Alcoholic Research Articles

Early life stress is associated with greater negative emotionality and peripheral inflammation in alcohol use disorder

Early life stress (ELS) increases risk for psychiatric illness, including alcohol use disorder (AUD). Researchers have hypothesized that individuals with and without a history of ELS who have the same primary DSM-5 diagnosis are clinically and biologically distinct. While there is strong support for this hypothesis in the context of mood disorders, the hypothesis remains largely untested in the context of AUD. This study investigated the impact of ELS on the neuroclinical phenomenology and inflammatory profile of individuals with AUD. Treatment-seeking adults with AUD (N = 163) completed the Adverse Childhood Experiences (ACE) Questionnaire and phenotypic battery as part of a pharmacotherapy trial for AUD (NCT03594435). Participants were classified as having “no-ELS,” (ACE = 0) “moderate-ELS,” (ACE = 1, 2 or 3) or “high-ELS” (ACE = 4 + ). The Addictions Neuroclinical Assessment domains incentive salience and negative emotionality were derived and used to assess the neuroclinical phenomenology of AUD. We tested (1) cumulative ELS as a predictor of ANA domains and (2) ELS group differences in ANA domains. A subset of participants (N = 98) provided blood samples for a biomarker of peripheral inflammation (C-reactive protein; CRP); analyses were repeated with CRP as the outcome variable. Greater ELS predicted higher negative emotionality and elevated CRP, but not incentive salience. The high-ELS group exhibited greater negative emotionality compared with the no-ELS and moderate-ELS groups, with no difference between the latter two groups. The high-ELS group exhibited elevated CRP compared with the no/moderate-ELS group. Findings suggest that high-ELS exposure is associated with a unique AUD neuroclinical presentation marked by greater negative emotionality, and inflammatory profile characterized by elevated peripheral CRP.

Protein kinase C epsilon-mediated modulation of T-type calcium channels underlies alcohol withdrawal hyperexcitability in the midline thalamus.

Millions of people struggle with alcohol use disorder (AUD). Abrupt abstinence after a period of chronic alcohol use can precipitate the alcohol withdrawal syndrome (AWS), which includes hyperexcitability and, potentially, seizures. We have shown that T-type Ca2+ channels are novel, sensitive targets of alcohol, an effect that is dependent upon protein kinase C (PKC). The purpose of this study was to (1) understand midline thalamic neuronal hyperexcitability during alcohol withdrawal and its dependence on PKC; (2) characterize T channel functional changes using both current clamp and voltage clamp methods; and (3) determine which PKC isoform may be responsible for alcohol withdrawal (WD) effects. Whole-cell patch clamp recordings were performed in midline thalamic neurons in brain slices prepared from C57bl/6 mice that underwent chronic intermittent alcohol exposure in a standard vapor chamber model. The recordings were compared to those from air-exposed controls. T-channel inactivation curves and burst responses were acquired through voltage-clamp and current-clamp recordings, respectively. Whole-cell voltage clamp recordings of native T-type current exhibited a depolarizing shift in the voltage-dependency of inactivation during alcohol withdrawal compared to air-exposed controls. A PKCε translocation inhibitor peptide mitigated this change. Current clamp recordings demonstrated more spikes per burst during alcohol withdrawal. Consistent with voltage clamp findings, the PKCɛ translocation inhibitor peptide reduced the number of spikes per burst after WD. We found that alcohol WD produces T channel-mediated hyperexcitability in the midline thalamus, produced in part by a shift in the inactivation curve consistent with greater availability of T current. WD effects on T current inactivation were reduced to control levels by blocking PKCε translocation. Our results demonstrate that PKCε translocation plays an important role in the regulation of alcohol withdrawal-induced hyperexcitability in midline thalamic circuitry.

Standard rodent diets differentially impact alcohol consumption, preference, and gut microbiome diversity.

Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 h intermittent access procedure. The three brands of chow tested were LabDiet 5,001 (LD5001), LabDiet 5,053 (LD5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo, respectively). Mice fed LD5001 and LD5053 displayed higher levels of alcohol consumption and preference compared to mice fed TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48 h prior to alcohol administration. Sucrose, saccharin, and quinine preferences were not altered, suggesting that the diets did not alter sweet and bitter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of compulsive behaviors such as alcohol consumption. We profiled the gut microbiome of water- and alcohol-drinking mice that were maintained on different diets and found significant differences in bacterial alpha- and beta-diversities, which could impact the gut-brain axis signaling and alcohol consumption.

Single-site iron-anchored amyloid hydrogels as catalytic platforms for alcohol detoxification.

Constructing effective antidotes to reduce global health impacts induced by alcohol prevalence is a challenging topic. Despite the positive effects observed with intravenous applications of natural enzyme complexes, their insufficient activities and complicated usage often result in the accumulation of toxic acetaldehyde, which raises important clinical concerns, highlighting the pressing need for stable oral strategies. Here we present an effective solution for alcohol detoxification by employing a biomimetic-nanozyme amyloid hydrogel as an orally administered catalytic platform. We exploit amyloid fibrils derived from β-lactoglobulin, a readily accessible milk protein that is rich in coordinable nitrogen atoms, as a nanocarrier to stabilize atomically dispersed iron (ferrous-dominated). By emulating the coordination structure of the horseradish peroxidase enzyme, the single-site iron nanozyme demonstrates the capability to selectively catalyse alcohol oxidation into acetic acid, as opposed to the more toxic acetaldehyde. Administering the gelatinous nanozyme to mice suffering from alcohol intoxication significantly reduced their blood-alcohol levels (decreased by 55.8% 300 min post-alcohol intake) without causing additional acetaldehyde build-up. Our hydrogel further demonstrates a protective effect on the liver, while simultaneously mitigating intestinal damage and dysbiosis associated with chronic alcohol consumption, introducing a promising strategy in effective alcohol detoxification.

Mode of mutual-help group attendance: Predictors and outcomes in a US national longitudinal survey of adults with lifetime alcohol use disorder

IntroductionAlthough attending substance use-focused mutual-help meetings online may reduce attendance barriers, associations of attendance mode with group participation and outcomes are unknown. Using longitudinal data from mutual-help group attendees, this study, after identifying differences in baseline characteristics by attendance mode, examined associations of attendance mode with mutual-help participation (number of meetings attended, involvement) and outcomes (alcohol abstinence, heavy drinking, alcohol problems). MethodsThe Peer Alternatives for Addiction Study 2021 Cohort sampled attendees of 12-step groups (e.g., Alcoholics Anonymous), Women for Sobriety, LifeRing Secular Recovery, and/or SMART Recovery in-person and/or online within 30 days before baseline. The baseline sample, recruited in fall 2021, was 531 adults with lifetime alcohol use disorder, followed at 6 (88 %) and 12 months (85 %). Differences in baseline characteristics by attendance mode were tested using Chi-squares and ANOVAs. GEE models examined associations of attendance mode, time, and their interactions with mutual-help group participation and alcohol outcomes. The in-person only mode was compared to the online-only, and to the in-person plus online, modes. ResultsAt baseline, 53.7 % of participants had attended only online meetings in the past 30 days, 33.7 % had attended both in-person and online meetings, and 12.6 % had attended only in-person meetings. Online meeting attendees were less likely to endorse lifetime abstinence as an alcohol recovery goal than in-person-only meeting attendees. In adjusted models (including for recovery goal), those attending online meetings only, or both online and in-person meetings, attended a greater number of meetings compared to those attending only in-person meetings. However, online-only attendance was associated with less involvement than in-person-only attendance. In adjusted models, compared to baseline, involvement increased and outcomes improved at follow-ups. Adjusted models examining alcohol outcomes found that no attendance at mutual-help groups at follow-ups was associated with more heavy drinking compared to in-person-only attendance. ConclusionsFindings inform efforts to ascertain benefits of mutual-help group participation by suggesting that online attendance is associated with attending more meetings, less involvement, and lower endorsement of abstinence as a recovery goal, and is comparable to in-person attendance on alcohol outcomes. In-person attendance may be more beneficial for less heavy drinking than terminating attendance.

Assisted Versus Unassisted Domiciliary Alcohol Detoxification: A Randomized Controlled Trial

Background: Detoxification stands as a crucial phase in the treatment of alcohol use disorders (AUD), yet only limited data is available on the outcomes of home-based detoxification. Assisted domiciliary detoxification involves monitoring an individual’s withdrawal progress, while offering psychosocial support and detoxification services in the comfort of their home. Aim: To study outcomes of assisted over routine domiciliary alcohol detoxification in randomized controlled trials. Methodology: 100 consenting male patients who were advised of domiciliary detoxification were randomized into intervention ( n = 49) and control ( n = 51) groups. A predesigned semi-structured questionnaire was used to assess the socio-demographic and drinking-related variables. Both groups received routine care for alcohol withdrawal from respective treating doctors. Additionally, the intervention group received two sessions of brief intervention for alcohol and daily phone call assistance. Records were kept for adverse events. Phone calls were discontinued once detoxification was completed. Outcomes were measured for successful completion of detoxification and abstention from alcohol at the end of one month. Results: The intervention group had significantly higher successful detoxification rates (85.7% vs. 62.7%, p = .008) and significantly higher abstinence days at the end of one month compared to the control group (22 vs. 10 days, p < .001) with an effect size of 1.2 (confidence interval (CI) 0.69–1.53). Conclusion: This study demonstrates that receiving assistance in the acute phase of domiciliary detoxification helps in a successful detoxification and achieving a significant level of abstinence at the end of one month compared to the control group.

Alcohol and cannabis use and co-use among Whites and Hispanics on and off the U.S./Mexico border in California

This paper examines self-reported rates of drinking and cannabis use and co-use among White and Hispanic adults randomly selected in four counties in California: Imperial on the border; and Kern, Tulare, and Madera in California’s Central Valley. Co-use was significantly higher among the U.S. born than among those born abroad, and in the Central Valley than on the border. Co-users were heavier drinkers, had higher rates of alcohol use disorder, other alcohol problems, and a positive history of illicit drug use than drinkers only.

Variants of the P3 event-related potential operate as indicators of distinct mechanisms contributing to problematic alcohol use.

Considerable research has linked relative reduction in the amplitude of the P3 event-related potential (ERP) during cognitive task performance (i.e., Target-P3) with increased risk of alcohol-related problems. A separate literature indicates that a relative increase in the amplitude of the P3 elicited by cues signaling alcohol availability (i.e., ACR-P3) also is associated with alcohol use and problems. To date, no research has integrated these seemingly discrepant findings. Here, we aimed to demonstrate that P3 amplitudes elicited in different task contexts reflect distinct domains of functioning relevant to problematic alcohol involvement (PAI), and therefore can inform heterogeneity in the etiology of PAI. 156 emerging adults (61% women; 88% White/Non-Hispanic) completed a mental rotation task and a picture-viewing task while ERPs were recorded. Participants also completed questionnaire measures of trait disinhibition, alcohol use, and alcohol-related problems. Findings from regression analyses indicated that (a) Target-P3 was negatively associated and ACR-P3 was positively associated with a PAI latent variable; (b) the two P3s accounted for unique variance in PAI, beyond that accounted for by recent drinking; and (c) the association between Target-P3 and PAI-but not ACR-P3 and PAI-was statistically mediated by trait disinhibition. The present findings highlight the unique contributions of distinct functional domains associated with disinhibition and incentive salience in the etiology of PAI. Moreover, findings are consistent with a nuanced understanding of the P3 ERP, whereby its specific meaning varies according to the task context in which it is elicited.

Assessing Self Control and Peer Pressure among Young Alcohol Addicts of Tripura

Assessing Self Control and Peer Pressure among Young Alcohol Addicts of Tripura

Peripheral blood transcriptomic profiling of molecular mechanisms commonly regulated by binge drinking and placebo effects

Molecular responses to alcohol consumption are dynamic, context-dependent, and arise from a complex interplay of biological and external factors. While many have studied genetic risk associated with drinking patterns, comprehensive studies identifying dynamic responses to pharmacologic and psychological/placebo effects underlying binge drinking are lacking. We investigated transcriptome-wide response to binge, medium, and placebo alcohol consumption by 17 healthy heavy social drinkers enrolled in a controlled, in-house, longitudinal study of up to 12 days. Using RNA-seq, we identified 251 and 13 differentially expressed genes (DEGs) in response to binge drinking and placebo, respectively. Eleven protein-coding DEGs had very large effect sizes in response to binge drinking (Cohen’s d > 1). Furthermore, binge dose significantly impacted the Cytokine-cytokine receptor interaction pathway (KEGG: hsa04060) across all experimental sequences. Placebo also impacted hsa04060, but only when administered following regular alcohol drinking sessions. Similarly, medium-dose and placebo commonly impacted KEGG pathways of Systemic lupus erythematosus, Neutrophil extracellular trap formation, and Alcoholism based on the sequence of drinking sessions. These findings together indicate the “dose-extending effects” of placebo at a molecular level. Furthermore, besides supporting alcohol dose-specific molecular changes, results suggest that the placebo effects may induce molecular responses within the same pathways regulated by alcohol.

Maternal 129S1/SvImJ background attenuates the placental phenotypes induced by chronic paternal alcohol exposure

Paternal alcohol use is emerging as a plausible driver of alcohol-related growth and patterning defects. Studies from our lab using an inbred C57Bl/6 J mouse model suggest that these paternally-inherited phenotypes result from paternally programmed deficits in the formation and function of the placenta. The 129S1/SvImJ genetic background is typically more susceptible to fetoplacental growth defects due to strain-specific differences in placental morphology. We hypothesized that these placental differences would sensitize 129S1/SvImJ-C57Bl/6 J hybrid offspring to paternally-inherited fetoplacental growth phenotypes induced by paternal alcohol exposure. Using a limited access model, we exposed C57Bl/6 J males to alcohol and bred them to naïve 129S1/SvImJ dams. We then assayed F1 hybrid offspring for alterations in fetoplacental growth and used micro-CT imaging to contrast placental histological patterning between the preconception treatments. F1 hybrid placentae exhibit larger placental weights than pure C57Bl/6 J offspring but display a proportionally smaller junctional zone with increased glycogen content. The male F1 hybrid offspring of alcohol-exposed sires exhibit modest placental hyperplasia but, unlike pure C57Bl/6 J offspring, do not display observable changes in placental histology, glycogen content, or measurable impacts on fetal growth. Although F1 hybrid female offspring do not exhibit any measurable alterations in fetoplacental growth, RT-qPCR analysis of placental gene expression reveals increased expression of genes participating in the antioxidant response. The reduced placental junctional zone but increased glycogen stores of 129S1/SvImJ-C57Bl/6 J F1 hybrid placentae ostensibly attenuate the previously observed placental patterning defects and fetal growth restriction induced by paternal alcohol use in the C57Bl/6 J strain.

Current trends in the role of neuroinflammation & α-synuclein in alcohol use disorder: A systematic quantitative literature review.

The neurodegenerative effects alcohol use disorder (AUD) have been well characterized and are likely due to the long-term effects of alcohol on the brain. The molecular events that underlie regional neuronal loss are a focus of current research. Chronic inflammation in the central nervous system, termed neuroinflammation, contributes to the progressive loss of neurons in the brain. Using data from genome-wide association studies and genetic and gene expression data, α-synuclein was identified as a gene of interest for AUD almost 10 years ago. Despite this and the well-recognized role of α-synuclein in mediating neuroinflammation in other neurodegenerative diseases, its role in alcohol-induced brain damage and AUD is yet to be elucidated. This systematic literature review quantifies and analyzes relationships between AUD, α-synuclein, and neuroinflammation. The review identified fewer studies focused on the role in AUD of α-synuclein (30) than on neuroinflammation (177), with published studies heavily centered on the myeloid differentiation primary response 88 (MyD88)-dependent toll-like receptor 4 (TLR4) pathway. The systematic review revealed that no original literature investigates the roles of α-synuclein and neuroinflammation in AUD and that there are significantly fewer published articles on the role of α-synuclein in AUD than in other neuroinflammatory conditions. Studies of the role of neuroinflammation in AUD are largely centered on the TLR4 signaling cascade, followed by TLR2 and TLR3, and soluble cytokines such as IL-10, IL-1β, and TNF-α. Key research themes identified in other neurodegenerative disorders provide new insights for further investigation in AUD.

Correlations of the CNR1 Gene with Personality Traits in Women with Alcohol Use Disorder.

Alcohol use disorder (AUD) is a significant issue affecting women, with severe consequences for society, the economy, and most importantly, health. Both personality and alcohol use disorders are phenotypically very complex, and elucidating their shared heritability is a challenge for medical genetics. Therefore, our study investigated the correlations between the microsatellite polymorphism (AAT)n of the Cannabinoid Receptor 1 (CNR1) gene and personality traits in women with AUD. The study group included 187 female subjects. Of these, 93 were diagnosed with alcohol use disorder, and 94 were controls. Repeat length polymorphism of microsatellite regions (AAT)n in the CNR1 gene was identified with PCR. All participants were assessed with the Mini-International Neuropsychiatric Interview and completed the NEO Five-Factor and State-Trait Anxiety Inventories. In the group of AUD subjects, significantly fewer (AAT)n repeats were present when compared with controls (p = 0.0380). While comparing the alcohol use disorder subjects (AUD) and the controls, we observed significantly higher scores on the STAI trait (p < 0.00001) and state scales (p = 0.0001) and on the NEO Five-Factor Inventory Neuroticism (p < 0.00001) and Openness (p = 0.0237; insignificant after Bonferroni correction) scales. Significantly lower results were obtained on the NEO-FFI Extraversion (p = 0.00003), Agreeability (p < 0.00001) and Conscientiousness (p < 0.00001) scales by the AUD subjects when compared to controls. There was no statistically significant Pearson's linear correlation between the number of (AAT)n repeats in the CNR1 gene and the STAI and NEO Five-Factor Inventory scores in the group of AUD subjects. In contrast, Pearson's linear correlation analysis in controls showed a positive correlation between the number of the (AAT)n repeats and the STAI state scale (r = 0.184; p = 0.011; insignificant after Bonferroni correction) and a negative correlation with the NEO-FFI Openness scale (r = -0.241; p = 0.001). Interestingly, our study provided data on two separate complex issues, i.e., (1) the association of (AAT)n CNR1 repeats with the AUD in females; (2) the correlation of (AAT)n CNR1 repeats with anxiety as a state and Openness in non-alcohol dependent subjects. In conclusion, our study provided a plethora of valuable data for improving our understanding of alcohol use disorder and anxiety.

Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk. Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones. Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20). Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Plasma cathepsin D as an early indicator of alcohol-related liver disease

Background & AimsPeople who excessively drink alcohol are at increased risk of developing metabolic dysfunction and alcohol-related liver disease (MetALD) or the more severe form alcohol-related liver disease (ALD). One of the most significant challenges concerns the early detection of MetALD/ALD. Previously, we have demonstrated that the lysosomal enzyme cathepsin D (CTSD) is an early marker for metabolic dysfunction-associated steatohepatitis (MASH). Here, we hypothesized that plasma CTSD can also serve as an early indicator to detect MetALD/ALD. MethodsWe included 303 persistent heavy drinkers classified as MetALD or ALD (n=152) and abstinent patients with a history of excessive drinking (n=151). Plasma CTSD levels of MetALD/ALD patients without decompensation were compared with 40 healthy controls. Subsequently, the relationship between plasma CTSD levels and hepatic histological scores was established. ROC-AUC curves were generated to assess the precision of plasma CTSD levels in detecting MetALD/ALD. Lastly, plasma CTSD levels were compared between abstainers and drinkers. ResultsPlasma CTSD levels were higher in MetALD/ALD patients compared to healthy controls. While hepatic disease parameters (AST/ALT ratio, transient elastography (TE)) were higher at advanced histopathological stages as assessed by liver biopsy, plasma CTSD levels were already elevated at early histopathological stages. Furthermore, combining plasma CTSD levels with TE and AST/ALT ratio yielded enhanced diagnostic precision (ROC-AUC: 0.872) in detecting MetALD/ALD in contrast to the utilization of CTSD alone (AUC 0.804). Plasma CTSD levels remained elevated in abstainers. ConclusionElevated levels of CTSD in the circulation can serve as an early indicator for MetALD/ALD.

The gut microbiome in alcohol use disorder and alcohol-associated liver disease: A systematic review of clinical studies.

Evidence suggests that a relationship exists between the gut microbiome and the pathogenesis of alcohol use disorder (AUD) and alcohol-associated liver disease (AALD). This systematic review identified studies that investigated the gut microbiome in individuals with an AUD or an AALD. A search was conducted on October 27, 2022, in PubMed, Web of Science, and Embase databases. Fifty studies satisfied eligibility criteria. Most studies found evidence for gut dysbiosis in individuals with AUD and AALD. Microbiome intervention studies have mostly been conducted in AALD patients; fecal microbial transplant interventions show the most promise. Because most studies were conducted cross-sectionally, the causal relationship between the gut microbiome and alcohol use is unknown. Furthermore, almost all studies have been conducted in predominantly male populations, leaving critical questions regarding sex differences and generalizability of the findings. The study summaries and recommendations provided in this review seek to identify areas for further research and to highlight potential gut microbial interventions for treating AUD and AALD.

Clinical features of individuals with laboratory values suggestive of advanced liver fibrosis when first treated for alcohol use disorder.

Effective screening for alcohol-associated liver disease is relevant in the context of chronic, excessive alcohol consumption. Patients with alcohol-associated liver disease are often not diagnosed until their liver disease is decompensated. We analyzed the prevalence and associations of Fibrosis-4 index (FIB-4) values suggestive of advanced liver fibrosis in patients referred for their first treatment of alcohol use disorder (AUD). We conducted a cross-sectional, multicenter study of noncirrhotic individuals referred for their first AUD treatment between March 2013 and April 2021. We obtained sociodemographic data, substance use characteristics, and blood samples at admission. We considered a FIB-4 value ≥2.67 suggestive of advanced liver fibrosis and used logistic regression analyses to identify features associated with this value. We included 604 patients (67% male), with a median age at admission of 48 years [IQR: 41-56 years]. The median duration of regular alcohol consumption was 21 years [IQR: 18-30 years] and the median alcohol consumption was 105 standard drink units (SDU)/week [IQR: 63-160 SDU/week]. A FIB-4 value ≥ 2.67 was present in 19.3% of cases. These patients reported more frequent binge drinking (75.4% vs. 66%, p = 0.05) than those with FIB-4 values below 2.67. In multivariate analysis, a history of binge drinking (OR 1.9, 95% CI, 1.05-3.47), anemia (OR 2.95, 95% CI, 1.42-6.11), leukopenia (OR 7.46, 95% CI, 2.07-26.8), and total serum bilirubin >1 mg/dL (OR 6.46, 95% CI, 3.57-11.7) were independently associated with FIB-4 values ≥2.67. One in five patients admitted to treatment for AUD without evidence of decompensated liver disease have FIB-4 values suggestive of advanced liver fibrosis. The presence of a binge drinking history, anemia, leukopenia, and elevated bilirubin levels is associated with high FIB-4 values.

Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors

Dysregulation of the dopamine (DA) system is a hallmark of substance use disorders, including alcohol use disorder (AUD). Of the DA receptor subtypes, the DA D2 receptors (D2Rs) play a key role in the reinforcing effects of alcohol. D2Rs are expressed in numerous brain regions associated with the regulation of appetitive behaviors. One such region is the bed nucleus of the stria terminalis (BNST), which has been linked to the development and maintenance of AUD. Recently, we identified alcohol withdrawal-related neuroadaptations in the periaqueductal gray/dorsal raphe to BNST DA circuit in male mice. However, the role of D2R-expressing BNST neurons in voluntary alcohol consumption is not well characterized. In this study, we used a CRISPR-Cas9-based viral approach, to selectively reduce the expression of D2Rs in BNST GABA neurons (BNSTvgat Drd2) and interrogated the impact on alcohol-related behaviors. In male mice, reduced BNSTvgat Drd2 expression potentiated the stimulatory effects of alcohol and increased voluntary consumption of 20% w/v alcohol in a two-bottle choice intermittent access paradigm. This effect was not specific to alcohol, as BNSTvgat Drd2 knockdown also increased sucrose intake in male mice. Interestingly, reduction in BNSTvgat Drd2 expression in female mice did not alter alcohol-related behaviors but lowered the threshold for mechanical pain sensitivity. Collectively, our findings suggest a role for postsynaptic BNST D2Rs in the modulation of sex-specific behavioral responses to alcohol and sucrose.

The Insular Cortex→Bed Nucleus of the Stria Terminalis Pathway during Early Abstinence from Chronic Alcohol Use: A Promising Target for Mitigating Negative Emotions and Relapse Risk.

The Insular Cortex→Bed Nucleus of the Stria Terminalis Pathway during Early Abstinence from Chronic Alcohol Use: A Promising Target for Mitigating Negative Emotions and Relapse Risk.

Sexism and alcohol-related problems among women: The role of social anxiety and coping motivated drinking.

Experiencing sexism is related to more alcohol-related problems, presumably via drinking to cope with negative affect associated with experiencing sexism. Yet no known studies have directly tested whether the relation of sexism to alcohol problems occurs via relevant negative emotions and drinking to cope with negative emotions. Given that sexism is a type of negative evaluation, social anxiety may be one type of negative affect that plays a role in sexism's relation with drinking behaviors. This study tested whether sexism was related to alcohol-related problems via the serial effects of social anxiety and coping-motivated alcohol use among 836 cis-female undergraduates who endorsed past-month alcohol use. Past-year experiences with sexism were positively correlated with coping and conformity-motivated alcohol use, alcohol problems (but not peak estimated blood alcohol content, eBAC), social anxiety, and depression. After statistically controlling for depression and peak eBAC, sexism was indirectly related to alcohol problems via the serial effects of social anxiety and drinking motives (coping, conformity). Results highlight the important role of social anxiety and drinking to cope with negative emotions and to fit in with peers who drink in relation of sexism with alcohol-related problems. This is the first known study to find that experiences of sexism are related to alcohol problems via the serial effects of social anxiety and coping and conformity-motivated drinking. This is also the first known study to find that sexism is related to more conformity-motivated drinking.