuse and dependence, effective prevention strategies as well as treatment options are largely missing to date. Accumulating evidence suggests that gene-environment interactions, including epigenetic mechanisms, play a role in the etiology of alcohol dependence. A recent epigenome-wide study reported widespread alterations of DNA methylation patterns in alcohol dependent patients compared to control individuals. In the present study, we validate and replicate one of the top findings from this previous investigation in an independent cohort: the hypomethylation of GDAP1 in patients. To our knowledge, this is the first independent replication of an epigenome-wide finding in alcohol dependence. Furthermore, the AUDIT as well as the GSI score were negatively associated with GDAP1 methylation and we found a trend toward a negative association between GDAP1 methylation and the years of alcohol dependency, pointing toward a potential role of GDAP1 hypomethylation as biomarker for disease severity. In addition, we show that the hypomethylation of GDAP1 in patients reverses during a short-term alcohol treatment program, suggesting that GDAP1 DNA methylation could also serve as a potential biomarker for treatment outcome. Our data add to the growing body of knowledge on epigenetic effects in alcohol dependence and support GDAP1 as a novel candidate gene implicated in this disorder. As the role of GDAP1 in alcohol dependence is unknown, this novel candidate gene should be followed up in future studies.
Trova, A C; Paparrigopoulos, Th; Liappas, I; Ginieri-Coccossis, M
With the exception of cardiovascular diseases, no other medical condition causes more serious dysfunction or premature deaths than alcohol-related problems. Research results indicate that alcohol dependent individuals present an exceptionally poor level of quality of life. This is an outcome that highlights the necessity of planning and implementing preventive interventions on biological, psychological or social level, to be provided to individuals who make alcohol abuse, as well as to their families. Preventive interventions can be considered on three levels of prevention: (a) primary prevention, which is focused on the protection of healthy individuals from alcohol abuse and dependence, and may be provided on a universal, selective or indicated level, (b) secondary prevention, which aims at the prevention of deterioration regarding alcoholic dependence and relapse, in the cases of individuals already diagnosed with the condition and (c) tertiary prevention, which is focused at minimizing deterioration of functioning in chronically sufferers from alcoholic dependence. The term "quaternary prevention" can be used for the prevention of relapse. As for primary prevention, interventions focus on assessing the risk of falling into problematic use, enhancing protective factors and providing information and health education in general. These interventions can be delivered in schools or in places of work and recreation for young people. In this context, various programs have been applied in different countries, including Greece with positive results (Preventure, Alcolocks, LST, SFP, Alcohol Ignition Interlock Device). Secondary prevention includes counseling and structured help with the delivery of programs in schools and in high risk groups for alcohol dependence (SAP, LST). These programs aim at the development of alcohol refusal skills and behaviors, the adoption of models of behaviors resisting alcohol use, as well as reinforcement of general social skills. In the
Karakike, Eleni; Moreno, Christophe; Gustot, Thierry
Severe alcoholic hepatitis (sAH), defined by a modified discriminant function ≥32, is the most severe form of alcohol-induced liver disease and is associated with a 1-month mortality rate of around 30%. Corticosteroid treatment remains the only therapeutic option that improves short-term survival. Infectious complications, occurring in approximately 50% of patients, are the main causes of death, even in patients who benefit from corticosteroids. Liver failure, recent alcohol consumption and immunosuppressive drugs contribute to this infectious risk. Although infection is a well-described feature of cirrhosis, little is known about the characteristics of infections in sAH. Infection is mainly of bacterial origin and frequently affects the respiratory tract. Pathogens classically observed in cirrhosis, such as gram-negative bacilli, are frequently involved, but opportunistic pathogens, such as fungi (Aspergillus fumigatus, Pneumocystis jirovecii) or viruses (Cytomegalovirus, Herpes simplex) may appear, mainly related to corticosteroid treatment. A high level of suspicion with systematic screening and prompt, adequate treatment are warranted to improve outcomes in these patients. Prophylactic strategies in this high-risk population should be assessed in well-designed trials. PMID:28243035
This review focuses on classical and recent research work in the field of alcohol dependence. Data from psychopathological studies trying to determine a "pre-addictive" personality are exposed. More recent studies assess personality disorders and dimensions of temperament associated to alcohol dependence. Sensation seeking, antisocial personality and novelty seeking appear as the main psychological parameters involved in dependence. Sensation seeking is a dimension of personality often associated to behavioral dependence. Sensation seeking is assessed with a five-component scale including general factor, thrill and adventure seeking, experience-seeking, disinhibition, and boredom susceptibility. Patients presenting alcohol dependence have a higher level of sensation seeking. Neurophysiological and genetic studies try to correlate these personality features to biological parameters. Preliminary results of these works are presented and discussed.
Graves, Erin; Goodwin, Lloyd R., Jr.
Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…
Mancha, Brent E.; Rojas-Neese, Vanessa C.; Latimer, William W.
This study created an alcohol use problem severity taxonomy and examined its association to engagement in other problem behaviors. Minnesota youths were categorized based on their frequency of alcohol use and DSM-IV alcohol abuse and dependence criteria. Greater alcohol use problem severity was generally associated with higher prevalence of…
Sonne, Morten Egede; Rudolph, Søren Finnemann; Pott, Frank Christian
Severe metabolic acidosis is associated with poor prognosis. We present a patient with profound alcohol and starvation-related combined lactic and keto acidosis (lactate = 29 mM; pH = 6.83) who made a good recovery following 18 hours of intensive care therapy. A brief summary of the proposed mechanism by which these metabolic derangements develop is presented.
Yoshimura, Atsushi; Maesato, Hitoshi; Hisatomi, Nobuko; Higuchi, Susumu
Since the 1990s, we have suggested the concept of pre-alcoholism which encompasses patients who have drunk a great deal of alcohol leading to alcohol related problems such as health issues, domestic violence, drunken driving and black-outs. Pre-alcoholism excludes alcohol-dependent patients who have experienced continuous drinking or withdrawal symptoms. We have treated many outpatients with pre-alcoholism for several years. Our regimen demands that the patients must be abstinent for half a year at the beginning of their treatment. After half a year they can choose whether they will continue to be abstinent or they will resume drinking with the aim of reducing their total alcohol consumption. The study clarified the character of pre-alcoholism by investigation of the patients' background and re-diagnosis of the patients based on the International Classification of Diseases, 10th Revision (ICD-10). A remarkable ratio of pre-alcoholic patients was diagnosed with alcohol dependence under ICD-10. We classified pre-alcoholic patients into two groups, one diagnosed as having ICD-10-classed alcohol dependence and the other which did not fulfill the ICD-10 diagnostic criteria of alcohol dependence, and examined the therapeutic processes of the two groups. It was shown that most pre-alcoholic patients could finally take required courses of treatment by themselves without regard to diagnosis under ICD-10, even if they chose any treatment and made alcohol related mistakes on the way. Our findings suggested that pre-alcoholic patients, a portion of whom may have exhibited mild alcohol dependence, could select drinking reduction as a primary goal of treatment after a certain period of abstinence.
Tambour, Sophie; Quertemont, Etienne
In recent years, advances in neuroscience led to the development of new medications to treat alcohol dependence and especially to prevent alcohol relapse after detoxification. Whereas the earliest medications against alcohol dependence were fortuitously discovered, recently developed drugs are increasingly based on alcohol's neurobiological mechanisms of action. This review discusses the most recent developments in alcohol pharmacotherapy and emphasizes the neurobiological basis of anti-alcohol medications. There are currently three approved drugs for the treatment of alcohol dependence with quite different mechanisms of action. Disulfiram is an inhibitor of the enzyme aldehyde dehydrogenase and acts as an alcohol-deterrent drug. Naltrexone, an opiate antagonist, reduces alcohol craving and relapse in heavy drinking, probably via a modulation of the mesolimbic dopamine activity. Finally, acamprosate helps maintaining alcohol abstinence, probably through a normalization of the chronic alcohol-induced hyperglutamatergic state. In addition to these approved medications, many other drugs have been suggested for preventing alcohol consumption on the basis of preclinical studies. Some of these drugs remain promising, whereas others have produced disappointing results in preliminary clinical studies. These new drugs in the field of alcohol pharmacotherapy are also discussed, together with their mechanisms of action.
Addolorato, Giovanni; Mirijello, Antonio; Leggio, Lorenzo; Ferrulli, Anna; Landolfi, Raffaele
Alcohol dependence represents a chronic and relapsing disease affecting nearly 10% of the general population both in the United States and in Europe, with a widespread burden of morbidity and mortality. Alcohol dependence represents the most common cause of liver damage in the Western Countries. Although alcoholic liver disease is associated primarily with heavy drinking, continued alcohol consumption, even in low doses after the onset of liver disease, increases the risk of severe consequences, including mortality. Consequently the ideal treatment of patients affected by alcohol dependence and alcoholic liver disease should aim at achieving long-term total alcohol abstinence and preventing relapse. The aim of the present review is to provide an update on the management of alcohol dependence in patients with alcoholic liver disease. Increasing evidences suggests the usefulness of psychosocial interventions and medications combined in order to reduce alcohol intake, promote abstinence and prevent relapse in alcohol dependent patients. Disulfiram, naltrexone and acamprosate have been approved for this indication; gamma-hydroxybutyric acid (GHB) is approved in Italy and Austria. However, these drugs have not been tested in patients with advanced liver disease. Amongst other emerging pharmacotherapies for alcoholism, topiramate, ondansetron, and baclofen seem the most promising ones. Both topiramate and ondansetron hold a safe profile in alcoholic patients; however, none of them has been tested in alcoholic patients with advanced liver disease. To date, baclofen represents the only anti-craving medication formally tested in a randomized clinical trial in alcoholic patients affected by liver cirrhosis, although additional confirmatory studies are warranted. PMID:23456576
Tikka, Deyashini Lahiri; Ram, Daya; Dubey, Indu; Tikka, Sai Krishna
Background: Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. Aim: To understand the relationships amongst various of the socio-emotional factors. Materials and Methods: Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score <3) were compared on attachment styles (on Relationship Scale Questionnaire), anger domains (on State Trait Anger Expression Inventory), and self-esteem (on Rosenberg Self-esteem Scale). Statistics and Analysis: Comparison using independent samples t test and chi square test; correlation using Pearson's correlation coefficient. Results: Patients had significantly higher anger expression, ‘anger in’ and ‘anger out,’ and lower self-esteem than healthy controls. Severity of alcohol dependence had significant correlation with ‘anger out,’ and self-esteem had significant negative correlation with anger expression. Conclusion: The present study suggests that the socio-emotional factors studied are developmentally linked to each other. PMID:24860216
Cui, Changhai; Noronha, Antonio; Warren, Kenneth R; Koob, George F; Sinha, Rajita; Thakkar, Mahesh; Matochik, John; Crews, Fulton T; Chandler, L Judson; Pfefferbaum, Adolf; Becker, Howard C; Lovinger, David; Everitt, Barry J; Egli, Mark; Mandyam, Chitra D; Fein, George; Potenza, Marc N; Harris, R Adron; Grant, Kathleen A; Roberto, Marisa; Meyerhoff, Dieter J; Sullivan, Edith V
This article highlights the research presentations at the satellite symposium on "Brain Pathways to Recovery from Alcohol Dependence" held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed.
Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar
Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures.
Cui, Changhai; Noronha, Antonio; Warren, Kenneth; Koob, George F.; Sinha, Rajita; Thakkar, Mahesh; Matochik, John; Crews, Fulton T.; Chandler, L. Judson; Pfefferbaum, Adolf; Becker, Howard C.; Lovinger, David; Everitt, Barry; Egli, Mark; Mandyam, Chitra; Fein, George; Potenza, Marc N.; Harris, R. Adron; Grant, Kathleen A.; Roberto, Marisa; Meyerhoff, Dieter J.; Sullivan, Edith V.
This article highlights the research presentations at the satellite symposium on “Brain Pathways to Recovery from Alcohol Dependence” held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed. PMID:26074423
Grant, Julia D.; Agrawal, Arpana; Bucholz, Kathleen K.; Madden, Pamela A.F.; Pergadia, Michele L.; Nelson, Elliot C.; Lynskey, Michael T.; Todd, Richard D.; Todorov, Alexandre A.; Hansell, Narelle K.; Whitfield, John B.; Martin, Nicholas G.; Heath, Andrew C.
Background Previous research has reported a significant genetic correlation between heaviness of alcohol consumption and alcohol dependence (AD), but this association might be driven by the influence of AD on consumption rather than the reverse. We test the genetic overlap between AD symptoms and a heaviness of consumption measure among individuals who do not have AD. A high genetic correlation between these measures would suggest that a continuous measure of consumption may have a useful role in the discovery of genes contributing to dependence risk. Methods Factor analysis of 5 alcohol use measures was used to create a measure of heaviness of alcohol consumption. Quantitative genetic analyses of interview data from the 1989 Australian Twin Panel (n=6257 individuals; M=29.9 years) assessed the genetic overlap between heaviness of consumption, DSM-IV AD symptoms, DSM-IV AD symptom clustering, and DSM-IV alcohol abuse. Results Genetic influences accounted for 30–51% of the variance in the alcohol measures and genetic correlations were 0.90 or higher for all measures, with the correlation between consumption and dependence symptoms among non-dependent individuals estimated at 0.97 (95% CI: 0.80–1.00). Conclusions Heaviness of consumption and AD symptoms have a high degree of genetic overlap even among non-dependent individuals in the general population, implying that genetic influences on dependence risk in the general population are acting to a considerable degree through heaviness of use, and that quantitative measures of consumption will likely have a useful role in the identification of genes contributing to AD. PMID:19576574
Staples, Miranda C.; Mandyam, Chitra D.
Alcohol use disorder currently affects approximately 18 million Americans, with at least half of these individuals having significant cognitive impairments subsequent to their chronic alcohol use. This is most widely apparent as frontal cortex-dependent cognitive dysfunction, where executive function and decision-making are severely compromised, as well as hippocampus-dependent cognitive dysfunction, where contextual and temporal reasoning are negatively impacted. This review discusses the relevant clinical literature to support the theory that cognitive recovery in tasks dependent on the prefrontal cortex and hippocampus is temporally different across extended periods of abstinence from alcohol. Additional studies from preclinical models are discussed to support clinical findings. Finally, the unique cellular composition of the hippocampus and cognitive impairment dependent on the hippocampus is highlighted in the context of alcohol dependence. PMID:27746746
de Timary, Philippe; Leclercq, Sophie; Stärkel, Peter; Delzenne, Nathalie
The vast majority of studies that assessed the importance of biological factors for the development of psychiatric disorders focused on processes occurring at the brain level. Alcohol-dependence is a very frequent psychiatric disorder where psycho-pharmacological interventions are only of moderate efficacy. Our laboratory has recently described that a subpopulation of alcohol-dependent subjects, that accounted for approximately 40% of individuals tested, presented with an increased intestinal permeability, with a dysbiosis, with alterations in the metabolomic content of faeces - that could play a role in the increased permeability - and finally with a more severe profile of alcohol-dependence than the other non-dysbiotic subpopulation. In this addendum, we discuss the implications of our observations for the pathophysiology of alcohol dependence where we try to discriminate which addiction dimensions are likely related to the gut microbiota alterations and whether these alterations are the cause or the consequence of drinking habits. PMID:26727422
de Timary, Philippe; Leclercq, Sophie; Stärkel, Peter; Delzenne, Nathalie
The vast majority of studies that assessed the importance of biological factors for the development of psychiatric disorders focused on processes occurring at the brain level. Alcohol-dependence is a very frequent psychiatric disorder where psycho-pharmacological interventions are only of moderate efficacy. Our laboratory has recently described that a subpopulation of alcohol-dependent subjects, that accounted for approximately 40% of individuals tested, presented with an increased intestinal permeability, with a dysbiosis, with alterations in the metabolomic content of faeces--that could play a role in the increased permeability--and finally with a more severe profile of alcohol-dependence than the other non-dysbiotic subpopulation. In this addendum, we discuss the implications of our observations for the pathophysiology of alcohol dependence where we try to discriminate which addiction dimensions are likely related to the gut microbiota alterations and whether these alterations are the cause or the consequence of drinking habits.
Vendruscolo, Leandro F.; Roberts, Amanda J.
Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be. PMID:24290310
Vendruscolo, Leandro F; Roberts, Amanda J
Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be.
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
Batki, Steven L.; Leontieva, Luba; Dimmock, Jacqueline A.; Ploutz-Snyder, Robert
Background Alcohol use disorders (AUDs) frequently co-occur with and exacerbate schizophrenia, yet the specific relationships between schizophrenia symptoms and alcohol use remain unclear. Methods PANSS scores were correlated with measures of alcohol and other substance use in patients with schizophrenia-spectrum disorders and AUDs entering a trial of monitored naltrexone treatment. Data were analyzed from the first 80 participants; 55% had schizophrenia and 45% had schizoaffective disorder. All had AUDs; 95% had alcohol dependence and 5% alcohol abuse; 34% also had cannabis abuse/dependence and 31% cocaine abuse/dependence. Results PANSS Negative scores were inversely correlated with Addiction Severity Index alcohol composite score, alcohol craving, quality of alcohol “high” (euphoria), and with frequency of cannabis use. An exploratory analysis indicated that the negative symptoms that may most strongly correlate with less alcohol use, craving or euphoria were passive/apathetic social withdrawal, blunted affect, difficulty in abstract thinking, and stereotyped thinking. Higher PANSS Composite scores, indicating the predominance of positive over negative PANSS symptoms, correlated with more alcohol craving and cannabis use. Higher PANSS General scores were associated with more alcohol craving. Conclusions These findings extend previous reports of the association of negative schizophrenia symptoms with less alcohol and substance use to patients with AUDs and indicate that this relationship also includes less alcohol craving and less alcohol euphoria. The findings may also provide some initial evidence that specific negative symptoms may be key to these relationships. PMID:18701256
Glass, J.M.; Buu, A.; Adams, K.M.; Nigg, J.T.; Puttler, L.I.; Jester, J.M.; Zucker, R.A.
Aims Neurocognitive deficits in chronic alcoholic men are well documented and include impairments in memory, visual-spatial processing, problem solving and executive function. The cause of these deficits is unclear, but could include direct effects of alcohol toxicity, pre-existing cognitive deficits that may predispose towards substance abuse, comorbid psychiatric disorders (e.g., depression) and comorbid abuse of substances other than alcohol. For example, cigarette smoking occurs at a much higher rate among persons with alcoholism and has been linked to poor cognitive performance. Until recently, the negative effects of smoking on cognitive function in alcoholism have been ignored. Methods The effects of alcoholism and smoking are examined in a community recruited sample of alcoholic and non-alcoholic men (N=240) using standard neuropsychological measures and reaction-time measures of executive function. Alcoholism severity was measured as an average of alcoholism diagnoses across the study duration (12 yrs). Smoking was measured in pack-years. Results Both alcoholism and smoking were negatively correlated with a composite executive function score. For component measures, alcoholism was negatively correlated with a broad range of measures, whereas smoking was negatively correlated with measures that emphasize response speed. In regression analyses, both smoking and alcoholism are significant predictors of executive function composite. However; when IQ is included in the regression analyses, alcoholism severity is no longer a significant predictor. Conclusions Both smoking and alcoholism were related to executive function. However, the effect of alcoholism on EF was not independent of IQ, suggesting that the alcoholism effect was generalized, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were independent of IQ, suggesting a more
Griffin, William C
Alcohol dependence continues to be an important health concern and animal models are critical to furthering our understanding of this complex disease. A hallmark feature of alcoholism is a significant increase in alcohol drinking over time. While several different animal models of excessive alcohol (ethanol) drinking exist for mice and rats, a growing number of laboratories are using a model that combines chronic ethanol exposure procedures with voluntary ethanol drinking with mice as experimental subjects. Primarily, these studies use a chronic intermittent ethanol (CIE) exposure pattern to render mice dependent and a 2-h limited access procedure to evaluate drinking behavior. Compared to non-dependent mice that also drink ethanol, the ethanol-dependent mice demonstrate significant increases in voluntary ethanol drinking. The increased drinking significantly elevates blood and brain ethanol concentrations compared to the non-dependent control mice. Studies report that the increased drinking by dependent mice is driven by neuroadaptations in glutamatergic and corticotropin-releasing factor signaling in different brain regions known to be involved in alcohol-related behaviors. The dysregulation of these systems parallels findings in human alcoholics and treatments that demonstrate efficacy in alcoholics can also reduce drinking in this model. Moreover, preclinical findings have informed the development of human clinical trials, further highlighting the translational potential of the model. As a result of these features, the CIE exposure and free-choice drinking model is becoming more widely used and promises to provide more insight into mechanisms of excessive drinking that may be important for developing treatments for human alcoholics. The salient features and possible future considerations for CIE exposure and free-choice drinking in mice are discussed.
Manzardo, Ann M.; Pendleton, Tiffany; Poje, Albert; Penick, Elizabeth C.; Butler, Merlin G.
Background Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with serious illness and neurological deficits that influence mood and cognition. We previously reported reduced alcohol consumption among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). As a follow-up, we have examined the relationship between lifetime alcoholism severity and psychiatric symptoms among the alcohol dependent men from this cohort and their response to BF treatment. Methods Eighty-five adult men (mean age = 48 ± 8 yrs) meeting DSM-IV-TR criteria for current alcohol dependence participated in a randomized, double-blind, placebo-controlled trial of 600 mg BF vs placebo (PL) for 6 months. Psychometric testing included a derived Lifetime Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months with data analyzed using ANOVA and MANOVA modeling. Results Baseline SCL-90-R scale scores for men with high alcoholism severity (AS ≥ 24; N=46 HAS) were significantly greater than for men with low alcoholism severity (AS < 24; N=39 LAS), but BIS scores did not differ. MANOVA modeling identified a significant treatment effect (F=2.5, df=10, p<0.03) and treatment x alcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, p<0.03) with SCL-90-R scores showing a reduction in symptoms among BF treated, high severity males. Conclustion BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with lifetime alcohol dependence and should be considered for adjuvant therapy in alcohol rehabilitation. PMID:25908323
Samokhvalov, Andriy V.; Popova, Svetlana; Room, Robin; Ramonas, Milita; Rehm, Jürgen
BACKGROUND Alcohol use disorders (AUD), i.e., alcohol dependence and abuse are major contributors to burden of disease. A large part of this burden is due to disability. However, there is still controversy about the best disability weighting for alcohol use disorders. The objective of this study was to provide an overview of alcohol-related disabilities. METHODS Systematic literature review and expert interviews. RESULTS There is heterogeneity in experts’ descriptions of disabilities related to AUD. The major core attributes of disability related to AUD are changes of emotional state, social relationships, memory and thinking. The most important supplementary attributes are anxiety, impairments of speech and hearing. CONCLUSIONS This review identified the main patterns of disability associated with alcohol use disorders. However, there was considerable variability, and data on less prominent patterns were fragmented. Further and systematic research is required for increasing the knowledge on disability related to alcohol use disorders and for application of interventions for reducing the associated burden. OBJECTIVE To provide an overview of disabilities associated with AUD. PMID:20662803
Rozatkar, Abhijit R.; Kapoor, Abhishek; Sidana, Ajeet; Chavan, Bir Singh
Introduction: Craving is recognized as a formidable barrier in the management of patients with alcohol dependence. Among pharmacological agents that have been used in experimental studies for reduction in craving, baclofen appears to have a significant advantage over other agents. Methodology: The study is retrospective chart review of patients (n = 113) who have been treated with baclofen for alcohol dependence in a tertiary hospital of North India. Baseline assessments included sociodemography, motivation, quantity-frequency of alcohol use, and other alcohol-related clinical parameters. Weekly assessments, for a period of 4 weeks, were extracted from records which included dose of baclofen, craving intensity, and alcohol consumption. Results: The study sample was predominantly male, mean age of 41.49 (±9.75) years, most having a family history of substance use (70.97%), and many reporting binge use pattern in last year (49.46%). Baseline assessment revealed 48.7% of the sample was in precontemplation phase for alcohol use and 70% reported severe and persistent craving. This persistent craving was reported by only 15% of the sample by the end of 4 weeks treatment with baclofen (20–40 mg/day). Thirty-four percent of patients reported continued problematic use of alcohol by the end of 4 weeks. Conclusion: Our clinical experience suggests that baclofen reduces craving and alcohol consumption including in those with poor motivation. The drug causes few side effects and does not add to the intoxication effect of alcohol. Considering that baclofen is safe in those with liver cirrhosis and reduces withdrawal symptoms due to alcohol, a controlled trial comparing it with standard treatment is required. PMID:28163402
Shukla, Lekhansh; Shukla, Tulika; Bokka, Spandana; Kandasamy, Arun; Benegal, Vivek; Murthy, Pratima; Chand, Prabhat
Alcohol dependence is a global concern. Baclofen has shown promise as an anti-craving agent but its efficiency remains to be settled. We reviewed 549 male cases diagnosed with alcohol dependence who received Acamprosate (201) or Baclofen (348). ‘Time to first drink’ was compared between two groups and multiple regression analysis was done in baclofen group to identify correlates of effectiveness. There was a significant difference in outcome measure between Baclofen (M = 4.44, SD = 3.75) and Acamprosate group (M = 3.73, SD = 2.19); t (547) = 2.45, P = 0.01. Initial regression analysis with six predictor variables (average daily alcohol units, current age, age at onset of dependence, family history, duration of dependence and dose of baclofen in mg/day) showed significant correlation of outcome variable with only two predictor variables — dose of baclofen and average daily intake. Using the hierarchical method it was found that ‘dose of baclofen’ and ‘average alcohol intake’ explain a significant amount of variance in ‘time to first drink’. [F (1, 345) = 182.8, P < 0.001, R2 = 0.52, R2adjusted = 0.51]. This information can be used to select patients in long term longitudinal studies and may explain variable results seen in clinical trials of baclofen done earlier. PMID:26664095
Evren, Cuneyt; Sar, Vedat; Karadag, Figen; Tamar Gurol, Defne; Karagoz, Mustafa
The aim of this study was to determine the prevalence of dissociative disorders among inpatients with alcohol dependency. The Dissociative Experiences Scale was used to screen 111 alcohol-dependent patients consecutively admitted to the inpatient unit of a dependency treatment center. Subgroups of 29 patients who scored 30.0 or above and 25 patients who scored below 10.0 were then evaluated with the Dissociative Disorders Interview Schedule and the Structured Interview for DSM-IV Dissociative Disorders. The interviewers were blind to the Dissociative Experiences Scale scores. Of the 54 patients evaluated, 10 (9.0% of the original 111) patients had a dissociative disorder. A considerable number of the remaining patients reported a high level of dissociative experiences. Among the dissociative disorder group, nine patients had dissociative disorder not otherwise specified and one patient had depersonalization disorder. Female gender, younger age, history of suicide attempt, childhood emotional and sexual abuse, and neglect were more frequent in the dissociative disorder group than among non-dissociative patients. The dissociative disorder group also had somatization disorder, borderline personality disorder, and lifetime major depression more frequently. For 9 of the 10 dissociative patients, dissociative symptoms started before the onset of alcohol use. Although the probability of having a comorbid dissociative disorder was not higher among alcohol-dependent inpatients than among the general psychiatric inpatients, the dissociative subgroup had distinct features. Many patients without a dissociative disorder diagnosis (predominantly men) provided hints of subtle dissociative psychopathology. Implications of comorbid dissociative disorders and dissociative experiences on prevention and treatment of alcohol dependency and the importance of gender-specific characteristics in this relationship require further study.
Gizer, Ian R.; Ehlers, Cindy L.; Vietan, Cassandra; Seaton-Smith, Kimberly L.; Feiler, Heidi S.; Lee, James V.; Segall, Samantha K.; Gilder, David A.; Wilhelmsen, Kirk C.
Ample data suggest alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31–p36.22, 2q37.3, 8q24.3, and 18p11.21–p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31–p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3–p24.1, 9p24.1–p23, and 22q12.3–q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence. PMID:20817416
Terranova, Claudio; Tucci, Marianna; Sartore, Daniela; Cavarzeran, Fabiano; Di Pietra, Laura; Barzon, Luisa; Palù, Giorgio; Ferrara, Santo D
The aim of this study was to analyze the connection between alcohol dependence and criminal behavior by an integrated genetic-environmental approach. The research, structured as a case-control study, examined 186 alcohol-dependent males; group 1 (N = 47 convicted subjects) was compared with group 2 (N = 139 no previous criminal records). Genetic results were innovative, highlighting differences in genotype distribution (p = 0.0067) in group 1 for single-nucleotide polymorphism rs 3780428, located in the intronic region of subunit 2 of the GABA B receptor gene (GABBR2). Some environmental factors (e.g., grade repetition) were associated with criminal behavior; others (e.g., attendance at Alcoholics Anonymous) were inversely related to convictions. The concomitant presence of the genetic and environmental factors found to be associated with the condition of alcohol-dependent inmate showed a 4-fold increase in the risk of antisocial behavior. The results need to be replicated on a larger population to develop new preventive and therapeutic proposals.
Haverfield, Marie C; Theiss, Jennifer A
Alcoholism is a highly stigmatized condition, with both alcohol-dependent individuals and family members of the afflicted experiencing stigmatization. This study examined the severity of a parent's alcoholism and family topic avoidance about alcohol as two factors that are associated with family members' perceptions of stigma. Three dimensions of stigma were considered: discrimination stigma, disclosure stigma, and positive aspect stigma. In addition, this study assessed associations between perceived stigmatization and individuals' experiences of depressive symptoms, self-esteem, and resilience. Adult children of alcoholics (N = 622) were surveyed about family conditions, perceived stigma, and their emotional and psychological well-being. Regression analyses revealed that the severity of a parent's alcoholism predicted all three types of stigma for females, but not for males. In addition, family topic avoidance about alcohol predicted all types of stigma for males and discrimination stigma and positive aspect stigma for females. With few exceptions, the three types of stigma predicted depressive symptoms, self-esteem, and resilience for both male and female adult children of alcoholics. The results are discussed in terms of their implications for promoting a family environment that mitigates stigma and encourages emotional and psychological well-being. In 2012, approximately 3.3 million deaths worldwide were due to the harmful use of alcohol (World Health Organization [WHO], 2014). Individuals who abuse alcohol are susceptible to a variety of negative health outcomes (Rehm et al., 2009) and display inappropriate social behaviors (Klingemann, 2001; Schomerus et al., 2011a). General societal perceptions tend to characterize alcohol-dependent individuals as irresponsible and lacking in self-control (Schomerus et al., 2011b). Research in the United Kingdom found that 54% of the population believes alcohol-dependent individuals are personally to blame for their own
Leksowski, W; Kawalaski, H; Czuba, Z; Krol, W; Gorczyca, P; Dworniczak, S; Rajca, M; Shani, J
Alcohol abuse is a major cause of abnormal liver development and activity. In addition to enzymatic malfunction, alcohol and its metabolites induce changes in the levels of some liver antigens, resulting in immunological disturbance. The purpose of the present study is to correlate the severity of liver function impairment with the length of alcohol abuse, in order to be able to use such tests as indicative of the severity of Alcohol Dependence Syndrome. Thirty-one alcohol abusers were allocated to three groups on the basis of the levels of their liver enzymes, and were tested for a variety of immunological parameters and skin reactions. The data indicate that even though not all immunological values measured differed significantly from the control values, in those that did (granulocytes, lymphocytes, CD4/CD8 ratio, C3, IgG, IgM and some skin positive reactions), the biggest difference was between the healthy volunteers and the group with the longest abuse period. It is suggested that changes in selected immunological parameters in alcohol abusers may indicate the severity of their liver dysfunction.
Martinotti, Giovanni; Di Nicola, Marco; Janiri, Luigi
Dopaminergic agonists and antagonists have both been examined for the treatment of substance abuse with contrasting results. To the best of our knowledge dopamine receptor partial agonists have not been investigated in alcohol use disorders. Thirteen detoxified alcohol-dependent subjects were treated with flexible doses of aripiprazole for 16 weeks. Six patients maintained an alcohol free condition for all the study period. All the subjects experienced a reduction of craving in both OCDS (p < .05) and VAS (p < .05), and a decrease of the SCL-90 General Severity Index (GSI) (p < .05). The data of this pilot clinical study, suggest a possible role for this drug in the treatment of individuals with alcohol problems.
Bahlmann, M; Preuss, U W; Soyka, M
Personality disorders, and particularly antisocial personality disorder (ASPD), frequently co-occur with alcohol dependence. ASPD is considered to be an important cofactor in the pathogenesis and clinical course of alcohol dependence. The chronological relationship between the onset of symptoms of ASPD and alcohol-dependence characteristics has not yet been studied in great detail and the role of ASPD in classification schemes of alcohol dependence as suggested by Cloninger and Schuckit has yet to be determined. We studied 55 alcohol-dependent patients to assess the prevalence and age at manifestation of ASPD, conduct disorder characteristics as well as alcohol dependence by employing the Semi-Structured Assessment for the Genetics of Alcoholism and the Structured Clinical Interview for DSM-III-R. Results indicate that the onset of ASPD characteristics precede that of alcohol dependence by some 4 years. This finding suggests that in patients with ASPD, alcohol dependence might be a secondary syndrome as suggested by previous research.
Richardson, Heather N.; Chan, Stephanie H.; Crawford, Elena F.; Lee, Youn Kyung; Funk, Cindy K.; Koob, George F.; Mandyam, Chitra D.
Experimenter-delivered alcohol decreases adult hippocampal neurogenesis, and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis was observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggests a loss in neuronal turnover and indicates that the hippocampal neurogenic niche is highly vulnerable to alcohol. PMID:19501165
Reich, T; Edenberg, H J; Goate, A; Williams, J T; Rice, J P; Van Eerdewegh, P; Foroud, T; Hesselbrock, V; Schuckit, M A; Bucholz, K; Porjesz, B; Li, T K; Conneally, P M; Nurnberger, J I; Tischfield, J A; Crowe, R R; Cloninger, C R; Wu, W; Shears, S; Carr, K; Crose, C; Willig, C; Begleiter, H
Alcohol dependence is a leading cause of morbidity and premature death. Several lines of evidence suggest a substantial genetic component to the risk for alcoholism: sibs of alcoholic probands have a 3-8 fold increased risk of also developing alcoholism, and twin heritability estimates of 50-60% are reported by contemporary studies of twins. We report on the results of a six-center collaborative study to identify susceptibility loci for alcohol dependence. A genome-wide screen examined 291 markers in 987 individuals from 105 families. Two-point and multipoint nonparametric linkage analyses were performed to detect susceptibility loci for alcohol dependence. Multipoint methods provided the strongest suggestions of linkage with susceptibility loci for alcohol dependence on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In addition, there was suggestive evidence for a protective locus on chromosome 4 near the alcohol dehydrogenase genes, for which protective effects have been reported in Asian populations.
Durbin-Johnson, Blythe; Halsted, Charles H.; Medici, Valentina
Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD. PMID:25702770
Zuo, Lingjun; Zhang, Heping; Malison, Robert T.; Li, Chiang-Shan R.; Zhang, Xiang-Yang; Wang, Fei; Lu, Lingeng; Lu, Lin; Wang, Xiaoping; Krystal, John H.; Zhang, Fengyu; Deng, Hong-Wen; Luo, Xingguang
Aims: Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference. Methods: A total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7–ADH1C–ADH1B–ADH1A–ADH6–ADH4–ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis. Results: We found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P = 0.045), European-Australians (Fp5: global P = 0.027; collapsing: P = 0.038) and African-Americans (Fp5: global P = 0.050; collapsing: P = 0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons. Conclusion: We conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence. PMID:23019235
Bernardin, Florent; Maheut-Bosser, Anne; Paille, François
Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units. PMID:25076914
Odlaug, B.L.; Gual, A.; DeCourcy, J.; Perry, R.; Pike, J.; Heron, L.; Rehm, J.
Aims Alcohol dependence is associated with high rates of co-occurring disorders which impact health-related quality of life (HRQoL) and add to the cost-of-illness. This study investigated the burden of alcohol dependence and associated co-occurring conditions on health and productivity. Methods A cross-sectional survey was conducted in eight European countries. Physicians (Psychiatrists and General Practitioners) completed patient record forms, which included assessment of co-occurring conditions, and patients completed matching self-completion forms. Drinking risk level (DRL) was calculated and the relationship between DRL, co-occurring conditions, work productivity, hospitalisations and rehabilitation stays was explored. Results Data were collected for 2979 alcohol-dependent patients (mean age 48.8 ± 13.6 years; 70% male). In total, 77% of patients suffered from moderate-to-severe co-occurring psychiatric and/or somatic conditions. High DRL was significantly associated with depression, greater work productivity losses, increased hospitalisations and rehabilitation stays. Co-occurring conditions were significantly associated with poorer HRQoL and decreased work productivity, with a statistical trend towards an increased frequency of rehabilitation stays. Conclusions Alcohol-dependent patients manifest high rates of co-occurring psychiatric and somatic conditions, which are associated with impaired work productivity and HRQoL. The continued burden of illness observed in these already-diagnosed patients suggests an unmet need in both primary and secondary care. PMID:26246514
McClain, Justin A; Morris, Stephanie A; Marshall, S Alexander; Nixon, Kimberly
The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence. Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence. Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively. The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence. Although these results mirror the magnitude of reactive neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults. The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats. Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.
Nordquist, Niklas; Göktürk, Camilla; Comasco, Erika; Nilsson, Kent W; Oreland, Lars; Hallman, Jarmila
Susceptibility to alcoholism and antisocial behavior exhibits an evident link to monoaminergic neurotransmission. The serotonin system in particular, which is associated with regulation of mood and behavior, has an influence on personality characters that are firmly connected to risk of developing alcoholism and antisocial behavior, such as impulsiveness, and aggression. The transcription factor TFAP2b has repeatedly been shown to be involved in monoaminergic transmission, likely due to a regulatory effect on genes that are fundamental to this system, e.g. monoamine oxidase type A, and the serotonin transporter. Recent research has identified a functional polymorphism in the gene encoding TFAP2B that regulates its level of expression. In the present study we have compared a sample of female alcoholics (n=107), sentenced to institutional care for their severe addiction, contrasted against a control sample of adolescent females (n=875). The results showed that parental alcohol misuse was significantly more common among the alcoholic females, and also that parental alcohol misuse was associated with a reduction in age of alcohol debut. We also addressed the question of whether a functional TFAP2b polymorphism was associated with alcoholism. Results showed that the high-functioning allele was significantly more common among the female alcoholics, compared to the non-alcoholic controls. Furthermore, the results also indicated that psychosocial factors, in terms of parental alcohol misuse, depression or psychiatric disorder, had an influence on the association. It was observed that the genetic association was restricted to the subset of cases that had not experienced these negative psychosocial factors.
Huang, Ming-Chyi; Schwandt, Melanie L; Chester, Julia A; Kirchhoff, Aaron M; Kao, Chung-Feng; Liang, Tiebing; Tapocik, Jenica D; Ramchandani, Vijay A; George, David T; Hodgkinson, Colin A; Goldman, David; Heilig, Markus
Alcohol withdrawal is associated with hypothalamic–pituitary–adrenal (HPA) axis dysfunction. The FKBP5 gene codes for a co-chaperone, FK506-binding protein 5, that exerts negative feedback on HPA axis function. This study aimed to examine the effects of single-nucleotide polymorphisms (SNPs) of the FKBP5 gene in humans and the effect of Fkbp5 gene deletion in mice on alcohol withdrawal severity. We genotyped six FKBP5 SNPs (rs3800373, rs9296158, rs3777747, rs9380524, rs1360780, and rs9470080) in 399 alcohol-dependent inpatients with alcohol consumption 48 h before admission and recorded scores from the Clinical Institute Withdrawal Assessment-Alcohol revised (CIWA-Ar). Fkbp5 gene knockout (KO) and wild-type (WT) mice were assessed for alcohol withdrawal using handling-induced convulsions (HICs) following both acute and chronic alcohol exposure. We found the minor alleles of rs3800373 (G), rs9296158 (A), rs1360780 (T), and rs9470080 (T) were significantly associated with lower CIWA-Ar scores whereas the minor alleles of rs3777747 (G) and rs9380524 (A) were associated with higher scores. The haplotype-based analyses also showed an association with alcohol withdrawal severity. Fkbp5 KO mice showed significantly greater HICs during withdrawal from chronic alcohol exposure compared with WT controls. This study is the first to show a genetic effect of FKBP5 on the severity of alcohol withdrawal syndrome. In mice, the absence of the Fkbp5 gene enhances sensitivity to alcohol withdrawal. We suggest that FKBP5 variants may trigger different adaptive changes in HPA axis regulation during alcohol withdrawal with concomitant effects on withdrawal severity. PMID:24603855
Rehm, Jürgen; Rehm, Maximilien X; Shield, Kevin D; Gmel, Gerrit; Gual, Antoni
Alcohol consumption in Spain has traditionally followed the Mediterranean drinking pattern, featuring daily drinking with meals, beer as the preferred beverage, and comparatively little drinking to intoxication. Alcohol dependence (AD), one of the most detrimental disorders caused by alcohol, was prevalent in 0.2% of women and 1.2% of men, corresponding to 31,200 women and 186,000 men in Spain with AD in 2005 in the age group of 15 to 64 year. These prevalence estimates of alcohol dependence are likely underestimated due to limitations in the World Mental Health Survey which cannot be fully corrected for; however, the estimates of AD for Spain represent the most accurate and up to date estimates available. Alcohol creates a significant health burden in Spain with 11.3 premature deaths in women per 100,000 aged 15 to 64 years, and 40.9 premature deaths in men per 100,000 in the same age group were due to alcohol consumption (data for 2004). This amounts to 8.4% of all female deaths and 12.3% of all the male deaths in this age group being attributable to alcohol consumption. A large percentage of these harms were due to heavy alcohol consumption and AD. AD is undertreated in Spain, with less than 10% of all people with AD treated. For those who are treated, psychotherapy is the most utilized form of treatment to avoid relapse. If 40% of AD patients in Spain were treated with pharmacological treatment (the most effective treatment method), 2.2% of female and 6.2% of male deaths due to AD would be prevented within one year. Thus by increasing treatment rates is an important means of reducing the alcohol-attributable mortality and health burden in Spain.
Heyser, Charles J.
Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence have identified specific neurotransmitter targets for the development of pharmacological treatments. Acamprosate, marketed under the brand name Campral, is an orally administered drug available by prescription in the U.S. and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in numerous clinical trials worldwide. Here we provide an overview of acamprosate in the context of the neurobiological underpinnings of alcohol dependence. We propose that unlike previously available pharmacotherapies, acamprosate represents a prototype of a neuromodulatory approach in the treatment of alcohol dependence. A neuromodulatory approach seeks to restore the disrupted changes in neurobiology resulting from chronic alcohol intake. It is our opinion that a neuromodulatory approach will provide a heuristic framework for developing more effective pharmacotherapies for alcohol dependence. PMID:20201812
Background Research investigating the differential effectiveness of Brief Motivational Interventions (BMI) among alcohol dependent and non-dependent patients in the medical setting is limited. Clinical guidelines suggest that BMI is most appropriate for patients with less severe alcohol problems. As a result, most studies evaluating the effectiveness of BMI have excluded patients with an indication of alcohol dependence. Methods A randomized controlled trial of brief intervention in the trauma care setting comparing BMI to treatment as usual plus assessment (TAU+) was conducted. Alcohol dependence status was determined for 1336 patients using DSM-IV diagnostic criteria. The differential effectiveness of BMI among alcohol dependent and non-dependent patients was determined with regard to volume per week, maximum amount consumed, percent days abstinent, alcohol problems at six and 12 month follow up. In addition, the effect of BMI on dependence status at six and 12 months was determined. Results There was a consistent interaction between BMI and alcohol dependence status, which indicated significantly higher reductions in volume per week at six and twelve month follow up (β=−.56, p=.03, β=−.63, p=.02, respectively), maximum amount at six months (β=−.31, p=.04), and significant decreases in percent days abstinent at twelve months (β=.11, p=.007) and alcohol problems at twelve months (β=−2.7, p12=.04) among patients with alcohol dependence receiving BMI. In addition, patients with alcohol dependence at baseline that received BMI were .59 (95% CI=.39–.91) times less likely to meet criteria for alcohol dependence at six months. Conclusions These findings suggest that BMI is more beneficial among patients with alcohol dependence who screen positive for an alcohol related injury. PMID:20493644
Latimer, William W.; Rojas, Vanessa Cecilia; Mancha, Brent Edward
Objectives The present study sought to: (a) categorize youths into groups based on their level of alcohol use and number of symptoms of alcohol abuse and dependence defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and (b) examine whether these categories were associated with other problem behaviors in which youths engage (marijuana use, sexual intercourse, and having been arrested or having trouble with the law). Methods The study is based on a cross-sectional survey administered to 972 school-based youths from one middle school and one high school in San Juan, Puerto Rico. Youths were categorized based on their alcohol use and alcohol problems. These categories were then examined for associations with lifetime marijuana use, lifetime sexual intercourse, and having been arrested or having had trouble with the law in the past year. The original eight categories of alcohol use were collapsed into six categories based on the results. Results For virtually every group characterized by higher severity of alcohol use and alcohol problems, researchers found an increasing prevalence of marijuana use in their lifetimes, increasing odds of sexual intercourse in their lifetimes, and having had trouble with the law in the past year. Conclusions Knowing about variations in alcohol use and alcohol problems may be instrumental in measuring the degree to which youths may also be engaging in a range of other elevated risk behaviors and a progression to more serious forms of alcohol and drug use. PMID:18510792
Lewis, Melissa A.; Neighbors, Clayton; Geisner, Irene Markman; Lee, Christine M.; Kilmer, Jason R.; Atkins, David C.
The present study examined a range of injunctive norms for alcohol use and related consequences from less severe behaviors (e.g., drinking with friends) to more severe behaviors (e.g., drinking enough alcohol to pass out), and their relationship with alcohol consumption and alcohol-related negative consequences among college students. In addition, this research aimed to determine if these relationships between injunctive norms and consequences were moderated by alcohol consumption and level of identification with the typical same-sex college student. A random sample (N = 1,002) of undergraduates (56.9% female) completed a Web–based survey that was comprised of measures of drinking behavior, perceived approval of drinking behaviors that ranged in severity (i.e., injunctive norms), and level of identification with the typical same-sex college student. Results suggest that the association between negative consequences and injunctive drinking norms depend on one's own drinking behavior, identification with other students, and the severity of the alcohol use and related consequences for which injunctive norms are assessed. Findings are discussed in terms of false consensus and false uniqueness effects, and deviance regulation perspectives. Implications for preventative interventions are discussed. PMID:20565144
Foroud, T; Bucholz, K K; Edenberg, H J; Goate, A; Neuman, R J; Porjesz, B; Koller, D L; Rice, J; Reich, T; Bierut, L J; Cloninger, C R; Nurnberger, J I; Li, T K; Conneally, P M; Tischfield, J A; Crowe, R; Hesselbrock, V; Schuckit, M; Begleiter, H
There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.
ZUO, Lingjun; ZHANG, Clarence K.; SAYWARD, Frederick G.; CHEUNG, Kei-Hoi; WANG, Kesheng; KRYSTAL, John H.; ZHAO, Hongyu; LUO, Xingguang
Background The organization of risk genes within signaling pathways may provide clues about the converging neurobiological effects of risk genes for alcohol dependence. Aim Identify risk genes and risk gene pathways for alcohol dependence. Methods We conducted a pathway-based genome-wide association study (GWAS) of alcohol dependence using a gene-set-rich analytic approach. Approximately one million genetic markers were tested in the discovery sample which included 1409 European-American (EA) alcohol dependent individuals and 1518 EA healthy comparison subjects. An additional 681 African-American (AA) cases and 508 AA healthy subjects served as the replication sample. Results We identified several genome-wide replicable risk genes and risk pathways that were significantly associated with alcohol dependence. After applying the Bonferroni correction for multiple testing, the ‘cellextracellular matrix interactions’ pathway (p<2.0E-4 in EAs) and the PXN gene (which encodes paxillin) (p=3.9E-7 in EAs) within this pathway were the most promising risk factors for alcohol dependence. There were also two nominally replicable pathways enriched in alcohol dependence-related genes in both EAs (0.015≤p≤0.035) and AAs (0.025≤p≤0.050): the ‘Na+/Cl- dependent neurotransmitter transporters’ pathway and the ‘other glycan degradation’ pathway. Conclusion These findings provide new evidence highlighting several genes and biological signaling processes that may be related to the risk for alcohol dependence. PMID:26120261
There is a high rate of comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of PTSD among individuals with...AD are at least twice as high as those in the general population. In addition, alcohol dependence is the most common comorbid condition in men with...sleep disturbance in combat veterans with PTSD and alcohol dependence . The objective of this study is to evaluate the efficacy of prazosis (16mg
Vélez-Moreno, Antonio; González-Saiz, Francisco; Ramírez López, Juan; Torrico Linares, Esperanza; Fernández-Calderón, Fermín; Rojas, Antonio J; Lozano, Óscar M
The Substance Dependence Severity Scale -SDSS- is one of the few scales that assesses substance dependence and abuse according DSM criteria in dimensional terms. Several studies have provided evidence of psychometric validity and reliability in its English version, but there is no Spanish version available. The aim of this work was to describe the adaptation process of the English version of the SDSS into Spanish, and provide preliminary results on its reliability and validity evidence. Participants were 146 patients (79.6% male), consumers of alcohol, cocaine, heroin and cannabis admitted to treatment in the Drug Abuse Centre Services of Huelva. Besides the SDSS, the EUROPASI and the Health Related Quality of Life for Drug Abusers test -HRQOLDA- were also administered. The Substance Dependence Severity Scale -SDSS- has shown adequate psychometric properties in terms of the rates of discrimination and internal consistency (α=0.881 for alcohol; α=0.814 for cocaine; α=0.531 for cannabis; α=0.785 for heroin). However, the scale assessing abuse showed poorer results. Concerning the validity evidence, the evidence based on internal structure showed a unidimensional structure. Furthermore, the evidence based from the relationships with other variables empirically support the theoretical relationships postulated. Preliminary results support the use of the Substance Dependence Severity Scale. The severity scale, which evaluates abuse criteria, needs further empirical evidence to assess its utility. Therefore, its current version is not recommended for use.
Wright, Tara M; Myrick, Hugh
Acamprosate, a medication that has been used in Europe for years, is the newest drug to be approved by the US Federal Drug Administration for the treatment of alcohol dependence. It has been shown to assist in the maintenance of abstinence in recently detoxified alcohol-dependent individuals. The following review delineates the proposed mechanism of action and pharmacokinetics of the drug. Findings of clinical trials are outlined and topics such as cost effectiveness, comparison with other medications used for the treatment of alcohol dependences as well as combination pharmacotherapy are discussed. In combination with psychosocial treatment, acamprosate is a promising tool for the maintenance of abstinence in alcohol-dependent patients after alcohol withdrawal. This review also illustrates the continued need to search for more effective treatments, as the overall effectiveness of our currently available pharmacotherapies remains limited in the long-term maintenance of recovery from alcohol dependence. PMID:19412493
Jayawickreme, Nuwan; Yasinski, Carly; Williams, Monnica; Foa, Edna B.
The current study examined gender-specific associations between trauma cognitions, alcohol cravings and alcohol-related consequences in individuals with dually diagnosed PTSD and alcohol dependence (AD). Participants (N = 167) had entered a treatment study for concurrent PTSD and AD; baseline information was collected from participants about PTSD-related cognitions in three areas: negative cognitions about self, negative cognitions about the world, and self-blame; and two aspects of AD, alcohol cravings and consequences of AD. Gender differences were examined while controlling for PTSD severity. The results indicate that negative cognitions about the self are significantly related to alcohol cravings in men but not women, and that interpersonal consequences of AD are significantly related to self-blame in women but not in men. These findings suggest that for individuals with comorbid PTSD and AD, psychotherapeutic interventions that focus on reducing trauma-related cognitions are likely to reduce alcohol cravings in men and relational problems in women. PMID:21480680
Ulmer, Albrecht; Müller, Markus; Frietsch, Bernhard
Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients. Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC) to 102 heavily alcohol addicted patients, later, also Buprenorphine, Clomethiazole (>6 weeks), Baclofen, and in one case Amphetamine, each on individual indication. This paper focuses on the data with DHC, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-steps scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details. Conclusion: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around 1/4 of the patients already. Many further
Rubio, Gabriel; Borrell, José; Jiménez, Mónica; Jurado, Rosa; Grüsser, Sabine M; Heinz, Andreas
Cue modulation of the startle reflex is a paradigm that has been used to understand the emotional mechanisms involved in alcohol dependence. Attenuation of the startle reflex has been demonstrated when alcohol-dependent subjects are exposed to alcohol-related stimuli. However, the role of clinical variables on the magnitude of this response is unknown. The objective of this study was to determine the relationship between a number of clinical variables-severity of alcoholism, family history of alcoholism (FHA+), personality traits related to the sensitivity to reward-and the startle reflex response when subjects with alcohol dependence were viewing alcohol-related cues. After detoxification, 98 participants completed self-report instruments and had eye blink electromyograms measured to acoustic startle probes [100-millisecond burst of white noise at 95 dB(A)] while viewing alcohol-related pictures, and standardised appetitive, aversive and neutral control scenes. Ninety-eight healthy controls were also assessed with the same instruments. There were significant differences on alcohol-startle magnitude between patients and controls. Comparisons by gender showed that women perceived alcohol cues and appetitive cues more appetitive than men. Male and female patients showed more appetitive responses to alcohol cues when compared with their respective controls. Our patients showed an appetitive effect of alcohol cues that was positively related to severity of alcohol dependence, sensitivity to reward and a FHA+. The data confirmed that the pattern of the modulation of the acoustic startle reflex reveals appetitive effects of the alcohol cues and extended it to a variety of clinical variables.
Gilpin, Nicholas W; Koob, George F
Alcoholism is a debilitating disorder for the individual and very costly for society. A major goal of alcohol research is to understand the neural underpinnings associated with the transition from alcohol use to alcohol dependence. Positive reinforcement is important in the early stages of alcohol use and abuse. Negative reinforcement can be important early in alcohol use by people self-medicating coexisting affective disorders, but its role likely increases following the transition to dependence. Chronic exposure to alcohol induces changes in neural circuits that control motivational processes, including arousal, reward, and stress. These changes affect systems utilizing the signaling molecules dopamine, opioid peptides, γ-aminobutyric acid, glutamate, and serotonin, as well as systems modulating the brain's stress response. These neuroadaptations produce changes in sensitivity to alcohol's effects following repeated exposure (i.e., sensitization and tolerance) and a withdrawal state following discontinuation of alcohol use. Chronic alcohol exposure also results in persistent neural deficits, some of which may fully recover following extended periods of abstinence. However, the organism remains susceptible to relapse, even after long periods of abstinence. Recent research focusing on brain arousal, reward, and stress systems is accelerating our understanding of the components of alcohol dependence and contributing to the development of new treatment strategies.
Dickter, Cheryl L.; Forestell, Catherine A.; Hammett, Patrick J.; Young, Chelsie M.
Rationale Previous work has indicated that implicit attentional biases to alcohol-related cues are indicative of susceptibility to alcohol dependence and escape drinking, or drinking to avoid dysphoric mood or emotions. Objective The goal of the current study was to examine whether alcohol dependence and escape drinking were associated with early neural attentional biases to alcohol cues. Methods EEG data were recorded from 54 college students who reported that they regularly drank alcohol, while they viewed alcohol and control pictures that contained human content (active) or no human content (inactive). Results Those who were alcohol dependent showed more neural attentional bias to the active alcohol-related stimuli than to the matched control stimuli early in processing, as indicated by N1 amplitude. Escape drinkers showed greater neural attention to the active alcohol cues than non-escape drinkers, as measured by larger N2 amplitudes. Conclusions While alcohol dependence is associated with enhanced automatic attentional biases early in processing, escape drinking is associated with more controlled attentional biases to active alcohol cues during a relatively later stage in processing. These findings reveal important information about the time-course of attentional processing in problem drinkers and have important implications for addiction models and treatment. PMID:24292342
Franck, Johan; Jayaram-Lindström, Nitya
The efficacy of medications for alcohol dependence remains modest, and there are no strong clinical predictors of treatment response. Approved medications include acamprosate (an N-methyl-d-aspartate receptor (NMDA) modulator), disulfiram (an acetaldehyde dehydrogenase inhibitor) and naltrexone (an opioid antagonist) while nalmefene (an opioid antagonist) is currently under review for approval in Europe. Clinical trials suggest that baclofen (a GABA-B agonist) and topiramate (an anticonvulsant) may be promising candidates, while several other drug candidates are currently evaluated at early clinical stages.
Sivolap, Iu P
Treatment of alcohol dependence consist of alcohol detoxification with withdrawal alleviation and relapse prevention or maintenance therapy. Drugs of choice for alcohol withdrawal cure are benzodiazepines and anticonvulsants are an alternative for them. Relapse prevention and alcohol abuse alleviation are carried out using disulfiram, acamprosate, naltrexone and nalmefene. Moreover, therapeutic possibilities of memantine, gabapentine, pregabalin, baclofen, modafinil, ondansetron D-cycloserine and aripiprazole are studying nowadays. Use of selective serotonin reuptake inhibitors including fluvoxamine for alcohol patients is of great importance due to frequent comorbidity of alcoholism, depression and anxiety. There are some doubtful methods of alcoholism treatment accepted in Russian addictive medicine such as clearance detoxification and use of antipsychotics for craving elimination.
... You are Not Alone Like any other chronic disease, addiction to alcohol and other drugs affects people of all ages regardless of income, educational background, country of origin, ethnicity, sexuality, and/or community where they live. ...
Witt, Ellen D
Sex differences in patterns of drinking and rates of alcohol abuse and dependence begin to emerge during the transition from late puberty to young adulthood. Increases in pubertal hormones, including gonadal and stress hormones, are a prominent developmental feature of adolescence and could contribute to the progression of sex differences in alcohol drinking patterns during puberty. This paper reviews experimental and correlational studies of gonadal and stress-related hormone changes and their effects on alcohol drinking and other associated actions of alcohol. Mechanisms are suggested by which reproductive hormones and stress-related hormones may modulate neural circuits within the brain reward system to produce sex differences in alcohol drinking patterns and vulnerability to alcohol abuse and dependence which become apparent during the late pubertal period.
McCutcheon, Vivia V.; Heath, Andrew C.; Edenberg, Howard J.; Grucza, Richard A.; Hesselbrock, Victor M.; Kramer, John R.; Bierut, Laura Jean; Bucholz, Kathleen K.
Purpose Data from the Collaborative Study on the Genetics of Alcoholism (COGA), a high-risk family study of alcohol dependence, were used to examine differences in alcohol diagnostic criteria endorsement and psychiatric and drug use disorders by gender and by number of DUI offenses. Results Individuals with two or more DUIs exhibited greater severity of alcohol dependence than those with none or one DUI. This severity was characterized in three ways: (1) higher endorsement of alcohol diagnostic criterion items, with evidence of greater severity among women, (2) higher prevalence of co-occurring lifetime psychiatric disorders, and (3) higher rates of drug use and of dependence on cocaine, stimulants, and, for women only, marijuana and opiates. Conclusions By examining gradations of disorder within a combination of two high-risk indicators, DUI and family vulnerability, this study provides useful information for clinical research about individuals with chronic and severe alcohol problems. In addition, the observed gender differences in this high-risk sample will contribute to the literature on alcohol dependence among women at the more severe end of the dependence spectrum. PMID:19167170
Sjoerds, Zsuzsika; Stufflebeam, Steven M; Veltman, Dick J; Van den Brink, Wim; Penninx, Brenda W J H; Douw, Linda
Alcohol dependence (AD) is characterized by corticostriatal impairments in individual brain areas such as the striatum. As yet however, complex brain network topology in AD and its association with disease progression are unknown. We applied graph theory to resting-state functional magnetic resonance imaging (RS-fMRI) to examine weighted global efficiency and local (clustering coefficient, degree and eigenvector centrality) network topology and the functional role of the striatum in 24 AD patients compared with 20 matched healthy controls (HCs), and their association with dependence characteristics. Graph analyses were performed based on Pearson's correlations between RS-fMRI time series, while correcting for age, gender and head motion. We found no significant group differences between AD patients and HCs in network topology. Notably, within the patient group, but not in HCs, the whole-brain network showed reduced average cluster coefficient with more severe alcohol use, whereas longer AD duration within the patient group was associated with a global decrease in efficiency, degree and clustering coefficient. Additionally, within four a-priori chosen bilateral striatal nodes, alcohol use severity was associated with lower clustering coefficient in the left caudate. Longer AD duration was associated with reduced clustering coefficient in caudate and putamen, and reduced degree in bilateral caudate, but with increased eigenvector centrality in left posterior putamen. Especially changes in global network topology and clustering coefficient in anterior striatum remained strikingly robust after exploratory variations in network weight. Our results show adverse effects of AD on overall network integration and possibly on striatal efficiency, putatively contributing to the increasing behavioral impairments seen in chronically addicted patients.
Sreekumar, Sreeja; Subhalakshmi, T. P.; Varghese, P. Joseph
Background and Objectives: Mental health and resilience of family members of individuals with alcohol dependence affect their ability to cope with stress, maintain emotional well-being, and to positively adapt to their difficult life circumstances. This study attempted to study resilience among wives of men with alcohol dependence syndrome. Materials and Methods: Consecutive patients with a diagnosis of alcohol dependence and their wives attending the Department of Psychiatry, MOSC Medical College, Kolenchery, Kerala, over a 1-year period were recruited. The wives were assessed using the Resilience Scale for Adults and the Hamilton Depressive Rating Scale, whereas their spouses were evaluated using severity of alcohol dependence questionnaire and a proforma to collect sociodemographic and clinical characteristics. Women with good resilience were compared to those with low scores using a case–control framework to evaluate factors associated with resilience. Multivariable analysis to adjust for common confounders was done using multiple linear regression. Results: Eighty patients and their spouses were recruited and evaluated. Resilience was inversely related to the severity of alcohol dependence, years of drinking in dependence pattern, history of domestic violence, and severity of depression in wives. Involvement in support groups was protective. Conclusion: Assessment of resilience in wives of individuals with alcohol dependence and identification and management of those with poor resilience should go hand in hand with their husband's treatment program. PMID:28066009
Lewis, Michael J
Alcohol is not only a drug of abuse but is also a food. This combination has a significant impact on the development and consequences of alcohol abuse and dependence. Understanding the neurobiological and behavioral processes that mediate them is perhaps best approached from the perspective of ingestive behavior. Research from the Hoebel laboratory has provided innovation and leadership in understanding that feeding neuropeptides plays a significant role in alcohol intake. The research reviewed here shows that galanin and other feeding peptides increase intake and also motivate abuse and the development of dependence. In addition, the consequences of long term alcohol abuse and dependence alter nutritional systems and drinking behavior. A major challenge is understanding the role of alcohol's dual properties and feeding neuropeptide in the motivation to drink.
Wu, Ping; Liu, Xinhua; Fang, Yunyun; Fan, Bin; Fuller, Cordelia J.; Guan, Zhiqiang; Yao, Zhongling; Kong, Junhui; Lu, Jin; Litvak, Iva J.
Aims: The aim of this study was to examine alcohol abuse/dependence symptoms among hospital employees exposed to a severe acute respiratory syndrome (SARS) outbreak, and the relationship between types of exposure to the SARS outbreak and subsequent alcohol abuse/dependence symptoms. Methods: A survey was conducted among 549 randomly selected hospital employees in Beijing, China, concerning the psychological impact of the 2003 SARS outbreak. Subjects were assessed on sociodemographic factors and types of exposure to the outbreak, and on symptoms of post-traumatic stress (PTS), alcohol abuse/dependence and depression. Results: Current alcohol abuse/dependence symptom counts 3 years after the outbreak were positively associated with having been quarantined, or worked in high-risk locations such as SARS wards, during the outbreak. However, having had family members or friends contract, SARS was not related to alcohol abuse/dependence symptom count. Symptoms of PTS and of depression, and having used drinking as a coping method, were also significantly associated with increased alcohol abuse/dependence symptoms. The relationship between outbreak exposure and alcohol abuse/dependence symptom count remained significant even when sociodemographic and other factors were controlled for. When the intrusion, avoidance and hyperarousal PTS symptom clusters were entered into the model, hyperarousal was found to be significantly associated with alcohol abuse/dependence symptoms. Conclusions: Exposure to an outbreak of a severe infectious disease can, like other disaster exposures, lead not only to PTSD but also to other psychiatric conditions, such as alcohol abuse/dependence. The findings will help policy makers and health professionals to better prepare for potential outbreaks of diseases such as SARS or avian flu. PMID:18790829
Schellekens, Arnt F A; Franke, Barbara; Ellenbroek, Bart; Cools, Alexander; de Jong, Cor A J; Buitelaar, Jan K; Verkes, Robbert-Jan
Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene-environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene-environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.
Beck, Aaron T.; And Others
Administered the Beck Hopelessness Scale to alcoholic (N=20) and heroin-addicted (N=20) women. Results indicated that although both groups expressed comparable levels of overall hopelessness, alcoholic women anticipated more success and better lives in the next 10 years than did the heroin-dependent women. (LLL)
Leggio, Lorenzo; Zywiak, William H.; Fricchione, Samuel R.; Edwards, Steven M.; de la Monte, Suzanne M.; Swift, Robert M.; Kenna, George A.
Background There is a need to identify novel pharmacological targets to treat alcoholism. Animal and human studies suggest a role of ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving. Methods This was a double-blind placebo-controlled human laboratory proof-of-concept study. Non-treatment seeking alcohol-dependent heavy drinking individuals were randomized to receive intravenous ghrelin 1mcg/kg, 3 mcg/kg or 0 mcg/kg (placebo), followed by a cuereactivity procedure, during which participants were exposed to neutral (juice) and alcohol cues. The primary outcome variable was the increase in alcohol craving (also called “urge”) for alcohol, assessed by the Alcohol Visual Analogue Scale. Results Out of 103 screenings, 45 individuals received the study drug. Repeated measures of ANCOVA revealed a group effect across ghrelin doses in increasing alcohol craving (p < .05). A dose-specific examination revealed a significant effect of ghrelin 3 mcg/kg vs. placebo in increasing alcohol craving (p < .05) with a large effect size (d = .94). By contrast, no significant ghrelin effect was found in increasing either urge to drink juice or food craving (p: n.s.). No significant differences in side effects were found (p: n.s.). Conclusions Intravenous administration of exogenous ghrelin increased alcohol craving in alcohol-dependent heavy drinking individuals. Although the small sample requires confirmatory studies, these findings provide preliminary evidence that ghrelin may play a role in the neurobiology of alcohol craving, thus demonstrating a novel pharmacological target for treatment. PMID:24775991
Dierker, Lisa; Selya, Arielle; Rose, Jennifer; Hedeker, Donald; Mermelstein, Robin
Background Despite the highly replicated relationship between symptoms associated with both alcohol and nicotine, little is known about this association across time and exposure to both drinking and smoking. In the present study, we evaluate if problems associated with alcohol use are related to emerging nicotine dependence symptoms and whether this relationship varies from adolescence to young adulthood, after accounting for both alcohol and nicotine exposure. Methods The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking Patterns Study which measured smoking, nicotine dependence, alcohol use and alcohol related problems over 6 assessment waves spanning 6 years. Analyses were based on repeated assessment of 864 participants reporting some smoking and drinking 30 days prior to individual assessment waves. Mixed-effects regression models were estimated to examine potential time, smoking and/or alcohol varying effects in the association between alcohol problems and nicotine dependence. Findings Inter-individual differences in mean levels of alcohol problems and within subject changes in alcohol problems from adolescence to young adulthood were each significantly associated with nicotine dependence symptoms over and above levels of smoking and drinking behaviour. This association was consistent across both time and increasing levels of smoking and drinking. Conclusions Alcohol related problems are a consistent risk factor for nicotine dependence over and above measures of drinking and smoking and this association can be demonstrated from the earliest experiences with smoking in adolescents, through the establishment of more regular smoking patterns across the transition to young adulthood. These findings add to accumulating evidence suggesting that smoking and drinking may be related through a mechanism that cannot be wholly accounted for by exposure to either substance. PMID:27610424
Bae, Sujin; Kang, Ilhyang; Lee, Boung Chul; Jeon, Yujin; Cho, Han Byul; Yoon, Sujung; Lim, Soo Mee; Kim, Jungyoon; Lyoo, In Kyoon
Alcohol dependence is a serious disorder that can be related with a number of potential health-related and social consequences. Cortical thickness measurements would provide important information on the cortical structural alterations in patients with alcohol dependence. Twenty-one patients with alcohol dependence and 22 healthy comparison subjects have been recruited and underwent high-resolution brain magnetic resonance (MR) imaging and clinical assessments. T1-weighted MR images were analyzed using the cortical thickness analysis program. Significantly thinner cortical thickness in patients with alcohol dependence than healthy comparison subjects was noted in the left superior frontal cortical region, correcting for multiple comparisons and adjusting with age and hemispheric average cortical thickness. There was a significant association between thickness in the cluster of the left superior frontal cortex and the duration of alcohol use. The prefrontal cortical region may particularly be vulnerable to chronic alcohol exposure. It is also possible that the pre-existing deficit in this region may have rendered individuals more susceptible to alcohol dependence. PMID:28035184
Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.
Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of…
Watanabe, Yukari; Kamimura, Kenya; Iwasaki, Tomohiro; Abe, Hiroyuki; Takahashi, Shunsaku; Mizuno, Ken-ichi; Takeuchi, Manabu; Eino, Atsushi; Narita, Ichiei; Terai, Shuji
Severe alcoholic hepatitis (AH) has a high mortality, and it is associated with encephalopathy, acute renal failure, sepsis, gastrointestinal bleeding, and endotoxemia. The 28-d mortality remains poor (34%-40%), because no effective treatment has been established. Recently, corticosteroids (CS) have been considered effective for significantly improving the prognosis of those with AH, as it prevents the production of pro-inflammatory cytokines. However, CS are not always appropriate as an initial therapeutic option, such as in cases with an infection or resistance to CS. We describe a patient with severe AH complicated by a severe infection caused by the multidrug resistance bacteria (Pseudomonas aeruginosa), and was successfully treated with granulocytapheresis monotherapy without using CS. The experience of this case will provide understanding of the disease and information treating cases without using CS. PMID:27900326
Morris, Laurel S; Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J; Orban, Csaba; Passetti, Filippo; Paterson, Louise M; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M; Bullmore, Edward T; Lingford-Hughes, Anne R; Deakin, Bill; Nutt, David J; Sahakian, Barbara J; Robbins, Trevor W; Voon, Valerie
Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.
Mohagheghi, Arash; Amiri, Shahrokh; Mousavi Rizi, Seyedreza; Safikhanlou, Salman
Objective. Emotional intelligence might play an important role in the onset and persistence of different psychopathologies. This study investigated the relationship between emotional intelligence and alcohol dependence. Methods. In this case-control study, participants included alcohol dependent individuals and mentally healthy inpatients. Each group consisted of 40 individuals (male/female: 1). The diagnosis was based on the criteria of the DSM-IV-TR using the Structured Clinical Interview for DSM-IV (SCID-IV). All the participants completed Bar-On emotional intelligence test. Results. 20 males and 20 females were included in each group. Mean age of alcohol dependent participants and controls was 31.28 ± 7.82 and 34.93 ± 9.83 years in that order. The analyses showed that the alcohol dependent individuals had a significant difference compared with the control group and received lower scores in empathy, responsibility, impulse control, self-esteem, optimism, emotional consciousness, stress tolerance, autonomy, problem-solving, and total score of emotional intelligence components. Conclusion. Patients with alcohol dependence have deficits in components of emotional intelligence. Identifying and targeted training of the individuals with lower scores in components of emotional intelligence may be effective in prevention of alcohol dependence. PMID:25893214
CENGİSİZ, Cengiz; DEVECİ, Artuner; YAPICI, Aslıhan
Introduction Treatment motivation in alcohol dependents is usually viewed as a strong predictor of seeking treatment and treatment success. The conditions affecting motivation in alcohol dependence, however, has not been clarified. In this study, it is aimed to determine the effects of depression on treatment motivation in male alcohol dependence. Methods The present study included 34 male alcohol dependents presenting to outpatient clinics in Manisa Hospital of Mental Disorders and Hospital of Celal Bayar University. The patients underwent evaluation using the socio-demographic and clinical information form, DSM-IV SCID-I Clinical Version, Treatment Motivation Questionnaire (TMQ), and Hamilton Depression Rating Scale (HDRS). Results A significant relationship was found between the total score of TMQ and HDRS (p=.039). Conclusion We believe that the present study, in which we examined the relationship between treatment motivation in male alcohol dependence and depression, would provide a significant contribution to literature. It is also important to investigate other factors that may affect treatment motivation in male alcohol dependence. Studies with larger samples are needed on this topic.
Wolitzky-Taylor, Kate; Brown, Lily A.; Roy-Byrne, Peter; Sherbourne, Cathy; Stein, Murray B.; Sullivan, Greer; Bystritsky, Alexander; Craske, Michelle G.
Objective The presence of anxiety disorders is associated with poorer alcohol use disorder treatment outcomes, but little is known about the impact of alcohol use problems on anxiety disorder treatment outcomes despite their high comorbidity. The current study examined the impact of alcohol use symptom severity on anxiety disorder treatment outcomes in a multi-site primary care effectiveness study of anxiety disorder treatment. Method Data came from the Coordinated Anxiety Learning and Management (CALM) effectiveness trial. Participants (N = 1004) were randomized to an evidence-based anxiety intervention (including cognitive behavioral therapy and medications) or usual care in primary care. Participants completed measures of alcohol use, anxiety, and depression a baseline, 6-mo, 12-mo, and 18-mo follow-up periods. Patients with alcohol dependence were excluded. Results There were no significant moderating (Treatment Group x Alcohol Use Severity) interactions. The majority of analyses revealed no predictive effects of alcohol use severity on outcome; however, alcohol problems at baseline were associated with somewhat higher anxiety and depression symptoms at the 18-mo follow-up. Conclusions These data indicate that patients with alcohol problems in primary care can be effectively treated for anxiety disorders. Baseline alcohol problems were associated with some poorer long-term outcomes, but this was evident across CALM and usual care. These findings provide preliminary evidence that there may be no need to postpone treatment of anxiety disorders until alcohol problems are addressed, at least among those who have mild to moderate alcohol problems. Replication with more severe alcohol use disorders is needed. PMID:25615523
Sarid-Segal, Ofra; Piechniczek-Buczek, Joanna; Knapp, Clifford; Afshar, Maryam; Devine, Eric; Sickles, Laurie; Uwodukunda, Emma; Richambault, Courtney; Koplow, Jillian; Ciraulo, Domenic
The aim of this open-label pilot study was to assess the efficacy and safety of the novel anticonvulsant agent, levetiracetam, for the treatment of alcohol dependence. A maximal dose of 2000 mg was administered daily for 10 weeks to alcohol dependent subjects (n = 20). Mean reported ethanol intake declined significantly from 5.3 to 1.7 standard drinks per day. Levetiracetam was well tolerated by most subjects. PMID:18584574
Collier, Andrew; Watts, Maggie; Ghosh, Sujoy; Rice, Peter; Dewhurst, Neil
Aims and Methods The UK’s Driver Vehicle Licensing Authority (DVLA) requires individuals to report if they have a medical condition such as alcohol dependence. General Medical Council guidance indicates that medical practitioners should ensure patients are aware of their impairment and requirement to notify the DVLA. Results In a survey of 246 people with known alcohol dependence, none were aware of advice on driving given by medical practitioners and none had self-reported. In addition, 362 doctors, either attending a college symposium or visiting a college website, were asked about their knowledge of DVLA regulations regarding alcohol dependence: 73% of those attending the symposium and 63% of those visiting the website answered incorrectly. In Scotland, over 20 000 people have alcohol dependence (over 1 million people with alcohol abuse), yet only 2548 people with alcohol problems self-reported to the DVLA in 2011. Clinical implications If the DVLA regulations were implemented, it could make an enormous difference to the behaviours of the driving public. PMID:26191423
Mason, Barbara J; Light, John M; Williams, Lauren D; Drobes, David J
There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence that may precipitate relapse in alcoholics, e.g. craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non-treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence and a strength of craving rating 1 SD or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1 week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral and unpleasant visual stimuli followed by alcohol or water cues. Gabapentin was associated with significantly greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoked craving. Gabapentin was also associated with significant improvement on several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue-reactivity studies as proof-of-concept screens for potential antirelapse drugs.
Ernst, Lena H; Plichta, Michael M; Dresler, Thomas; Zesewitz, Anna K; Tupak, Sara V; Haeussinger, Florian B; Fischer, Matthias; Polak, Thomas; Fallgatter, Andreas J; Ehlis, Ann-Christine
An approach bias for alcohol stimuli (i.e. faster approach than avoidance reactions) might facilitate relapses in alcohol dependence. Neurobiological models suggest hypersensitivity in the reward system [inter alia nucleus accumbens and orbitofrontal cortex (OFC)] to cause pathologically enhanced approach impulses towards alcohol stimuli. At the same time, in alcohol dependence, these structures are only insufficiently controlled by a hypoactive dorsolateral prefrontal cortex (DLPFC). The present study investigated the cortical aspects of this model with functional near-infrared spectroscopy in 21 alcohol-dependent in-patients and 21 healthy controls (HC; comparable in age, gender and education) during performance of the Approach-Avoidance Task (AAT) for the first time. Complementing previous findings, in reaction times (RTs), patients showed stronger approach preferences for alcohol than non-alcohol stimuli. For non-alcohol stimuli, patients even displayed avoidance preferences. The reversed pattern was found in HC. Group differences in activity of the OFC were identical to those in RTs, revealing patients to assign higher subjective value to approaching alcohol stimuli. In both groups, regulatory activity in the right DLPFC was stronger during avoiding than approaching alcohol pictures. Probable awareness of the behavioural hypotheses due to explicit task instructions and patients' deficient prefrontal function might account for this equally aligned pattern. Results are discussed with regard to recent findings revealing a reduced behavioural approach bias and risk for relapse by applying a retraining version of the AAT. Functional measurements might serve as a method for monitoring the corresponding neurobiological changes and-possibly-predicting the success of such a training.
Opalach, Cezary; Romaszko, Jerzy; Jaracz, Marcin; Kuchta, Robert; Borkowska, Alina; Buciński, Adam
Background and Objectives The ways in which homeless individuals cope with stress may differ from those relied upon by the members of the general population and these differences may either be the result or the cause of their living conditions. The aim of the study was to determine the preferred coping style among the homeless and its relationship with alcohol dependence. Methods The study included 78 homeless individuals and involved the collection of demographic, sociological, psychological and medical data from each participant. Coping styles relied upon when dealing with stressful situations were assessed using a Polish adaptation of the Coping Inventory for Stressful Situations. Alcohol dependence was assessed using the Michigan Alcoholism Screening Test (MAST) and a quantitative analysis of alcohol consumption. Results Men accounted for 91.93% of the study population. Nearly 75% of the subjects met the alcohol dependence criterion. Significant relationships were observed between the individual's age, preferred coping style and alcohol consumption level. As an individual’s age increased, the use of emotion-oriented coping styles decreased, while an increase in alcohol consumption was associated with a more frequent use of emotion- and avoidance-oriented strategies. Conclusions The findings of this study, similarly to those of many other studies of homeless individuals but investigating other areas (e.g. epidemiology of tuberculosis and traumatic injuries), are an exaggerated representation of associations observed in the general population. The results describe a group of people living on the margins of the society, often suffering from extremely advanced alcoholism, with clear evident psychodegradation. The presence of specific ways of coping with stress related to excessive alcohol consumption in this group of individuals may interfere with active participation in support programmes provided for the homeless and may further exacerbate their problems. PMID
Grazioli, Véronique S; Hicks, Jennifer; Kaese, Greta; Lenert, James; Collins, Susan E
Chronically homeless individuals with alcohol dependence experience severe alcohol-related consequences. It is therefore important to identify factors that might be associated with reduced alcohol-related harm, such as the use of safer-drinking strategies. Whereas effectiveness of safer-drinking strategies has been well-documented among young adults, no studies have explored this topic among more severely affected populations, such as chronically homeless individuals with alcohol dependence. The aims of this study were thus to qualitatively and quantitatively document safer-drinking strategies used in this population. Participants (N=31) were currently or formerly chronically homeless individuals with alcohol dependence participating in a pilot study of extended-release naltrexone and harm-reduction counseling. At weeks 0 and 8, research staff provided a list of safer-drinking strategies for participants to endorse. Implementation of endorsed safer-drinking strategies was recorded at the next appointment. At both time points, strategies to buffer the effects of alcohol on the body (e.g., eating prior to and during drinking) were most highly endorsed, followed by changing the manner in which one drinks (e.g., spacing drinks), and reducing alcohol consumption. Quantitative analyses indicated that all participants endorsed safer-drinking strategies, and nearly all strategies were implemented (80-90% at weeks 0 and 8, respectively). These preliminary findings indicate that chronically homeless people with alcohol dependence use strategies to reduce harm associated with their drinking. Larger randomized controlled trials are needed to test whether interventions that teach safer-drinking strategies may reduce overall alcohol-related harm in this population.
Grynberg, Delphine; de Timary, Philippe; Philippot, Pierre; D'Hondt, Fabien; Briane, Yasmine; Devynck, Faustine; Douilliez, Céline; Billieux, Joël; Heeren, Alexandre; Maurage, Pierre
Emotional and interpersonal deficits play a crucial role in alcohol-related disorders as they predict alcohol consumption and relapse. Recent models of emotion regulation in psychopathology postulate that these deficits are centrally related to increased abstract/analytic repetitive thinking, combined with reduced concrete/experiential repetitive thinking. As this assumption has not been tested in addictions, this study aimed at investigating repetitive thinking modes in a large sample of alcohol-dependent individuals. One hundred recently detoxified alcohol-dependent individuals (29 females; mean age = 49.51-years-old) recruited during the 3rd week of their treatment in a detoxification center were compared to 100 healthy controls (29 females; mean age = 48.51-years-old) recruited in the experimenters' social network, matched at the group level for age, gender, and educational level. All participants completed the Mini Cambridge Exeter Repetitive Thought Scale measuring abstract/analytic and concrete/experiential repetitive thinking modes as well as complementary psychopathological measures (Beck Depression Inventory and State/Trait Anxiety Inventory). Alcohol-dependent individuals have similar levels of concrete repetitive thinking as controls but report significantly higher levels of abstract repetitive thinking (p < 0.001; d = 1.28). This effect remains significant after controlling for depression and anxiety. Relative to healthy controls, alcohol-dependent patients report more frequent use of abstract/analytic repetitive thinking, with preserved concrete/experiential thinking. Despite the cross-sectional nature of the study, the frequent use of abstract repetitive thinking thus appears to constitute a main feature of alcohol-dependence.
Martins-Oliveira, Juliana Gabrielle; Jorge, Kelly Oliva; Ferreira, Raquel Conceição; Ferreira, Efigênia Ferreira E; Vale, Míriam Pimenta; Zarzar, Patrícia Maria
The present study evaluated the possible alcohol dependence and related problems among adolescents and determined possible associations with socioeconomic factors and gender. A cross-sectional study was conducted with a representative sample of 936 adolescents aged 15 to 19 years enrolled at public and private schools in the city of Belo Horizonte, Brazil. Data related to alcohol consumption and associated problems were collected using the Alcohol Use Disorder Identification Test (AUDIT). The Social Vulnerability Index (SVI), mother's schooling and type of school were used to assess socioeconomic factors. Statistical analysis involved the chi-square test (p < 0.05) and Poisson regression. The prevalence of possible dependence was 16.4%, 52.1% reported concern of a family member regarding the adolescent's alcohol consumption. Female adolescents were less likely to exhibit possible dependence in comparison to males. Participants with living in a low vulnerability area were more likely to consume alcohol in comparison to those living in underprivileged areas. The results of the present study demonstrate that possible dependence was significantly associated with the male gender and low social vulnerability.
Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.
Few studies examining alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of post-treatment alcohol outcomes. The present study uses a multivariate approach based on a theoretical model to study the relationship between psychosocial factors and post treatment-initiation alcohol use. Predictors of alcohol use outcomes were examined in 278 individuals diagnosed with a current DSM-IV schizophrenia-spectrum or bipolar disorder and an alcohol use disorder (AUD). At 6-months follow-up after initiating treatment, 144 of 228 available participants (63%) had good clinical outcomes. The results of structural equation modeling indicated that type of pretreatment residential setting was directly related to treatment with participants living in supervised settings (41%) reporting significantly more days of treatment (β = .34, p < .001). In addition, participants with more psychiatric symptoms, assessed by the Brief Symptom Inventory and Structured Clinical Interview for the Positive and Negative Syndrome Scale, reported significantly fewer treatment days (β = −.20, p < .001). Number of days participants attended treatment was indirectly associated with alcohol use outcomes and was mediated by use of alcohol coping skills, such that more frequent use of alcohol-specific coping skills was associated with less post treatment-initiation alcohol use (β = −.34, p < .001). This study emphasizes the favorable prognosis for alcohol outcomes among treated individuals with a SMI and AUD and the importance of psychosocial interventions, particularly those that result in better alcohol-specific coping skills. PMID:19968390
Bozkurt, Muge; Evren, Cuneyt; Umut, Gokhan; Evren, Bilge
Purpose Attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to a higher risk of developing psychiatric problems such as depressive disorders, substance use disorder, and impulsivity. Adults who have comorbid ADHD and alcohol use disorder (AUD) are at greater risk of negative outcomes. Thus, it is important to evaluate the relationship of ADHD symptoms and the severity of alcohol-related problems among patients with AUD. The aim of the present study was to evaluate the effect of ADHD symptoms on severity of alcohol-related problems, while controlling the effects of depression and impulsivity in a sample of inpatients with AUD. Patients and methods Participants (n=190) were evaluated with the Beck Depression Inventory, the Short Form Barratt Impulsiveness Scale, the Michigan Alcohol Screening Test, and the Adult ADHD Self-Report Scale. Results Severity of the scale scores was positively correlated with each other. Although severity of depression and impulsivity (particularly non-planning impulsivity) predicted the severity of alcohol-related problems in a linear regression model, when severity of ADHD symptoms was included in the analysis, the inattentive subscale score, in particular, predicted the severity of alcohol-related problems together with non-planning impulsivity, whereas depression was no longer a predictor. Conclusion These findings suggest that, together with non-planning impulsivity, symptoms of ADHD (particularly inattentive factor) are an important factor that predict alcohol-related problems, while controlling the severity of depressive symptoms among inpatients with AUD. PMID:27462159
Chassin, Laurie; Fora, David B; King, Kevin M
This study describes trajectories of substance use and dependence from adolescence to adulthood. Identified consumption groups include heavy drinking/heavy drug use, moderate drinking/experimental drug use, and light drinking/rare drug use. Dependence groups include alcohol only, drug only, and comorbid groups. The heavy drinking/heavy drug use group was at risk for alcohol and drug dependence and persistent dependence and showed more familial alcoholism, negative emotionality, and low constraint. The moderate drinking/experimental drug use group was at risk for alcohol dependence but not comorbid or persistent dependence and showed less negative emotionality and higher constraint. Familial alcoholism raised risk for alcohol and drug use and dependence in part because children from alcoholic families were more impulsive and lower in agreeableness.
Donadon, M.F.; Osório, F.L.
Non-adaptive personality traits may constitute risk factors for development of psychiatric disorders such as depression and anxiety. We aim to evaluate associations and the predictive value of personality traits among alcohol-dependent individuals, with or without psychiatric comorbidities. The convenience sample comprised two groups of males over 18 years of age: one with subjects who had an alcohol dependence diagnosis (AG, n=110), and a control group without abuse and/or alcohol dependence diagnosis (CG, n=110). The groups were assessed by means of the Structured Clinical Interview DSM-IV (SCID-IV). AG participants were recruited among outpatients from the university hospital, whereas CG participants were recruited from a primary healthcare program. Data collection was done individually with self-assessment instruments. Parametric statistics were performed, and a significance level of P=0.05 was adopted. A positive correlation was observed between openness and the length of time that alcohol has been consumed, as were significant and negative correlations between conscientiousness and both the length of time alcohol has been consumed and the number of doses. For alcoholics, extraversion emerged as a protective factor against depression development (P=0.008) and tobacco abuse (P=0.007), whereas openness worked as a protective factor against anxiety (P=0.02). The findings point to specific deficits presented by alcoholics in relation to personality traits with or without psychiatric comorbidities and to the understanding that therapeutic approaches should favor procedures and/or preventive measures that allow more refined awareness about the disorder. PMID:26628399
Rolland, Benjamin; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Gautier, Sophie; Auffret, Marine; Pignon, Baptiste; Valin, Thomas; Bordet, Régis; Cottencin, Olivier
High-dose baclofen, i.e., 300 mg/d or more, has recently emerged as a strategy for treating alcohol dependence. The impact that the co-exposure of large amounts of alcohol and baclofen has on sedation is unclear. In a prospective cohort of 253 subjects with alcohol dependence, we collected daily alcohol and baclofen doses across the first year of baclofen treatment and the monthly maximum subjective sedation experienced by each patient (0-10 visual analog scale). For each patient-month, we determined the average weekly alcohol consumption (AWAC; standard-drinks/week) and the maximum daily dose of baclofen (DDB; mg/d). The occurrence of an episode of major sedation (EMS) during a patient-month was defined as a sedation score ≥7. The relationship between the EMS occurrence and the concurrent AWAC and DDB was investigated using a generalized estimating equation model. In total, 1528 patient-months were compiled (70 with an EMS). Univariate analyses demonstrated that the rate of patient-month to EMS increased gradually with AWAC (p<0.001), from 0.9% for AWAC=0 to 9.4% for AWAC >35. There was also a significant gradual risk for EMS associated with DDB (<0.001). Multivariate analysis demonstrated a significant interaction between DDB and AWAC on EMS risk (p=0.047). Each 20mg/d increase in DDB was associated with an OR of EMS in AWAC >35 of 1.22 (95%CI, 1.08-1.38) versus 1.11 (95%CI, 0.96-1.29) in AWAC=1-35, and 0.95 (95%CI, 0.76-1.19) in AWAC=0. The level of sedation observed in patients using baclofen for alcohol dependence appears to directly depend on the immediate doses of both the baclofen and the alcohol.
Li, Peng; Wu, Ping; Xin, Xue; Fan, Yun-Li; Wang, Gui-Bin; Wang, Fan; Ma, Meng-Ying; Xue, Ming-Ming; Luo, Yi-Xiao; Yang, Fu-De; Bao, Yan-Ping; Shi, Jie; Sun, Hong-Qiang; Lu, Lin
Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts.
Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella
Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.
Alcohol-based hand sanitizers are an alternative to hand washing with soap and water when water is unavailable. Their use has increased over the last decade. Cases of acute intoxication have been reported in children after accidental ingestion of alcohol-based hand sanitizers, sometimes leading to inebriation, agitation, drowsiness, impaired consciousness, and blood alcohol levels sometimes exceeding 2 g/I. In practice, alcohol-based hand sanitizers should be kept out of reach of children and should only be used when hand washing with soap and water is not possible. The possibility of alcohol intoxication should be borne in mind when a child suddenly presents with behaviour problems or altered consciousness.
Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L; Musselman, Samuel C; Forbes, Erika E
Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.
Gazdzinski, Stefan; Durazzo, Timothy C; Meyerhoff, Dieter J
Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage.
Lowinger, Robert Jay
A sample of 201 college students were surveyed with respect to their perceptions of severity and willingness to seek psychological help for drug and alcohol problems. Results indicated that students perceive alcohol problems as significantly less serious than drug problems and are significantly less willing to seek help for alcohol problems. Males…
Kovatchev, Boris; Breton, Marc; Johnson, Bankole
In this paper we view alcohol dependence and the response to treatment as a recurrent bio-behavioral process developing in time and propose formal models of this process combining behavior and biology in silico. The behavioral components of alcohol dependence and treatment are formally described by a stochastic process of human behavior, which serves as an event generator challenging the metabolic system. The biological component is driven by the biochemistry of alcohol intoxication described by deterministic models of ethanol pharmacodynamics and pharmacokinetics to enable simulation of drinking addiction in humans. Derived from the known physiology of ethanol and the literature of both ethanol intoxication and ethanol absorption, the different models are distilled into a minimal model (as simple as the complexity of the data allows) that can represent any specific patient. We use these modeling and simulation techniques to explain responses to placebo and ondansetron treatment observed in clinical studies. Specifically, the response to placebo was explained by a reduction of the probability of environmental reinforcement, while the effect of ondansetron was explained by a gradual decline in the degree of ethanol-induced neuromodulation. Further, we use in silico experiments to study critical transitions in blood alcohol levels after specific average number of drinks per day, and propose the existence of two critical thresholds in the human – one at 5 and another at 11 drinks/day – at which the system shifts from stable to critical and to super critical state indicating a state of alcohol addiction. The advantages of such a model-based investigation are that (1) the process of instigation of alcohol dependence and its treatment can be deconstructed into meaningful steps, which allow for individualized treatment tailoring, and (2) physiology and behavior can be quantified in different (animal or human) studies and then the results can be integrated in silico
Chauhan, Vinay Singh; Azad, Sudip
Introduction Social factors play vital role in unfolding of alcohol use disorders in any given population. Several factors beyond the confines of treatment settings influence treatment outcome in alcohol dependence syndrome. Social support has positive effect in treatment outcome of alcohol dependence syndrome. This has not been much studied in India in past. Therefore we decided to study the perception of social support in cases of alcohol dependence syndrome admitted in a busy hospital in armed forces. Aim The aim was to study the perception of social support across relapsed and abstinent group and see if it reached any statistical proportion and also to see if any socio-demographic variables also affected perception of social support. Materials and Methods Fifty five consecutive male patients of alcohol dependent syndrome without a co-morbid neurological/psychiatric diagnosis were assessed for their perception of social support after taking informed consent. They were explained the procedure and their alcoholic milestones were recorded in specially designed pro-forma. Subjects were then divided in abstinent and relapsed group. Subsequently they were assessed for their perception of social support by administering Social provision scale and Social support questionnaire. Statistical Analysis Data were tabulated and statistically analysed by using chi square test, Mann Whitney U-Test and Rank ANOVA test where applicable p-value <.05 was taken as significant. Results Results indicated that perception of social support across abstinent (n=18) and relapsed (n= 37) group reached significant statistical proportion as measured by social provision scale and social support questionnaire. Duration of use, dependence and family history of alcoholism did not influence perception of social support across patient population. There was inverse relationship between patients with alcohol related problem and their perception of social support. Professional and qualified soldiers
Meszaros, K; Willinger, U; Fischer, G; Schönbeck, G; Aschauer, H N
C.R. Cloninger proposed a biosocial model for personality, linking personality traits to patterns of responses to various external stimuli, including alcohol. The Tridimensional Personality Questionnaire (TPQ) was administered in a multicenter study to detoxified alcohol-dependent patients (N = 521). The objectives of the study were to evaluate (1) the expression of the three personality dimensions, novelty-seeking (NS), harm avoidance (HA), and reward dependence (RD), of the TPQ in this sample, and (2) the influence of different variables on these personality dimensions. The following variables were selected for a multiple and a stepwise regression analysis: sex, family history for major psychiatric disorders, marital status, occupation, age at study enrollment, age of onset of alcoholism, serum cholesterol level, intake of neuroleptics or benzodiazepines for detoxification, and severity of depression and anxiety. In comparison to Austrian normative data, both sexes of detoxified alcohol addicts scored higher in HA. The variables examined explain 23% of the variance of NS and 35% of HA. Only one variable, namely age of onset, is significantly influencing NS (19% explained variance). HA is significantly influenced by three variables: anxiety state, anxiety trait, and sex (32% explained variance). RD is not influenced by any of the variables examined.
Soyka, Michael; Zill, Peter; Koller, Gabi; Samochowiec, Agnieszka; Grzywacz, Anna; Preuss, Ulrich W
Aggression, violence and antisocial behavior are common in alcoholism, but their biological basis is poorly understood. Several studies and recent meta-analyses indicate that in schizophrenia the catecholamine-O-methyltransferase (COMT) Val158Met genotype may be associated with aggression, most often in methionine allele carriers. We tested this hypothesis in a sample of treatment-seeking alcohol-dependent in-patients (293 German patients and 499 controls, and additional 190 Polish patients as replication sample). As expected, patients with a history of violent or non-violent crime were more often male, had an earlier onset of alcoholism and more withdrawal seizures and delirium tremens, and were more likely to have a history of suicide attempts. COMT genotype was not associated with a history of violent or non-violent crime. More studies are needed on the neurobiological basis of aggression and violence in alcoholism.
Kim, Dai-Jin; Park, Byung Lae; Yoon, Sujung; Lee, Hae-Kook; Joe, Keun-Ho; Cheon, Young-Hoon; Gwon, Do-Hoon; Cho, Sung-Nam; Lee, Hye Won; NamGung, Suk; Shin, Hyoung Doo
Multiple dopamine receptors in the dopaminergic system may be prime candidates for genetic influence on alcohol abuse and dependence due to their involvement in reward and reinforcing mechanisms. Genetic polymorphisms in dopamine receptor genes are believed to influence the development and/or severity of alcoholism. To examine the genetic effects of the Dopamine Receptor D1 (DRD) gene family (DRD1-DRD5) in the Korean population, 11 polymorphisms in the DRD gene family were genotyped and analyzed in 535 alcohol-dependent subjects and 273 population controls. Although none of the polymorphisms of DRD1-5 genes were found to be associated with the risk of alcoholism, one 5' UTR polymorphism in the DRD1 (DRD1-48A>G) gene was significantly associated with severity of alcohol-related problem, as measured by the Alcohol Use Disorders Identification Test (AUDIT) in a gene dose-dependent manner, i.e., 24.37 (+/-8.19) among patients with -48A/A genotype, 22.37 (+/-9.49) among those with -48A/G genotype, and 17.38 (+/-8.28) among those with -48G/G genotype (P=0.002). The genetic effects of DRD1-48A>G were further analyzed with other phenotypes among alcohol-dependent subjects. Interestingly, the DRD1-48A>A genotype was also found to be associated with novelty seeking (NC), harm avoidance (HA), and persistence (P) (P =0.01, 0.02, and 0.003, respectively). The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups.
Seguí, J; Márquez, M; Canet, J; Cascio, A; García, L; Ortiz, M
High rates of anxiety disorders, including panic disorder (PD), have been found in patients suffering from alcohol dependence (AD). It has been suggested that alcoholic subjects with PD represent a more severe subgroup of patients. Eighty-nine patients with 'pure' AD (without abuse of other drugs) were examined and compared for the presence of PD. Several clinical scales were administered to assess symptomatology and severity. Twenty-three patients (25.8%) met the criteria for PD. The mean age at onset for alcohol use was 18.7 versus 28.5 years for PD onset. Our finding of an earlier onset for alcoholism than for PD in a sample of Spanish patients illustrates the potential importance of transcultural factors. These patients were more likely to be women and to have first-degree relatives with PD. Overall, alcoholic patients with comorbid PD showed greater clinical severity. They were found to have more comorbidity with axis I disorders (major depression and dysthymia), greater clinical severity, and a history of more suicide attempts.
... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism
De Sousa, Avinash
Alcohol dependence is a major health problem worldwide. Various pharmacological agents have been used in the management of alcohol dependence. This review looks at the role of topiramate and other anticonvulsants in the management of alcohol dependence. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence. The literature on topiramate is reviewed and critically analyzed, along with its proposed mechanism of action in alcohol dependence. A review of data available on other anticonvulsants like carbamazepine, oxcarbazepine, sodium valproate, gabapentin and levetiracetam are presented and their potential in the treatment of alcohol dependence is considered, together with future research directions.
Hoggatt, Katherine J; Jamison, Andrea L; Lehavot, Keren; Cucciare, Michael A; Timko, Christine; Simpson, Tracy L
We conducted a systematic literature review on substance misuse, abuse, and dependence in women veterans, including National Guard/reserve members. We identified 837 articles published between 1980 and 2013. Of 56 included studies, 32 reported rates of alcohol misuse, binge drinking, or other unhealthy alcohol use not meeting diagnostic criteria for abuse or dependence, and 33 reported rates of drug misuse or diagnosed alcohol or drug use disorders. Rates ranged from 4% to 37% for alcohol misuse and from 7% to 25% for binge drinking; among Veterans Health Administration (VA) health-care system outpatients, rates ranged from 3% to 16% for substance use disorder. Studies comparing women veterans and civilians reported no clear differences in binge or heavy drinking. Substance misuse rates were generally lower among women veterans than men veterans. Substance misuse was associated with higher rates of trauma, psychiatric and medical conditions, and increased mortality and suicide rates. Most studies included only VA patients, and many used only VA medical record data; therefore, the reported substance misuse rates likely do not reflect true prevalence. Rates also varied by assessment method, source of data, and the subgroups studied. Further efforts to develop epidemiologically valid prevalence estimates are needed to capture the true health burden of substance misuse in women veterans, particularly those not using VA care.
Heavy drinking contributes to involuntary body movements such as akathisia. Quetiapine has been shown to alleviate symptoms of akathisia; however, its efficacy in the alcohol dependent population is not well established. Thus, we aimed to identify efficacy of Quetiapine in treating akathisia in very heavy drinking alcohol dependent patients. 108 male and female heavy alcohol consuming study participants received 13 weeks of Quetiapine XR. Drinking history (Timeline Followback, TLFB), depression (Montgomery-Asberg Depression Rating Scale, MADRS), and movement (Barnes Akathisia Scale, BARS) measures were collected at baseline (0 W), week 6 (6 W), and week 12 (12 W). The role of drinking, symptoms of depression, and efficacy of Quetiapine for treating akathisia were assessed. In patients with no symptoms of depression (low MADRS), Quetiapine treatment decreased symptoms of akathisia. Patients with clinically significant depression (high MADRS) reported a significant increase in akathisia measures at 6 W which eventually decreased at 12 W to below baseline levels. The increase in akathisia at 6 W corresponded with a significant increase in the patients' total drinks and heavy drinking pattern. Treatment with Quetiapine progressively lowered the occurrence of akathisia in alcohol dependent patients who do not show symptoms of depression. Quetiapine treatment lowered akathisia over time in heavy drinkers who had clinically significant symptoms of depression. PMID:27847671
Jones, Gail Yvonne; Hoffmann, Norman G
Background In light of the emphasis on drug abuse, this study explored the relative prevalence of substance use disorders among United Kingdom (UK) prison inmates in the context of findings from a general inmate population in the United States (US). The lead author of the report conducted a structured diagnostic interview with 155 new admissions to one of two prisons in the UK using the CAAPE (Comprehensive Addiction And Psychological Evaluation), a structured diagnostic interview, to ensure consistent assessments. The US sample consisted of 6,881 male inmates in a state prison system evaluated with an automated version of the SUDDS-IV (Substance Use Disorder Diagnostic Schedule-IV) interview. Results Alcohol dependence emerged as the most prevalent substance use disorder in both UK prisons and in the US sample. Relative frequencies of abuse and dependence for alcohol and other drugs revealed that dependence on a given substance was more prevalent than abuse ad defined by the current diagnostic criteria. Conclusion Despite the emphasis on drugs in correctional populations, alcohol dependence appears to be the most prominent substance use disorder among the incarcerated in both the US and UK and must be considered in developing treatment programs and policy priorities. PMID:17092339
Loas, G; Otmani, O; Lecercle, C; Jouvent, R
Several authors have shown that alexithymia, emotional and perceptual dependency characterize patients suffering from substance abuse. The aim of the study is to test the hypothesis that the emotional and cognitive components of alexithymia are associated with dependency in alcoholics. Three groups were investigated: 60 inpatients meeting the DSM-IV criteria for alcohol dependence, 57 healthy subjects, 144 university students. All subjects completed the following rating scales: The 20-item Toronto Alexithymia Scale (TAS-20), the Interpersonal Dependency Inventory (IDI), the Beck Depression Inventory (BDI), and the Embedded Figures Test (EFT). Partial correlations, using the BDI score as constant, were calculated. In normal subjects, the 'Emotion' subscale of the TAS-20 correlated with the 'Lack of social self-confidence' subscale of the IDI and the 'Cognitive' subscale of the TAS-20 did not correlate with the EFT score. In alcoholics, the 'Cognitive' subscale of the TAS-20 correlated with the 'Lack of social self-confidence' subscale, with the EFT score and with the 'Affirmation of autonomy' subscale. A particular cognitive style characterized by externally oriented thinking, affirmation of autonomy as denial of emotional dependency and field dependence could characterize alcoholics.
Leggio, Lorenzo; Kenna, George A; Fenton, Miriam; Bonenfant, Erica; Swift, Robert M
The goal of typology research is to identify subtypes of alcohol dependent (AD) patients sharing fundamental characteristics and try to match each subtype, with the most precise treatment strategy. This review provides a comprehensive history of the literature on alcohol dependent subtypes starting from the earliest attempt made by Jellinek. The binary models identified most closely with Cloninger and Babor as well as the successively more complex classifications are discussed. Typology classification potentially useful in guiding the treatment of AD patients, especially in the case of the serotonergic medications. Contrasting data suggests that other factors could influence the response to a medication and/or that more complex typologies should be identified. In summary, typology models may assist in the ascertainment criteria for clinical trials performed in behavioral and pharmacotherapeutic interventions. Greater emphasis, however, must be made to more clearly delineate this field of research, while moving toward more standardized typologies.
Potthast, Nadine; Neuner, Frank; Catani, Claudia
Studies reporting a link between child maltreatment and addiction have typically focused on physical and sexual abuse. In contrast, emotional maltreatment has rarely been studied in substance-abusing samples although it is associated with a wide range of dysfunction. The current study aimed to determine the specific impact of different types of maltreatment and peer victimization on alcohol dependence and to examine the potentially mediating role of psychopathology. A sample of treatment seeking adults with alcohol dependence (N=72) underwent an extensive clinical examination including both a standardized interview and self-report measures. Child maltreatment, peer victimization, severity of alcohol dependence, and general psychopathology were assessed. Regression analyses revealed that emotional maltreatment was the strongest predictor of alcohol dependence severity whereas a unique contribution of peer victimization was not found. Our findings suggest that emotional maltreatment might have a major role in the etiology of AD that seems to exceed the contribution of other abuse and victimization experiences. Thereby, the study underscores the need for considering child maltreatment experiences in the prevention and treatment of AD.
Keating, Gillian M
A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients. Sodium oxybate was generally well tolerated. The risk of sodium oxybate abuse is generally low when it is administered to alcohol-dependent patients at its approved dosage, under the supervision of a designated family member and with continuous strict medical surveillance. However, certain patient groups, such as patients with alcohol dependence and borderline personality disorder or who are in remission from heroin or cocaine addiction, may not be suitable candidates for sodium oxybate therapy because of an increased risk of abuse. In conclusion, sodium oxybate is a useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence.
Henderson, Claire; Liu, Xinhua; Diez Roux, Ana V; Link, Bruce G; Hasin, Deborah
Mental health is likely to be influenced by contextual variables that emerge only at the level of the group. We studied the effect of two such group-level variables, within-state income inequality and alcohol tax policy, on symptoms of current depression and alcohol dependence in a US national sample, controlling for state-level and individual characteristics. A cross-sectional US national probability sample provided the individual-level data. State income data were obtained from the 1990 US census. The Gini coefficient (raw and adjusted) indicated income inequality. Outcome measures included current symptoms of depression and alcohol dependence. Controlling for individual-level variables and state median income, the odds of depressive symptoms was not positively associated with state income inequality. Controlling for individual-level variables, state median income and alcohol distribution method, a weak negative association between Gini and alcohol dependence was observed in women, but this association disappeared after additional adjustment for beer tax. No association was observed in men. Higher state beer tax was significantly associated with lower prevalence of alcohol dependence symptoms for both men and women. The results suggest that state income inequality does not increase the experience of alcohol dependence or depression symptoms. However, evidence was found for a protective effect of increased beer taxation against alcohol dependence symptoms, suggesting the need to further consider the impact of alcohol policies on alcohol use disorders.
Pendharkar, Shreyas; Mattoo, Surendra K.; Grover, Sandeep
Background & objectives: Sexual dysfunctions have been reported in alcohol-dependent men. Most of the studies conducted had limitation of using non-validated measures of sexual dysfunction and sampling design. This study was, therefore, conducted to determine the typology, demographic and clinical correlates of sexual dysfunction in alcohol-dependent men. Methods: One hundred and one patients with alcohol dependence (AD) attending the Drug De-addiction and Treatment Centre and 50 healthy controls were evaluated in this cross-sectional study. Participants in both the groups were assessed on Arizona Sexual experience scale (ASEX), Dyadic Adjustment Scale (DAS), Hamilton Depression Rating Scale (HDRS) and State-Trait Anxiety Inventory (STAI). In addition, patients with AD were assessed on Severity of Alcohol Dependence Questionnaire (SADQ) for severity of AD and revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) to ensure that no participant was in active alcohol withdrawal state. Results: Overall, 58.4 per cent of patients in the AD group had sexual dysfunction. Among the domains, the highest frequency was seen for dysfunction for arousal (57.4%), followed by problems in desire (54.4%), erection (36.6%), satisfaction with orgasm (34.6%) and ability to reach orgasm was least affected (12.87%). The patient and control groups differed significantly in overall dyadic adjustment, in the domains of dyadic satisfaction and affective expression. Interpretation & conclusions: The finding of this study showed that a significant proportion of patients with AD has sexual dysfunction. Longitudinal studies using validated assessment tools should be done to confirm these findings. PMID:28139538
Evren, Cuneyt; Evren, Bilge; Dalbudak, Ercan
Objective. The aim of this study was to determine the relationship of alexithymia and temperament and character model of personality with depression and anxiety symptoms in detoxified male alcohol-dependent inpatients. Method. The subjects consisted of 176 male alcohol-dependent inpatients according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Patients were investigated with the Beck Depression Inventory, Beck Anxiety Inventory, State and Trait Anxiety Inventory, Michigan Alcoholism Screening Test (MAST), Toronto Alexithymia Scale (TAS-20) and Temperament and Character Inventory (TCI). Results. MAST score and scores of all three factors of the TAS-20 significantly predicted depression scale and anxiety scales. Difficulty in identifying feelings and difficulty in describing feelings factors were particularly effective, relative to the externally orientated thinking factor of the TAS-20 for prediction depression and anxiety. The TCI dimensions emerged as distinct and conceptually meaningful predictors for the depression scale and anxiety scales. Conclusion. Depression and anxiety symptoms among detoxified male alcohol dependents are associated with alexithymia, a broad range of personality dimensions and higher severity of alcohol-related problems, which make these related factors highly relevant for clinical practice.
Suh, Jesse J.; Pettinati, Helen M.; Kampman, Kyle M.; O’Brien, Charles P.
Recently, we reported that naltrexone at 150mg/day significantly decreased cocaine and alcohol use for men, but not women with co-occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender response to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems, or nausea while in treatment. Further research on the impact of pre-treatment and in-treatment gender differences with naltrexone is warranted. PMID:19034737
Martinez, Diana; Slifstein, Mark; Gil, Roberto; Hwang, Dah-Ren; Huang, Yiyun; Perez, Audrey; Frankle, W. Gordon; Laruelle, Marc; Krystal, John; Abi-Dargham, Anissa
Background Rodent models as well as studies in humans have suggested alterations in serotonin (5HT) innervation and transmission in early onset genetically determined or type II alcoholism. This study examines two indices of serotonergic transmission, 5HT transporter levels and 5-HT1A availability, in vivo, in type II alcoholism. This is the first report of combined tracers for pre and post-synaptic serotonergic transmission in the same alcoholic subjects and the first study of 5HT1A receptors in alcoholism. Method Fourteen alcohol dependent subjects were scanned (11 with both tracers, 1 with [11C]DASB only and two with [11C]WAY100635 only). Twelve healthy controls (HC) subjects were scanned with [11C]DASB and another 13 were scanned with [11C]WAY100635. Binding Potential (BPp, mL/cm3) and the specific to nonspecific partition coefficient (BPND, unitless) were derived for both tracers using 2 tissue compartment model and compared to HC across different brain regions. Relationships to severity of alcoholism were assessed. Results No significant differences were observed in regional BPp or BPND between patients and controls in any of the regions examined. No significant relationships were observed between regional 5HT transporter availability, 5-HT1A availability, and disease severity with the exception of a significant negative correlation between SERT and years of dependence in amygdala and insula. Conclusion This study did not find alterations in measures of 5-HT1A or 5HT transporter levels in patients with type II alcoholism. PMID:18962444
O'Neil, Carol; Maranda, Michael
The purpose of this research was to develop the Identification of Alcohol Dependence in Women (IADW) Scale, which is a 51-question instrument, designed to discriminate between alcohol and non-alcohol dependent women. Questions focus on physical, psychological, family and home life, and use of alcohol. Initial testing of the IADW Scale provides preliminary evidence that it is reliable, has content validity, and is capable of correctly classifying group membership with accuracy. Eighty-six percent of the cases in the alcohol dependent group and 98% of the non-alcohol dependent group were correctly classified using direct and stepwise methods of discriminant analysis.
Marshall, E Jane
In 1976 Edwards & Gross proposed the concept of the alcohol dependence syndrome, based on the clinical observation that heavy drinkers manifested an inter-related clustering of signs and symptoms. That this modest 'provisional description' turned out to be so significant and influential is perhaps unsurprising when the context in which it was made is appreciated. Griffith Edwards and his colleagues at the Maudsley Hospital had undergone a rigorous 3-year training in clinical psychiatry, during which they had been taught to think critically and were grounded in the art of clinical observation. As he assessed patients for various alcohol research studies he realized that there was a clustering of certain elements. Thus clinical observation and an appreciation of the patient's drinking history contributed to the genesis of the concept. This paper reflects on the integration of his rigorous training at the Maudsley, his enquiring mind and encyclopaedic knowledge of the historical and research literature which enabled him to formulate a testable hypothesis about the alcohol dependence syndrome.
Rationale Genetic and environmental influences on the development of alcohol and drug dependence are equally important. Exposure to early life stress, that is unfortunately common in the general population, has been shown to predict a wide range of psychopathology, including addiction. Objective This review will look at the characteristics of early life stress that may be specific predictors for adolescent and adult alcohol and drug dependence and will focus on studies in humans, non-human primates and rodents. Results Experiencing maltreatment and cumulative stressful life events prior to puberty and particularly in the first few years of life is associated with early onset of problem drinking in adolescence and alcohol and drug dependence in early adulthood. Early life stress can result in permanent neurohormonal and hypothalamic-pituitary-adrenal axis changes, morphological changes in the brain and gene expression changes in the mesolimbic dopamine reward pathway, all of which are implicated in the development of addiction. However, a large proportion of children who have experienced even severe early life stress do not develop psychopathology indicating that mediating factors such as gene-environment interactions and family and peer relationships are important for resilience. Conclusions There appears to be a direct pathway from chronic stress exposure in pre-pubertal children via adolescent problem drinking to alcohol and drug dependence in early adulthood. However, this route can be moderated by genetic and environmental factors. The role that gene-environment interactions play in the risk-resilience balance is being increasingly recognized. PMID:20596857
Garcia-Marchena, Nuria; Pavon, Francisco J; Pastor, Antoni; Araos, Pedro; Pedraz, Maria; Romero-Sanchiz, Pablo; Calado, Montserrat; Suarez, Juan; Castilla-Ortega, Estela; Orio, Laura; Boronat, Anna; Torrens, Marta; Rubio, Gabriel; de la Torre, Rafael; Rodriguez de Fonseca, Fernando; Serrano, Antonia
Acylethanolamides are a family of endogenous lipid mediators that are involved in physiological and behavioral processes associated with addiction. Recently, oleoylethanolamide (OEA) has been reported to reduce alcohol intake and relapse in rodents but the contribution of OEA and other acylethanolamides in alcohol addiction in humans is unknown. The present study is aimed to characterize the plasma acylethanolamides in alcohol dependence. Seventy-nine abstinent alcohol-dependent subjects (27 women) recruited from outpatient treatment programs and age-/sex-/body mass-matched healthy volunteers (28 women) were clinically assessed with the diagnostic interview PRISM according to the DSM-IV-TR after blood extraction for quantification of acylethanolamide concentrations in the plasma. Our results indicate that all acylethanolamides were significantly increased in alcohol-dependent patients compared with control subjects (p < 0.001). A logistic model based on these acylethanolamides was developed to distinguish alcohol-dependent patients from controls and included OEA, arachidonoylethanolamide (AEA) and docosatetraenoylethanolamide (DEA), providing a high discriminatory power according to area under the curve [AUC = 0.92 (95%CI: 0.87-0.96), p < 0.001]. Additionally, we found a significant effect of the duration of alcohol abstinence on the concentrations of OEA, AEA and DEA using a regression model (p < 0.05, p < 0.01 and p < 0.001, respectively), which was confirmed by a negative correlation (rho = -0.31, -0.40 and -0.44, respectively). However, acylethanolamides were not influenced by the addiction alcohol severity, duration of problematic alcohol use or diagnosis of psychiatric comorbidity. Our results support the preclinical studies and suggest that OEA, AEA and DEA are altered in alcohol-dependence during abstinence and that might act as potential markers for predicting length of alcohol abstinence.
Heinz, Adrienne J; Fogler, Kethera A; Newcomb, Michael E; Trafton, Jodie A; Bonn-Miller, Marcel O
Problematic alcohol use has been shown to negatively impact cognitive functions germane to achieving optimal HIV health outcomes. The present study, a secondary data analysis, examined the impact of problematic alcohol use on aspects of everyday memory functioning in a sample of 172 HIV-infected individuals (22 % female; Mage = 48.37 years, SD = 8.64; 39 % Black/non-Hispanic). Additionally, we tested whether self-reported memory functioning explained the relation between problematic alcohol use and HIV symptom severity. Results indicated that problematic patterns of alcohol use were associated with lower total memory functioning, retrieval (e.g., recall-difficulty) and memory for activity (e.g., what you did yesterday) and greater HIV symptom severity. Memory functioning mediated the relation between problematic alcohol use and HIV symptom severity. However, the direction of this relation was unclear as HIV symptom severity also mediated the relation between problematic alcohol use and memory functioning. Findings highlight the importance of integrated care for HIV and alcohol use disorders and suggest that routine alcohol and cognitive screenings may bolster health outcomes among this vulnerable population.
Kim, Theresa W; Saitz, Richard; Cheng, Debbie M; Winter, Michael R; Witas, Julie; Samet, Jeffrey H
We examined the effect of the quality of primary care-based chronic disease management (CDM) for alcohol and/or other drug (AOD) dependence on addiction outcomes. We assessed quality using (1) a visit frequency based measure and (2) a self-reported assessment measuring alignment with the chronic care model. The visit frequency based measure had no significant association with addiction outcomes. The self-reported measure of care-when care was at a CDM clinic-was associated with lower drug addiction severity. The self-reported assessment of care from any healthcare source (CDM clinic or elsewhere) was associated with lower alcohol addiction severity and abstinence. These findings suggest that high quality CDM for AOD dependence may improve addiction outcomes. Quality measures based upon alignment with the chronic care model may better capture features of effective CDM care than a visit frequency measure.
Bobova, Lyuba; Finn, Peter R; Rickert, Martin E; Lucas, Jesolyn
Increased discounting of delayed rewards may reflect a decision bias that contributes to excessive use of alcohol and more generally, to an impulsive, disinhibitory predisposition that is characterized by a preference for immediate over long-term rewards. The current study examined the association between delay discounting of rewards and the covariation among several types of disinhibitory problems that are often comorbid with alcohol dependence (AD). Lifetime problems with alcohol, marijuana, other drugs, childhood conduct disorder, and adult antisocial behavior were assessed in a sample of 426 young adults, 257 of whom had a lifetime diagnosis of AD. Higher delay discounting rates were associated with the covariation among all domains of disinhibitory problems and were not uniquely associated with any one domain. Higher delay discounting rates also were associated with lower intelligence, lower working memory capacity, and higher trait impulsivity. The results suggest that increased delay discounting of rewards may reflect aspects of a general vulnerability to externalizing, disinhibitory disorders.
Skidmore, Jessica R; Murphy, James G; Martens, Matthew P
The aims of the current study were to examine the associations among behavioral economic measures of alcohol value derived from 3 distinct measurement approaches, and to evaluate their respective relations with traditional indicators of alcohol problem severity in college drinkers. Five behavioral economic metrics were derived from hypothetical demand curves that quantify reward value by plotting consumption and expenditures as a function of price, another metric measured proportional behavioral allocation and enjoyment related to alcohol versus other activities, and a final metric measured relative discretionary expenditures on alcohol (RDEA). The sample included 207 heavy-drinking college students (53% female) who were recruited through an on-campus health center or university courses. Factor analysis revealed that the alcohol valuation construct comprises 2 factors: 1 factor that reflects participants' levels of alcohol price sensitivity (demand persistence), and a second factor that reflects participants' maximum consumption and monetary and behavioral allocation toward alcohol (amplitude of demand). The demand persistence and behavioral allocation metrics demonstrated the strongest and most consistent multivariate relations with alcohol-related problems, even when controlling for other well-established predictors. The results suggest that behavioral economic indices of reward value show meaningful relations with alcohol problem severity in young adults. Despite the presence of some gender differences, these measures appear to be useful problem indicators for men and women.
Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard
This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.
Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K
Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol.
Heilig, Markus; Egli, Mark
Alcoholism is a major public health problem and resembles, in many ways, other chronic relapsing medical conditions. At least 2 separate dimensions of its symptomatology offer targetable pathophysiological mechanisms. Systems that mediate positive reinforcement by alcohol are likely important targets in early stages of the disease, particularly in genetically susceptible individuals. In contrast, long term neuroadaptive changes caused by chronic alcohol use primarily appear to affect systems mediating negative affective states, and gain importance following a prolonged history of dependence. Feasibility of pharmacological treatment in alcoholism has been demonstrated by a first wave of drugs which consists of 3 currently approved medications, the aldehyde dehydrogenase blocker disulfiram, the opioid antagonist naltrexone (NTX) and the functional glutamate antagonist acamprosate (ACM). The treatment toolkit is likely to be expanded in the near future. This will improve overall efficacy and allow individualized treatment, ultimately taking in account the patient's genetic makeup. In a second wave, early human efficacy data are available for the 5HT3 antagonist ondansetron, the GABA-B agonist baclofen and the anticonvulsant topiramate. The third wave is comprised of compounds predicted to be effective based on a battery of animal models. Using such models, a short list of additional targets has accumulated sufficient preclinical validation to merit clinical development. These include the cannabinoid CB1 receptor, receptors modulating glutamatergic transmission (mGluR2, 3 and 5), and receptors for stress-related neuropeptides corticotropin releasing factor (CRF), neuropeptide Y (NPY) and nociceptin. Once novel treatments are developed, the field faces a major challenge to assure their delivery to patients.
Thoma, Patrizia; Winter, Natalia; Juckel, Georg; Roser, Patrik
Impaired social cognition has been associated with interpersonal problems and with the development of and relapse into alcohol abuse. In the present study, self-reported trait empathy, decoding of complex mental states and cognitive and affective mental state reasoning were assessed in alcohol-dependent participants, and the association with executive function and psychopathological characteristics was investigated. Twenty recently detoxified alcohol-dependent patients and 20 matched healthy controls were assessed with an abbreviated German version of the interpersonal reactivity index, the revised reading the mind in the eyes test, the faux pas story test, the trail making test and the letter-number-sequencing test. Patients were impaired relative to controls with regard to mental state decoding on the eyes test and showed reduced faux pas detection and impaired mental state reasoning reflected by lower faux pas understanding and faux pas empathy scores. There were no group differences regarding self-reported trait empathy. Performance on the sociocognitive measures was related to executive functioning and the severity of depressive symptoms. Although self-report measures might not always reliably detect impairments of social cognition, behavioural measures suggest pronounced impairments of mental state decoding and mental state reasoning in association with alcohol dependence. Findings ought to be incorporated into current treatment strategies.
Le Strat, Yann; Grant, Bridget F.; Ramoz, Nicolas; Gorwood, Philip
Objective The accurate cut-off of an early onset of alcohol dependence is unknown. The objectives of this analysis are (1) to confirm that ages at onset variability in alcohol dependence is best described as a two sub-groups entity, (2) to define the most appropriate cut-off, and (3) to test the relevancy of such distinction. Method Data were drawn the Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This study focused on the 4,782 adults with lifetime alcohol dependence. Results The best-fit model distinguished two subgroups of age at onset of alcohol dependence, with a cut-off point at 22 years. Subjects with an earlier onset of alcohol dependence (≤22 years old) reported higher lifetime rates of specific phobia, antisocial behaviors and nearly all addictive disorders. Conclusions The early onset of alcohol dependence is best defined as beginning before the age of 22 years. PMID:20018459
Miele, G M; Carpenter, K M; Cockerham, M S; Trautman, K D; Blaine, J; Hasin, D S
The Substance Dependence Severity Scale (SDSS) is a semistructured interview that assesses the severity of the DSM-IV diagnoses of dependence and abuse and the ICD-10 diagnoses of substance dependence and harmful use across a wide range of substances. Previous research has demonstrated that the SDSS' DSM-IV dependence scales are reliable and valid indicators of diagnostic severity. However, the ICD-10 scales have not been psychometrically tested. This study investigated the test-retest reliability, internal consistency, diagnostic concordance, and concurrent validity of the SDSS' ICD-10 dependence and harmful use scales in 180 (112 male and 68 female) treated substance users. Test-retest reliabilities for the ICD-10 dependence scales ranged from good to excellent for alcohol, cocaine, heroin, and cannabis. Test-retest reliabilities for the SDSS' ICD-10 harmful use scales were in the good range for alcohol, cocaine, and heroin and the poor to fair range for cannabis. Internal consistency, diagnostic concordance, and concurrent validity results were comparable to the test-retest findings. These results support the use of the SDSS for assessing the severity of the ICD-10 dependence and harmful use diagnoses.
Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel
In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.
Berking, Matthias; Margraf, Matthias; Ebert, David; Wupperman, Peggilee; Hofmann, Stefan G.; Junghanns, Klaus
Objective: As emotion regulation is widely considered to be a primary motive in the misuse of alcohol, our aim in the study was to investigate whether deficits in adaptive emotion-regulation skills maintain alcohol dependence (AD). Method: A prospective study investigated whether emotion-regulation skills were associated with AD and whether these…
Buck, Cara L; Malavar, Jordan C; George, Olivier; Koob, George F; Vendruscolo, Leandro F
Rats emit 50kHz ultrasonic vocalizations (USVs) in situations of increased motivation, such as during the anticipation of palatable food or drugs of abuse. Whether the same holds true for the anticipation of alcohol intake remains unknown. Alcohol drinking in a nondependent state is thought to be mediated by its rewarding effects (positive reinforcement), whereas drinking in the dependent state is motivated by alcohol's stress-relieving effects (negative reinforcement). Here, we measured context-elicited 50kHz USVs in alcohol-dependent (alcohol vapor-exposed) and nondependent rats immediately before operant alcohol self-administration sessions. Dependent rats showed escalated levels of alcohol intake compared with nondependent rats. Overall, dependent and nondependent rats showed similar levels of anticipatory 50kHz USVs. However, the number of anticipatory USVs was positively correlated with alcohol intake in dependent rats but not nondependent rats. Additionally, dependent rats with higher alcohol intake displayed increased anticipatory 50kHz USVs compared with rats that had lower alcohol intake, whereas no difference was observed between rats with high and low alcohol intake in the nondependent group. Increased 50kHz USVs were specific for the anticipation of alcohol self-administration and did not generalize to a novel environment. These findings suggest that anticipatory 50kHz USVs may be an indicator of context-elicited negative reinforcement learning.
McKellar, John; Stewart, Eric; Humphreys, Keith
A positive corelation between Alcoholics Anonymous (AA) involvement and better alcohol-related outcomes has been identified in research studies, but whether this correlation reflects a causal relationship remains a subject of meaningful debate. The present study evaluated the question of whether AA affiliation appears causally related to positive alcohol-related outcomes in a sample of 2,319 male alcohol-dependent patients. An initial structural equation model indicated that 1-year posttreatment levels of AA affiliation predicted lower alcohol-related problems at 2-year follow-up, whereas level of alcohol-related problems at 1-year did not predict AA affiliation at 2-year follow-up. Additional models found that these effects were not attributable to motivation or psychopathology. The findings are consistent with the hypothesis that AA participation has a positive effect on alcohol-related outcomes.
Sugawara, Tazuko; Morita, Noriaki; Nakatani, Youji
The aim of this study was to develop a scale to evaluate characteristics of how alcohol-dependent people perceive the attitudes of their partners toward alcohol dependency. Based on previous research, we created the "Attitudes of partners toward alcohol dependency" scale, from the perspective of the alcohol dependent individual. Using the new scale, 71 alcohol-dependent people (52 men, 19 women) were surveyed after obtaining their consent, and the reliability and validity of the scale were tested. The results identified 3 factors, "indifference", "acceptance" and "hypersensitivity", and factorial validity was verified. Relatively high reliability was obtained on each sub-scale (alpha = .60-.82). Furthermore, correlations were obtained with the alcohol-dependency "Denial and Awareness Scale (for alcohol-dependent people)" and with the 13-item "Usefulness of heterosexual love relations for recovery from alcohol dependency" questionnaire, which includes content on "beneficial" or "obstructive" to recovery, and with the satisfaction and the importance of relations. This demonstrates that the "Attitudes of partners toward alcohol dependency" scale has reliability and criterion-related validity. The scale facilitates evaluation of types of attitudes of partners toward alcohol dependency, and may thus be useful as one tool for investigating the influence of partners in heterosexual love relationships for recovery, and for providing advice.
Goldstein, Brittany; Bradley, Bekh; Ressler, Kerry J.
Objective The purpose of this study was to examine how emotion dysregulation (ED) might help explain the relationship between posttraumatic stress disorder (PTSD) and alcohol dependence (AD) symptoms in females. Method Participants included 260 women from primary, diabetes, and gynecological clinics of an urban public hospital. This is a primarily African American sample (96.9%), including individuals reporting exposure to at least 1 traumatic event. We examined the associations and predictability patterns between severity of PTSD symptoms, ED, and AD symptoms. Results Using linear regression analyses, PTSD avoidance and numbing symptoms and ED were significant predictors of AD symptoms. When looking at specific dimensions of ED, one's inability to engage in goal‐directed behavior under strong emotional influences showed a full indirect effect on the relationship between PTSD avoidance and numbing symptoms and AD symptoms. Conclusion Our findings suggest that having poor emotion regulation skills may help explain why females with PTSD become dependent on alcohol. PMID:27467499
Barnas, C; Miller, C H; Sperner, G; Sperner-Unterweger, B; Beck, E; Hinterhuber, H; Fleischhacker, W W
Urine samples from 402 victims of ski accidents were analyzed for the presence of benzodiazepines (BZD) and alcohol. Eighty-one (20%) samples were positive for alcohol; BZD were detected in 34 (8.5%) cases. Ten of the samples (2.5%) were found to be positive for both alcohol and BZD. Subjects who were positive for either alcohol or BZD or both were older than the other persons examined. The prevalence of alcohol was significantly higher among male accident victims. BZD intake could be demonstrated to have a significant influence on the severity of injuries. Besides an increased awareness of the need for skier education regarding drug use, heightened attention of medical caregivers is warranted to inform their patients about potential accident hazards in sport activities when BZD are prescribed.
Walitzer, Kimberly S.; Deffenbacher, Jerry L.; Shyhalla, Kathleen
A randomized controlled trial for an innovative alcohol-adapted anger management treatment (AM) for outpatient alcohol dependent individuals scoring moderate or above on anger is described. AM treatment outcomes were compared to those of an empirically-supported intervention, Alcoholics Anonymous Facilitation treatment (AAF). Clients in AM, relative to clients in AAF, were hypothesized to have greater improvement in anger and anger-related cognitions and lesser AA involvement during the six-month follow-up. Anger-related variables were hypothesized to be stronger predictors of improved alcohol outcomes in the AM treatment condition and AA involvement was hypothesized to be a stronger predictor of alcohol outcomes in the AAF treatment group. Seventy-six alcohol dependent men and women were randomly assigned to treatment condition and followed for six months after treatment end. Both AM and AAF treatments were followed by significant reductions in heavy drinking days, alcohol consequences, anger, and maladaptive anger-related thoughts and increases in abstinence and self-confidence regarding not drinking to anger-related triggers. Treatment with AAF was associated with greater AA involvement relative to treatment with AM. Changes in anger and AA involvement were predictive of posttreatment alcohol outcomes for both treatments. Change in trait anger was a stronger predictor of posttreatment alcohol consequences for AM than for AAF clients; during-treatment AA meeting attendance was a stronger predictor of posttreatment heavy drinking and alcohol consequences for AAF than for AM clients. Anger-related constructs and drinking triggers should be foci in treatment of alcohol dependence for anger-involved clients. PMID:26387049
Hirth, Natalie; Meinhardt, Marcus W.; Noori, Hamid R.; Salgado, Humberto; Torres-Ramirez, Oswaldo; Uhrig, Stefanie; Broccoli, Laura; Vengeliene, Valentina; Roßmanith, Martin; Perreau-Lenz, Stéphanie; Köhr, Georg; Sommer, Wolfgang H.; Spanagel, Rainer; Hansson, Anita C.
A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior. Here we set out to study systematically the neuroadaptive changes in the DA system during the addiction cycle in alcohol-dependent patients and rats. In postmortem brain samples from human alcoholics we found a strong down-regulation of the D1 receptor- and DA transporter (DAT)-binding sites, but D2-like receptor binding was unaffected. To gain insight into the time course of these neuroadaptations, we compared the human data with that from alcohol-dependent rats at several time points during abstinence. We found a dynamic regulation of D1 and DAT during 3 wk of abstinence. After the third week the rat data mirrored our human data. This time point was characterized by elevated extracellular DA levels, lack of synaptic response to D1 stimulation, and augmented motor activity. Further functional evidence is given by a genetic rat model for hyperdopaminergia that resembles a phenocopy of alcohol-dependent rats during protracted abstinence. In summary, we provide a new dynamic model of abstinence-related changes in the striatal DA system; in this model a hyperdopaminergic state during protracted abstinence is associated with vulnerability for relapse. PMID:26903621
Buck, Cara L.; Malavar, Jordan C.; George, Olivier; Koob, George F.; Vendruscolo, Leandro F.
Rats emit 50 kHz ultrasonic vocalizations (USVs) in situations of increased motivation, such as during the anticipation of palatable food or drugs of abuse. Whether the same holds true for the anticipation of alcohol intake remains unknown. Alcohol drinking in a nondependent state is thought to be mediated by its rewarding effects (positive reinforcement), whereas drinking in the dependent state is motivated by alcohol’s stress-relieving effects (negative reinforcement). Here, we measured context-elicited 50 kHz USVs in alcohol-dependent (alcohol vapor-exposed) and nondependent rats immediately before operant alcohol self-administration sessions. Dependent rats showed escalated levels of alcohol intake compared with nondependent rats. Overall, dependent and nondependent rats showed similar levels of anticipatory 50 kHz USVs. However, the number of anticipatory USVs was positively correlated with alcohol intake in dependent rats but not nondependent rats. Additionally, dependent rats with higher alcohol intake displayed increased anticipatory 50 kHz USVs compared with rats that had lower alcohol intake, whereas no difference was observed between rats with high and low alcohol intake in the nondependent group. Increased 50 kHz USVs were specific for the anticipation of alcohol self-administration and did not generalize to a novel environment. These findings suggest that anticipatory 50 kHz USVs may be an indicator of context-elicited negative reinforcement learning. PMID:24914463
Clarke, Toni-Kim; Smith, Andrew H; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Hall, Lynsey S; Fernandez-Pujals, Ana M; MacIntyre, Donald J; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; Thomson, Pippa A; Porteous, David J; Deary, Ian J; McIntosh, Andrew M
Alcohol dependence is frequently co-morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome-wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n = 2750; Yale-Penn GWAS: n = 2377) in a population-based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P = 0.009, β = -0.027; Yale-Penn: P = 0.001, β = -0.034) and VF (SAGE: P = 0.0008, β = -0.036; Yale-Penn: P = 0.00005, β = -0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P = 5.2 × 10(-7) , β = -0.054; Yale-Penn: P = 0.000012, β = -0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders.
Caetano, Raul; Ramisetty-Mikler, Suhasini; Rodriguez, Lori A
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.
Prazosin for Treatment of Patients with PTSD and Comorbid Alcohol Dependence PRINCIPAL INVESTIGATOR...of Patients with PTSD and Comorbid Alcohol Dependence 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-2-0075 5c. PROGRAM ELEMENT NUMBER 6...comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of TSD among individuals with AD are at least twice
Hillmer, Ansel T.; Mason, Graeme F.; Fucito, Lisa M.; O’Malley, Stephanie S.; Cosgrove, Kelly P.
Neuroimaging studies have dramatically advanced our understanding of the neurochemical basis of alcohol dependence, a major public health issue. In this paper we review the research generated from neurochemical-specific imaging modalities including magnetic resonance spectrometry (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in studies of alcohol dependence and withdrawal. We focus on studies interrogating γ-aminobutryic acid (GABA), glutamate, and dopamine, as these are prominent neurotransmitter systems implicated in alcohol dependence. Highlighted findings include diminished dopaminergic functioning and modulation of the GABA system by tobacco smoking during alcohol withdrawal. Then, we consider how these findings impact the clinical treatment of alcohol dependence and discuss directions for future experiments to address existing gaps in the literature, e.g., sex differences and smoking comorbidity. These and other considerations provide opportunities to build upon the current neurochemistry imaging literature of alcohol dependence and withdrawal, which may usher in improved therapeutic and relapse prevention strategies. PMID:26510169
Walt, Lisa C.; Kinoti, Elias; Jason, Leonard A.
Developing countries’ industrialization and urbanization attempts have been linked to psychological distress and alcohol abuse. We used Hobfoll’s COR theory to examine the relationship between gender, perceived resource loss (an indicator of industrialization stress), and alcohol abuse and dependence in a sample of Kenyan rural village men and women (N = 186). Regression analyses indicated that both gender and COR loss predicted alcohol abuse and dependence. Additionally, results suggested that gender moderated the relationship between COR loss and alcohol dependence; such that higher COR loss scores predicted higher alcohol dependence for men, but COR loss scores did not predict alcohol dependence for women. Thus, we suggest that gender differences in substance abuse may be due less to actual differences in resource loss, but rather to gender differences in the response to resource loss. Limitations and opportunities for future research are discussed. PMID:24489525
Mon, Anderson; Durazzo, Timothy C.; Abe, Christoph; Gazdzinski, Stefan; Pennington, David; Schmidt, Thomas; Meyerhoff, Dieter J.
Background Over 50% of individuals with alcohol use disorders (AUD) also use other substances. Therefore, brain structural abnormalities observed in alcohol dependent individuals may not be entirely related to alcohol consumption. This MRI study assessed differences in brain regional tissue volumes between short-term abstinent alcohol dependent individuals without (ALC) and with current substance use dependence (polysubstance users, PSU). Methods Nineteen, one-month-abstinent PSU and 40 ALC as well as 27 light-drinkers (LD) were studied on a 1.5 Tesla MR system. Whole brain T1-weighted images were segmented automatically into regional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes. MANOVA assessed group differences of intracranial volume-normalized tissue volumes of the frontal, parietal, occipital, and temporal lobes as well as regional subcortical GM volumes. The volumetric measures were correlated with neurocognitive measures to assess their functional relevance. Results Despite similar lifetime drinking and smoking histories, PSU had significantly larger normalized WM volumes than ALC in all lobes. PSU also had larger frontal and parietal WM volumes than LD, but smaller temporal GM volumes as well as smaller lenticular and thalamic nuclei than LD. By contrast, ALC had smaller frontal, parietal, and temporal GM, thalamic GM and cerebellar volumes than LD. ALC also had more sulcal CSF volumes than both PSU and LD. Conclusion One-month-abstinent ALC and PSU exhibited different patterns of gross brain structural abnormalities. The larger lobar WM volumes in PSU in the absence of widespread GM volume loss contrast with widespread GM atrophy in ALC. These structural differences between ALC and PSU may demand different treatment approaches to mitigate specific functionally relevant brain abnormalities. PMID:25263262
Zhu, Xi; Cortes, Carlos R; Mathur, Karan; Tomasi, Dardo; Momenan, Reza
Alcohol dependence is characterized by impulsiveness toward consumption despite negative consequences. Although neuro-imaging studies have implicated some regions underlying this disorder, there is little information regarding its large-scale connectivity pattern. This study investigated the within- and between-network functional connectivity (FC) in alcohol dependence and examined its relationship with clinical impulsivity measures. Using probabilistic independent component analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 alcohol-dependent (AD) and 26 healthy control (HC) participants, we compared the within- and between-network FC between AD and HC. Then, the relationship between FC and impulsiveness as measured by the Barratt Impulsiveness Scale (BIS-11), the UPPS-P Impulsive Scale and the delay discounting task (DDT), was explored. Compared with HC, AD exhibited increased within-network FC in salience (SN), default mode (DMN), orbitofrontal cortex (OFCN), left executive control (LECN) and amygdala-striatum (ASN) networks. Increased between-network FC was found among LECN, ASN and SN. Between-network FC correlations were significantly negative between Negative-Urgency and OFCN pairs with right executive control network (RECN), anterior DMN (a-DMN) and posterior DMN (p-DMN) in AD. DDT was significantly correlated with the between-network FC among the LECN, a-DMN and SN in AD. These findings add evidence to the concept of altered within-network FC and also highlight the role of between-network FC in the pathophysiology of AD. Additionally, this study suggests differential neurobiological bases for different clinical measures of impulsivity that may be used as a systems-level biomarker for alcohol dependence severity and treatment efficacy.
Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R
Objectives Alcohol is responsible for a proportion of emergency admissions to hospital, with acute alcohol intoxication and chronic alcohol dependency (CAD) implicated. This study aims to quantify the proportion of hospital admissions through our emergency department (ED) which were thought by the admitting doctor to be (largely or partially) a result of alcohol consumption. Setting ED of a UK tertiary referral hospital. Participants All ED admissions occurring over 14 weeks from 1 September to 8 December 2012. Data obtained for 5497 of 5746 admissions (95.67%). Primary outcome measures Proportion of emergency admissions related to alcohol as defined by the admitting ED clinician. Secondary outcome measures Proportion of emergency admissions due to alcohol diagnosed with acute alcohol intoxication or CAD according to ICD-10 criteria. Results 1152 (21.0%, 95% CI 19.9% to 22.0%) of emergency admissions were thought to be due to alcohol. 74.6% of patients admitted due to alcohol had CAD, and significantly greater than the 26.4% with ‘Severe’ or ‘Very Severe’ acute alcohol intoxication (p<0.001). Admissions due to alcohol differed to admissions not due to alcohol being on average younger (45 vs 56 years, p<0.001) more often male (73.4% vs 45.1% males, p<0.001) and more likely to have a diagnosis synonymous with alcohol or related to recreational drug use, pancreatitis, deliberate self-harm, head injury, gastritis, suicidal ideation, upper gastrointestinal bleeds or seizures (p<0.001). An increase in admissions due to alcohol on Saturdays reflects a surge in admissions with acute alcohol intoxication above the weekly average (p=0.003). Conclusions Alcohol was thought to be implicated in 21% of emergency admissions in this cohort. CAD is responsible for a significantly greater proportion of admissions due to alcohol than acute intoxication. Interventions designed to reduce alcohol-related admissions must incorporate measures to tackle CAD. PMID:27324707
Chermack, Stephen T; Wryobeck, John M; Walton, Maureen A; Blow, Frederic C
This study examined the relationships among distal (paternal and maternal family history of alcohol problems and violence) and proximal (general alcohol use, acute use associated with conflict incidents, alcohol-aggression expectancies) factors and physical aggression severity among 125 men and 125 women recruited from substance abuse treatment. Paternal alcohol problem history (PA) was related to alcohol-aggression expectancies, but no family history factors were related to general or acute alcohol use. Separate analyses examining predictors of aggression were conducted, one with general alcohol use and one with acute alcohol use. In both analyses, alcohol use and the maternal violence (MV) by PA interaction were significant. Specifically, MV was associated with aggression severity for those with a history of PA. The general alcohol use model also revealed significant alcohol by expectancy and MV by gender interactions. The findings suggest that expectancies are not the primary mediator of the alcohol-aggression relationship, alcohol use measurement issues may impact whether expectancies are observed to moderate the alcohol-aggression relationship, and that both maternal and paternal family history factors appear to impact aggression severity.
Cosgrove, Kelly P.; Esterlis, Irina; Mason, Graeme F.; Bois, Frederic; O'Malley, Stephanie S.; Krystal, John H.
This paper reviews evidence suggesting that nicotine and tobacco smoke profoundly modulate the effects of alcohol on γ-aminobutyric acid (GABA) neuronal function, specifically at the GABAA-benzodiazepine receptor (GABAA-BZR). The focus of this paper is on recent neuroimaging evidence in preclinical models as well as clinical experiments. First, we review findings implicating the role of alcohol at the GABAA-BZR and discuss the changes in GABAA-BZR availability during acute and prolonged alcohol withdrawal. Second, we discuss preclinical evidence that suggests nicotine affects GABA neuronal function indirectly by a primary action at neuronal nicotinic acetylcholine receptors. Third, we show how this evidence converges in studies that examine GABA levels and GABAA-BZRs in alcohol-dependent smokers and nonsmokers, suggesting that tobacco smoking attenuates the chemical changes that occur during alcohol withdrawal. Based on a comprehensive review of literature, we hypothesize that tobacco smoking minimizes the changes in GABA levels that typically occur during the acute cycles of drinking in alcohol-dependent individuals. Thus, during alcohol withdrawal, the continued tobacco smoking decreases the severity of the withdrawal-related changes in GABA chemistry. PMID:21276806
Chakravorty, Subhajit; Chaudhary, Ninad S; Brower, Kirk J
Sleep-related complaints are widely prevalent in those with alcohol dependence (AD). AD is associated not only with insomnia, but also with multiple sleep-related disorders as a growing body of literature has demonstrated. This article will review the various aspects of insomnia associated with AD. In addition, the association of AD with other sleep-related disorders will be briefly reviewed. The association of AD with insomnia is bidirectional in nature. The etiopathogenesis of insomnia has demonstrated multiple associations and is an active focus of research. Treatment with cognitive behavioral therapy for insomnia is showing promise as an optimal intervention. In addition, AD may be associated with circadian abnormalities, short sleep duration, obstructive sleep apnea, and sleep-related movement disorder. The burgeoning knowledge on insomnia associated with moderate-to-severe alcohol use disorder has expanded our understanding of its underlying neurobiology, clinical features, and treatment options.
Zandberg, Laurie J.; Rosenfield, David; McLean, Carmen P.; Powers, Mark B.; Asnaani, Anu; Foa, Edna B.
Objective The present study examined predictors and moderators of treatment response among 165 adults meeting DSM-IV criteria for comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD) who were randomized to 24 weeks of naltrexone (NAL), NAL and prolonged exposure (PE), pill placebo, or pill placebo and PE. All participants received supportive counseling for alcohol use. Method Six domains of predictors/moderators (23 variables) were evaluated using measures of PTSD (Posttraumatic Stress Symptom Scale Interview; PSS-I) and AD (percent days drinking from the Timeline Follow-Back Interview) collected every four weeks throughout treatment. Multi-level modeling using the Fournier approach was employed to evaluate predictors and moderators of rates of symptom improvement and post-treatment outcomes. Results Combat trauma, sexual assault trauma, and higher baseline anxiety sensitivity predicted slower improvement and poorer PTSD outcome. Combat trauma, white race, and higher baseline drinking severity predicted poorer drinking outcome. PTSD severity moderated the efficacy of PE on PTSD outcomes, such that the benefit of PE over no-PE was greater for participants with higher baseline PTSD severity. Baseline depressive severity moderated the efficacy of PE on drinking outcomes, whereby the benefit of PE over no-PE was greater for participants with higher depressive symptoms. NAL effects were most beneficial for those with the longest duration of alcohol dependence. Conclusions These results suggest that concurrent, trauma-focused treatment should be recommended for PTSD-AD patients who present with moderate or severe baseline PTSD and depressive symptoms. Future research should examine the mechanisms underlying poorer outcome among identified sub-groups of PTSD-AD patients. PMID:26460570
Martinotti, G; Di Nicola, M; Di Giannantonio, M; Janiri, L
Substantial evidence suggests that both partial dopamine agents and mixed 5-HT1A/2A receptor drugs independently show significant efficacy in reducing alcohol use in both animals and humans. Aripiprazole, which acts as a dopamine/5-HT system stabilizer, approaches the optimal characteristics sought in medication to be considered for testing in the treatment of alcohol dependence. In this randomised, double-blind, confrontation trial with naltrexone, we aimed to investigate the efficacy of aripiprazole on alcohol-drinking indices. Craving and psychiatric symptom improvements were the secondary end points. Seventy-five alcohol dependent subjects were detoxified and were subsequently randomised into two groups, receiving 50 mg of naltrexone and 5-15 mg of aripiprazole, respectively. Craving (Visual Analogue Scale; Obsessive and Compulsive Drinking Scale) and withdrawal (Clinical Institute Withdrawal Assessment) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List 90-Revised. The number of subjects remained alcohol free for the entire study period (16 weeks) and the number of subjects relapsed were not significantly different in the two groups. The survival function showed that patients treated with aripiprazole remained abstinent from any alcohol amount for a longer time with respect to those treated with naltrexone. As for craving scores, patients treated with naltrexone showed a better outcome. Results from this study globally place aripiprazole at the same range of efficacy of naltrexone, one of the approved drugs used in alcohol relapse prevention. If it could be demonstrated in placebo-controlled trials that aripiprazole is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a powerful agent for the treatment of alcohol-dependent subjects.
Currently detoxification of drug and alcohol dependent patients is pharmacologically unresolved, and long-term treatment following the acute phase is also not very successful including a high number of relapses. We would need medications that on the short term cease: the severe vegetative symptoms, the pain, the extremely distressing psychosyndrome characterised by restlessness, anxiety or acute depressive symptoms, and the craving. The optimal would be if there was one medication capable of simultaneously alleviating or diminishing all the above symptoms without causing dependency and preventing relapse in the long-term. Dependency is almost all cases accompanied by primary and/or secondary mood disorder or sleep disorder which should also be treated. It should be considered, however, that following withdrawal of the agent benzodiazepine dependency often develops. The serotonin antagonist and reuptake inhibitor (SARI) trazodone is effective in the treatment of depression accompanied by sleeping disorder and it has also shown efficacy in alcohol and benzodiazepine-dependency. Its administration may improve the efficacy of detoxification and treatment of following conditions, may decrease medication load and the risk of the development of benzodiazepine dependency. In our clinical practice we frequently use this agent to treat our patients simultaneously suffering from depression and addiction problems, gaining experience comparing it to other pharmacotherapies (benzodiazepines or other antidepressants). The medication is not approved for alcohol and drug dependence, however, treatment t of comorbid conditions is not against to the official recommendations. Our aim was, in addition to reviewing the literature, to share our experience which, although cannot be considered an evidence based study, we deemed worthy of publishing. We cannot, at this point, put forward a protocol addressing all related scientific problems and problems of off-label treatment, and we could
Walker, Brendan M.; Valdez, Glenn R.; McLaughlin, Jay P.; Bakalkin, Georgy
This review represents the focus of a symposium that was presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 and organized / chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN / KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders. PMID:22459870
Walker, Brendan M; Valdez, Glenn R; McLaughlin, Jay P; Bakalkin, Georgy
This review represents the focus of a symposium that was presented at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference in Volterra, Italy on May 3-6, 2011 and organized/chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN/KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders.
Kuerbis, Alexis; Morgenstern, Jon; Hail, Lisa
Understanding for whom moderated drinking is a viable, achievable, and sustainable goal among those with a range of alcohol use disorders (AUD) remains an important public health question. Despite common acceptance as severe risk factors, there is little empirical evidence to conclude whether co-occurring mental health disorders or drug dependence contribute to an individual’s inability to successfully moderate his drinking. Utilizing secondary data analysis, the purpose of this study was to identify predictors of moderation among both treatment seeking and non-treatment seeking, primarily alcohol dependent, problem drinking men who have sex with men (MSM), with an emphasis on the high risk factors psychiatric comorbidity and drug dependence. Problem drinkers (N=187) were assessed, provided feedback about their drinking, given the option to receive brief AUD treatment or change their drinking on their own, and then followed for 15 months. Findings revealed that neither psychiatric comorbidity or drug dependence predicted ability to achieve moderation when controlling for alcohol dependence severity. Those who were younger, more highly educated, and had more mild alcohol dependence were more likely to achieve moderated drinking. Impact of treatment on predictors is explored. Limitations of this study and arenas for future research are discussed. PMID:22201219
Carrà, Giuseppe; Johnson, Sonia; Crocamo, Cristina; Angermeyer, Matthias C; Brugha, Traolach; Azorin, Jean-Michel; Toumi, Mondher; Bebbington, Paul E
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.
Kittles, R A; Long, J C; Bergen, A W; Eggert, M; Virkkunen, M; Linnoila, M; Goldman, D
Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism-antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism.
Luczak, Susan E.; Glatt, Stephen J.; Wall, Tamara J.
Meta-analyses were conducted to determine the magnitude of relationships between polymorphisms in 2 genes, ALDH2 and ADH1B, with alcohol dependence in Asians. For each gene, possession of 1 variant [asterisk]2 allele was protective against alcohol dependence, and possession of a 2nd [asterisk]2 allele did not offer significant additional…
Gulliver, Suzy Bird; Longabaugh, Richard; Davidson, Dena; Swift, Robert
Estimates of the prevalence of alcohol dependence among Americans approach 14% (Read, Kahler, & Stevenson, 2001). Alcohol dependence was once considered among the most recalcitrant of problem behaviors, with only 20% to 30% attaining sustained abstinence (Hunt Barnett & Branch 1971). Although current definitions of treatment success now consider…
Howland, Jonathan; Rohsenow, Damaris J; Greece, Jacey; Almeida, Alissa; Minsky, Sara J; Allensworth-Davies, Donald; Arnedt, J Todd; Hermos, John
Background Differential propensity for hangover may play a role in determining individuals’ drinking practices so predictors of incidence and severity are needed. Methods Data were combined from three randomized crossover trials investigating the residual effects of heavy drinking on next-day performance. All 172 participants received either an alcoholic beverage (M=.115 g% breath alcohol concentration [BrAC]) or placebo matched on type and amount one night and a week later received the other beverage. Alcoholic beverages were vodka, bourbon or high alcohol beer. After each drinking session, following a 9-hour period for sleep and breakfast, participants completed questionnaire a hangover measure. Results No hangover was reported by 24% of participants, mild hangover by 44% and moderate hangover by 32%. Neither alcoholic beverage type nor participant characteristics (sex, age, drinking practices, tobacco use, or family history of alcohol problems) were associated with incidence of hangover. Conclusion The majority of people experienced mild to moderate hangover the morning after this level of intoxication. Further studies are required to investigate other hypothesized causes of variation in the propensity for hangover. PMID:18412754
Rhodes, Sharyn S.; Jasinski, Donald R.
The study found that 40 percent of 25 adult alcoholics were found to have had special education, remedial services, or repeated grade failure concurrent with a familial history of alcoholism and current discrepancies indicative of learning disabilities. Results suggest that childhood learning disorders may be related to the development of…
Abbas, Syed Farhat; Farooq, Madeeha; Rasheed, Amna; Ali, Furqan
Acute alcohol intoxication is a common cause of emergency visits worldwide. Although moderate alcohol consumption is protective against coronary artery disease, binge drinking is associated with adverse cardiovascular and neurological outcomes and may even cause sudden death. Although, few past accounts of venous thrombosis with alcohol binge drinking are available, arterial thrombosis with the condition has never been reported in the literature. We present the unusual case of a young Afghan male, who presented to us with painful, tender and swollen legs three days after a heavy alcohol binge on a Saturday night. He was diagnosed as a case of acute limb ischemia secondary to massive abdominal aorta and bilateral femoral artery thrombosis. He also had acute renal failure secondary to rhabdomyolysis. Cardiac workup revealed new onset paroxysmal atrial fibrillation and a large thrombus in the left ventricular cavity. His blood ethanol level was high. He was treated by a multidisciplinary team; urgent surgical thrombectomy for thrombotic complications, intravenous fluid hydration and later renal replacement therapy for acute renal failure. To the best of our knowledge, such a constellation of clinical features in association with severe acute alcohol intoxication has not been reported in the literature. We believe, the procoagulant nature of high blood ethanol levels and the onset of atrial fibrillation after the heavy alcohol binge, known as the holiday heart syndrome, precipitated the thrombotic events leading to rhabdomyolysis and acute renal failure. Through this case, we conclude that a very heavy alcohol binge may cause thrombotic occlusion of the abdominal aorta and femoral arteries resulting in ischemic rhabdomyolysis and acute renal failure. A high index of suspicion must be kept, especially for a patient presenting with tender, swollen lower limbs and acute renal failure after an alcohol binge. PMID:28083449
Elliott, Jennifer C.; Stohl, Malka; Wall, Melanie M.; Keyes, Katherine M.; Goodwin, Renee D.; Skodol, Andrew E.; Krueger, Robert F.; Grant, Bridget F.; Hasin, Deborah
Background and aims Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. Design Physical, sexual, and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over three years of follow-up, with and without control for other childhood adversities. Setting National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Participants NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n=1,172) and nicotine dependence (n=4,017). Measurements Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment, and other adverse childhood experiences (e.g., parental divorce). Findings Controlling for demographics only, physical, sexual, and emotional abuse, and physical neglect, predicted three-year persistence of alcohol dependence (adjusted odds ratios [AORs]: 1.50–2.99, 95% CIs 1.04–4.68) and nicotine dependence (AORs: 1.37–1.74, 95% CIs 1.13–2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AORs: 1.53–3.02, 95% CIs 1.07–4.71) and nicotine persistence (AORs: 1.35–1.72, 95% CIs 1.11–2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AORs: 1.19–1.36, 95% CIs 1.11–1.56). Conclusions A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of
Evren, Cuneyt; Sar, Vedat; Dalbudak, Ercan; Cetin, Rabia; Durkaya, Mine; Evren, Bilge; Celik, Selime
The aim of this study was to investigate the impact of lifetime posttraumatic stress disorder (PTSD), dissociation and a history of childhood trauma on quality of life (QoL) among men with alcohol dependency. A consecutive series of alcohol-dependent men (N=156) admitted to an inpatient treatment unit were screened using the Michigan Alcoholism Screening Test, the Clinician Administered PTSD Scale, the Dissociative Experiences Scale, and the Childhood Trauma Questionnaire. QoL was assessed using the Medical Outcomes Study Short-Form 36-item health survey. Fifty (32.1%) patients had lifetime diagnosis of PTSD. Besides problems related to severity of alcohol use, the lifetime PTSD group was impaired on several physical and mental components of QoL. While the lifetime PTSD group and remaining patients did not differ on reports of childhood trauma and dissociation, in lifetime PTSD group, dissociative patients had higher scores of childhood emotional abuse than those of the non-dissociative patients. In multivariate covariance analysis, both dissociation and lifetime PTSD predicted impairment in physical functioning, general health, vitality, and mental health components of QoL. Among alcohol-dependent men with lifetime PTSD, a history of childhood emotional abuse contributes to impairment of QoL through its relationship with dissociation.
Gokturk, Camilla; Schultze, Stefan; Nilsson, Kent W; von Knorring, Lars; Oreland, Lars; Hallman, Jarmila
The serotonin system is known to play a pivotal role for mood, behaviour and psychic illness as e.g. alcoholism. Alcoholism in both males and females has been associated with polymorphisms in genes encoding for proteins of importance for central serotonergic function. Genotyping of two functional polymorphisms in the promoter region of the serotonin transporter and monoamine oxidase-A, respectively, (5-HTT-LPR and MAOA-VNTR), was performed in a group of women with severe alcohol addiction. A large sample of adolescent females from a normal population was used as controls. A significantly higher frequency of the LL 5-HTT genotype (high activity) was found in female addicts without a known co-morbid psychiatric disorder than in the controls. Genotype of the MAOA-VNTR polymorphism did not differ significantly between addicts and controls. However, within the group of alcoholics, when the patients with known co-morbid psychiatric disorders were excluded, aggressive anti-social behaviour was significantly linked to the presence of the high activity MAOA allele. The pattern of associations between genotypes of 5-HTT-LPR and MAOA-VNTR in women with severe alcoholism differs from most corresponding studies on males.
Simons, Jeffrey S.; Wills, Thomas A.; Emery, Noah N.; Marks, Russell M.
Research on alcohol use depends heavily on the validity of self-reported drinking. The present paper presents data from 647 days of self-monitoring with a transdermal alcohol sensor by 60 young adults. We utilized a bio chemical measure, transdermal alcohol assessment with the WrisTAS, to examine the convergent validity of three approaches to collecting daily self-report drinking data: experience sampling, daily morning reports of the previous night, and 1-week timeline follow-back (TLFB) assessments. We tested associations between three pharmacokinetic indices (peak concentration, area under the curve (AUC), and time to reach peak concentration) derived from the transdermal alcohol signal and within- and between-person variation in alcohol dependence symptoms. The WrisTAS data corroborated 85.74% of self-reported drinking days based on the experience sampling data. The TLFB assessment and combined experience sampling and morning reports agreed on 87.27% of drinking days. Drinks per drinking day did not vary as a function of wearing or not wearing the sensor; this indicates that participants provided consistent reports of their drinking regardless of biochemical verification. In respect to self-reported alcohol dependence symptoms, the AUC of the WrisTAS alcohol signal was associated with dependence symptoms at both the within- and between-person level. Furthermore, alcohol dependence symptoms at baseline predicted drinking episodes characterized in biochemical data by both higher peak alcohol concentration and faster time to reach peak concentration. The results support the validity of self-report alcohol data, provide empirical data useful for optimal design of daily process sampling, and provide an initial demon stration of the use of transdermal alcohol assessment to characterize drinking dynamics associated with risk for alcohol dependence. PMID:26160523
Gilpin, Nicholas W.; Roberto, Marisa
Alcohol use disorders are characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and withdrawal syndrome in the absence of drug. The central amygdala (CeA) and neighboring regions (extended amygdala) mediate alcohol-related behaviors and chronic alcohol-induced plasticity. Acute alcohol suppresses excitatory (glutamatergic) transmission whereas chronic alcohol enhances glutamatergic transmission in CeA. Acute alcohol facilitates inhibitory (GABAergic) transmission in CeA, and chronic alcohol increases GABAergic transmission. Electrophysiology techniques are used to explore the effects of neuropeptides/neuromodulators (CRF, NPY, nociceptin, dynorphin, endocannabinoids, galanin) on inhibitory transmission in CeA. In general, pro-anxiety peptides increase, and anti-anxiety peptides decrease CeA GABAergic transmission. These neuropeptides facilitate or block the action of acute alcohol in CeA, and chronic alcohol produces plasticity in neuropeptide systems, possibly reflecting recruitment of negative reinforcement mechanisms during the transition to alcohol dependence. A disinhibition model of CeA output is discussed in the context of alcohol dependence- and anxiety-related behaviors. PMID:22101113
Gilpin, Nicholas W; Roberto, Marisa
Alcohol use disorders are characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and withdrawal syndrome in the absence of drug. The central amygdala (CeA) and neighboring regions (extended amygdala) mediate alcohol-related behaviors and chronic alcohol-induced plasticity. Acute alcohol suppresses excitatory (glutamatergic) transmission whereas chronic alcohol enhances glutamatergic transmission in CeA. Acute alcohol facilitates inhibitory (GABAergic) transmission in CeA, and chronic alcohol increases GABAergic transmission. Electrophysiology techniques are used to explore the effects of neuropeptides/neuromodulators (CRF, NPY, nociceptin, dynorphin, endocannabinoids, galanin) on inhibitory transmission in CeA. In general, pro-anxiety peptides increase, and anti-anxiety peptides decrease CeA GABAergic transmission. These neuropeptides facilitate or block the action of acute alcohol in CeA, and chronic alcohol produces plasticity in neuropeptide systems, possibly reflecting recruitment of negative reinforcement mechanisms during the transition to alcohol dependence. A disinhibition model of CeA output is discussed in the context of alcohol dependence- and anxiety-related behaviors.
Schacht, Joseph P.; Anton, Raymond F.; Randall, Patrick K.; Li, Xingbao; Henderson, Scott; Myrick, Hugh
Rationale The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. Objectives This pilot study tested varenicline’s effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Methods Thirty-five such individuals (mean age = 30, 57% male, 76% heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Results Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. Conclusions These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption. PMID:24647921
Vernig, Peter M; Orsillo, Susan M
Drinking motivated by the desire to cope with painful emotions has been shown to be strongly related to alcohol dependence; the resulting maladaptive pattern of substance use can, therefore, be conceptualized as a form of experiential avoidance (an attempt to decrease contact with unpleasant internal states). Acceptance-based interventions, which specifically address experiential avoidance, are multifaceted, and the mechanisms of action are only beginning to be understood. Using a treatment analogue design to look at the underlying components of acceptance-based interventions, the authors tested the effects of brief mindfulness instructions on the emotional responding of alcohol-dependent college students and compared these results with those from a sample of nondependent students. Multidimensional self-reported and psychophysiological emotional responses to pleasant, unpleasant, and neutral pictorial stimuli did not differ between alcohol-dependent and nondependent participants or between the alcohol-dependent participants receiving the mindfulness versus neutral condition. Alcohol-dependent participants' severity of alcohol dependence was found to be related to both self-reported and psychophysiological responses to the unpleasant pictures; these results support the notion that alcohol-dependent participants may use alcohol to cope with unpleasant emotions.
Momeni, Shima; Roman, Erika
Experimental animal models are critical for understanding the genetic, environmental and neurobiological underpinnings of alcohol use disorders. Limited studies investigate alcohol-induced effects on behavior using free-choice paradigms. The aims of the present experiment were to study voluntary alcohol intake using a modified intermittent access paradigm, investigate the effects of voluntary alcohol intake on behavioral profiles in water- and alcohol-drinking rats, and select extreme low- and high-drinking animals for a more detailed behavioral characterization. Sixty outbred male Wistar rats were randomized into water and alcohol groups. Behavioral profiles in the multivariate concentric square field™ (MCSF) test were assessed prior to and after voluntary alcohol intake. The animals had intermittent access to 20% alcohol and water for three consecutive days per week for seven weeks. The results revealed increased alcohol intake over time. No major alcohol-induced differences on behavior profiles were found when comparing water- and alcohol-drinking animals. The high-drinking animals displayed an alcohol deprivation effect, which was not found in the low-drinking animals. High-drinking rats had lower risk-taking behavior prior to alcohol access and lower anxiety-like behavior after voluntary alcohol intake compared to low-drinking rats. In conclusion, the modified intermittent access paradigm may be useful for pharmacological manipulation of alcohol intake. With regard to behavior, the present findings highlights the importance of studying subgroup-dependent differences and add to the complexity of individual differences in behavioral traits of relevance to the vulnerability for excessive alcohol intake.
Quintana, M. I.; Bressan, R. A.; Mello, M. F.; Andreoli, S. B.
Objective. To verify the association between violence and alcohol dependence syndrome in sample populations. Method. Population-wide survey with multistage probabilistic sample. 3,744 individuals of both genders, aged from 15 to 75 years, were interviewed from the cities of São Paulo and Rio de Janeiro using the Composite International Diagnostic Interview (CIDI 2.1). Results. In both cities, alcohol dependence was associated with the male gender, having suffered violence related to criminality, and having suffered familial violence. In both cities, urban violence, in more than 50% of cases, and familial violence, in more than 90% of cases, preceded alcohol dependence. The reoccurrence of traumatic events occurred in more than half of individuals dependent on alcohol. In São Paulo, having been diagnosed with PTSD is associated with violence revictimization (P = 0.014; Odds = 3.33). Conclusion. Alcohol dependence syndrome is complexly related to urban and familial violence in the general population. Violence frequently precedes alcoholism, but this relationship is dependent on residence and traumatic events. This vicious cycle contributes to perpetuating the high rates of alcoholism and violence in the cities. Politicians ordering the reduction of violence in the large metropolises can, potentially, reduce alcoholism and contribute to the break of this cycle. PMID:26000304
Naim-Feil, Jodie; Fitzgerald, Paul B; Bradshaw, John L; Lubman, Dan I; Sheppard, Dianne
Alcohol dependence, a chronic relapsing disorder, is characterized by an impaired ability to regulate compulsive urges to consume alcohol. Very few empirical studies have examined the presence of these executive deficits, how they relate to craving, and the enduring nature of these deficits during abstinence. As such, the current study aimed to characterize these cognitive deficits within a sample of 24 alcohol-dependent participants post-detoxification and 23 non-alcohol-dependent participants. Participants were administered the Sustained Attention to Response Task to measure response inhibition and sustained attention and the Random Number Generation Task to examine executive deficits. Correlations between cognitive performance and clinical measures of alcohol dependence were examined. As predicted, the alcohol-dependent group exhibited poorer performance across the domains of response inhibition, executive function, and attentional control. Cognitive performance was related to clinical measures of craving and years of alcohol consumption, whereas the duration of abstinence was not associated with improved cognitive performance. These findings highlight the need for therapeutic strategies to target these enduring neurocognitive deficits in improving the treatment of alcohol dependence.
Smith, Andrew H.; Gelernter, Joel; Kranzler, Henry R.; Farrer, Lindsay A.; Hall, Lynsey S.; Fernandez‐Pujals, Ana M.; MacIntyre, Donald J.; Smith, Blair H.; Hocking, Lynne J.; Padmanabhan, Sandosh; Hayward, Caroline; Thomson, Pippa A.; Porteous, David J.; Deary, Ian J.; McIntosh, Andrew M.
Abstract Alcohol dependence is frequently co‐morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome‐wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n = 2750; Yale‐Penn GWAS: n = 2377) in a population‐based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P = 0.009, β = −0.027; Yale‐Penn: P = 0.001, β = −0.034) and VF (SAGE: P = 0.0008, β = −0.036; Yale‐Penn: P = 0.00005, β = −0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P = 5.2 × 10−7, β = −0.054; Yale‐Penn: P = 0.000012, β = −0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders. PMID:25865819
Kapoor, M; Chou, Y-L; Edenberg, H J; Foroud, T; Martin, N G; Madden, P A F; Wang, J C; Bertelsen, S; Wetherill, L; Brooks, A; Chan, G; Hesselbrock, V; Kuperman, S; Medland, S E; Montgomery, G; Tischfield, J; Whitfield, J B; Bierut, L J; Heath, A C; Bucholz, K K; Goate, A M; Agrawal, A
Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement. PMID:27003187
Shawcross, Debbie L; Mookerjee, Rajeshwar P; Jalan, Rajiv
Of the numerous precipitants of hepatic decompensation in chronic liver disease, there are no reports in the literature documenting an acute decompensation following an acute episode of severe dermatitis. This case highlights the haemodynamic consequences of a severe flare up of exfoliative dermatitis in a patient with stable chronic alcoholic liver disease, speculates on the mechanism by which this may provoke clinical decompensation and the impact this may have upon liver failure.
Jarmolowicz, David P.; Bickel, Warren K.; Gatchalian, Kirstin M.
Background Research on delay discounting has expanded our understanding of substance dependence in many ways. Recently, orderly discounting of sexual rewards has been demonstrated in both substance-dependent individuals, and healthy controls. Less clear, however, is if rates of sexual discounting are higher than controls in alcohol-dependent-individuals. Methods 20 Alcohol-dependent individuals and 21 healthy control participants completed two delay-discounting tasks. One task involved monetary rewards, whereas the other involved the discounting of sexual rewards (i.e., number of sex acts). Results Alcohol dependent individuals discounted sexual rewards at significantly higher rates than did controls. There was a trend towards, but not a similarly significant relation for the discounting of monetary rewards. Conclusions Rates of sexual discounting are elevated in alcohol dependent individuals. If this relation is replicated in other at risk populations, the rapid devaluation of sexual rewards may be a behavioral marker of impulsive sexual choices. PMID:23312341
Kalman, David; Kahler, Christopher W; Garvey, Arthur J; Monti, Peter M
This study reports findings from an investigation of the efficacy of high-dose nicotine patch (NP) therapy for heavy smokers with a history of alcohol dependence. One hundred thirty participants were randomly assigned to 42 or 21 mg of transdermal nicotine. Follow-up assessments were conducted at 4, 12, 24, and 36 weeks. Differences between dose conditions were nonsignificant, although, unexpectedly, outcomes favored participants in the 21-mg NP condition. Nicotine abstinence rates in the 21- and 42-mg NP conditions on Week 36 follow-up were 16.9% and 9.2%, respectively. Patch condition did not interact with severity of nicotine dependence. However, nicotine abstinence at follow-up was related to a longer length of alcohol abstinence. No evidence was found for better outcomes as a function of the percentage of baseline cotinine replaced by NPs. Future research should focus primarily on investigating ways to improve smoking quit rates for smokers in early alcohol recovery.
Lenz, Bernd; Kraus, Thomas; Sperling, Wolfgang; Bayerlein, Kristina; Biermann, Teresa; Stoessel, Christina
The ratio of the lengths of the second and fourth finger (2D∶4D) has been described as reflecting the degree of prenatal androgen exposure in humans. 2D∶4D is smaller for males than females and is associated with traits such as left-handedness, physical aggression, attention-deficit-hyperactivity disorder and a genetic polymorphism of the androgen receptor. All of these traits are known to be correlated to the vulnerability for alcohol dependency. We therefore hypothesized low 2D∶4D in patients with alcohol dependency. In the present study on 131 patients suffering from alcohol dependency and 185 healthy volunteers, we found that alcohol dependent patients had smaller 2D∶4D ratios compared to controls with preserved sexual dimorphism but with reduced right-left differences. The detection of alcohol dependency based on 2D∶4D ratios was most accurate using the right hand of males (ROC-analysis: AUC 0.725, sensitivity 0.667, specificity 0.723). These findings provide novel insights into the role of prenatal androgen exposure in the development of alcohol dependency and for the use of 2D∶4D as a possible trait marker in identifying patients with alcohol dependency. PMID:21547078
Gilpin, Nicholas W
Neuropeptide Y (NPY) is abundant in the extended amygdala, a conceptual macrostructure in the basal forebrain important for regulation of negative affective states. NPY has been attributed a central role in anxiety-like behavior, fear, nociception, and reward in rodents. Deletion of the NPY gene in mice produces a high-anxiety high-alcohol-drinking phenotype. NPY infused into the brains of rats selectively bred to consume high quantities of alcohol suppresses alcohol drinking by those animals, an effect that is mediated by central amygdala (CeA). Likewise, alcohol-preferring rats exhibit basal NPY deficits in CeA. NPY infused into the brains of alcohol-dependent rats blocks excessive alcohol drinking by those animals, an effect that also has been localized to the CeA. NPY in CeA may rescue dependence-induced increases in anxiety and alcohol drinking via inhibition of downstream effector regions that receive GABAergic inputs from CeA. It is hypothesized here that NPY modulates anxiety-like behavior via Y2R regulation of NPY release, whereas NPY modulation of alcohol-drinking behavior in alcohol-dependent animals occurs via Y2R regulation of GABA release.
Roltsch Hellard, Emily A; Impastato, Renata A; Gilpin, Nicholas W
Humans diagnosed with alcohol use disorder are more sensitive to painful stimuli during withdrawal, which suggests that excessive alcohol drinking worsens pain outcomes. Alcohol-dependent rats exhibit increases in nociceptive sensitivity during withdrawal. Data from animal models suggest that brain melanocortin-4 receptors (MC4Rs) mediate alcohol drinking and nociception. Here we tested: (1) the effect of alcohol dependence on thermal nociception in rats, and (2) the ability of acute alcohol and (3) MC4R antagonists to reverse hyperalgesia during withdrawal in alcohol-dependent rats. Rats were trained to self-administer operant alcohol and were tested for baseline thermal nociception. Half of the rats were made dependent on alcohol, then all rats were cannulated in the lateral ventricle. We tested the effects of acute alcohol drinking, acute fixed-dose alcohol, intra-ventricular agouti-related protein (endogenous MC4R antagonist), intra-ventricular HS014 (synthetic MC4R antagonist) and intra-nasal HS014 on hyperalgesia during withdrawal in alcohol-dependent rats, relative to non-dependent drinkers and alcohol-naïve controls. Alcohol-dependent rats exhibit thermal hyperalgesia that is abolished by alcohol drinking, bolus alcohol and intra-ventricular and intra-nasal MC4R antagonists. These manipulations did not affect thermal nociception in non-dependent drinkers and alcohol-naïve controls, suggesting that alcohol dependence produces neuroadaptations in brain MC4R systems. These results suggest that brain MC4R systems may be an effective therapeutic target for reducing nociception in the alcohol-dependent organism.
Adams, Zachary W.; Schacht, Joseph P.; Randall, Patrick; Anton, Raymond F.
Objective: People consume alcohol at problematic levels for many reasons. These different motivational pathways may have different biological underpinnings. Valid, brief measures that discriminate individuals’ reasons for drinking could facilitate inquiry into whether varied drinking motivations account for differential response to pharmacotherapies for alcohol use disorders. The current study evaluated the factor structure and predictive validity of a brief measure of alcohol use motivations developed for use in randomized clinical trials, the Reasons for Heavy Drinking Questionnaire (RHDQ). Method: The RHDQ was administered before treatment to 265 participants (70% male) with alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, in three pharmacotherapy randomized clinical trials. Principal components analysis was used in half the sample to determine the RHDQ factor structure. This structure was verified with confirmatory factor analysis in the second half of the sample. The factors derived from this analysis were evaluated with respect to alcohol dependence severity indices. Results: A two-factor solution was identified. Factors were interpreted as Reinforcement and Normalizing. Reinforcement scores were weakly to moderately associated with severity, whereas normalizing scores were moderately to strongly associated with severity. In all cases in which significant associations between RHDQ scores and severity indices were observed, the relationship was significantly stronger for normalizing than for reinforcing. Conclusions: The RHDQ is a promising brief assessment of motivations for heavy alcohol use, particularly in the context of randomized clinical trials. Additional research should address factor structure stability in non–treatment-seeking individuals and the RHDQ’s utility in detecting and accounting for changes in drinking behavior, including in response to intervention. PMID:26997195
Miele, G M; Carpenter, K M; Smith Cockerham, M; Dietz Trautman, K; Blaine, J; Hasin, D S
This study investigated the concurrent and predictive validity of the Substance Dependence Severity Scale (SDSS), a clinician-administered interview designed to assess the severity and frequency of DSM-IV dependence symptoms for a range of substances. A total of 172 (107 males and 66 females) treated substance users participated in the study. Of those, 89% (n=153) received at least one follow-up interview within 1-6 months of an initial assessment. For alcohol, cocaine and heroin, convergent and discriminant validity was supported by significant relationships between SDSS scores at baseline and other baseline measures of substance use consequences, such as the Addiction Severity Index (ASI), as well as significant relationships between SDSS change scores from baseline to follow-up and change scores of other measures of consequences. SDSS scores were significantly associated with time to first post treatment use of alcohol, cocaine and heroin, although the nature of the associations was complex. Scale applications and areas for further study are discussed.
Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida
Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644
Littlewood, Rae A.; Claus, Eric D.; Arenella, Pamela; Bogenschutz, Michael; Karoly, Hollis; Feldstein Ewing, Sarah W.; Bryan, Angela D.; Hutchison, Kent E.
Rationale It is well-established that the rewarding effects of alcohol are modulated by the mesolimbic dopaminergic system. Olanzapine, a D2 dopamine antagonist, has been shown to reduce alcohol craving and consumption. Objective To clarify whether olanzapine has clinical utility in the treatment of alcohol dependence, a 12-week, double-blind, randomized clinical trial was conducted. Methods One-hundred twenty-nine treatment-seeking alcohol dependent adults were randomly assigned to 12-weeks of olanzapine (5mg vs. 2.5mg) or placebo. Outcomes examined were average drinks per drinking day (DDD), proportion of drinking days to total days in treatment (PDD), alcohol craving, and impaired control over alcohol use. Mixed models were used to examine medication effects during the course of treatment on specified outcomes. Results All of the analyses indicated a main effect for time, such that there were reductions in alcohol use and craving and an increase in control over alcohol use across treatment conditions. Dose-response analyses indicated that, in comparison to placebo, participants in the 5mg group experienced reduced craving for alcohol and participants in the 2.5mg group decreased in PDD and increased in their control over alcohol use. Better control over alcohol use remained significant 6 months post-treatment for the 2.5mg group. Subjective experiences of the medication suggest that 2.5mg and 5mg were equally well-tolerated. Conclusions Results provide some support for the notion that dosage is an important consideration in relation to effectiveness; however, the cost-benefit balance does not support the clinical utility of olanzapine in treating alcohol dependence. PMID:25304864
Walt, Lisa C.; Kinoti, Elias; Jason, Leonard A.
Developing countries' industrialization and urbanization attempts have been linked to psychological distress and alcohol abuse. We used Hobfoll's COR theory to examine the relationship between gender, perceived resource loss (an indicator of industrialization stress), and alcohol abuse and dependence in a sample of Kenyan rural village men and…
... Age 12 and Older Dependent on or Abusing Alcohol and Illicit Drugs Alcohol / 17,876 Marijuana / 4,476 Pain Relievers / 1,921 Sedatives / 162 Tranquilizers / 521 Stimulants / 357 Heroin / ... Health Services Administration, 2005 National Survey on Drug Use and Health
Reviews ethical and practical dilemmas associated with clients who have hidden alcohol dependencies, and proposes an approach rooted in Gestalt counseling theory which confronts these issues and is compatible with a current emerging alcohol-treatment model. Suggests specific activities for addressing client resistance to revealing a hidden alcohol…
Bagga, D; Singh, N; Modi, S; Kumar, P; Bhattacharya, D; Garg, M L; Khushu, S
Neuropsychological studies have shown that alcohol dependence is associated with neurocognitive deficits in tasks requiring memory, perceptual motor skills, abstraction and problem solving, whereas language skills are relatively spared in alcoholics despite structural abnormalities in the language-related brain regions. To investigate the preserved mechanisms of language processing in alcohol-dependents, functional brain imaging was undertaken in healthy controls (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took more time than controls for performing the task but there was no significant difference in their response accuracy. fMRI data analysis revealed that while performing the task, the alcoholics showed enhanced activations in left supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle temporal gyrus as compared to control subjects. The extensive activations observed in alcoholics as compared to controls suggest that alcoholics recruit additional brain areas to meet the behavioural demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting compensatory mechanisms for the execution of task for showing an equivalent performance or decreased neural efficiency of relevant brain networks. However, on direct comparison of the two groups, the results did not survive correction for multiple comparisons; therefore, the present findings need further exploration.
Emery, Clifton R; Wu, Shali; Yang, Hyerin; Lee, Hotaek; Kim, Junpyo; Chan, Ko Ling
Although previous research documents a reliable relationship between physical intimate partner violence (IPV) victimization and alcoholism, relatively little research has examined new theoretical constructs in IPV research that may increase risk for or help buffer women from alcohol abuse/dependence. The purpose of the present study was to examine informal social control of IPV by family members as a protective factor against and coercive control as a risk factor for alcohol abuse/dependence in a small population sample of married women in Seoul, South Korea. We hypothesized that (a) informal social control by family members would be negatively associated with victim alcohol abuse/dependence and (b) husband's coercive control would be positively associated with victim alcohol abuse/dependence. We measured alcohol abuse/dependence (CAGE scale), IPV and coercive control by husbands, and informal social control of IPV (ISC_IPV) by extended family members in a three-stage random cluster sample of 462 married women in Seoul, South Korea. Both random effects regression and zero-inflated Poisson regression models found that ISC_IPV by extended family members was associated with a significantly lower CAGE scores, and coercive control was associated with significantly higher CAGE scores. Interventions to boost ISC_IPV by extended family members may mitigate some of the risk of alcohol abuse/dependence by victims.
Garbusow, Maria; Schad, Daniel J; Sebold, Miriam; Friedel, Eva; Bernhardt, Nadine; Koch, Stefan P; Steinacher, Bruno; Kathmann, Norbert; Geurts, Dirk E M; Sommer, Christian; Müller, Dirk K; Nebe, Stephan; Paul, Sören; Wittchen, Hans-Ulrich; Zimmermann, Ulrich S; Walter, Henrik; Smolka, Michael N; Sterzer, Philipp; Rapp, Michael A; Huys, Quentin J M; Schlagenhauf, Florian; Heinz, Andreas
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Fleshman, Allison M; Forsythe, Grant E; Petrowsky, Matt; Frech, Roger
The location of the hydroxyl group in monohydroxy alcohols greatly affects the temperature dependence of the liquid structure due to hydrogen bonding. Temperature-dependent self-diffusion coefficients, fluidity (the inverse of viscosity), dielectric constant, and density have been measured for several 1-alcohols and 3-alcohols with varying alkyl chain lengths. The data are modeled using the compensated Arrhenius formalism (CAF). The CAF follows a modified transition state theory using an Arrhenius-like expression to describe the transport property, which consists of a Boltzmann factor containing an energy of activation, Ea, and an exponential prefactor containing the temperature-dependent solution dielectric constant, εs(T). Both 1- and 3-alcohols show the Ea of diffusion coefficients (approximately 43 kJ mol(-1)) is higher than the Ea of fluidity (approximately 35 kJ mol(-1)). The temperature dependence of the exponential prefactor in these associated liquids is explained using the dielectric constant and the Kirkwood-Frölich correlation factor, gk. It is argued that the dielectric constant must be used to account for the additional temperature dependence due to variations in the liquid structure (e.g., hydrogen bonding) for the CAF to accurately model the transport property.
Pettinati, H M; Volpicelli, J R; Luck, G; Kranzler, H R; Rukstalis, M R; Cnaan, A
Clinical studies that have evaluated serotonergic medications to reduce alcohol consumption have yielded conflicting results. These studies primarily treated patients with alcohol dependence, excluding those with a current depressive disorder, in an effort to differentiate any medication effects directly on drinking from those on mood. Yet despite the exclusion of current depression, a group of alcohol-dependent patients who are not depressed can be highly heterogeneous. For example, this subgroup can include those with a lifetime depressive disorder. If these patients were more sensitive to serotonergic medications than patients without a lifetime depressive disorder, medication effects in a subgroup of patients who were not depressed could be obscured. Thus, the purpose of this study was to examine the efficacy of sertraline for treating alcohol dependence in patient groups that were differentiated by the presence or absence of lifetime depression. This study examined the effectiveness of sertraline (200 mg/day) or placebo for 14 weeks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a lifetime diagnosis of comorbid depression. Sertraline treatment seemed to provide an advantage in reducing drinking in alcohol-dependent patients without lifetime depression, illustrated best with a measure of drinking frequency during treatment. However, sertraline was no better than placebo in patients with a diagnosis of lifetime comorbid depression, and current depression did not change the results. Treatment with selective serotonin reuptake inhibitors may be useful in alcohol-dependent patients who are not depressed. Subtyping those with alcohol dependence on the basis of the absence versus the presence of a lifetime depressive disorder may help to resolve conflicting findings in the literature on the treatment of alcohol dependence with serotonergic medications.
Beghè, F; Carpanini, M T
Gamma-hydroxybutyric acid (GHB) has been in clinical use in Italy since 1991 for treatment of alcohol dependence. Results of phase III and phase IV studies have shown that the drug is effective and well tolerated in the treatment of alcohol withdrawal syndrome and in reducing alcohol consumption and alcohol craving. Pharmacosurveillance indicates that abuse of gamma-hydroxybutyric acid is a limited phenomenon in clinical settings when the drug is dispensed under strict medical surveillance and entrusted to a referring familiar member of the patient.
Cerdá, Magdalena; Moffitt, Terrie E; Meier, Madeline H; Harrington, HonaLee; Houts, Renate; Ramrakha, Sandhya; Hogan, Sean; Poulton, Richie; Caspi, Avshalom
With the increasing legalization of cannabis, understanding the consequences of cannabis use is particularly timely. We examined the association between cannabis use and dependence, prospectively assessed between ages 18-38, and economic and social problems at age 38. We studied participants in the Dunedin Longitudinal Study, a cohort (n=1,037) followed from birth to age 38. Study members with regular cannabis use and persistent dependence experienced downward socioeconomic mobility, more financial difficulties, workplace problems, and relationship conflict in early midlife. Cannabis dependence was not linked to traffic-related convictions. Associations were not explained by socioeconomic adversity, childhood psychopathology, achievement orientation, or family structure; cannabis-related criminal convictions; early onset of cannabis dependence; or comorbid substance dependence. Cannabis dependence was associated with more financial difficulties than alcohol dependence; no difference was found in risks for other economic or social problems. Cannabis dependence is not associated with fewer harmful economic and social problems than alcohol dependence.
... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...
If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...
Gomez, Juan L; Cunningham, Christopher L; Finn, Deborah A; Young, Emily A; Helpenstell, Lily K; Schuette, Lindsey M; Fidler, Tara L; Kosten, Therese A; Ryabinin, Andrey E
An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.
Gomez, Juan L.; Cunningham, Christopher L.; Finn, Deborah A.; Young, Emily A.; Helpenstell, Lily K.; Schuette, Lindsey M.; Fidler, Tara L.; Kosten, Therese A.; Ryabinin, Andrey E.
An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increased alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects to ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies. PMID:26051399
Issues Although screening and brief intervention (BI) in the primary-care setting reduces unhealthy alcohol use, its efficacy among patients with dependence has not been established. This systematic review sought to determine whether evidence exists for BI efficacy among patients with alcohol dependence identified by screening in primary-care settings. Approach We included randomised controlled trials (RCTs) extracted from eight systematic reviews and electronic-database searches published through September 2009. These RCTs compared outcomes among adults with unhealthy alcohol use identified by screening who received BI in a primary-care setting with those who received no intervention. Key Findings Sixteen RCTs including 6839 patients met the inclusion criteria. Of these, 14 excluded some or all persons with very heavy alcohol use or dependence; one in which 35% of 175 patients had dependence found no difference in an alcohol severity score between groups; and one in which 58% of 24 female patients had dependence showed no efficacy. Conclusion and Implications Alcohol screening and BI has efficacy in primary care for patients with unhealthy alcohol use but, there is no evidence for efficacy among those with very heavy use or dependence. Since alcohol screening identifies both dependent and non-dependent unhealthy use, the absence of evidence for the efficacy of BI among primary-care patients with screening-identified alcohol dependence raises questions regarding the efficiency of screening and BI, particularly in settings where dependence is common. The finding also highlights the need to develop new approaches to help such patients, particularly if screening and BI are to be disseminated widely. PMID:20973848
Eames, Sarah F.; Businelle, Michael S.; Suris, Alina; Walker, Robrina; Rao, Uma; North, Carol S.; Xiao, Hong; Adinoff, Bryon
Objective This study sought to clarify the relationship between childhood trauma and adversity with later alcohol consumption and the moderating effects of adult psychosocial stress. Method Seventy-seven recently abstinent alcohol-dependent men attending residential treatment programs were assessed. Childhood trauma/adversity was assessed with the Childhood Trauma Questionnaire (CTQ), drinks per drinking day (DDD) with the TimeLine Follow Back, and chronic psychosocial stress with the UCLA Stress Interview. Drinking and stress were retrospectively assessed for six months prior to the present treatment episode. Direct associations between childhood trauma/adversity and alcohol consumption and the moderating effects of recent psychosocial stress were assessed. All measures were considered as continuous variables. Results Pretreatment drinking severity (DDD) was associated with CTQ Total score (p = .009) and the Emotional Abuse (p < .001) and Physical Abuse (p < .01) subscales. UCLA Total Stress significantly moderated the effects of CTQ Total score on drinking severity (p = .04). Whereas higher CTQ scores were significantly associated with a greater amount of pretreatment drinking in participants with high UCLA stress scores (p = .01), CTQ scores were not associated with the amount of drinking in those with low UCLA stress scores (p = .63). Conclusions Childhood trauma predicts drinking severity in alcohol-dependent men and this effect is stronger in participants with ongoing stress in adult life. These findings suggest that early childhood trauma/adversity may sensitize stress-response systems. PMID:24635549
Rozeboom, Henriëtte J; Yu, Shukun; Mikkelsen, Rene; Nikolaev, Igor; Mulder, Harm J; Dijkstra, Bauke W
The quinone-dependent alcohol dehydrogenase (PQQ-ADH, E.C. 184.108.40.206) from the Gram-negative bacterium Pseudogluconobacter saccharoketogenes IFO 14464 oxidizes primary alcohols (e.g. ethanol, butanol), secondary alcohols (monosaccharides), as well as aldehydes, polysaccharides, and cyclodextrins. The recombinant protein, expressed in Pichia pastoris, was crystallized, and three-dimensional (3D) structures of the native form, with PQQ and a Ca(2+) ion, and of the enzyme in complex with a Zn(2+) ion and a bound substrate mimic were determined at 1.72 Å and 1.84 Å resolution, respectively. PQQ-ADH displays an eight-bladed β-propeller fold, characteristic of Type I quinone-dependent methanol dehydrogenases. However, three of the four ligands of the Ca(2+) ion differ from those of related dehydrogenases and they come from different parts of the polypeptide chain. These differences result in a more open, easily accessible active site, which explains why PQQ-ADH can oxidize a broad range of substrates. The bound substrate mimic suggests Asp333 as the catalytic base. Remarkably, no vicinal disulfide bridge is present near the PQQ, which in other PQQ-dependent alcohol dehydrogenases has been proposed to be necessary for electron transfer. Instead an associated cytochrome c can approach the PQQ for direct electron transfer.
Kissler, Jessica L; Walker, Brendan M
Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence. PMID:26105136
Nuutinen, Saara; Vanhanen, Jenni; Mäki, Tiia; Panula, Pertti
The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders. PMID:22629238
Nuutinen, Saara; Vanhanen, Jenni; Mäki, Tiia; Panula, Pertti
The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders.
Szücs, Attila; Berton, Fulvia; Sanna, Pietro Paolo; Francesconi, Walter
Alcohol dependence and withdrawal has been shown to cause neuroadaptive changes at multiple levels of the nervous system. At the neuron level, adaptations of synaptic connections have been extensively studied in a number of brain areas and accumulating evidence also shows the importance of alcohol dependence-related changes in the intrinsic cellular properties of neurons. At the same time, it is still largely unknown how such neural adaptations impact the firing and integrative properties of neurons. To address these problems, here, we analyze physiological properties of neurons in the bed nucleus of stria terminalis (jcBNST) in animals with a history of alcohol dependence. As a comprehensive approach, first we measure passive and active membrane properties of neurons using conventional current clamp protocols and then analyze their firing responses under the action of simulated synaptic bombardment via dynamic clamp. We find that most physiological properties as measured by DC current injection are barely affected during protracted withdrawal. However, neuronal excitability as measured from firing responses under simulated synaptic inputs with the dynamic clamp is markedly reduced in all 3 types of jcBNST neurons. These results support the importance of studying the effects of alcohol and drugs of abuse on the firing properties of neurons with dynamic clamp protocols designed to bring the neurons into a high conductance state. Since the jcBNST integrates excitatory inputs from the basolateral amygdala (BLA) and cortical inputs from the infralimbic and the insular cortices and in turn is believed to contribute to the inhibitory input to the central nucleus of the amygdala (CeA) the reduced excitability of the jcBNST during protracted withdrawal in alcohol-dependent animals will likely affect ability of the jcBNST to shape the activity and output of the CeA.
Soyka, Michael; Rösner, Susanne
Alcohol dependence is a widespread psychiatric disorder. While relapse prevention therapy in alcoholism was exclusively dominated by social and psychological treatments for many years, in the last decades the benefits of pharmacological agents for the rehabilitation treatment in alcoholism have become increasingly evident. Naltrexone, an opiate receptor antagonist, blocks the pleasant and reinforcing effects of alcohol by preventing the stimulation of opioid receptors and the reduction of dopamine release in the ventral tegmental area (VTA). Clinical evidence about the effectiveness of the substance is not always consistent, but meta-analyses confirm naltrexone's effect on the risk of heavy drinking. Evidence about the abstinence-maintaining effects of the substance comes from a relatively small database and needs further investigation. The evaluation of differential effects of naltrexone depending on biological or psychological profiles, which could further enhance the effectiveness of treatments for alcohol dependence, remains a challenge. Nalmefene, another opioid antagonist, as well as naltrexone depot, a sustained release formulation of naltrexone, are further promising strategies for the treatment of alcohol dependence. The review at hand gives on overview of the current evidence on opioid antagonists for the treatment of alcohol dependence regarding the possible mechanism of action, the substances' safety profiles and their effectiveness. The corresponding evidence is critically reviewed taking into consideration the influence of the study design on the magnitude and consistency of effect sizes as well the impact of patient characteristics on the response to the treatment with opioid antagonists. Future studies on the role of different subtypes of alcoholics according to their genetic or psychological profile to explain or even predict the effects of opioid antagonists in the treatment of alcohol dependence are needed.
Talley, Amelia E; Brown, Jennifer L; Stevens, Angela K; Littlefield, Andrew K
Objective: The current study examines the relation between peer descriptive norms for alcohol involvement and alcohol-dependence symptomatology and whether this relation differs as a function of sexual self-concept ambiguity (SSA). This study also examines the associations among peer descriptive norms for alcohol involvement, alcohol-dependence symptomatology, and lifetime HIV risk-taking behavior and how these relations are influenced by SSA. Method: Women between ages 18 and 30 years (N = 351; M = 20.96, SD = 2.92) completed an online survey assessing sexual self-concept, peer descriptive norms, alcohol-dependence symptomatology, and HIV risk-taking behaviors. Structural equation modeling was used to test hypotheses of interest. Results: There was a significant latent variable interaction between SSA and descriptive norms for peer alcohol use. There was a stronger positive relationship between peer descriptive norms for alcohol and alcohol-dependence symptomatology when SSA was higher compared with when SSA was lower. Both latent variables exhibited positive simple associations with alcohol-dependence symptoms. Peer descriptive norms for alcohol involvement directly and indirectly influenced HIV risk-taking behaviors, and the indirect influence was conditional based on SSA. Conclusions: The current findings illustrate complex, nuanced associations between perceived norms, identity-related self-concepts, and risky health behaviors from various domains. Future intervention efforts may be warranted to address both problem alcohol use and HIV-risk engagement among individuals with greater sexual self-concept ambiguity. PMID:25343661
08-2-0075 TITLE: Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence PRINCIPAL INVESTIGATOR: Ismene...page. Subject terms on next page. 6 Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence Ismene Petrakis Yale University New...PTSD. There is evidence of common neurobiological mechanisms that underlie both AD and PTSD. Prazosin is an alpha-! adrenergic •ceptor antagonist
Serý, Omar; Sťastný, František; Zvolský, Petr; Hlinomazová, Zuzana; Balcar, Vladimir J
Brain-derived neurotrophic factor (BDNF) is a protein encoded, in humans, by BDNF gene on chromosome 11. BDNF protects adult neurons and promotes growth and differentiation during ontogenetic development but the nature and magnitude of its effects could be influenced by functional polymorphisms. The BDNF polymorphism Val66Met (rs6265) has been studied in the context of etiology of mental diseases including alcoholism. Alcoholism - a complex disorder known to be linked to several genes - has multiple manifestations, including sensory deficits such as those affecting vision. In the present study we examined a relationship between the Val66Met polymorphism, alcohol dependence and colour vision deficiency (CVD) in 167 alcohol-dependent men and 289 control male subjects. Statistical analysis revealed that almost half (about 48%) of the alcohol dependent men had a CVD. In addition we found that CVD was significantly associated (P=0.005) with the Val66Met polymorphism. The A allele containing 66Met promotes BDNF expression and this may protect humans against CVD induced by long-term excessive alcohol intake. The present findings indicate that alcohol-induced CVD does not depend solely on excessive alcohol consumption but is significantly influenced by genetic predisposition in the form of a specific BDNF polymorphism.
Wright, Alison K.; Ashcroft, Darren M.; van Staa, Tjeerd P.; Pirmohamed, Munir
This study aims to investigate the incidence and annual presentation rates of alcohol dependence in general practice in the UK, and examine age-, gender-, socioeconomic-, and region-specific variation. We conducted a retrospective 'open' cohort study using the Clinical Practice Research Datalink (CPRD), an anonymised primary care database. Prior to data extraction, a case definition for alcohol dependence in CPRD was established using 47 Read codes, which included primary alcohol dependence and consequences of alcohol dependence. Directly standardised rates for incidence and annual presentation were calculated for each year between 1990 and 2013. Rates were compared by gender, age, UK home nation, and practice-level Index of Multiple Deprivation. The directly standardised annual incidence rates were 8.3 and 3.7 per 10,000 male and female patients, respectively. The estimated annual rates of presentation per 10,000 were 17.1 for males and 7.6 for females. Female to male rate ratios were: 0.40 (95% CI: 0.39–0.41) for incident cases; and 0.37 (95% CI: 0.36–0.39) for annual presentation. Rates were highest in those aged 35–54 for both measures and across genders, and lowest in those aged over 75 years. With England as the reference nation, Northern Ireland and Scotland had significantly higher rates for both measures. Patients from the most deprived areas had the highest incidence and annual presentation rates. There is unequal distribution of patients with severe alcohol dependence across population subgroups in general practice. Given the health and economic burden associated with dependent drinking, these data will be useful in informing future public health initiatives. PMID:28362848
In 1979, "Alcoholism Diagnosis Committee, the Ministry of Health and Welfare" established the diagnostic criteria for alcohol dependence syndrome, which included "the resistance to negative reinforcement". The author raises a question about this criterion which indicates the condition that "an individual continues to drink despite alcohol-related physical diseases, rejection by his/her family or economic poverty and drinking-related criminal problem." The author defines this condition not as "resistance to negative reinforcement" but as "resistance to punishment." Furthermore, the author can not find the data supporting that "the resistance to negative reinforcement" in the correct sense exists in the individuals with alcohol dependence syndrome. In a theoretical sense, an opposite idea seems to exist. There is an observed fact that can be regarded as a phenomenon that explains the involvement of "negative reinforcement" in enhancement of psychological dependence as in the case of the secondary development of psychological dependence. Consequently, the author would have to say that defining "the resistance to negative reinforcement" as one of common features of alcohol dependence syndrome or one of diagnostic criteria for alcohol dependence syndrome is inappropriate.
Stuewig, Jeffrey; Tangney, June Price; Mashek, Debra; Forkner, Peter; Dearing, Ronda
This article examines the relationship of shame, guilt, and symptoms of alcohol dependence to pre-incarceration HIV risk behaviors in an ongoing study in a metropolitan jail. Between 2002 and 2004 an ethnically diverse sample of 368 male inmates (mean age = 31, SD = 9.7), were interviewed on a variety of constructs including shame- and guilt-proneness (TOSCA-SD; Hanson and Tangney, 1996), alcohol dependence (TCU-CRTF; Simpson and Knight, 1998), and HIV risk behavior (TCU-ARA; Simpson, 1997). Symptoms of alcohol dependence were associated with elevated levels of HIV risk behavior (risky needle use and unprotected sex) prior to incarceration. Guilt-proneness was negatively related to risky sexual behavior. In addition, there was an interaction between shame and symptoms of alcohol dependence. Specifically, among those who were low on alcohol dependence, shame-proneness was negatively related to risky sexual behavior. The study's limitations are noted and findings are discussed in the context of the importance of considering moral emotions and alcohol dependence when designing programs to reduce HIV risk.
Brower, Kirk J; Krentzman, Amy; Robinson, Elizabeth A R
Insomnia is common, persistent, and increases the risk for relapse in alcohol-dependent (AD) patients. Abstinence has long been considered the best strategy for allowing sleep to normalize, although how many and which patients respond to abstinence is unknown. The aims of this study were to investigate the prevalence and correlates of both baseline and persistent insomnia in AD patients. The course of sleep problems in response to abstinence, moderate drinking, or relapse following treatment was also examined. A naturalistic longitudinal outcomes study interviewed 267 patients (69% male; mean age of 44 years) with DSM-IV alcohol dependence at baseline and 6 months later (84% follow-up rate) . The Sleep Problems Questionnaire, Time-Line Follow-Back Interview, and Brief Symptom Inventory measured insomnia, drinking, and psychiatric symptoms, respectively. Simple correlations, logistic regression, and repeated measures analysis of variance were used to analyze the data. At baseline, 47% of patients were classified with insomnia, which was independently predicted by female gender and psychiatric severity. Both abstinence and moderate drinking outcomes significantly predicted a reduction of insomnia symptoms after controlling for gender and psychiatric severity. Among patients with baseline insomnia, however, insomnia persisted in over 60% of cases, which was predicted by baseline insomnia severity. Moreover, insomnia persisted in one-quarter of patients despite abstinence. Treatment aimed at preventing relapse to heavy drinking provides good first-line therapy for insomnia in AD patients, but some may require insomnia-specific evaluation and treatment in addition to substance-focused treatment and psychiatric care.
... de los dientes Video: Getting an X-ray Alcohol KidsHealth > For Kids > Alcohol Print A A A What's in this article? ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...
Evren, Cuneyt; Evren, Bilge; Yancar, Cenk; Erkiran, Murat
The aims of this study were to evaluate the differences in dimensions of temperament and character in Turkish alcohol- and drug-dependent inpatients, and to examine which dimensions would predict drug dependency. The subjects consisted of 111 alcohol-dependent and 93 drug-dependent inpatients according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Subjects were tested using Cloninger's Temperament and Character Inventory (TCI). Among the temperament dimensions, novelty seeking score was higher and reward dependency score was lower in drug-dependent patients than in alcohol-dependent patients. Among the character dimensions, self-directedness and cooperativeness scores were lower in drug-dependent patients. Low age and novelty seeking predicted drug dependency in forward logistic regression model. Subscales that predicted drug dependency other than young age were lower scores on compassion vs revengefulness (C4) and helpfulness (C3), and higher score on spiritual acceptance vs rational materialism (ST3). As in previous studies, which indicate an association between personality and substance choice, in the present study, TCI was shown to be an efficient tool in discriminating alcohol and drug dependents; thus, it seems to be important to consider TCI dimensions in planning the treatment of substance dependency.
Anton, Raymond F; Myrick, Hugh; Baros, Alicia M; Latham, Patricia K; Randall, Patrick K; Wright, Tara M; Stewart, Scott H; Waid, Randy; Malcolm, Robert
Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.
Meszaros, K; Lenzinger, E; Hornik, K; Füreder, T; Willinger, U; Fischer, G; Schönbeck, G; Aschauer, H N
Personality traits have been found as strong predictors for treatment response in different psychiatric disorders. We administered the Tridimensional Personality Questionnaire, which measures the three personality dimensions: novelty seeking, harm avoidance (HA), and reward dependence, as introduced by Cloninger in a multicenter study (11 centers in the United Kingdom, Eire, Switzerland, and Austria) with detoxified alcohol-dependent patients (n = 521). The objective of this study was to evaluate a possible predictive value of these three dimensions on relapse over 1 -year follow up. A logistic regression analysis showed that novelty seeking is a strong predictor for relapse in detoxified male alcoholics (p = 0.0007; p values adjusted for treatment), but not in females. In both sexes, HA and reward dependence were of no predictive value. However, we found a trend for significance of HA for predicting "early" relapse (4 weeks) in females (p = 0.074). Our results show that Tridimensional Personality Questionnaire personality traits have direct clinical applications for prediction of relapse in detoxified alcohol dependents and indicate the necessity of additional therapeutic treatment in risk groups.
Raman, Vijaya; Prasad, Suveera; Appaya, M. Prakash
Background: Children of people with alcohol dependence (COAs) are at high risk for behavioral and cognitive problems. Aim: Aim of this study was to compare the nature and extent of these problems in children of men with and without alcohol dependence. Materials and Methods: 32 children (17 in study group and 15 controls) were evaluated for psychopathology, neurodevelopment, cognitive functioning and family environment. Tools used were: Socio-demographic data sheet, Malin’s Intelligence Scale for Indian Children (MISIC), Child Behavior Checklist, Trail Making Test, Neurodevelopment Scale and the Family Environment Scale. Results: Children of men with alcohol dependence had higher externalizing than internalizing scores. Children of alcohol-dependent fathers had higher scores on the neurodevelopment scale and lower scores on the performance scale of the MISIC than the children in control group. These children also made more errors on the Trail Making Test. The family environment of COAs was characterized by lack of independence for its members, greater perceived control and lack of adequate cultural and intellectual activities. Conclusion: Our findings suggest that children of men with alcohol dependence have difficulties with frontal lobe functions and neurodevelopmental tasks. There are also difficulties in the family, which are related to alcohol consumption by the father. PMID:21267372
Fortuna, Jeffrey L
Contemporary research has shown that a high number of alcohol-dependent and other drug-dependent individuals have a sweet preference, specifically for foods with a high sucrose concentration. Moreover, both human and animal studies have demonstrated that in some brains the consumption of sugar-rich foods or drinks primes the release of euphoric endorphins and dopamine within the nucleus accumbens, in a manner similar to some drugs of abuse. The neurobiological pathways of drug and "sugar addiction" involve similar neural receptors, neurotransmitters, and hedonic regions in the brain. Craving, tolerance, withdrawal and sensitization have been documented in both human and animal studies. In addition, there appears to be cross sensitization between sugar addiction and narcotic dependence in some individuals. It has also been observed that the biological children of alcoholic parents, particularly alcoholic fathers, are at greater risk to have a strong sweet preference, and this may manifest in some with an eating disorder. In the last two decades research has noted that specific genes may underlie the sweet preference in alcohol- and drug-dependent individuals, as well as in biological children of paternal alcoholics. There also appears to be some common genetic markers between alcohol dependence, bulimia, and obesity, such as the A1 allele gene and the dopamine 2 receptor gene.
Han, Doug Hyun; Kim, Sun Mi; Choi, Jung Eun; Min, Kyung Joon; Renshaw, Perry F.
The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits. We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone. Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups. At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated. During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups. In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23.3±8.4 to 14.3±4.9, compared with those of the escitalopram group of from 21.6±8.4 to 19.3±7.1 (F=13.1, p<0.01). The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group. The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol. These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder. PMID:23325372
Han, Doug Hyun; Kim, Sun Mi; Choi, Jung Eun; Min, Kyung Joon; Renshaw, Perry F
The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits. We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone. Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups. At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated. During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups. In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23.3±8.4 to 14.3±4.9, compared with those of the escitalopram group of from 21.6±8.4 to 19.3±7.1 (F=13.1, p<0.01). The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group. The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol. These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder.
Fein, George; McGillivray, Shannon; Finn, Peter
Background Research suggests that substance abusers make more disadvantageous decisions on the simulated gambling task (SGT); such decisions are associated with deviance proneness and antisocial symptoms. This study examines decision-making on the SGT in young adults with alcohol dependence that are treatment-naïve (TxN). Methods 116 subjects (58 controls, 58 TxNs) were tested on the SGT, where participants choose cards from 4 different decks that vary in terms of the magnitude of the immediate gain (large/small) and the magnitude of long-term loss (larger/smaller). Participants also were assessed on measures of externalizing symptoms, personality traits reflecting social deviance, neuropsychological function, and the density of the family history of alcoholism. Results TxNs did not differ from controls on measures of SGT decision-making. SGT performance was not associated with externalizing symptoms, social deviance proneness, or a familial density of alcoholism. Although, TxNs had higher levels of externalizing symptoms, social deviance and familial density of alcoholism compared with controls, these variables were only modestly elevated compared with previous samples of long-term abstinent alcohol dependent individuals who showed decision-making deficits on the SGT. Conclusions The results suggest that our sample of young adult TxN adults with alcohol dependence do not have global deficits in decision-making as measured by the SGT, and that their poor decisions regarding their alcohol consumption are more specific to drinking. PMID:16737453
Han, Changwoo; Bae, Hwallip; Lee, Yu-Sang; Won, Sung-Doo; Kim, Dai Jin
Objective The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. Methods In this study, we recruited 87 male patients with alcohol dependence from the alcohol center of one psychiatric hospital and 52 healthy male volunteers who were all employees in the same hospital as controls. We captured images of the right and left hands of patients and controls using a scanner and extracted data with a graphics program. We measured the 2D:4D of each hand and compared the alcohol dependence group with the control group. We analyzed these ratios using an independent-samples t-test. Results The mean 2D:4D of patients was 0.934 (right hand) and 0.942 (left hand), while the mean 2D:4D of controls was 0.956 (right hand) and 0.958 (left hand). Values for both hands were significantly lower for patients than controls (p<0.001, right hand; p=0.004, left hand). Conclusion Patients who are alcohol dependent have a significantly lower 2D:4D than controls, similar to the results of previous studies, which suggest that a higher prenatal testosterone level in the gonadal period is related to alcoholism. Furthermore, 2D:4D is a possible predictive marker of alcohol dependence. PMID:27121425
Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian
Background Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Methods Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Results Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. Conclusions These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity. PMID:27575491
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82 Pensions... Agencies § 17.82 Contracts for outpatient services for veterans with alcohol or drug dependence or abuse... requirements of the “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR part 2) and...
... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82 Pensions... Agencies § 17.82 Contracts for outpatient services for veterans with alcohol or drug dependence or abuse... requirements of the “Confidentiality of Alcohol and Drug Abuse Patient Records” (42 CFR part 2) and...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Alcohol and drug... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
Zhou, Qing; King, Kevin M; Chassin, Laurie
This study examined the prospective relations among family history density of alcoholism (FHD), adolescent family harmony, and young adults' alcohol and drug dependence. Family harmony was rated by mothers and fathers in adolescence, and young adults' substance dependence diagnoses were obtained through structured interviews. Higher FHD predicted lower adolescent family harmony, which in turn increased young adults' odds of being diagnosed with drug dependence (with and without alcohol dependence) compared to no diagnoses or to alcohol dependence only. Family harmony also interacted with FHD such that the protective effect of family harmony on young adults' drug dependence with or without alcohol dependence decreased as FHD rose, and was nonsignificant at high levels of FHD. The findings suggest the importance of distinguishing among alcohol and drug dependence disorders and examining their differential etiological pathways, and also suggest that the protective effects of harmonious family environments on substance dependence may be limited at high levels of FHD.
Wang, Ke-Sheng; Liu, Xuefeng; Aragam, Nagesh; Mullersman, Jerald E; Jian, Xueqiu; Pan, Yue; Liu, Yali
Personality traits like novelty seeking (NS), harm avoidance (HA), and reward dependence (RD) are known to be moderately heritable (30-60%). These personality traits and their comorbidities, such as alcohol dependence (AD), may share genetic components. We examined 11,120 single nucleotide polymorphisms (SNPs) genotyped in 292 nuclear families from the Genetic Analysis Workshop 14, a subset from the Collaborative Study on the Genetics of Alcoholism (COGA). A family-based association analysis was performed using the FBAT program. NS, HA, and RD were treated as quantitative traits and AD as a binary trait. Based on a multivariate association test of three quantitative traits in FBAT, we observed 20 SNPs with p < 10(-3). Interestingly, several genes (TESK2, TIPARP, THEMIS, ABLIM1, RFX4, STON2 and LILRA1) are associated with three personality traits with p < 10(-3) using single trait analysis and AD. Especially, SNP rs727532 within ABLIM1 gene at 10q25 showed the most significant association (p = 6.4 × 10(-5)) in the multivariate test and strong associations with NS, HA, RD, and AD (p = 4.48 × 10(-4), 1.2 × 10(-5), 5.6 × 10(-5), 3.12 × 10(-4), respectively) in the COGA sample. In addition, the association of rs727532 with AD was confirmed in a replication study. This study reports some newly recognized associations between several genetic loci and both AD and three personality traits.
Winham, Stacey J.; Preuss, Ulrich W.; Geske, Jennifer R.; Zill, Peter; Heit, John A.; Bakalkin, Georgy; Biernacka, Joanna M.; Karpyak, Victor M.
We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states, and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p = 0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285 G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific. PMID:26502829
Karlsson, Oskar; Roman, Erika
The acute effects of alcohol administration are age-, dose-, time- and task-dependent. Although generally considered to be a sedative drug, alcohol has both stimulatory and depressant effects on behavior, depending on dose and time. Alcohol-induced motor activating effects are consistently shown in mice but rarely demonstrated in adult, outbred rats using conventional behavioral tests. The aim of the present experiment was to study acute alcohol-induced effects on behavioral profiles in a more complex environment using the novel multivariate concentric square field™ (MCSF) test, designed for assessing different behaviors in the same trial including locomotor activity. Adult male Wistar rats (Sca:WI) were administered one intraperitoneal (i.p.) injection of alcohol (0.0 g/kg, 0.5 g/kg, 1.0 g/kg, or 1.5 g/kg) 5 min prior to the 30-min MCSF test. The two highest doses induced marked motor-suppressing effects. A significant interaction between group and time was found in general activity when comparing rats exposed to alcohol at 0.0 g/kg and 0.5 g/kg. In contrast to the 0.0 g/kg dose that increased the activity over time, animals administered the low dose (0.5 g/kg) demonstrated an initial high activity followed by a decline over time. No indications for acute alcohol-induced anxiolytic-like effects were found. The multivariate setting in the MCSF test appears to be sensitive for detecting motor-activating effects of low doses of alcohol as well as reduced locomotion at doses lower than in other behavioral tasks. The detection of subtle changes in behavior across time and dose is important for understanding alcohol-induced effects. This approach may be useful in evaluating alcohol doses that correspond to different degrees of intoxication in humans.
Zakiniaeiz, Yasmin; Scheinost, Dustin; Seo, Dongju; Sinha, Rajita; Constable, R Todd
Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC), mid (MCC) and posterior cingulate cortex (PCC), voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome). Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC) participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.
Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Feeder, Scott E; Choi, Doo-Sup; Port, John D
Although the precise drug mechanism of action of acamprosate remains unclear, its antidipsotropic effect is mediated in part through glutamatergic neurotransmission. We evaluated the effect of 4 weeks of acamprosate treatment in a cohort of 13 subjects with alcohol dependence (confirmed by a structured interview, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) on proton magnetic resonance spectroscopy glutamate levels in the midline anterior cingulate cortex (MACC). We compared levels of metabolites with a group of 16 healthy controls. The Pennsylvania Alcohol Craving Scale was used to assess craving intensity. At baseline, before treatment, the mean cerebrospinal fluid-corrected MACC glutamate (Glu) level was significantly elevated in subjects with alcohol dependence compared with controls (P = 0.004). Four weeks of acamprosate treatment reduced glutamate levels (P = 0.025), an effect that was not observed in subjects who did not take acamprosate. At baseline, there was a significant positive correlation between cravings, measured by the Pennsylvania Alcohol Craving Scale, and MACC (Glu) levels (P = 0.019). Overall, these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence. Further research is needed to evaluate the use of these findings for clinical practice, including monitoring of craving intensity and individualized selection of treatment with antidipsotropic medications in subjects with alcohol dependence.
Alba-Ferrara, L.; Fernandez, F.; Salas, R.; de Erausquin, G. A.
Alcohol dependence is a major social, economic, and public health problem. Alcoholism can lead to damage of the gastrointestinal, nervous, cardiovascular, and respiratory systems and it can be lethal, costing hundreds of billions to the health care system. Despite the existence of cognitive-behavioral therapy, psychosocial interventions, and spiritually integrated treatment to treat it, alcohol dependence has a high relapse rate and poor prognosis, albeit with high interindividual variability. In this review, we discuss the use of two neuromodulation techniques, namely repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), and their advantages and disadvantages compared to first-line pharmacological treatment for alcohol dependence. We also discuss rTMS and DBS targets for alcohol dependence treatment, considering experimental animal and human evidence, with careful consideration of methodological issues preventing the identification of feasible targets for neuromodulation treatments, as well as inter-individual variability factors influencing alcoholism prognosis. Lastly, we anticipate future research aiming to tailor the treatment to each individual patient by combining neurofunctional, neuroanatomical and neurodisruptive techniques optimizing the outcome. PMID:25598743
Brevers, Damien; Bechara, Antoine; Cleeremans, Axel; Kornreich, Charles; Verbanck, Paul; Noël, Xavier
Background Alcohol dependence is associated with poor decision-making under ambiguity, that is, when decisions are to be made in the absence of known probabilities of reward and loss. However, little is known regarding decisions made by individuals with alcohol dependence in the context of known probabilities (decision under risk). In this study, we investigated the relative contribution of these distinct aspects of decision making to alcohol dependence. Methods Thirty recently detoxified and sober asymptomatic alcohol-dependent individuals, and thirty healthy control participants were tested for decision-making under ambiguity (using the Iowa Gambling Task), and decision-making under-risk (using the Cups Task and Coin Flipping Task). We also tested their capacities for working memory storage (Digit-span Forward), and dual-tasking (Operation-span Task). Results Compared to healthy control participants, alcohol-dependent individuals made disadvantageous decisions on the Iowa Gambling Task, reflecting poor decisions under ambiguity. They also made more risky choices on the Cups and Coin Flipping Tasks reflecting poor decision-making under risk. In addition, alcohol-dependent participants showed some working memory impairments, as measured by the dual tasking, and the degree of this impairment correlated with high-risk decision-making, thus suggesting a relationship between processes sub-serving working memory and risky decisions. Conclusion These results suggest that alcohol dependent individuals are impaired in their ability to decide optimally in multiple facets of uncertainty (i.e., both risk and ambiguity), and that at least some aspects of these deficits are linked to poor working memory processes. PMID:24948198
Vitali, Mario; Napolitano, Carmen; Berman, Marlene Oscar; Minuto, Simona Flamminii; Battagliese, Gemma; Attilia, Maria Luisa; Braverman, Eric R; Romeo, Marina; Blum, Kenneth; Ceccanti, Mauro
Background In 1987, Cloninger proposed a clinical description and classification of different personality traits genetically defined and independent from each other. Moreover, he elaborated a specific test the TCI to investigate these traits/states. The study of craving in Alcohol Use Disorder (AUD) assumed a greater significance, since ever more data seems to suggest a direct correlation between high levels of craving and a higher risk of relapse in alcoholics. Thus, our study aim is to explore the possible correlations among TCI linked molecular neurobiological pattern (s), craving and alcohol addiction severity measures in a sample of Italian alcoholics. Materials and Methods 191 alcoholics were recruited in a Day Hospital (DH) setting at the Alcohol Addiction Program Latium Region Referral Center, Sapienza University of Rome. After 7 days detoxification treatment a psychodiagnostic protocol was administered, including TCI, VAS-C, ASI and SADQ. All patients signed an Institutional Review Board (IRB) approved informed consent. Results Principally, we detected a significant positive correlation between HA-scale scores and the VAS scale: increasing in HA-scale corresponds to an increase in craving perception for both intensity (r=0.310; p ≤ 0.001) and frequency (r=0.246; p ≤ 0.001). Moreover, perception of dependence severity, measured with SADQ was also found to be significantly associated positively to both HA-scale (r=0.246; p ≤ 0.001) and NS-scale (r=0.224; p ≤ 0.01). While, for character scales, Persistence (r=−0.195; p=.008) and Self-directedness (r=−0.294; p ≤ 0.001) was negatively associated with ASI linked to alcohol problems. Self-directedness was also negatively correlated with ASI linked to family and social problems (r=−0.349; p ≤ 0.001), employment and support problems (r=−0.220; p=0.003) and psychiatric problems (r=−0.358; p ≤ 0.001). Cooperativeness was a negative correlate with Legal Problems (r=−0.173; p=0.019). and Self
Falk, Daniel E.; Castle, I-Jen P.; Ryan, Megan; Fertig, Joanne; Litten, Raye Z.
Objectives To explore if varenicline (Chantix®) showed more efficacy in treating certain subgroups of patients. In a recent multi-site trial, varenicline was shown to be effective in reducing drinking in alcohol dependent patients, both smokers and nonsmokers. Given the heterogeneity among alcohol dependent patients, secondary analyses were conducted to determine if certain subgroups responded more favorably than others to treatment with varenicline. Methods Data were drawn from a Phase 2 randomized, double-blind, placebo-controlled multi-site 13-week trial of varenicline in alcohol dependent patients (Litten et al., 2013). Seventeen moderator variables were selected for exploratory testing on the basis of theoretical and scientific interest. Results Of the 17 moderator variables assessed, four were statistically significant, including cigarettes per day reduction, treatment drinking goal, years drinking regularly, and age of patient. Two other variables—the type of adverse events experienced by patients and the severity of alcohol-related consequences—appeared to moderate the varenicline treatment effect at borderline statistical significance. Individuals who reduced the number of cigarettes per day experienced a significant effect from varenicline in reducing drinking, whereas those who did not change or who increased their number of cigarettes observed no beneficial effect. Reviewing the moderators related to severity, varenicline appeared to have greater efficacy than placebo among less severely-dependent patients. Conclusions Varenicline appears to be more efficacious in certain subgroups, particularly in those who reduced their smoking and in the “less severe” patient. Additional studies are warranted to confirm the results of these exploratory analyses. PMID:26083958
Slósarska, M; Wójcik, M; Habrat, B
Heart rate, respiratory rate, postural muscle tone and tapping in 14 alcohol dependent patients (type II ac. Cloninger) during 10 days of detoxification were investigated. Despite subjective mood increased, no longer observed were tachycardia and clinical symptoms of alcohol withdrawal; increased muscle tonus and faster respiration rhythm were observed. The observed physiological changes in alcohol dependent patients after 10 days of abstinence suggest that continuation of pharmacotherapy and psychotherapy after detoxification in acute alcohol withdrawal is recommended.
Podschus, J; Dufeu, P; Schmidt, L G; Sallstrom-Baum, S; Rommelspacher, H
Plasma dopamine, β-carbolines (norharman, harman) and isoquinolines ((R)- and (S)-salsolinol) were examined for their relationship to antisocial tendencies in 138 drinking men with an alcohol dependence syndrome according to ICD-10 criteria. Antisociality was assessed according to the following criteria: delinquency, involvement in fist-fights and homelessness. The personality structure was documented by the Tridimensional Personality Questionnaire of Cloninger. An early age of onset of alcohol dependence and a high degree of 'novelty seeking' were associated with antisocial tendencies. Of the β-carbolines and isoquinolines, harman and (S)-salsolinol were significantly decreased among antisocial alcoholics. Norharman, (R)-salsolinol and dopamine were not associated with antisocial personality. The contribution of endogenous alkaloids to the biological characterization of antisocial tendencies in alcoholics is described.
... parents and other adults use alcohol socially — having beer or wine with dinner, for example — alcohol seems ... besides just hanging out in someone's basement drinking beer all night. Plan a trip to the movies, ...
Padma, Lakshminarayana; Swaminath, Gopalrao; Thimmaiah, Rohini S.
Background: Currently, benzodiazepines are the preferred drugs in the management of alcohol withdrawal symptoms. Chlordiazepoxide and diazepam, the most frequently used drugs have a long duration of action and are converted to active metabolites in the liver, while lorazepam is shorter acting, with no active metabolites. Objective: To compare and evaluate the safety and efficacy of lorazepam and chlordiazepoxide in patients with alcohol dependence syndrome with symptoms of alcohol withdrawal. Materials and Methods: This was a prospective, randomized, double-blind, study carried out at a teaching hospital in Bangalore. Sixty patients aged ≥18 y with alcohol dependence syndrome with mild-to-moderate withdrawal symptoms were allocated at a ratio of 1:1 to either lorazepam or chlordiazepoxide, by means of a computer-generated randomization chart. Thirty patients each were started with lorazepam tablets 8 mg/day and chlordiazepoxide 80 mg/day. For both treatment groups, the dose was tapered and at the end of 8 days, the patients were drug-free. The severity of alcohol dependence was assessed using the Severity of Alcohol Dependence Questionnaire (SADQ). The CIWA-Ar was used for quantification of withdrawal symptoms. Liver function tests were performed at baseline and at the end of the study. Results: Of the 60 patients included in the study, 15 patients each had mild and moderate withdrawal symptoms in the chlordiazepoxide group and 17 and 13 patients respectively in the lorazepam group, based on the SADQ score. At baseline, the mean CIWA-Ar scores were similar in both the treatment groups: 24.77±5.98 in the chlordiazepoxide group and 24.90±6.12 in the lorazepam group. There was a significant intragroup decrease in the CIWA-Ar scores measured from baseline to the end of 8 days (p<0.0001) and 12 days (p<0.0001) in both treatment groups; however, there was no significant difference between the two groups. There was no significant difference observed in the liver
de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F.; Hope, Bruce T.; Brennan, Molly; Cole, Maury; Koob, George F.
Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. SIGNIFICANCE STATEMENT Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These
Caliguri, Joseph P., Ed.
This extensive annotated bibliography provides a compilation of documents retreived from a computerized search of the ERIC, Social Science Citation Index, and Med-Line databases on the topic of alcoholism. The materials address the following areas of concern: (1) attitudes toward alcohol users and abusers; (2) characteristics of alcoholics and…
Graham, Kathryn; Bernards, Sharon; Wilsnack, Sharon C.; Gmel, Gerhard
This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13…
Quiñones-Laveriano, Dante Manuel; Espinoza-Chiong, César; Scarsi-Mejia, Ottavia; Rojas-Camayo, José; Mejia, Christian Richard
The aim of this study was to determine the association between alcohol dependence and altitude of residence in 11 villages in two high altitude areas of Peru. An analytical cross-sectional study was performed using a survey conducted by physicians in primary health care in 11 villages until 2013, that were divided into low altitude (≤2500m asl (above sea level)), and high altitude (>2500m asl) areas. The CAGE test for alcoholism (cut point, ≥2) was applied to those who responded positively when asked if they consumed alcohol. Statistical associations were obtained with generalised linear models Of the 737 participants, 51% were women and the median age was 36 years [interquartile range, 25-50], 334 (45%) lived at low altitude, and 113 (15%) had alcohol dependence. The highest frequency of alcoholism was positively associated with being a village considered extremely poor (Likelihood Ratio (LP)=2.42; 95%CI, 1.40-4.19), while being female (LP=0.44; 95%CI, 0.23-0.89) and residing at high altitude (LP=0.15; 95%CI, 0.07-0.31) were negatively associated. These were adjusted for nine socio-occupational and pathological variables. According to these data, there is a higher frequency of alcohol dependence in being, male, extremely poor, and residing at low altitude. These results should be taken into account by professionals who work in primary care and those involved in mental health care, because of their implications in society.
Rouvinen-Lagerström, Noora; Lahti, Jari; Alho, Hannu; Kovanen, Leena; Aalto, Mauri; Partonen, Timo; Silander, Kaisa; Sinclair, David; Räikkönen, Katri; Eriksson, Johan G.; Palotie, Aarno; Koskinen, Seppo; Saarikoski, Sirkku T.
Aims: The molecular epidemiological studies on the association of the opioid receptor µ-1 (OPRM1) polymorphism A118G (Asn40Asp, rs1799971) and alcohol use disorders have given conflicting results. The aim of this study was to test the possible association of A118G polymorphism and alcohol use disorders and alcohol consumption in three large cohort-based study samples. Methods: The association between the OPRM1 A118G (Asn40Asp, rs1799971) polymorphism and alcohol use disorders and alcohol consumption was analyzed using three different population-based samples: (a) a Finnish cohort study, Health 2000, with 503 participants having a DSM-IV diagnosis for alcohol dependence and/or alcohol abuse and 506 age- and sex-matched controls; (b) a Finnish cohort study, FINRISK (n = 2360) and (c) the Helsinki Birth Cohort Study (n = 1384). The latter two populations lacked diagnosis-based phenotypes, but included detailed information on alcohol consumption. Results: We found no statistically significant differences in genotypic or allelic distribution between controls and subjects with alcohol dependence or abuse diagnoses. Likewise no significant effects were observed between the A118G genotype and alcohol consumption. Conclusion: These results suggest that A118G (Asn40Asp) polymorphism may not have a major effect on the development of alcohol use disorders at least in the Finnish population. PMID:23729673
Vargas, Wanette M.; Bengston, Lynn; Gilpin, Nicholas W.; Whitcomb, Brian W.
Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism. PMID:25355229
Hyman, Scott M; Garcia, Miguel; Sinha, Rajita
We examined associations between types of childhood maltreatment and the onset, escalation, and severity of substance use in cocaine dependent adults. In men (n = 55), emotional abuse was associated with a younger age of first alcohol use and a greater severity of substance abuse. In women (n = 32), sexual abuse, emotional abuse, and overall maltreatment was associated with a younger age of first alcohol use, and emotional abuse, emotional neglect, and overall maltreatment was associated with a greater severity of substance abuse. There was no association between childhood maltreatment and age of nicotine or cocaine use. However, age of first alcohol use predicted age of first cocaine use in both genders. All associations were stronger in women. Findings suggest that early intervention for childhood victims, especially females, may delay or prevent the early onset of alcohol use and reduce the risk for a more severe course of addiction.
Chiang, T; Sansuk, K
Background and Purpose δ Opioid receptor agonists are being developed as potential treatments for depression and alcohol use disorders. This is particularly interesting as depression is frequently co‐morbid with alcohol use disorders. Yet we have previously shown that δ receptor agonists range widely in their ability to modulate alcohol intake; certain δ receptor agonists actually increase alcohol consumption in mice. We propose that variations in β‐arrestin 2 recruitment contribute to the differential behavioural profile of δ receptor agonists. Experimental Approach We used three diarylmethylpiperazine‐based non‐peptidic δ receptor selective agonists (SNC80, SNC162 and ARM390) and three structurally diverse δ receptor agonists (TAN‐67, KNT127 and NIH11082). We tested these agonists in cAMP and β‐arrestin 2 recruitment assays and a behavioural assay of alcohol intake in male C57BL/6 mice. We used β‐arrestin 2 knockout mice and a model of depression‐like behaviour to further study the role of β‐arrestin 2 in δ receptor pharmacology. Key Results All six tested δ receptor agonists were full agonists in the cAMP assay but displayed distinct β‐arrestin 2 recruitment efficacy. The efficacy of δ receptor agonists to recruit β‐arrestin 2 positively correlated with their ability to increase alcohol intake (P < 0.01). The effects of the very efficacious recruiter SNC80 on alcohol intake, alcohol place preference and depression‐like behaviour were β‐arrestin 2‐dependent. Conclusions and Implications Our finding that δ receptor agonists that strongly recruit β‐arrestin 2 can increase alcohol intake carries important ramifications for drug development of δ receptor agonists for treatment of alcohol use disorders and depressive disorders. © 2015 The British Pharmacological Society PMID:26507558
Disorder 3.30% Cannabis Abuse or Dependence 6.70% Cocaine Abuse or Dependence 16.70% Sedative Abuse or Dependence 6.70% Opiate Abuse or Dependence 3.30...of Cannabis Use in the Past 90 Days [n = 9] 45 (9–90, 78) No. of Days of Cocaine Use in the Past 90 Days [n = 3] 37.0 (45.9) No. of Days of Opiate Use...Dependence Yes No Lifetime alcohol dependence Yes No ______ Cannabis Abuse Yes No Cannabis Dependence Yes No Cocaine Abuse
Burnett, Elizabeth J; Chandler, L Judson; Trantham-Davidson, Heather
Introduction Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. Objective To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Results Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure and up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, changes in NMDA receptors and additional glutamatergic neuroadaptations are often circuit and cell-type specific. Discussion Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. Conclusion While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover
Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Owusu-Duku, Beverly; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A.; Miguel-Hidalgo, Jose J.
Background Alcohol-dependent (ALC) subjects exhibit glial and neuronal pathology in the prefrontal cortex (PFC). However, in many patients, neurophysiological disturbances are not associated with catastrophic cell depletion despite prolonged alcohol abuse. It is still unclear how some relevant markers of a cell’s propensity to degenerate or proliferate are changed in the PFC of ALC subjects without major neurological disorders. Methods Levels of pro-apoptotic caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 non-psychiatric comparison subjects. Results ALC subjects had significantly higher levels of the 14kDa C8 fragment (C8-14), an indicator of C8 activation. However, there was no change in the levels of DIABLO, XIAP or in the DIABLO/XIAP ratio. PCNA protein level and density of Ki-67-IR cells were not significantly changed in alcoholics, although PCNA levels were increased in older ALC subjects as compared to controls. Conclusions Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in XIAP level, DIABLO/XIAP ratio, or Ki-67 labeling. These results would help to explain the absence of catastrophic cell loss in the PFC of many alcohol dependent subjects, while still being consistent with an alcoholism-related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics. PMID:25421516
Miguel-Hidalgo, José Javier; Wilson, Barbara A; Hussain, Syed; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A
Reduced density of glial cells and low levels of some astrocyte proteins have been described in the orbitofrontal cortex (OFC) in depression and alcoholism, two disorders often comorbid. These regressive changes may also involve the communication between astrocytes via gap junctions and hemichannels, which play important regulatory roles in neurotransmission. We determined levels and morphological immunostaining parameters of connexin 43 (Cx43), the main protein subunit of astrocyte gap junctions/hemichannels, in the OFC of subjects with depression, alcoholism or comorbid depression/alcoholism as compared to non-psychiatric subjects. Postmortem brain samples from 23 subjects with major depressive disorder (MDD), 16 with alcohol dependence, 13 with comorbid MDD and alcohol dependence, and 20 psychiatrically-normal comparison subjects were processed for western blots to determine Cx43 levels. Area fraction of Cx43 immunoreactivity, and density and average size of immunoreactive puncta were measured in histological sections. There was a significant, larger than 60 percent decrease in Cx43 level in the three psychiatric groups as compared to controls. Area fraction of immunoreactivity and immunoreactive punctum size were reduced in all psychiatric groups, but Cx43-immunoreactive puncta density was reduced only in alcohol-dependent subjects. Among psychiatric subjects, no difference in Cx43 levels or immunostaining was found between suicides and non-suicides. The present data suggest that dysfunction of the OFC is accompanied by reduction in the levels of gap junction protein Cx43 in depression and alcoholism, and reduction in density of Cx43 immunoreactive puncta only in alcoholism, pointing to altered gap junction or hemichannel-based communication in the pathophysiology of those disorders.
Miguel-Hidalgo, José Javier; Wilson, Barbara A.; Hussain, Syed; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A.
Reduced density of glial cells and low levels of some astrocyte proteins have been described in the orbitofrontal cortex (OFC) in depression and alcoholism, two disorders often comorbid. These regressive changes may also involve the communication between astrocytes via gap junctions and hemichannels, which play important regulatory roles in neurotransmission. We determined levels and morphological immunostaining parameters of connexin 43 (Cx43), the main protein subunit of astrocyte gap junctions/hemichannels, in the OFC of subjects with depression, alcoholism or comorbid depression/alcoholism as compared to non-psychiatric subjects. Postmortem brain samples from 23 subjects with major depressive disorder (MDD), 16 with alcohol dependence, 13 with comorbid MDD and alcohol dependence, and 20 psychiatrically-normal comparison subjects were processed for western blots to determine Cx43 levels. Area fraction of Cx43 immunoreactivity, and density and average size of immunoreactive puncta were measured in histological sections. There was a significant, larger than 60 percent decrease in Cx43 level in the three psychiatric groups as compared to controls. Area fraction of immunoreactivity and immunoreactive punctum size were reduced in all psychiatric groups, but Cx43-immunoreactive puncta density was reduced only in alcohol-dependent subjects. Among psychiatric subjects, no difference in Cx43 levels or immunostaining was found between suicides and non-suicides. The present data suggest that dysfunction of the OFC is accompanied by reduction in the levels of gap junction protein Cx43 in depression and alcoholism, and reduction in density of Cx43 immunoreactive puncta only in alcoholism, pointing to altered gap junction or hemichannel-based communication in the pathophysiology of those disorders. PMID:24774648
Zhu, Xi; Sundby, Kelsey; Bjork, James M.; Momenan, Reza
Alcohol dependence is associated with heightened risk tolerance and altered decision-making. This raises the question as to whether alcohol dependent patients (ADP) are incapable of proper risk assessment. We investigated how healthy controls (HC) and ADP engage neural networks to cope with the increased cognitive demands of risky decisions. We collected fMRI data while 34 HC and 16 ADP played a game that included “safe” and “risky” trials. In safe trials, participants accrued money at no risk of a penalty. In risky trials, reward and risk simultaneously increased as participants were instructed to decide when to stop a reward accrual period. If the participant failed to stop before an undisclosed time, the trial would “bust” and participants would not earn the money from that trial. Independent Component Analysis was used to identify networks engaged during the anticipation and the decision execution of risky compared with safe trials. Like HC, ADP demonstrated distinct network engagement for safe and risky trials at anticipation. However, at decision execution, ADP exhibited severely reduced discrimination in network engagement between safe and risky trials. Although ADP behaviorally responded to risk they failed to appropriately modify network engagement as the decision continued, leading ADP to assume similar network engagement regardless of risk prospects. This may reflect disorganized network switching and a facile response strategy uniformly adopted by ADP across risk conditions. We propose that aberrant salience network (SN) engagement in ADP might contribute to ineffective network switching and that the role of the SN in risky decisions warrants further investigation. PMID:27064561
Clarke, Toni-Kim; Laucht, Manfred; Ridinger, Monika; Wodarz, Norbert; Rietschel, Marcella; Maier, Wolfgang; Lathrop, Mark; Lourdusamy, Anbarasu; Zimmermann, Ulrich S; Desrivieres, Sylvane; Schumann, Gunter
Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p=0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p=0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.
Bob, Petr; Jasova, Denisa; Bizik, Gustav; Raboch, Jiri
Background Alcohol dependence during withdrawal and also in abstinent period in many cases is related to reduced inhibitory functions and kindling that may appear in the form of psychosensory symptoms similar to temporal lobe epilepsy frequently in conditions of normal EEG and without seizures. Because temporal lobe epileptic activity tend to spread between hemispheres, it is possible to suppose that measures reflecting interhemispheric information transfer such as electrodermal activity (EDA) might be related to the psychosensory symptoms. Methods and Findings We have performed measurement of bilateral EDA, psychosensory symptoms (LSCL-33) and alcohol craving (ACQ) in 34 alcohol dependent patients and 32 healthy controls. The results in alcohol dependent patients show that during rest conditions the psychosensory symptoms (LSCL-33) are related to EDA transinformation (PTI) between left and right EDA records (Spearman r = 0.44, p<0.01). Conclusions The result may present potentially useful clinical finding suggesting a possibility to indirectly assess epileptiform changes in alcohol dependent patients. PMID:21541318
Mercincavage, Melissa; Smyth, Joshua M.; Branstetter, Steven A.; Catley, Delwyn
Background The time to first cigarette (TTFC) of the day is an emerging single-item indicator of nicotine dependence due to its robust associations with indices of physical dependence. However, it is unclear if this measure adequately captures other dimensions of dependence. The Severity of Dependence Scale (SDS) is a brief questionnaire used to assess psychological aspects of dependence that has not yet been extensively applied to smoking research. Methods We examined associations between the SDS and TTFC among 255 smokers during the baseline session of a cessation trial. We also examined associations of the SDS and TTFC with biobehavioral dependence indices, quitting behaviors, and cognitive-affective variables, and compared the relative contributions of both measures in predicting these variables. Results TTFC was unrelated to SDS total score, but was related to individual SDS items. TTFC, but not SDS, was correlated with indices of physical dependence (e.g., CPD, CO). Both TTFC and SDS were associated with quitting behaviors, with opposite directionality of associations. TTFC and SDS were both associated with cognitive-affective variables, but SDS outperformed TTFC in strength and number of these relationships. Including both the SDS and TTFC as regression model predictors often increased the amount of variance explained. Conclusions Findings suggest that SDS and TTFC assess different constructs of nicotine dependence; among smokers, the SDS appears to tap into non-physical components of dependence (e.g., loss of control) that relate to quitting motivation and affect. Assessing nicotine dependence using only the SDS may fail to capture physical dependence and, further, may not reflect the same domains of addiction the SDS assesses in other drugs of abuse. Nonetheless, using three SDS items in addition to TTFC may offer utility over using TTFC alone. PMID:26566575
Denaës, Timothé; Lodder, Jasper; Chobert, Marie-Noële; Ruiz, Isaac; Pawlotsky, Jean-Michel; Lotersztajn, Sophie; Teixeira-Clerc, Fatima
Kupffer cells, the resident macrophages of the liver, play a major role in the pathogenesis of alcoholic liver disease. We have previously demonstrated that CB2 receptor protects against alcoholic liver disease by inhibiting alcohol-induced inflammation and steatosis via the regulation of Kupffer cell activation. Here, we explored the mechanism underlying these effects and hypothesized that the anti-inflammatory properties of CB2 receptor in Kupffer cells rely on activation of autophagy. For this purpose, mice invalidated for CB2 receptor (CB2(Mye-/-) mice) or for the autophagy gene ATG5 (ATG5(Mye-/-) mice) in the myeloid lineage, and their littermate wild-type mice were subjected to chronic-plus-binge ethanol feeding. CB2(Mye-/-) mice showed exacerbated alcohol-induced pro-inflammatory gene expression and steatosis. Studies in cultured macrophages demonstrated that CB2 receptor activation by JWH-133 stimulated autophagy via a heme oxygenase-1 dependent pathway. Moreover, JWH-133 reduced the induction of inflammatory genes by lipopolysaccharide in wild-type macrophages, but not in ATG5-deficient cells. The CB2 agonist also protected from alcohol-induced liver inflammation and steatosis in wild-type mice, but not in ATG5(Mye-/-) mice demonstrating that macrophage autophagy mediates the anti-inflammatory and anti-steatogenic effects of CB2 receptor. Altogether these results demonstrate that CB2 receptor activation in macrophages protects from alcohol-induced steatosis by inhibiting hepatic inflammation through an autophagy-dependent pathway.
Caetano, Raul; Caetano Vaeth, Patrice A.; Mills, Britain A.; Rodriguez, Lori A.
BACKGROUND This paper examines the prevalence, the symptom profile, and the drinking and sociodemographic predictors of current (past 12 month) DSM-IV alcohol abuse and dependence among Mexican Americans living along the U.S.-Mexico border and those living in metropolitan areas away from the border. METHODS Respondents in the non-border areas (primarily Houston and Los Angeles) constitute a multistage probability sample (N=1,288) of these areas, interviewed as part of the 2006 Hispanic Americans Baseline Alcohol Survey (HABLAS). Respondents in the border area (N=1,307) constitute a household probability sample of Mexican Americans living on the border. In both surveys, data were collected during computer assisted interviews conducted in respondents’ homes. The HABLAS and the border sample response rates were 76% and 67%, respectively. RESULTS Although bivariate analyses revealed no overall differences between border and non-border locations, (negative) age trends were more pronounced on the border for male abuse and for dependence among both genders. Among females aged 18–29, border residence was linked to significantly higher rates of dependence. In multivariable analyses, the prevalence of male abuse declined more rapidly with age on the border than off the border. Other unique predictors of male abuse were Jewish/other religion and weekly volume of alcohol consumption. Being married or out of the workforce, attaining a higher education, no religious preference, and weekly volume uniquely predicted female dependence. Age and weekly volume uniquely predicted male dependence. CONCLUSIONS The prevalence of alcohol use disorders among Mexican Americans on and off the U.S.-Mexico border largely mirrors previously documented patterns of alcohol consumption in these areas. For young Mexican-American women in particular, border residence is linked to heightened vulnerability to alcohol dependence. PMID:23278433
... Alcohol Awareness Month April is Alcohol Awareness Month Biosensor Challenge Learn more College Drinking Learn More Alcohol Dependence Get the facts Alcohol Awareness Month Biosensor Challenge College Drinking Alcohol Dependence Latest News New & ...
ABBEY, ANTONIA; CLINTON-SHERROD, A. MONIQUE; McAUSLAN, PAM; ZAWACKI, TINA; BUCK, PHILIP O.
Researchers have suggested that intoxicated perpetrators may act more violently than other perpetrators, although empirical findings have been mixed. Past research has focused on whether or not alcohol was consumed, rather than the quantity consumed, and this may explain these inconsistent findings. The authors hypothesized that the quantity of alcohol consumed would have a curvilinear relationship to the severity of the assault. Data were collected from 113 college men who reported that they had committed a sexual assault since the age of 14. The quantity of alcohol that perpetrators consumed during the assault was linearly related to how much aggression they used and was curvilinearly related to the type of sexual assault committed. The quantity of alcohol that victims consumed during the assault was linearly related to the type of sexual assault committed. Strategies for improving assessment of alcohol consumption in sexual assault research are discussed. PMID:14675511
Merinov, A V; Shustov, D I
The effect of the suicidal activity in men with alcohol dependence on suicidal indexes, personal-codependency and psychological specifics of their wives has been studied. It has been found that women married to suicidal men with alcohol dependence significantly more frequently demonstrate suicidal activity (a phenomenon of suicidal matrimonial comorbidity) compared to wives of "non-suicidal" men. They also reveal non-suicidal behavioral patterns more frequently and prosuicidal predictors are quite common in them. This contingent of women has high suicidal potential that needs special attention during the therapeutic work.
... dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. 17... of Services of Other Federal Agencies § 17.80 Alcohol and drug dependence or abuse treatment and rehabilitation in residential and nonresidential facilities by contract. (a) Alcohol and drug dependence or...
Plurad, David; Demetriades, Demetrios; Gruzinski, Ginger; Preston, Christy; Chan, Linda; Gaspard, Donald; Margulies, Daniel; Cryer, Gill
The effect of alcohol ingestion on short-term outcomes for trauma patients is indeterminate. Experimental and clinical reports often conflict. The objective of this study was to investigate the prevalence of positive alcohol screens, the effect of alcohol ingestion on injury patterns, severity, and outcomes in patients who were involved in motor vehicle crashes (MVC). MVC patients aged > 10 years treated in any of the 13 trauma centers in Los Angeles County during the calendar year 2003 were studied. All patients underwent routine alcohol screening on admission. The alcohol negative group ("no ETOH") had a blood alcohol level (BAL) of < or = 0.005 g/dL. Low and high alcohol groups ("low ETOH" and "high ETOH") had a BAL of > 0.005 g/dL to < 0.08 g/dL and > or = 0.08 g/dL, respectively. Logistic regression was performed to compare injury severity, complications, survival, and length of hospital stay among the three groups. Of the 3025 patients studied, 2013 (67%) were in the no ETOH group, 216 (7%) were in the low ETOH group, and 796 (26%) were in the high ETOH group. Levels were not associated with injury severity, Emergency Department hypotension, or Intensive Care Unit length of stay. Patients with an injury severity score > 15 and a high BAL had a higher incidence of severe head trauma (head abbreviated injury score > 3) and increased incidence of sepsis. However, in this group of severely injured, the high ETOH group had a significantly better survival rate than patients in the no ETOH group (adjusted odds ratio 0.41, 95% confidence interval 0.16-0.94, p = 0.05). Severely injured MVC victims with a high BAL have a higher incidence of severe head trauma and septic complications than no ETOH patients. However, the high ETOH group had superior adjusted survival rates.
Zaniewska, Agnieszka; Borzym-Kluczyk, Malgorzata; Szajda, Slawomir D; Romatowski, Jacek; Gil, Andrzej; Knas, Malgorzata; Dobryniewski, Jacek; Zwierz, Krzysztof
The aim of this study was to determine the activity of the lysosomal exoglycosidases: alpha-mannosidase (MAN), alpha-fucosidase (FUC), and beta-glucuronidase (GLUCUR) in serum of alcohol-dependent men supplemented and not supplemented with borage oil enriched with vitamin E. Serum was collected from eight social drinkers and 16 alcohol-dependent men after a drinking period. The activity of exoglycosidases and the concentration of protein in serum were determined. The increase in specific activity of MAN and GLUCUR was significant in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E, in comparison with the specific activity in serum of social drinkers. In serum of alcohol-dependent men treated with borage oil enriched with vitamin E, specific activity of MAN and GLUCUR fluctuated in comparison with alcohol-dependent men not supplemented. Specific activity of FUC in serum of alcohol-dependent men both not supplemented and supplemented with borage oil enriched with vitamin E showed a tendency to increase, in comparison with social drinkers. Specific activity of FUC had a tendency to decrease in serum of alcohol-dependent men supplemented with borage oil enriched with vitamin E, in comparison with alcohol-dependent men not supplemented. Thus, supplementation of alcohol-dependent men after a long-lasting drinking period with borage oil and vitamin E did not change the rate of catabolism of the oligosaccharide chains of glycoconjugates, as evaluated by serum activity of exoglycosidases.
Zwierzyńska, Ewa; Andrzejczak, Dariusz; Pietrzak, Bogusława
New antiepileptic drugs have been investigated for their potential role in the treatment of alcohol dependence. One of these drugs is retigabine and this study examines the effect of retigabine co-administered with ethanol on the development of alcohol dependence and the course of acute withdrawal syndrome. A pharmaco-EEG method was used to examine this impact in selected brain structures of rabbits (midbrain reticular formation, hippocampus and frontal cortex). Retigabine was administered p.o. at a dose of 5mg/kg/day with ethanol ad libitum for 6 weeks and then alone for 2 weeks during an abstinence period. Changes in bioelectric activity, which demonstrated the inhibitory effect of alcohol on the brain structures, were already visible after 2 weeks of ethanol administration. In the abstinence period, changes were of a different nature and significant neuronal hyperactivity was observed, particularly in the midbrain reticular formation and the hippocampus. This findings reveal that retigabine decreased ethanol-induced changes during both alcohol administration and abstinence periods. In particular, the modulatory effect of retigabine on the hippocampus may be a significant element of its mechanism of action in alcohol dependence therapy.
Mathies, Laura D; Blackwell, GinaMari G; Austin, Makeda K; Edwards, Alexis C; Riley, Brien P; Davies, Andrew G; Bettinger, Jill C
Alcohol abuse is a widespread and serious problem. Understanding the factors that influence the likelihood of abuse is important for the development of effective therapies. There are both genetic and environmental influences on the development of abuse, but it has been difficult to identify specific liability factors, in part because of both the complex genetic architecture of liability and the influences of environmental stimuli on the expression of that genetic liability. Epigenetic modification of gene expression can underlie both genetic and environmentally sensitive variation in expression, and epigenetic regulation has been implicated in the progression to addiction. Here, we identify a role for the switching defective/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in regulating the behavioral response to alcohol in the nematode Caenorhabditis elegans. We found that SWI/SNF components are required in adults for the normal behavioral response to ethanol and that different SWI/SNF complexes regulate different aspects of the acute response to ethanol. We showed that the SWI/SNF subunits SWSN-9 and SWSN-7 are required in neurons and muscle for the development of acute functional tolerance to ethanol. Examination of the members of the SWI/SNF complex for association with a diagnosis of alcohol dependence in a human population identified allelic variation in a member of the SWI/SNF complex, suggesting that variation in the regulation of SWI/SNF targets may influence the propensity to develop abuse disorders. Together, these data strongly implicate the chromatin remodeling associated with SWI/SNF complex members in the behavioral responses to alcohol across phyla.
Kallupi, Marsida; Vendruscolo, Leandro F; Carmichael, Casey Y; George, Olivier; Koob, George F; Gilpin, Nicholas W
Electrophysiological data suggest a dual role of Y2 receptors (Y2 Rs) as autoreceptors regulating neuropeptide Y release and heteroceptors regulating gamma-aminobutyric acid release in the central amygdala (CeA). Here, we report that neither systemic (JNJ-31020028) nor intra-CeA (BIIE0246) Y2 R antagonism altered operant alcohol responding by alcohol-dependent or non-dependent rats. Conversely, BIIE0246 in the CeA reduced anxiety-like behavior in alcohol-dependent and alcohol-naïve rats. The finding that Y2 R antagonism reduces anxiety-like behavior but not alcohol drinking suggests that these two effects may occur via different functions of the Y2 R (e.g. autoreceptor versus heteroceptor function).
Lee, Jinhee; Kresina, Thomas F.; Campopiano, Melinda; Lubran, Robert; Clark, H. Westley
Substance-related and addictive disorders are chronic relapsing conditions that substantially impact public health. Effective treatments for these disorders require addressing substance use/dependence comprehensively as well as other associated comorbidities. Comprehensive addressing of substance use in a medical setting involves screening for substance use, addressing substance use directly with the patient, and formulating an appropriate intervention. For alcohol dependence and opioid dependence, pharmacotherapies are available that are safe and effective when utilized in a comprehensive treatment paradigm, such as medication assisted treatment. In primary care, substance use disorders involving alcohol, illicit opioids, and prescription opioid abuse are common among patients who seek primary care services. Primary care providers report low levels of preparedness and confidence in identifying substance-related and addictive disorders and providing appropriate care and treatment. However, new models of service delivery in primary care for individuals with substance-related and addictive disorders are being developed to promote screening, care and treatment, and relapse prevention. The education and training of primary care providers utilizing approved medications for the treatment of alcohol use disorders and opioid dependence in a primary care setting would have important public health impact and reduce the burden of alcohol abuse and opioid dependence. PMID:25629034
Wang, Jen C; Hinrichs, Anthony L; Stock, Heather; Budde, John; Allen, Rebecca; Bertelsen, Sarah; Kwon, Jennifer M; Wu, William; Dick, Danielle M; Rice, John; Jones, Kevin; Nurnberger, John I; Tischfield, Jay; Porjesz, Bernice; Edenberg, Howard J; Hesselbrock, Victor; Crowe, Ray; Schuckit, Mark; Begleiter, Henri; Reich, Theodore; Goate, Alison M; Bierut, Laura J
Several correlated phenotypes, alcohol dependence, major depressive syndrome, and an endophenotype of electrophysiological measurements, event-related oscillations (EROs), have demonstrated linkage on the long arm of chromosome 7. Recently, we reported both linkage and association between polymorphisms in the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) and EROs. In this study, we evaluated whether genetic variation in the CHRM2 gene is also a risk factor for the correlated clinical characteristics of alcoholism and depression. The CHRM2 gene contains a single coding exon and a large 5' untranslated region encoded by multiple exons that can be alternatively spliced. Families were recruited through an alcohol dependent proband, and multiplex pedigrees were selected for genetic analyses. We examined 11 single nucleotide polymorphisms (SNPs) spanning the CHRM2 gene in these families. Using the UNPHASED pedigree disequilibrium test (PDTPHASE), three SNPs (one in intron 4 and two in intron 5) showed highly significant association with alcoholism (P=0.004-0.007). Two SNPs (both in intron 4) were significantly associated with major depressive syndrome (P=0.004 and 0.017). Haplotype analyses revealed that the most common haplotype (>40% frequency), T-T-T (rs1824024-rs2061174-rs324650), was under-transmitted to affected individuals with alcohol dependence and major depressive syndrome. Different complementary haplotypes were over-transmitted in alcohol dependent and depressed individuals. These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders.
Paulus, Daniel J; Vujanovic, Anka A; Schuhmann, Bailee B; Smith, Lia J; Tran, Jana
Depression, posttraumatic stress, and alcohol use are highly prevalent among firefighters. However, no study has evaluated the interactive effects of depression and posttraumatic stress with regard to alcohol use among firefighters. The current study examined main and interactive effects of depression and posttraumatic stress in terms of alcohol dependence symptoms, positive alcohol dependence screen, and drinks per occasion. Participants included 2707 male urban firefighters. There was a main effect of posttraumatic stress in relation to all alcohol-related outcomes and a main effect of depression only for alcohol dependence symptoms. There was a significant interaction of depression and posttraumatic stress with regard to symptoms of alcohol dependence, positive screen for alcohol dependence, and number of drinks per occasion. Interactions were evident above main effects and covariates (age, presence of a spouse/partner, tenure in the fire department, history of active duty in the U.S. armed forces, and racial/ethnic minority status). Overall, heightened depression was positively associated with alcohol-related outcomes for those with lower but not higher levels of posttraumatic stress in all models. Posttraumatic stress and depression may pose unique interactive risks for alcohol dependence in urban male firefighters. Implications for clinical intervention in firefighters are discussed.
Strac, Dubravka Svob; Erjavec, Gordana Nedic; Perkovic, Matea Nikolac; Sviglin, Korona Nenadic; Borovecki, Fran; Pivac, Nela
Alcohol dependence is a common chronic disorder precipitated by the complex interaction between biological, genetic and environmental risk factors. Recent studies have demonstrated that polymorphisms of the gene encoding the GABAA receptor α2 subunit (GABRA2) are associated with alcohol dependence in different populations of European ancestry. As aggression often occurs in the context of alcohol dependence, the aim of this study was to examine the allelic and haplotypic association of GABRA2 gene with alcohol dependence and related aggressive behavior in subjects of Eastern European (Croatian) origin. Genotyping of the 3 single nucleotide polymorphisms (SNPs) across the GABRA2 gene (rs567926, rs279858 and rs9291283) was performed in patients with alcohol dependence (N=654) and healthy control subjects (N=574). Alcohol-dependent participants were additionally subdivided according to the presence/absence of aggressive behavior and type of alcohol dependence according to the Cloninger's classification. The association of rs279858 with alcohol dependence yielded nominal significance level. Haplotype analysis revealed a high degree of linkage disequilibrium (LD) for rs567926 and rs279858, but not for rs9291283 polymorphism in the GABRA2 gene. In patients with alcohol dependence, the A-C (rs567926 and rs279858) haplotype carriers were more likely to demonstrate aggressive behavior. The same haplotype (present only in 1.6% of all subjects) was significantly more often present in patients with a combination of early onset alcohol abuse and aggression, corresponding to the Cloninger's type II alcoholism subgroup. These findings support the involvement of GABRA2 gene in alcohol dependence-related aggressive behavior.
Sethi, Monica; Heyer, Jessica; Wall, Stephen; DiMaggio, Charles; Shinseki, Matthew; Slaughter, Dekeya; Frangos, Spiros G
Alcohol use is a risk factor for severe injury in pedestrians struck by motor vehicles. Our objective was to investigate alcohol use by bicyclists and its effects on riding behaviors, medical management, injury severity, and mortality within a congested urban setting. A hospital-based, observational study of injured bicyclists presenting to a Level I regional trauma center in New York City was conducted. Data were collected prospectively from 2012 to 2014 by interviewing all bicyclists presenting within 24 h of injury and supplemented with medical record review. Variables included demographic characteristics, scene-related data, Glasgow Coma Scale (GCS), computed tomography (CT) scans, and clinical outcomes. Alcohol use at the time of injury was determined by history or blood alcohol level (BAL) >0.01 g/dL. Of 689 bicyclists, 585 (84.9%) were male with a mean age of 35.2. One hundred four (15.1%) bicyclists had consumed alcohol prior to injury. Alcohol use was inversely associated with helmet use (16.5% [9.9–25.1] vs. 43.2% [39.1–47.3]). Alcohol-consuming bicyclists were more likely to fall from their bicycles (42.0% [32.2–52.3] vs. 24.2% [20.8–27.9]) and less likely to be injured by collision with a motor vehicle (52.0% [41.7–62.1] vs. 67.5% [63.5–71.3]). 80% of alcohol-consuming bicyclists underwent CT imaging at presentation compared with 51.5% of non-users. Mortality was higher among injured bicyclists who had used alcohol (2.9% [0.6–8.2] vs. 0.0% [0.0–0.6]). Adjusted multivariable analysis revealed that alcohol use was independently associated with more severe injury (Adjusted Odds Ratio 2.27, p = 0.001, 95% Confidence Interval 1.40–3.68). Within a dense urban environment, alcohol use by bicyclists was associated with more severe injury, greater hospital resource use, and higher mortality. As bicycling continues to increase in popularity internationally, it is important to heighten awareness about the risks and consequences of bicycling while
Momeni, Shima; Segerström, Lova; Roman, Erika
Alcohol use disorder (AUD) is a worldwide public health problem and a polygenetic disorder displaying substantial individual variation. This work aimed to study individual differences in behavior and its association to voluntary alcohol intake and subsequent response to naltrexone in a seamless heterogenic group of animals. Thus, by this approach the aim was to more accurately recapitulate the existing heterogeneity within the human population. Male Wistar rats from three different suppliers (Harlan Laboratories B.V., RccHan™:WI; Taconic Farms A/S, HanTac:WH; and Charles River GmbH, Crl:WI) were used to create a heterogenic group for studies of individual differences in behavior, associations to intermittent voluntary alcohol intake and subsequent response to naltrexone. The rats were tested in the open field prior to the Y-maze and then given voluntary intermittent access to alcohol or water in the home cage for 6 weeks, where after, naltrexone in three different doses or saline was administered in a Latin square design over 4 weeks and alcohol intake and preference was measured. However, supplier-dependent differences and concomitant skew subgroup formations, primarily in open field behavior and intermittent alcohol intake, resulted in a shifted focus to instead study voluntary alcohol intake and preference, and the ensuing response to naltrexone in Wistar rats from three different suppliers. The results showed that outbred Wistar rats are diverse with regard to voluntary alcohol intake and preference in a supplier-dependent manner; higher in RccHan™:WI relative to HanTac:WH and Crl:WI. The results also revealed supplier-dependent differences in the effect of naltrexone that were dose- and time-dependent; evident differences in high-drinking RccHan™:WI rats relative to HanTac:WH and Crl:WI rats. Overall these findings render RccHan™:WI rats more suitable for studies of individual differences in voluntary alcohol intake and response to naltrexone and
Momeni, Shima; Segerström, Lova; Roman, Erika
Alcohol use disorder (AUD) is a worldwide public health problem and a polygenetic disorder displaying substantial individual variation. This work aimed to study individual differences in behavior and its association to voluntary alcohol intake and subsequent response to naltrexone in a seamless heterogenic group of animals. Thus, by this approach the aim was to more accurately recapitulate the existing heterogeneity within the human population. Male Wistar rats from three different suppliers (Harlan Laboratories B.V., RccHan™:WI; Taconic Farms A/S, HanTac:WH; and Charles River GmbH, Crl:WI) were used to create a heterogenic group for studies of individual differences in behavior, associations to intermittent voluntary alcohol intake and subsequent response to naltrexone. The rats were tested in the open field prior to the Y-maze and then given voluntary intermittent access to alcohol or water in the home cage for 6 weeks, where after, naltrexone in three different doses or saline was administered in a Latin square design over 4 weeks and alcohol intake and preference was measured. However, supplier-dependent differences and concomitant skew subgroup formations, primarily in open field behavior and intermittent alcohol intake, resulted in a shifted focus to instead study voluntary alcohol intake and preference, and the ensuing response to naltrexone in Wistar rats from three different suppliers. The results showed that outbred Wistar rats are diverse with regard to voluntary alcohol intake and preference in a supplier-dependent manner; higher in RccHan™:WI relative to HanTac:WH and Crl:WI. The results also revealed supplier-dependent differences in the effect of naltrexone that were dose- and time-dependent; evident differences in high-drinking RccHan™:WI rats relative to HanTac:WH and Crl:WI rats. Overall these findings render RccHan™:WI rats more suitable for studies of individual differences in voluntary alcohol intake and response to naltrexone and
King, Serena M.; Keyes, Margaret; Malone, Stephen M.; Elkins, Irene; Legrand, Lisa N.; Iacono, William G.; McGue, Matt
Aim To examine the genetic and environmental influences of parental alcoholism on offspring disinhibited behavior. Design We compared the effect of parental alcoholism history on offspring in adoptive and non-adoptive families. In families with a history of parental alcohol dependence, we examined the effect of exposure to parental alcoholism symptoms during the lifetime of the adolescent. Setting Assessments occurred at the University of Minnesota from 1998-2004. Participants Adolescents adopted in infancy were systematically ascertained from records of three private Minnesota adoption agencies; non-adopted adolescents were ascertained from Minnesota birth records. Adolescents and their rearing parents participated in in-person assessments. Measurements For adolescents, measures included self- reports of delinquency, deviant peers, substance use, antisocial attitudes, and personality. For parents, we conducted DSM-IV clinical assessments of alcohol abuse and dependence. Findings A history of parental alcohol dependence was associated with higher levels of disinhibition only when adolescents were biologically related to their rearing parents. Within families with a history of parental alcoholism, exposure to parental alcohol misuse during the lifetime of the adolescent was associated with increased odds of using alcohol in adopted adolescents only. Conclusions These findings suggest that the association between a history of parental alcohol dependence and adolescent offspring behavioral disinhibition is largely attributable to genetic rather than environmental transmission. We also obtained some evidence for parental alcohol misuse as a shared environmental risk factor in adoptive families. PMID:19215604
Cardenas, VA; Durazzo, TC; Gazdzinski, S; Mon, A; Studholme, C; Meyerhoff, DJ
Background We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers. Methods Individuals in alcohol dependence treatment (N=75) underwent magnetic resonance imaging approximately 6 ± 4 days after their last alcoholic drink, and 40 age-matched non-smoking light drinkers were studied as controls. At follow-up 7.8 ± 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and light drinkers. Results Compared to light drinkers, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex, and bilaterally in the thalamus and adjacent subcortical white matter (WM), and had larger volume in the left lateral orbitofrontal region. Compared to light drinkers, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared to future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities. Conclusion At entry into alcohol dependence treatment, the brain structure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry may confer greater risk for resumption of hazardous drinking after treatment and may contribute to the definition of a neurobiological relapse risk profile in alcohol dependence. PMID:21601177
Samek, Diana R; Keyes, Margaret A; Hicks, Brian M; Bailey, Jennifer; McGue, Matt; Iacono, William G
Objective: This study builds on previous work delineating a hierarchical model of family environmental risk in relation to a hierarchical model of externalizing disorders (EXTs) by evaluating for gene–environment interplay in these relationships. The associations between parent–child relationship quality (conflict, bonding, and management) and substance-specific adolescent family environments (parental/sibling tobacco/alcohol use) in relation to young adult EXTs (age ∼22 years nicotine, alcohol, and other drug dependence; antisocial and risky sexual behavior) were evaluated. Method: The sample included 533 adopted offspring and 323 biological offspring. Because adopted youth do not share genes with their parents, a significant association between parent–child relationship quality and EXTs would provide evidence against passive gene–environment correlation (rGE). Significant associations between parental tobacco/alcohol use in relation to offspring nicotine/alcohol dependence in the adopted offspring support common environmental influence. Significant associations detected for the biological offspring only suggest common genetic influence. Results: For both adoptive and biological offspring, there was a significant association between parent–child relationship quality and EXTs. Parental tobacco/alcohol use was unrelated to EXTs. Sibling tobacco/alcohol use was related to EXTs, but only for the biological siblings. Parental tobacco use was associated with the residual variance in nicotine dependence in adopted offspring. Conclusions: Findings replicate a long-term influence of adolescent parent–child relationship quality on adult EXTs. Findings extend previous research by providing evidence against passive rGE in this association. The association between parental tobacco use and adult nicotine dependence appears to be environmentally mediated, but caution is warranted as we found this relationship only for adopted youth. PMID:24988261
Graham, Kathryn; Bernards, Sharon; Wilsnack, Sharon C; Gmel, Gerhard
This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13 countries as part of the GENACIS collaboration. Respondents described the most physically aggressive act done to them by a partner in the past 2 years, rated the severity of aggression on a scale of 1 to 10, and reported whether either partner had been drinking when the incident occurred. Severity ratings were significantly higher for incidents in which one or both partners had been drinking compared to incidents in which neither partner had been drinking. The relationship did not differ significantly for men and women or by country. We conclude that alcohol consumption may serve to potentiate violence when it occurs, and this pattern holds across a diverse set of cultures. Further research is needed that focuses explicitly on the nature of alcohol's contribution to intimate partner aggression. Prevention needs to address the possibility of enhanced dangers of intimate partner violence when the partners have been drinking and eliminate any systemic factors that permit alcohol to be used as an excuse. Clinical services for perpetrators and victims of partner violence need to address the role of drinking practices, including the dynamics and process of aggressive incidents that occur when one or both partners have been drinking.
Nelson, Elliot C.; Agrawal, Arpana; Pergadia, Michele L.; Wang, Jen C.; Whitfield, John B.; Saccone, F. Scott; Kern, Jason; Grant, Julia D.; Schrage, Andrew J.; Rice, John P.; Montgomery, Grant W.; Heath, Andrew C.; Goate, Alison M.; Martin, Nicholas G.; Madden, Pamela A.F.
Animal research supports a central role for corticotropin releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a CRHR1 polymorphism, and negative events. CRHR1 and at least 4 other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (N=1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from 4 indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA (p<0.017). A similar G × E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95%CI 0.20 – 0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence. PMID:19878140
McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J Michael; Sullivan, Sean D; Spackman, D Eldon; Neumann, Peter J; Cohen, Joshua; Stern, Yaakov
This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression.
Rose, Gail L.; Skelly, Joan M.; Badger, Gary J.; Ferraro, Tonya A.; Helzer, John E.
Background Relapse rates following cognitive behavioral therapy (CBT) for alcohol dependence are high. Continuing care programs can prolong therapeutic effects but are underutilized. Thus there is need to explore options having greater accessibility. Methods This randomized controlled trial tested the efficacy of a novel, fully automated continuing care program, Alcohol Therapeutic Interactive Voice Response (ATIVR). ATIVR enables daily monitoring of alcohol consumption and associated variables, offers targeted feedback, and facilitates use of coping skills. Upon completing 12 weeks of group CBT for alcohol dependence, participants were randomly assigned to either four months of ATIVR (n=81) or usual care (n=77). Drinking behavior was assessed pre- and post-CBT, then at 2 weeks, 2 months, 4 months, and 12 months post-randomization. Results Drinking days per week increased over time for the control group but not the intervention group. There were no significant differences between groups on the other alcohol-related outcome measures. Comparisons on the subset of participants abstinent at the end of CBT (n=72) showed higher rates of continuous abstinence in the experimental group. Effect sizes for the other outcome variables were moderate but not significant in this subgroup. Conclusions For continuing care, ATIVR shows some promise as a tool that may help clients maintain gains achieved during outpatient treatment. However, ATIVR may not be adequate for clients who have not achieved treatment goals at the time of discharge. PMID:25452069
Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth
Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented.
Browne, Kendall C; Wray, Tyler B; Stappenbeck, Cynthia A; Krenek, Marketa; Simpson, Tracy L
Research has demonstrated the positive association between alcohol craving and alcohol use and has identified craving as a central component of alcohol use disorders (AUD). Despite potential clinical implications, few studies have examined the relationship between craving and alcohol use in individuals with AUD and common psychiatric comorbidities or explored possible moderators of the craving-alcohol use relationship. The current study used daily monitoring data to: 1) replicate previous findings detecting a positive relationship between craving and alcohol use in individuals with AUD and co-occurring posttraumatic stress disorder (PTSD) and 2) extend these findings by examining the influence of initial change motivation on the craving-use relationship and within-day associations among craving, efforts to control craving, and alcohol consumption. Participants were 84 individuals with alcohol dependence and PTSD enrolled in an intervention study. Generalized estimating equations using pre-treatment baseline daily data revealed significant main effects for craving, craving control, and motivation to change alcohol use. Daily craving was positively related to alcohol use. Greater change motivation and craving control (i.e., efforts to resist craving, avoidance of thoughts and feelings related to craving) were negatively related to alcohol use. A significant interaction was detected between baseline change motivation and daily craving indicating that the association between craving and alcohol use was significantly stronger for those with low baseline change motivation. A significant interaction was also detected between craving control and daily craving, suggesting that participants were more likely to consume alcohol when experiencing high levels of craving if they reported low levels of craving control. Findings bolster the idea that efforts to prevent or ameliorate craving are critical to treatment success for individuals with AUD and PTSD who are seeking to
Cano, Miguel Ángel
Individuals, including Hispanics, tend to drink most heavily during emerging adulthood (ages 18-25 years old). Research has suggested that intercultural stressors (e.g., ethnic discrimination) may increase levels of alcohol use among Hispanics. However, the relationship between intracultural stressors (e.g., accusations of assimilation-when Hispanics accuse a member of their heritage group of acculturating to U.S. culture) and alcohol use has been examined to a lesser extent. Accordingly, the present study aimed to (a) examine the association between family accusations of assimilation and alcohol use severity; and (b) examine if acculturation domains, enculturation domains, and gender moderated that association. A hierarchical multiple regression and moderation analyses were conducted on a cross-sectional sample of 181 Hispanic emerging adults. Results indicated that higher family accusations of assimilation were associated with higher levels of alcohol use severity (β = .18, p < .05), and all variables entered in the model accounted for ΔR2 = 15.1% of the variance of alcohol use severity. A moderation analysis indicated that higher family accusations of assimilation were associated with higher alcohol use severity among men, but not women. Of the four acculturation/enculturation domains, none had a moderation effect. However, there was a statistically significant three-way interaction among family accusations of assimilation, gender, and affective enculturation. This three-way interaction suggests that among men, higher family accusations of assimilation were associated with higher alcohol use severity at lower levels of affective enculturation. This study addresses a literature gap on intracultural stressors and substance use among Hispanics, and discusses recommendations for future research. (PsycINFO Database Record
Seo, Sambu; Mohr, Johannes; Beck, Anne; Wüstenberg, Torsten; Heinz, Andreas; Obermayer, Klaus
In alcohol dependence, individual prediction of treatment outcome based on neuroimaging endophenotypes can help to tailor individual therapeutic offers to patients depending on their relapse risk. We built a prediction model for prospective relapse of alcohol-dependent patients that combines structural and functional brain images derived from an experiment in which 46 subjects were exposed to alcohol-related cues. The patient group had been subdivided post hoc regarding relapse behavior defined as a consumption of more than 60 g alcohol for male or more than 40 g alcohol for female patients on one occasion during the 3-month assessment period (16 abstainers and 30 relapsers). Naïve Bayes, support vector machines and learning vector quantization were used to infer prediction models for relapse based on the mean and maximum values of gray matter volume and brain responses on alcohol-related cues within a priori defined regions of interest. Model performance was estimated by leave-one-out cross-validation. Learning vector quantization yielded the model with the highest balanced accuracy (79.4 percent, p < 0.0001; 90 percent sensitivity, 68.8 percent specificity). The most informative individual predictors were functional brain activation features in the right and left ventral tegmental areas and the right ventral striatum, as well as gray matter volume features in left orbitofrontal cortex and right medial prefrontal cortex. In contrast, the best pure clinical model reached only chance-level accuracy (61.3 percent). Our results indicate that an individual prediction of future relapse from imaging measurement outperforms prediction from clinical measurements. The approach may help to target specific interventions at different risk groups.
Park, Aesoon; Sher, Kenneth J.; Todorov, Alexandre A.; Heath, Andrew C.
The manifestation of alcohol dependence at different developmental stages may be associated with different genetic and environmental factors. Taking a developmental approach, the current study characterized interaction between the dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism and developmentally specific environmental factors (childhood adversity, college/Greek involvement, and delayed adult role transition) on alcohol dependence during emerging and young adulthood. Prospective data were obtained from a cohort of 234 Caucasian individuals (56% female) followed up at ages 18 through 34. A longitudinal hierarchical factor model was estimated to model a trait-like persistent alcohol dependence factor throughout emerging and young adulthood and two residual state-like alcohol dependence factors limited to emerging adulthood and young adulthood, respectively. To account for those alcohol dependence factors, three two-way interaction effects between the DRD4 VNTR polymorphism and the three developmentally specific environment factors were modeled. Carriers of the DRD4 long allele showed greater susceptibility to environmental effects; they showed more persistent alcohol dependence symptoms as childhood adversity increased and more alcohol dependence symptoms limited to emerging adulthood as college/Greek involvement increased. Alcohol dependence among non-carriers of the long allele, however, did not differ as a function of those environments. Although replication is necessary, these findings highlight the importance of repeated phenotypic assessments across development and modeling both distal and proximal environments and their interaction with genetic susceptibility at specific developmental stages. PMID:21381802
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
Brickham, Dana M.
People with alcohol abuse/dependence disabilities are often faced with a complex recovery process due to the exacerbating and chronic aspects of their condition. Vocational rehabilitation for people with alcohol abuse/dependence can help individuals access and maintain employment, and through employment can enhance physical and psychological…
... services for veterans with alcohol or drug dependence or abuse disabilities. 17.82 Section 17.82 Pensions... Agencies § 17.82 Contracts for outpatient services for veterans with alcohol or drug dependence or abuse disabilities. (a) Contracts for treatment services authorized under § 17.80 may be awarded in accordance...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Limitations on payment for alcohol and drug dependence or abuse treatment and rehabilitation. 17.83 Section 17.83 Pensions... Agencies § 17.83 Limitations on payment for alcohol and drug dependence or abuse treatment...
Cornelius, Jack R.; Douaihy, Antoine B.; Clark, Duncan B.; Chung, Tammy; Wood, D. Scott; Daley, Dennis
Objective This was a first pilot study evaluating the acute phase (8-week) efficacy of the antidepressant medication mirtazapine for the treatment of depressive symptoms and drinking of subjects with comorbid major depressive disorder and alcohol dependence (MDD/AD). We hypothesized that mirtazapine would demonstrate within-group efficacy for the treatment of both depressive symptoms and drinking in these subjects. Methods We conducted a first open label study of the second generation antidepressant mirtazapine in 12 adult outpatient subjects with comorbid major depressive disorder/alcohol dependence. The pharmacological profile of that medication is unique among antidepressants, unrelated to tricyclics or selective serotonin reuptake inhibitors. Results Mirtazapine was well tolerated in this treatment population. Self-reported depressive symptoms decreased from 31.8 to 8.3 on the Beck Depression Inventory, a 74.0% decrease (p<0.001), and drinking decreased from 33.9 to 13.3 drinks per week, a 60.8% decrease (p<0.05). None of the subjects were employed full-time at baseline, but 9 of the 12 (75%) were employed full-time at end-of-study. Conclusions These preliminary findings suggest efficacy for mirtazapine for treating both the depressive symptoms and excessive alcohol use of comorbid major depressive disorder and alcohol dependence. Double-blind studies are warranted to further clarify the efficacy of mirtazapine in this population. PMID:23230395
Ipek, Okan Ufuk; Yavuz, Kaasim Fatih; Ulusoy, Sevinc; Sahin, Oktay; Kurt, Erhan
Background: Both alcohol and other substances are utilized for emotional and cognitive regulation. Objectives: The purpose of the present study was to compare metacognitive styles and distress intolerance in patients with alcohol and other substance dependence. Patients and Methods: According to DSM-IV TR criteria, 45 patients with alcohol dependence (AD), 44 patients with substance dependence (SD), and 43 volunteers without AD or SD (control group) were enrolled. Socio-demographic information form, Distress Tolerance Scale (DTS), and metacognitive questionaire-30 (MCQ-30) were used to evaluate the participants. Results: Patients with AD had significantly lower “tolerance” subscale and total DTS scores than those with SD and control group (P = 0.008 for SD sample and P = 0.004 for control group). Patients with SD had significantly higher scores in “appraisal” subscale DTS than control group (P = 0.005). Patients of both AD and SD groups had significantly higher scores in “positive beliefs” subscale of MCQ-30 than control group (P = 0.012 for AD group and P = 0. 001 for SD group). There was no significant difference between AD and SD groups in any MCQ-30 subscale and total scores (P = 0.440). Conclusions: Metacognitive regulation strategies are more considerable prediction than emotional regulation strategies in SD group than in AD group. Individuals with AD use alcohol as a means of both cognitive and emotional regulation strategy. PMID:26495260
Gilpin, Nicholas W; Misra, Kaushik; Koob, George F
The anxiolytic effects of neuropeptide Y (NPY) are mediated in part by the central nucleus of the amygdala (CeA), a brain region involved in the regulation of alcohol-drinking behaviors. Centrally administered NPY suppresses alcohol drinking in subpopulations of rats vulnerable to the development of high alcohol-drinking behavior. The purpose of the current study was to determine the role of NPY in the CeA on elevated alcohol drinking produced by alcohol dependence. Adult male Wistar rats were trained to respond for 10% w/v alcohol in an operant situation with the use of a supersaccharin fading procedure. Following stabilization of responding, rats were divided into two groups matched for intake and given daily access to either alcohol-containing (9.2% v/v) liquid diet or an isocaloric control diet. Following extended access to the diet and reliable separation of operant responding between dependent and non-dependent rats during 6-h withdrawal tests, all rats were implanted bilaterally with cannulae aimed at the CeA. Rats were then infused with 4 NPY doses (0.0, 0.25, 0.5, 1.0 microg/0.5 microl aCSF) in a within-subjects Latin-square design during acute withdrawal and tested for operant alcohol responding 30 min later. Alcohol-dependent rats exhibited higher operant alcohol responding than non-dependent rats when infused with vehicle, but responding was similar in the two groups following infusion of all doses of NPY. These results indicate that NPY abolishes dependence-induced elevations in alcohol drinking and implicate the recruitment of limbic NPY systems in the motivational drive to consume alcohol following the transition to dependence.
... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria ... change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...
Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)
Danielsson, O; Jörnvall, H
Analysis of the activity and structure of lower vertebrate alcohol dehydrogenases reveals that relationships between the classical liver and yeast enzymes need not be continuous. Both the ethanol activity of class I-type alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 220.127.116.11) and the glutathione-dependent formaldehyde activity of the class III-type enzyme [formaldehyde:NAD+ oxidoreductase (glutathione-formylating), EC 18.104.22.168] are present in liver down to at least the stage of bony fishes (cod liver: ethanol activity, 3.4 units/mg of protein in one enzyme; formaldehyde activity, 4.5 units/mg in the major form of another enzyme). Structural analysis of the latter protein reveals it to be a typical class III enzyme, with limited variation from the mammalian form and therefore with stable activity and structure throughout much of the vertebrate lineage. In contrast, the classical alcohol dehydrogenase (the class I enzyme) appears to be the emerging form, first in activity and later also in structure. The class I activity is present already in the piscine line, whereas the overall structural-type enzyme is not observed until amphibians and still more recent vertebrates. Consequently, the class I/III duplicatory origin appears to have arisen from a functional class III form, not a class I form. Therefore, ethanol dehydrogenases from organisms existing before this duplication have origins separate from those leading to the "classical" liver alcohol dehydrogenases. The latter now often occur in isozyme forms from further gene duplications and have a high rate of evolutionary change. The pattern is, however, not simple and we presently find in cod the first evidence for isozymes also within a class III alcohol dehydrogenase. Overall, the results indicate that both of these classes of vertebrate alcohol dehydrogenase are important and suggest a protective metabolic function for the whole enzyme system. Images PMID:1409630
Casey, Carol A; McVicker, Benita L; Donohue, Terrence M; McFarland, Melinda A; Wiegert, Robert L; Nanji, Amin A
It has been demonstrated that the oral administration of ethanol (Lieber-DeCarli liquid diet) to rats results in a decreased expression and content of the asialoglycoprotein receptor (ASGP-R) in the resultant fatty liver. In the present study, we wanted to determine whether the extent of impaired receptor content was correlated with the severity of liver pathology by using the intragastric feeding model. When ASGP-R protein and mRNA levels were measured in animals infused with ethanol or dextrose in the presence of fish oil (FO) or medium-chain triglyceride as the source of fat, more significant impairments to the ASGP-R were observed in the FO-ethanol group compared with the medium-chain triglyceride-ethanol group. Furthermore, only the FO-ethanol group showed pathological liver changes. These results demonstrate that a correlation exists between the progression of alcohol-associated liver injury, as defined by the severity of liver pathology, and an ethanol-induced decline in ASGP-R content.
Crescentini, Cristiano; Matiz, Alessio; Fabbro, Franco
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.
Haber, Jon Randolph; Grant, Julia D.; Sartor, Carolyn E.; Koenig, Laura B.; Heath, Andrew; Jacob, Theodore
The contention that Religion/Spirituality (R/S) influences the development of alcohol dependence (AD) is increasingly supported, but risk factors have not been adequately examined together with protective R/S factors so as to determine the nature and relative strength of these domains at different stages in the development of alcoholism. Secondary data analysis of a sample of 4,002 young adult female twins used conditional Cox proportional hazards survival models to examine three distinct stages in the development of alcoholism: years to initiation of drinking, years from first drink to at-risk drinking, and years from at-risk drinking to AD. Risk and protective factors from models of alcoholism etiology and studies of R/S dimensionality were modeled simultaneously as predictors of each discrete stage and compared. Findings demonstrated that both risk factors and R/S variables influenced initiation of alcohol use; only R/S variables influenced subsequent progression to at-risk drinking; and risk factors primarily influenced further progression to AD. Protective factors (R/S variables being an exemplar) appeared to be critical determinants of intermediate-stage progression, thus suggesting that R/S factors and other psychosocial interventions might be particularly effective in delaying progression toward AD at this stage. In contrast, after the onset of at-risk drinking, the influence of (genetically based) risk factors appeared to accelerate AD regardless of most other influences. Thus, the timing of psychosocial interventions appears critical to their potency and impact. PMID:23528196
Haber, Jon Randolph; Grant, Julia D; Sartor, Carolyn E; Koenig, Laura B; Heath, Andrew; Jacob, Theodore
The contention that Religion/Spirituality (R/S) influences the development of alcohol dependence (AD) is increasingly supported, but risk factors have not been adequately examined together with protective R/S factors so as to determine the nature and relative strength of these domains at different stages in the development of alcoholism. Secondary data analysis of a sample of 4,002 young adult female twins used conditional Cox proportional hazards survival models to examine three distinct stages in the development of alcoholism: years to initiation of drinking, years from first drink to at-risk drinking, and years from at-risk drinking to AD. Risk and protective factors from models of alcoholism etiology and studies of R/S dimensionality were modeled simultaneously as predictors of each discrete stage and compared. Findings demonstrated that both risk factors and R/S variables influenced initiation of alcohol use; only R/S variables influenced subsequent progression to at-risk drinking; and risk factors primarily influenced further progression to AD. Protective factors (R/S variables being an exemplar) appeared to be critical determinants of intermediate-stage progression, thus suggesting that R/S factors and other psychosocial interventions might be particularly effective in delaying progression toward AD at this stage. In contrast, after the onset of at-risk drinking, the influence of (genetically based) risk factors appeared to accelerate AD regardless of most other influences. Thus, the timing of psychosocial interventions appears critical to their potency and impact.
Lee, Jong-Sun; Mathews, Andrew; Shergill, Sukhi; Yiend, Jenny
The present study investigated the hypothesis that the magnitude of negative interpretation bias displayed by those with depression is related to the degree of depression they experience. Seventy one depressed participants (scoring 14 and above on the Beck Depression Inventory II) completed tasks spanning three domains of possible negative interpretations: semantic ambiguity; nonverbal ambiguity and situational ambiguity. Regression analyses revealed that just under half of the variance in depressive symptom severity was explained by the combination of negative interpretation bias tasks, with the strongest predictor of depressive symptom severity being negative interpretation of semantic ambiguity when reading ambiguous text descriptions. Subsidiary group analyses confirmed that severely depressed individuals interpreted emotionally ambiguous information in a more negative way than did their mildly or moderately depressed counterparts. These findings indicate that the degree of negative interpretive bias is closely related to depression severity and that bias manifests especially strongly at the most severe levels of depression. Our findings may help us to refine cognitive theories of depression and be helpful in guiding therapy.
Müller, Astrid; Loeber, Sabine; Söchtig, Johanna; Te Wildt, Bert; De Zwaan, Martina
Background and Aims Exercise dependence (EXD) is considered a behavioral addiction that is often associated with eating disorders. To date, only few studies examined the potential overlap between EXD and other addictive behaviors. Therefore, the present study aimed at investigating the relationship of EXD with pathological buying, pathological video gaming (offline and online), hypersexual behavior, and alcohol use disorder in a sample of clients of fitness centers. Methods The following questionnaires were answered by 128 individuals (age M = 26.5, SD = 6.7 years; 71.7% men, 74.2% university students): Exercise Dependence Scale, Eating Disorder Examination-Questionnaire, Compulsive Buying Scale, Pathological Computer-Gaming Scale, Hypersexual Behavior Inventory, and Alcohol Use Disorders Identification Test (AUDIT). Results 7.8% of the sample were at-risk for EXD, 10.9% reported eating disorder pathology, 2.3% pathological buying, 3.1% hypersexual behavior, and none of the participants suffered from pathological video gaming. The criteria for severe alcohol disorder pathology (AUDIT ≥ 16) were fulfilled by 10.2%. With regard to continuous symptom scores, EXD symptoms were positively correlated with both eating disorder pathology and pathological buying but not with pathological video gaming, hypersexuality or alcohol use disorder. It is noteworthy that more symptoms of pathological buying corresponded with more symptoms of hypersexual behavior. The correlation pattern did not differ by gender. Discussion The co-occurrence of EXD, pathological buying and hypersexual behavior on a subclinical level or in the early stage of the disorders should be taken into account when assessing and treating patients. More research is warranted in order to investigate possible interactions between these conditions. PMID:26690622
Durazzo, Timothy C.; Mon, Anderson; Pennington, David; Abé, Christoph; Gazdzinski, Stefan; Meyerhoff, Dieter J.
Chronic alcohol use disorders (AUD) have been shown to interact with normal age-related volume loss to exacerbate brain atrophy with increasing age. However, chronic cigarette smoking, a highly comorbid condition in AUD, and its influence on age-related brain atrophy has not been evaluated. We performed 1.5T quantitative MRI in non-smoking controls (nsCON; n=54), smoking light drinking controls (sCON, n=34), and 1-week-abstinent, treatment-seeking non-smoking alcohol dependent individuals (nsALC, n=35) and smoking ALC (sALC, n=43), to evaluate the independent and interactive effects of alcohol dependence and chronic smoking on regional cortical and subcortical brain volumes, emphasizing the brain reward/executive oversight system (BREOS),. nsCON and sALC showed greater age-related volume losses than nsALC in the dorsal prefrontal cortex (DPFC), total cortical BREOS, superior parietal lobule and putamen. nsALC and sALC demonstrated smaller volumes than nsCON in most cortical ROIs. sCON had smaller volumes than nsCON in the DPFC, insula, inferior parietal lobule, temporal pole/parahippocampal region and all global cortical measures. nsALC and sALC had smaller volumes than sCON in the DPFC, superior temporal gyrus, inferior and superior parietal lobules, precuneus and all global cortical measures. Volume differences between nsALC and sALC were observed only in the putamen. Alcohol consumption measures were not related to volumes in any ROI for ALC; smoking severity measures were related to corpus callosum volume in sCON and sALC. The findings indicate that consideration of smoking status is necessary for a better understanding of the factors contributing to regional brain atrophy in AUD. PMID:22943795
Joos, Leen; Goudriaan, Anna E; Schmaal, Lianne; Fransen, Erik; van den Brink, Wim; Sabbe, Bernard G C; Dom, Geert
Poor impulse control plays an important role in the development, course and relapse of substance use disorders. Therefore, improving impulse control may represent a promising approach in the treatment of alcohol dependence. This study aimed to test the effect of modafinil on impulse control and alcohol use in alcohol dependent patients (ADP) in a randomized, double-blind, placebo-controlled trial. Eighty-three abstinent ADP were randomized to 10 weeks modafinil (300 mg/d) or placebo. Alcohol use was quantified using the timeline follow-back method and was assessed until 6 months after treatment discontinuation. Impulsivity was assessed using self-report questionnaires (Barratt Impulsiveness Scale; State Impulsivity questionnaire) and neurocognitive tasks (Stop Signal Task; Delay Discounting Task) administered before, during and after treatment. Modafinil significantly improved self-report measures of state impulsivity, but had no effect on percentage of abstinent days or percentage of heavy drinking days, nor on the behavioral measures of impulsivity. However, subgroup analysis revealed that modafinil prolonged the time to relapse (p=.022) and tended to increase the percentage of abstinent days (p=.066) in ADP with poor response inhibition at baseline, whereas modafinil increased the percentage of heavy drinking days (p=.003) and reduced the percentage of abstinent days (p=.002) in patients with better baseline response inhibition. Overall results do not favor the use of modafinil in order to reduce relapse or relapse severity in ADP, and caution is required in prescribing modafinil to a non-selected sample of ADP. Further research on the effect of modafinil in ADP with poor baseline response inhibition is warranted.
Ghosh, Abhishek; Malhotra, Savita; Basu, Debasish
Background & objectives: The subtyping of alcohol dependence (AD) into early-onset (EO) and late-onset (LO) subgroups has been shown to have clinical and biological validity. As externalizing disorders (EDs) predate AD, the link of ED with age of onset of alcohol dependence needs to be investigated. The aim of this study was to examine the relationship of EDs such as disruptive behaviour disorder (DBD) and attention deficit hyperactivity disorder (ADHD) with age at onset of AD in a sample of male subjects. Methods: One hundred consecutive male subjects with AD presenting to the De-Addiction Services and an equal number of biologically unrelated non-substance-dependent control subjects were included in the study. The AD subjects were divided into EO (age of onset of AD ≤25 yr; n = 21) and LO (age of onset of AD >25 yr; n = 79). Subjects were examined for evidence of DBD and ADHD in childhood, and current ADHD using structured instruments such as Semi-Structured Assessment for the Genetic of Alcoholism-IV (SSAGA-IV) and Kiddie – SADS – Present and Lifetime Version (K-SADS-PL). The odds ratio of association of EDs with EO and LO AD was calculated by comparing these subgroups with the biologically unrelated control group. Later, both the subgroups of alcohol dependence were compared for the presence of EDs. Results: All EDs (DBDs/childhood or adult ADHD) were more common in AD individuals as compared to the controls. However, when AD subgroups were compared with controls, the association of DBDs and ADHD reached a significant level only in the EO subgroup. A comparison of EO and LO AD showed that more EO individuals had history of both childhood disruptive disorder and ADHD compared to LO subgroup. Adult ADHD was also over-represented in EO subgroup. Interpretation & conclusions: Our study showed more EDs in alcohol dependent individuals compared to controls. Further, the association observed between EDs and EO alcohol dependence points towards a developmental
Kose, Samet; Steinberg, Joel L; Moeller, F Gerard; Gowin, Joshua L; Zuniga, Edward; Kamdar, Zahra N; Schmitz, Joy M; Lane, Scott D
Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM-IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity.
Kose, Samet; Steinberg, Joel L.; Moeller, F. Gerard; Gowin, Joshua L.; Zuniga, Edward; Kamdar, Zahra N.; Schmitz, Joy M.; Lane, Scott D.
Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM–IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity. PMID:25664566
Gilburt, Helen; Burns, Tom; Copello, Alex; Crawford, Michael; Day, Ed; Deluca, Paolo; Godfrey, Christine; Parrott, Steve; Rose, Abigail; Sinclair, Julia; Coulton, Simon
Abstract Aims A pilot randomized controlled trial (RCT) to assess the feasibility and potential efficacy of assertive community treatment (ACT) in adults with alcohol dependence. Methods Single blind, individually randomized, pilot RCT of 12 months of ACT plus treatment as usual (TAU) versus TAU alone in adults (age 18+ years) with alcohol dependence and a history of previous unsuccessful alcohol treatment attending specialist community alcohol treatment services. ACT aimed to actively engage participants for 12 months with assertive, regular, minimum weekly contact. ACT was combined with TAU. TAU comprised access to the full range of services provided by the community teams. Primary outcome is mean drinks per drinking day and percent days abstinent at 12 months follow up. Analysis of covariance was conducted using 80% confidence intervals, appropriate in the context of a pilot trial. Results A total of 94 participants were randomized, 45 in ACT and 49 in TAU. Follow-up was achieved with 98 and 88%, respectively at 12 months. Those in ACT had better treatment engagement, and were more often seen in their homes or local community than TAU participants. At 12 months the ACT group had more problems related to drinking and lower quality of life than TAU but no differences in drinking measures. The ACT group had a higher percentage of days abstinent but lower quality of life at 6 months. The ACT group had less unplanned healthcare use than TAU. Conclusions An trial of ACT was feasible to implement in an alcohol dependent treatment population. Trial registration ISRCTN22775534 PMID:27940571
Nagy, József; Kolok, Sándor; Boros, András; Dezső, Péter
Long-term alcohol exposure gives rise to development of physical dependence on alcohol in consequence of changes in certain neurotransmitter functions. Accumulating evidence suggests that the glutamatergic neurotransmitter system, especially the N-methyl-D-aspartate (NMDA) type of glutamate receptors is a particularly important site of ethanol’s action, since ethanol is a potent inhibitor of the NMDA receptors (NMDARs) and prolonged ethanol exposition leads to a compensatory “upregulation” of NMDAR mediated functions supposedly contributing to the occurrence of ethanol tolerance, dependence as well as the acute and delayed signs of ethanol withdrawal. Recently, expression of different types of NMDAR subunits was found altered after long-term ethanol exposure. Especially, the expression of the NR2B and certain splice variant forms of the NR1 subunits were increased in primary neuronal cultures treated intermittently with ethanol. Since NMDA ion channels with such an altered subunit composition have increased permeability for calcium ions, increased agonist sensitivity, and relatively slow closing kinetics, the abovementioned alterations may underlie the enhanced NMDAR activation observed after long-term ethanol exposure. In accordance with these changes, the inhibitory potential of NR2B subunit-selective NMDAR antagonists is also increased, demonstrating excellent potency against alcohol withdrawal-induced in vitro cytotoxicity. Although in vivo data are few with these compounds, according to the effectiveness of the classic NMDAR antagonists in attenuation, not only the physical symptoms, but also some affective and motivational components of alcohol withdrawal, novel NR2B subunit selective NMDAR antagonists may offer a preferable alternative in the pharmacotherapy of alcohol dependence. PMID:18369402
Hussong, Andrea M.; Huang, Wenjing; Curran, Patrick J.; Chassin, Laurie; Zucker, Robert A.
Although previous studies show that children of alcoholic parents have higher rates of externalizing symptoms compared to their peers, it remains unclear whether the timing of children's externalizing symptoms is linked to that of their parent's alcohol-related symptoms. Using a multilevel modeling approach, we tested whether children aged 2…
Smith, Sandi W.; LaPlante, Carolyn; Wibert, Wilma Novales; Mayer, Alex; Atkin, Charles K.; Klein, Katherine; Glazer, Edward; Martell, Dennis
High-risk alcohol consumption is a significant problem on college campuses that many students see as a rite of passage in their development into adulthood. Developing effective prevention campaigns designed to lessen or avert the risks associated with alcohol consumption entails understanding how students perceive harmful consequences as well as…
Mancha, Brent E.; Rojas, Vanessa C.; Latimer, William W.
This study examined the association between alcohol use problem severity, defined by number of DSM-IV alcohol Abuse and Dependence symptoms and frequency of alcohol use, and problem behavior engagement among Mexican students. A confidential survey was administered to 1229 students in grades 7–12 at two schools in a northern border city in Mexico. Youths were categorized into five groups based on their alcohol use frequency and symptoms of DSM-IV alcohol Abuse and Dependence, specifically: no lifetime alcohol use, lifetime alcohol use but none in the past year, past year alcohol use, one or two alcohol Abuse or Dependence symptoms, and three or more alcohol Abuse or Dependence symptoms. The association between five levels of alcohol use problem severity and three problem behaviors, lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble, was examined using chi-square or Fisher’s exact tests. Several alcohol use problem severity categories were significantly different with respect to rates of lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble. Higher alcohol use problem severity was associated with greater endorsement of problem behaviors. Knowing about variations in adolescent alcohol use and alcohol problems may be instrumental in determining if youths are also engaging in a range of other risk behaviors. Considering varying levels of alcohol use and alcohol problems is important for effective targeted prevention and treatment interventions. PMID:22840814
Blanco, Carlos; Xu, Yang; Brady, Kathleen; Pérez-Fuentes, Gabriela; Okuda, Mayumi; Wang, Shuai
Background Despite the high rates of comorbidity of post-traumatic stress disorder (PTSD) and alcohol dependence (AD) in clinical and epidemiological samples, little is known about the prevalence, clinical presentation, course, risk factors and patterns of treatment-seeking of co-occurring PTSD-AD among the general population. Methods The sample included respondents of the Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Weighted means, frequencies and odds ratios (ORs) of sociodemographic correlates, prevalence of psychiatric disorders and rates of treatment-seeking were computed. Results: In the general population, the lifetime prevalence of PTSD only, AD only and PTSD-AD was 4.83%, 13.66% and 1.59%, respectively. Individuals with comorbid PTSD-AD were more likely than those with PTSD or AD only to have suffered childhood adversities and had higher rates of Axis I and II disorders and suicide attempts. They also met more PTSD diagnostic criteria, had earlier onset of PTSD and were more likely to use drugs and alcohol to relieve their PTSD symptoms than those with PTSD only; they also met more AD diagnostic criteria than those with AD only and had greater disability. Individuals with PTSD-AD had higher rates of treatment seeking for AD than those with AD only, but similar rates than those with PTSD only. Conclusion PTSD-AD is associated with high levels of severity across a broad range of domains even compared with individuals with PTSD or AD only, yet treatment-seeking rates are very low. There is a need to improve treatment access and outcomes for individuals with PTSD-AD. PMID:23702490
Wietschorke, Katharina; Lippold, Julian; Jacob, Christian; Polak, Thomas; Herrmann, Martin J
Alcohol craving has been shown to be an important factor for relapses in alcohol-dependent patients. Furthermore, brain activity in reward-related areas in response to alcohol-related cues is positively related to the amount of post-relapse alcohol consumption. On the other hand, it has been shown that cue-exposure based extinction training (CET) leads to larger decrease of striatal and left dorsolateral prefrontal cortex (dLPFC) cue-induced activation compared to standard clinical day-care treatment, but the effect sizes are relatively small. The question of this study was, whether it is possible to change cue-reactivity and subjective craving by applying bilateral prefrontal transcranial direct current stimulation (tDCS). We stimulated 30 detoxified alcohol-dependent patients (50 % with a sham and 50 % with left cathodal/right anodal stimulation) and presented emotional as well as alcohol-related pictures. We measured the emotional startle modulation and found significantly increased startle amplitudes in the verum stimulation condition for alcohol-related cues, indicating a more negative processing of this cues in alcohol-dependent patients after verum tDCS stimulation. Additionally we found tendencies for stronger reduction in subjective craving in verum-stimulated patients. Therefore our study underscores the positive value of DCS in reducing craving and might help to improve the understanding and therapy of alcohol dependence.
Keller, Thomas E.; Blakeslee, Jennifer E.; Lemon, Stephenie C.; Courtney, Mark E.
Objective: Distinctive combinations of factors are likely to be associated with serious alcohol problems among adolescents about to emancipate from the foster care system and face the difficult transition to independent adulthood. This study identifies particular subpopulations of older foster youths that differ markedly in the probability of a lifetime diagnosis for alcohol abuse or dependence. Method: Classification and regression tree (CART) analysis was applied to a large, representative sample (N = 732) of individuals, 17 years of age or older, placed in the child welfare system for more than 1 year. CART evaluated two exploratory sets of variables for optimal splits into groups distinguished from each other on the criterion of lifetime alcohol-use disorder diagnosis. Results: Each classification tree yielded four terminal groups with different rates of lifetime alcohol-use disorder diagnosis. Notable groups in the first tree included one characterized by high levels of both delinquency and violence exposure (53% diagnosed) and another that featured lower delinquency but an independent-living placement (21% diagnosed). Notable groups in the second tree included African American adolescents (only 8% diagnosed), White adolescents not close to caregivers (40% diagnosed), and White adolescents closer to caregivers but with a history of psychological abuse (36% diagnosed). Conclusions: Analyses incorporating variables that could be comorbid with or symptomatic of alcohol problems, such as delinquency, yielded classifications potentially useful for assessment and service planning. Analyses without such variables identified other factors, such as quality of caregiving relationships and maltreatment, associated with serious alcohol problems, suggesting opportunities for prevention or intervention. PMID:20946738
Giorgi, Ines; Ottonello, Marcella; Vittadini, Giovanni; Bertolotti, Giorgio
Background Alcohol-dependent patients usually experience negative affects under the influence of alcohol, and these affective symptoms have been shown to decrease as a result of alcohol-withdrawal treatment. A recent cognitive–affective model suggests an interaction between drug motivation and affective symptoms. The aim of this multicenter study was to evaluate the psychological changes in subjects undergoing a residential rehabilitation program specifically designed for alcohol addiction, and to identify at discharge patients with greater affective symptoms and therefore more at risk of relapse. Materials and methods The sample included 560 subjects (mean age 46.91±10.2 years) who completed 28-day rehabilitation programs for alcohol addiction, following a tailored routine characterized by short duration and high intensity of medical and psychotherapeutic treatment. The psychological clinical profiles of anxiety, depression, psychological distress, psychological well-being, and self-perception of a positive change were assessed using the Cognitive Behavioral Assessment – Outcome Evaluation questionnaire at the beginning and at the end of the program. The changes in the psychological variables of the questionnaire were identified and considered as outcome evaluation of the residential intervention. Moreover, differences in the psychological functioning between patients with different characteristics were investigated. Results The score measured by the Cognitive Behavioral Assessment – Outcome Evaluation showed significant improvements in all the psychological characteristics assessed, and the profile at discharge was within the normal scores. Some significant differences were found in relation to specific characteristics of the sample, such as age, sex, level of education, type of intervention, and polysubstance use. Conclusion This study shows the changes in psychological profile in subjects undergoing residential rehabilitation from alcohol and how this
Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the Collaborative Study on the Genetics of Alcoholism
Johnson, Catherine; Drgon, Tomas; Liu, Qing-Rong; Walther, Donna; Edenberg, Howard; Rice, John; Foroud, Tatiana; Uhl, George R
Association genome scanning can identify markers for the allelic variants that contribute to vulnerability to complex disorders, including alcohol dependence. To improve the power and feasibility of this approach, we report validation of “100k” microarray-based allelic frequency assessments in pooled DNA samples. We then use this approach with unrelated alcohol dependent vs control individuals sampled from pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA). Allele frequency differences between alcohol-dependent and control individuals are assessed in quadruplicate at 104,268 autosomal SNPs in pooled samples. One hundred eighty eight SNPs provide 1) the largest allele frequency differences between dependent vs control individuals, 2) t values ≥ 3 for these differences and 3) clustering, so that 51 relatively small chromosomal regions contain at least three SNPs that satisfy criteria 1 and 2 above (Monte Carlo p=0.00034). These positive SNP clusters nominate interesting genes whose products are implicated in cellular signaling, gene regulation, development, “cell adhesion” and Mendelian disorders. The results converge with linkage and association results for alcohol and other addictive phenotypes. The data support polygenic contributions to vulnerability to alcohol dependence These SNPs provide new tools to aid the understanding, prevention and treatment of alcohol abuse and dependence. PMID:16894614
Hussong, Andrea M; Huang, Wenjing; Curran, Patrick J; Chassin, Laurie; Zucker, Robert A
Although previous studies show that children of alcoholic parents have higher rates of externalizing symptoms compared to their peers, it remains unclear whether the timing of children's externalizing symptoms is linked to that of their parent's alcohol-related symptoms. Using a multilevel modeling approach, we tested whether children aged 2 through 17 showed elevated mother-, father- and child-reported externalizing symptoms (a) at the same time that parents showed alcohol-related consequences (time-varying effects), (b) if parents showed greater alcohol-related consequences during the study period (proximal effects), and (c) if parents had a lifetime diagnosis of alcoholism that predated the study period (distal effects). We used integrative data analysis to combine samples from two prospective studies to test these hypotheses. Distal effects of parent alcoholism on increased child externalizing symptoms were large and consistent. In addition, proximal and time-varying effects of parent alcohol symptoms were also found. Implications for preventing escalations in externalizing symptoms among this high-risk population are discussed.
Background Heavy drinking jeopardizes the health of patients in HIV primary care. In alcohol dependent patients in HIV primary care, a technological enhancement of brief intervention, HealthCall administered via interactive voice response (HealthCall-IVR) was effective at reducing heavy drinking. The smartphone offered a technology platform to improve HealthCall. Methods Working with input from patients, technology experts, and HIV clinic personnel, we further developed HealthCall, harnessing smartphone technological capacities (HealthCall-S). In a pilot study, we compared rates of HealthCall-S daily use and drinking outcomes in 41 alcohol dependent HIV-infected patients with the 43 alcohol dependent HIV-infected patients who used HealthCall-IVR in our previous efficacy study. Procedures, clinic, personnel, and measures were largely the same in the two studies, and the two groups of patients were demographically similar (~90% minority). Results Pilot patients used HealthCall-S a median of 85.0% of the 60 days of treatment, significantly greater than the corresponding rate (63.8%) among comparison patients using HealthCall-IVR (p < .001). Mean end-of-treatment drinks per drinking day was similar in the two groups. Patients were highly satisfied with HealthCall-S (i.e., 92% reported that they liked using HealthCall-S). Conclusions Among alcohol dependent patients in HIV primary care, HealthCall delivered via smartphone is feasible, obtains better patient engagement than HealthCall-IVR, and is associated with decreased drinking. In HIV primary care settings, HealthCall-S may offer a way to improve drinking outcomes after brief intervention by extending patient engagement with little additional demands on staff time. PMID:24533631
Fuster, Daniel; Sanvisens, Arantza; Bolao, Ferran; Zuluaga, Paola; Rivas, Inmaculada; Tor, Jordi; Muga, Robert
Inflammation and intestinal permeability are believed to be paramount features in the development of alcohol-related liver damage. We aimed to assess the impact of 3 surrogate markers of inflammation (anemia, fibrinogen, and ferritin levels) on mid-term mortality of patients with alcohol dependence. This longitudinal study included patients with alcohol dependence admitted for hospital detoxification between 2000 and 2010. Mortality was ascertained from clinical charts and the mortality register. Associations between markers of inflammation and all-cause mortality were analyzed with mortality rates and Cox proportional hazards regression models. We also performed a subgroup analysis of mortality rates in patients with anemia, based on their mean corpuscular volume (MCV). We included 909 consecutive patients with alcohol dependence. Patients were mostly male (80.3%), had a median age of 44 years (interquartile range [IQR]: 38-50), and upon admission, their median alcohol consumption was 192 g/day (IQR: 120-265). At admission, 182 (20.5%) patients had anemia; 210 (25.9%) had fibrinogen levels >4.5 mg/dL; and 365 (49.5%) had ferritin levels >200 ng/mL. At the end of follow-up (median 3.8 years [IQR: 1.8-6.5], and a total of 3861.07 person-years), 118 patients had died (12.9% of the study population). Cox regression models showed that the presence of anemia at baseline was associated with mortality (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11-2.52, P < 0.01); no associations were found between mortality and high fibrinogen or high ferritin levels. A subgroup of patients with anemia was analyzed and compared to a control group of patients without anemia and a normal MCV. The mortality ratios of patients with normocytic and macrocytic anemia were 3.25 (95% CI: 1.41-7.26; P < 0.01) and 3.39 (95% CI: 1.86-6.43; P < 0.01), respectively. Patients with alcohol dependence admitted for detoxification had an increased risk of death when anemia
Arcury, Thomas A.; Talton, Jennifer W.; Summers, Phillip; Chen, Haiying; Laurienti, Paul J.; Quandt, Sara A.
Aims To describe alcohol consumption behavior of male Latino migrant farmworkers, compare their alcohol consumption behavior with that of other male Latino immigrants, and determine factors associated with risk for alcohol dependence among Latino immigrant workers. Methods Cross-sectional data were drawn from baseline interviews conducted as part of a larger community-based participatory research project examining the cognitive and neurological outcomes of pesticide exposure. A total of 235 farmworkers and 212 non-farmworkers completed interviews between May and August, 2012. Results Although 17.5% of the North Carolina Latino farmworkers report never having drunk alcohol, and a total of 34.5% report not having drunk alcohol in the previous three months, 48.5% engaged in heavy episodic drinking (HED) in the previous 3 months, and 23.8% frequently engaged in HED during this period. Farmworkers and non-farmworkers did not differ significantly in alcohol consumption behavior. Farmworkers and non-farmworkers did differ significantly in each component of the CAGE scale, with 37.9% of farmworkers and 16.0% of non-farmworkers being at risk for alcohol dependence (p<0.0001). Significant factors for being at risk for alcohol dependence were stress (Odds Ratio 1.06, 95% Confidence Interval 1.03, 1.09) and being a farmworker (Odds Ratio 3.58, 95% Confidence Interval 2.12, 6.06). Being married reduced the risk of alcohol dependence (Odds Ratio 0.45, 95% Confidence Interval 0.39, 0.87). Conclusions Latino farmworkers and non-farmworkers consume relatively large amounts of alcohol and engage in heavy episodic drinking at relatively high rates. Latino farmworkers have very high rates of risk for alcohol dependence. Policy changes and public health interventions are needed to address these concerns for a population that is vital to the agricultural economy. PMID:26842256
Prisciandaro, James J.; Schacht, Joseph P.; Prescot, Andrew P.; Renshaw, Perry F.; Brown, Truman R.; Anton, Raymond F.
Background Proton magnetic resonance spectroscopy (1H-MRS) studies have consistently found abnormal brain concentrations of N-acetylaspartate (NAA) and glutamate in individuals with alcohol use disorders (AUD) relative to light drinkers. However, most such studies have focused on individuals in treatment for severe alcohol dependence and few studies have investigated associations between neurochemical concentrations and recent alcohol consumption. The present study focused on associations between recent drinking and prefrontal neurometabolite concentrations in non-severe, non-treatment seeking individuals with AUD. Methods Nineteen treatment naïve alcohol-dependent individuals aged 21–40 completed a 1H-MRS scan. Single-voxel 1H-MRS spectra were acquired in dorsal anterior cingulate (dACC) using a Two-dimensional J-resolved Point Resolved Spectroscopy (2D J-PRESS) sequence. Associations between recent heavy drinking, assessed using the Timeline FollowBack, and dACC metabolite concentrations were estimated via regression controlling for within-voxel tissue composition. Results Participants provided a negative breathalyzer reading and reported between 1 and 5 days (M = 2.45, SD = 1.23) since their last drink. Number of heavy drinking days in the 14 days preceding the scan (M = 4.84, SD = 3.32) was significantly inversely associated with both glutamate/water (β = −0.63, t(17) = −3.37, p = 0.004) and NAA/water concentrations (β = −0.59, t(17) = −2.98, p = 0.008). Conclusions The present study extends the literature by demonstrating inverse associations between recent heavy drinking and dACC glutamate and NAA concentrations in a sample of non-severe, non-treatment seeking individuals with AD. These findings may support the hypothesis that amount of recent alcohol consumption may account for differences in neuronal metabolism, even in non-severe, non-treatment seeking alcoholics. PMID:26853538
Borowska-Solonynko, Aleksandra; Dabkowska, Agnieszka; Raczkowska, Zuzanna; Kwietniewski, Wojciech
The paper is a review of the most current academic literature published in the English language and addressing the effect of alcohol consumption on the severity of injuries, prognosis and mortality with special emphasis placed on the consultative usefulness of such publications. The report was inspired by repeated questions asked in association with expert opinions on the effects of injuries and addressing a possible effect of alcohol consumption by the victims on the severity of injuries and prognosis. In case of such questions, a valuable supplement to an opinion based on on the expert's professional experience may be found in an analysis of publications focusing on the subject. The present review was based on two databases "Web of science" and "Medline" (2000-2011). Initially, 372 abstracts were taken into account. Subsequently, 42 articles were thoroughly studied. The analyzed material represented both experimental and research approaches to the problem. The experimental approach was based on tests carried out on animals in laboratories, whereas the research approach was based on the observations of patients admitted to hospitals with injuries. The literature overview indicates a neuroprotective feature of alcohol and an improved prognosis in intoxicated people suffering from isolated head injuries, even though the severity of their injuries is much higher than in the cases of sober people. In cases of polytrauma injuries, the influence of alcohol is explicitly negative, but does not increase mortality.
Walker, Brendan M
This article represents one of five contributions focusing on the topic "Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure" that were developed by awardees participating in the Young Investigator Award Symposium at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference in Volterra, Italy on May 3-6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms.
Ehlers, Cindy L.; Gizer, Ian R.; Vieten, Cassandra; Gilder, Allison; Gilder, David A.; Stouffer, Gina M.; Lau, Philip; Wilhelmsen, Kirk C.
We examined gender differences in age of onset, clinical course, and heritability of alcohol dependence in 2524 adults participating in the University of California San Francisco (UCSF) family study of alcoholism. Men were significantly more likely than women to have initiated regular drinking during adolescence. Onset of regular drinking was not found to be heritable but was found to be significantly associated with a shorter time to onset of alcohol dependence. A high degree of similarity in the sequence of alcohol-related life events was found between men and women, however, men experienced alcohol dependence symptoms at a younger age and women had a more rapid clinical course. Women were found to have a higher heritability estimate for alcohol dependence (h2 =0.46) than men (h2 =0.32). These findings suggest that environmental factors influencing the initiation of regular drinking rather than genetic factors associated with dependence may in part underlie some of the gender differences seen in the prevalence of alcohol dependence in this population. PMID:20163381
Reis, Alessandra Diehl; Laranjeira, Ronaldo
The purpose of this paper is to supply a narrative review of the concepts, history, functions, methods, development and theoretical bases for the use of halfway houses for patients with mental disorders, and their correlations, for the net construction of chemical dependence model. This theme, in spite of its relevance, is still infrequently explored in the national literature. The authors report international and national uses of this model and discuss its applicability for the continuity of services for alcohol dependents. The results suggest that this area is in need of more attention and interest for future research. PMID:19061008
Jovanovic, Mirjana; Antunovic, Marko
Alcohol continues to occupy a leading position in Europe as a popular substance of abuse. According to WHO sources together with cigarette smoking and obesity, alcohol is a major cause of preventable diseases. Harmful use of alcohol is one of the main factors contributing to premature deaths and disability and has a major impact on public health. The consequences of alcohol use on human health are enormous. Additionally, alcohol use can have harmful effects that do not directly affect person who consumes alcohol (e.g., fetal alcohol syndrome violations that are related to alcohol use, etc.). It is well known that the harmful effects and consequences of alcohol use (e.g., acute and chronic illness, injuries in fights, at the workplace, in traffic, violent behavior, and death) create a great burden for the economic development of society. Persons who have been diagnosed with alcoholism and currently drinking have a less chance to achieve a life insurance cover. On the contrary, recovering alcoholic with a significant abstinent period can get a good life insurance quote. The abstinence of a year or 2 is usually enough for a person to get an average price of life insurance. Furthermore, new consequent relapses could also be considered as potential aggravating factor to accomplish this kind of financial benefits. So far, the research (and interventions) focused on the effects on the population level, such as the increase in taxes, advertising bans, and the implementation of laws that prevent the use of alcohol in traffic. However, it seems that the problem may be viewed at the individual level. The models of the treatment should be designed according to the needs of the individual. These models should incorporate not only the reduction of alcohol intake but also the path to abstinence. The plan should take into account the different (individual) needs for treatment, with regard to the degree of alcohol dependence and health status and also include the needs of the
Jovanovic, Mirjana; Antunovic, Marko
Alcohol continues to occupy a leading position in Europe as a popular substance of abuse. According to WHO sources together with cigarette smoking and obesity, alcohol is a major cause of preventable diseases. Harmful use of alcohol is one of the main factors contributing to premature deaths and disability and has a major impact on public health. The consequences of alcohol use on human health are enormous. Additionally, alcohol use can have harmful effects that do not directly affect person who consumes alcohol (e.g., fetal alcohol syndrome violations that are related to alcohol use, etc.). It is well known that the harmful effects and consequences of alcohol use (e.g., acute and chronic illness, injuries in fights, at the workplace, in traffic, violent behavior, and death) create a great burden for the economic development of society. Persons who have been diagnosed with alcoholism and currently drinking have a less chance to achieve a life insurance cover. On the contrary, recovering alcoholic with a significant abstinent period can get a good life insurance quote. The abstinence of a year or 2 is usually enough for a person to get an average price of life insurance. Furthermore, new consequent relapses could also be considered as potential aggravating factor to accomplish this kind of financial benefits. So far, the research (and interventions) focused on the effects on the population level, such as the increase in taxes, advertising bans, and the implementation of laws that prevent the use of alcohol in traffic. However, it seems that the problem may be viewed at the individual level. The models of the treatment should be designed according to the needs of the individual. These models should incorporate not only the reduction of alcohol intake but also the path to abstinence. The plan should take into account the different (individual) needs for treatment, with regard to the degree of alcohol dependence and health status and also include the needs of the
Mosquera Nogueira, Jacinto; Rodríguez-Míguez, Eva
Alcohol dependence causes multiple problems not only for the person suffering dependence but also for others. In this study, the contingent valuation method is proposed to measure the intangible effects of alcohol dependence from the perspective of the persons directly involved: the patients and their relatives. Interviews were conducted with 145 patients and 61 relatives. Intangible effects of alcohol dependence were determined based on willingness to pay for a hypothetical treatment for dependence, with different success scenarios (100% and 50%). The mean monthly willingness to pay among the alcohol-dependent population was €129 and €168, respectively, for the treatments with 100% and 50% success. The willingness to pay of relatives was greater in both scenarios (€307 and €420, respectively), which could be explained by their greater perception of the family, labour, and health problems resulting from alcohol dependence. Regression analysis showed that patients' willingness to pay is positively related to treatment efficacy, personal income and moderate health deterioration, and negatively related to feeling discouraged and depressed. The results from this study can be applied to economic valuation studies that aim to measure the benefits of programs intended to reduce the prevalence of alcohol dependence. The intangible costs estimated can be added to the direct and indirect costs commonly used.
Weinrieb, Robert M; Van Horn, Deborah H A; Lynch, Kevin G; Lucey, Michael R
Alcohol is the second most common cause of cirrhosis necessitating liver transplantation in the United States, yet rates of posttransplant drinking approach 50% and no controlled clinical trials of alcoholism treatment exist in this population. Eligible patients were randomly assigned to receive Motivational Enhancement Therapy (MET), or referral to local treatment sources ("treatment as usual" [TAU]). Addictive behavior, mood states, and general health were compared. Candor concerning alcohol use was encouraged by keeping drinking questionnaires in confidence, except in medical emergencies. Ninety-one subjects were studied; 46 received MET, 45 received TAU, 29 proceeded to transplantation (MET, n = 13; TAU, n = 16). A total of 69 subjects completed 24 weeks of observation, and 25 subjects were assessed at 96 weeks. No difference in study attendance was observed, but significantly more MET subjects attended 1 or more treatment sessions. Twenty-three subjects (25% of sample) drank after randomization but before transplant. Excluding an extreme outlier, MET drinkers had significantly fewer drinks per drinking days than TAU drinkers. Neither treatment plan resulted in significant variances in measures of psychosocial health. In conclusion, although MET afforded no significant benefit over TAU for mood or general health outcomes, this study provides some degree of support for MET to limit the quantity and frequency of pretransplant alcohol consumption among liver transplant candidates with alcohol dependence. However, because of the limited number of study subjects, these data must be interpreted cautiously. Further research to validate our findings or to identify better methods to identify and intervene with patients at risk of pretransplant and posttransplant drinking should continue.
Brevers, Damien; Noël, Xavier; Hanak, Catherine; Verbanck, Paul; Kornreich, Charles
Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls performed an ultimatum game (UG), in which participants had to respond to take-it-or-leave-it offers, ranging from fair to unfair and made by a fictive proposer. Emotional state was recorded during UG offers presentation and was indexed by the amplitude of skin conductance response (SCR). Results showed that AD decided to reject unfair offers more frequently than their controls, confirming previous data. The proportion of rejected unfair UG offers was correlated with SCR, in the AD but not in the control group. This finding suggests that deciding to accept or reject unfair UG offers is influenced by arousal-affective activity in AD, but not in controls. Heightened emotional reactivity may have driven AD to punish the proposer rather than acting as a rational economic agent. An implication of present findings is that AD might have difficult to cope with unfair situations triggered by social interactions. Future studies are needed in order to examine whether—emotional and behavioral—reactivity to unfairness during the UG could impact alcohol consumption and relapse in AD. PMID:26217293
Bierut, Laura Jean; Rice, John P; Goate, Alison; Hinrichs, Anthony L; Saccone, Nancy L; Foroud, Tatiana; Edenberg, Howard J; Cloninger, C Robert; Begleiter, Henri; Conneally, P Michael; Crowe, Raymond R; Hesselbrock, Victor; Li, Ting-Kai; Nurnberger, John I; Porjesz, Bernice; Schuckit, Marc A; Reich, Theodore
Smoking is a highly heritable, addictive disorder that commonly co-occurs with alcohol dependence. The purpose of this study is to perform a genomic screen for habitual smoking and comorbid habitual smoking and alcohol dependence in families from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per day or more for at least 6 months). Sixty seven multi-generational families with 154 independent sibling pairs affected with habitual smoking were genotyped in a screening sample. Analyses on 79 multi-generational families with 173 independent sibling pairs were repeated in a replication sample. Sibpair analyses were performed using ASPEX. Four chromosomal regions in the screening sample had increased allele sharing among sibling pairs for habitual smoking with a LOD score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on chromosome 9 (LOD = 2.02; allele sharing 58.9%). Four chromosomal regions also had modest evidence for linkage to the comorbid phenotype habitual smoking and alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on chromosome 2 (LOD = 3.30; allele sharing 69.1%). Previously identified areas (chromosomes 1 and 7) implicated in the development of alcohol dependence in this same data set did not provide evidence for linkage to habitual smoking in the screening sample. In the replication data set, there continued to be increased allele sharing near peaks identified in the screening sample on chromosomes 2 and 9, but the results were modest. An area on chromosome 7, approximately 60 cM from a location previously identified in linkage analysis with alcohol dependence, had increased allele sharing for the comorbid habitual smoking and alcohol dependence. These data provide evidence of specific genetic regions involved in the
Kiefer, Falk; Jiménez-Arriero, Miguel Angel; Klein, Oliver; Diehl, Alexander; Rubio, Gabriel
Naltrexone is an opiate receptor antagonist mainly at the micro-receptor that is thought to reduce the positively reinforcing, pleasurable effects of alcohol and to reduce craving. An increase in time to first relapse to heavy drinking has been the most consistent finding obtained with naltrexone, although not all trials including two of the largest have been positive. Inconsistent outcome data suggest that effectiveness varies among different subgroups of patients. This paper re-evaluates recent data on the effectiveness of naltrexone in subjects differentiated according to Cloninger Type I and II. Moreover, it combines and cross-validates results of two recent European studies that found naltrexone treatment more beneficial in alcohol-dependent patients with early age at onset of drinking problems (Cloninger Type II). It is discussed whether especially these subjects should be targeted for pharmacological relapse prevention treatment with naltrexone.
Sofin, Yvonne; Danker-Hopfe, Heidi; Gooren, Tina; Neu, Peter
Aims. This prospective study aims to identify patient characteristics as predictors for treatment outcome during inpatient detoxification treatment for drug and alcohol dependent patients. Methods. A mixed gender sample of 832 consecutively admitted drug and alcohol dependent patients were interviewed by an experienced physician. The impact of a variety of factors concerning social environment, therapy motivation, impulsivity related variables, medical history, and addiction severity on treatment outcome was examined. Results. 525 (63.1%) of the patients completed detoxification treatment whereas 307 (36.9%) dropped out prematurely. Being female, living in a partnership, having children, being employed, and having good education were predictive for a positive outcome. Family, health, the fear of losing the job, prosecution, and emergency admission were significant motivational predictors for treatment outcome. Being younger, history of imprisonment, and the number of previous drop-outs were predictive for a negative outcome. Conclusions. Variables concerning social environment and the number of previous drop-outs have been identified as best predictors for treatment outcome. Socially stable patients benefit from the current treatment setting and treatment shall be adapted for patients with negative predictors. Treatment may consequently be tailored with respect to intervention type, duration, and intensity to improve the outcome for those patients that fulfil criteria with negative impact on treatment retention.
Danker-Hopfe, Heidi; Gooren, Tina
Aims. This prospective study aims to identify patient characteristics as predictors for treatment outcome during inpatient detoxification treatment for drug and alcohol dependent patients. Methods. A mixed gender sample of 832 consecutively admitted drug and alcohol dependent patients were interviewed by an experienced physician. The impact of a variety of factors concerning social environment, therapy motivation, impulsivity related variables, medical history, and addiction severity on treatment outcome was examined. Results. 525 (63.1%) of the patients completed detoxification treatment whereas 307 (36.9%) dropped out prematurely. Being female, living in a partnership, having children, being employed, and having good education were predictive for a positive outcome. Family, health, the fear of losing the job, prosecution, and emergency admission were significant motivational predictors for treatment outcome. Being younger, history of imprisonment, and the number of previous drop-outs were predictive for a negative outcome. Conclusions. Variables concerning social environment and the number of previous drop-outs have been identified as best predictors for treatment outcome. Socially stable patients benefit from the current treatment setting and treatment shall be adapted for patients with negative predictors. Treatment may consequently be tailored with respect to intervention type, duration, and intensity to improve the outcome for those patients that fulfil criteria with negative impact on treatment retention. PMID:28367351
Staples, Miranda C.; Kim, Airee; Mandyam, Chitra D.
Prolonged alcohol exposure has been previously shown to impair the structure and function of the hippocampus, although the underlying structural and biochemical alterations contributing to these deleterious effects are unclear. Also unclear is whether these changes persist into prolonged periods of abstinence. Previous work from our lab utilizing a clinically relevant rodent model of alcohol consumption demonstrated that alcohol dependence (induced by chronic intermittent ethanol vapor exposure or CIE) decreases proliferation and survival of neural stem cells in the hippocampal subgranular zone and hippocampal neurogenesis in the dentate gyrus, implicating this region of the cortex as particularly sensitive to the toxic effects of prolonged ethanol exposure. For this study, we investigated seven weeks of CIE-induced morphological changes (dendritic complexity and dendritic spine density) of dentate gyrus (DG) granule cell neurons, CA3, and CA1 pyramidal neurons and the associated alterations in biochemical markers of synaptic plasticity and toxicity (NMDA receptors and PSD-95) in the hippocampus in ethanol-experienced Wistar rats 3h (CIE) and 21 days (protracted abstinence) after the last ethanol vapor exposure. CIE reduced dendritic arborization of DG neurons and this effect persisted into protracted abstinence. CIE enhanced dendritic arborization of pyramidal neurons and this effect did not persist into protracted abstinence. The architectural changes in dendrites did not correlate with alterations in dendritic spine density, however, they were associated with increases in the expression of pNR2B, total NR2B, and total NR2A immediately following CIE with expression levels returning to control levels in prolonged abstinence. Overall, these data provide the evidence that CIE produces profound changes in hippocampal structural plasticity and in molecular tools that maintain hippocampal structural plasticity, and these alterations may underlie cognitive dysfunction
Maurage, Pierre; Grynberg, Delphine; Noël, Xavier; Joassin, Frédéric; Hanak, Catherine; Verbanck, Paul; Luminet, Olivier; de Timary, Philippe; Campanella, Salvatore; Philippot, Pierre
It has been repeatedly shown that alcohol dependence is associated with emotional impairments, particularly for emotional facial expression decoding. Nevertheless, most earlier studies focused on basic emotions and did not explore more subtle affective states. In order to obtain a more accurate evaluation, and in view of earlier results showing impaired performance for this task among high-risk children of alcohol-dependent participants, the "Reading the Mind in the Eyes" test was used here to explore emotional recognition in alcohol dependence. We showed that the deficit described earlier for basic negative emotions is (1) generalizable to complex and positive emotions; and (2) specific for emotional features. This strengthens the proposition of a general face recognition impairment in alcohol dependence.
Jansen, Jochem M; van Holst, Ruth J; van den Brink, Wim; Veltman, Dick J; Caan, Matthan W A; Goudriaan, Anna E
Cognitive flexibility has been associated with prefrontal white matter (WM) integrity in healthy controls (HCs), showing that lower WM integrity is associated with worse performance. Although both cognitive flexibility and WM integrity have been found to be aberrant in alcohol-dependent (AD) patients, the relationship between the two has never been tested. In this study, we investigated the association between WM tract density and cognitive flexibility in patients with AD (n = 26) and HCs (n = 22). In order to assess the influence of AD severity, we also included a group of problematic drinkers (PrDs; n = 23) who did not meet the AD criteria. Behavioral responses and brain activity during a cognitive flexibility task were measured during functional magnetic resonance imaging. Probabilistic fiber tracking was performed between the dorsolateral prefrontal cortex and the basal ganglia; two crucial regions for task switching. Finally, the task-related functional connectivity between these areas was assessed. There were no significant group differences in the task performance. However, compared with HCs, AD patients and PrDs showed decreased WM integrity and increased prefrontal brain activation during task switching. Evidence is presented for a compensatory mechanism, involving recruitment of additional prefrontal resources in order to compensate for WM and neural function impairments in AD patients and PrDs. Although present in both alcohol groups, the PrDs were more successful in invoking this compensatory mechanism when compared to the AD patients. We propose that this may therefore serve as a protective factor, precluding transition from problematic drinking into alcohol dependence.
Ehlers, Cindy L.; Gilder, David A.; Criado, Jose R.; Caetano, Raul
Objectives Mexican Americans comprise one of the most rapidly growing populations in the U.S. and within this population the process of acculturation has been suggested to be associated with some mental health problems. This study sought to ascertain quantitative information indexing acculturation stress and its association with mental health disorders in a select community sample of Mexican Americans. Methods Demographic information, DSM-III-R diagnoses, and information on cultural identity and acculturation stress were obtained from 240 Mexican American young adults that were recruited by fliers and were residing in selected areas of San Diego. Results No associations were found between measures of cultural identification and lifetime diagnoses of drug or alcohol dependence, major depressive disorder, anxiety disorders or antisocial personality disorder/conduct disorder in this sample of Mexican American young adults. However, lifetime diagnoses of alcohol dependence, substance dependence, and anxiety disorders were associated with elevations in acculturation stress. Conclusion Quantitative measures of acculturation stress, but not cultural identity per se, were found to be significantly associated with substance dependence and anxiety disorders in this select population of Mexican American young adults. These data may be helpful in designing prevention and intervention programs for this high risk population. PMID:20161543
This paper describes the factor structure of the concept of alcohol dependence as proposed in two psychiatric classifications, the DSM-III-R and the ICD-10. Subjects are 219 men and 162 women who were interviewed while in treatment for alcohol-related problems in nine different treatment programs in Contra Costa county, California. Tests of hypotheses supporting a single factor and a dual factor structure of dependence were rejected by confirmatory factor analysis. Results from exploratory factor analysis show a four factor structure for the concept of dependence in DSM-III-R. For ICD-10 there is a four factor solution among men and a three factor solution among women. The item composition of these factors vary by gender and across the two classifications. However, there is good agreement between dependence as measured by DSM-III-R and ICD-10 criteria. Since work on DSM-IV is now under way, the present research aims to provide some empirical base for how future changes should be made.
Zarkin, Gary A.; Bray, Jeremy W.; Aldridge, Arnie; Mitra, Debanjali; Couper, David J.; Cisler, Ron A.
Context The COMBINE clinical trial recently evaluated the efficacy of medications, behavioral therapies, and their combinations for the outpatient treatment of alcohol dependence. The costs and cost-effectiveness of these combinations are unknown and of interest to clinicians and policy makers. Objective To evaluate the costs and cost-effectiveness of the COMBINE interventions at the end of 16 weeks of treatment. Design, Setting, and Participants A prospective cost and cost-effectiveness study of patients in COMBINE, a randomized controlled clinical trial (RCT) involving 1383 patients with diagnoses of primary alcohol dependence across 11 US clinical sites. Interventions Nine treatment arms, with 4 arms receiving medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or placebo; 4 arms receiving the same options as above but delivered with combined behavioral intervention (CBI); and 1 arm receiving CBI only. Main Outcomes Measures Incremental cost per percentage point increase in percent days abstinent (PDA), incremental cost per patient of avoiding heavy drinking, and incremental cost per patient of achieving a good clinical outcome. Results Based on the mean values of cost and effectiveness, 3 interventions are cost-effective options relative to the other interventions for all three outcomes: medical management (MM) with placebo ($409 cost per patient), MM + naltrexone ($671 cost per patient), and MM + naltrexone + acamprosate ($1003 cost per patient). Conclusions This is only the second prospective RCT-designed cost-effectiveness study that has been performed for the treatment of alcohol dependence. Focusing just on effectiveness, MM + naltrexone + acamprosate is not significantly better than MM + naltrexone. However, looking at cost and effectiveness, MM + naltrexone + acamprosate may be a cost-effective choice, depending on whether the cost of the incremental increase in effectiveness is worth it to the decision maker. PMID
Urban, Alexander E
In their paper "Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence" Lin and colleagues report on the association between alcohol dependence and 2 duplication CNVs in the genome sequence, one containing 8 genes within its boundaries and another that contains no genes. In this commentary, I point out some of the opportunities and challenges that arise from such a finding.
Lane, Sean P.; Sher, Kenneth J.
Within DSM-5, some diagnoses are now associated with a severity gradient based on the number of diagnostic criteria satisfied. Reasons for questioning the validity of this approach include the implicit assumptions of equal criterion severity and strict additivity of criteria combinations. To assess the implications of heterogeneity of criterion configurations on severity grading, we examined the association between all observed combinations of DSM-5 alcohol use disorder criteria endorsement, at each level of number of criteria endorsed, and multiple validity measures among 22,177 past-year drinkers from Wave 2 of the NESARC. Substantial variability of implied severity across criteria combinations was observed at each level of endorsement, with nontrivial overlap in implied severity across criterion counts. Findings suggest severity indices are at best imprecise and, potentially, misleading. These problems are likely inherent in traditional polythetic approaches to diagnosis and almost certainly applicable to other disorders. Approaches for improving severity grading are proposed. PMID:26783505
D'Hondt, Fabien; Campanella, Salvatore; Kornreich, Charles; Philippot, Pierre; Maurage, Pierre
Studies that have carried out experimental evaluation of emotional skills in alcohol-dependence have, up to now, been mainly focused on the exploration of emotional facial expressions (EFE) decoding. In the present paper, we provide some complements to the recent systematic literature review published by Donadon and de Lima Osório on this crucial topic. We also suggest research avenues that must be, in our opinion, considered in the coming years. More precisely, we propose, first, that a battery integrating a set of emotional tasks relating to different processes should be developed to better systemize EFE decoding measures in alcohol-dependence. Second, we propose to go below EFE recognition deficits and to seek for the roots of those alterations, particularly by investigating the putative role played by early visual processing and vision-emotion interactions in the emotional impairment observed in alcohol-dependence. Third, we insist on the need to go beyond EFE recognition deficits by suggesting that they only constitute a part of wider emotional deficits in alcohol-dependence. Importantly, since the efficient decoding of emotions is a crucial ability for the development and maintenance of satisfactory interpersonal relationships, we suggest that disruption of this ability in alcohol-dependent individuals may have adverse consequences for their social integration. One way to achieve this research agenda would be to develop the field of affective and social neuroscience of alcohol-dependence, which could ultimately lead to major advances at both theoretical and therapeutic levels.
Karaiskos, Ilias; Katsarolis, Ioannis; Stefanis, Leonidas
We present the case of a non-alcoholic man, who, following severe malnutrition, presented with dysphagia that necessitated gastrostomy tube placement. The patient subsequently developed encephalopathy, at which point thiamine deficiency was suspected and thiamine supplementation initiated. The encephalopathy and the dysphagia resolved, but the patient was left with a dense amnestic deficit consistent with Korsakoff syndrome. MRI at the time of the encephalopathy revealed lesions consistent with Wernicke-Korsakoff syndrome. This case represents a remarkable example of Wernicke-Korsakoff syndrome that for a prolonged time period had as its sole manifestation severe dysphagia. To our knowledge, there is only one similar case reported in the literature. This case serves to alert neurologists that isolated dysphagia may be the presenting symptom of this classic neurological syndrome even in the absence of alcoholism.
Saito, Atsushi; Taniguchi, Yu; Kim, Sun-Hong; Selvakumar, Balakrishnan; Perez, Gabriel; Ballinger, Michael D; Zhu, Xiaolei; Sabra, James; Jallow, Mariama; Yan, Priscilla; Ito, Koki; Rajendran, Shreenath; Hirotsune, Shinji; Wynshaw-Boris, Anthony; Snyder, Solomon H; Sawa, Akira; Kamiya, Atsushi
Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.
Gongvatana, Assawin; Morgan, Erin E.; Iudicello, Jennifer E.; Letendre, Scott L.; Grant, Igor; Woods, Steven Paul
Background Excessive alcohol use is common among people living with HIV. Given the growing prevalence of older HIV+ adults, and observations indicating higher risk for neurocognitive impairment in older adults with either HIV infection or alcoholism, an increased understanding of their combined impact in the context of this increasingly aged population is crucial. Methods We conducted comprehensive neurocognitive assessment in 112 older HIV+ individuals aged 50 to 69 years. Regression analyses were conducted to examine the interaction between age and the presence of lifetime alcohol dependence on neurocognitive measures, controlling for years of education, hepatitis C serostatus, and lifetime non-alcohol substance use disorder. Results Significant interactions of age and alcohol dependence history were found for global neurocognitive function, which was driven by the domains of executive function, processing speed, and semantic memory. Follow-up analyses indicated adverse effects of alcohol use history on neurocognitive measures that were evident only in HIV+ individuals 60 years and older. Conclusions While mounting evidence in younger cohorts indicates adverse synergistic HIV/alcohol effects on neurocognitive function, our novel preliminary findings in this elderly HIV+ cohort demonstrated the importance of even a relatively distant alcohol use history on the expression of HIV-associated neurocognitive disorders that may not become apparent until much later in life. PMID:25201556
Zhou, Zhenhe; Zhu, Hongmei; Li, Cui; Wang, Jun
Internet addiction disorder (IAD) should belong to a kind of behavioral addiction. Previous studies indicated that there are many similarities in the neurobiology of behavior and substance addictions. Up to date, although individuals with IAD have difficulty in suppressing their excessive online behaviors in real life, little is known about the patho-physiological and cognitive mechanisms responsible for IAD. Neuropsychological test studies have contributed significantly to our understanding of the effect of IAD on the cognitive function. The purpose of the present study was to examine whether Internet addictive individuals share impulsivity and executive dysfunction with alcohol-dependent individuals. Participants include 22 Internet addictive individuals, 22 patients with alcohol dependence (AD), and 22 normal controls (NC). All participants were measured with BIS-11, go/no-go task, Wisconsin Card Sorting Test, and Digit span task under the same experimental condition. Results showed that Barratt impulsiveness scale 11 scores, false alarm rate, the total response errors, perseverative errors, failure to maintain set of IAD and AD group were significantly higher than that of NC group, and hit rate, percentage of conceptual level responses, the number of categories completed, forwards scores, and backwards scores of IAD and AD group were significantly lower than that of NC group, however, no differences in above variables between IAD group and AD group were observed. These results revealed that the existence of impulsivity, deficiencies in executive function and working memory in an IAD and an AD sample, namely, Internet addictive individuals share impulsivity and executive dysfunction with alcohol-dependent patients. PMID:25202248
Elajaili, Hanan B; Biller, Joshua R; Eaton, Sandra S; Eaton, Gareth R
The spin-lattice relaxation rates at 293 K for three anionic semiquinones (2,5-di-t-butyl-1,4-benzosemiquinone, 2,6-di-t-butyl-1,4-benzosemiquinone, and 2,3,5,6-tetramethoxy-1,4-benzosemiquinone) were studied at up to 8 frequencies between 250 MHz and 34 GHz in ethanol or methanol solution containing high concentrations of OH(-). The relaxation rates are about a factor of 2 faster at lower frequencies than at 9 or 34 GHz. However, in perdeuterated alcohols the relaxation rates exhibit little frequency dependence, which demonstrates that the dominant frequency-dependent contribution to relaxation is modulation of dipolar interactions with solvent nuclei. The relaxation rates were modeled as the sum of two frequency-independent contributions (spin rotation and a local mode) and two frequency-dependent contributions (modulation of dipolar interaction with solvent nuclei and a much smaller contribution from modulation of g anisotropy). The correlation time for modulation of the interaction with solvent nuclei is longer than the tumbling correlation time of the semiquinone and is consistent with hydrogen bonding of the alcohol to the oxygen atoms of the semiquinones.
Mishra, Biswa Ranjan; Maiti, Rituparna; Nizamie, S Haque
The authors studied cerebral hemodynamics in alcohol dependence and evaluated their changes with application of high-frequency rTMS. A prospective, single-blind, randomized, parallel-group, sham-controlled clinical study was conducted with patients with alcohol dependence (DSM-IV-TR). The study population comprised 25 subjects each in active rTMS, sham rTMS, and healthy control groups. At baseline, cerebral hemodynamic indices were measured with transcranial Doppler sonography. Subjects in the active rTMS group received 10 sessions of rTMS daily; the sham group was administered sham rTMS with the same parameters. Cerebral hemodynamic parameters were repeated 5 minutes after the last rTMS session. At baseline, mean velocity (MV) of both middle cerebral artery (MCA; R-MCA: p=0.003; L-MCA: p=0.002) and anterior cerebral artery (ACA; R-ACA: p=0.003; L-ACA: p=.001) was significantly reduced. Pulsatility index (PI) of MCA (p<0.001) and resistance index (RI) of ACA (R-ACA: p=0.009; L-ACA: p=0.008) were increased in alcohol-dependent subjects in comparison with healthy controls. In the active rTMS group, except L-MCA PI, significant differences were observed in values of MV, PI, and RI of both MCA and ACA following rTMS intervention; such changes were not evident in the sham rTMS group. The changes in mean difference in MV of L-MCA (p=0.006) and L-ACA (p=0.015) were statistically significant in the active rTMS group, in comparison with the sham group. Significant differences were also observed between the two groups postintervention, in RI of L-MCA (p=0.001) and ACA (R-ACA: p=0.010; L-ACA: p=0.015). Alcohol dependence may result in altered cerebral hemodynamic parameters, which can be improved with high-frequency rTMS application.
Awan, Saima; Samokhvalov, Andriy V; Aleem, Nadia; Hendershot, Christian S; Irving, Julie Anne; Kalvik, Anne; Lefebvre, Lisa; Le Foll, Bernard; Quilty, Lena; Voore, Peter
Integrated care pathways (ICPs) provide an approach for delivering evidence-based treatment in a hospital setting. This column describes the development and pilot implementation in a clinical setting of an ICP for patients with concurrent major depressive disorder and alcohol dependence at the Centre for Addiction and Mental Health (CAMH), an academic tertiary care hospital, in Toronto, Canada. The ICP methodology includes evidence reviews, knowledge translation, process reengineering, and change management. Pilot results indicate high patient satisfaction, evidence of symptom improvement, and excellent retention.
Charriau, Violaine; Elyakoubi, M'hammed; Millet, Bruno; Drapier, Dominique; Robin, Didier; Moirand, Romain
Generalized Anxiety Disorder (GAD) is a frequent disabling disorder that often occurs with alcohol dependence. However comorbidity between substance use disorders and psychiatric disorders is often under-diagnosed. This study tried to evaluate an under-recognition of GAD by clinicians in alcoholic inpatients. Two groups of alcohol-dependent inpatients, hospitalized in the same non-academic psychiatric hospital in France, were included. The first group (Group 1) (n = 205) was included retrospectively within all patients hospitalized for alcohol dependence from may to November 2007. A record review was performed to determine the number of GAD (and other psychiatric disorders) diagnosis which was reported on these files by the clinicians. The second group (Group 2) (n = 199) was included prospectively from May to November 2008. GAD diagnosis was screened with the Worry and Anxiety Questionnaire and then confirmed with the Mini International Neurodiagnostic Interview. The two groups were similar in terms of social and demographic variables. GAD prevalence rate was significantly higher in Group 2 (30.7% with Confidence Interval [0.242; 0.371]) than in Group 1 (2.4% with Confidence Interval [0.003; 0.045]). This study confirms our hypothesis of an under-recognition of GAD by clinicians in alcohol dependant inpatients. It also confirms the high prevalence rate of comorbidity between alcohol dependence and GAD.
Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C
Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255
Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C
Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse.
Myerson, Joel; Green, Leonard; van den Berk-Clark, Carissa; Grucza, Richard A.
Rationale Alcohol dependence is known to be associated with steep discounting of delayed rewards, but its relation to the discounting of delayed losses and probabilistic rewards is unclear. Moreover, patterns of alcohol consumption vary considerably between communities, but previous research has not examined the relation between discounting and alcohol dependence in low-income African Americans. Objectives The goal of the present study was to determine whether low-income, alcohol-dependent African Americans differ from controls in the degree to which they discount delayed rewards, delayed losses, or probabilistic rewards. Methods African American participants, both cases and controls, were recruited from the same low-income neighborhoods, and propensity-score matching was used to further control for demographic differences. Participants performed three tasks that assessed their discounting of hypothetical monetary outcomes: delayed rewards, delayed losses, and probabilistic rewards. Results Alcohol-dependent cases discounted delayed gains, but not delayed losses or probabilistic gains, more steeply than their matched controls. The difference in discounting of delayed gains was localized to the male cases, whose discounting was steeper than either the male controls or the female cases; no gender difference was observed between male and female controls. Conclusions The present results extend findings regarding discounting by substance abusers to a previously unstudied group, low-income African Americans, and suggest that in this group at least, alcohol dependence, particularly in males, may be more a reflection of choosing immediate rewards than of ignoring their delayed negative consequences. PMID:26387518
Corrigan, Frances; Wu, Yue; Tuke, Jonathan; Coller, Janet K.; Rice, Kenner C.; Diener, Kerrilyn R.; Hayball, John D.; Watkins, Linda R.; Somogyi, Andrew A.; Hutchinson, Mark R.
Increasing evidence demonstrates induction of proinflammatory Toll-like receptor (TLR) 2 and TLR4 signaling by morphine and, TLR4 signaling by alcohol; thus indicating a common site of drug action and a potential novel innate immune-dependent hypothesis for opioid and alcohol drug interactions. Hence, the current study aimed to assess the role of TLR2, TLR4, MyD88 (as a critical TLR-signalling participant), NF-κB, Interleukin-1β (IL-1β; as a downstream proinflammatory effector molecule) and the µ opioid receptor (MOR; as a classical site for morphine action) in acute alcohol-induced sedation (4.5 g/kg) and alcohol (2.5 g/kg) interaction with morphine (5 mg/kg) by assessing the loss of righting reflex (LORR) as a measure of sedation. Wild-type male Balb/c mice and matched genetically-deficient TLR2, TLR4, and MyD88 strains were utilized, together with pharmacological manipulation of MOR, NF-κB, TLR4 and Interleukin-1β. Alcohol induced significant LORR in wild-type mice; this was halved by MyD88 and TLR4 deficiency, and surprisingly nearly completely eliminated by TLR2 deficiency. In contrast, the interaction between morphine and alcohol was found to be MOR-, NF-κB-, TLR2- and MyD88-dependent, but did not involve TLR4 or Interleukin-1β. Morphine-alcohol interactions caused acute elevations in microglial cell counts and NF-κB-p65 positive cells in the motor cortex in concordance with wild-type and TLR2 deficient mouse behavioral data, implicating neuroimmunopharmacological signaling as a pivotal mechanism in this clinically problematic drug-drug interaction. PMID:25542736
Hasegawa, Toshio; Nakatani, Kenta; Fujihara, Takashi; Yamada, Hideo
Turmeric is a popular material that plays an important role in the flavor and fragrance industries. Although many compounds have been reported as components of turmeric, its aroma profile has not been clarified. Recently we have developed a new approach for evaluating the complex odors of materials based on recent research on the mechanism of odor recognition. Here we report the characteristic aroma properties of turmeric obtained through the investigation of its aroma profile. The hexane extract of turmeric had a turmeric-like odor, whereas the steam distillate of turmeric had a pungent, non-turmeric-like odor. We carried out bulb-to-bulb distillations of the extract and the steam distillate. For the hexane extract, two fractions with completely different odors were obtained. One was a high boiling point fraction (group A) with a turmeric-like odor, which consisted of ar-turmerone and β-turmerone as the main components, and the other was a low boiling point fraction (group B), which consisted of α-curcumene and β-sesquiphellandrene. In contrast, the bulb-to-bulb distillation of the steam distillate gave a fraction (group C) with a very different odor from groups A and B. Group C was composed of several kinds of alcohols that were not present in groups A and B. These results indicate that the group C fraction causes the different, pungent odor of the turmeric oil obtained by steam distillation. The variation in the aroma of turmeric depended on the combination of these three groups of odor constituents.
Agrawal, Arpana; Narayanan, Gitanjali; Oltmanns, Thomas F
The present study examined the association between personality pathology (PP) and alcohol dependence (AD; both lifetime and in the past 12 months) among middle-aged to older adults incorporating three sources of assessment, specifically, diagnostic interviews as well as self- and informant reports. We collected data from a representative sample of community participants (N = 1,630; ages 54-65 years) and their informants (N = 1,462). Measures employed were the substance use disorder sections of the Mini-International Neuropsychiatric Interview Schedule for Mental Disorders, the Structured Interview for DSM-IV Personality (American Psychiatric Association, 2000, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text rev.; DSM-IV-TR SIDP) and the NEO-Personality Inventory-Revised (Costa, P. T., & McCrae, R. R., Revised NEO-Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) manual, 1992, Odessa, FL, Psychological Assessment Resources; self-report and informant versions). To complement the diagnostic interview for personality disorders (PDs), we utilized a PD-count technique derived from the five-factor model (FFM), which provided an index of PP liability. Factors representing lifetime and past-12 month AD were regressed on each of the 10 PP factors constructed from the SIDP interview, as well as self-report and informant FFM-count scores. Lifetime diagnosis of AD was positively associated with higher scores on several PP measures, including paranoid, schizotypal, antisocial, borderline, histrionic, and narcissistic PP. There was an inverse relation between lifetime AD and the factor score for obsessive-compulsive PP. With regard to AD in the past 12 months, antisocial, borderline, histrionic, and narcissistic PP factors were significantly associated with increased risk for AD, whereas the obsessive-compulsive and schizoid PP factors were associated with decreased risk for AD. The present data indicate that features of antisocial and
Criado, José R.; Ehlers, Cindy L.
The relationship between the P450 component elicited by affective stimuli and: a personal history of alcohol dependence, antisocial personality disorder/conduct disorder (ASPD/CD) or affective anxiety disorders (ANYAXAF) was examined in Mexican Americans, a group with high rates of heavy drinking. Data from two hundred and twenty two young adults between the ages of 18 and 30 were used in the analyses. ERPs were collected using a task that required discrimination between faces with neutral, sad and happy facial expressions. DSM-IIIR diagnoses were obtained using a structured interview and personality traits were indexed using the Maudsley personality inventory. Men had significantly diminished P450 responses, when compared to women which were further reduced in men with ASPD/CD; whereas, a significant increase in P450 amplitudes was seen in those participants with ANYAXAF. P450 amplitudes were also significantly increased in men with high extraversion scores and in women with high neuroticism scores. No significant associations were seen between the P450 amplitude and the diagnosis of alcohol dependence. These data suggest that interpretations of P450 responses in Mexican Americans need to take into account the interactions between gender, the affective valence of the eliciting stimuli, as well as psychiatric status. PMID:17764730
Byrne, Shannon A.; Petry, Nancy M.
Concurrent alcohol dependence (AD) among polysubstance abusers has been associated with negative consequences, although it may not necessarily lead to poor treatment outcomes. One of the most efficacious treatments for cocaine abuse is contingency management (CM), but little research has explored the impact of AD on abstinence outcomes, particularly among patients in methadone maintenance. Using data from three trials of CM for cocaine use, we compared baseline characteristics and post-treatment and follow-up cocaine outcomes between methadone maintained, cocaine dependent patients (N=193) with and without concurrent AD, randomized to standard care (SC) with or without CM. Patients with and without concurrent AD had similar baseline characteristics, with the exception that AD patients reported more alcohol use. AD patients achieved longer durations of cocaine abstinence and were more likely to submit a cocaine negative sample at follow-up than non-AD patients. Patients randomized to CM achieved better outcomes than those randomized to SC, but there was no interaction between treatment condition and AD status. These findings suggest that cocaine using methadone patients with AD achieve greater cocaine abstinence than their non-AD counterparts and should not be necessarily viewed as more difficult to treat. PMID:21463068
Müller, Christian A; Geisel, Olga; Pelz, Patricia; Higl, Verena; Krüger, Josephine; Stickel, Anna; Beck, Anne; Wernecke, Klaus-Dieter; Hellweg, Rainer; Heinz, Andreas
Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence.
Hartung, Daniel M; McCarty, Dennis; Fu, Rongwei; Wiest, Katharina; Chalk, Mady; Gastfriend, David R
Through improved adherence, once-monthly injectable extended-release naltrexone (XR-NTX) may provide an advantage over other oral agents approved for alcohol and opioid dependence treatment. The objective of this study was to evaluate cost and utilization outcomes between XR-NTX and other pharmacotherapies for treatment of alcohol and opioid dependence. Published studies were identified through comprehensive search of two electronic databases. Studies were included if they compared XR-NTX to other approved medicines and reported economic and healthcare utilization outcomes in patients with opioid or alcohol dependence. We identified five observational studies comparing 1,565 patients using XR-NTX to other therapies over 6 months. Alcohol dependent XR-NTX patients had longer medication refill persistence versus acamprosate and oral naltrexone. Healthcare utilization and costs was generally lower or as low for XR-NTX-treated patients relative to other alcohol dependence agents. Opioid dependent XR-NTX patients had lower inpatient substance abuse-related utilization versus other agents and $8170 lower total cost versus methadone.
Butterworth, R F; Kril, J J; Harper, C G
Chronic alcoholism results in thiamine deficiency as a consequence of poor nutrition, impaired absorption, and decreased phosphorylation to the enzyme cofactor form of the vitamin, thiamine pyrophosphate (TPP). Results of this study demonstrate significant reductions of TPP-dependent enzymes [pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH), and transketolase] in autopsied cerebellar vermis samples from alcoholic patients with the clinical and neuropathologically confirmed diagnosis of Wernicke-Korsakoff Syndrome (WKS). Enzyme activities in brain samples from alcoholics without WKS were within normal limits and activities of a nonthiamine-dependent enzyme, glutamate dehydrogenase, were not significantly different from control values in brain samples from alcoholics with or without WKS. These findings provide evidence, for the first time, of a direct implication of TPP-related metabolic processes in the pathogenesis of WKS. Decreased activities of alpha KGDH could be the trigger for a sequence of metabolic events resulting in energy compromise, and ultimately neuronal death in this syndrome.
Hulin, Mary W.; Amato, Russell J.; Porter, Johnny R.; Filipeanu, Catalin M.; Winsauer, Peter J.
Despite the prevalence of alcohol abuse and dependence in the US and Europe, there are only five approved pharmacotherapies for alcohol dependence. Moreover, these pharmacotherapeutic options have limited clinical utility. The purpose of this paper is to present pertinent literature suggesting that both alcohol and the neurosteroids interact at the GABAA receptor complex and that the neurosteroid sites on this receptor complex could serve as new targets for the development of novel therapeutics for alcohol abuse. This paper will also present data collected by our laboratory showing that one neurosteroid in particular, dehydroepiandrosterone (DHEA), decreases ethanol intake in rats under a variety of conditions. In the process, we will also mention relevant studies from the literature suggesting that both particular subtypes and subunits of the GABAA receptor play an important role in mediating the interaction of neurosteroids and ethanol. PMID:22110489
Pelletier, Stéphanie; Alarcon, Régis; Rigole, Hélène; Perney, Pascal
Background. Cognitive dysfunction is a common feature in alcohol use disorders. Its persistence following alcohol detoxification may impair quality of life and increase the risk of relapse. We analyzed cognitive impairment changes using the Montreal Cognitive Assessment (MoCA) score in a large sample of alcohol-dependent inpatients hospitalized for at least 4 weeks. Method. This was an observational longitudinal survey. Inclusion criteria were alcohol dependence (DSM-IV) and alcohol abstinence for at least one week. The MoCA test was administered on admission and at discharge. Results. 236 patients were included. The mean MoCA score significantly increased from 22.1 ± 3.7 on admission to 25.11 ± 3.12 at discharge. The corresponding effect-size of improvement was high, 1.1 [95% CI 1.0–1.2]. The degree of improvement was inversely correlated with the baseline MoCA score. The rate of high and normal, that is, >26, MoCA values increased from 15.8% on admission to 53.8% at discharge. MoCA score improvement was not correlated with the total length of abstinence prior to admission. Conclusion. The MoCA score seems to be a useful tool for measuring changes in cognitive performance in alcohol-dependent patients. A significant improvement in cognitive function was observed whatever the degree of impairment on admission and even after a long abstinence period. PMID:28044121
McDonell, Michael G.; Skalisky, Jordan; Leickly, Emily; McPherson, Sterling; Battalio, Samuel; Nepom, Jenny R.; Srebnik, Debra; Roll, John; Ries, Richard K.
Aims This study investigated which ethyl glucuronide immunoassay (EtG-I) cutoff best detects heavy versus light drinking over five days in alcohol dependent outpatients. Methods A total of 121 adults with alcohol use disorders and co-occurring psychiatric disorders taking part in an alcohol treatment study. Participants provided self-reported drinking data and urine samples three time per week for 16-weeks (total samples = 2761). Agreement between low (100 ng/mL, 200 ng/mL), and moderate (500 ng/mL) EtG-I cutoffs and light (women ≤3 standard drinks, men ≤ 4 standard drinks) and heavy drinking (women >3, men >4 standard drinks) were calculated over one to five days. Results The 100 ng/mL cutoff detected >76% of light drinking for two days, and 66% at five days. The 100 ng/mL cutoff detected 84% (1 day) to 79% (5 days) of heavy drinking. The 200 ng/mL cutoff detected >55% of light drinking across five days and >66% of heavy drinking across five days. A 500 ng/mL cutoff identified 68% of light drinking and 78% of heavy drinking for one day, with detection of light (2–5 days <58%) and heavy drinking (2–5 days <71%) decreasing thereafter. Relative to 100 ng/mL, the 200 ng/mL and 500 ng/mL cutoffs were less likely to result in false positives. Conclusions An EtG-I cutoff of 100 ng/mL is most likely to detect heavy drinking for up to five days and any drinking during the previous two days. Cutoffs of ≥ 500 ng/mL are likely to only detect heavy drinking during the previous day. PMID:26475403
Ahlers, Katelin E; Karaçay, Bahri; Fuller, Leah; Bonthius, Daniel J; Dailey, Michael E
Fetal alcohol exposure is the most common known cause of preventable mental retardation, yet we know little about how microglia respond to, or are affected by, alcohol in the developing brain in vivo. Using an acute (single day) model of moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or P8 mice, we found that alcohol-induced neuroapoptosis in the neocortex is closely correlated in space and time with the appearance of activated microglia near dead cells. The timing and molecular pattern of microglial activation varied with the level of cell death. Although microglia rapidly mobilized to contact and engulf late-stage apoptotic neurons, apoptotic bodies temporarily accumulated in neocortex, suggesting that in severe cases of alcohol toxicity the neurodegeneration rate exceeds the clearance capacity of endogenous microglia. Nevertheless, most dead cells were cleared and microglia began to deactivate within 1-2 days of the initial insult. Coincident with microglial activation and deactivation, there was a transient increase in expression of pro-inflammatory factors, TNFα and IL-1β, after severe (5 g/kg) but not moderate (3 g/kg) EtOH levels. Alcohol-induced microglial activation and pro-inflammatory factor expression were largely abolished in BAX null mice lacking neuroapoptosis, indicating that microglial activation is primarily triggered by apoptosis rather than the alcohol. Therefore, acute alcohol exposure in the developing neocortex causes transient microglial activation and mobilization, promoting clearance of dead cells and tissue recovery. Moreover, cortical microglia show a remarkable capacity to rapidly deactivate following even severe neurodegenerative insults in the developing brain.
Ooteman, Wendy; Naassila, Mickaël; Koeter, Maarten W J; Verheul, Roel; Schippers, Gerard M; Houchi, Hakim; Daoust, Martine; van den Brink, Wim
Acamprosate and naltrexone are effective medications in the treatment of alcoholism. However, effect sizes are modest. Pharmacogenomics may improve patient-treatment-matching and effect sizes. It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system, whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system. Alcohol-dependent subjects were randomly assigned to either acamprosate or naltrexone. Subjects participated in a cue-exposure experiment at the day before and at the last day of medication. Reductions in cue-induced craving and physiological cue reactivity were measured. Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid, dopamine, glutamate and GABA-receptors. Significant matching effects were found for polymorphisms at the DRD2, GABRA6 and GABRB2 gene. In addition, a trend was found for the OPRM1 polymorphism. This provides evidence for the matching potential of genotypes. It is expected that more effective treatments can be offered when genetic information is used in patient-treatment-matching.
Khemiri, Lotfi; Guterstam, Joar; Franck, Johan; Jayaram-Lindström, Nitya
Recent studies indicate that emotional processes, mediated by the ventromedial prefrontal cortex (VMPC), are of great importance for moral judgment. Neurological patients with VMPC dysfunction have been shown to generate increased utilitarian moral judgments, i.e. are more likely to endorse emotionally aversive actions in order to maximize aggregate welfare, when faced with emotionally salient personal moral dilemmas. Patients with alcohol dependence (AD) also exhibit impairments in functions mediated by the prefrontal cortex, but whether they exhibit increased utilitarian moral reasoning has not previously been investigated. The aim of this study was to investigate moral judgment in AD patients (n = 20) compared to healthy controls (n = 20) matched by sex, age and education years. Each subject responded to a battery of 50 hypothetical dilemmas categorized as non-moral, moral impersonal and moral personal. They also responded to a questionnaire evaluating explicit knowledge of social and moral norms. Results confirmed our hypothesis that AD patients generated increased utilitarian moral judgment compared to controls when faced with moral personal dilemmas. Crucially, there was no difference in their responses to non-moral or impersonal moral dilemmas, nor knowledge of explicit social and moral norms. One possible explanation is that damage to the VMPC, caused by long term repeated exposure to alcohol results in emotional dysfunction, predisposing to utilitarian moral judgment. This work elucidates a novel aspect of the neuropsychological profile of AD patients, namely a tendency to generate utilitarian moral judgment when faced with emotionally salient moral personal dilemmas. PMID:22761922
Conroy, Deirdre A.; Arnedt, J. Todd; Brower, Kirk J.; Strobbe, Stephen; Consens, Flavia; Hoffmann, Robert; Armitage, Roseanne
Background Subjective and objective measures of poor sleep in alcoholic insomniacs predict relapse to drinking. Non-alcoholic insomniacs underestimate their total sleep time (TST), and overestimate their sleep onset latency (SOL) and wake time after sleep onset (WASO) compared to polysomnography (PSG). This study evaluated three hypotheses: (1) subjective SOL would predict frequency of drinking during and after treatment; (2) participants would overestimate SOL and WASO and underestimate TST; and (3) higher amounts of over- and underestimates of sleep at baseline would predict worse drinking outcomes during and after treatment. Methods Participants (N=18), mean age 44.6 years (±13.2) underwent an adaptation night and two nights of PSG. They provided morning estimates of SOL, WASO, TST, and sleep efficiency (SE). Following PSG, participants were randomized to 6 weeks of placebo or gabapentin as part of a separate study. After 6 weeks, participants discontinued medication and were followed to week 12. A two-way ANOVA (night x method of measuring sleep) compared results and regression analyses predicted drinking. Drinking outcomes were defined as number of days drinking (DD) and number of heavy drinking days (HDD) during two consecutive 6-week periods. Results Most participants (72%) overestimated SOL by a mean of 21.3 (±36) minutes compared to PSG, F (1, 14) =7.1, p<.03. Unexpectedly, 89% underestimated WASO by a mean difference of 48.7 (±49) minutes, F (1, 14) =15.6, p<.01. Drinking during the 6-week study period was predicted by both subjective estimates of WASO and their accuracy. Post-treatment drinking was also predicted by subjective estimations of sleep and REM sleep latency. Conclusion Greater subjective accuracy of wakefulness at night provided by the patient predicted drinking during treatment. Unlike non-alcoholic insomniacs, this alcoholic sample significantly underestimated WASO compared to PSG values. The predictive ability of sleep parameters
Bjurstrom, Martin F.; Olmstead, Richard
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
Gelernter, J; Kranzler, HR; Sherva, R; Almasy, L; Koesterer, R; Smith, AH; Anton, R; Preuss, UW; Ridinger, M; Rujescu, D; Wodarz, N; Zill, P; Zhao, H; Farrer, LA
We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus, showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P = 1.17 × 10−31; AAs: Arg369Cys, P = 6.33 × 10−17) and ADH1C in AAs (Thr151Thr, P = 4.94 × 10−10), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P = 2.63 × 10−11), PDLIM5 in EAs (P = 2.01 × 10−8), and METAP in AAs (P = 3.35 × 10−8). We also identified a novel GWS association (1.17 × 10−10) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits. PMID:24166409
Nishizawa, Daisuke; Han, Wenhua; Hasegawa, Junko; Ishida, Takafumi; Numata, Yukio; Sato, Tadahiro; Kawai, Atsuko; Ikeda, Kazutaka
Ethanol is considered to activate the brain reward system by increasing the release of an endogenous opioid receptor ligand, beta-endorphin. The polymorphism A118G in the mu-opioid receptor gene (OPRM1) causes the amino acid change Asn40Asp and has been reported to affect the affinity of the ligand for the receptor. The association of this polymorphism with the vulnerability to alcohol dependence has been studied in many populations, but not yet in Japanese people. In the present study, we compared the frequencies of the polymorphism OPRM1 A118G between patients with alcohol dependence and healthy control subjects living in a Japanese provincial prefecture. We also genotyped a polymorphism, G1510A, in the acetaldehyde dehydrogenase 2 gene (ALDH2), in which the A allele causes poor metabolism of acetaldehyde, a major metabolite of alcohol. Both OPRM1 118G and ALDH2 1510G were significantly associated with alcohol dependence. These results suggest that OPRM1 118G in addition to ALDH2 1510G might be one of the risk factors for alcohol dependence in Japanese people.
Conde López, V; Pacheco Yáñez, L; Pérez Puente, C
The authors refer on introduction to a former research where they describe results from 150 inpatients diagnosed of "Alcohol Dependence" and "Alcohol Abuse Syndromes" admitted during 1980-1984 at the Psychiatry Department of University Hospital of Valladolid. A comparison of epidemiologic, clinic, diagnostic and care patients patterns is made versus three other studies , where similar groups of alcoholic patients are studied through 47 variables. The first investigation reports findings from 613 alcoholic out patients demanding psychiatric care at University Hospital in Valladolid. The second one study 134 alcoholic patients (70% outpatients and 30% inpatients) at the Hospital General in Burgos. The last one reports finding from 403 alcoholic inpatients at the Psychiatric Service of "Ramón y Cajal" Hospital of Madrid. A group of 130 patients are studied as a whole, 1,127 males (86.89%) and 173 females (13.3%). Fifty per cent of the sample (n = 653) were inpatients and the remainder were outpatients; 28.30% (n = 368) were diagnosed by means of CIE-8a; 61.38% (n = 798) by means of CIE-9a; and 10.30 by DSM-III diagnostic criteria. The variables evaluated were population, age, sex, civil state, place of birth, place of living, level of education, profession, work capability, economical status and current social class, working and marriage adaptation, place composition, first work age, emigration, family psychiatric problems, affective deprivation, personal background, former treatment for drinking problems, start of drinking average age, abuse average time, kind of drinking, drinking day average amount, motive of abuse increments, consultation motive, somatic and psychiatric diagnoses, others drugs consultations, TAC and EEG results, first pharmacologic treatment, inpatient average time, and later hospitalizations. A table, a graphic and 83 bibliographic quotations, part of which belong to a former work, are included.
Conde López, V; Pacheco Yáñez, L; Pérez Puente, C
The authors refer on introduction to a former research where they describe results from 150 inpatients diagnosed of "Alcohol Dependence" and "Alcohol Abuse Syndromes" admitted during 1980-1984 at the Psychiatry Department of University Hospital of Valladolid. A comparison of epidemiologic, clinic, diagnostic and care patients patterns is made versus three others researches, where similar groups of alcoholic patients are studied through 47 variables. The first ++ investigation reports findings from 613 alcoholic out patients demanding psychiatric care at University Hospital in Valladolid. The second one study 134 alcoholic patients (70% out patients and 30% in patients) at the Hospital General in Burgos. The last one reports finding from 403 alcoholic in patients at the Psychiatric Service of "Ramon y Cajal" Hospital of Madrid. A group of 130 patients are studied as a whole, 1127 males (86.89%) and 173 females (13.3%). Fifty per cent of the simple (n = 653) were in-patient and the remainder were out-patients; 28.30% (n = 368) were diagnosed by means of CIE-8 , 61.38% (n = 798) by means of CIE-9 and 10.30 by DSM-III diagnostic criteria. The variables evaluated were population, age, sex, civil state, place of birth, place of living, level of education, profession, work capability, economical status and current social class, working and marriage adaptation, place composition, first work age, emigration, family psychiatric problems, affective deprivation, personal background, former treatment for drinking problems, start of drinking average age, abuse average time, kind of drinking, drinking day average amount, motive of abuse increments, consultation motive, somatic and psychiatric diagnoses, other drug consumptions, TAC and EEG results, first pharmacologic treatment, in-patient average time, and later hospitalisations. A table, a graphic, and 83 bibliographic quotations, part of which belong to a former work, are included.
Carlson, Marie D.; Harden, K. Paige; Kretsch, Natalie; Corbin, William R.; Fromme, Kim
Social experiences may moderate genetic influences on alcohol dependence (AD) symptoms. Consistent with this hypothesis, Park, Sher, Todorov, and Heath (2011) previously reported interactions between the dopamine D4 receptor gene (DRD4) and developmentally specific environments in the etiology of AD symptoms during emerging and young adulthood. Using a longitudinal cohort of n = 367 White participants followed from ages 18–27 we examine a series of similar interactions between DRD4 and developmentally sensitive contexts including childhood adversity and work and family roles. In contrast to previous results, we observed no significant interactions between DRD4 and childhood adversity. Overall, results further highlight the need for longitudinal studies of gene × environment interaction in the behavioral sciences and the difficulty of identifying candidate gene × environment interaction effects that are consistent across studies. PMID:26595480
Carlson, Marie D; Harden, K Paige; Kretsch, Natalie; Corbin, William R; Fromme, Kim
Social experiences may moderate genetic influences on alcohol dependence (AD) symptoms. Consistent with this hypothesis, Park, Sher, Todorov, and Heath (2011) previously reported interactions between the dopamine D4 receptor gene (DRD4) and developmentally specific environments in the etiology of AD symptoms during emerging and young adulthood. Using a longitudinal cohort of n = 367 White participants followed from ages 18 to 27 years, we examine a series of similar interactions between DRD4 and developmentally sensitive contexts including childhood adversity and work and family roles. In contrast to previous results, we observed no significant interactions between DRD4 and childhood adversity. Overall, results further highlight the need for longitudinal studies of Gene × Environment interaction in the behavioral sciences and the difficulty of identifying candidate Gene × Environment interaction effects that are consistent across studies.
Dupouy, Julie; Fournier, Jean-Pascal; Jouanjus, Émilie; Palmaro, Aurore; Poutrain, Jean-Christophe; Oustric, Stéphane; Lapeyre-Mestre, Maryse
Recently, baclofen has been widely promoted for treatment of alcohol dependence in France. Our aim was firstly to describe the incidence of patients newly treated with baclofen for alcohol dependence in France from 2007 to 2011, and secondly to describe baclofen prescription patterns and prescribers. A retrospective cohort study of patients newly treated with baclofen was conducted using the "Echantillon Généraliste des Bénéficiaires" database (EGB). Patients with a first dispensation of baclofen between 01/01/2007 and 31/12/2011, followed by a second in the next 120 days, were included. Patients were considered treated with baclofen for neurological conditions if at least one of the following conditions was found to be true: (1) presence of a neurological condition for which baclofen could be prescribed, (2) dispensation of dantrolene, another anti-spastic drug, or (3) hospitalization for a neurological condition for which baclofen could be prescribed. We assumed that all the remaining patients were treated for alcohol dependence. During the 5-year period, 676 patients were incident users. While the annual incidence rate of patients newly treated with baclofen for neurological conditions remained stable, the annual incidence rate of patients newly treated with baclofen for alcohol dependence increased by a factor of 2.9 between 2007 (0.09/1000 person-years) and 2011 (0.26/1000 person-years). In the alcohol dependence group, median duration of baclofen treatment was 143.5 [74.0; 377.0] days; median daily dose was 24.4 [14.8; 39.5] mg. This study demonstrated the rapidly increasing use of baclofen in France for treatment of alcohol dependence.
Thurang, Anna Maria; Palmstierna, Tom; Tops, Anita Bengtsson
The aim of the present study is to describe and understand the meaning of living with alcohol dependency (AD) as a man. Studies point out a high prevalence of AD in men and the reasons for, and consequences of, that are complex. However, today there is a lack of knowledge about men's lived experiences of having AD. In-depth interviews were conducted with 15 alcohol dependent men and analyzed using a phenomenological-hermeneutic approach. In the comprehensive understanding, findings from the naïve understanding and the structural analysis were interpreted with help from both gender and caring theoretical perspectives. "A Fallible Man" and "A Man with Powerfulness" were disclosed as two main gender formations influencing senses of well-being. A Fallible Man involved varying experiences of restrictions, being in control, and meaninglessness. Being in control promoted a sense of well-being. A Man with Powerfulness involved energetic activity, and the development and maintaining of interests as well as risk-taking. Being powerful diminished feelings of meaninglessness, cravings, and social alienation. The results show, among other things, that the men live an incompatible life and, because of that, need support and guidance to find a more meaningful life. This can be accomplished if caregivers allow men to be in focus and involved in planning their own care. To avoid limiting the men while they are in treatment, the health care professionals also need to focus on the men's everyday life. This focus involves acknowledging the men's individual experiences of what enriches and limits their everyday lives.
Cannady, Reginald; McGonigal, Justin T; Newsom, Ryan J; Woodward, John J; Mulholland, Patrick J; Gass, Justin T
Identifying novel treatments that facilitate extinction learning could enhance cue-exposure therapy and reduce high relapse rates in alcoholics. Activation of mGlu5 receptors in the infralimbic prefrontal cortex (IL-PFC) facilitates learning during extinction of cue-conditioned alcohol-seeking behavior. Small-conductance calcium-activated potassium (KCa2) channels have also been implicated in extinction learning of fear memories, and mGlu5 receptor activation can reduce KCa2 channel function. Using a combination of electrophysiological, pharmacological, and behavioral approaches, this study examined KCa2 channels as a novel target to facilitate extinction of alcohol-seeking behavior in rats. This study also explored related neuronal and synaptic mechanisms within the IL-PFC that underlie mGlu5-dependent enhancement of extinction learning. Using whole-cell patch clamp electrophysiology, activation of mGlu5 in ex vivo slices significantly reduced KCa2 channel currents in layer V IL-PFC pyramidal neurons, confirming functional down-regulation of KCa2 channel activity by mGlu5 receptors. Additionally, positive modulation of KCa2 channels prevented mGlu5 receptor-dependent facilitation of long-term potentiation in the IL-PFC. Systemic and intra-IL-PFC treatment with apamin (KCa2 channel allosteric inhibitor) significantly enhanced extinction of alcohol-seeking behavior across multiple extinction sessions; an effect that persisted for 3 weeks, but was not observed after apamin treatment in the prelimbic PFC. Positive modulation of IL-PFC KCa2 channels significantly attenuated mGlu5-dependent facilitation of alcohol cue-conditioned extinction learning. These data suggest that mGlu5-dependent facilitation of extinction learning and synaptic plasticity in the IL-PFC involves functional inhibition of KCa2 channels. Moreover, these findings demonstrate that KCa2 channels are a novel target to facilitate long-lasting extinction of alcohol-seeking behavior
Chattopadhyay, Ava; Förster-Fromme, Karin; Jendrossek, Dieter
Growth of Pseudomonas aeruginosa on acyclic terpene alcohols such as geraniol depends on the presence of the atuRABCDEFGH gene cluster and a functional acyclic terpene utilisation (Atu) pathway. The proteins encoded by the atu gene cluster are necessary but not sufficient for growth on acyclic terpenes. Comparative 2-dimensional polyacrylamide gel electrophoresis of soluble P. aeruginosa proteins revealed the presence of an additional spot (besides Atu proteins) that is specifically expressed in geraniol cells but is absent in isovalerate-grown cells. The spot was identified as PA1982 gene product a pyrroloquinoline quinone (PQQ) dependent ethanol oxidoreductase (QEDH). Inactivation of PA1982 by insertion mutagenesis resulted in inability of the mutant to utilise ethanol and in reduced growth on geraniol. Growth on ethanol was restored by transferring an intact copy of the PA1982 gene into the mutant. The PA1982 gene product was purified from recombinant Escherichia coli and revealed PQQ-dependent oxidoreductase activity with a variety of substrates including acyclic terpene derivates at comparable V(max)-values. Our results show that QEDH participates in oxidation of acyclic terpene derivates in addition to the well-known function in ethanol metabolism.
Zhang, H; Kranzler, HR; Yang, B-Z; Luo, X; Gelernter, J
Eleven single-nucleotide polymorphisms (SNPs) spanning OPRD1 were examined in 1063 European Americans (EAs) (620 cases with substance dependence (SD), including 557 with alcohol dependence (AD), 225 with cocaine dependence (CD) and 111 with opioid dependence (OD), and 443 controls). Nominally significant associations (P < 0.05) of five SNPs with SD were observed; only the association of the non-synonymous variant G80T with OD remained significant after correction for multiple testing using SNPSpD. Haplotype analyses with six tag SNPs indicated that a specific haplotype GCAACT, which harbors G80T G-allele and C921T C-allele, was significantly associated with AD (χ2 = 14.82, degrees of freedom (d.f.) = 1, P < 0.001), CD (χ2 = 9.19, d.f. = 1, P=0.002) and OD (χ2 = 20.68, d.f. = 1, P < 0.001). Logistic regression analyses, with sex and age being considered, demonstrated that this haplotype had a risk effect on AD (P = 0.03, β = 1.86, odds ratio (OR) = 6.43) and especially on OD (P< 0.001, β = 3.92, OR= 50.57). Moreover, seven SNPs covering OPRK1 were examined in the majority of the above subjects (390 cases, including 327 AD, 177 CD and 97 OD subjects, and 358 controls). Although no significant differences in allele, genotype or haplotype frequency distributions were seen between cases and controls, a specific OPRK1 haplotype, GGCTTCT, was significantly associated with AD (χ2 = 8.12, d.f. = 1, P=0.004). Logistic regression analyses also revealed its risk effect on AD (P = 0.009, β = 1.06, OR= 2.90). Population stratification artifact was not observed in the sample. Taken together, our findings supported a positive association between OPRD1 variants and SD, and a positive haplotypic association between OPRK1 and AD in EAs. PMID:17622222
Singh, Huidrom Suraj; Salam, Kabita; Saraswathy, Kallur Nava
Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (P > 0.05). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (P > 0.05). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41-5.01, P > 0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers.
Linton, Kristen F; Perrin, Paul B
Research shows connections between substance use and traumatic brain injury (TBI), high rates of substance use and interpersonal violence (IPV) in American Indians with TBI, and connections between IPV and TBI. This study assessed the effects of substance use at the time of a violent TBI and possible mediators such as American Indian race on injury severity (injury severity score [ISS]). A secondary data analysis of 3,351 individuals who experienced a TBI due to violence was conducted. American Indians with TBI were more likely to experience IPV (χ(2) = 4.19; p = .04) and had significantly higher blood alcohol content level (BAC) scores (t = - 16.78; p = .000) than other racial groups. A regression model explained 27% of the variance in ISS. Significant interaction terms uncovered positive relationships between: (a) American Indian race and ISS when the injury aetiology was not IPV and BAC scores were lower than the legal limit, and (b) IPV and ISS when patients were not American Indian. Alcohol was negatively associated with ISS among American Indians, suggesting that BAC may impact individuals with TBI differentially as a function of race.
Loderer, Christoph; Dhoke, Gaurao V; Davari, Mehdi D; Kroutil, Wolfgang; Schwaneberg, Ulrich; Bocola, Marco; Ansorge-Schumacher, Marion B
Zinc-dependent alcohol dehydrogenases (ADHs) are a class of enzymes applied in different biocatalytic processes ranging from lab to industrial scale. However, one drawback is the limited substrate range, necessitating a whole array of different ADHs for the relevant substrate classes. In this study, we investigated structural determinants of the substrate spectrum in the zinc-dependent ADH carbonyl reductase 2 from Candida parapsilosis (CPCR2), combining methods of mutational analysis with in silico substrate docking. Assigned active site residues were genetically randomized, and the resulting mutant libraries were screened with a selection of challenging carbonyl substrates. Three variants (C57A, W116K, and L119M) with improved activities toward different substrates were detected at neighboring positions in the active site. Thus, all possible combinations of the mutations were generated and characterized for their substrate specificity, yielding several improved variants. The most interesting were a C57A variant, with a 27-fold increase in specific activity for 4'-acetamidoacetophenone, and the double mutant CPCR2 B16-(C57A, L119M), with a 45-fold improvement in the kcat ⋅KM (-1) value. The obtained variants were further investigated by in silico docking experiments. The results indicate that the mentioned residues are structural determinants of the substrate specificity of CPCR2, being major players in the definition of the active site. Comparison of these results with closely related enzymes suggests that these might even be transferred to other ADHs.
Lane, S. P.; Steinley, D.; Sher, K. J.
Background Item response theory (IRT) analyses of alcohol use disorder (AUD) and other psychological disorders are a predominant method for assessing overall and individual criterion severity for psychiatric diagnosis. However, no investigation has established the consistency of the relative criteria severities across different samples. Method PubMed/Medline, PsycINFO, Web of Science and ProQuest databases were queried for entries relating to alcohol use and IRT. Study data were extracted using a standardized data entry sheet. Consistency of reported criteria severities across studies was analysed using generalizability theory to estimate generalized intraclass correlations (ICCs). Results A total of 451 citations were screened and 34 papers (30 unique samples) included in the research synthesis. The AUD criteria set exhibited low consistency in the ordering of criteria using both traditional [ICC = 0.16, 95% confidence interval (CI) 0.06–0.56] and generalized (ICC = 0.18, 95% CI 0.15–0.21) approaches. These results were partially accounted for by previously studied factors such as age and type of sample (e.g. clinical v. community), but the largest source of unreliability was the diagnostic instrument employed. Conclusions Despite the robust finding of unidimensional structure of AUDs, inconsistency in the relative severities across studies suggests low replicability, challenging the generalizability of findings from any given study. Explicit modeling of well-studied factors like age and sample type is essential and increases the generalizability of findings. Moreover, while the development of structured diagnostic interviews is considered a landmark contribution toward improving psychiatric research, variability across instruments has not been fully appreciated and is substantial. PMID:27019218
Lind, Penelope A; Macgregor, Stuart; Vink, Jacqueline M; Pergadia, Michele L; Hansell, Narelle K; de Moor, Marleen HM; Smit, August B; Hottenga, Jouke-Jan; Richter, Melinda M; Heath, Andrew C; Martin, Nicholas G; Willemsen, Gonneke; de Geus, Eco JC; Vogelzangs, Nicole; Penninx, Brenda W; Whitfield, John B; Montgomery, Grant W; Boomsma, Dorret I; Madden, Pamela AF
Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically-influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genome wide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (i) AD, 1224 cases and 1162 controls; (ii) ND, 1273 cases and 1113 controls; and (iii) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10,000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5×10−8) for ND (rs964170 in ARHGAP10 on chromosome 4, p=4.43×10−8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p=1.90×10−9), rs1784300 near DDX6 on chromosome 11 (p=2.60×10−9) and rs12882384 in KIAA1409 on chromosome 14 (p=4.86×10−8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepresentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be required before the detailed causes of comorbidity between AD and ND are understood. PMID:20158304
Sulovari, Arvis; Kranzler, Henry R; Farrer, Lindsay A; Gelernter, Joel; Li, Dawei
In archival samples of European-ancestry subjects, light-eyed individuals have been found to consume more alcohol than dark-eyed individuals. No published population-based studies have directly tested the association between alcohol dependence (AD) and eye color. We hypothesized that light-eyed individuals have a higher prevalence of AD than dark-eyed individuals. A mixture model was used to select a homogeneous sample of 1,263 European-Americans and control for population stratification. After quality control, we conducted an association study using logistic regression, adjusting for confounders (age, sex, and genetic ancestry). We found evidence of association between AD and blue eye color (P = 0.0005 and odds ratio = 1.83 (1.31-2.57)), supporting light eye color as a risk factor relative to brown eye color. Network-based analyses revealed a statistically significant (P = 0.02) number of genetic interactions between eye color genes and AD-associated genes. We found evidence of linkage disequilibrium between an AD-associated GABA receptor gene cluster, GABRB3/GABRG3, and eye color genes, OCA2/HERC2, as well as between AD-associated GRM5 and pigmentation-associated TYR. Our population-phenotype, network, and linkage disequilibrium analyses support association between blue eye color and AD. Although we controlled for stratification we cannot exclude underlying occult stratification as a contributor to this observation. Although replication is needed, our findings suggest that eye pigmentation information may be useful in research on AD. Further characterization of this association may unravel new AD etiological factors. © 2015 Wiley Periodicals, Inc.
Malhotra, Savita; Basu, Debasish; Ghosh, Abhishek; Khullar, Madhu; Kakkar, Neeraj
Objectives: Two cluster solutions for the subtyping of alcohol dependence (AD) was investigated in an Indian male population. Subtypes were compared for various personality traits and childhood externalizing disorders. They were also compared with respect to single-nucleotide polymorphisms (SNP) of various candidate genes. Materials and Methods: This was a clinic-based study conducted among 202 patients with AD. All patients were assessed with SSAGA-II for comorbid antisocial personality disorder (ASPD) and childhood conduct disorder (CD), oppositional defiant disorder (ODD), and attention deficit hyperactivity disorder (ADHD). For the assessment of personality traits, the Indian Adaptation of Sensation Seeking Scale (SSS) and Barratt's Impulsiveness Scale were administered. SNP genotyping was done using taqmann assay by real-time polymerase chain reaction. Results: Among those with AD, the two-cluster model which was able to produce the maximum degree of cohesion among disorders in the same cluster and separateness from the other cluster was the one with or without ASPD and CD. The quality of the cluster analysis was reduced when ODD and ADHD were included in the model along with ASPD and CD. Thus, in our index population, there are two distinct clusters of AD, one with ASPD and CD or the externalizing cluster (Cluster 2) and the other without ASPD and CD or the nonexternalizing cluster (Cluster 1). Externalizing cluster had significantly higher score in both the impulsiveness and the SSS. This cluster was also significantly associated with childhood ADHD and ODD. The genotype frequencies of all candidate genes were found to be nonsignificantly distributed among the two groups. Conclusion: Our study has conferred a cross-cultural validation of the known alcoholism subtypes. PMID:28196992
Liu, Ran; Zhu, Fayin; Lu, Lei; Fu, Aisi; Lu, Jiankai; Deng, Zixin; Liu, Tiangang
Fatty alcohols are important components of surfactants and cosmetic products. The production of fatty alcohols from sustainable resources using microbial fermentation could reduce dependence on fossil fuels and greenhouse gas emission. However, the industrialization of this process has been hampered by the current low yield and productivity of this synthetic pathway. As a result of metabolic engineering strategies, an Escherichia coli mutant containing Synechococcus elongatus fatty acyl-ACP reductase showed improved yield and productivity. Proteomics analysis and in vitro enzymatic assays showed that endogenous E. coli AdhP is a major contributor to the reduction of fatty aldehydes to fatty alcohols. Both in vitro and in vivo results clearly demonstrated that the activity and expression level of fatty acyl-CoA/ACP reductase is the rate-limiting step in the current protocol. In 2.5-L fed-batch fermentation with glycerol as the only carbon source, the most productive E. coli mutant produced 0.75 g/L fatty alcohols (0.02 g fatty alcohol/g glycerol) with a productivity of up to 0.06 g/L/h. This investigation establishes a promising synthetic pathway for industrial microbial production of fatty alcohols.
Aquino Neto, Sidney; Hickey, David P; Milton, Ross D; De Andrade, Adalgisa R; Minteer, Shelley D
In this paper, we explore the bioelectrooxidation of ethanol using pyrroloquinoline quinone (PQQ)-dependent alcohol and aldehyde dehydrogenase (ADH and AldDH) enzymes for biofuel cell applications. The bioanode architectures were designed with both direct electron transfer (DET) and mediated electron transfer (MET) mechanisms employing high surface area materials such as multi-walled carbon nanotubes (MWCNTs) and MWCNT-decorated gold nanoparticles, along with different immobilization techniques. Three different polymeric matrices were tested (tetrabutyl ammonium bromide (TBAB)-modified Nafion; octyl-modified linear polyethyleneimine (C8-LPEI); and cellulose) in the DET studies. The modified Nafion membrane provided the best electrical communication between enzymes and the electrode surface, with catalytic currents as high as 16.8 ± 2.1 µA cm(-2). Then, a series of ferrocene redox polymers were evaluated for MET. The redox polymer 1,1'-dimethylferrocene-modified linear polyethyleneimine (FcMe2-C3-LPEI) provided the best electrochemical response. Using this polymer, the electrochemical assays conducted in the presence of MWCNTs and MWCNTs-Au indicated a Jmax of 781 ± 59 µA cm(-2) and 925 ± 68 µA cm(-2), respectively. Overall, from the results obtained here, DET using the PQQ-dependent ADH and AldDH still lacks high current density, while the bioanodes that operate via MET employing ferrocene-modified LPEI redox polymers show efficient energy conversion capability in ethanol/air biofuel cells.
Joos, Leen; Goudriaan, Anna E; Schmaal, Lianne; van den Brink, Wim; Sabbe, Bernard G C; Dom, Geert
Cognitive deficits are highly prevalent in alcohol-dependent (AD) patients and may have a detrimental impact on treatment response and treatment outcome. Enhancing cognitive functions may improve treatment success. Modafinil is a promising compound in this respect. Therefore, a randomized double-blind placebo-controlled trial was conducted with modafinil (300 mg/d) or placebo in 83 AD patients for 10 weeks. Various cognitive functions (digit span task, Tower of London task, Stroop task) were measured at baseline, during and after treatment. Compared to placebo, modafinil improved verbal short-term memory (number of forward digit spans) (p=0.030), but modafinil exerted a negative effect on the working memory score of the digit span task (p=0.003). However, subgroup analyses revealed that modafinil did improve both working memory and verbal short-term memory in AD patients with a poor working memory ability at baseline (25% worst performers), whereas no significant treatment effect of modafinil was found on these two dependent variables in patients with good working memory skills at baseline (25% best performers). No effect of modafinil was found on measures of planning (Tower of London task) and selective attention (Stroop task). Further research is needed to better understand the relationship between cognitive remediation and treatment outcome in order to design targeted treatments.
Rosell, Albert; Valencia, Eva; Parés, Xavier; Fita, Ignacio; Farrés, Jaume; Ochoa, Wendy F
The amphibian enzyme ADH8, previously named class IV-like, is the only known vertebrate alcohol dehydrogenase (ADH) with specificity towards NADP(H). The three-dimensional structures of ADH8 and of the binary complex ADH8-NADP(+) have been now determined and refined to resolutions of 2.2A and 1.8A, respectively. The coenzyme and substrate specificity of ADH8, that has 50-65% sequence identity with vertebrate NAD(H)-dependent ADHs, suggest a role in aldehyde reduction probably as a retinal reductase. The large volume of the substrate-binding pocket can explain both the high catalytic efficiency of ADH8 with retinoids and the high K(m) value for ethanol. Preference of NADP(H) appears to be achieved by the presence in ADH8 of the triad Gly223-Thr224-His225 and the recruitment of conserved Lys228, which define a binding pocket for the terminal phosphate group of the cofactor. NADP(H) binds to ADH8 in an extended conformation that superimposes well with the NAD(H) molecules found in NAD(H)-dependent ADH complexes. No additional reshaping of the dinucleotide-binding site is observed which explains why NAD(H) can also be used as a cofactor by ADH8. The structural features support the classification of ADH8 as an independent ADH class.
Miele, G M; Carpenter, K M; Smith Cockerham, M; Trautman, K D; Blaine, J; Hasin, D S
No existing diagnostic interview assesses severity of dependence based on DSM-IV criteria across a range of substances. The Substance Dependence Severity Scale (SDSS) was designed to serve this purpose, consisting of substance-specific scales of both severity and frequency of DSM-IV criteria. This study investigated the reliability and validity of the SDSS. The test-retest reliability of the SDSS in 175 (112 male and 63 female) treated substance users ranged from good to excellent for alcohol, cocaine, heroin and sedatives (interclass correlation coefficients (ICCs)=0.75-0.88 for severity, 0.67-0.85 for frequency). Results for cannabis were lower, ranging from fair to good (ICCs=0.50-0.62). Results for joint rating and internal consistency reliability were comparable to test-retest findings. In addition to indicators of concurrent validity, scale applications are presented and discussed.
Adamson, Simon J; Sellman, J Douglas; Foulds, James A; Frampton, Christopher M A; Deering, Daryle; Dunn, Alistair; Berks, John; Nixon, Lee; Cape, Gavin
Despite the high rate of co-occurrence of major depression and alcohol dependence, the role of pharmacotherapy in their treatment remains unclear. In the new era of naltrexone for alcohol dependence, it is notable that only 1 study to date has examined the efficacy of antidepressant medication prescribed concurrently with naltrexone. We aimed to determine whether combining naltrexone with citalopram produced better treatment outcomes than naltrexone alone in patients with co-occurring alcohol dependence and depression, and to investigate whether either sex or depression type (independent or substance-induced depression) moderated treatment response. Participants were 138 depressed alcohol-dependent adults who were not required to be abstinent at the commencement of the trial. They were randomized to 12 weeks of citalopram or placebo, plus naltrexone and clinical case management. Treatment was well attended, and medications were reasonably well tolerated with high adherence rates. Substantial improvements in both mood and drinking occurred in both groups, with no significant differences between groups on any of the mood or drinking outcome measures, whether or not other variables were controlled for. No interaction effect was found for independent/substance-induced depression status, whereas there was a marginal effect found by sex, with greater improvement in 1 drinking outcome measure (percent days abstinent) in women taking citalopram. These findings suggest that citalopram is not a clinically useful addition to naltrexone and clinical case management in this treatment population. Independent/substance-induced depression status did not predict treatment response. Findings for sex were equivocal.
Ohtani, Nobuyo; Narita, Shin; Yoshihara, Eiji; Ohta, Mitsuaki; Iwahashi, Kazuhiko
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.
McPherson, A; Martin, C R
The findings from the present study reveal that the Beck Depression Inventory (BDI) is a reliable and valid instrument for measuring depression in a variety of populations. This realization should enable nurses and other health professionals to utilize the tool with added confidence and assurance. * The main finding was that the BDI would probably be a reliable and valid screening tool in an alcohol-dependent population. This conclusion appears to echo the relationship that alcohol consumption generally has with depression. This finding is important to those practitioners using the BDI in this population in that it provides further evidence to enhance their practical experience. Abstract A psychometric evaluation of the Beck Depression Inventory (BDI) was carried out on contemporary studies to ascertain its suitability for use in an alcohol-dependent population. Three criteria were used for this: factor analysis, test-retest reliability and internal consistency reliability. Factor analysis revealed that its structure is consistent with either two or three factor models, depending on the population. Test-retest results concluded that the correlation coefficient remained above the recommended threshold and internal consistency reliability highlighted alpha coefficient results consistently above suggested scores, leading to the conclusion that the BDI is probably an effective screening tool in an alcohol-dependent population.