Abstinent Alcohol-dependent Patients Research Articles

6 Semantic and Phonemic Fluency in Alcohol Dependent Individuals

Objective:Verbal fluency consists of semantic and phonemic fluency and is often used to detect verbal ability and executive control (Shao et al., 2014). While research has found general verbal fluency impairments in chronic alcohol use, few studies have examined semantic and phonemic fluency separately (Stavro et al., 2012; Stephan et al., 2017). This meta-analytical study examines the performance of abstinent alcohol-dependent individuals on semantic fluency (categories) and phonemic fluency (letters).Participants and Methods:As part of a larger study, two researchers independently searched eight databases, extracted required data, and calculated effect sizes on neuropsychological data in alcohol dependent (AD) individuals. Inclusion criteria for articles were: (a) comparison of abstinent alcohol-dependent patients to healthy controls, (b) matched control group on age, education, or IQ, and (c) standardized neuropsychological testing. Exclusion criteria included: (a) diagnosis of Axis I disorders (other than alcohol dependence), (b) comorbidity with other disorders that impact neuropsychological functioning, or (c) not published or translated into English. A total of 31 articles (AD n=1,080 and HC n=1,090) was analyzed in this study.Results:Semantic fluency evidenced a statistically significant and medium effect size estimate (g = 0.632, p < 0.001). The heterogeneity for semantic fluency was statistically significant (Q=152.468, df=20, p=0.000). Phonemic fluency evidenced a statistically significant and medium effect size estimate (g = 0.572, p < 0.001). The heterogeneity for phonemic fluency was also statistically significant (Q=236.697, df=24, p=0.000).Conclusions:Deficits in semantic and phonemic fluency are both associated with alcohol dependence. Although some previous research has reported more frontal lobe impact of alcohol, which would be expected to impact phonemic more readily than semantic fluency, this is not evident in the current data. There are many possible reasons for this failure to observe this dissociation meta-analytically. Some potential reasons include the possibility that alcohol affects multiple regions of the brain, that both these measures are affected by alcohol but miss the subtlety associated with frontal damage, or the likelihood that when studies are aggregated in meta-analysis the heterogeneity results in a regression to the mean effect size. These and other reasons are not mutually exclusive and future research should attempt to examine these and other hypotheses.

Genetic Variability of Incretin Receptors and Alcohol Dependence: A Pilot Study.

Alcohol dependence is a chronic mental disorder that leads to decreased quality of life for patients and their relatives and presents a considerable burden to society. Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are endogenous gut-brain peptides, which can travel across the blood-brain barrier and access the nervous system. Their respective receptors, GIPR and GLP-1R, are expressed in the reward-related brain areas and are involved in memory formation and neurogenesis, which results in behavioral changes in rodent models. The current study investigated the potential association of genetic variability of incretin receptors with alcohol dependence and alcohol-related psychosymptomatology. Alcohol dependence and comorbid psychosymptomatology were assessed in a cohort of Slovenian male participants, comprised of 89 hospitalized alcohol-dependent patients, 98 abstinent alcohol-dependent patients, and 93 healthy blood donors. All participants were genotyped for GIPR rs1800437 and GLP1R rs10305420 and rs6923761 polymorphisms. For the statistical analysis Kruskal–Wall and Mann–Whitney tests were used in additive and dominant genetic models. Our findings indicated that GIPR rs1800437 genotypes were associated with an increased risk of alcohol dependence. Statistically significant association between GIPR rs1800437 GG genotype and Brief Social Phobia Scale scores were observed in the abstinent alcohol-dependent patients, while GLP1R rs6923761 GG genotype was associated with Zung anxiety scores in healthy controls. Our pilot study indicates that GIPR rs1800437 may play some role in susceptibility to alcohol dependence, as well as in alcohol-related psychosymptomatology symptoms. To our knowledge, this is the first study that indicates the involvement of GIPR in alcohol dependence. However, studies with larger cohorts are needed to confirm these preliminary findings.

Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study

Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

Cortical Glutamate and GABA Changes During Early Abstinence in Alcohol Dependence and Their Associations With Benzodiazepine Medication.

In this report, we present cross-sectional and longitudinal findings from single-voxel MEGA-PRESS MRS of GABA as well as Glu, and Glu + glutamine (Glx) concentrations in the ACC of treatment-seeking alcohol-dependent patients (ADPs) during detoxification (first 2 weeks of abstinence). The focus of this study was to examine whether the amount of benzodiazepine administered to treat withdrawal symptoms was associated with longitudinal changes in Glu, Glx, and GABA. The tNAA levels served as an internal quality reference; in agreement with the vast majority of previous reports, these levels were initially decreased and normalized during the course of abstinence in ADPs. Our results on Glu and Glx support hyperglutamatergic functioning during alcohol withdrawal, by showing higher ACC Glu and Glx levels on the first day of detoxification in ADPs. Withdrawal severity is reflected in cumulative benzodiazepine requirements throughout the withdrawal period. The importance of withdrawal severity for the study of GABA and Glu changes in early abstinence is emphasized by the benzodiazepine-dependent Glu, Glx, and GABA changes observed during the course of abstinence.

Plasma calcium concentration during detoxification predicts neural cue-reactivity and craving during early abstinence in alcohol-dependent patients

Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of N = 115 alcohol-dependent patients. Alcohol cue-reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol cue-reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence.Trial registration number: DRKS00003388; date of registration: 14.12.2011.

Do Social Cognition Deficits Recover with Abstinence in Alcohol-Dependent Patients?

BackgroundDespite growing evidence of the presence and clinical relevance of deficits in social cognition in individuals with alcohol use disorder (AUD), less is known about the potential of “natural” recovery with abstinence in this neurocognitive domain. This study investigated the abstinence‐based recovery of neurocognitive social abilities in alcohol‐dependent patients (ADP) using a prospective longitudinal design with follow‐up assessment under controlled conditions of abstinence during alcohol dependence inpatient treatment.MethodsSeventy‐seven participants (42 ADP and 35 healthy controls [HC]) performed social cognition testing, including facial emotion recognition, perspective taking, and affective responsiveness twice (baseline/T1 and follow‐up/T2) during comparable follow‐up periods. Assessment of social cognition in abstinent ADP was conducted at the beginning (T1; within the first 2 weeks) and at the end (T2; within the last 2 weeks) of long‐term (2 months) abstinence‐oriented alcohol dependence inpatient treatment. Only patients abstinent for >14 days (last heavy drinking day >21 days) at baseline (T1) and who remained abstinent at follow‐up (T2) were included.ResultsADP, who on average were nearly 2 months abstinent at T1, showed poorer social cognition in all 3 areas (emotion recognition, perspective taking, and affective responsiveness) than HC. There was no difference between groups on the change in performance over time, and group differences (ADP vs. HC) remained significant at T2, indicating persistent social cognition deficits in ADP following controlled abstinence during inpatient treatment.ConclusionsOur findings indicate no natural recovery of social cognition impairments in ADP during an intermediate to long‐term period of abstinence (2+ months), the usual active treatment phase. Research aimed at developing interventions that focus on the improvement of social cognition deficits (e.g., social cognition training) and determining whether they benefit short‐ and long‐term clinical outcomes in AUD seems warranted.

The association of plasma acyl ghrelin level with alcohol craving in early abstinent alcohol dependent patients

Background:Craving plays an important role in maintenance of alcohol dependence. Earlier studies have analyzed the role of ghrelin in craving and their results have been heterogenous. Acyl ghrelin is its more active form as it crosses the blood brain barrier. Hence we aimed to examine the relationship between plasma acyl ghrelin and craving in Indian patients having alcohol dependence syndrome.Methods:The present study was a hospital-based prospective study. A total of 60 drug-naive patients of alcohol dependence and 30 healthy controls were included. After taking informed consent fasting blood samples were collected from them on day 1 and tested for plasma acyl ghrelin level. Fasting blood samples were repeated in all cases on day 14. During this time, we also assessed the patients' cravings by obsessive compulsive drinking scale, and alcohol craving questionnaire; and withdrawal by clinical institute withdrawal assessment for alcohol scale. These scales were repeated on day 14. Data analysis was done by SPSS version 25.0.Results:Plasma concentrations of acyl ghrelin increased significantly during early abstinence in patients from day 1 to day 14 (P < 0.0001). Pearson correlation test revealed a trend of positive correlation between plasma concentration of acyl ghrelin on day 14 and severity of craving on day 1.Conclusion:Our results suggest the plasma concentration of acyl ghrelin may be a predictor of severity of alcohol craving during early abstinence. Anti-craving drugs acting on acyl ghrelin level in brain may open an innovative avenue for optimum treatment of alcohol dependence.

Chronic alcohol exposure differentially modulates structural and functional properties of amygdala: A cross‐sectional study

AbstractAnimal models have shown that chronic alcohol exposure is associated with persistent neuroadaptations in amygdala synaptic function, whereas human studies have consistently reported amygdala grey‐matter volume (GMV) reductions in alcohol dependent patients (ADP). We hypothesised that chronic alcohol use associated with neuroadaptations may entail a reconfiguration of the amygdala's functional interactions and that these mechanisms may be affected by structural atrophy. We compared amygdala resting state functional connectivity (RSFC) using a whole brain seed‐based approach and amygdala GMV in abstinent ADP (n = 20) and healthy controls (HC; n = 39), balanced for age, gender and levels of head motion. The potential moderating influence of age, cumulative alcohol exposure, abstinence length and head motion was further examined in the two groups separately using correlational analyses. We found increased amygdala RSFC with substantia nigra/ventral tegmental area (SN/VTA) in ADP compared with HC. As expected, amygdala GMV was lower in ADP. Multiple regression analyses of the ADP group showed that amygdala‐SN/VTA RSFC increases were primarily associated with cumulative alcohol exposure rather than age, whereas amygdala GMV reductions were primarily associated with age rather than cumulative alcohol exposure. The same association between age and amygdala GMV was not observed amongst HC. Importantly, amygdala GMV and amygdala‐SN/VTA RSFC were uncorrelated in ADP, and neither measure was correlated with abstinence length. These results suggest that chronic alcohol exposure is associated with persistent elevations in amygdala‐SN/VTA RSFC and accelerated age‐related grey‐matter atrophy through potentially distinct mechanisms.

Delta resting-state functional connectivity in the cognitive control network as a prognostic factor for maintaining abstinence: An eLORETA preliminary study

BackgroundCortical regions that support cognitive control are increasingly well recognized, but the functional mechanisms that promote such control over emotional and behavioral hyperreactivity to alcohol in recently abstinent alcohol-dependent patients are still insufficiently understood. This study aimed to identify neurophysiological biomarkers of maintaining abstinence in alcohol-dependent individuals after alcohol treatment by investigating the resting-state EEG-based functional connectivity in the cognitive control network (CCN). MethodsLagged phase synchronization between CCN areas by means of eLORETA as well as the Barratt Impulsiveness Scale (BIS-11) and Beck Depression Inventory (BDI) were assessed in abstinent alcohol-dependent patients recruited from treatment centers. A preliminary prospective study design was used to classify participants into those who did and did not maintain abstinence during a follow-up period (median 12 months) after discharge from residential treatment. ResultsAlcohol-dependent individuals, who maintained abstinence (N = 18), showed significantly increased lagged phase synchronization between the left dorsolateral prefrontal cortex (DLPFC) and the left posterior parietal cortex (IPL) as well as between the right anterior insula cortex/frontal operculum (IA/FO) and the right inferior frontal junction (IFJ) in the delta band compared to those who later relapsed (N = 16). Regression analysis showed that the increased left frontoparietal delta connectivity in the early period of abstinence significantly predicted maintaining abstinence over the ensuing 12 months. Furthermore, right frontoinsular delta connectivity correlated negatively with impulsivity and depression measures. ConclusionsThese results suggest that the increased delta resting-state functional connectivity in the CCN may be a promising neurophysiological predictor of maintaining abstinence in individuals with alcohol dependence.

Leptin predicts cortical and subcortical gray matter volume recovery in alcohol dependent patients: A longitudinal structural magnetic resonance imaging study

The neuroprotective effects of leptin and its role in addictive disorders has been highlighted by several recent studies. However, its potential effects on morphological alterations in alcohol dependence are yet to be investigated.Associations between leptin and the longitudinal courses of gray matter volume (GMV) and cortical thickness (CT) were investigated in N = 62 alcohol-dependent patients that underwent structural magnetic resonance imaging after a mean abstinence of 12 (baseline) and 27 days (follow-up) respectively. Blood samples were collected at baseline to determine leptin levels. A cohort of N = 74 healthy individuals served as a reference sample.At baseline, alcohol-dependent patients compared to healthy controls displayed smaller GMV in the insula, parts of the superior, middle and inferior frontal gyri and hippocampal regions and thinner CT in the insula, parts of the superior and middle frontal cortices, the lateral orbitofrontal cortex and parts of the occipital and lingual cortices that partially recovered during abstinence (pFWE < 0.05). In alcohol-dependent patients, leptin was a significant predictor of GMV and CT recovery in the areas that showed the strongest whole-brain effects, specifically GMV in the right insula (R2 = 0.070, pFDR = 0.040) and left inferior frontal triangular gyrus (R2 = 0.076, pFDR = 0.040), as well as CT in the left insula (R2 = 0.158, pFDR = 0.004) and right superior frontal cortex (R2 = 0.180, pFDR = 0.004). Present results support the role of leptin in predicting GMV and CT recovery during the first month of abstinence in alcohol-dependent patients.

Peripheral proinflammatory markers are upregulated in abstinent alcohol-dependent patients but are not affected by cognitive bias modification: Preliminary findings

BackgroundInflammatory pathways are known to be negatively affected in patients with alcohol use disorder (AUD). Cognitive bias modification (CBM), an emerging behavioral treatment that involves the ‘re-training’ of cognitive biases using computerized tasks, has been reported to reduce alcohol craving and relapse rates. The aim of this study was to compare peripheral concentrations of the proinflammatory biomarkers IL-18, IL-6, IL-1β, TNF-α and CRP in AUD patients versus controls and to identify whether CBM treatment affected these biomarkers in AUD patients. MethodsThis 3-week double-blind randomized controlled study tested 36 male abstinent AUD patients receiving CBM or placebo-training, who were also compared to 18 male healthy controls. The approach avoidance task (AAT) was used to test the AUD patients before and after training. CBM training took place over 6 sessions, using a joystick-based approach-avoidance task. Blood samples were collected after the pre- and post-AAT test sessions for the AUD groups, and during an outpatient appointment with the controls. ResultsAUD patients, versus controls, presented with significantly higher plasma levels of TNF- α (P < 0.0001) and CRP (P = 0.0031). No changes in the CBM versus placebo groups were noted in IL-18, TNF-α and CRP concentrations following pre-post change or within group pretest- posttest analysis. IL-6 and IL-1β levels fell under the lower detection limit, thus were not included in the final analyses. ConclusionsThis study confirms that the inflammatory system is altered in AUD. This was the first study that investigated whether CBM training affected proinflammatory markers in AUD patients.

F209. The Effect of Acamprosate Treatment on Cue Reactivity and Central Glutamate Activity in Recently Abstinent Alcohol Dependent Patients: A fMRI and MRS Study

F209. The Effect of Acamprosate Treatment on Cue Reactivity and Central Glutamate Activity in Recently Abstinent Alcohol Dependent Patients: A fMRI and MRS Study

A comparison of implicit and explicit reward learning in low risk alcohol users versus people who binge drink and people with alcohol dependence

Chronic alcohol use leads to specific neurobiological alterations in the dopaminergic brain reward system, which probably are leading to a reward deficiency syndrome in alcohol dependence. The purpose of our study was to examine the effects of such hypothesized neurobiological alterations on the behavioral level, and more precisely on the implicit and explicit reward learning. Alcohol users were classified as dependent drinkers (using the DSM-IV criteria), binge drinkers (using criteria of the USA National Institute on Alcohol Abuse and Alcoholism) or low-risk drinkers (following recommendations of the Scientific board of trustees of the German Health Ministry). The final sample (n = 94) consisted of 36 low-risk alcohol users, 37 binge drinkers and 21 abstinent alcohol dependent patients. Participants were administered a probabilistic implicit reward learning task and an explicit reward- and punishment-based trial-and-error-learning task. Alcohol dependent patients showed a lower performance in implicit and explicit reward learning than low risk drinkers. Binge drinkers learned less than low-risk drinkers in the implicit learning task. The results support the assumption that binge drinking and alcohol dependence are related to a chronic reward deficit. Binge drinking accompanied by implicit reward learning deficits could increase the risk for the development of an alcohol dependence.

High-frequency repetitive transcranial magnetic stimulation (rTMS) in alcohol dependence: effects on emotion processing and reappraisal and neural mechanisms: an fMRI study

In neurobiological models on the working mechanisms of addiction, the important role of changes in the motivational (limbic brain) circuitry, which overreacts to addictive stimuli and the diminished functioning of cortical regulatory systems such as the frontal-anterior cingulate circuit is central. Neurostimulation with repetitive high-frequency transcranial magnetic stimulation (rTMS) has been shown to affect both cortical and subcortical functions, but its working mechanisms in addiction are scarcely studied. In this presentation therefore, (1) results are presented on direct effects of 10Hz rTMS (real vs sham) in a sample of 39 abstinent alcohol dependent patients on regulation of emotion, compared to 39 healthy controls. Specifically, the behavioral and neural (fMRI) effects of performing an emotion regulation task after real or sham rTMS are presented. Both in alcohol dependent patients as well as in healthy controls, changes in emotional processing and reappraisal were present, but a group by stimulation effect indicated differential effects in ADPs and healthy controls. In ADPs experienced emotions were reduced by high-frequency rTMS, whereas in healthy controls, the impact of affective pictures was strengthened. Changes in emotion regulation, were accompanied by changes in the frontal circuitry, specifically in the bilateral superior frontal gyrus in ADPs but not in healthy controls. Effects of rTMS on resting state functioning in alcohol dependence indicate that high-frequency rTMS in alcohol dependence influences resting state functioning and functional connectivity of fronto-striatal circuitry, indicating that DLPFC stimulation also affects deeper lying brain circuits. Findings of these acute effects of rTMS in alcohol dependent patients who are abstinent and in treatment will be discussed in relation to cognitive effects of rTMS in addiction, as recently summarized in a systematic review by our group, and to mechanisms of rTMS add-on clinical trials in addiction. Keywords: addiction, emotion regulation, rTMS, fMRI

Combining gray matter volume in the cuneus and the cuneus-prefrontal connectivity may predict early relapse in abstinent alcohol-dependent patients.

BackgroundDeveloping more effective strategies to prevent relapse remains one of the major challenges of treating substance dependence. Previous studies have identified brain abnormalities in abstinent alcoholics. However, whether these persistent brain deficits in abstinence could predict early relapse to alcohol use has not been well established. This study aimed to identify biomarkers of relapse vulnerability by investigating persistent brain abnormalities in abstinent alcohol-dependent patients.MethodsBrain imaging and impulsive behavior data were collected from 56 abstinent alcohol-dependent male inpatients and 33 age-matched male healthy controls. Voxel-based morphometry was used to investigate the differences of grey matter volume between the groups. The resting-state functional connectivity was examined using brain areas with gray matter deficits as seed regions. A preliminary prospective study design was used to classify patients into abstainers and relapsers after a 62-day average abstinence period.ResultsCompared with healthy controls, both relapsers and abstainers exhibited significantly reduced gray matter volume in the cuneus. Functional connectivity analysis revealed that relapsers relative to abstainers demonstrated increased cuneus-centered negative functional connectivity within a network of brain regions which are involved in executive control and salience. Abnormal gray matter volume in the left cuneus and the functional connectivity between the right cuneus and bilateral dorsolateral prefrontal cortex could successfully predict relapse during the 3-month follow-up period.ConclusionsFindings suggest that the abnormal gray matter volume in the cuneus and resting-state cuneus-prefrontal functional connectivity may play an important role in poor treatment outcomes in alcoholics and serve as useful neural markers of relapse vulnerability.

Smoking and Promoter-Specific Deoxyribonucleic Acid Methylation of the Atrial Natriuretic Peptide Gene: Methylation of Smokers and Non-Smokers Differs Significantly during Withdrawal

Background: Atrial natriuretic peptide (ANP) is well known in psychiatric disorders to modulate hypothalamic-pituitary-adrenal axis activity. Disturbances of ANP have been described in early abstinent alcohol-dependent patients. This is the first longitudinal investigation on cytosine-phosphatidyl-guanine (CpG)-island promoter methylation of the ANP gene in the blood of tobacco-dependent patients. Methods: In a longitudinal approach, we investigated whether changes in ANP serum levels correlated to CpG methylation of the respective gene promoters on days 1, 7, and 14 of tobacco withdrawal. Results and Conclusion: Compared to non-smokers, promoter-related deoxyribonucleic acid methylation of the ANP promoter was significantly elevated on days 7 and 14 of withdrawal in tobacco-dependent patients. Baseline methylation status of the ANP promoter was not significantly different from controls, arguing for an impaired regulation during withdrawal.

Effect of short-term heart rate variability biofeedback on long-term abstinence in alcohol dependent patients \u2013 a one-year follow-up

BackgroundA randomized controlled study (RCT) recently showed that short-term heart rate variability (HRV) biofeedback in addition to standard rehabilitation care for alcohol dependence can reduce craving, anxiety and improve cardiovascular autonomic function. In this one-year follow-up study we aimed to explore whether completion of 2-week HRV-Biofeedback training is associated with long-term abstinence. Furthermore, we sought to identify potential predictors of post-treatment abstinence.MethodsWe conducted a survey on abstinence in patients with alcohol dependence 1 year after completion of an RCT comparing HRV-biofeedback in addition to inpatient rehabilitation treatment alone (controls). Abstinence rates were compared and analysed for association with demographic data as well as psychometric and autonomic cardiac assessment before and after completion of the biofeedback training using bivariate and multivariate regression analyses.ResultsOut of 48 patients who participated in the RCT, 27 patients (9 females, ages 42.9 ± 8.6, mean ± SD) completed our one-year follow-up. When including in the analysis only patients who completed follow-up, the rate of abstinence tended to be higher in patients who underwent HRV-biofeedback 1 year earlier compared to those who received rehabilitative treatment alone (66.7% vs 50%, p = ns). This non-significant trend was also observed in the intention-to-treat analysis where patients who did not participate in the follow-up were assumed to have relapsed (46,7% biofeedback vs. 33.3% controls, p = ns). Neither cardiac autonomic function nor psychometric variables were associated with abstinence 1 year after HRV-biofeedback.ConclusionOur follow-up study provide a first indication of possible increase in long-term abstinence after HRV-biofeedback for alcohol dependence in addition to rehabilitation.Trial registrationThe original randomized controlled trial was registered in the German Clinical Trials Register (DRKS00004618). This one-year follow-up survey has not been registered.

Drug therapy for alcohol dependence in primary care in the UK: A Clinical Practice Research Datalink study.

AimTo evaluate drug therapy for alcohol dependence in the 12 months after first diagnosis in UK primary care.DesignOpen cohort study.SettingGeneral practices contributing data to the UK Clinical Practice Research Database.Participants39,980 people with an incident diagnosis of alcohol dependence aged 16 years or older between 1 January 1990 and 31 December 2013.Main outcome measureUse of pharmacotherapy (acamprosate, disulfiram, naltrexone, baclofen and topiramate) to promote abstinence from alcohol or reduce drinking to safe levels in the first 12 months after a recorded diagnosis of alcohol dependence.FindingsOnly 4,677 (11.7%) of the cohort received relevant pharmacotherapy in the 12 months following diagnosis. Of the 35,303 that did not receive pharmacotherapy, 3,255 (9.2%) received psychosocial support. The remaining 32,048 (80.2%) did not receive either mode of treatment in the first 12 months. Factors that independently reduced the likelihood of receiving pharmacotherapy included: being male (Odds Ratio [OR] 0.74; 95% CI 0.69 to 0.78); older (65-74 years: OR 0.61; 95% CI 0.49 to 0.77); being from a practice based in the most deprived quintile (OR 0.58; 95% CI 0.53 to 0.64); and being located in Northern Ireland (OR 0.78; 95% CI 0.67 to 0.91). The median duration to initiation of pharmacotherapy was 0.80 months (95% CI 0.70 to 1.00) for acamprosate and 0.60 months (95% CI 0.43 to 0.73) for disulfiram. Persistence analysis for those receiving acamprosate and disulfiram revealed that many patients never received a repeat prescription; persistence at 6 months was 27.7% for acomprosate and 33.2% for disulfiram. The median duration of therapy was 2.10 months (95% CI 1.87 to 2.53) for acamprosate and 3.13 months (95% CI 2.77 to 3.36) for disulfiram.ConclusionDrug therapy to promote abstinence in alcohol dependent patients was low, with the majority of patients receiving no therapy, either psychological or pharmacological. When drug therapy was prescribed, persistence was low with most patients receiving only one prescription. Our data show that treatment for alcohol dependence is haphazard, and there is an urgent need to explore strategies for improving clinical management of this patient group.

Do alcohol-dependent patients show different neural activation during response inhibition than healthy controls in an alcohol-related fMRI go/no-go-task?

Alcohol dependence is associated with impaired response inhibition and heightened cue reactivity towards alcohol-related stimuli. Several brain areas, but mainly prefrontal structures, have been linked to response inhibition in addiction. This study aimed at combining both aspects: salience of drug-associated cues and response inhibition using a go/no-go task with alcohol-associated stimuli during functional magnetic resonance imaging (fMRI). Nineteen abstinent alcohol-dependent patients (ADP) and 21 healthy control subjects (HC) were compared on blood oxygen level-dependent (BOLD) responses during successful inhibition of no-go stimuli and successful reactions to go stimuli. ADP and HC did not significantly differ in their behavioural performance in the task. However, both groups performed worse during the inhibition of alcoholic-associated stimuli compared to neutral stimuli. On the neural level, ADP displayed enhanced BOLD activity relative to HC during successful response inhibition in several areas involved in visual processing, cognitive and impulse control, including occipital structures, anterior cingulate gyrus, medial frontal gyrus and medial orbitofrontal cortex. We interpret these findings as a possible compensation strategy for impaired cognitive processing. Furthermore, the results underline the impact of salience of alcohol-related stimuli on response inhibition, which seems to affect both ADP and HC.

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.