Alcohol-dependent Participants Research Articles

Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders.

While progress has been made in determining the genetic basis of antisocial behaviour, little progress has been made for antisocial personality disorder (ASPD), a condition that often co-occurs with other psychiatric conditions including substance use disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. This study aims to improve the understanding of the genetic risk for ASPD and its relationship with other disorders and traits. We conducted a genome-wide association study (GWAS) of the number of ASPD diagnostic criteria data from 3217 alcohol-dependent participants recruited in the UK (UCL, N = 644) and the USA (Yale-Penn, N = 2573). We identified rs9806493, a chromosome 15 variant, that showed a genome-wide significant association ( Z -score = -5.501, P = 3.77 × 10 -8 ) with ASPD criteria. rs9806493 is an eQTL for SLCO3A1 (Solute Carrier Organic Anion Transporter Family Member 3A1), a ubiquitously expressed gene with strong expression in brain regions that include the anterior cingulate and frontal cortices. Polygenic risk score analysis identified positive correlations between ASPD and smoking, ADHD, depression traits, and posttraumatic stress disorder. Negative correlations were observed between ASPD PRS and alcohol intake frequency, reproductive traits, and level of educational attainment. This study provides evidence for an association between ASPD risk and SLCO3A1 and provides insight into the genetic architecture and pleiotropic associations of ASPD.

Emotional Processing and Maltreatment During Childhood as Factors of Vulnerability to Alcohol Abuse in Young Adults

AbstractDifferent studies suggest a strong association between childhood abuse and alcohol use disorders (AUDs). The modulation of the startle response has been used to assess emotional processing in AUDs. The main objective of the study was to investigate the startle reflex responses to different stimuli in young adults with varying types of childhood abuse in comparison with a control group according to their current alcohol consumption and the presence of a parent with alcohol dependence or not. A clinical sample of 606 adolescents, divided into five groups: no abuse, physical neglect, emotional neglect, emotional abuse, physical abuse, and sexual abuse, were assessed on their pattern of alcohol consumption and their family history of alcoholism. The proportion of participants with at least one alcohol-dependent parent was higher in all types of abuse. The proportion of heavy drinkers and alcohol-dependent participants was higher in the groups with physical neglect and sexual abuse. Heavy drinkers and alcohol dependents showed a lower startle reflex response to emotional pictures, especially alcohol-related ones. Adolescents exposed to physical and sexual abuse during childhood showed a mitigated startle response to appetitive and alcohol-related pictures. The results of this exploratory study reveal that childhood maltreatment modulates emotional processing to alcohol-related stimuli during adolescence. The evaluation of these patients’ startle response could be considered a prognostic biomarker for establishing personalized preventive strategies during the adolescent stage to avoid, to a large extent, future problems derived from alcohol consumption.

Ghrelin and impulsivity relationship in alcohol-dependent patients and healthy individuals.

Abundant research indicates that ghrelin hormone levels are associated with alcohol use and addiction. One of the mediators of this association may be impulsivity, which is one of the common traits observed in alcohol addiction and some eating disorders. This study evaluated participants with alcohol dependency and healthy volunteers to determine whether trait impulsivity and ghrelin levels are associated. This study analyzed trait impulsivity scores and fasting serum ghrelin levels of 44 males with alcohol dependency and 48 healthy male participants. The Barratt Impulsiveness Scale and the UPPS Impulsive Behaviour Scale (UPPS) were used to measure trait impulsivity levels. Penn Alcohol Craving Scale and Yale Brown Obsessive Compulsive Drinking Scale for heavy drinking were used to assess craving at the baseline and after the detoxification period. Alcohol-dependent patients' fasting ghrelin levels were significantly higher than that of healthy participants. Ghrelin plasma levels were positively correlated with UPPS total impulsivity scores and sensation-seeking among healthy individuals. In alcohol-dependent participants, there was a positive correlation between UPPS urgency scores obtained at the baseline and fasting ghrelin levels before and after the detoxification period. Ghrelin-impulsivity relationship could be observed in certain dimensions of impulsivity in both alcohol-dependent and healthy individuals and even independent of the effect of alcohol. Although the associated impulsivity dimensions differ in different groups, the results are parallel to other studies in terms of demonstrating the relationship between ghrelin and impulsivity.

Impaired Decision-Making and Skin Conductance Responses Are Associated with Reward and Punishment Sensitivity in Individuals with Severe Alcohol Use Disorder

Introduction: Individuals with alcohol use disorder (AUD) have difficulties regulating alcohol consumption, despite adverse drinking-related consequences. This may be due to incapacity incorporating previous negative feedback from drinking, resulting in impaired decision-making. Methods: We assessed whether decision-making is impaired in participants with AUD related to severity of AUD, indexed by severe negative drinking consequences using the Drinkers Inventory of Consequences (DrInC) and reward and punishment sensitivity with the Behavioural Inhibition System Behavioural Activation System (BIS BAS) scales. 36 treatment-seeking alcohol-dependent participants completed the Iowa gambling task (IGT) with skin conductance responses (SCRs) measured continuously as an index of somatic autonomic arousal to evaluate impaired expectancy of negative outcomes. Results: Two-thirds of the sample showed behavioural impairment during the IGT, with greater AUD severity related to worse performance. BIS moderated IGT performance according to severity of AUD, with increased anticipatory SCRs for those with fewer reported DrInC severe consequences. Participants with more DrInC severe consequences showed IGT deficits and reduced SCRs regardless of BIS scores. BAS-Reward was associated with increased anticipatory SCRs to disadvantageous deck choices among those with lower AUD severity, while SCRs did not differ related to AUD severity for reward outcomes. Discussion: Effective decision-making in the IGT and adaptive somatic responses were moderated by punishment sensitivity contingent on severity of AUD in these drinkers, with impairments in expectancy to negative outcomes from risky choices, including reduced somatic responses, resulting in poor decision-making processes that may help explain impaired drinking and worse drinking-related consequences.

The Effects of Citalopram and Thalamic Dopamine D2/3 Receptor Availability on Decision-Making and Loss Aversion in Alcohol Dependence.

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients who misuse alcohol, especially in the context of comorbid depressive symptoms. Deficits in impulse control and decision-making are linked to routine alcohol consumption and alcohol dependence. The goal of this study was to determine the effects of a single dose of citalopram on measures of impulsivity, decision-making, and/or brain dopamine receptor availability in alcohol-dependent individuals. A double-blind, placebo-controlled, within-subject, outpatient study was conducted with active alcohol-dependent (DSM-IV-TR criteria) participants (n = 12) and matched healthy controls (n = 13). Serial doses of both citalopram (40 mg) and saline were administered intravenously before laboratory tests of decision-making (Balloon Analogue Risk Task, delay discounting task, and Loss Aversion Gambling Task) and positron emission tomography with [18F]-fallypride to measure dopamine D2/3 receptor availability, separated by at least one week. Alcohol-dependent participants demonstrated greater loss aversion than healthy controls, but there were no group differences in risk taking on the Balloon Analogue Risk Task. Citalopram increased delay discounting across groups, with no group difference in the effect. There were no effects of citalopram on risk taking on the Balloon Analogue Risk Task. PET showed a negative correlation between thalamic dopamine D2/3 receptor availability and loss aversion across groups. The effect of citalopram to decrease the valuation of monetary reward as a function of delay raises the possibility that SSRIs can influence risky decision-making in clinical populations. In addition, these results suggest that altered thalamic dopamine signaling may play an important role in disproportionately valuing losses in patients with Alcohol Use Disorder. This trial is registered under ClinicalTrials.gov registration NCT01657760.

Associations of NLRP3 and CARD8 gene polymorphisms with alcohol dependence and commonly related psychiatric disorders: a preliminary study.

We investigated two functional polymorphisms in NLRP3 inflammasome genes (NLRP3 rs35829419 and CARD8 rs2043211) and their association with alcohol dependence and related anxiety, depression, obsession-compulsion, or aggression in 88 hospitalised alcohol-dependent patients, 99 abstinent alcohol-dependent participants, and 94 controls, all male Caucasian. Alcohol dependence-related psychiatric disorders were assessed with the Zung Depression and Anxiety scale, Buss-Durkee Hostility Inventory, Alcohol Use Disorders Identification Test, Brief Social Phobia Scale, Obsessive Compulsive Drinking Scale, and Yale-Brown Obsessive-Compulsive Scale. For genotyping we used the allele-specific quantitative polymerase chain reaction-based methods. The three groups differed significantly in CARD8 rs2043211 distribution (P=0.049; chi-squared=9.557; df=4). The NLPR3 rs35829419 polymorphism was not significantly associated with alcohol dependence. In hospitalised alcohol-dependent patients the investigated polymorphisms were not associated with scores indicating alcohol consumption or comorbid symptoms. In abstinent alcohol-dependent subjects homozygotes for the polymorphic CARD8 allele presented with the highest scores on the Zung Anxiety Scale (p=0.048; df=2; F=3.140). Among controls, CARD8 genotype was associated with high scores on the Obsessive Compulsive Drinking Scale (P=0.027; df=2; F=3.744). In conclusion, our results reveal that CARD8 rs2043211 may play some role in susceptibility to alcohol dependence, expression of anxiety symptoms in abstinent alcohol-dependent subjects, and in obsessive compulsive drinking in healthy controls. However, further studies with larger cohorts are required to confirm these preliminary findings.

Diminished cortical response to risk and loss during risky decision making in alcohol use disorder

BackgroundRisky decision-making is an important facet of addiction. Individuals with alcohol dependence show abnormalities in gambling and other risk-taking tasks. In one such measure, the Balloon Analogue Risk Task (BART), participants sequentially choose to pump a virtual balloon to increase potential reward while the risk of explosion increases, or to cash-out and take earnings. In a prior study, alcohol-dependent participants differed from controls in brain activation during decision-making on the BART, but the relationship between risk/reward magnitude and brain activation was not studied, nor were participants compared to controls. Here we compared the degree to which risk and magnitude of reward influenced brain activation in alcohol-dependent participants vs. controls during decision-making on the BART. MethodsThirty-two participants (16 alcohol-dependent, 16 control; 5 females/group) performed the BART during fMRI. A parametric analysis tested for a relationship between risk/reward magnitude and activation in rDLPFC and bilateral striatum regions of interest when participants chose to take risk or to cash out. An exploratory whole-brain voxel-wise analysis of mean activation during pumping, cash-out, and explosion events was also conducted. ResultsCompared with controls, alcohol-dependent participants displayed less modulation of activation in the rDLPFC when taking risk. Exploratory analyses found that alcohol-dependent participants showed less activation than controls during explosions in a cluster including the insula. No differences were seen in striatal activation. ConclusionsInsensitivity of the rDLPFC to risk and of the insula to loss may contribute to decision-making deficits in alcohol dependence.

Intravenous Alcohol Administration Selectively Decreases Rate of Change in Elasticity of Demand in Individuals With Alcohol Use Disorder.

Alcohol demand is a key behavioral economic concept that provides an index of alcohol's relative reinforcing value. Initial studies have reported that alcohol demand increases during alcohol administration and in response to alcohol cues. However, the extent to which these effects are observed explicitly in samples composed of individuals with alcohol use disorder (AUD) and are operative in conjunction with each other has not been studied. To address this gap in the literature, we assessed alcohol demand during an alcohol challenge and subsequent alcohol cue-exposure paradigm in non-treatment-seeking, alcohol-dependent (i.e., DSM-IV criteria) participants (N=27). Specifically, participants completed 2 counterbalanced intravenous, placebo-controlled, alcohol administration sessions followed by a controlled cue-exposure paradigm. At baseline and at breath alcohol concentration of 0.06g/dl, participants completed the alcohol purchase task, assessing estimated alcohol consumption at escalating prices. Participants were also assessed for alcohol demand following each cue exposure. During alcohol administration, there was a significant decrease in the rate of change in elasticity compared with placebo, and during the cue-reactivity paradigm, there was a significant main effect such that alcohol cues decreased the rate of change in elasticity relative to water cues. There were no statistically significant differences in other demand indices. These findings provide further evidence that alcohol administration increases price insensitivity and extends the literature on alcohol's effects on demand by using a clinical sample with AUD and by adding a placebo-alcohol condition.

Quality of life of alcohol-dependent adults

Introduction: Alcohol dependence is the most prevalent addiction disorder that develops gradually as an interplay of individual and social factors. It impacts the quality of life of affected individuals. The purpose of this study was to examine the quality of life of alcohol-dependent people at different stages of treatment compared to individuals without alcohol dependence.Methods: A mixed-methods study was conducted. First, a cross-sectional study (n = 502) was conducted using a validated Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Focus groups for subjective quality of life assessment were also conducted. Data were analysed using descriptive and inference methods (Mann Whitney U Test) with the SPSS, version 20 programme.Results: Non-dependent participants are significantly more satisfied with each of the quality of life component than alcohol-dependent participants. Differences were demonstrated in a sense of well-being and leisure-time activities. Differences between alcohol-dependent and non-dependent participants were seen in the domains of physical health, work satisfaction and social relationships.Discussion and conclusion: Alcohol-dependent participants reported a lower quality of life than non-alcohol dependent participants as alcohol dependents confront numerous problems associated with their dependence. There is a need for further research in the field of alcohol dependence in relation to the quality of life.

Slow associative learning in alcohol dependence and the alcohol cue exposure treatment paradox.

To examine two explanations for the observation that cue-exposure treatment has not been clearly effective in the treatment of alcohol dependence: do alcohol-dependent individuals have either (1) slower extinction and/or (2) greater contextual specificity of extinction than non-dependent individuals? In two exploratory laboratory experiments we used mixed factorial designs with two-group between-subjects factors and within-subjects factors corresponding to performance in different parts of a computer-based learning task. University of Southampton psychology research laboratories and two addiction treatment services in the city of Southampton, UK. Experiment 1: 74 (54 female) undergraduates from the University of Southampton (age mean=20.4years). Experiment 2: 102 (40 female) participants from the University of Southampton, the local community, and from two Southampton alcohol treatment services (age mean=41.3years). The Alcohol Use Disorders Identification Test, a 1-week time-line follow-back alcohol consumption questionnaire, the Barratt Impulsiveness Scale (11th edn), and a computerized learning task. Experiment 2 additionally used the 44-item Big Five Inventory, a drug use history checklist, and the Hospital Anxiety and Depression Scale. Experiment 1: light and heavy drinkers did not differ significantly in extinction [extinction block×drinking status interaction, P=0.761, , 95% confidence interval (CI)= (0,0.028)] or on contextual control of extinction [recovery block×drinking status interaction, P=0.514, , 95% CI=(0,0.084)]. Experiment 2: slower extinction in abstinent alcohol-dependent participants compared with light drinkers [extinction block×drinking status interaction, P=0.023, , 95% CI=0,0.069)] but no significant difference on contextual control of extinction [recovery block×drinking status interaction, P=0.069, , 95% CI=(0,0.125)]. Abstinent alcohol-dependent people may have slower extinction learning for alcohol-related cues than non-dependent light drinkers.

Exploring autobiographical memory specificity and narrative emotional processing in alexithymia

Abstract Alexithymia encompasses difficulties in identifying and expressing feelings along with an externally oriented cognitive style. While previous studies found that higher alexithymia scores were related to an impaired memory for emotional content, no study so far investigated how alexithymia affects autobiographical narratives. Narrating personal events, however, is impaired in emotionally disturbed patients in that they tend to recall overgeneral descriptions instead of specific episodes, which impairs their narrative emotional processing. Adopting a qualitative approach, this pilot study explored autobiographical memory specificity, cognitive, perceptual and emotional word use, and narrative closure in eight alcohol-dependent participants scoring very high or low in alexithymia. High alexithymia participants showed no reduced memory specificity but impaired emotional processing and narrative elaboration, especially when talking about negative events. Presumably because of this we found no group differences regarding narrative closure. Results are discussed in terms of cognitive and emotional processing, avoidance strategies, and narrative psychology.

Ultra-brief breath counting (mindfulness) training promotes recovery from stress-induced alcohol-seeking in student drinkers

The therapeutic effect of mindfulness interventions on problematic drinking is thought to be driven by increased resilience to the impact of stress on negative mood and alcohol-seeking behaviour, but this claim needs empirical support. To address this hypothesis, the current study tested whether brief training of one component of mindfulness – breath counting – would reduce drinkers’ sensitivity to the effect of noise stress on subjective mood and alcohol-seeking behaviour. Baseline alcohol-seeking was measured by choice to view alcohol versus food thumbnail pictures in 192 student drinkers. Participants then received a 6-minute audio file which either trained breath counting or recited a popular science extract, in separate groups. All participants were then stressed by a loud industrial noise and alcohol-seeking was measured again simultaneously to quantify the change from baseline. Subjective mood was measured after all three stages (baseline, post intervention, post stress test). The breath counting group were instructed to deploy this technique during the stress test. Results showed that the breath counting versus control intervention improved subjective mood relative to baseline, attenuated the worsening of subjective mood produced by stress induction, and accelerated recovery from a stress induced increase in alcohol-seeking behaviour. Exploratory moderation analysis showed that this accelerated recovery from stress induced alcohol-seeking by breath counting was weaker in more alcohol dependent participants. Mindfulness therapies may improve problematic drinking by increasing resilience to stress induced negative mood and alcohol-seeking, as observed in this study. The weaker therapeutic effect of breath counting in more dependent drinkers may reveal limitations to this intervention strategy.

A-17 Category Test performance in individuals with alcohol versus methamphetamine dependence

Abstract Objective The Category Test (CT) has consistently been found to be sensitive at detecting the effects of alcohol on the brain. However, this test has not been as widely used in examining the effects of methamphetamine. The current meta-analysis compared effect sizes of studies that have examined performance on the CT in alcohol versus methamphetamine dependent participants. Data selection Three researchers independently searched nine databases (e.g., PsycINFO, Pubmed, ProceedingsFirst), extracted required data, and calculated effect sizes. Inclusion criteria identified studies that had (a) compared alcohol or methamphetamine dependent groups to healthy controls and (b) matched groups on either age, education, or IQ (at least 2 out of 3). Studies were excluded if participants were reported to have Axis I diagnoses (other than alcohol or methamphetamine dependence) or comorbidities known to impact neuropsychological functioning. Sixteen articles were coded and analyzed for the current study. Data synthesis Alcohol studies showed a large effect size (g = 0.745, p < 0.001) while methamphetamine studies evidenced a moderate effect size (g = 0.406, p = 0.001); both without statistically significant heterogeneity (I2 = 0). Subgroup analysis revealed a statistically significant difference between the effect sizes from alcohol versus methamphetamine studies (Q-between = 5.647, p = 0.017). Conclusions The CT is sensitive to the effects of both alcohol and methamphetamine and should be considered when examining dependent patients who might exhibit problem solving, concept formation, and set loss difficulties in everyday living.

Risk Factors for Fracture in Alcohol-dependent, Pre-menopausal Females

Aims: Alcoholism is known to be associated with increased risk of fracture. This study aimed to study bone turnover following alcohol detoxification and to investigate lifestyle factors for low bone density that might coexist with alcohol dependency, which might be amenable to modification. Method: Pre-menopausal female participants were recruited from an alcohol-use dependency unit to a cross-sectional study. A lifestyle questionnaire, including alcohol history, smoking, physical activity, dietary calcium intake, falls, and fracture history was completed. Quantitative heel ultrasonography was performed and broadband ultrasound attenuation (BUA), speed of sound (SOS), t score, and z score were recorded. Blood was taken for bone-turnover markers at baseline and day 5 following admission for alcohol withdrawal.Results: The mean age (SD) of alcohol dependent participants was 41.6 (8.3) years, with participants reporting high levels of current cigarette smoking, physical inactivity, and falls. BUA, SOS, t scores, and z scores were lower than the age-matched reference range in alcohol-dependent participants. Levels of type 1 procollagen (P1NP) increased significantly after five days (p < .001). Conclusions: Alcohol-dependent, pre-menopausal individuals have multiple risk factors for fracture, beyond alcohol excess. These should be addressed and targeted as modification may reduce fracture risk, especially given the apparent recovery of bone turnover on the withdrawal of alcohol.

Neurometabolite Levels in Alcohol Use Disorder Patients During Baclofen Treatment and Prediction of Relapse to Heavy Drinking.

Background and Aims: Baclofen, a GABAB agonist, is used as a treatment for alcohol dependence. We aimed to examine brain metabolites following administration of baclofen or placebo in alcohol dependent individuals enrolled in a randomized placebo-controlled trial.Methods: Participants included 31 alcohol dependent individuals (recent drinking: N = 16; and abstinent: N = 15) who had received daily baclofen (BAC 30–75 mg = 20) or placebo (PL = 11) for at least 2 weeks (average 17 days). Using in vivo proton magnetic resonance spectroscopy (1H-MRS), spectra from the right parietal lobe were analyzed to obtain measures of GABA, Glutamate (Glu), Glutathione (GSH) and N-Acetyl Apartate (NAA) 120 min following administration of PL or BAC.Results: When weighting alcohol dependent participants according to recent alcohol consumption (within 24 h), there were significant differences between BAC and PL on parietal concentrations of GSH (p < 0.01) and NAA (p < 0.05). Multiple linear regression revealed a significant predictive effect of GSH on heavy drinking days at 12 weeks follow-up (Model: F = 14.28, R2 = 0.85; GSH: B = −1.22, p = 0.01) and also percentage days abstinent at 12 weeks follow-up (Model: F = 6.50, R2 = 0.72; GSH: B = 0.99, p = 0.06).Conclusion: Our data provide preliminary evidence that the effect of baclofen may be mediated by increased parietal concentrations of the antioxidant GSH and NAA in recently drinking alcohol dependent patients. GSH/Cr levels were also predictive of improved drinking outcomes in the trial and suggests a role for neural oxidative stress in alcohol use disorder.

Topiramate versus naltrexone for alcohol use disorder: study protocol for a genotype-stratified, double-blind randomised controlled trial (TOP study)

BackgroundCurrent treatments for alcohol use disorders have limited efficacy and there is a high degree of variability in treatment response. In a randomised, placebo-controlled clinical trial, there was a large effect size for topiramate in people homozygous for the GRIK1 rs2832407*C allele. The primary aim of the TOP study is to examine prospectively the therapeutic and cost-effectiveness of topiramate versus an active control (naltrexone) in improving treatment outcomes for alcohol dependence. Participants will be stratified on rs2832407 to compare C-allele homozygotes with A-allele carriers to examine the moderating effect of rs2832407 on drinking outcomes. An exploratory aim is to examine the moderating effects of rs1799971, a polymorphism in OPRM1, on the response to naltrexone by comparing Asn40 homozygotes with Asp40 carriers.Methods/designThis double-blind trial will randomise 180 alcohol-dependent participants to a 12-week regime of either topiramate (titrating the dose up to 200 mg/day) or naltrexone (50 mg/day). Participants will be stratified on the two polymorphisms before randomisation. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days per week and secondary drinking outcomes will include the time to relapse, the time to lapse and the percentage of abstinent days. Other secondary outcomes will include body mass index, tobacco use, anxiety symptoms and depressive symptoms.DiscussionIf successful, the TOP study will improve management strategies for alcohol dependence by providing support for the use of genetic biomarkers to inform medication selection.Trial registrationClinicalTrials.gov, NCT03479086. Registered on 27 March 2018.

The OPRM1 A118G polymorphism: converging evidence against associations with alcohol sensitivity and consumption.

The endogenous opioid system may be involved in the development and maintenance of alcohol use disorder (AUD) and is a target for existing AUD pharmacotherapies. A functional polymorphism of the mu-opioid receptor gene (OPRM1 A118G, rs1799971) may alter the risk of developing AUD. Human laboratory studies have demonstrated that minor allele carriers self-administer more alcohol, show greater sensitivity to alcohol's effects, and exhibit increased alcohol-induced dopamine release. On the other hand, large genome-wide association studies and meta-analyses of candidate gene studies have not found an association between this genotype and alcohol dependence diagnosis. Given this discrepancy, the present study sought to verify whether OPRM1 A118G was associated with alcohol self-administration, subjective response to alcohol, and craving in a sample of 106 social drinkers of European ancestry who completed an intravenous alcohol self-administration session. We found no relationship between OPRM1 rs1799971 genotype and subjective response to alcohol or craving. OPRM1 genotype was not associated with total alcohol exposure or likelihood of attaining a binge-level exposure (80 mg%) during the intravenous alcohol self-administration session. Analysis of 90-day Timeline Followback interview data in a larger sample of 965 participants of European ancestry found no relationship between OPRM1 genotype and alcohol consumption in either alcohol dependent or non-dependent participants. These findings suggest that there may not be an association between OPRM1 rs1799971 genotype and alcohol consumption or sensitivity in individuals of European ancestry.

Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans.

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol-dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol-dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to nonalcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent premorbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. (PsycINFO Database Record

Randomized open-label trial of baclofen for relapse prevention in alcohol dependence

ABSTRACTBackground: Alcohol dependence is a progressive chronic disorder characterized by narrowing of the drinking repertoire, salience of drinking, tolerance and withdrawal phenomenon, compulsion to drink, and frequent relapses. Baclofen has been shown to promote abstinence, to reduce craving, and to reduce anxiety in alcohol-dependent individuals, and it promises to be a useful agent, although clinical data are limited at present. Objective: The current study aimed to test the utility of baclofen, a GABA agonist, in improving the relapse rates in alcohol-dependent subjects. Methods: A total of 122 alcohol-dependent subjects were randomized into two groups. Groups were administered baclofen (30 mg/day) or benfothiamine (a nutritional supplement) using an open label design. Both groups received brief motivational intervention. Subjects were assessed at 0, 2, 4, 8, and 12 weeks for the primary outcome measures: time to first relapse, heavy drinking days, cumulative abstinence duration, and craving (measured by the Obsessive Compulsive Drinking Scale (OCDS)). Results: Seventy-two participants received baclofen, and 50 received benfothiamine. Participants receiving baclofen remained abstinent for significantly more days than the benfothiamine group (p < 0.05). The percentage of heavy drinking days was significantly lower in the baclofen group (p = 0.001). Craving and anxiety scores (Hamilton Anxiety Rating Scale) were also significantly decreased in the baclofen group relative to the control group (p = 0.001). Time to first relapse was similar in both groups. Conclusion: In this open-label trial, alcohol-dependent participants receiving baclofen showed significant improvements in drinking outcomes compared with participants receiving benfothiamine. This study provides further evidence that baclofen is useful for the treatment of alcohol dependence.

The effect of alcohol dependence on automatic visuo-spatial perspective taking

BackgroundAlcoholism is associated with cognitive deficits that affect social functioning. Previous research has shown that alcoholism is associated with deficits in conscious, deliberate social processing. However, little is known about whether alcoholism also affects rapid, spontaneous processing. We therefore investigated the extent to which alcoholism affects the ability to spontaneously adopt the viewpoint of another in a visuo-spatial perspective taking (VSPT) task. MethodsVSPT was measured in participants responding to a dot probe presented for 35ms alongside neutral faces, fearful faces and baseline stimuli (rectangles). ResultsNon alcohol dependent participants showed the standard reaction time cost to fearful faces, but not neutral faces relative to baseline. However, Alcohol dependent (AD) participants showed a reaction time cost to both fearful and neutral faces. ConclusionsAD participants are not impaired in their ability to automatically adopt the perspective of another. However, unlike non-AD participants, they show automatic perspective taking to both neutral and fearful faces.