Relapse In Alcohol-dependent Patients Research Articles

Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice.

Alcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute withdrawal and neuroinflammation can be harmful in themselves, and lasting withdrawal symptoms contribute to relapse. Here, we conducted an initial feasibility study assessing several behavioral and neurochemical factors in female C3H/HeNRj (C3H) and C57BL/6JRj (B6) mice to determine which strain showed the clearest alcohol withdrawal symptoms during long-term abstinence and neurochemical alterations following re-exposure. Female C3H and B6 mice (n = 12 per group/strain) were intermittently exposed to alcohol-containing or control liquid diets for 3 weeks. Acute and prolonged withdrawal symptoms were assessed over a period of 3 weeks using a battery of behavioral test, comprised of alcohol self-administration, anhedonia, hyperalgesia, anxiety-like and depressive-like disturbances. Brain inflammation was measured by multiplex cytokine assay. Monoamine levels in the hippocampus and striatum, as well as exploratory analyses of cations levels in the cerebellum, were assessed by High-Performance Liquid Chromatography (HPLC). Both C3H and B6 alcohol-exposed mice displayed decreased saccharin intake or preference and higher stress levels assessed by ultrasonic vocalizations (USVs) recordings. B6 but not C3H alcohol-exposed mice also exhibited a slower decline of alcohol oral self-administration (OSA), hyperalgesia, elevated brain TNF-α and elevated serotonin turnover. Our findings highlight the suitability of the B6 strain to study the behavioral and neurochemical alterations caused by alcohol withdrawal and the potential efficacy of experimental treatments, not only in early detoxification, but also in prolonged abstinence. The feasibility of these assays is important because long-lasting withdrawal symptoms are often the main cause of relapse in alcohol-dependent patients.

Automatic Approach Behaviors in Alcohol Dependence: Does a Cognitive Bias Modification Training Affect Pavlovian-to-Instrumental Transfer Effects?

Introduction: Positively conditioned Pavlovian cues tend to promote approach and negative cues promote withdrawal in a Pavlovian-to-instrumental transfer (PIT) paradigm, and the strength of this PIT effect was associated with the subsequent relapse risk in alcohol-dependent (AD) patients. When investigating the effect of alcohol-related background cues, instrumental approach behavior was inhibited in subsequent abstainers but not relapsers. An automatic approach bias towards alcohol can be modified using a cognitive bias modification (CBM) intervention, which has previously been shown to reduce the relapse risk in AD patients. Here we examined the effects of such CBM training on PIT effects and explored its effect on the relapse risk in detoxified AD patients. Methods: N = 81 recently detoxified AD patients performed non-drug-related and drug-related PIT tasks before and after CBM versus placebo training. In addition, an alcohol approach/avoidance task (aAAT) was performed before and after the training to assess the alcohol approach bias. Patients were followed up for 6 months. Results: A stronger alcohol approach bias as well as a stronger non-drug-related PIT effect predicted relapse status in AD patients. No significant difference regarding relapse status or the number of heavy drinking days was found when comparing the CBM training group versus the placebo group. Moreover, there was no significant modulation effect of CBM training on any PIT effect or the aAAT. Conclusion: A higher alcohol approach bias in the aAAT and a stronger non-drug-related PIT effect both predicted relapse in AD patients, while treatment outcome was not associated with the drug-related PIT effect. Unlike expected, CBM training did not significantly interact with the non-drug-related or the drug-related PIT effects or the alcohol approach bias.

P.033 Attenuation of alcohol-cue modulated insula connectivity by naltrexone predicts relapse in alcohol-dependent patients: a longitudinal clinical neuroimaging trial

The goal of the current study was to use tree-based methods to identify moderators of acamprosate effect on abstinence from heavy drinking in COMBINE, the largest study of pharmacotherapy for alcoholism in the United States to date. We used three different tree-based methods for identification of subgroups with enhanced treatment response on acamprosate based on over 100 predictors measured at baseline in COMBINE. No heavy drinking during the last two months of treatment was the considered outcome. All three methods identified consecutive days of abstinence prior to treatment as the most important moderator of treatment effect. Acamprosate was beneficial for participants with shorter abstinence (1 week or less) especially when body mass index was low or normal. In this group, 46% of participants receiving active acamprosate abstained from heavy drinking compared to 23% of those receiving placebo acamprosate. Prior treatment, age, drinking goal and cognitive inefficiency were identified as moderators of acamprosate effects by one of the three methods. In conclusion, acamprosate may be beneficial for participants with shorter abstinence who are not overweight or obese. One hypothesis for this finding is that this subgroup may have greater glutamatergic hyperactivity, a target of acamprosate, and may achieve better drug plasma levels based on their lower BMI. In contrast, those with extended pretreatment abstinence who have anotherwise good prognosis did not benefit from acamprosate. Further validation of the results in independent data sets is necessary.

Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking

BackgroundPavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. MethodsRecently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. ResultsWhen training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging–based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Δ = −24.4 ± 6.0 g vs. −5.7 ± 3.6 g; p = .019). ConclusionsThese results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.

Sodium Oxybate Therapy for Alcohol Withdrawal Syndrome and Keeping of Alcohol Abstinence.

Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous and endogenous molecule with neuromodulator properties. In the United States, GHB is an approved drug for the treatment of narcolepsy and narcolepsy with cataplexy in adults. In some European Union countries, sodium oxybate is applied for the treatment of opioid and alcohol withdrawal. The aim of the present review was to describe the state of art of the pre-clinical research and the clinical evidence related to GHB used alone or in combination with other treatments in alcohol withdrawal syndrome and alcohol abstinence maintenance. Internationally published pre-clinical findings and clinical studies investigating the effects of GHB on alcohol withdrawal syndrome and alcohol abstinence maintenance were collected and described considering seven clinical studies involving GHB in the treatment of alcohol withdrawal abstinence and five clinical studies involving GHB in the treatment of alcohol abstinence maintenance. Furthermore, GHB pharmacology and characteristics of abuse were briefly detailed. Clinical evidence indicates that GHB is effective in reducing symptoms of alcohol withdrawal syndrome and produces beneficial effects comparable to those of benzodiazepines or chlometiazole. GHB proved effective in increasing alcohol abstinence maintenance and in reducing alcohol craving, but it did not show any influence in relapses of heavy drinkers when given alone. Conversely, it seems to be effective in reducing relapses in alcohol dependent patients when given in combination with naltrexone and escitalopram. Despite this bunch of evidence, studies are still limited and investigations including a larger number of patients are needed. In addition, some safety concerns, such as insufficiency against hallucinations in alcohol withdrawal and potential development of GHB dependence have to be more investigated.

Alcohol Abstinence and Relapse in ALD Patients, Predicting the Unpredictable

1. Abstract <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=>1.1. <span style=font-size:10.0pt;font-family: times= new= roman,serif=>Objectives: <span style=font-size:10.0pt; font-family: times= new= roman,serif=> Alcoholism is a chronic relapsing disorder. Alcoholism is common, and continues to be the source of great cost to afflicted individuals, their families and the community at large. Alcohol dependence is characterized by a prolonged course of alcohol-related problems and a persistent vulnerability to relapse. Even though there is an improvement in multiple domains of life after alcohol treatment, the risk of relapse remains high following treatment. This prospective and retrospective study of 451 patients with alcohol use disorders was done with an intent to assess various factors affecting remission and relapse and improve outcome for individuals with alcohol dependence. Demographic variables, clinical parameters and certain psychosocial factors were evaluated. Early identification of risk factors may help us in defining a more rigorous follow up protocol in these sub group of patients. 1.2. Methods: Patients with ethanol related liver disease and alcohol dependence were enrolled after their presentation in gastroenterology clinic and followed thereafter at 1, 3, 6, and 12 months. Initial assessments included USG abdomen LFT RFT, UGI Endoscopy and other relevant investigations. Semi structured clinical interviews, the Symptom Checklist 90-Revised (SCL90-R), Addiction Severity Index (ASI), the Beck Depression Inventory (BDI) were recorded. <span style=font-size:10.0pt; font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=> High-Risk Alcoholism Relapse Scale based score was calculated.2 Patients were reassessed at six and twelve months to determine treatment outcome (abstinence status and duration of continuous abstinence). Data were coded, validated and analyzed using descriptive statistics. 1.3. Results: A majority of the sample 70 percent (n=315) had significant psychiatric symptoms at intake: 22 percent (N=70) presented with depressive symptoms, 17 percent (N=15) with anxiety symptoms, and 41 percent (N=192) with combined depressive and anxiety symptoms. Fourty percent of patients who presented with combined depression and anxiety symptoms were abstinent at six months. These patients had worse prognosis than less symptomatic cohort at intake, including those who presented with depression symptoms alone; in the latter group, 60 percent were abstinent at six months. Key predictor variables included days in treatment, primary drug of abuse, frequency of drug use, and report of concurrent depression or anxiety symptoms at intake. <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=>1.4. <span style=font-size:10.0pt;font-family: times= new= roman,serif=>Conclusions: <span style=font-size:10.0pt; font-family: times= new= roman,serif=> Concurrent depression or anxiety symptoms low education, lack of motivation for abstinence had a significant negative predictive effect on treatment outcome. Craving was noted as most common cause for relapse in alcohol dependent patients. Higher relapse rate was seen in concomitant opioid dependence, high risk’ situations, previous relapses Positive predictors were more number of coping strategies, principally adaptive ones. There is significant association between age at first drink, age at dependence, duration of dependence, other Co-morbid diagnosis of patients and relapse. Early consideration of these risk factors and more rigorous follow up can help in reducing incidence of relapses.

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

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

Deficient inhibition in alcohol-dependence: a transcranial magnetic stimulation study.

Event Abstract Back to Event Deficient inhibition in alcohol-dependence: a transcranial magnetic stimulation study. Caroline Quoilin1*, Philippe De Timary1 and Julie Duque1 1 Institute of Neuroscience, Catholic University of Leuven, Belgium Background: The development, maintenance, and relapse phenomena in alcohol-dependence has been related to an impaired inhibitory control, but the neural correlates of this deficit are still unclear1. As impaired inhibition has been classically understood as a pure cognitive deficit, most studies have focused on prefrontal areas, while little attention has been given to the role of more “primary” structures, such as the motor system. Importantly, recent transcranial magnetic stimulation (TMS) studies have observed profound inhibitory changes in the motor output pathway during the preparation of actions2-6; this neural motor inhibition is thought to assist goal-directed behaviors by suppressing neural activity that could cause premature or inappropriate responses7-9. Thus, as inhibition of the motor system supports the ability to subjugate inappropriate behaviors and because this aptitude is altered in alcohol-dependence, we tested the hypothesis that alcohol-dependent (AD) patients may suffer from a shortage of neural motor inhibition. Methods: Single TMS pulses were applied over the right and the left primary motor cortex to elicit motor-evoked potentials (MEPs) in the left and the right hand, respectively, of 20 detoxified ADs and 20 matched healthy subjects performing a choice reaction time task. In addition, behavioral inhibitory aptitudes and trait impulsivity were assessed in all participants. Finally, the patients were called back one year after the experiment to evaluate their relapse status and the potential relationship with motor inhibition. Results: As expected, AD patients exhibited poorer behavioral inhibition and higher trait impulsivity than control subjects. More importantly, the TMS experiment revealed a considerable shortage of neural motor inhibition in AD patients. Interestingly, the patients who resumed consuming alcohol within the year following the experiment were those displaying the strongest deficits, both at the behavioral and the neural levels, while the relapse status did not depend on the trait impulsivity measure. Conclusions: Our data suggest a strong motor component in the neural correlate of altered inhibitory control in AD patients. They also highlight an intriguing relationship with relapse and the perspective of a new biomarker to follow strategies aiming at reducing relapse in AD patients. Short lay summary: Impaired inhibitory control is a core element of alcohol-dependence. So far, most studies investigating the neural correlates of this deficit have focused on prefrontal areas, overlooking the contribution of more “primary” structures, such as the motor cortex. Yet, appropriate neural motor inhibition may be a central aspect of healthy behavior. Here, by using transcranial magnetic stimulation, we revealed a deficit in neural motor inhibition in alcohol-dependent patients relative to control subjects. Moreover, this alteration was stronger in patients who ended-up relapsing during the year following the experiment, suggesting that it may represent a new biomarker of the risk for relapse.

V1b Receptor Antagonist SSR149415 and Naltrexone Synergistically Decrease Excessive Alcohol Drinking in Male and Female Mice.

A recent clinical trial found that pharmacological blockade of V1b receptors reduces alcohol relapse in alcohol-dependent patients. SSR149415 is a selective V1b receptor antagonist that has potential for development as an alcohol dependency treatment. In this study, we investigated whether SSR149415 alone or in combination with the mu-opioid receptor (MOP-r) antagonist naltrexone (NTN) would alter excessive alcohol drinking in mice. Both sexes of C57BL/6J (B6) mice were subjected to a chronic intermittent access (IA) drinking paradigm (2-bottle choice, 24-hour access every other day) for 3weeks. Sucrose and saccharin drinking were used as controls for alcohol-specific drug effects. Neuronal proopiomelanocortin (POMC) enhancer (nPE) knockout mice with hypothalamic-specific loss of POMC (including beta-endorphin, the main endogenous ligand of MOP-r) were used as a genetic control for the effects of NTN. Acute administration of SSR149415 (1 to 30mg/kg) reduced alcohol intake and preference in a dose-dependent manner in both male and female B6 mice after IA. To investigate potential synergistic effects between NTN and SSR149415, we tested 6 different combination doses of SSR149415 and NTN, and found that a combination of SSR149415 (3mg/kg) and NTN (1mg/kg) reduced alcohol intake profoundly at doses lower than the individual effective doses in both sexes of B6 mice. We confirmed the effect of SSR149415 on reducing alcohol intake in nPE-/- male mice, consistent with independent mechanisms by which SSR149415 and NTN decrease alcohol drinking. The combination of V1b antagonist SSR149415 with NTN at individual subthreshold doses shows potential in alcoholism treatment, possibly with less adverse effects.

Life events in past one year in alcohol-dependent patients presenting with relapse

ABSTRACTObjective: Stressful life events may be an important factor in relapse in alcohol-dependent patients. This study was carried out to examine the life events in past one year in alcohol-dependent patients presenting with relapse.Methods: Thirty consecutive patients, aged 18 to 60 years, ICD-10 Diagnostic Criteria for Research for alcohol dependence syndrome, with current relapse were assessed on Severity Alcohol Dependence Questionnaire (SADQ) to measure alcohol dependence severity level and Presumptive Stressful Life Events Scale (PSLES) to identify life events in past one year prior to the relapse.Results: The mean number of life events among patients in past one year was 3.06 (SD 1.81). The mean number of undesirable life events was significantly higher than desirable events (p < .001). The most common life event was financial loss or problems (43%), followed by large loan and marital conflict (27%).Conclusion: There were a mean of three life events in the year preceding relapse in patients with alcohol dependence. Psychosocial treatment targeting stressful life events could be useful adjunct in the management of alcohol dependence.

One Year Clinical Correlates of EtG Positive Urine Screening in Alcohol-Dependent Patients: A Survival Analysis.

Little evidence exists supporting the efficacy of regular alcohol urine screening (RAUS) in the management of alcohol dependence, despite recent improvements in urine biomarkers. In this study, we aimed at investigating 1 year, differential clinical correlates between a positive and a negative baseline urine ethyl glucuronide (EtG) screening. Alcohol-dependent outpatients participating in a previous cross-sectional study where EtG and ethanol diagnostic performances were compared in a double blind design were included. After 1 year, the presence of relapse, the number of hospitalizations and whether patients had abandoned treatment or not were assessed from electronic medical records. A survival analysis was conducted to compare time to relapse between EtG negative and positive subjects. Regression models were performed to compare the mean number of days hospitalized between groups, the risk of being lost to follow-up and treatment expenses. Of note, 152 patients (mean age 52, 67% males) were included. The mean time to relapse was of 163 days in EtG positive subjects, compared to 329 days in those with a negative result. In the Cox-regression model, only EtG positivity yielded significant results, with a hazard ratio of 5:3 (95% CI: 3.1-9.1). EtG positive was also the only significant predictor of a greater number of hospitalization days and treatment expenses. Younger age was the only variable predicting a greater risk of treatment abandonment. RAUS with sensible biomarkers could improve clinicians' ability to assess patients' relapse risk. Further prospective studies will have to determine if this can be translated into a better prevention capacity. Positive urine screenings, when conducted with highly sensible alcohol biomarkers, significantly indicate a greater risk of relapse in alcohol-dependent patients and have the capacity to predict a greater risk of hospitalization and greater treatment expenses.

Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse.

The glutamatergic system plays a key role in the maintenance of drug use and development of drug-related conditioned behaviours. In particular, hyper-glutamatergic activity and N-methyl-D-aspartate receptor (NMDAR) activation may drive drug craving and relapse. Inhibition of kynurenine-3-monooxygenase (KMO) shifts the metabolic kynurenine pathway towards production of kynurenic acid, which leads to a reduction of glutamatergic/NMDAR activity via different mechanisms. In this study, we investigated whether drug-seeking and relapse behaviour could be modified by the metabolic shift of endogenous kynurenine pathway. An inhibitor of kynurenine-3-monooxygenase (KMO) Ro61-8048 (4 and 40mg/kg) and its prodrug JM6 (100 and 200mg/kg) were tested in two behavioural rat models for drug seeking and relapse-the alcohol deprivation effect (ADE) model in long-term alcohol-drinking rats and the model of cue-induced reinstatement of alcohol- and cocaine-seeking behaviour. Our results show that relapse-like alcohol drinking during the ADE was abolished by repeated intraperitoneal administration of Ro61-8048 and significantly reduced by its oral prodrug JM6. Cue-induced reinstatement of both alcohol- and cocaine-seeking behaviour was also abolished by administration of Ro61-8048. Pharmacological enhancement of endogenous kynurenic acid levels provides a novel treatment strategy to interfere with glutamatergic/NMDAR activity as well as with craving and relapse in alcohol-dependent patients and drug addicts.

Doctors' views of disulfiram and their response to relapse in alcohol-dependent patients, Free State, 2009.

BackgroundDisulfiram is the oldest and best known drug to prevent relapse after detoxification from alcohol. Effective use of the drug is dependent on stringent monitoring and high levels of external motivation. Doctors’ perceptions about the drug have not been investigated extensively.AimWe investigated the perceptions and practices of doctors involved in relapse prevention in alcoholics with regard to disulfiram and their response to relapse.SettingThe study population consisted of 60 doctors from the Free State Province, involved in the follow-up of alcoholics across various work settings.MethodsA cross-sectional descriptive study design was used, and data collection involved the use of a questionnaire and semi-structured interviews. Quantitative results are presented in figures and percentages to provide a background for the qualitative findings that are clustered in themes.ResultsA quarter of participants did not prescribe disulfiram, another quarter prescribed disulfiram routinely after detoxification, and half of them prescribed it for selected cases only. Subject to affordability, selection of disulfiram was mainly determined by the perceived level of the patient’s motivation. External motivation sometimes took the form of threats of bodily harm or death caused by drinking. Some participants regarded relapse as confirmation of poor motivation and even a valid reason for terminating the doctor-patient relationship.ConclusionDoctors perceive disulfiram as a psychological tool to induce motivation through creating fear of drinking. Failure and success are perceived as related to the level of motivation. These perceptions could be unfair as biological factors in inter-patient variability in response are ignored.

Efecto de Zhubin (KI9) para reducir el deseo de consumir alcohol en pacientes alcohólicos: un ensayo aleatorizado con grupo de placebo y control

ObjectiveTo examine the effect of acupuncture on Zhubin (KI9) in reducing alcohol craving in alcohol-dependent patients. MethodsTwenty male alcohol-dependent patients were randomly assigned to two groups, a treatment group (10 cases, age 43.0±6.8 years) and a placebo group (10 cases, age 44.5±7.9 years). The treatment group was treated with real needle acupuncture on Zhubin (KI9) twice a week for 4 weeks, and the control group was treated with placebo needle acupuncture. Both groups were given acupuncture treatment using Park Sham Device (PSD). Alcohol craving was measured by the Visual Analogue Scale (VAS) before treatment to establish a baseline, and after 1, 2, and 4 weeks of treatment. Repeated measures ANOVA was used to determine the main and interaction effects of time and on the outcome measure (VAS). ResultsThere was a significant effect of time on VAS score (df=3; F=13.3; P<.01). Main effect of group on VAS score was significant (df=1; F=10.9; P<.01) and the time símbolo de multiplicación group interaction was also significant (df=3; F=4.7; P<.01). ConclusionsReal-needle acupuncture therapy on Zhubin (KI9) showed effectiveness in reducing alcohol craving. These results strongly suggest the usefulness of acupuncture therapy on Zhubin (KI9) in preventing a relapse in alcohol dependent patients.

Transcranial direct current stimulation of the prefrontal cortex reduces cue-reactivity in alcohol-dependent patients.

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.

Hair ethyl glucuronide and serum carbohydrate deficient transferrin for the assessment of relapse in alcohol-dependent patients

ObjectivesEthyl glucuronide in hair (hEtG) and serum carbohydrate deficient transferrin (%CDT) are valuable markers for alcohol abuse, but their diagnostic accuracy to monitor abstinence and relapse is unclear. Here, we investigate to what extent repeated measurements of hEtG and %CDT can be used to monitor relapse in alcohol-dependent patients during abstinence treatment. Design and methodsHEtG and %CDT were measured in individuals starting treatment for alcohol dependence both at treatment entry and 3months later. Alcohol consumption and relapse episodes were recorded using the Time Line Follow Back and by alcohol breath and urine tests, and correlated with hEtG and %CDT measurements. ResultsFifteen patients completed the study, of which nine had one or more relapses. Hair EtG and serum %CDT identified whether a relapse occurred in 78% and 57% of cases, respectively. Only hEtG correlated with the amount of alcohol consumed before treatment entry (Pearson r=0.92; p<0.001). The specificity of %CDT to assess abstinence during treatment was 100%. HEtG had a specificity of only 17%; however, in all patients who remained abstinent, hEtG decreased with >85% from initial values. Mean hEtG, but not %CDT, differed significantly between patients who relapsed and patients who remained abstinent (p=0.034). ConclusionsHEtG was more sensitive than serum %CDT to assess relapse in alcohol-dependent patients and was positively correlated with the amounts of alcohol consumed. In contrast, serum %CDT was more specific for assessing abstinence. We highlight the benefit of repeated measurements of hEtG and serum %CDT for monitoring abstinence during treatment.

Neurocognitive rehabilitation for addiction medicine: From neurophysiological markers to cognitive rehabilitation and relapse prevention.

Currently, relapse prevention remains the main challenge in addiction medicine, indicating that the established treatment methods combining psychotherapy with neuropharmacological interventions are not entirely effective. Therefore, there is a push to develop alternatives to psychotherapy- and medication-based approaches to addiction treatment. Two major cognitive factors have been identified that trigger relapse in addicted patients: attentional biases directed toward drug-related cues, which increase the urge to consume, and impaired response inhibition toward these cues, which makes it more difficult for addicted people to resist temptation. Recent studies on newly detoxified alcoholic patients have shown that by using the appropriate tasks to index these cognitive functions with event-related potentials (ERPs), it is possible to discriminate between future relapsers and nonrelapsers. These preliminary data suggest that the ERP technique has great clinical potential for preventing relapse in alcohol-dependent patients, as well as for addictive states in general. Indeed, ERPs may help to identify patients highly vulnerable to relapse and allow the development of individually adapted cognitive rehabilitation programs. The implementation of this combined approach requires an intense collaboration between psychiatry departments, clinical neurophysiology laboratories, and neuropsychological rehabilitation centers. The potential pitfalls and limitations of this approach are also discussed.

Attentional Bias and Approach/Avoidance Tendencies Do Not Predict Relapse or Time to Relapse in Alcohol Dependency.

Implicit processes such as attentional bias (AB) and automatic approach/avoidance tendencies (AA) play a role in substance use disorders. Whether these processes can predict a relapse in alcohol-dependent patients is still unclear and must be examined in more detail than has been done previously. We aimed to establish whether AB and AA measured during treatment would predict relapse in alcohol-dependent patients. We also investigated whether these implicit processes predicted time to relapse better than a more common binary relapse variable. A total of 50 alcohol-dependent outpatients undergoing treatment completed the study. Patients completed the Addiction Stroop Task, which assesses AB, and the relevant Stimulus-Response Compatibility Task, which measures AA. Time to relapse was assessed 1, 2, and 3 months after the bias assessment. Twenty patients (40%) relapsed during the follow-up period. The average time to relapse was 40 days after the first session. Overall, participants had an AB for alcohol-related stimuli and a tendency to avoid these stimuli. Neither relapse nor time to relapse was predicted by either bias type. Although both AB and avoidance tendencies were present in our sample, these measures did not predict relapse or time to relapse in an outpatient alcohol-dependent sample in the following 3 months. Future research should focus on studying the predictive value of these biases in the short term, for example, using ecological momentary assessment techniques to assess implicit processes shortly before a relapse.

Could cognitive event-related potentials be used to orient neuropsychological rehabilitation? A perspective paper through the example of alcohol dependence

The prevention of relapse is a main challenge to face with in alcohol dependence. Two major cognitive factors can partially account for alcoholics' inability to remain abstinent: attentional biases directed towards alcohol-related stimuli that increase the urge to drink, and impaired response inhibition towards these cues that makes it more difficult for alcoholics to resist temptation. A recent study of ours investigated response inhibition in alcohol dependent patients, by means of an event-related potentials (ERP) modified Go/No-Go paradigm, right after a three weeks detoxification cure. Main results of the study are: (1) among 27 recently detoxified patients, 13 relapsed after a three month follow-up period; (2) at a behavioural level, patients displayed more commission errors than healthy matched controls; however, behavioural data did not allow to discriminate between future relapsers and non-relapsers; and (3) the only parameter discriminating relapsers and non-relapsers was the No-Go P300 component: future relapsers displayed increased amplitudes, suggesting that patients who involve more neural resources to perform inhibition will be those of higher risk to relapse. These preliminary data suggest a great clinical potential of the ERP technique in preventing relapse in alcohol dependent patients, as using cognitive ERP may orient an individual patient to an adapted cognitive rehabilitation program.

Usefulness of Gamma Glutamyl Transferase as Reliable Biological Marker in Objective Corroboration of Relapse in Alcohol Dependent Patients.

The development of reliable diagnostic tool for assessing alcoholism is an utmost necessity in treating and preventing damage due to alcoholism to both individual and armed forces as alcoholism represents a serious health issue with major socioeconomic consequences. To observe, gamma glutamyl transferase (GGT) can serve the practical utility of firmly establishing alcohol dependence /relapse in Armed Forces patients and aid in fair disposals. Fifty two consecutive cases of alcohol dependence syndrome admitted to a peripheral hospital were evaluated for the biological marker gamma glutamyl transferase (GGT) and compared against the gold standard of psychiatrist assessment. The cases were followed up for one year at three months, six months, nine months and 12 months interval. The GGT value of the cases was correlated with the abstinent /relapse status to find the cutoff levels of the GGT as a biological marker. At cutoff level of 50 IU/lit GGT exhibited specificity of 100% and sensitivity varying from 56% to 100%. At lower cut off levels chances of false positive cases with adverse consequences on service prospects of the individuals are high. The mean difference in GGT levels across relapse and abstinent group reached significant statistical proportion at admission and during follow-up at 3 months /6 months/9 months and 12 months. GGT can serve the practical utility of firmly establishing alcohol dependence syndrome in armed forces to aid in fair disposal of cases. It helps in providing motivational inputs to patients. Clinician should pay due consideration to clinical profile, ward observation and unit report as the diagnosis of alcohol dependence syndrome has serious implications towards service prospects of a soldier.