Severe Alcohol Use Disorder Research Articles

Alcohol use disorder and fitness to drive: Discrepancies between health professionals' evaluations and objective measures of alcohol use and cognitive functioning.

Aims: In this study, we investigated if health professionals' evaluations of driving ability corresponded with measures of severity of alcohol use and measures of cognitive functions necessary for safely driving a car. Methods: A total of 90 participants from a multicentre study were included. Participants were categorised into three groups: (1) the group judged fit to drive (FIT); (2) the group judged not fit to drive (UNFIT); and (3) the group who had lost their driver's licence due to legal sanctions (LEGAL). The participants' AUDIT scores, earlier treatment episodes and results from neuropsychological tests of reaction time, attention and visuospatial ability were included in the analyses. Results: We found a significant difference in the severity of alcohol use disorder (AUD) and visuospatial abilities between the FIT and UNFIT groups. Half of the UNFIT group had at least mild visuospatial difficulties, compared to only a quarter in the FIT group. There were no group differences in reaction time or attentional measures. The LEGAL group had more severe AUD than the other groups. Conclusion: The FIT group did not perform differently from the UNFIT group on attention and reaction time measures. The UNFIT group had more visuospatial impairments, but even half of this group had normal scores. It is uncertain whether the differences between the two groups are of practical significance. The quality of health professionals' evaluations may be questioned, and the results highlight the need for more reliable and valid criteria for doing fitness to drive evaluations.

A CROSS-SECTIONAL STUDY OF PSYCHOSIS AND PERSONALITY PROFILE IN PATIENTS DIAGNOSED WITH ALCOHOL USE DISORDER

Objectives: The objectives of the study are (1) to study personality profile in patients diagnosed with alcohol use disorder (AUD) and (2) to study incidence of psychosis in patients with AUD. Methods: This was a cross-sectional study conducted in the department of psychiatry of a tertiary care medical college. 70 patients presenting with a history of alcohol intake underwent diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for AUD were enrolled in the study on the basis of pre-defined inclusion and exclusion criteria. Post a 2-week detoxification period, psychiatric symptoms encompassing depression, anxiety, hallucinations, and unusual behavior were assessed using the brief psychiatric rating scale (BPRS), while personality profiles were evaluated with the NEO Personality Inventory-3. Alcohol dependence levels were measured using the Severity of Alcohol Dependence Questionnaire. Results: There were 60 (85.71%) males and 10 (14.29%) females. There was a significant male preponderance in studied cases with M:F ratio of 1:0.16. Highest number of patients, i.e., 63 (90%) patients were married, followed by 4 (5.71%) patients were unmarried and 3 (4.29%) patients were divorced. Among 70 studied cases, 5 (7.14%) patients were found to have some or the other degree of psychotic symptoms. There was a significant correlation between being unskilled worker and having low literacy or low income and AUD (p<0.05). There was no statistically significant association between severity of AUD and education (p=0.70), occupation (p=0.94), income (p=0.84), and family history of alcohol consumption (p=0.58). Participants have mild severity shown low to average score on neuroticism, average scores on extraversion, very low to low scores on openness, high to very high scores on agreeableness, and high to very high scores on conscientiousness. Conclusion: We found a significant correlation of AUD with increasing age, male gender, early alcohol initiation, and prolonged dependence. Lower education and unskilled occupations were also linked to AUD. Personality trait analysis revealed distinct patterns based on the severity of physical dependency.

Altered attentional processing of facial expression features in severe alcohol use disorder: An eye-tracking study.

Social cognition impairments, and notably emotional facial expression (EFE) recognition difficulties, as well as their functional and clinical correlates, are increasingly documented in severe alcohol use disorder (SAUD). However, insights into their underlying mechanisms are lacking. Here, we tested if SAUD was associated with alterations in the attentional processing of EFEs. In a preregistered study, 40 patients with SAUD and 40 healthy controls (HCs) had to identify the emotional expression conveyed by faces while having their gaze recorded by an eye-tracker. We assessed indices of initial (first fixation locations) and later (number of fixations and dwell-time) attention with reference to regions of interest corresponding to the eyes, mouth, and nose, which carry key information for EFE recognition. We centrally found that patients had less first fixations to key facial features in general, as well as less fixations and dwell time to the eyes specifically, relative to the rest of the face, compared to controls. These effects were invariant across emotional expressions. Additional exploratory analyses revealed that patients with SAUD had a less structured viewing pattern than controls. These results offer novel, direct, evidence that patients with SAUD's socioaffective difficulties already emerge at the facial attentional processing stage, along with precisions regarding the nature and generalizability of the effects. Potential implications for the mechanistic conceptualization and treatment of social cognition difficulties in SAUD are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Nicotine Addiction, Alcohol Use Disorder and Bipolar Disorder

Bipolar affective disorder has a wide range of effects on human health and is extremely harmful, and the mortality rate of patients continues to grow. Meanwhile, most people, especially those with mental illness, tend to numb themselves by smoking and drinking. Unfortunately, tobacco and alcohol abuse are also extremely harmful to human health, moreover, the cost of living will be increased due to addiction of these things. At the same time, the unconscious mind after using alcohol and tobacco has also brought great uneasiness to society, thus leading to increased burden on individuals and society. This review discusses the genetics, comorbidity, and treatment of nicotine dependence, alcohol use disorder, and bipolar disorder, and finds that the severity of bipolar disorder patients is positively correlated with the severity of alcohol use disorder and nicotine dependence. Both patients with bipolar disorder and alcohol use disorder exhibit mutations in the BDNF gene, and an age peak in bipolar disorder coincides with a peak in nicotine dependence. In the end, it is believed that the interaction between comorbidities may become a breakthrough in the diagnosis or treatment of bipolar disorder in the future, and the easy-to-observe alcohol and nicotine intake can be used to assist in judging the current state of patients.

Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats

Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin’s general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.

Associations between alcohol use disorder polygenic score andremission in participants from high-risk families and the Indiana Biobank.

In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGSAUD ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGSAUD would be negatively associated with remission. Individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met lifetime criteria for AUD, and two EA cohorts ascertained for studies of liver diseases and substance use disorders from the Indiana Biobank were included. In COGA, 12-month remission was defined as any period of ≥12 consecutive months without meeting AUD criteria except craving and was further categorized as abstinent and non-abstinent. In the Indiana Biobank, remission was defined based on ICD codes and could not be further distinguished as abstinent or non-abstinent. Sex and age were included as covariates. COGA analyses included additional adjustment for AUD severity, family history of remission, and AUD treatment history. In COGA EA, PGSAUD was negatively associated with 12-month and non-abstinent remission (p ≤ 0.013, βs between -0.15 and -0.10) after adjusting for all covariates. In contrast to the COGA findings, PGSAUD was positively associated with remission (p = 0.004, β = 0.28) in the Indiana Biobank liver diseases cohort but not in the Indiana Biobank substance use disorder cohort (p = 0.17, β = 0.15). PGSAUD was negatively associated with 12-month and non-abstinent remission in COGA EA, independent of behavioral measures of AUD severity and family history of remission. The discrepant results in COGA and the Indiana Biobank could reflect different ascertainment strategies: the Indiana Biobank participants were older and had higher rates of liver disease, suggesting that these individuals remitted due to alcohol-related health conditions that manifested in later life.

Reduction of alcohol use and increase in psychological flexibility after a naturalistic psychedelic experience: a retrospective survey.

Alcohol use can be significantly associated with negative social, professional, and health outcomes. Even more so, alcohol use disorder (AUD) is a critical public health issue and major avoidable risk factor. This study aimed to examine the effect of a naturalistic psychedelic experience on alcohol use and related measures. A retrospective online survey was conducted on 160 individuals who reported a psychedelic experience and a concomitant drinking habit but did not necessarily have an AUD. Demographic data, characteristics of the psychedelic experience, and changes in alcohol consumption and psychological flexibility were surveyed. Results: The mean number of drinking days per week and AUDIT scores significantly decreased after the psychedelic experience (P < .001). Subjects who quit or reduced drinking had a more severe AUD (P < .01) and lower psychological flexibility (P = .003) before the psychedelic session. Alcohol use reduction was significantly associated with the intensity of the mystical experience (P = .03). Psychological flexibility increased more in participants who reduced their alcohol use (P < .001), and the change in psychological flexibility was one of the predictors of alcohol use improvement (P = .003). Conclusion: Our findings suggest that a naturalistic psychedelic experience could be associated with a reduction in alcohol use and dependency. Such positive health outcomes can be associated with the intensity of the mystical experience as well as an increase in psychological flexibility.

Alcohol use disorder in alcohol-associated liver disease: Two sides of the same coin.

Alcohol-associated liver disease (ALD) has emerged as the leading indication for liver transplantation (LT) worldwide, with 40% of LTs in the United States performed for ALD in 2019. The ALD-related health care burden accelerated during the COVID-19 pandemic, especially in young individuals. Alcohol use disorder (AUD), which focuses on the negative effects of alcohol on psychosocial, physical, and mental health, is present in the majority of patients with ALD, with moderate to severe AUD in 75%-80%. During the last decade, early liver transplantation (eLT) has emerged as a lifesaving treatment for selected patients with alcohol-associated hepatitis; these patients may have a higher risk of using alcohol after LT. The risk of alcohol use recurrence may be reduced during the pretransplant or post-transplant period with AUD treatment using behavioral and/or pharmacological therapies and with regular monitoring for alcohol use (self-reported and complemented with biomarkers like phosphatidylethanol). However, AUD treatment in patients with ALD is challenging due to patient, clinician, and system barriers. An integrated model to provide AUD and ALD care by hepatologists and addiction experts in a colocated clinic starting from LT evaluation and selection to monitoring listed candidates and then to following up on recipients of LT should be promoted. However, the integration of addiction and hepatology teams in an LT program in the real world is often present only during evaluation and candidate selection for LT. Data are emerging to show that a multidisciplinary integrated AUD treatment within an LT program reduces recurrent alcohol use after LT. If we want to continue using early liver transplantation for patients with severe alcohol-associated hepatitis, LT programs should focus on building integrated multidisciplinary care teams for the integrated treatment of both AUD and ALD.

Alcohol cues increase behavioral economic demand and craving for alcohol in nontreatment-seeking and treatment-seeking heavy drinkers.

Behavioral economic research has revealed significant increases in alcohol demand following exposure to alcohol-related cues. Prior research has focused exclusively on nontreatment-seeking heavy drinkers, included only male participants, or used heterogeneous methods. The current studies sought to replicate and extend existing findings in treatment-seeking and nontreatment-seeking heavy drinkers while also examining sex effects and moderation by alcohol use disorder (AUD) severity. Study 1 included 117 nontreatment-seeking heavy drinkers (51.5% women; M age 34.69; 56.4% AUD+), and Study 2 included 89 treatment-seeking heavy drinkers with AUD (40.4% women; M age = 41.35). In both studies, alcohol demand was measured using a hypothetical alcohol purchase task (APT), and subjective alcohol craving was measured using visual analog scales. Measures were collected following exposure to neutral (water) cues in a standard room and alcohol cues in a bar lab. Alcohol demand (intensity, Omax , breakpoint, and elasticity) and craving were significantly increased following alcohol cues compared to neutral cues (ps < 0.005) with effect sizes ranging from small to large (ηp 2 = 0.074-0.480). Participants with AUD (Study 1) or with higher AUD severity (Study 2) reported higher craving and higher demand for most indices (i.e., main effects; ps < 0.032, ηp 2 = 0.043-0.239). A larger alcohol cue increase in Omax was found for AUD+ participants in Study 1 compared to non-AUD participants (p = 0.028, ηp 2 = 0.041) but not for any other indices in Study 1 or Study 2. There were no significant sex effects. These findings replicate and extend prior research by offering additional insight into alcohol cue effects on the reinforcing value of alcohol and subjective motivation to drink. The results also suggest that sex and AUD severity do not meaningfully impact cue effects across most indices of demand.

Relationship between self-stigma about alcohol dependence and severity of alcohol drinking and craving

BackgroundThe correlates and consequences of stigma surrounding alcohol use are complex. Alcohol use disorder (AUD) is typically accompanied by self-stigma, due to numerous factors, such as shame, guilt and negative...

Alcohol consumption and health-related quality of life in regional, rural and metropolitan Australia: analysis of cross-sectional data from the Community Health and Rural/Regional Medicine (CHARM) study

BackgroundRelationships between alcohol consumption and health are complex and vary between countries, regions, and genders. Previous research in Australia has focused on estimating the effect of alcohol consumption on mortality. However, little is known about the relationships between alcohol consumption and health-related quality of life (QoL) in Australia. This study aimed to investigate the levels of alcohol intake and QoL in males and females in rural, regional and metropolitan areas of Australia.MethodParticipants (n = 1717 Australian adults) completed an online cross-sectional study. Males and females were compared on measures including the AUDIT-C and WHOQOL-BREF. Data were stratified into risk of alcohol use disorder (AUD) and associations were examined between alcohol consumption and QoL, adjusting for sociodemographic variables.ResultsMales had higher alcohol consumption and were at greater risk of AUD than females (20% vs 8%). Relationships between alcohol consumption and QoL were positive or non-significant for low–moderate AUD risk categories and negative in the severe AUD risk category. Males in regional communities reported higher alcohol consumption (AUDIT-C score 6.6 vs 4.1, p < 0.01) than metropolitan areas. Regression analyses identified that after adjusting for sociodemographic variables, alcohol consumption was positively related to overall, environmental, and physical QoL and general health.ConclusionThe results indicate that alcohol consumption is negatively related to QoL only in those with severe risk of AUD. Males in regional areas reported higher alcohol consumption than those in metropolitan areas. These results provide further information about relationships between alcohol intake and health in Australia that can help inform prevention, screening and delivery of interventions.

The Impact of the COVID-19 Pandemic on the Severity of Alcohol Use Disorder: Significance of Dual Disorders.

The coronavirus disease 2019 (COVID-19) pandemic has been assumed to impact patients diagnosed with alcohol use disorder (AUD). The severity of the influence that the COVID-19 pandemic had on the symptoms of AUD has not yet been revealed in detail. The aim of this study was to examine the impact of the COVID-19 pandemic on patients diagnosed with AUD. This retrospective study was conducted between 11 March 2017 and 31 May 2022 in Hungary. Medical charts (N = 1082) of inpatients with the diagnosis of AUD were reviewed. Based on the dates of admissions, two groups were created: the 'before COVID-19' group (11 March 2017-10 March 2020) and the 'during COVID-19' group (11 March 2020-31 May 2022). Chi-square tests, independent-sample t-tests, and multinomial logistic regressions were performed. The occurrence of delirium tremens (DT) and psychiatric co-morbidities was significantly higher during the pandemic. Our results showed that the occurrence of DT and psychiatric co-morbidities significantly increased during the pandemic. Our results revealed that the pandemic enhanced the severe consequences of AUD, and the development of AUD might have increased in frequency among individuals previously diagnosed with mental illness during the pandemic. These findings indicate the significance of dual disorders in the post-pandemic period.

Diagnostic Criteria for Identifying Individuals at High Risk of Progression From Mild or Moderate to Severe Alcohol Use Disorder

Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnoses of substance use disorders rely on criterion count-based approaches, disregarding severity grading indexed by individual criteria. To examine correlates of alcohol use disorder (AUD) across count-based severity groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative of greater severity, and evaluate whether specific criteria within mild-to-moderate AUD differentiate across relevant correlates and manifest in greater hazards of severe AUD development. This cohort study involved 2 cohorts from the family-based Collaborative Study on the Genetics of Alcoholism (COGA) with 7 sites across the United States: cross-sectional (assessed 1991-2005) and longitudinal (assessed 2004-2019). Statistical analyses were conducted from December 2022 to June 2023. Sociodemographic, alcohol-related, psychiatric comorbidity, brain electroencephalography (EEG), and AUD polygenic score measures as correlates of DSM-5 AUD levels (ie, mild, moderate, severe) and criterion severity-defined mild-to-moderate AUD diagnostic groups (ie, low-risk vs high-risk mild-to-moderate). A total of 13 110 individuals from the cross-sectional COGA cohort (mean [SD] age, 37.8 [14.2] years) and 2818 individuals from the longitudinal COGA cohort (mean baseline [SD] age, 16.1 [3.2] years) were included. Associations with alcohol-related, psychiatric, EEG, and AUD polygenic score measures reinforced the role of increasing criterion counts as indexing severity. Yet within mild-to-moderate AUD (2-5 criteria), the presence of specific high-risk criteria (eg, withdrawal) identified a group reporting heavier drinking and greater psychiatric comorbidity even after accounting for criterion count differences. In longitudinal analyses, prior mild-to-moderate AUD characterized by endorsement of at least 1 high-risk criterion was associated with more accelerated progression to severe AUD (adjusted hazard ratio [aHR], 11.62; 95% CI, 7.54-17.92) compared with prior mild-to-moderate AUD without endorsement of high-risk criteria (aHR, 5.64; 95% CI, 3.28-9.70), independent of criterion count. In this cohort study of a combined 15 928 individuals, findings suggested that simple count-based AUD diagnostic approaches to estimating severe AUD vulnerability, which ignore heterogeneity among criteria, may be improved by emphasizing specific high-risk criteria. Such emphasis may allow better focus on individuals at the greatest risk and improve understanding of the development of AUD.

Metadehumanization, fundamental needs and coping strategies: A comparison of drinkers at low versus high risk of alcohol use disorder

The interpersonal difficulties documented in chronic excessive drinking might foster the progression toward severe alcohol use disorder (SAUD). Characterizing these interpersonal difficulties and their commonalities with patients already presenting a diagnosed SAUD is needed to develop targeted prophylactic interventions. Patients with SAUD present metadehumanization (i.e., the perception of being considered as less than human by others), which is associated with deleterious consequences (e.g., reduced fundamental needs satisfaction, increased negative emotions, reduced self-esteem, disrupted coping strategies) involved in the persistence of this disorder. No study has investigated metadehumanization among individuals not diagnosed with SAUD but at high risk of alcohol use disorder. We measured metadehumanization, emotions, self-esteem, coping strategies, and fundamental needs threat among such high-risk drinkers (N = 86; AUDIT score higher than 15), and matched low-risk drinkers (N = 100, AUDIT score <8). Compared to low-risk drinkers, high-risk drinkers felt more dehumanized and reported increased fundamental needs threat, negative emotions, anxiety, depression, and more frequent use of both adaptive and maladaptive coping strategies, including alcohol use. Mediation analyses controlling for anxiety/depression revealed that the differences in emotions and coping strategies were explained by metadehumanization and fundamental needs threat. Despite not being diagnosed with SAUD and being untreated, high-risk drinkers are more similar to patients with SAUD than to low-risk drinkers. In view of its links with factors favoring SAUD, metadehumanization should be considered in experimental studies among high-risk drinkers and treated by specific interventions.

Assessment of alcohol withdrawal syndrome: new perspectives

Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in non-specific and secondly in psychiatric/addictive in- or outpatient units. On the other hand, alcohol withdrawal syndrome is one of the most important outcomes of the severity of alcohol use disorder, further, it can lead to the development of alcohol-related seizure and delirium tremens. Hence, early recognition and optimal treatment of alcohol withdrawal syndrome have a critical importance. Therefore, the main goal of the present review was - by systematically summarizing the scientific data published during the past two decades - to form a unique diagnostic and therapeutic algorithm. During the recognition and the course of alcohol withdrawal syndrome, the Clinical Institute Withdrawal Assessment for Alcohol, Revised scale, while in the risk assessment the Prediction of Alcohol Withdrawal Severity Scale are the recommended psychometric tools. Benzodiazepines are the key elements of the pharmacotherapy of alcohol withdrawal syndrome. Many studies have evaluated that diazepam, chlordiazepoxide, lorazepam and oxazepam with distinct indications have sufficient evidence in the treatment of alcohol withdrawal syndrome. However, in the past few years some authors have recommended the importance of non-benzodiazepine medications. The efficacy of propofol, phenobarbital, carbamazepin, oxcarbamazepin and alpha-2 receptor agonists in the treatment of alcohol withdrawal syndrome have been revealed. Furthermore, it has been evaluated that benzodiazepines are recommended in the treatment of alcohol-related seizure and delirium tremens. In the present review, our aim was to construct a unique, up-to-date diagnostic and therapeutic algorithm by summarizing the related papers published during the past two decades. Hence this scheme may be useful in the optimal treatment of patients diagnosed with alcohol use disorder and it could help to conduct further clinical researches. Orv Hetil. 2023; 164(38): 1487-1496.

Patterns of drinking behavior around a treatment episode for alcohol use disorder: Predictions from pre-treatment measures.

Alcohol use disorder (AUD) has been described as a chronic disease given the high rates that affected individuals have in returning to drinking after a change attempt. Many studies have characterized predictors of aggregated alcohol use (e.g., percent heavy drinking days) following treatment for AUD. However, to inform future research on predicting drinking as an AUD outcome measure, a better understanding is needed of the patterns of drinking that surround a treatment episode and which clinical measures predict patterns of drinking. We analyzed data from the Project MATCH and COMBINE studies (MATCH: n = 1726; 24.3% female, 20.0% non-White; COMBINE: n = 1383; 30.9% female, 23.2% non-White). Daily drinking was measured in the 90 days prior to treatment, 90 days (MATCH) and 120 days (COMBINE) during treatment, and 365 days following treatment. Gradient boosting machine learning methods were used to explore baseline predictors of drinking patterns. Drinking patterns during a prior time period were the most consistent predictors of future drinking patterns. Social network drinking, AUD severity, mental health symptoms, and constructs based on the addiction cycle (incentive salience, negative emotionality, and executive function) were associated with patterns of drinking prior to treatment. Addiction cycle constructs, AUD severity, purpose in life, social network, legal history, craving, and motivation were associated with drinking during the treatment period and following treatment. There is heterogeneity in drinking patterns around an AUD treatment episode. This study provides novel information about variables that may be important to measure to improve the prediction of drinking patterns during and following treatment. Future research should consider which patterns of drinking they aim to predict and which period of drinking is most important to predict. The current findings could guide the selection of predictor variables and generate hypotheses for those predictors.

Adaptor protein complex 2 in the orbitofrontal cortex predicts alcohol use disorder.

Alcohol use disorder (AUD) is a life-threatening disease characterized by compulsive drinking, cognitive deficits, and social impairment that continue despite negative consequences. The inability of individuals with AUD to regulate drinking may involve functional deficits in cortical areas that normally balance actions that have aspects of both reward and risk. Among these, the orbitofrontal cortex (OFC) is critically involved in goal-directed behavior and is thought to maintain a representation of reward value that guides decision making. In the present study, we analyzed post-mortem OFC brain samples collected from age- and sex-matched control subjects and those with AUD using proteomics, bioinformatics, machine learning, and reverse genetics approaches. Of the 4,500+ total unique proteins identified in the proteomics screen, there were 47 proteins that differed significantly by sex that were enriched in processes regulating extracellular matrix and axonal structure. Gene ontology enrichment analysis revealed that proteins differentially expressed in AUD cases were involved in synaptic and mitochondrial function, as well as transmembrane transporter activity. Alcohol-sensitive OFC proteins also mapped to abnormal social behaviors and social interactions. Machine learning analysis of the post-mortem OFC proteome revealed dysregulation of presynaptic (e.g., AP2A1) and mitochondrial proteins that predicted the occurrence and severity of AUD. Using a reverse genetics approach to validate a target protein, we found that prefrontal Ap2a1 expression significantly correlated with voluntary alcohol drinking in male and female genetically diverse mouse strains. Moreover, recombinant inbred strains that inherited the C57BL/6J allele at the Ap2a1 interval consumed higher amounts of alcohol than those that inherited the DBA/2J allele. Together, these findings highlight the impact of excessive alcohol consumption on the human OFC proteome and identify important cross-species cortical mechanisms and proteins that control drinking in individuals with AUD.

Craving modulates attentional bias towards alcohol in severe alcohol use disorder: An eye-tracking study.

Competing models disagree on three theoretical questions regarding alcohol-related attentional bias (AB), a key process in severe alcohol use disorder (SAUD): (1) is AB more of a trait (fixed, associated with alcohol use severity) or state (fluid, associated with momentary craving states) characteristic of SAUD; (2) does AB purely reflect the over-activation of the reflexive/reward system or is it also influenced by the activity of the reflective/control system and (3) does AB rely upon early or later processing stages? We addressed these issues by investigating the time-course of AB and its modulation by subjective craving and cognitive load in SAUD. A free-viewing eye-tracking task, presenting pictures of alcoholic and non-alcoholic beverages, combined with a concurrent cognitive task with three difficulty levels. A laboratory setting in the detoxification units of three Belgian hospitals. We included 30 patients with SAUD self-reporting craving at testing time, 30 patients with SAUD reporting a total absence of craving and 30 controls matched on sex and age. All participants from SAUD groupsmet the DSM-5 criteria for SAUD. We assessed AB through early and late eye-tracking indices. We evaluated the modulation of AB by craving (comparison between patients with/without craving) and cognitive load (variation of AB with the difficulty level of the concurrent task). Dwell time measure indicated that SAUDpatients with craving allocated more attention towards alcohol-related stimuli than patients without craving (P < 0.001, d = 1.093), resulting in opposite approach/avoidance AB according to craving presence/absence. SAUD patients without craving showed a stronger avoidance AB than controls (P = 0.003, d = 0.806). AB did not vary according to cognitive load (P = 0.962, η2 p = 0.004). The direction of alcohol-related attentional bias (approach/avoidance) appears to be determined by patients' subjective craving at testing time and does not function as a stable trait of severe alcohol use disorder. Alcohol-related attentional bias appears to rely on later/controlled attentional stages but is not modulated by the saturation of the reflective/control system.

The efficacy of virtual reality exposure therapy for the treatment of alcohol use disorder among adult males: a randomized controlled trial comparing with acceptance and commitment therapy and treatment as usual.

This multicenter, three-armed, parallel, single-blind randomized controlled trial (RCT) primarily aims to compare the efficacy of virtual reality exposure therapy (VRET) with that of acceptance and commitment therapy (ACT) and treatment as usual (TAU) to depreciate the degree of alcohol craving among alcohol use disorder patients who have undergone in-patient detoxification across four timelines (t0 = baseline prior to intervention, t1 = 4 weeks after baseline, t2 = 12 weeks after baseline, and t3 = 24 weeks after baseline). The secondary aims of this RCT are to compare the efficacy of VRET with that of ACT and TAU to alleviate the severity of alcohol use disorder, dissipate comorbid depressive and anxiety symptoms, and normalize event-related potential (ERP) in electroencephalogram (EEG) monitoring across the four timelines. Initially, after 2 weeks of in-patient detoxification, 120 patients with alcohol use disorder will be randomized into three groups (VRET, ACT, and TAU control groups) via stratified permuted block randomization in a 1:1:1 ratio. Baseline assessment (t0) commences, whereby all the participants will be administered with sociodemographic, clinical, and alcohol use characteristics questionnaire, such as Alcohol Use Disorder Identification Test (AUDIT), Penn Alcohol Craving Scale (PACS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D), while event-related potential (ERP) detection in electroencephalogram (EEG) will also be carried out. Then, 4 weeks of VRET, ACT, and non-therapeutic supportive activities will be conducted in the three respective groups. For the subsequent three assessment timelines (t1, t2, and t3), the alcohol use characteristic questionnaire, such as AUDIT, PACS, HAM-D, HAM-A, and ERP monitoring, will be re-administered to all participants. As data on the effects of non-pharmacological interventions, such as VRET and ACT, on the treatment of alcohol craving and preventing relapse in alcohol use disorder are lacking, this RCT fills the research gap by providing these important data to treating clinicians. If proven efficacious, the efficacy of VRET and ACT for the treatment of other substance use disorders should also be investigated in future. NCT05841823 (ClinicalTrials.gov).

Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.

Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.