Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: A double-blind, sham-controlled study

Background: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. Methods: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30 s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. Results: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p < 0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. Conclusions: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Cocaine effects on mouse incentive-learning and human addiction are linked to alpha 2 subunit-containing GABA(A) receptors

Because GABA(A) receptors containing alpha 2 subunits are highly represented in areas of the brain, such as nucleus accumbens (NAcc), frontal cortex, and amygdala, regions intimately involved in signaling motivation and reward, we hypothesized that manipulations of this receptor subtype would influence processing of rewards. Voltage-clamp recordings from NAcc medium spiny neurons of mice with alpha 2 gene deletion showed reduced synaptic GABA(A) receptor-mediated responses. Behaviorally, the deletion abolished cocaine`s ability to potentiate behaviors conditioned to rewards (conditioned reinforcement), and to support behavioral sensitization. In mice with a point mutation in the benzodiazepine binding pocket of alpha 2-GABA(A) receptors (alpha 2H101R), GABAergic neurotransmission in medium spiny neurons was identical to that of WT (i.e., the mutation was silent), but importantly, receptor function was now facilitated by the atypical benzodiazepine Ro 15-4513 (ethyl 8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4] benzodiazepine-3-carboxylate). In alpha 2H101R, but not WT mice, Ro 15-4513 administered directly into the NAcc-stimulated locomotor activity, and when given systemically and repeatedly, induced behavioral sensitization. These data indicate that activation of alpha 2-GABA(A) receptors (most likely in NAcc) is both necessary and sufficient for behavioral sensitization. Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.

Compulsive features in behavioural addictions: the case of pathological gambling

Aims To describe, in the context of DSM-V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG). Methods A systematic literature review of evidence for the proposed re-classification of PG as an addiction. Results Findings include: (i) phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego-syntonic/ego-dystonic dichotomy; (ii) common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); (iii) neuroimaging support for shared neurocircuitries between behavioural and substance addictions and differences between obsessivecompulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; (iv) genetic findings more closely related to endophenotypic constructs such as compulsivity and impulsivity than to psychiatric disorders; (v) psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; (vi) community and pharmacotherapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioural therapies, such as exposure therapy, appear applicable to OCD, PG or SUDs, suggesting some commonalities across disorders. Conclusions PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD.

Role of Two Clusters of Male Alcoholics in Treatment Retention

Aims: This study aimed to classify alcohol-dependent outpatients on the basis of clinical factors and to verify if the resulting types show different treatment retention. Methods: The sample comprised 332 alcoholics that were enrolled in three different pharmacological trials carried out at Sao Paulo University, Brazil. Based on four clinical factors problem drinking onset age, familial alcoholism, alcohol dependence severity, and depression - K-means cluster analysis was performed by using the average silhouette width to determine the number of clusters. A direct logistic regression was performed to analyze the influence of clusters, medication groups, and Alcoholics Anonymous ( AA) attendance in treatment retention. Results: Two clusters were delineated. The cluster characterized by earlier onset age, more familial alcoholism, higher alcoholism severity, and less depression symptoms showed a higher chance of discontinuing the treatment, independently of medications used and AA attendance. Participation in AA was significantly related to treatment retention. Discussion: Health services should broaden the scope of services offered to meet heterogeneous needs of clients, and identify treatment practices and therapists which improve retention. Information about patients' characteristics linked to dropout should be used to make treatment programs more responsive and attractive, combining pharmacological agents with more intensive and diversified psychosocial interventions. Copyright (C) 2012 S. Karger AG, Basel

Psychosocial and clinical predictors of retention in outpatient alcoholism treatment

Objective: One of the factors associated with low rates of compliance in the treatment for alcoholism seems to be the intensity of craving for alcohol. This study aimed to evaluate the associations between alcohol craving and biopsychosocial addiction model-related variables and to verify whether these variables could predict treatment retention. Methods: The sample consisted of 257 male alcoholics who were enrolled in two different pharmacological trials conducted at the Universidade de Sao Paulo in Brazil. Based on four factors measured at baseline - biological (age, race, and family alcoholism), psychiatric (depression symptoms), social (financial and marital status), and addiction (craving intensity, severity of alcohol dependence, smoking status, drinking history, preferential beverage, daily intake of alcohol before treatment) - direct logistic regression was performed to analyze these factors' influence on treatment retention after controlling for medication groups and AA attendance. Results: Increasing age, participation in Alcoholics Anonymous groups, and beer preference among drinkers were independently associated with higher treatment retention. Conversely, higher scores for depression increased dropout rates. Conclusion: Health services should identify the treatment practices and therapists that improve retention. Information about patients' characteristics linked to dropouts should be studied to render treatment programs more responsive and attractive, combining pharmacological agents with more intensive and diversified psychosocial interventions.

Gender differences in drinking patterns and alcohol-related problems in a community sample in Sao Paulo, Brazil

OBJECTIVE: To investigate drinking patterns and gender differences in alcohol-related problems in a Brazilian population, with an emphasis on the frequency of heavy drinking. METHODS: A cross-sectional study was conducted with a probability adult household sample (n = 1,464) in the city of Sao Paulo, Brazil. Alcohol intake and ICD-10 psychopathology diagnoses were assessed with the Composite International Diagnostic Interview 1.1. The analyses focused on the prevalence and determinants of 12-month non-heavy drinking, heavy episodic drinking (4-5 drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3 times/week), as well as associated alcohol-related problems according to drinking patterns and gender. RESULTS: Nearly 22% (32.4% women, 8.7% men) of the subjects were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest frequency of heavy drinking reported the most problems. Among subjects who did not engage in heavy drinking, men reported more problems than did women. A gender convergence in the amount of problems was observed when considering heavy drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers to present lifetime depressive disorders. Lifetime nicotine dependence was associated with all drinking patterns. Heavy and frequent drinking was not restricted to young ages. CONCLUSIONS: Heavy and frequent episodic drinking was strongly associated with problems in a community sample from the largest city in Latin America. Prevention policies should target this drinking pattern, independent of age or gender. These findings warrant continued research on risky drinking behavior, particularly among persistent heavy drinkers at the non-dependent level.

Use of alcohol and other drugs among Brazilian college students: effects of gender and age

Objective: To assess the frequency of drug use among Brazilian college students and its relationship to gender and age. Methods: A nationwide sample of 12,721 college students completed a questionnaire concerning the use of drugs and other behaviors. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST-WHO) criteria were used to assess were used to assess hazardous drug use. A multivariate logistic regression model tested the associations of ASSIST-WHO scores with gender and age. The same analyses were carried out to measure drug use in the last 30 days. Results: After controlling for other sociodemographic, academic and administrative variables, men were found to be more likely to use and engage in the hazardous use of anabolic androgenic steroids than women across all age ranges. Conversely, women older than 34 years of age were more likely to use and engage in the hazardous use of amphetamines. Conclusions: These findings are consistent with results that have been reported for the general Brazilian population. Therefore, these findings should be taken into consideration when developing strategies at the prevention of drug use and the early identification of drug abuse among college students.

Gender differences in drinking patterns and alcohol-related problems in a community sample in São Paulo, Brazil

OBJECTIVE: To investigate drinking patterns and gender differences in alcohol-related problems in a Brazilian population, with an emphasis on the frequency of heavy drinking. METHODS: A cross-sectional study was conducted with a probability adult household sample (n = 1,464) in the city of São Paulo, Brazil. Alcohol intake and ICD-10 psychopathology diagnoses were assessed with the Composite International Diagnostic Interview 1.1. The analyses focused on the prevalence and determinants of 12-month nonheavy drinking, heavy episodic drinking (4-5 drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3 times/week), as well as associated alcohol-related problems according to drinking patterns and gender. RESULTS: Nearly 22% (32.4% women, 8.7% men) of the subjects were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest frequency of heavy drinking reported the most problems. Among subjects who did not engage in heavy drinking, men reported more problems than did women. A gender convergence in the amount of problems was observed when considering heavy drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers to present lifetime depressive disorders. Lifetime nicotine dependence was associated with all drinking patterns. Heavy and frequent drinking was not restricted to young ages. CONCLUSIONS: Heavy and frequent episodic drinking was strongly associated with problems in a community sample from the largest city in Latin America. Prevention policies should target this drinking pattern, independent of age or gender. These findings warrant continued research on risky drinking behavior, particularly among persistent heavy drinkers at the non-dependent level.