Severe Alcohol Use Disorder Research Articles

Predictors of polysubstance use in patients with severe alcohol use disorder: the role of reward craving

BackgroundDifferent craving typologies (i.e., reward, relief, obsessive) have been identified in alcohol use disorder (AUD) but have been less investigated in specific populations like AUD patients with polysubstance use (PSU). The role of dysfunctional personality traits and reward pathways has been reported in both AUD and PSU. We hypothesized that patients with AUD-PSU might show a prevalent reward craving, alongside specific sociodemographic, clinical, and personality features, and aimed at investigating differences in 423 severe AUD outpatients with and without PSU. MethodsOne hundred fifteen patients (27.1% of the sample, 67% males, 42 ± 11.6 years old) displayed PSU. Sociodemographic, clinical features and psychopathological/personality dimensions were assessed through: Craving Typologies Questionnaire (CTQ); Obsessive–Compulsive Drinking Scale (OCDS); UPPS-P Impulsive Behavior Scale (S-UPPS-P); Difficulties in Emotion Regulation Scale (DERS). A binomial logistic regression explored factors associated with PSU. ResultsWe found higher CTQ ‘reward’ scores (p < 0.001) in AUD-PSU patients, and a significant association between reward craving and PSU through logistic regression (OR:1.13; p = 0.005). Earlier AUD onset (p < 0.001), greater rates of binge drinking (p = 0.029), more legal problems (p = 0.015), but no significantly higher S-UPPS-S and DERS scores, were detected in AUD-PSU patients. ConclusionsReward craving was associated with increased risk for PSU in severe AUD patients. Given AUD-PSU participants greater severity and detrimental treatment responses imputed to PSU, identifying prevalent craving types among risk factors for PSU in AUD may help to implement therapeutic strategies. Addressing neurobiological and behavioral mechanisms through combined psychotherapies, pharmacological and neuromodulation treatments could support tailored interventions with better long-term outcome.

Learning from others' experience: Social fear conditioning deficits in patients with severe alcohol use disorder.

Alcohol use disorder (AUD) is a significant public health problem. A better understanding of the psychosocial factors contributing to AUD is important for developing public health policy. The purpose of this study was to identify social mechanisms involved in AUD and, more specifically, to determine whether vicarious learning deficits are related to the disorder. A secondary objective was to evaluate the role of empathy in social fear conditioning. Patients with severe AUD (n = 30) and healthy participants (n = 30) performed a social fear learning (SFL) task. The task assesses how an association between a stimulus and an aversive consequence is acquired through social means. Specifically, participants observed a person receiving an electric shock (unconditioned stimulus; US) that was associated (conditioned stimulus; CS+) or not (CS-) with a neutral CS. The skin conductance response was used to measure the effect of learning. Individuals with severe AUD showed a deficit in SFL, indicating that they had difficulty learning from another's negative experience. Patients also evaluated the emotional experience as less unpleasant than healthy participants. This study is the first to show that patients with severe AUD have social learning deficits. The findings suggest that these individuals do not learn from another's negative experience. At a fundamental level, the findings demonstrate the importance of understanding the role of social mechanisms in AUD. At a clinical level, the study highlights the potential for using social learning enhancement to prevent relapse in individuals with severe AUD.

Who benefits from brief motivational intervention among young adults presenting to the emergency department with alcohol intoxication: A latent-class moderation analysis.

Research has not identified which patients optimally benefit from brief Motivational Interviewing (bMI) for heavy drinking when delivered to young adults in the Emergency Department (ED). We conducted secondary analyses of data from a randomized controlled trial in which 344 young adults (18-35 years) presenting to the ED with alcohol intoxication received either bMI or Brief Advice (BA, control group). We used Latent Class Analysis to derive participants' profiles from baseline characteristics (i.e., sex, age, severity of alcohol use disorder, attribution of ED admission to alcohol use, importance, and confidence to change, cognitive discrepancy, anxiety, depression, and trait reactance). We then conducted a moderation analysis to assess the number of heavy drinking days at short-term (1-month) and long-term (12-month) follow-up using negative binomial regressions with interactions between the intervention and derived classes. Fit statistics indicated that a 4-class solution best fit the data. Class 3 (high severity, importance and discrepancy, and low confidence and anxiety) benefitted more from bMI than BA at short- and long-term follow-up than Class 1 (younger; lowest severity, importance, discrepancy, reactance, anxiety and depression, and highest confidence). Class 2 (older; highest severity, importance, discrepancy, reactance, anxiety and depression, and lowest confidence) also benefitted more from bMI than BA than did Class 1 at short-term follow-up. In these significant contrasts, Class 1 benefitted more from BA than bMI. There were no significant interactions involving Class 4 (more likely to be women; low severity; high levels of anxiety, depression, and reactance). This study identified the patient profiles that benefitted more from bMI than BA among nontreatment-seeking young adults who present intoxicated to the ED. The findings have implications for intervention design and argue for the importance of research aimed at developing intervention content tailored to patient profiles.

Time Since Last Drink is Positively Associated with Heart Rate Variability in Outpatients with Alcohol Use Disorder: Further Evidence of Psychophysiological Recovery in Early Alcohol Use Disorder Recovery.

Heart rate variability (HRV) is a biomarker of psychological and physiological health with greater variability reflecting greater psychophysiological regulatory capacity. The damaging effects of chronic, heavy alcohol use on HRV have been well explored, with greater alcohol use associated with lower resting HRV. In this study we sought to replicate and extend our previous finding that HRV improves as individuals with alcohol use disorder (AUD) reduce or stop drinking and engage in treatment. With a sample of treatment engaged adults in the first year of a current AUD recovery attempt (N = 42), we used general linear models to explore associations between indices of HRV (dependent variables) and time since last alcoholic drink at study baseline assessed using timeline follow-back (independent variable), with checks for effects of age, medication, and baseline AUD severity. As predicted, HRV increased as a function of time since last drink, however, contrary to hypotheses, HR did not decrease. Effect sizes were largest for HRV indices fully under parasympathetic control, and these significant associations remained after controlling for age, medications, and AUD severity. Because HRV is an indicant of psychophysiological health, as well as self-regulatory capacity that may portend subsequent relapse risk, assessing HRV in individuals entering AUD treatment could provide important information about patient risk. At-risk patients may do well with additional support and may especially benefit from interventions like Heart Rate Variability Biofeedback that exercise the psychophysiological systems regulating brain/cardiovascular communication.

Prescribing Medications for Alcohol Use Disorder: A Qualitative Study of Primary Care Physician Decision Making.

Over 29 million Americans have alcohol use disorder (AUD). Though there are effective medications for AUD (MAUD) that can be prescribed within primary care, they are underutilized. We aimed to explore how primary care physicians familiar with MAUD make prescribing decisions and to identify reasons for underuse of MAUD within primary care. We conducted semistructured interviews with 19 primary care physicians recruited from a large online database of medical professionals. Physicians had to have started a patient on MAUD within the last 6 months in an outpatient setting. Inductive and deductive thematic analysis was informed by the theory of planned behavior. Physicians endorsed that it is challenging to prescribe MAUD due to several reasons, including: (1) somewhat negative personal beliefs about medication effectiveness and likelihood of patient adherence; (2) competing demands in primary care that make MAUD a lower priority; and, (3) few positive subjective norms around prescribing. To make MAUD prescribing a smaller component of their practice, physicians reported applying various rules of thumb to select patients for MAUD. These included recommending MAUD to the patients who seemed the most motivated to reduce drinking, those with the most severe AUD, and those who were also receiving other treatments for AUD. There is a challenging implementation context for MAUD due to competing demands within primary care. Future research should explore which strategies for identifying a subset of patients for MAUD are the most appropriate and most likely to improve population health and health equity.

Management of alcohol use disorder in patients with chronic liver disease.

Alcohol use disorder (AUD) rates have risen dramatically in the United States, resulting in increasing rates of alcohol-associated liver disease (ALD), but many patients struggle to access alcohol use treatment. AUD treatment improves outcomes, including mortality, and represents the most urgent means by which care can be improved for those with liver disease (including ALD and others) and AUD. AUD care for those with liver disease involves 3 steps: detecting alcohol use, diagnosing AUD, and directing patients to alcohol treatment. Detecting alcohol use can involve questioning during the clinical interview, the use of standardized alcohol use surveys, and alcohol biomarkers. Identifying and diagnosing AUD are interview-based processes that should ideally be performed by a trained addiction professional, but nonaddiction clinicians can use surveys to determine the severity of hazardous drinking. Referral to formal AUD treatment should be made, especially where more severe AUD is suspected or identified. Therapeutic modalities are numerous and include different forms of one-on-one psychotherapy, such as motivational enhancement therapy or cognitive behavior therapy, group therapy, community mutual aid societies (such as Alcoholics Anonymous), inpatient addiction treatment, and relapse prevention medications. Finally, integrated care approaches that build strong relationships between addiction professionals and hepatologists or medical providers caring for those with liver disease are crucial to improving care for this population.

Rejection sensitivity in severe alcohol use disorder: Increased anxious anticipation of rejection

Rejection sensitivity (RS) reflects the disposition to anxiously expect, readily perceive, and disproportionately react to rejection. It is linked to interpersonal problems and psychopathological symptoms, which are frequent in severe alcohol use disorder (SAUD) and are known to influence clinical outcomes. Consequently, RS has been put forward as a process of interest in this disorder. However, empirical studies investigating RS in SAUD are scarce and focused on its last two components, leaving the core process of anxious expectations of rejection unexplored. To fil this gap, 105 patients with SAUD and 73 age-and-gender-matched controls completed the validated Adult Rejection Sensitivity Scale. We computed anxious anticipation (AA), and rejection expectancy (RE) scores, corresponding to the affective and cognitive dimensions of anxious expectations of rejection, respectively. Participants also completed measures of interpersonal problems and psychopathological symptoms. We found that patients with SAUD had higher AA (affective dimension) but not RE (cognitive dimension) scores. Moreover, AA was associated with interpersonal problems as well as psychopathological symptoms in the SAUD sample. These findings meaningfully extend the RS and social cognition literatures in SAUD by showing that difficulties already arise at the anticipatory stage of socio-affective information processing. Moreover, they shed light on the affective component of anxious expectations of rejection as a novel, clinically relevant process in this disorder.

Identifying Treatment Responders to Varenicline for Alcohol Use Disorder Using Two Machine-Learning Approaches

Varenicline has shown promise for treating alcohol use disorder (AUD); however, not everyone will respond to varenicline. Machine-learning methods are well suited to identify treatment responders. In the present study, we examined data from the National Institute on Alcohol Abuse and Alcoholism Clinical Intervention Group multisite clinical trial of varenicline using two machine-learning methods. Baseline characteristics taken from a randomized clinical trial of varenicline were examined as potential moderators of treatment response using qualitative interaction trees ( N = 199) and group least absolute shrinkage and selection operator interaction nets ( N = 200). Results align with prior research, highlighting smoking status, AUD severity, medication adherence, and drinking goal as predictors of treatment response. Novel findings included the interaction between age and cardiovascular health in predicting clinical response and stronger medication effects among individuals with lower craving. With increased integration of machine-learning methods, studies that effectively integrate methods and medication development have high potential to inform clinical practice.

Ketogenic diet enhances the effects of oxycodone in mice

Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.

Sticking with it? Factors associated with exercise adherence in people with alcohol use disorder

BackgroundEmerging evidence suggests that exercise may be an efficacious treatment for alcohol use disorder (AUD), but adherence is suboptimal. We examined factors associated with adherence to an exercise intervention for non-treatment seeking adults with AUD. MethodsThis secondary analysis of a randomized controlled trial included 95 physically inactive adults aged 18–75 years with clinician-diagnosed AUD. Study participants were randomly assigned to 12-weeks fitness centre-based, supervised aerobic exercise or yoga classes and asked to attend at least three times/week. Adherence was assessed both objectively (based on use of a keycard at entry) and subjectively using an activity calendar. The association between AUD and other predictor variables with adherence was assessed using logistic and Poisson regression models. ResultsJust under half of participants (47/95, 49%) completed ≥ 12 supervised exercise sessions. When both supervised classes and self-reported sessions were included, 32/95 (34%) participants completed ≤ 11 sessions, 28/95 (29%) did 12–23 sessions and 35/95 (37%) completed ≥ 24 sessions. In univariate logistic regression analyses, lower education was associated with non-adherence (<12 sessions) (OR = 3.02, 95%CI = 1.19–7.61). In models adjusted for demographic and clinical variables, moderate AUD (OR = 0.11, 95%CI = 0.02–0.49) and severe AUD (OR = 0.12, 95%CI = 0.02–0.69) were associated with non-adherence, when compared to low severity AUD. Higher body mass index (OR = 0.80, 95%CI = 0.68–0.93) was also associated with non-adherence. Results were materially the same when objective and subjective adherence data were combined. ConclusionAdults with AUD can be supported to engage in yoga and aerobic exercise. Additional support may be required for those with moderate or severe AUD, higher BMI, and lower education.

Strategies to maintain recovery from alcohol problems during the COVID-19 pandemic: Insights from a mixed-methods national survey of adults in the United States.

The COVID-19 pandemic has been associated with poorer mental health and, in some cases, increased alcohol consumption; however, little is known about the pandemic's effects on people in recovery from alcohol use disorder (AUD), especially how they have coped with novel stressors. Our mixed-methods study investigated strategies used to maintain recovery during the pandemic, with attention to variation by gender. We analyzed data obtained in fall 2020 from an online US national survey of adults with resolved AUD (n = 1,492) recruited from KnowledgePanel, a probability-based cohort of non-institutionalized adults maintained by Ipsos for internet-based research. Participants endorsed possible coping strategies on a 19-item choose-all-that-apply list, which were analyzed using chi-square tests. In addition, 1,008 participants provided text responses to an open-ended question about their strategies to maintain recovery during the pandemic, which were coded and analyzed using an inductive, thematic approach. The majority of our sample met criteria for severe lifetime AUD (72.9%), reported being in recovery more than five years (75.5%), and had never used specialty AUD services or mutual-help groups (59.7%). The ordering of the coping strategies was quite similar for women and men; however, the top strategy (talking with family and friends by phone, text, or video) was endorsed more frequently by women than men (49.7% vs. 36.1%; p < .001). Among qualitative themes, "staying connected" was the most common. It was dominated by statements about family, with women mentioning children more often than men. Among other themes, "cognitive strategies" mirrored established therapeutic modalities, and "active pursuits" aligned with many recent recommendations for service providers working with substance-using populations during the pandemic. A minority of participants invoked "willpower" for recovery or stated that pandemic restrictions helped by reducing exposure to relapse risks. These findings shed light on recovery mechanisms during the COVID-19 pandemic and suggest potential intervention targets to support recovery during other catastrophic events, such as natural disasters.

Wearable Sensor and Mobile App–Based mHealth Approach for Investigating Substance Use and Related Factors in Daily Life: Protocol for an Ecological Momentary Assessment Study

Digital health technologies using mobile apps and wearable devices are a promising approach to the investigation of substance use in the real world and for the analysis of predictive factors or harms from substance use. Moreover, consecutive repeated data collection enables the development of predictive algorithms for substance use by machine learning methods. We developed a new self-monitoring mobile app to record daily substance use, triggers, and cravings. Additionally, a wearable activity tracker (Fitbit) was used to collect objective biological and behavioral data before, during, and after substance use. This study aims to describe a model using machine learning methods to determine substance use. This study is an ongoing observational study using a Fitbit and a self-monitoring app. Participants of this study were people with health risks due to alcohol or methamphetamine use. They were required to record their daily substance use and related factors on the self-monitoring app and to always wear a Fitbit for 8 weeks, which collected the following data: (1) heart rate per minute, (2) sleep duration per day, (3) sleep stages per day, (4) the number of steps per day, and (5) the amount of physical activity per day. Fitbit data will first be visualized for data analysis to confirm typical Fitbit data patterns for individual users. Next, machine learning and statistical analysis methods will be performed to create a detection model for substance use based on the combined Fitbit and self-monitoring data. The model will be tested based on 5-fold cross-validation, and further preprocessing and machine learning methods will be conducted based on the preliminary results. The usability and feasibility of this approach will also be evaluated. Enrollment for the trial began in September 2020, and the data collection finished in April 2021. In total, 13 people with methamphetamine use disorder and 36 with alcohol problems participated in this study. The severity of methamphetamine or alcohol use disorder assessed by the Drug Abuse Screening Test-10 or the Alcohol Use Disorders Identification Test-10 was moderate to severe. The anticipated results of this study include understanding the physiological and behavioral data before, during, and after alcohol or methamphetamine use and identifying individual patterns of behavior. Real-time data on daily life among people with substance use problems were collected in this study. This new approach to data collection might be helpful because of its high confidentiality and convenience. The findings of this study will provide data to support the development of interventions to reduce alcohol and methamphetamine use and associated negative consequences. DERR1-10.2196/44275.

Links between psychopathological symptoms and cortical thickness in men with severe alcohol use disorder: A Magnetic Resonance Imaging study.

Anxiety and depression are psychopathological states frequently co-occurring with severe alcohol use disorder (SAUD). These symptoms generally disappear with abstinence but may persist in some patients, increasing the relapse risk. The cerebral cortex thickness of 94 male patients with SAUD was correlated with symptoms of depression and anxiety, both measured at the end (2-3 weeks) of the detoxification treatment. Cortical measures were obtained using surface-based morphometry implemented with Freesurfer. Depressive symptoms were associated with reduced cortical thickness in the superior temporal gyrus of the right hemisphere. Anxiety level was correlated with lower cortical thickness in the rostral middle frontal region, inferior temporal region, and supramarginal, postcentral, superior temporal, and transverse temporal regions of the left hemisphere, as well as with a large cluster in the middle temporal region of the right hemisphere. At the end of the detoxification stage, the intensity of depressive and anxiety symptoms is inversely associated with the cortical thickness of regions involved in emotions-related processes, and the persistence of the symptoms could be explained by these brain deficits.

Pasteurella multocida Bacteremia in a Large Community Teaching Hospital, 2011–2020: A Quality Improvement Project—Lessons Learned Regarding Immunizations

Abstract Introduction Pasteurella multocida is a small, pleomorphic, nonflagellated, gram-negative coccobacillus found as a commensal of the upper respiratory tract of mammals and birds. Human infections are linked primarily to dog and cat bites, scratches, and licks. As part of an institutional review board–approved quality improvement project, we reviewed 10 years of experience (2011–2020) with P. multocida bacteremia (PMB) at our institution. Materials and Methods We identified all episodes of PMB at our institution from January 1, 2011, to December 31, 2020, from computerized blood culture records. We recorded information regarding epidemiology, source of bacteremia, comorbid medical conditions, laboratory data, radiographic data, antimicrobial treatment, and patient outcomes as well as information regarding providers' inquiries about animal contact, animal rabies vaccine status, and patient tetanus immunization status. Results During the 10-year study period, we identified 21 patients with 20 episodes of PMB. One patient experienced 2 episodes of PMB 1 year apart. The mean/median ages of patients with PMB were 71/68 years, respectively. Of the 21 PMB episodes, 17 (81%) occurred in women. Notably, 8 of 21 episodes (38%) occurred in patients with underlying liver dysfunction: 5 with severe alcohol use disorder (AUD), 1 with chronic hepatitis C virus infection, and 2 with nonalcoholic cirrhosis. Three of 21 patients (14%) died because of complications of PMB despite appropriate antimicrobial therapy. All 3 fatal cases were women who met criteria for severe AUD. In 14 of 21 episodes (65%), the patient was asked about pet exposure: 12 of 14 exposures (86%) involved a cat. Rabies vaccination status of the pet was documented in 3 of 21 episodes (14%). Tetanus vaccination status of the patient was explored in 7 of 21 PMB episodes (33%). Conclusions There were 21 episodes of PMB in 20 patients during the 10-year study period. Pasteurella multocida bacteremia was associated with female sex (81%), multiple comorbid conditions, and, notably, with liver dysfunction resulting from severe AUD, hepatitis C virus infection, or cirrhosis from other causes. Mortality was 3/21 (14%) and all 3 patients who died had underlying liver disease. Opportunities for improvement in patients with PMB were identified including routine inquiries about patient's animal exposure, rabies vaccination status of involved animal, and tetanus verification/administration of patients with PMB. In addition, women with cirrhosis/AUD are at high risk for severe, fatal PMB when it occurs.

Alcohol Craving and Severity are Associated with Dorsal Anterior Cingulate Choline Levels in Individuals with an Alcohol Use Disorder.

Magnetic resonance spectroscopy (MRS) has been used to probe inflammation in the brain. While altered MRS metabolite levels have previously been found in individuals with alcohol use disorder (AUD), the relationship between potential metabolite markers of inflammation and the clinical correlates of AUD remains understudied. Therefore, this exploratory study sought to elucidate the clinical significance of inflammation in AUD by examining relationships between metabolites, AUD severity, alcohol consumption, and craving in individuals with AUD. Data for this secondary analysis are derived from a two-week clinical trial of ibudilast to treat AUD. Forty-three non-treatment-seeking individuals with an AUD (26M/17F) completed an MRS scan and alcohol-related questionnaires. MRS was performed using a multi-voxel array placed above the corpus callosum, extending from the pregnenual anterior cingulate to premotor cortex. The dorsal anterior cingulate was selected as the volume of interest. Metabolite levels of choline-compounds (Cho), myo-inositol (mI), and creatine+phosphocreatine (Cr) were quantified. Separate hierarchical regression models were used to evaluate the independent effects of metabolite levels on alcohol craving, alcohol problem severity, and alcohol consumption. Dorsal anterior cingulate Cho predicted alcohol craving and alcohol problem severity over and above demographics, medication, and alcohol consumption measures. mI and Cr did not predict alcohol craving or alcohol problem severity. Metabolite markers were not predictive of alcohol consumption. This preliminary study indicates that dACC Cho is sensitive to clinical characteristics of AUD. This is a further step in advancing neurometabolites, particularly Cho, as potential biomarkers and treatment targets for AUD.

Can thiamine substitution restore cognitive function in alcohol use disorder?

While clinical consequences of thiamine deficiency in alcohol use disorder (AUD) are severe, evidence-based recommendations on dosage, type of administration and duration of thiamine substitution (TS), and its' target levels remain sparse. This study aimed to compare the effect of two best practice TS regimens on thiamine blood levels (i.e. thiamine pyrophosphate, TPP) and cognitive function. In 50 patients undergoing in-patient alcohol-withdrawal treatment, TPP levels were determined at baseline and end of weeks 1, 2 and 8 following administration of oral TS (3 × 100mg/day for 7days followed by 1 × 100mg/day thereafter) either with or without preceding intravenous TS (3 × 100mg/day for 5days). An extensive psychiatric assessment was conducted at baseline, including an evaluation of AUD severity and depressive symptoms. Additionally, cognitive function and depressive symptoms were repeatedly evaluated. Relevant increases (mean increase by 100.2nmol/l [CI 76.5-123.8], P < 0.001) in peripheral blood TPP levels were observed in all patients at the end of weeks 1 and 2. Furthermore, no relevant difference between the intravenous and the oral group was found (average difference between increases: 2.3nmol/l, P = 0.912). Importantly, an association between the 'extent of the response' to TS and the performance in a memory task was revealed in secondary analyses. TS was associated with improving cognitive function in patients with AUD, independently of the substitution regime. Thus, in clinical practice, oral TS might be a sufficient but obligatory medication to prevent cognitive decline in AUD in the absence of Wernicke-Korsakoff Syndrome.

The Microbiome-Gut-Brain axis regulates social cognition &craving in young binge drinkers.

Binge drinking is the consumption of an excessive amount of alcohol in a short period of time. This pattern of consumption is highly prevalent during the crucial developmental period of adolescence. Recently, the severity of alcohol use disorders (AUDs) has been linked with microbiome alterations suggesting a role for the gut microbiome in its development. Furthermore, a strong link has emerged too between microbiome composition and socio-emotional functioning across different disorders including AUD. The aim of this study was to investigate the potential link (and its predictive value) between alcohol-related altered microbial profile, social cognition, impulsivity and craving. Young people (N=71) aged 18-25 reported their alcohol use and underwent a neuropsychological evaluation. Craving was measured at baseline and three months later. Diet was controlled for. Blood, saliva and hair samples were taken for inflammatory, kynurenine and cortisol analysis. Stool samples were provided for shotgun metagenomic sequencing and short-chain fatty acids (SCFAs) were measured. Binge drinking was associated with distinct microbiome alterations and emotional recognition difficulties. Associations were found for several microbiome species with emotional processing and impulsivity. Craving showed a strong link with alterations in microbiome composition and neuroactive potential over time. In conclusion, this research demonstrates alterations in the gut microbiome of young binge drinkers (BDs) and identifies early biomarkers of craving. Associations between emotional processing and microbiome composition further support the growing literature on the gut microbiome as a regulator of social cognition. These findings are of relevance for new gut-derived interventions directed at improving early alcohol-related alterations during the vulnerability period of adolescence. C.C. and R.G-C. received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 754535. APC Microbiome Ireland is a research centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan [grant no. SFI/12/RC/2273_P2]. J.F.C has research support from Cremo, Pharmavite, DuPont and Nutricia. He has spoken at meetings sponsored by food and pharmaceutical companies. G.C. has received honoraria from Janssen, Probi, and Apsen as an invited speaker; is in receipt of research funding from Pharmavite, Fonterra, Nestle and Reckitt; and is a paid consultant for Yakult, Zentiva and Heel pharmaceuticals. All the authors declare no competing interests.

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.

Impact of alcohol use disorder severity on human immunodeficiency virus (HIV) viral suppression and CD4 count in three international cohorts of people with HIV.

Alcohol use has been linked to worse human immunodeficiency virus (HIV) immunologic/virologic outcomes, yet few studies have explored the effects of alcohol use disorder (AUD). This study assessed whether AUD severity is associated with HIV viral suppression and CD4 count in the three cohorts of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium. People with HIV (PWH) in Uganda (n= 301), Russia (n= 400), and Boston (n= 251), selected in-part based on their alcohol use, were included in analyses. Logistic and linear regressions were used to assess the cross-sectional associations between AUD severity (number of DSM-5 diagnostic criteria) and (1) HIV viral suppression, and (2) CD4 count (cells/mm3 ) adjusting for covariates. Analyses were conducted separately by site. The proportion of females was 51% (Uganda), 34% (Russia), and 33% (Boston); mean age (SD) was 40.7 (9.6), 38.6 (6.3), and 52.1 (10.5), respectively. All participants in Uganda and all but 27% in Russia and 5% in Boston were on antiretroviral therapy. In Uganda, 32% met criteria for AUD, 92% in Russia, and 43% in Boston. The mean (SD) number of AUD criteria was 1.6 (2.4) in Uganda, 5.6 (3.3) in Russia, and 2.4 (3.1) in Boston. Most participants had HIV viral suppression (Uganda 92%, Russia 57%, Boston 87%); median (IQR) CD4 count was 673 (506, 866), 351 (201, 542), and 591 (387, 881), respectively. In adjusted models, there were no associations between AUD severity and HIV viral suppression: adjusted odds ratios (AOR) (95%CI) per 1 additional AUD criterion in Uganda was 1.08 (0.87, 1.33); Russia 0.98 (0.92, 1.04); and Boston 0.95 (0.84, 1.08) or CD4 count: mean difference (95%CI) per 1 additional criterion: 5.78 (-7.47, 19.03), -3.23 (-10.91, 4.44), and -8.18 (-24.72, 8.35), respectively. In three cohorts of PWH, AUD severity was not associated with HIV viral suppression or CD4 count. PWH with AUD in the current era of antiretroviral therapy can achieve virologic control.

Prevalence, characteristics, and health burden of rheumatoid arthritis in the U.S. veteran population

ObjectiveTo examine the prevalence, characteristics, and physical and mental health burden of rheumatoid arthritis (RA) in a nationally representative sample of U.S. military veterans. MethodsData were analyzed from the 2019–2020 National Health and Resilience in Veterans Study (NHRVS), which surveyed a contemporary, nationally representative sample of 4,069 U.S. veterans. Veterans with RA (n = 227) were compared to veterans with any other medical condition(s) (n = 3,444) on measures of sociodemographic, military, trauma, medical and psychiatric characteristics. Multivariable analyses were then conducted to examine independent associations between RA and health conditions. ResultsA total of 5.3% (95% confidence interval = 4.5–6.2%) of primarily male U.S. veterans reported having been diagnosed with RA. Relative to controls, veterans with RA were older, and more likely to be racial/ethnic minorities, unpartnered, lower income, and combat veterans. They also reported greater cumulative trauma burden, more medical conditions (i.e., osteoarthritis, chronic pain, respiratory and cardiovascular conditions), and greater severity of somatic symptoms, and were more likely to screen positive for current insomnia and subthreshold posttraumatic stress disorder (PTSD), and lifetime alcohol use disorder (AUD). In adjusted analyses, RA remained associated with number of medical conditions, more severe somatic symptoms, insomnia, subthreshold PTSD, and AUD. ConclusionsOne of 20 U.S. veterans has RA, which is more prevalent among certain sociodemographic subsets, and is associated with elevated physical and mental health burden. Results provide insight into risk correlates of RA and underscore the importance of assessing, monitoring, and treating medical and psychiatric conditions/symptoms that co-occur with RA in this population.