Alcohol Use Disorder Patients Research Articles

S1059 Treatment of Alcohol Use Disorder in Patients Admitted with Alcohol-Associated Liver Disease: A Retrospective Cohort Study

S1059 Treatment of Alcohol Use Disorder in Patients Admitted with Alcohol-Associated Liver Disease: A Retrospective Cohort Study

Brain+ AlcoRecover: A Randomized Controlled Pilot-Study and Feasibility Study of Multiple-Domain Cognitive Training Using a Serious Gaming App for Treating Alcohol Use Disorders.

Background: Patients with alcohol use disorder (AUD) exhibit deficits in various cognitive domains, including executive functioning, working memory, and learning and memory, which impede the effectiveness of conventional AUD treatment and enhance relapse. Mobile health (mHealth) services are promising in terms of delivering cognitive training in gamified versions. So far, studies examining the effects of mHealth-based cognitive training in AUD patients have, however, focused on specific rather than multiple cognitive domains and overlooked the importance of clinical outcomes. Furthermore, research has yet to investigate the acceptability and feasibility of this type of cognitive training.Aims: The aims of this pilot study are to examine (1) whether using smartphone-based, multi-domain cognitive training with gamified elements as part of conventional treatment for AUD indicate effect, and (2) whether the intervention is acceptable and feasible as a part of conventional treatment for AUD.Methods: Patients from the alcohol outpatient clinic, Odense Municipality, Denmark will be invited to participate in the study on a consecutive basis until a total of 60 patients have been recruited. The study will be performed as a combined parallel randomized controlled trial (RCT) and qualitative feasibility study. The patients will be randomly assigned to one of two groups. The intervention group (n = 30) will receive smartphone-based, multi-domain cognitive training with gamified elements together with treatment as usual (TAU). The active control group (n = 30) will receive a sham version of the same cognitive training together with TAU. Cognitive outcomes will be assessed via the training application at baseline and post-treatment. Clinical outcomes will be assessed at baseline, post-treatment, and at 6-month follow-up using the Addiction Severity Index. Furthermore, the 30 patients randomized to the intervention group will be invited to participate in the second phase, that is the feasibility study, at post-treatment. A questionnaire inquiring about the use of mHealth treatment in general will be administered. Further, feedback regarding functionality and meaningfulness of the application in addition to other qualitative aspects relating to the use of the application will be collected. The patients will also be asked to provide suggestions about how to improve and potentially implement the tool.Implications: It is anticipated that this pilot study will provide tentative evidence for the effectiveness of smartphone-based, multi-domain cognitive training as well as information about the usability and feasibility of this type of training, including acceptability and compliance. The study will also contribute with feedback derived from the patients about how to improve and implement the tool. If promising, the findings will be used to plan a large-scale RCT. Since cognitive deficits are not addressed in current treatments for AUD, gamified cognitive training delivered through smartphones may increase the effectiveness of current treatment for AUD as well as introduce more mHealth-based treatment that is both accessible and cost-effective.

Patients with alcohol use disorder increase pain and analgesics use: A nationwide population-based cohort study

BackgroundAlcohol has dual effects on many systems, including the pain system. We will test whether and how chronic alcohol consumption enhances pain sensation to develop pain disorder. MethodsWe conducted a retrospective matched cohort study using data from the National Health Insurance Research Database (NHIRD) in Taiwan, in patients with and without alcohol use disorder (AUD). This study enrolled 19,174 individuals with AUD as study cohort and 19,174 propensity score-matched individuals without AUD as comparison cohort. The outcome was the incidence of pain disorders and the need for analgesics. The hazard ratios of pain disorders and the need for analgesics were evaluated using Cox proportional hazard regression analysis after adjusting for age, sex, index year, comorbidities, urbanization, areas of residence, and insurance premium. ResultsThe 14 years of follow-up showed that AUD patients had a higher adjusted hazard ratio (aHR) for developing pain disorders than in non-AUD controls [aHR= 1.290, 95% confidence interval (CI): 1.045–1.591]. Besides, AUD patients had a higher risk of analgesic use (aHR = 1.081, 95% CI: 1.064–1.312), including opioids and non-opioid analgesics. Most importantly, AUD patients required more days of analgesic use, increased dose of analgesics, and higher costs of analgesics. Moreover, AUD patients had more anemia (aHR=2.772, 95% CI: 2.581–2.872), which could be a mediating factor. ConclusionsAUD patients had higher risks of developing pain disorders and subsequently increased analgesic demand. These results suggest that AUD worsened pain, and pain syndrome is correlated with the duration of chronic alcohol exposure.

Statins and the risks of decompensated liver cirrhosis and hepatocellular carcinoma determined in patients with alcohol use disorder

BackgroundAlcohol-related liver disease (ALD) is the most common cause of liver disease. No medication can improve ALD and abstinence from alcohol is the sole effective strategy. Statin use has been demonstrated to have protective effects against liver cirrhosis and hepatocellular carcinoma (HCC) in patients with virus-related liver diseases. Whether statin use has a similar association among patients with alcohol use disorder (AUD) that can lead to ALD, is unknown. MethodWe conducted a population-based cohort study using Taiwan’s National Health Insurance Research Database from 1997 to 2013 to compare risks of decompensated liver cirrhosis and hepatocellular carcinoma (HCC) between the statin exposed and unexposed groups in the patients with AUD. The incidence rates of decompensated liver cirrhosis and HCC were calculated between patients exposed and unexposed to statins with 1:4 propensity score matching. Cox proportional hazard regressions were performed to evaluate hazard ratios (HRs). ResultsThe incidence rates of decompensated liver cirrhosis and HCC in the statin-exposed group differed from those in the unexposed group (decompensated cirrhosis: 269.9 vs. 628.9 cases per 100,000 person-years; HCC: 116.7 vs. 318.3 cases per 100,000 person-years). The HRs for decompensated liver cirrhosis and HCC were 0.43 (95% CI, 0.37–0.51) and 0.40 (95% CI, 0.31–0.51), respectively, after adjustment. ConclusionsStatin use was associated with reduced risk of decompensated liver cirrhosis and HCC among AUD patients in a cumulative dose effect manner. Statins might have some potential effects on mitigating ALD progression beside abstinence from alcohol. Further research is needed.

Faux Pas Recognition and Executive Processes in Patients with Alcohol Use Disorder: Toward an Investigation of Interindividual Heterogeneity.

Impairment of executive functions (EF) has been documented for decades in patients with alcohol use disorders (AUD), while more recent studies have also reported impaired theory of mind. Both have been associated with negative outcomes, particularly a high risk of relapse. However, the interrelatedness of EF and theory of mind impairments remains subject to debate. About 19 AUD outpatients and 20 healthy controls (HC) were asked to complete measures of motor inhibition, mental flexibility, and updating to assess EF, and the faux pas test to assess theory of mind. As expected, patients' mean performances on EF and faux pas measures were poorer than those of HC. Correlational analyses revealed that executive processes were differentially related to faux pas subscores. Additional single-case analyses corroborated the strong association between EF and faux pas interpretation, as patients with AUD mostly had congruent performances (i.e., both EF and faux pas impaired or both EF and faux pas preserved). This study highlights the interrelatedness of EF and faux pas performances in AUD, but also emphasizes the incomplete overlap of the cognitive processes involved in these tasks, with heterogeneous patterns of association. Based on these findings, tailored cognitive rehabilitation programs that simultaneously target EF and faux pas recognition could be developed to favor patients' social inclusion and reduce the risk of relapse. Results also argue in favor of systematic screening for EF and theory of mind impairments among AUD patients.

Higher-Order Language Dysfunctions in Individuals with Alcohol Use Disorder.

Patients with alcohol use disorders (AUD) have difficulties with certain aspects of higher-order language functions (HOLF) but there is no data on a wide range of these functions in this group. Therefore, the aim of this study was to compare different aspects of HOLF in patients with AUD and healthy controls (HC). A total of 31 patients with AUD and 44 HC took part in the study. We assessed HOLF with the Right Hemisphere Language Battery (RHLB) and measured control variables: depression using the Patient Health Questionnaire (PHQ) as well as the speed of processing and executive functions with the Color Trails Test (CTT). Patients with AUD had lower results on nine RHLB tests. Moreover, AUD patients had higher scores on PHQ and longer reaction times on CTT. The differences in most RHLB results remained significant after co-varying the control variables. Patients with AUD have difficulties with making inferences from the text, understanding the meaning of individual words, metaphorical content, and prosody, which may impede the comprehension and production of discourse in which linguistic elements must be integrated with non-verbal cues and contextual information. These disturbances may impact various spheres of everyday life and negatively influence social, private, and professional functioning.

Alcohol use disorder in the COVID-19 era: Position paper of the Italian Society on Alcohol (SIA).

Coronavirus disease 2019 (COVID‐19) first emerged in China in November 2019. Most governments have responded to the COVID‐19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID‐19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID‐19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID‐19 era (group activities, telemedicine, outpatients treatment, alcohol‐related liver disease and liver transplantation, collecting samples); (d) AUD and SARS‐CoV‐2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID‐19 disease will need implementation. Thus, the COVID‐19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in‐depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment.

Antagonism of GluK1-containing kainate receptors reduces ethanol consumption by modulating ethanol reward and withdrawal

Alcohol use disorder (AUD) is a neuropsychiatric condition affecting millions of people worldwide. Topiramate (TPM) is an antiepileptic drug that has been shown to reduce ethanol drinking in humans. However, TPM is associated with a variety of adverse effects due to its interaction with many receptor systems and intracellular pathways. GluK1-containing kainate receptors (GluK1*KARs) are non-selectively inhibited by TPM, and genetic association studies suggest that this receptor system could be targeted to reduce drinking in AUD patients. We examined the efficacy of LY466195, a selective inhibitor of GluK1*KAR, in reducing ethanol consumption in the intermittent two-bottle choice paradigm in mice. The effect of LY466195 on various ethanol-related phenotypes was investigated by quantification of alcohol intake, physical signs of withdrawal, conditioned place preference (CPP) and in vivo microdialysis in the nucleus accumbens. Selective GluK1*KAR inhibition reduced ethanol intake and preference in a dose-dependent manner. LY466195 treatment attenuated the physical manifestations of ethanol withdrawal and influenced the rewarding properties of ethanol. Interestingly, LY466195 injection also normalized changes in dopamine levels in response to acute ethanol in ethanol-dependent mice, but had no effect in ethanol-naïve mice, suggesting ethanol state-dependent effects. The data point to GluK1*KARs as an attractive pharmacological target for the treatment of AUD.

Irregular Autonomic Modulation Predicts Risky Drinking and Altered Ventromedial Prefrontal Cortex Response to Stress in Alcohol Use Disorder.

Autonomic dysfunction has been associated with risky drinking and alcohol use disorder (AUD). Although autonomic nervous system (ANS) activity has been attributed to the ventromedial prefrontal cortex (VmPFC)-limbic-striatal regions, the specific role of ANS disruption in AUD and its association with these regions remain unclear. Using functional magnetic resonance imaging (fMRI) and concurrent electrocardiogram (ECG), the current study examined neural correlates of ANS activity in AUD and its role in AUD pathology. Demographically matched 20 AUD patients and 20 social drinkers (SD) completed an fMRI task involving repeated exposure to stress, alcohol-cue and neutral-relaxing images in a block design. Based on the known VmPFC-limbic-striatal functions involved in emotions, reward and the ANS, we performed a regions of interest (ROI) analysis to examine the associations between ANS activity and neural responses in the VmPFC, amygdala, and ventral striatum. Across conditions, AUD patients showed significantly higher levels of overall heart rate (HR) and approximate entropy (ApEn) compared to SD (Ps < 0.05). In all participants, increased HR was associated with greater drinking volume (P < 0.05). In addition, higher ApEn levels were associated with greater drinking volume (P < 0.05) and decreased right VmPFC response to stress (P < 0.05). Our findings demonstrate ANS disruption in AUD indexed by high overall HR and ApEn. The association between ApEn and rVmPFC response suggests that ApEn may play a role in modulating drinking via interactions with neural regions of emotion regulation. These findings provide insight into patterns of ANS disruption and their relevance to AUD pathology.

Increased network centrality of the anterior insula in early abstinence from alcohol.

Abnormal resting‐state functional connectivity, as measured by functional magnetic resonance imaging (MRI), has been reported in alcohol use disorders (AUD), but findings are so far inconsistent. Here, we exploited recent developments in graph‐theoretical analyses, enabling improved resolution and fine‐grained representation of brain networks, to investigate functional connectivity in 35 recently detoxified alcohol dependent patients versus 34 healthy controls. Specifically, we focused on the modular organization, that is, the presence of tightly connected substructures within a network, and on the identification of brain regions responsible for network integration using an unbiased approach based on a large‐scale network composed of more than 600 a priori defined nodes. We found significant reductions in global connectivity and region‐specific disruption in the network topology in patients compared with controls. Specifically, the basal brain and the insular–supramarginal cortices, which form tightly coupled modules in healthy subjects, were fragmented in patients. Further, patients showed a strong increase in the centrality of the anterior insula, which exhibited stronger connectivity to distal cortical regions and weaker connectivity to the posterior insula. Anterior insula centrality, a measure of the integrative role of a region, was significantly associated with increased risk of relapse. Exploratory analysis suggests partial recovery of modular structure and insular connectivity in patients after 2 weeks. These findings support the hypothesis that, at least during the early stages of abstinence, the anterior insula may drive exaggerated integration of interoceptive states in AUD patients with possible consequences for decision making and emotional states and that functional connectivity is dynamically changing during treatment.

A combination of support vector machine and voxel-based morphometry in adult male alcohol use disorder patients with cognitive deficits

Cognitive performance deteriorates with drinking. However, the neural basis of cognitive deficits in alcohol use disorder (AUD) is still incompletely understood. Here we examined the relationship between overall drinking, brain structural alterations and cognitive deficits in AUD. A total of 40 middle-aged AUD males and 40 healthy controls (HC) underwent high-resolution anatomical imaging scans, and the data were analyzed using voxel-based morphometry, support vector machine (SVM) classification and mediation analysis. The AUD patients demonstrated reduced gray matter (GM) volumes that included left amygdala, thalamus, hippocampus, precentral gyrus, cerebellum, calcarine, right supplementary motor area and bilateral superior temporal gyri (voxel-wise p < 0.05, FWE corrected). The SVM results could distinguish AUD from HC with satisfactory classification results (0.8275). GM volumes in the bilateral cerebellum and thalamus, left anterior medial temporal lobe, left nucleus ambiguus + parahippocampus gyrus, left fusiform gyrus, left lingual gyrus, left hippocampus, and right nucleus accumbens had positive correlations with the Montreal Cognitive Assessment (MoCA) scores. Further mediation analysis showed that left cerebellum crus 1 partially mediated the relationship between overall drinking and MoCA scores (standardized beta coefficient = −0.0973, SE = 0.0002, 95% CI = (−0.0006, 0.0000)). Our findings showed widespread GM atrophies and many of these atrophies also mirrored cognitive deficits and were robustly distinguishable. Critically, the left cerebellum crus 1 partially mediated the relationship betweem overall drinking and MoCA scores, suggesting a pathway by which alcohol abuse impairs cognition and accelerates brain ageing in middle-aged AUD males.

Relationship between alcohol craving dimensions and features of comorbid mental health in an alcohol dependent sample

Background and aimsNegative affect and alcohol craving are common features of Alcohol Use Disorder (AUD). Both independently contribute to AUD severity and poorer treatment outcomes, but their relationship is poorly understood. Multidimensional alcohol craving measures now allow for examination of key dimensions of craving. This study explored the relationship between depression, anxiety, stress, and the alcohol craving dimensions of intensity, imagery and intrusiveness. MethodFive-hundred and twenty-five treatment seeking AUD patients (mean age of 39.79 years, SD = 11.57 years, 67% male) completed the Depression Anxiety Stress Scales (DASS), Alcohol Use Disorder Identification Test-Consumption items (AUDIT-C), and Alcohol Craving Experience (ACE-F) questionnaire, which measured the frequency of craving intensity, imagery and intrusiveness. Regression models predicted main effects of predictors and moderation by alcohol consumption. ResultsHigher levels of stress were independently associated with increased craving intensity, imagery and intrusiveness. Significant positive associations were also found between anxiety and craving imagery. The association between depression and craving was not significant after controlling for other predictors. ConclusionsAUD patients experienced higher cravings when stressed and greater imagery when anxious. These results support the need to consider the relationships between stress and craving when managing alcohol dependence.

Adult attention-deficit/hyperactivity disorder among alcohol use disorder inpatients is associated with food addiction and binge eating, but not BMI

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is associated with binge eating (BE), food addiction (FA), and obesity/higher BMI in individuals without alcohol use disorder (AUD). ADHD is highly prevalent in patients with AUD, but it is unknown whether the presence of comorbid AUD might change the nature of the association between ADHD, BE, FA and BMI (food and alcohol may either compete for the same brain neurocircuitry or share vulnerability risk factors). Here, we filled this gap by testing the association between ADHD and FA/BE in adult patients hospitalized for AUD, with the strength of simultaneously assessing childhood and adult ADHD. We also investigated the association between ADHD and BMI, and the other factors associated with BMI (FA/BE, AUD severity). MethodsWe included 149 AUD inpatients between November 2018 and April 2019. We assessed both childhood and adulthood ADHD (Wender Utah Render Scale and Adult ADHD Self-Report Scale), FA (modified Yale Food Addiction Scale 2.0), BE (Binge Eating Scale), and BMI and AUD (clinical assessment). ResultsIn multivariable analyses adjusted for age, adult ADHD was associated with higher BE scores (p = .048), but not significant BE (9% vs. 7%; p = .70). ADHD was also associated with FA diagnosis and the number or FA symptoms, with larger effect size for adult (ORs: 9.45[95%CI: 2.82–31.74] and 1.38[1.13–1.69], respectively) than childhood ADHD (ORs: 4.45[1.37–14.46] and 1.40[1.13–1.75], respectively). In multivariable analysis, BMI was associated with both significant BE (p < .001) and FA diagnosis (p = .014), but not adult ADHD nor AUD severity. ConclusionIn patients hospitalized for AUD, self-reported adult ADHD was associated with FA and BE, but not BMI. Our results set the groundwork for longitudinal research on the link between ADHD, FA, BE, and BMI in AUD inpatients.

Epigenetic moderators of naltrexone efficacy in reducing heavy drinking in Alcohol Use Disorder: a randomized trial.

Polymorphisms in genes associated with opioid signaling and dopamine reuptake and inactivation may moderate naltrexone efficacy in Alcohol Use Disorder (AUD), but the effects of epigenetic modification of these genes on naltrexone response are largely unexplored. This study tested interactions between methylation in the μ-opioid receptor (OPRM1), dopamine transporter (SLC6A3), and catechol-O-methyltransferase (COMT) genes as predictors of naltrexone effects on heavy drinking in a 16-week randomized, placebo-controlled trial among 145 treatment-seeking AUD patients. OPRM1 methylation interacted with both SLC6A3 and COMT methylation to moderate naltrexone efficacy, such that naltrexone-treated individuals with lower methylation of the OPRM1 promoter and the SLC6A3 promoter (p=.006), COMT promoter (p=.005), or SLC6A3 3’ untranslated region (p=.004), relative to placebo and to those with higher OPRM1 and SLC6A3 or COMT methylation, had significantly fewer heavy drinking days. Epigenetic modification of opioid- and dopamine-related genes may represent a novel pharmacoepigenetic predictor of naltrexone efficacy in AUD.

Markers of Monocyte Activation, Inflammation, and Microbial Translocation Are Associated with Liver Fibrosis in Alcohol Use Disorder

Background: The association between markers of inflammation (interleukin (IL)-6 and IL-10), monocyte activation (sCD163 and sCD14), and microbial translocation (lipopolysaccharide (LPS) and LPS binding protein) and liver fibrosis in patients with alcohol use disorder (AUD) and no overt liver disease is not well established. Methods: We studied patients admitted for treatment of AUD at two hospitals in Barcelona. Advanced liver fibrosis (ALF) was defined as FIB-4 > 3.25. Results: A total of 353 participants (76.3% male) were included and 94 (26.5%) had ALF. In adjusted correlation analyses, sCD163, sCD14, IL-6, IL-10, and LPS binding protein levels directly correlated with FIB-4 values (adjusted correlation coefficients 0.214, 0.452, 0.317, 0.204, and 0.171, respectively). However, LPS levels were inversely associated with FIB-4 (−0.283). All plasma marker levels in the highest quartile, except LPS, were associated with ALF (sCD163, sCD14, IL-6, IL-10, and LPS binding protein: adjusted odds ratio (aOR) 11.49 (95% confidence interval 6.42–20.56), 1.87 (1.11–3.16), 2.99 (1.79–5.01), 1.84 (1.11–3.16), and 2.13 (1.30–3.50), respectively). Conversely, LPS levels in the lowest quartile were associated with ALF (aOR 2.58 (1.48–4.58), p < 0.01). Conclusion: In AUD patients, plasma levels of the markers of inflammation, monocyte activation, and microbial translocation are associated with ALF.

Posterior fronto-medial atrophy reflects decreased loss aversion, but not executive impairment, in alcohol use disorder.

Decreased punishment sensitivity in alcohol use disorder (AUD) might reflect a reduction in the typical human tendency to overweigh negative choice outcomes compared with equivalent positive ones, that is, 'loss aversion.' While this hypothesis is supported by previous reports of reduced loss aversion in AUD, it is still unknown whether such decreased sensitivity to prospective losses represents a specific facet of altered decision-making or a secondary effect of executive/working-memory impairments. We addressed this issue by assessing whether lower loss aversion in 22 AUD patients compared with 19 healthy controls is explained by their differential executive or working-memory performance and by investigating its neural basis in terms of grey matter density and cortical thickness via voxel- and surface-based morphometry, respectively. A significant decrease of loss aversion in patients, unrelated to their impaired executive/working-memory performance, reflected the reduction of posterior fronto-medial grey matter density and right frontopolar cortical thickness. Rather than their executive deficits, patients' reduced loss aversion reflects the structural damage of the posterior fronto-medial cortex previously associated with solving conflicts at the response level, where earlier functional magnetic resonance imaging (fMRI) studies have shown a 'neural loss aversion' pattern of steeper deactivation for losses than activation for gains, and of the frontopolar cortex in charge of managing competing goals. These findings highlight possible directions for addressing AUD patients' high relapse rate, for example, cognitive-behavioural rehabilitative interventions enhancing the awareness of the adverse outcomes of addiction or neurostimulation protocols targeting the regions processing their salience.

Regionally specific gray matter volume is lower in alcohol use disorder: Implications for noninvasive brain stimulation treatment.

There is growing interest in neuromodulation-based therapeutics as tools for individuals with alcohol use disorder (AUD). Through electromagnetic induction, techniques such as transcranial magnetic stimulation (TMS) can noninvasively depolarize cortical cells in the induced electrical field and monosynaptic afferents. The ability of TMS to modulate the brain is dependent upon two factors, which may be compromised in individuals with AUD: (1) gray matter volume (GMV) at the site of stimulation and (2) scalp-to-cortex (STC) distance. This study tested the hypotheses that these aspects of neural architecture are compromised in AUD patients, and thus AUD patients may need a higher TMS dose to depolarize the cortex. High-resolution magnetic resonance images were acquired from 44 individuals with AUD and 44 age-matched healthy controls (n=88). Whole-brain voxel-based morphometry was conducted. Subsequent region-of-interest analysis was performed at three EEG 10-20 sites commonly used in TMS for AUD: FP1 (left frontal pole), F3 (left DLPFC), and C3 (left motor cortex). STC distance and TMS electric fields were assessed at these EEG sites. Individuals with AUD had significantly lower GMV in the bilateral orbitofrontal cortices, supramarginal gyri, and the left DLPFC (voxel-threshold p<0.05, cluster-threshold p<0.05) and within all 3 TMS target locations, F (1, 264)=14.12, p=0.0002. There was no significant difference in STC distance between the AUD and the healthy control group at any tested cortical location, F (3, 252)=1.906, p=0.129. Individuals with AUD had significantly lower GMV in multiple areas of interest for TMS treatment; however, these volumetric reductions did not impact STC distance. Given previous studies that have shown TMS-evoked changes in cortical and subcortical activity to be dependent on GMV, these data suggest that individuals with AUD may require higher doses of TMS to sufficiently modulate the neural circuits of interest.

Effects of Chronic Alcohol Use Disorder on the Visual Tilt Illusion.

Rationale: Among the serious consequences of alcohol use disorder (AUD) is the reduced ability to process visual information. It is also generally agreed that AUD tends to occur with disturbed excitation–inhibition (EI) balance in the central nervous system. Thus, a specific visual behavioral probe could directly qualify the EI dysfunction in patients with AUD. The tilt illusion (TI) is a paradigmatic example of contextual influences on perception of central target. The phenomenon shows a characteristic dependence on the angle between the inducing surround stimulus and the central target test. For small angles, there is a repulsion effect; for larger angles, there is a smaller attraction effect. The center-surround inhibition in tilt repulsion is considered to come from spatial orientational interactions between orientation-tuned neurons in the primary visual cortex (V1), and tilt attraction is from higher-level effects of orientation processing in the visual information processing.Objectives: The present study focuses on visual spatial information processing and explores whether chronic AUD patients in abstinence period exhibited abnormal TI compared with healthy controls.Methods: The participants are 30 male volunteers (20–46 years old) divided into two groups: the study group consists of 15 clinically diagnosed AUD patients undergoing abstinence from alcohol, and the control group consists of 15 healthy volunteers. The TI consists of a center target surround with an annulus (both target and annulus are sinusoidal grating with spatial frequency = 2 cycles per degree). The visual angle between center and surround is a variable restricted to 0°, ±15°, ±30°, or ±75°. For measuring the TI, participants have to report whether the center target grating orientation tilted clockwise or counterclockwise from the internal vertical orientation by pressing corresponding keys on the computer keyboard. No feedback is provided regarding response correctness.Results: The results reveal significantly weaker tilt repulsion effect under surround orientation ±15° (p < 0.05) and higher lapse rate (attention limitation index) under all tested surround orientations (all ps < 0.05) in patients with chronic AUD compared with health controls.Conclusions: These results provide psychophysical evidence that visual perception of center-contextual stimuli is different between AUD and healthy control groups.

Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder.

BackgroundAlcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein.MethodsWe studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples.ResultsPatients with AUD had significantly increased abundance of the genera Candida, Debaryomyces, Pichia, Kluyveromyces, and Issatchenkia, and of the species Candida albicans and Candida zeylanoides compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera Candida, Malassezia, Pichia, Kluyveromyces, Issatchenkia, and the species C. albicans and C. zeylanoides. This was mirrored by significantly higher specific anti-C. albicans immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti-C. albicans IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus Malassezia was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease.ConclusionIn conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of Candida and Malassezia, and lower serum anti-C. albicans IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.

Rehabilitation Gaming System for Alcohol-Related Cognitive Impairment: A Pilot Usability Study.

Cognitive impairment in patients with alcohol use disorder (AUD) is highly prevalent, and it negatively impacts treatment outcome. However, this condition is neither systematically assessed nor treated. Thus, we aimed to explore the usability of a virtual reality-based protocol ('Rehabilitation Gaming System', RGS) for patients with AUD. Twenty AUD patients (50% also cognitive impairment) underwent a single session of the RGS protocol (four cognitive training tasks, 10minutes each). System Usability Scale (SUS) and Post-Study System Usability Questionnaire (PSSUQ) were applied to assess the RGS usability and patients' satisfaction with it. Also, the Perceived Competence Scale was administered to assess the patients' feelings of competence when using the training protocol. Comparisons of the responses to these questionnaires were performed between AUD patients with cognitive impairment and those without cognitive impairment. RGS usability was very positively rated (median SUS score=80, Interquartile Range, IQR=68.13-86-88). No significant differences were found in the median SUS scores for any of the sociodemographic or clinical variables, excepting for gender (women median score=85; IQR=80-94.38 vs. men median score=71.25; IQR=61.25-89.25; P-value=0.035). The quality of the information provided by the RGS training scenarios and the usability were positively rated (PSSUQ), and patients experienced high feelings of competence. The RGS has been found to be usable in the short term and patients with AUD stated to be satisfied with it. Future larger, randomized trials are needed to explore the effectiveness of this tool to help overcome the cognitive deficits in AUD patients.