Abstinent Alcohol-dependent Patients Research Articles

Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation in alcohol dependence.

Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward.

Self-defining memories in recently detoxified alcohol-dependent patients.

Patients with alcohol dependence have been shown to be impaired in recalling specific autobiographical events, yet little is known on how changes in the memory of these events may impact their self-representation. In this study, we examined Self-Defining Memories (SDMs), a specific type of autobiographical memory that plays a key role in the construction of personal identity, in 25 patients with alcohol dependence, abstinent from alcohol from 10 days to 6 months, compared to 28 control subjects. We observed that SDMs in patients were significantly less specific and included more reference to alcohol than those of controls. Patients also reported more SDMs with negative emotional valence and higher emotional intensity. These results suggest that recently abstinent alcohol-dependent patients may be prone to define themselves by negative events referring to alcohol consumption, which may contribute to an unfavorable perception of their self and subsequently of their ability to remain abstinent. These findings should be taken into account to optimize psychological approaches in the treatment of alcohol-dependence.

Effects of repetitive imagination of alcohol consumption on craving in alcohol-dependent patients: A pilot study

BackgroundIn the majority of patients with alcohol use disorder (AUD), the clinical course is characterized by multiple relapses to drinking, frequently preceded by intense craving for alcohol. The present pilot study aimed to assess the effects of a repetitive imaginary cue-exposure protocol in reducing craving in recently abstinent alcohol-dependent patients. MethodsSixty-four patients were randomly assigned to six intervention groups and were instructed to repetitively imagine: i) drinking a glass of their preferred alcoholic drink (low vs. high number of repetitions); or ii) drinking a glass of water (low vs. high number of repetitions); or iii) performing an analogous movement or performed no imagination. Additionally, 10 healthy controls were instructed to repetitively imagine drinking a glass of their preferred alcoholic drink (high number of repetitions). The levels of craving before and after intervention were measured using the Alcohol Urge Questionnaire (AUQ) and the Visual Analogue Scale for Craving (VASC). ResultsRepetitive imagination of alcohol consumption did not lead to a significant decrease in craving in alcohol-dependent patients as measured by the AUQ and VASC. In contrast, healthy controls showed a nearly significant decrease of the urge to drink alcohol after applying the protocol with a high number of repetitions. ConclusionsThe findings of this pilot study might indicate an aberrant ability to habituate to alcohol-related stimuli in patients with AUD compared to healthy subjects. Future studies in larger samples are needed to further explore the effectiveness of imaginary cue-exposure interventions in alcohol dependence.

Calcium as a treatment option for alcohol dependence

In the last couple of decades anti-craving drugs have been developed. Acamprosate was described as an effective treatment option to support alcohol abstinence with a low side effect profile. Moreover its molecular mode of action is highly controversial. Recently, calcium salt was described to be the active part of Acamprosate.Using a clinical sample of placebo (n = 10) vs. Acamprosate-treated (n = 19) abstinent alcohol-dependent patients, we measured calcium plasma concentrations after the 1st, 2nd and 3rd month after the treatment commenced. Before treatment, the same physiological calcium concentration of about 2.4 mmol/l was found in both groups respectively. We found significant correlations in the Acamprosate group while no correlations in the placebo group were observed.The very well regulated extracellular calcium serum concentration seems to get out of balance in association with the severity of alcohol dependence in inpatients during withdrawal.Accordingly, in another clinical sample (n = 57) we found a negative correlation between calcium serum concentration and craving (r2= 0.125; P = 0.011) on day 1 of detoxification. The measurement of craving was carried out by a self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS). Furthermore a low calcium level correlated with high breathalyser readings and the number of alcohol inpatient detoxification's.Disclosure of interestThe authors have not supplied their declaration of competing interest.

PMH43 - Reducing Consumption Versus Maintaining Abstinence: Market Access Challenges Facing a Novel Treatment Pathway for Alcohol Addiction in the Eu5

Nalmefene (Lundbeck’s Selincro) is the only marketed drug that aims to reduce alcohol consumption rather than maintain abstinence in alcohol-dependent patients. By examining reimbursement and uptake of nalmefene in the EU5, we explore market access challenges for the novel treatment pathway this drug represents. In February 2015, 253 psychiatrists in France, Germany, Italy, Spain, and the UK were surveyed regarding their prescribing of nalmefene. In addition, 15 EU5 payers involved in determining and regulating access to alcohol addiction pharmaceuticals were interviewed. On average, 10% (UK) to 30% (France) of surveyed physicians’ drug-treated alcohol-addicted patients receive nalmefene. The most commonly cited reasons for not prescribing nalmefene are unfamiliarity with the drug (especially in the UK), a belief that the treatment goal should be abstinence, and preference for another pharmacotherapy. Furthermore, 20% of all surveyed EU5 psychiatrists cite maintaining abstinence/reducing relapse as the greatest unmet need in the pharmacological treatment of alcohol addiction, while 18% (UK) to 38% (France) identify efficacy for maintaining complete abstinence from alcohol after withdrawal and detoxification as their key driver for prescribing a new therapy. Interviewed payers similarly consider nalmefene’s goal of reducing alcohol consumption rather than maintaining abstinence to be a reimbursement challenge, and one that, alongside perceived modest efficacy, has contributed to suboptimal HTA ratings in France and Germany, and to total lack of reimbursement in Italy. Perception of abstinence as the main aim of treatment for alcohol addiction is a considerable market access hurdle for nalmefene and emerging alcohol consumption-reducing agents. Robust superiority over comparators, persuasive marketing that illustrates the benefits of alcohol reduction versus abstinence, and effective targeting of national, regional and local stakeholders are essential to encourage payers to think beyond the price tag, and to maximize familiarity with and use of this novel treatment pathway among prescribers.

Calcium for the treatment of alcohol-dependence

Using a clinical sample of placebo vs. acamprosate-treated abstinent alcohol-dependent patients, we measured calcium plasma concentrations. Before treatment, the same physiological calcium concentration of about 2.4 mmol/l were found in the placebo and acamprosate group. Additionally, blood was drawn after 1, 2 and 3 months of treatment. Although calcium levels are extremely tightly controlled by the kidneys and parathyroid hormone and are more or less constant in each individual. We found tendency (p < 0.1) of enhanced calcium plasma levels in acamprosate vs. placebo treated patients. When correlating the primary efficacy parameters of first drink (rho = 0.64; p < 0.01), severe relapse (rho = 0.43; p = 0.057) and cumulative abstinence (rho = 0.57; p < 0.01) with calcium plasma levels, we found significant correlations in the acamprosate group. We did not find any correlation in the placebo group. Furthermore deviation from the calcium plasma concentration in inpatient alcohol dependent patients during withdrawal seems to be associated with severity of alcohol dependence and craving. This study was supported by DFG

The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving.

The aim of the current study was to determine genotype effects of four single nucleotide polymorphisms (SNPs) in the genes of the N-Methyl-d-aspartate receptor (GRIN1, GRIN2A, GRIN2C) and kainate receptor (GRIK1), which have been previously associated with alcoholism, on behavior, neural cue-reactivity and drinking outcome. Eighty-six abstinent alcohol dependent patients were recruited from an in-patient setting. Neuropsychological tests, genotyping and functional magnetic resonance imaging (fMRI) were used to study genotype effects. GRIN2C risk allele carriers displayed increased alcohol cue-induced activation in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC). Neural activation in the ACC positively correlated with craving for alcohol (r = 0.201, P = 0.032), whereas activation in the dlPFC showed a negative association (r = -0.215, P = 0.023). In addition, dlPFC activation predicted time to first relapse (HR = 2.701, 95%CI 1.244-5.864, P = 0.012). GRIK1 risk allele carriers showed increased cue-induced activation in the medial prefrontal (PFC) and orbitofrontal cortex (OFC) and in the lateral PFC and OFC. Activation in both clusters positively correlated with alcohol craving (rmedOFC, medPFC = 0.403, P = 0.001, rlatOFC, latPFC = 0.282, P = 0.008), and activation in the cluster that encompassed the medial OFC predicted time to first relapse (HR = 1.911, 95%CI 1.030-3.545, P = 0.040). Findings indicate that SNPs in the GRIN2C and GRIK1 genes are associated with altered cue-induced brain activation that is related to craving for alcohol and relapse risk.

Acamprosate: A Review of Its Use in Alcohol Dependence.

Acamprosate (Campral(®), Aotal(®), Regtect(®)) is one of a limited number of pharmacological treatment options approved as an adjunct to psychosocial interventions to facilitate the maintenance of abstinence in alcohol-dependent patients. It has been used in Europe, the USA and other countries for many years and was recently approved for this indication in Japan. In several randomized, double-blind, placebo-controlled trials (without active comparators), acamprosate in conjunction with psychosocial therapy for 3-12 months was generally significantly better than placebo plus psychosocial interventions in improving various key outcomes, including the proportion of patients who maintained complete abstinence from alcohol (complete abstinence rate), the mean cumulative abstinence duration, the percentage of alcohol-free days and the median time to first drink. Acamprosate as an adjunct to psychosocial interventions also demonstrated efficacy in some randomized, active-comparator trials of similar duration. Although results were not always consistent across individual trials, overall findings were generally favourable for acamprosate in a recent meta-analysis, which showed that alcohol-consumption outcomes were similarly improved with acamprosate or naltrexone. Acamprosate is generally well tolerated, has a low propensity for drug interactions and may be used without dosage adjustment in patients with mild to moderate hepatic impairment, although dosage adjustments or contraindications are recommended in patients with renal impairment. Thus, the use of acamprosate as an adjunct to psychosocial interventions in alcohol-dependent patients provides modest but potentially valuable improvements in alcohol-consumption outcomes and is generally well tolerated.

Increased mesolimbic cue-reactivity in carriers of the mu-opioid-receptor gene OPRM1 A118G polymorphism predicts drinking outcome: A functional imaging study in alcohol dependent subjects

The endogenous opioid system is involved in the pathophysiology of alcohol-use disorders. Genetic variants of the opioid system alter neural and behavioral responses to alcohol. In particular, a single nucleotide polymorphism rs1799971 (A118G) in the mu-opioid receptor gene (OPRM1) is suggested to modulate alcohol-related phenotypes and neural response in the mesocorticolimbic dopaminergic system. Little is known about the clinical implications of these changes. The current study investigated the relationship of genotype effects on subjective and neural responses to alcohol cues and relapse in a sample of abstinent alcohol-dependent patients. Functional magnetic resonance imaging (fMRI) was used to investigate alcohol cue-reactivity and drinking outcome of 81 abstinent alcohol-dependent patients. G-allele carriers displayed increased fMRI cue-reactivity in the left dorsal striatum and bilateral insulae. Neural responses to alcohol cues in these brain regions correlated positively with subjective craving for alcohol and positive expectations of alcohol׳s effects. Moreover, alcohol cue-reactivity in the left dorsal striatum predicted time to first severe relapse. Current results show that alcohol-dependent G-allele carriers׳ increased cue-reactivity is associated with an increased relapse risk. This suggests that genotype effects on cue-reactivity might link the OPRM1 A118G risk allele with an increased relapse risk that was reported in earlier studies. From a clinical perspective, risk-allele carriers might benefit from treatments, such as neuro-feedback or extinction-based therapy that are suggested to reduce mesolimbic reactivity.

Effects of d-cycloserine on extinction of mesolimbic cue reactivity in alcoholism: a randomized placebo-controlled trial

Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by cue-exposure-based extinction training (CET). Evidence from preclinical studies suggests that the extinction of conditioned alcohol-seeking behavior might be facilitated by drugs increasing N-methyl-D-aspartate (NMDA) receptor-associated memory consolidation. In this study, we assessed the efficacy of CET treatment supplemented with the partial NMDA-receptor agonist D-cycloserine (DCS) at reducing mesolimbic cue reactivity (CR), craving, and relapse risk in alcoholism. In a randomized, placebo-controlled, double-blind study, we recruited 76 recently detoxified abstinent alcohol-dependent patients. Thirty-two (16 DCS, 16 placebo) patients showed cue-induced ventral-striatal activation measured with functional magnetic resonance imaging (fMRI) prior to treatment and were thus included in the efficacy analyses. After inpatient detoxification, patients underwent nine sessions of CET spaced over 3weeks, receiving either 50mg DCS or placebo 1h prior to each CET session. FMRI was conducted before treatment and 3weeks after treatment onset. Following treatment with CET plus DCS, cue-induced brain activation in the ventral and dorsal striatum was decreased compared to treatment with CET plus placebo. Elevated posttreatment ventral striatal CR and increased craving (assessed using the Obsessive Compulsive Drinking Scale) were associated with increased relapse risk. DCS was shown to augment the effect of CET for alcohol-dependent subjects. The interaction between craving and ventral-striatal CR on treatment outcome suggests that CET might be especially effective in patients exhibiting both high craving and elevated CR.

Effects of cognitive bias modification training on neural alcohol cue reactivity in alcohol dependence.

In alcohol-dependent patients, alcohol cues evoke increased activation in mesolimbic brain areas, such as the nucleus accumbens and the amygdala. Moreover, patients show an alcohol approach bias, a tendency to more quickly approach than avoid alcohol cues. Cognitive bias modification training, which aims to retrain approach biases, has been shown to reduce alcohol craving and relapse rates. The authors investigated effects of this training on cue reactivity in alcohol-dependent patients. In a double-blind randomized design, 32 abstinent alcohol-dependent patients received either bias modification training or sham training. Both trainings consisted of six sessions of the joystick approach-avoidance task; the bias modification training entailed pushing away 90% of alcohol cues and 10% of soft drink cues, whereas this ratio was 50/50 in the sham training. Alcohol cue reactivity was measured with functional MRI before and after training. Before training, alcohol cue-evoked activation was observed in the amygdala bilaterally, as well as in the right nucleus accumbens, although here it fell short of significance. Activation in the amygdala correlated with craving and arousal ratings of alcohol stimuli; correlations in the nucleus accumbens again fell short of significance. After training, the bias modification group showed greater reductions in cue-evoked activation in the amygdala bilaterally and in behavioral arousal ratings of alcohol pictures, compared with the sham training group. Decreases in right amygdala activity correlated with decreases in craving in the bias modification but not the sham training group. These findings provide evidence that cognitive bias modification affects alcohol cue-induced mesolimbic brain activity. Reductions in neural reactivity may be a key underlying mechanism of the therapeutic effectiveness of this training.

La respuesta de sobresalto y la inhibición prepulso en los trastornos por uso de alcohol. Implicaciones para la práctica clínica

In recent years, the addictive processes and more specifically Alcohol Use Disorders (AUD) have been studied using different neuropsychological and neurophysiological approaches, including the Startle Response (SR) and the Prepulse Inhibition (PPI). In this article we present the results of three studies carried out by our group. The first study included 19 male patients who had alcohol dependence and were detoxified for a period of 10-14 days, undergoing testing for SR and PPI at baseline and after the detoxification treatment. The second study included 60 abstinent alcoholic men who had been abstinent for more than a month and who were compared with healthy controls. The sample of the third studied included 40 alcohol dependent men, who proceeded from study 2, and who were assessed with laboratory impulsivity paradigms after having been tested on SR and PPI. Our studies have found that alcohol dependent patients exhibit a reduced magnitude of the SR and impairments in the PPI compared to healthy controls. Impairments in the PPI are even more evident when the subject is actively consuming alcohol and during early detoxification, and tend to partially improve after the detoxification process is successfully completed, although percentages of PPI do not reach the levels of healthy controls. Finally, we found that variables of the SR and variables of impulsivity were correlated in abstinent alcohol dependent patients, but not in controls. In conclusion, SR and PPI could be useful tools for the assessment of patients with alcohol dependence. They could either be considered as vulnerability markers for the development of alcohol or be an index of alcohol neurotoxicity in the central nervous system.

Efficacy of Baclofen on Abstinence and Craving in Alcohol-dependent Patients: a Meta-analysis of Randomized Controlled Trials

PurposeWe conducted a meta-analysis in order to estimate the efficacy of baclofen on the maintenance of abstinence and the decrease of craving in alcohol-dependent patients. MethodsAll randomized controlled clinical trials assessing baclofen for at least four weeks’ treatment duration versus placebo or other comparators were included. The primary outcome measure was the percentage of patients who had not consumed alcohol at the end of the treatment. Measures of cumulative abstinence and indexes of craving were also assessed. ResultsCompared to placebo, baclofen was associated with a significant increase of 179% in the percentage of abstinent patients at the end of the trial, without heterogeneity. For secondary outcome measures, based on a random-effect model, no significant effect of baclofen was observed compared to placebo. ConclusionsOur meta-analysis brings weak support towards an efficacy of low dosages of baclofen on the maintenance of abstinence in alcohol-dependent patients.

Abnormal white matter integrity in long-term abstinent alcohol dependent patients

A number of diffusion tensor imaging (DTI) studies have reported substantial white matter (WM) abnormalities in alcohol-dependent patients. These studies were usually performed in recovering alcohol-dependent patients who had been abstinent for days to several weeks. The current study was designed to examine WM microstructure and decision-making in a sample of long-term abstinent alcohol-dependent patients. The study included 12 subjects with alcohol dependence who had been abstinent for at least 6 months before testing and scanning and 13 healthy control subjects. The Iowa Gambling Task (IGT) was used to measure decision-making. We found that the long-term abstinent alcohol-dependent group had significantly higher radial and axial diffusivity (RD and AD, respectively) values in frontal, temporal and parietal WM than was found in the healthy control group despite showing no difference in fractional anisotropy (FA) values in comparison to controls. In conclusion, we found widespread WM changes in long-term abstinent alcohol-dependent patients compared with healthy controls. Our findings suggested that AD and RD should be included in analyses of DTI data in addition to the more commonly studied FA. In the current study, FA values of the detoxified alcoholics had recovered and were comparable to those of the controls, whereas significant changes in AD and RD were still observed in some clusters in the frontal, parietal and temporal lobes of detoxified alcoholics even after 27.8 months.

In Vivo Imaging of Cerebral Dopamine D3 Receptors in Alcoholism

Animal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [(11)C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60 mg p.o.). In striatal regions of interest, where the [(11)C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [(11)C]PHNO binding between the groups at baseline. However, baseline [(11)C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (VT: 16.5 ± 4 vs 13.7 ± 2.9, p = 0.040), a region in which the [(11)C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (VT) following a single oral dose of GSK598809 (60 mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in VT following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [(11)C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic strategies to treat alcohol abuse.

EPA-0299 - Agomalatine is effective in reducing insomnia in abstinent alcohol-dependent patients

Among abstinent alcohol-dependent patients, sleep disorders are a wide-spread and persistent problem and have been associated with the risk of alcohol relapse. The melatonin-agonist agomelatine has been shown to improve overall sleep quality without daytime sedation. To examine the effect of agomelatine on sleep quality in abstinent alcohol-dependet patients suffering from chronic sleep disorders. 9 alcohol-dependet patients suffering from chronic sleep disorders received nightly doses between 25 and 50 mg of agomelatine. Sleep quality was assesed using the Pittsburgh Sleep Quality Index prior and following 6 weeks of treatment with agomelatine. Prior and during treatment with agomelatine all patients were monitored for serum levels of liver enzymes. After 6 weeks of agomelatine treatment, the Pittsburgh Sleep Quality Index global score for all patients had decreased significantly. The present data suggest that agomelatine may improve the sleep quality of alcohol-dependent patients suffering from chronic sleep disorders.

Alcohol-Induced Changes in Methylation Status of Individual CpG Sites, and Serum Levels of Vasopressin and Atrial Natriuretic Peptide in Alcohol-Dependent Patients during Detoxification Treatment

Disturbances of volume-regulating peptides like vasopressin (AVP) and atrial natriuretic peptide (ANP) have been described in early abstinent alcohol-dependent patients. In a longitudinal approach, we investigated whether changes in AVP and ANP serum levels correlated to cytosine-phosphatidyl-guanine (CpG) methylation of the respective gene promoters on days 1, 7 and 14 of alcohol withdrawal. We analyzed the blood samples of 99 patients suffering from alcohol dependence alongside age- and BMI-matched controls. Concerning AVP promoter methylation, we observed an interaction between time of measurement and CpG loci with CpG 2 showing a significant increase in methylation from day 1 to 14. Serum levels of AVP were significantly decreased in the patient group. Compared to healthy controls, promoter-related DNA methylation of the ANP promoter was significantly reduced on days 7 and 14. Moreover, we detected a significant interaction between CpG position and group. In both cases the difference was mainly observed at CpG 1. The present study shows significant changes in the methylation status of individual CpG sites of AVP and ANP. Observing respective alterations of AVP serum protein levels in alcohol-dependent patients during detoxification treatment, we consider methylation as a possible mode of regulation for these proteins during alcohol detoxification.

Sodium Oxybate: A Review of Its Use in Alcohol Withdrawal Syndrome and in the Maintenance of Abstinence in Alcohol Dependence

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.

Behavioral and neuroimaging evidence for overreliance on habit learning in alcohol-dependent patients

Substance dependence is characterized by compulsive drug-taking despite negative consequences. Animal research suggests an underlying imbalance between goal-directed and habitual action control with chronic drug use. However, this imbalance, and its associated neurophysiological mechanisms, has not yet been experimentally investigated in human drug abusers. The aim of the present study therefore was to assess the balance between goal-directed and habit-based learning and its neural correlates in abstinent alcohol-dependent (AD) patients. A total of 31 AD patients and 19 age, gender and education matched healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during completion of an instrumental learning task designed to study the balance between goal-directed and habit learning. Task performance and task-related blood oxygen level-dependent activations in the brain were compared between AD patients and healthy matched controls. Findings were additionally associated with duration and severity of alcohol dependence. The results of this study provide evidence for an overreliance on stimulus-response habit learning in AD compared with HC, which was accompanied by decreased engagement of brain areas implicated in goal-directed action (ventromedial prefrontal cortex and anterior putamen) and increased recruitment of brain areas implicated in habit learning (posterior putamen) in AD patients. In conclusion, this is the first human study to provide experimental evidence for a disturbed balance between goal-directed and habitual control by use of an instrumental learning task, and to directly implicate cortical dysfunction to overreliance on inflexible habits in AD patients.

Resting state synchrony in anxiety-related circuits of abstinent alcohol-dependent patients

Background: Anxiety has been linked to initiation, maintenance and relapse of alcohol dependence. Neurobiological models of anxiety have proposed important roles for amygdala–insula and amygdala–medial prefrontal cortex interactions in the generation and regulation of anxiety states, respectively. Objectives: This study tested the hypotheses that abstinent alcohol-dependent patients would show a disruption of synchrony in these circuits as measured by resting state functional MRI. Methods: The study examined recently abstinent (n = 13), longer-term abstinent (n = 16) alcohol-dependent patients and healthy controls (n = 22). Resting-state synchrony (RSS) was examined in specific circuits, where degree of synchrony has been found to correlate with state anxiety levels in previous studies. Results: Alcohol-dependent patients showed significantly elevated scores on anxiety and depression inventories compared with controls. No significant group differences in synchrony were observed between right amygdala and right ventromedial prefrontal cortex (vmPFC), between left amygdala and left vmPFC, or, after correction for multiple comparisons, right amygdala and dorsomedial prefrontal cortex (dmPFC). However, significantly decreased positive synchrony was found between left basolateral amygdala and left anterior insula, in patients relative to controls. Conclusion: Both early and longer-term abstinent alcohol-dependent patients showed increased anxiety levels relative to controls and altered resting state synchrony in circuits previously linked to state anxiety. Notably, the significant group differences in synchrony were in the opposite direction to our predictions based on the literature. These results may point to a lack of generalizability of models derived from young healthy homogeneous samples.