Severe Alcohol Use Disorder Research Articles

The Feasibility, Tolerability, and Safety of Administering a Very High Alcohol Dose to Drinkers with Alcohol Use Disorder.

There remains a paucity of research quantifying alcohol's effects in drinkers with alcohol use disorder (AUD), particularly responses to very high alcohol doses (≥0.8g/kg). As drinkers with AUD frequently engage in very heavy drinking (8 to 10 drinks/occasion), doses of ≤0.8g/kg may lack ecological validity. The present study examined the feasibility, tolerability, and safety of administering a very high alcohol dose (1.2g/kg) to non-treatment-seeking AUD participants. Sixty-one young adult AUD drinkers enrolled in the Chicago Social Drinking Project and completed 3 laboratory sessions at which they consumed a beverage with 1.2, 0.8, and 0.0g/kg alcohol. Physiological responses (vital signs, nausea and vomiting, breath alcohol concentrations [BrAC]) were monitored throughout the sessions. After each session, participants completed a next-day survey of substance use, engagement in risky behaviors, and related consequences. Overall, the sample demonstrated good compliance with study procedures; 93% of participants adhered to presession alcohol abstinence requirements (indicated by BrAC<0.003g/dl), with no participants exhibiting serious alcohol withdrawal symptoms at arrival to study visits. The 1.2g/kg alcohol dose achieved an expected mean peak BrAC of 0.13g/dl at 60minutes after drinking, which was well tolerated; the majority of the sample did not experience nausea (70%) or vomiting (93%), and dose effects on vital signs were not clinically significant. Finally, we demonstrated that the 1.2g/kg alcohol dose is safe and not associated with postsession consequences, including reduced sleep time, atypical substance use, accidents or injuries, and severe hangovers. Results support the feasibility, tolerability, and safety of administering a very high alcohol dose to young adult drinkers with AUD within the context of a well-validated laboratory alcohol challenge paradigm. Utilizing an alcohol dose more consistent with naturalistic drinking patterns may foster greater ecological validity of laboratory paradigms for persons with moderate to severe AUD.

Development of alcohol use disorder in young Swiss men: the influence of retrospectively perceived parenting profiles

This four-wave longitudinal study aimed to examine the associations between retrospectively perceived parenting profiles in adolescence and the development of alcohol use disorder (AUD) throughout emerging adulthood. The cohort consisted of 190 young Swiss men who completed retrospective reports of parenting at baseline and a short AUD self-report screening tool at four measurement times (mean age at baseline = 20.18; Time 1: 21.52; Time 2: 25.61; Time 3: 26.99). Latent profile analysis revealed three parenting profiles in adolescence based on retrospective measures of parenting styles and practices: Optimal (the highest levels of involvement, structure and knowledge; 69%), Uninformed (high levels of involvement, moderate levels of structure and the lowest levels of knowledge; 17%), Low Support (the lowest levels of involvement, moderate levels of structure and knowledge; 14%). Using latent growth curve analysis, we found that young men in the Low Support profile experienced a greater increase in AUD severity compared with those in the Uninformed and Optimal profiles. Young men in the Uninformed profile reported higher levels of AUD severity at baseline than those in the Optimal profile. These findings highlight the associations between retrospectively perceived parenting profiles during adolescence and the development of AUD during emerging adulthood.

23.2 ALCOHOL USE DISORDER VS CANNABIS USE DISORDER SYMPTOMATOLOGY IN ADOLESCENTS IS DIFFERENTIALLY ASSOCIATED WITH DYSFUNCTIONS IN NEURAL REPRESENTATIONS OF PREDICTION ERROR FOLLOWING EXPLORATION OF NOVEL STIMULI IN AN INSTRUMENTAL LEARNING TASK

Two of the most commonly used substances by adolescents are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with decision-making impairments in adolescents. Recent work has shown that adolescents with elevated levels of AUD symptoms show reduced striatal responsivity to reward in the context of both the monetary incentive delay task and an instrumental learning task. Theoretical models of substance use disorders (SUDs) suggest that novelty seeking is a key trait associated with the development of SUDs. Neurobiological models of novelty seeking indicate that novelty seeking is related to striatal reward processing and prediction error (PE) representation. The goal of the current study was to investigate neurocomputational impairments associated with AUD vs CUD symptom severity.

Predictors of Changes in Alcohol Craving Levels during a Virtual Reality Cue Exposure Treatment among Patients with Alcohol Use Disorder.

Background/Objective: Determining the predictive variables associated with levels of alcohol craving can ease the identification of patients who can benefit from treatments. This study aimed to describe changes (improvement or no change/deterioration) in alcohol craving levels and explore the predictors of these changes from admission to discharge in outpatients with alcohol use disorder (AUD) undergoing treatment-as-usual (TAU), or treatment-as-usual supplemented with virtual reality cue-exposure therapy (TAU + VR-CET). Method: A prospective cohort study was conducted amongst 42 outpatients with AUD (n = 15 TAU + VR-CET and n = 27 TAU) from a clinical setting. Changes in the levels of alcohol craving between admission and discharge were assessed with the Multidimensional Alcohol Craving Scale. Sociodemographic characteristics (age, gender, education, and socioeconomic and civil status), cognitive-affective behavioral patterns (AUD severity, abstinence duration, psychiatric comorbidity, state anxiety, attentional bias, and substance use), and type of treatment (TAU + VR-CET and only TAU) were also evaluated. Results: The TAU + VR-CET group showed greater changes of improvement in the levels of alcohol craving than the TAU group (χ2 = 10.996; p = 0.001). Intragroup changes in alcohol craving from pre to post-treatment were significant in the TAU + VR-CET group (χ2 = 13.818; p = 0.003) but not within the TAU group (χ2 = 2.349; p = 0.503). The odds of an improvement in any of the craving levels between pre- and post-test was 18.18 (1/0.055) times higher in the TAU + VR-CET group with respect to the TAU group. The use of illicit drugs in the month prior to the test increased the odds of having a positive change by 18.18 (1/0.055) with respect to not having consumed. Conclusions: Including VR-CET in TAU programs may provide benefits in the treatment of AUDs mainly among patients with intense alcohol craving and individuals having used illicit substances prior to treatment.

Association between severity of alcohol use disorder and consent to follow up in the emergency department.

Association between severity of alcohol use disorder and consent to follow up in the emergency department.

A latent class analysis of alcohol and posttraumatic stress symptoms among offspring of parents with and without alcohol use disorder

The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is widely known, yet few studies have examined whether and how AUD symptoms co-occur with PTSD symptom clusters of hypervigilance, avoidance/numbing, and re-experiencing. The purpose of this study was to examine potential overlap between AUD and posttraumatic stress symptomatology, and to characterize the resultant latent classes in terms of demographics, drinking behaviors, parental AUD, and specific traumas experienced (physical violence, sexual violence, and non-assaultive trauma). We hypothesized that classes would be differentiated by type and severity of AUD and PTS symptoms. Drawing from a sample of white and Black participants from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined young adults between the ages of 18–35 who had experienced trauma (N = 2478). A series of LCA models based on the type of trauma experienced, posttraumatic stress symptoms and problematic alcohol use were then fitted to the data. A four-class solution provided the best fit, consisting of a low symptom class (N = 1134), moderate alcohol/low PTS severity (N = 623), mild alcohol/high PTS severity (N = 544), and high symptom severity (N = 177). Higher prevalence of sexual assault was associated with membership in high PTS severity classes, and parent AUD was associated with membership in each class, particularly when the mother or both parents had the disorder. Using person-centered methods such as LCA is a commonsense approach to understanding the heterogeneity of symptoms, trauma types, and individual-level characteristics associated with trauma-exposed individuals and comorbid AUD-PTSD, and our study is one of relatively few to empirically ascertain the co-occurrence of alcohol and PTS symptoms in a high-risk family sample.

Neurocognitive performance in alcohol use disorder using the NIH toolbox: Role of severity and sex differences

AimsSustained heavy alcohol consumption is associated with a range of neurocognitive deficits. Yet, past research centers on a severe profile of alcohol use disorder (AUD), with persons recruited from in-patient settings. The current project aims to compare neurocognitive performance between individuals seeking AUD outpatient treatment with healthy comparisons while considering the association between performance, disorder severity, and sex. MethodsEnrollment included two matched groups (N = 125; 34 % female): 77 treatment-seeking individuals with AUD; 48 healthy comparison individuals with low drinking patterns. Neurocognitive performance on NIH Toolbox subtests measuring attention, inhibition, episodic memory, working memory, language, and processing speed were compared across groups. Within the AUD group, analyses examined the relationship between performance, disorder severity, recent alcohol consumption, and sex. ResultsAUD group did not perform significantly lower than healthy comparisons on neurocognition subtests assessed. Within AUD group, females displayed significantly higher processing speeds than males (p = .007). Disorder severity and alcohol consumption were not significantly related to performance. However, a significant interaction between disorder severity and sex emerged (p = .010), with higher severity associated with poorer performance in males but not females, on a subtest measuring attention and inhibition. ConclusionsEffect of heavy alcohol use on neurocognitive performance was not detected in this outpatient AUD sample. Weaknesses in domains of attention and inhibition may be correlated with AUD severity among males, but not females. Further research on AUD severity and sex in understanding individual differences in neurocognition is warranted, particularly using novel tools for large scale phenotyping, such as the NIH Toolbox.

A Comparison of Disability Weights for Alcohol Use Disorders

Objective: This study aims to determine and compare the disability weights of alcohol use disorders (AUD) based on responses from AUD patients and a non-patient population using three valuation methods. Material and Methods: Cross-sectional data were collected from three hospitals in southern Thailand. Two groups of participants were recruited: 150 patients diagnosed with AUD and a control group containing 150 persons without AUD. Both groups were asked to rate the AUD health states using a visual analogue scale (VAS), and again using either the European Quality of Life-5 Dimension (EQ-5D) instrument or the time trade-off (TTO) technique. Data were collected via face-to-face interviews. Results: The mean disability weights, based on the VAS, TTO and EQ-5D valuation methods obtained from AUD patients were: 0.485, 0.405, and 0.311, respectively, while those obtained from the control group were: 0.541, 0.330, and 0.237, respectively. Disability weights had a positive correlation with AUD severity levels. Employment status and family income were significantly associated with VAS disability weight among the control group. Conclusion: The use of three different instruments to calculate disability weights for people with AUD is feasible in Thailand. The disability weights differ depending on the valuation methods used and respondent groups.

Racial/ethnic discrimination and alcohol use disorder severity among United States adults

BackgroundRacism, and resultant racial/ethnic discrimination is a ubiquitous social determinant of health that is linked to adverse alcohol-related outcomes. To our knowledge, no studies have examined whether manifestations of racial/ethnic discrimination increase risk of DSM-5 alcohol use disorder (AUD) severity levels. MethodsAnalyses were conducted among 17,115 racial/ethnic minority respondents of the National Epidemiologic Survey on Alcohol-Related Conditions III (NESARC-III), a cross-sectional survey fielded in 2012−2013. We used multinomial logistic regression to examine the associations between measures of racial/ethnic discrimination and past-year AUD severity levels following the DSM-5 definition, while adjusting for poverty thresholds set by the U.S. Census Bureau, and race/ethnicity (American Indian or Alaskan Native; Asian, Native Hawaiian, or Other Pacific Islander; Black or African American; Hispanic or Latino). We also evaluated whether associations between discrimination and AUD severity varied by poverty status and race/ethnicity. ResultsCovariate-adjusted multinomial logistic regressions suggested that in comparison to those who did not experience discrimination, those who experienced discrimination had a 1.5-fold greater risk of mild AUD, a 1.6-fold greater risk of moderate AUD, and a 2.3-fold greater risk of severe AUD. We found no evidence to suggest that the strength of the association between racial/ethnic discrimination and AUD severity varied across race/ethnic group or poverty status. ConclusionsExperience of racial/ethnic discrimination is associated with greater AUD severity in the U.S. regardless of one’s specific racial/ethnic group membership or poverty status. Strategies to reduce risk for severe AUD should include efforts to minimize the occurrence and impact of interpersonal and institutional racism.

Early Adolescent Binge Drinking Increases Risk of Psychopathology in Post-9/11 Veterans and Mild Traumatic Brain Injury Exacerbates Symptom Severity.

To demonstrate that early adolescent binge drinking (BD) increases the risk for and/or severity of psychopathology in post-9/11 Veterans and determine if mild traumatic brain injury (mTBI) modifies risk. Post-9/11 Veterans (n = 375) were classified into two groups: 57 Veterans with a history of early adolescent BD (E-BD; age of onset <15) and 318 who did not BD until age 15 or older (late-BD or L-BD; age of onset ≥15). History of military mTBI and mental health disorders were also assessed following military service. Logistic regression and analysis of variance (ANOVA) analyses revealed that the E-BD's had significantly higher prevalence of alcohol use disorders (AUDs) and more severe symptoms of AUD, substance use disorder (SUD), depression and stress. Two-way ANOVAs showed that history of military mTBI was differentially associated with posttraumatic stress disorder (PTSD) incidence and severity among Veterans who had engaged in early adolescent BD. Specifically, Veterans with a history of both early adolescent BD and military mTBI were at greater risk for a PTSD diagnosis and had more severe symptoms of PTSD than those with only a history of adolescent BD. The greater PTSD symptom severity in the comorbid group was driven by hyperarousal symptoms. A history of BD during early adolescence is prevalent among Veterans and is related to higher risk for AUD and more severe AUD, SUD, mood and stress symptoms later in life. Veterans with early BD and military mTBI showed greater incidence and severity of PTSD, indicating that mTBI, a common comorbidity among post-9/11 Veterans, exacerbates risk.

Trial study design to test a bilingual digital health tool for alcohol use disorders among Latino emergency department patients

We describe an emergency department (ED)-based, Latino patient focused, unblinded, randomized controlled trial to empirically test if automated bilingual computerized alcohol screening and brief intervention (AB-CASI), a digital health tool, is superior to standard care (SC) on measures of alcohol consumption, alcohol-related negative behaviors and consequences, and 30-day treatment engagement. The trial design addresses the full spectrum of unhealthy drinking from high-risk drinking to severe alcohol use disorder (AUD). In an effort to surmount known ED-based alcohol screening, brief intervention, and referral to treatment process barriers, while addressing racial/ethnic alcohol-related health disparities among Latino groups, this trial will purposively use a digital health tool and seek enrollment of English and/or Spanish speaking self-identified adult Latino ED patients. Participants will be randomized (1:1) to AB-CASI or SC, stratified by AUD severity and preferred language (English vs. Spanish). The primary outcome will be the number of binge drinking days assessed using the 28-day timeline followback method at 12 months post-randomization. Secondary outcomes will include mean number of drinks/week and number of episodes of driving impaired, riding with an impaired driver, injuries, arrests, and tardiness and days absent from work/school. A sample size of 820 is necessary to provide 80% power to detect a 1.14 difference between AB-CASI and SC in the primary outcome. Showing efficacy of this promising bilingual ED-based brief intervention tool in Latino patients has the potential to widely and efficiently expand prevention efforts and facilitate meaningful contact with specialized treatment services.

The Influences of Impulsivity and Education Levels on Severity of Alcohol Dependence

BackgroundImpulsivity contributes to the severity of alcohol use disorder. The association is affected by expectation towards alcohol use, emotional regulation and self-control. Here we investigated the influences of self-reported impulsivity and levels of education on severity of alcohol dependence.MethodWe retrospectively analyzed the basic demographic information, alcohol consumption state, education years, depression and anxiety state, Alcohol Use Disorder Identification Test (AUDIT) and Barrett Impulsivity Scales (BIS) from a group of 66 AUD patients.ResultImpulsivity significantly predicted alcohol dependence severity (R 2 = 0.069, F = 4.724, p = 0.034). In addition, education years served as a moderator in the relationship between impulsivity and alcohol dependence severity (ΔR2 = 0.059, F = 4.414, p = 0.040).ConclusionSelf-reported impulsivity affects the severity of alcohol dependence, which might be different in patients with different education levels.

Hostile attributional bias in severe alcohol use disorder

Impairments in social cognition have been documented in severe alcohol use disorder (SAUD) over the past two decades. They have been linked with lower social functioning and poor treatment outcomes, illustrating their key role in the disorder. However, studies investigating social cognition in SAUD have largely focused on emotional decoding and theory of mind abilities, neglecting other important processes. We expand this line of research by exploring the association between SAUD and hostile attributional biases (i.e., the tendency to attribute hostile intentions to others), another clinically relevant subcomponent of social cognition. Thirty-five patients with SAUD and thirty-five matched healthy controls completed the short version of the Ambiguous Intentions Hostility Questionnaire, a validated measure assessing participants’ perceived hostility, blame attribution and aggression in relation to vignettes depicting social situations with negative outcomes and ambiguous intent. Patients with SAUD attributed more hostile intentions to others than did healthy controls. Moreover, this hostile attributional bias was associated with increased interpersonal problems in SAUD, as measured through the Inventory of Interpersonal Problems. We thus evidence hostile attributional bias in SAUD and extend the growing literature on social cognition impairments in this population. Furthermore, these findings corroborate the recent proposal that patients with SAUD exhibit biases toward socially threatening information. The association between hostile attributional bias and interpersonal problems suggests that targeting this bias in treatment may reduce the relapse risk resulting from interpersonal deficits. Recommendations are made to further explore the clinical relevance of hostile attributional bias in SAUD.

Toward a better understanding of the influence of repetitive negative thinking in alcohol use disorder: An examination of moderation effect of metacognitive beliefs and gender

Repetitive negative thinking (RNT), the most studied forms of which are depressive ruminations and anxious worry, is a unique transdiagnostic process responsible for the development and maintenance of many mental disorders. Over the past decade, studies have shown that RNT could be involved in the development and maintenance of alcohol use disorder (AUD). However, to date, little is known about the factors that can influence this relationship, even though some theoretical and empirical arguments suggest that variables such as gender or metacognitive beliefs may determine the role of RNT in the onset of symptoms. The aim of the present study was to test the moderation effect of metacognitive beliefs and gender in the relationship between RNT and AUD. Eighty-one AUD patients were administered measures of AUD severity, RNT, metacognitive beliefs about thinking and alcohol use, anxiety, and depression. Results indicated that the ‘capture mental resources’ factor of RNT is a significant predictor of AUD severity, independent from anxiety and depression, and that this effect is moderated by metacognitive beliefs and gender. RNT is a significant predictor of AUD severity only for people with high negative beliefs about thoughts regarding uncontrollability and danger. Furthermore, RNT was found to predict AUD severity only for men with high beliefs about the need to control thoughts and for men with high positive beliefs about emotional self-regulation. Treatments that reduce attentional impairments caused by RNT and modify dysfunctional metacognitive beliefs could be promising for some patients with AUD.

Predictors of premature treatment termination in a large residential addiction medicine program

BackgroundWhile inpatient programs are a common setting for addiction treatment, patients' premature termination is a major concern. Predicting premature treatment termination has the potential to substantially improve patient outcomes by identifying high-risk profiles and suggesting care paths that might reduce dropout. The current study examined the predictors of premature termination from an inpatient addiction medicine service. MethodsIn 1082 patients admitted to a large inpatient addiction medicine service, we used intake assessments of severity of alcohol use disorder, illicit drug use disorder, post-traumatic stress disorder (PTSD), anxiety disorders, and major depressive disorder to predict planned termination (n = 922) or premature termination (n = 160). We used two complementary analytic approaches—traditional binary logistic regression and a data-driven latent profile analysis (LPA). ResultsBinary logistic regression revealed that alcohol use severity, illicit drug use severity, and PTSD severity significantly predicted termination status, although alcohol use severity notably exhibited an inverse relationship. The LPA revealed four distinct profiles, with one profile exhibiting a significantly higher rate of premature termination and another exhibiting a significantly lower rate of premature termination. The high-risk profile was characterized by high drug severity, high comorbid psychopathology (PTSD, depression, and anxiety symptoms), but low alcohol severity. The low-risk profile was characterized by high alcohol severity, but low drug use and low comorbid psychopathology. ConclusionsThese results provide converging evidence that illicit drug severity and psychiatric severity, and particularly PTSD, were associated with premature termination. Moreover, the LPA revealed distinct latent subgroups of patients with meaningfully higher and lower risk of premature termination, suggesting that addiction services should develop strategies for identifying high-risk individuals or develop care paths for high-risk symptom clusters. Approaches that are trauma-informed or otherwise focus on the management of comorbid psychiatric conditions may be particularly appropriate for reducing premature termination.

Developing and Validating an Item Bank for Alcohol Use Disorder Screening in the Chinese Population by Using the Computerized Adaptive Testing.

ObjectiveTo detect the individual’s severity of alcohol use disorder (AUD) in an effective and accurate manner, this study aimed to build an item bank for AUD screening and derive the computerized adaptive testing (CAT) version of AUD (CAT-AUD).MethodsThe initial CAT-AUD item bank was selected from the Chinese version of the questionnaires related to AUD according to the DSM-5 criteria. Then 915 valid Chinese samples, covering the healthy individuals and the AUD high-risk individuals, completed the initial CAT-AUD item bank. By testing the unidimensionality, test fit, item fit, discrimination parameter and differential item functioning of the initial item bank, the final CAT-AUD item bank confirming to the requirements of the item response theory (IRT) were obtained. Subsequently, the CAT-AUD simulation study based on the real data of the final item bank conducted to detect characteristics, reliability, validity, and predictive utility (sensitivity and specificity) of CAT-AUD.ResultsThe CAT-AUD item bank meeting the IRT psychometric measurement requirements could be well geared into the graded response model. The Pearson’s correlation between the estimated theta via CAT-AUD and the estimated theta via the full-length item bank reached 0.95, and the criterion-related validity was 0.63. CAT-AUD can provide highly reliable test results for subjects whose theta above −0.8 with an average of 16 items. Besides, the predictive utility of CAT-AUD was better than AUDIT and AUDIT-C.ConclusionIn brief, the CAT-AUD developed in this study can effectively screen the AUD high-risk group and accurately measure the AUD severity of individuals.

Childhood Trauma Predicts Less Remission from PTSD among Patients with Co-Occurring Alcohol Use Disorder and PTSD.

Post-traumatic stress disorder (PTSD) is highly prevalent among patients hospitalized for an alcohol use disorder (AUD). Hospitalization can improve PTSD and AUD outcomes in some but not all patients, but we lack data on the baseline predictors of PTSD non-remission. This study aimed to determine the baseline risk factors for non-remitted PTSD in patients hospitalized for an AUD. Of 298 AUD inpatients recruited in a rehabilitation center (Le Courbat, France), we included 91 AUD inpatients with a co-occurring PTSD and a longitudinal assessment at baseline (T1) and before discharge (T2: 8 weeks later). Patients were assessed for PTSD diagnosis/severity (PCL-5=PTSD Checklist for DSM-5), different types of trauma including childhood trauma (LEC-5=Life Events Checklist for DSM-5/CTQ-SF=Childhood Trauma Questionnaire, Short-Form), and AUD diagnosis/severity (clinical interview/AUDIT=Alcohol Use Disorders Identification Test). Rate of PTSD remission between T1 and T2 was 74.1%. Non-remitted PTSD at T2 was associated with a history of childhood trauma (physical, emotional or sexual abuse, physical negligence), but not with other types of trauma experienced, nor baseline PTSD or AUD severity. Among patients hospitalized for an AUD with co-occurring PTSD, PTSD remission was more strongly related to the existence of childhood trauma than to AUD or PTSD severity at admission. These patients should be systematically screened for childhood trauma in order to tailor evidence-based interventions.

A Novel Sulfonamide, 4-FS, Reduces Ethanol Drinking and Physical Withdrawal Associated With Ethanol Dependence.

Carbonic anhydrase (CA) is abundant in glial cells in the brain and CA type II isoform (CA II) activity in the hippocampus plays an important role in buffering extracellular pH transients produced by neural activity. Chronic ethanol exposure results in respiratory and metabolic acidosis, producing shifts in extracellular pH in the brain and body. These neurophysiological changes by ethanol are hypothesized to contribute to the continued drinking behavior and physical withdrawal behavior in subjects consuming ethanol chronically. We explored whether chronic ethanol self-administration (ethanol drinking, 10% v/v; ED) without or under the influence of chronic intermittent ethanol vapor (CIE-ED) experience alters the expression of CA II in the hippocampus. Postmortem hippocampal tissue analyses demonstrated that CA II levels were enhanced in the hilus region of the hippocampus in ED and CIE-ED rats. We used a novel molecule—4-fluoro-N-(4-sulfamoylphenyl) benzenesulfonamide (4-FS)—a selective CA II inhibitor, to determine whether CA II plays a role in ethanol self-administration in ED and CIE-ED rats and physical withdrawal behavior in CIE-ED rats. 4-FS (20 mg/kg, i.p.) reduced ethanol self-administration in ED rats and physical withdrawal behavior in CIE-ED rats. Postmortem hippocampal tissue analyses demonstrated that 4-FS reduced CA II expression in ED and CIE-ED rats to control levels. In parallel, 4-FS enhanced GABAA receptor expression, reduced ratio of glutamatergic GluN2A/2B receptors and enhanced the expression of Fos, a marker of neuronal activation in the ventral hippocampus in ED rats. These findings suggest that 4-FS enhanced GABAergic transmission and increased activity of neurons of inhibitory phenotypes. Taken together, these findings support the role of CA II in assisting with negative affective behaviors associated with moderate to severe alcohol use disorders (AUD) and that CA II inhibitors are a potential therapeutic target to reduce continued drinking and somatic withdrawal symptoms associated with moderate to severe AUD.

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder

RationaleCompared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity.ObjectivesIn this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task.MethodsOut of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task (“Simon-task”) and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses.ResultsThe four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions.ConclusionsOur findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Metadehumanization in severe alcohol-use disorders: Links with fundamental needs and clinical outcomes

BackgroundDehumanization, i.e., the denial of one’s humanity, has important consequences for social interactions. Earlier works mainly studied the dehumanizer’s perspective, neglecting victims and particularly psychiatric populations. This study’s goal is thus to investigate if patients with severe alcohol-use disorders (SAUD) feel dehumanized by others and to reveal factors linked to metadehumanization. MethodsA cross-sectional study in 120 patients with SAUD as diagnosed by their psychiatrist using DSM-IV criteria. ResultsParticipants reported significant levels of metadehumanization, which were directly or indirectly linked to fundamental needs threat (γ = 0.41, p < .001), decreased positive emotions (indirect effect = −0.11, p < .05), reduced self-esteem (indirect effect = −0.16, p < .01), reduced use of functional coping strategies focused on the search of social support (γ = −0.20, p < .05), and increased use of dysfunctional coping strategies (indirect effect = 0.15, p < .01) such as excessive alcohol use (indirect effect = 0.10, p < .05). ConclusionsPatients feel dehumanized by others, an experience linked to important deleterious consequences for patients’ wellbeing and treatment.