Alcohol Use Disorder Patients Research Articles

Treatment of alcohol use disorder in patients with liver disease.

Treatment of alcohol use disorder in patients with liver disease.

Increased Incidence of Depression and Chronic Pain in Traumatic Spinal Cord Injury Patients With Pre-Injury Alcohol Use Disorder: Longitudinal Analysis of Insurance Claim Database.

Alcohol use disorder (AUD) increases risk of traumatic spinal cord injury (SCI) and is associated with depression, anxiety, and chronic pain. Given that these neuropsychiatric morbidities are frequently observed in SCI patients, the effects of pre-injury AUD on risk of depression, anxiety, or chronic pain were analyzed using an insurance claim database. Of 10,591 traumatic SCI patients, 507 had AUD-associated claims in a 12-month period before injury. Those AUD-positive SCI patients showed distinct demographic characteristics, including greater representation of men, younger age, more comorbidities, lower coverage by commercial insurance, and more cervical-level injuries. The AUD group also showed elevated pre-injury comorbidity of depression, anxiety, and chronic pain. However, multi-regression analysis revealed an increased odds ratio (OR) of de novo diagnosis of post-SCI depression in AUD patients 6 months (1.671; 95% confidence interval [CI]: 1.124, 2.483) and 1 year post-injury (1.511; 95% CI: 1.071, 2.131). The OR of de novo post-SCI anxiety was unaffected by pre-injury AUD. Finally, 1 year after SCI, pre-injury AUD increased the OR of de novo diagnosis of post-injury chronic pain (1.545; 95% CI: 1.223, 1.951). Thus, pre-injury AUD may be a risk factor for development of depression and chronic pain after traumatic SCI.

A Complex Interplay between Nutrition and Alcohol use Disorder: Implications for Breaking the Vicious Cycle.

Approximately 16.5% of the United States population met the diagnostic criteria for substance use disorder (SUD) in 2021, including 29.5 million individuals with alcohol use disorder (AUD). Individuals with AUD are at increased risk for malnutrition, and impairments in nutritional status in chronic alcohol users can be detrimental to physical and emotional well-being. Furthermore, these nutritional deficiencies could contribute to the never-ending cycle of alcoholism and related pathologies, thereby jeopardizing the prospects of recovery and treatment outcomes. Improving nutritional status in AUD patients may not only compensate for general malnutrition but could also reduce adverse symptoms during recovery, thereby promoting abstinence and successful treatment of AUD. In this review, we briefly summarize alterations in the nutritional status of people with addictive disorders, in addition to the underlying neurobiological mechanisms and clinical implications regarding the role of nutritional intervention in recovery from alcohol use disorder.

Exploring core symptoms of alcohol withdrawal syndrome in alcohol use disorder patients: a network analysis approach.

Understanding the interplay between psychopathology of alcohol withdrawal syndrome (AWS) in alcohol use disorder (AUD) patients may improve the effectiveness of relapse interventions for AUD. Network theory of mental disorders assumes that mental disorders persist not of a common functional disorder, but from a sustained feedback loop between symptoms, thereby explaining the persistence of AWS and the high relapse rate of AUD. The current study aims to establish a network of AWS, identify its core symptoms and find the bridges between the symptoms which are intervention target to relieve the AWS and break the self-maintaining cycle of AUD. Graphical lasso network were constructed using psychological symptoms of 553 AUD patients. Global network structure, centrality indices, cluster coefficient, and bridge symptom were used to identify the core symptoms of the AWS network and the transmission pathways between different symptom clusters. The results revealed that: (1) AWS constitutes a stable symptom network with a stability coefficient (CS) of 0.21-0.75. (2) Anger (Strength = 1.52) and hostility (Strength = 0.84) emerged as the core symptom in the AWS network with the highest centrality and low clustering coefficient. (3) Hostility mediates aggression and anxiety; anger mediates aggression and impulsivity in AWS network respectively. Anger and hostility may be considered the best intervention targets for researching and treating AWS. Hostility and anxiety, anger and impulsiveness are independent but related dimensions, suggesting that different neurobiological bases may be involved in withdrawal symptoms, which play a similar role in withdrawal syndrome.

Assessment of Common Mental Disorders in Patients with Alcohol use Disorder

Alcohol use disorder (AUD) is a pattern of alcohol use that involves problems like controlling drinking, being preoccupied with alcohol, continuing to use alcohol even when it causes problems, urge to drink more to get the same effect and having withdrawal symptoms when discontinued abruptly. According to the World Health Organization (WHO), there are approximately two billion alcoholic beverage consumers and 76.3 million people worldwide with diagnosable alcohol-use disorders. Co-occurrence of alcohol use disorders with common mental disorders, such as depression, anxiety, stress and bipolar disorder, is relatively common. Individuals with alcohol-related problems can be more vulnerable to develop mental health disorders and vice versa which is a significant public health concern globally. The purpose of this study was to evaluate AUD as the primary disorder, in which people start drinking alcohol as a social habit and progress to chronic alcoholism, which can lead to the development of common mental disorders (CMD) such as depression, anxiety, and stress. The study was carried in ESIC hospital's inpatient general medicine department in Bengaluru. A self-designed data collection form and validated questionnaires were used to collect data for an educational observational study involving 87 patients. According to the study, 74.7% of 87 AUD patients had minimal anxiety, 72.41% had mild depression, and 59.7% had mild stress. The majority of the AUD population was low-income, illiterate, and self-employed. This study contributes to a better understanding of the relationship between Alcohol Use Disorder (AUD) and Common Mental Disorders (CMD) in relation to patients' socio-demographics which can aid in the early detection of individuals at risk, design targeted interventions, and the implementation of preventive measures to address the co-occurrence of these disorders eventually leading to improved public health outcomes.

One-month assessment of Th-cell axis related inflammatory cytokines, IL-17 and IL-22 and their role in alcohol-associated liver disease.

Changes in the expression of cyto- and chemokines due to alcohol-associated liver disease (ALD) have been reported to be both protective and pathogenic. This study examined plasma levels of two key cytokines, Il-17 and Il-22, which construct the proinflammatory vs. anti-inflammatory axes across the spectrum of alcohol use disorder (AUD) and ALD including alcohol-associated hepatitis (AH) to determine the underlying status of the inflammation. Forty-two males and females aged 25-63 yrs. were grouped as healthy controls (HV[n=8]), AUD with no liver injury (AUDNLI [n=8]), AUD with liver injury (AUDLI [n=8]), non-severe alcohol-associated hepatitis (NSAH [n=9]), and severe alcohol-associated hepatitis (SAH [n=9]). Demographic, drinking, and clinical data were collected. Blood samples were collected at baseline (BL, all subjects) and during week 4 (W4, only patients) for IL-17 and IL-22; and statistically analyzed. IL-17 was highly elevated in the SAH group both at BL and post-SOC. LTDH and BL IL-22 in non-severe AH patients were associated significantly. LTDH significantly predicted W4 IL-22 levels, positively (increasing) in NSAH and inversely (lowering) in SAH patients. BL and W4 IL-22 levels were significantly higher (4-fold, p≤0.001) in all AH patients compared to all AUD patients (AUROC=0.988, p≤0.001). IL-22 showed significant affinity with AST, AST: ALT ratio, total bilirubin, INR, and PT both at BL and W4. IL-22 was inversely associated with IL-1β; and positively with TNF-α and IL-8 both at BL, and W4. BL IL-17 showed a positive correlation with MELD (p=0.017) in all AH patients. In SAH, > 2-fold W4 IL-17 level compared to BL showed significant within subjects' effects, p=0.006. In AUD patients without AH, the drop in IL-17 at W4 vs. BL showed a significant within subjects' effect, p=0.031. Drinking chronicity predicted opposite effects in IL-22 levels in NSAH (antiinflammatory) and SAH (pro-inflammatory) patients at post-SOC. BL IL-22 levels differentiated AH patients robustly from the AUD patients (with or without liver injury); and showed corresponding increases stepwise with the stages of ALD. IL-22 was closely associated with progression and injury markers of the liver; and response to the cytokines of pro-inflammatory nature. Pro-inflammatory indicator of IL-17 cell axis, IL-17 showed a strong positive association with MELD, a severity indicator of AH.

Inpatient Screening, Brief Intervention, and Referral to Treatment for Alcohol Use Disorder in Patients Admitted with Alcohol-associated Liver Disease Is Not Universally Implemented in Practice, But Can Reduce Readmissions for Alcohol-associated Hepatitis.

The management of alcohol-related liver disease requires a multidisciplinary approach to treat alcohol use disorder. We aimed to determine the proportion of actively drinking patients admitted for alcohol-associated hepatitis (AAH) or decompensated alcohol-related cirrhosis (DARLC) who were offered or underwent screening, brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during admission and if inpatient SBIRT is associated with reduced readmissions for alcohol-related liver disease. We conducted a retrospective cohort study of actively drinking patients admitted to our institution from January 2017 to December 2021 with AAH or DARLC. Logistic regression was used to identify factors, such as conducting SBIRT, that were associated with 30-day and 90-day readmissions for recurrent AAH or DARLC. There were 120 AAH admissions (mean age 47.7 ± 13.6 years), and 177 DARLC admissions (mean age 58.2 ± 9.5 years). SBIRT was conducted in only 51.7% of AAH admissions, and 23.7% of DARLC admissions. For AAH, conducting SBIRT was associated with significantly reduced 30-day (OR 0.098, P = 0.001, 95% CI 0.024-0.408) and 90-day (OR 0.166, P = 0.003, 95% CI 0.052-0.534) readmissions. For DARLC, there was no association between conducting SBIRT and 30-day or 90-day readmissions. SBIRT was conducted with actively drinking patients in only 51.7% of AAH admissions and 23.7% of DARLC admissions. Patients admitted for AAH who received inpatient SBIRT had decreased 30-day and 90-day readmission rates for AAH or DARLC.

Positive Predictive Value of Cirrhosis and Chronic Pancreatitis Diagnoses in Individuals with Alcohol Use Disorder: A Single-Center Study.

Although accuracy of diagnosis codes for cirrhosis and chronic pancreatitis (CP) has been evaluated in multiple studies, none have focused on patients with alcohol use disorders (AUD). We evaluated the positive predictive value (PPV) for a verified diagnosis of cirrhosis and CP in AUD patients treated at a tertiary care center. We performed a detailed review of electronic health records for AUD patients assigned ICD-9 or 10 codes for alcoholic cirrhosis (ALC) (n = 199), CP (n = 200), or both (n = 200). We calculated PPV for a verified diagnosis of cirrhosis and CP and performed multivariable regression analysis to assess the impact of relevant factors on PPV for a verified diagnosis. PPV of cirrhosis was 81.2% (95% CI 77.0 to 84.9%) which increased to 87.5% (95% CI 83.8 to 90.6%) if the definition was relaxed to include alcohol-related hepatitis. PPV of CP was 54.5% (95% CI 49.5 to 59.5%) which increased to 78% (95% CI 73.6 to 82.0%) when recurrent acute pancreatitis was included in the definition. In multivariable analyses, the odds of a verified diagnosis were significantly higher in individuals aged 65+ years for both cirrhosis (OR 12.23, 95% CI 2.19 to 68.42) and CP (OR 8.84, 95% CI 2.7 to 28.93) and in ever smokers for CP (OR 1.95, 95% CI 1.05 to 3.65). PPV for diagnosis codes in AUD patients is high for a verified diagnosis of cirrhosis but only modest for CP. While administrative datasets can provide reliable information for cirrhosis, future studies should focus on ways to boost the diagnostic validity of administrative datasets for CP.

Abstract 14287: Real-World Healthcare Resource Utilization Among Patients With Hypertension or Congestive Heart Failure and Comorbid Alcohol Use Disorder

Introduction: Excessive alcohol consumption has been associated with increased risk of cardiovascular (CV) disease. Hypertension (HTN) is a known risk factor for CV disease, in general, including congestive heart failure (CHF). Healthcare resource utilization (HRU) and costs associated with comorbid alcohol use disorder (AUD) among patients with HTN or CHF were evaluated. Methods: This retrospective cohort study identified adults with moderate-to-severe AUD from patients with ≥1 inpatient, or ≥2 outpatient claims on separate days, for HTN or CHF (MarketScan® and Medicare [1/1/2016-12/31/2020], Medicaid [1/1/2016-12/31/2019] databases), and ≥1 year of continuous healthcare enrollment prior to diagnosis (baseline) and 3 months after. Monthly HRU and costs were compared between propensity-score matched patients based on AUD presence using rate ratios in generalized linear models. Results: Of 4,015,785 patients with HTN, 1% were diagnosed with AUD. Use of HTN pharmacotherapy was similar for all patients, except for less frequent use of angiotensin receptor blockers (ARBs) in those with AUD. HTN patients with comorbid AUD had a higher risk of inpatient visits (89%), ED visits (39%), longer inpatient stays (98%), and outpatient visits (9%) relative to non-AUD patients. Of 294,892 patients with CHF, 2% had comorbid AUD. CHF pharmacotherapy use was similar for all patients, except for less frequent ARB use in those with AUD. CHF with comorbid AUD had a higher risk of inpatient visits (31%), ED visits (25%), and longer inpatient stays (34%) relative to non-AUD patients. Outpatient visits were 5% lower in CHF patients with AUD. AUD was associated with higher acute care costs, fewer pharmacy claims, and lower pharmacy costs in both HTN and CHF cohorts. Patients with AUD in both cohorts were more likely to be younger, male, enrolled in Medicaid, with a higher comorbidity burden. Conclusion: In this real-world study, the presence of AUD in patients with either HTN or CHF was associated with greater comorbidity burden, higher acute care utilization and costs, and lower outpatient pharmacy utilization relative to patients without AUD. These findings suggest that AUD impacts care for both HTN and CHF, which could be an opportunity for improved screening and treatment.

Update on Pharmacological Treatment for Comorbid Major Depressive and Alcohol Use Disorders: The Role of Extended-release Trazodone.

Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are major public health concerns because of their high prevalence and clinical and functional severity. MDD and AUD commonly co-occur, but effective therapeutic approaches for comorbidity are still scarce. Available evidence on selective serotonin reuptake inhibitors and tricyclic antidepressants held mixed results, and further pharmacological categories have been less investigated. Trazodone is an approved antidepressant drug for adults and has shown efficacy on symptoms like anxiety and insomnia observed in AUD patients as well. Thus, this study aims to evaluate the effect of extended-release trazodone on clinical and functional features in MDD + AUD subjects. One hundred MDD + AUD outpatients were retrospectively evaluated at 1, 3, and 6 months of treatment with extended-release trazodone (150-300 mg/day, flexibly dosed). Improvement in depressive symptoms was the primary outcome measure. Changes in anxiety, sleep, functioning, quality of life, clinical global severity, and alcohol craving were also investigated. Trazodone reduced depressive symptoms (p < 0.001) with 54.5% remission at the endpoint. Similar improvements were observed in all secondary outcomes, including anxiety, sleep alterations, and craving (p < 0.001). Only mild side effects were reported and disappeared over time. Extended-release trazodone displayed good antidepressant properties in MDD + AUD patients, ameliorating overall symptomatology, functioning, and quality of life, with a good safety/ tolerability profile. Further, it significantly improved sleep disturbances and craving symptoms, which are associated with drinking relapse and worse outcomes. Therefore, trazodone might represent a promising pharmacological option for MDD + AUD patients.

Effect of a health service integration on health care use of patients with alcohol disorders

Abstract Background In North Karelia, Finland an integration of all levels of health and social services was carried out in 2017. One of the usual targets in the service integration is to increase the performance of the service system especially in the care of patients with high use of services. The aim of this study was to assess the impact of the performed integration on the use of health services among patients with alcohol use disorders (AUD). Methods Data on all health care contacts of patients with AUD (n = 4344) covering both primary and specialized care was obtained from the electronic patient records for years 2016 to 2020. Patients having AUD were identified using AUD related ICD-10 diagnosis codes that were either set permanent for the patients or recorded at health care contacts. Information on the type of the contact (appointments and remote contacts), reason of contacts (ICD-10 code) and the professional providing the service (physician, nurse or other health professional) was collected. Results The proportion of patients with any yearly contact to health services was about 90% and did not change after the integration. The proportion of those having alcohol related contacts declined in the whole patient population, but not among the cohort having AUD related diagnosis already in 2016. Appointments decreased and remote contacts increased, but this was not associated with the year of the integration. Especially remote contacts to nurses in outpatient services increased remarkably during the two last years of the study. Conclusions Integration had very little effect on service use of AUD patients. It seemed that the overall trend with increasing remote contacts and decreasing appointments in the health services explain the observed changes. The decline of alcohol related contacts in the whole patient cohort can be explained by the identification of patients with less complicated and advanced diseases as the recording of diagnosis codes has improved. Key messages • Organizational integration of health and social services had very little impact on the service use of patients with alcohol use disorders. • There is a need of better functional integration.

The Effect of Shared Decision-Making by Mental Health Nurses on Medication Adherence in Patients with Alcohol Use Disorders: Provider-Patient Communication Pathway Model

The involvement of patients with mental health issues in their own treatment decision-making has often been overlooked. This study aimed to investigate the impact of shared decision-making between mental health nurses and patients with alcohol use disorders (AUD) on medication adherence. The provider-patient communication pathway model was utilized to examine the ways in which therapeutic communication strategies employed by mental health nurses positively influence medication adherence. The study employed a percentile bootstrap method and pairwise comparison tests in structural equation modeling. The results revealed that shared decision-making between AUD patients and mental health nurses directly enhanced medication adherence, as well as indirectly influenced adherence through the mediating factors of therapeutic alliance and alcohol abstinence self-efficacy. These findings hold both theoretical and practical implications for involving patients with AUD in therapeutic decision-making within psychiatric and mental health nursing settings, as well as for improving medication adherence among this patient population.

Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.

Alcohol Use Disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to SARS-CoV-2 infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared to non-AUD cells. Bronchial epithelial cells from AUD patients showed a significant decrease in barrier function 72 h post infection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1, indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased β-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple pro-inflammatory cytokines including TNFα, IL-1β, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines EGF and GM-CSF was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and barrier dysfunction in response to infection by SARS-CoV-2.

How Does Alcohol Use Disorder Impact Morbidity, Readmission Rates, and HealthCare Expenditures Following Open Reduction and Internal Fixation of Bimalleolar Fractures?

Category: Ankle; Trauma Introduction/Purpose: Bimalleolar ankle fractures are a common injury that can be treated with open reduction and internal fixation (ORIF). However, there is a paucity of literature evaluating the impact of patients with alcohol use disorder (AUD) on postoperative complications following ORIF of bimalleolar ankle fractures. Therefore, the purpose of this study is to investigate whether patients with AUD undergoing ORIF of bimalleolar ankle fractures have higher odds of (1) morbidity; (2) readmissions; and (3) costs of care. Methods: A retrospective query of the PearlDiver nationwide claims database was performed between January 2010 and October 2020. Baseline demographics were analyzed using Pearson’s Chi-Square Analyses. Multivariate binomial logistic regression was utilized to calculate the effect of AUD on 90-day medical complications. Costs of care were compared using Welch’s t-tests. A P value less than 0.001 was considered to be statistically significant. Results: The query yielded 64,563 patients within the study (AUD = 8,177; control = 56,386). Patients who have AUD were found to have significantly higher incidence and odds of developing 90-day medical complications (59.35% vs. 18.77; OR: 2.30; 95% CI: 2.16 to 2.46; p &lt; 0.0001). AUD patients were found to have higher incidences of 90-day readmissions (9.14% vs. 5.56; OR: 0.95; 95% CI: 0.86 to 1.05; p=0.361); however, this failed to reach statistical significance. Patients with AUD also incurred significantly higher day of surgery costs ($4,433.33 vs. $3,979.85, p&lt; 0.0001) and 90-day episode of care costs ($8,523.40 vs. $6,976.95, p&lt; 0.0001). Conclusion: AUD patients have higher odds of 90-day postoperative complications and costs of care following ORIF of bimalleolar ankle fractures. The findings of this study can be used by orthopaedic surgeons to reduce healthcare costs as well as improve postsurgical outcomes by educating patients who have AUD on the potential complications that they may encounter after their procedure.

Levels of IL-6 are Associated with Lifetime Attempted Suicide in Alcohol Use Disorder Patients.

Patients with alcohol use disorder (AUD) have an increased risk of suicide. Neuroimmunological measures, such as cytokines, are shown to deviate in people with attempted suicide. Few studies have investigated this among AUD patients. One-hundred and fourteen patients undergoing residential treatment for AUD were interviewed on lifetime suicide attempts (SA) along with several other background variables and clinical characteristics. Serum blood samples were drawn for analysis of cytokines. Thirty-one patients (27%) reported at least one SA. These patients had more symptoms of current affective disorders and more severe dependence. In bivariate analysis only IL-6 and IL-10 appeared to be associated with lifetime SA but without reaching statistical significance. In multivariate linear regression, adjusting for sex, nicotine use, somatic illness, and the use of anti-inflammatory drugs, IL-6 was associated to SA (p = 0.033). The cytokine IL-6 has repeatedly been found to be associated with suicidality. The present study concurs with this role of IL-6 in a naturalistic observational study of AUD patients.

Novel paradigms for the gut-brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder.

Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1β and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. ClinicalTrials.gov, identifier: NCT# 00106106.

Neural activations during cognitive and affective theory of mind processing in healthy adults with a family history of alcohol use disorder.

Social cognition impairments are a common feature of alcohol use disorders (AUD). However, it remains unclear whether these impairments are solely the consequence of chronic alcohol consumption or whether they could be a marker of vulnerability. The present study implemented a family history approach to address this question for a key process of social cognition: theory of mind (ToM). Thirty healthy adults with a family history of AUD (FH+) and 30 healthy adults with a negative family history of AUD (FH-), matched for age, sex, and education level, underwent an fMRI cartoon-vignette paradigm assessing cognitive and affective ToM. Participants also completed questionnaires evaluating anxiety, depressive symptoms, childhood trauma, and alexithymia. Results indicated that FH+ individuals differed from FH- individuals on affective but not cognitive ToM processing, at both the behavioral and neural levels. At the behavioral level, the FH+ group had lower response accuracy for affective ToM compared with the FH- group. At the neural level, the FH+ group had higher brain activations in the left insula and inferior frontal cortex during affective ToM processing. These activations remained significant when controlling for depressive symptoms, anxiety, and childhood trauma. These findings highlight difficulties during affective ToM processing among first-degree relatives of AUD patients, supporting the idea that some of the impairments exhibited by these patients may already be present before the onset of AUD and may be considered a marker of vulnerability.

Epigenetic regulation of GABA catabolism in iPSC-derived neurons: The molecular links between FGF21 and histone methylation

ObjectiveFibroblast growth factor 21 (FGF21) analogs have been tested as potential therapeutics for substance use disorders. Prior research suggests that FGF21 administration might affect alcohol consumption and reward behaviors. Our recent report showed that plasma FGF21 levels were positively correlated with alcohol use in patients with alcohol use disorder (AUD). FGF21 has a short half-life (0.5–2 h) and crosses the blood–brain barrier. Therefore, we set out to identify molecular mechanisms for both the naïve form of FGF21 and a long-acting FGF21 molecule (PF-05231023) in induced pluripotent stem cell (iPSC)-derived forebrain neurons. MethodsWe performed RNA-seq in iPSC-derived forebrain neurons treated with naïve FGF21 or PF-05231023 at physiologically relevant concentrations. We obtained plasma levels of FGF21 and GABA from our previous AUD clinical trial (n = 442). We performed ELISA for FGF21 in both iPSC-derived forebrain neurons and forebrain organoids. We determined protein interactions using co-immunoprecipitation. Finally, we applied ChIP assays to confirm the occupancy of REST, EZH2 and H3K27me3 by FGF21 using iPSC-derived forebrain neurons with and without drug exposure. ResultsWe identified 4701 and 1956 differentially expressed genes in response to naïve FGF21 or PF-05231023, respectively (FDR < 0.05). Notably, 974 differentially expressed genes overlapped between treatment with naïve FGF21 and PF-05231023. REST was the most important upstream regulator of differentially expressed genes. The GABAergic synapse pathway was the most significant pathway identified using the overlapping genes. We also observed a significant positive correlation between plasma FGF21 and GABA concentrations in AUD patients. In parallel, FGF21 and PF-05231023 significantly induced GABA levels in iPSC-derived neurons. Finally, functional genomics studies showed a drug-dependent occupancy of REST, EZH2, and H3K27me3 in the promoter regions of genes involved in GABA catabolism which resulted in transcriptional repression. ConclusionsOur results highlight a significant role in the epigenetic regulation of genes involved in GABA catabolism related to FGF21 action.(The ClinicalTrials.gov Identifier: NCT00662571)

Psychological interventions to treat alcohol use disorder in patients with liver disease.

Psychological interventions to treat alcohol use disorder in patients with liver disease.

Neurocognitive Recovery in Abstinent Patients with Alcohol Use Disorder: A Scoping Review for Associated Factors.

Studies have reported inconsistent results regarding the extent to which neurocognitive recovery occurs in abstinent patients with alcohol use disorder (AUD). In addition to abstinence, other factors may have influenced this process and contributed to the inconsistencies. This review examines the factors investigated in this regard and describes the possible influence of each factor based on the evidence collected. PubMed was systematically searched for articles published between January 2000 and July 2023. Longitudinal humane studies investigating neurocognitive recovery in abstinent adult AUD patients were included. Studies with a cross-sectional design were excluded, as were studies that did not classify AUD according to the DSM-IV or 5 criteria, only examined binge use, did not report neuropsychological outcomes or duration of abstinence, or where neurological disorders were present. Sixteen categories of factors were distinguished from 31 full-text articles. Consistent patterns were found, indicating an association between neurocognitive recovery and the "smoking" and 'brain volume" factors. Consistent patterns were also found indicating that there is no relationship with "quantities of alcohol used" and "education level." A similar consistent pattern was also found for "polysubstance use", "gender" and "verbal reading", but the number of studies is considered limited. The association with "age" is studied frequently but with inconsistent findings. The remaining eight factors were regarded as understudied. The clearest patterns emerging from the evidence are a predominantly negative influence of smoking on neurocognitive recovery, associations between changes in brain area volume and neurocognitive recovery, and no association between neurocognitive recovery and the amount of alcohol consumed, as measured by self-report, nor with educational attainment. Future research on the understudied factors and factors with inconsistent evidence is needed, preferably through longitudinal designs with multiple assessment periods starting after at least two weeks of abstinence.