Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence.

Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD. Evidence implicates the endogenous dynorphin (DYN)/κ-opioid receptor (KOR) system recruitment in dysphoric and negative emotional states in AUD to promote maladaptive behavioral regulation. The nucleus accumbens shell (AcbSh), mediating motivational and emotional processes that is a component of the mesolimbic dopamine system and the extended amygdala, is an important site related to alcohol's reinforcing actions (both positive and negative) and neuroadaptations in the AcbSh DYN/KOR system have been documented to induce maladaptive symptoms in AUD. We have previously shown that in other nodes of the extended amygdala, site-specific KOR antagonism can distinguish different symptoms of alcohol dependence and withdrawal. In the current study, we examined the role of the KOR signaling in the AcbSh of male Wistar rats in operant alcohol self-administration, measures of negative affective-like behavior, and physiological symptoms during acute alcohol withdrawal in alcohol-dependence. To induce alcohol dependence, rats were exposed to chronic intermittent ethanol vapor for 14 h/day for three months, during which stable escalation of alcohol self-administration was achieved and pharmacological AcbSh KOR antagonism ensued. The results showed that AcbSh KOR antagonism significantly reduced escalated alcohol intake and negative affective-like states but did not alter somatic symptoms of withdrawal. Understanding the relative contribution of these different drivers is important to understand and inform therapeutic efficacy approaches in alcohol dependence and further emphasis the importance of the KOR/DYN system as a target for AUD therapeutics.

Deaths of despair-associated mortality rates globally: a 2000-2019 sex-specific disparities analysis.

OBJECTIVES: The aim of this study was to explore sex-specific disparities in rates of deaths of despair across 183 countries from 2000 to 2019. STUDY DESIGN: Secondary analysis of cross-sectional population-level data. METHODS: Data were obtained from the World Health Organization Health Inequality Data Repository. We analysed data on mortality due to alcohol, drug-use disorders, and self-harm (as a proxy for suicide). We calculated the average rate of deaths of despair by year and sex, trends in these rates, and cause-specific mortality trends. We then fitted mixed-effect generalised linear models to compare mortality rates by sex and country. RESULTS: Analyses revealed significant disparities by sex, with a 3.3-fold higher rate among men than among women globally (95% confidence interval: 3.1-3.5, P < 0.001). There was a significant decline in deaths of despair globally and among both sexes during the assessed period (5% per 5 years). Lesotho, Belarus, the US, the Russian Federation, Guyana, and Slovenia ranked among the top 10 countries out of 183 with the highest mortality rates for both sexes. Canada, the Republic of Korea, Belgium, and Finland were countries with the highest mortality rates among women, whereas Ukraine, Lithuania, Mongolia, and Eswatini have the highest rates among men. In the US, 5-year mortality rates increased by 35% for women and 21% for men: drug-use mortality showed a significant increase over time, whereas suicide rates decreased for both sexes in the given country. Additionally, mortality rates from alcohol use decreased among women. CONCLUSIONS: This global analysis shed light on health disparities by sex in deaths of despair, especially concerning trends in the US. It identified countries and groups in need of targeted mental health and substance-use programs. Moreover, the disparities by sex revealed in this analysis suggest that mental health and substance-use interventions and programs may need to be more attentive to sex and/or gender, such as inequitable social norms and restrictive forms of masculinities, which have been shown to be contributing factors to deaths of despair.

Associations Between Divorce Histories and Unhealthy Alcohol Use Among Middle Aged and Older Adults.

Background: Unhealthy alcohol use has been considered a coping strategy related to stressful and traumatic life events such as relationship loss. Yet, the effects of marital status on health behaviors are generally studied cross-sectionally or over one transition. We explored associations between the frequency and quantity of alcohol use with the number of episodes and duration of separation/divorce events across adulthood among English adults in mid to later life. Methods: This study used life history data from wave 3 (2006/07) of the English Longitudinal Study of Aging to compute marital sequences based on marital status at each year of age from 18 years of 6,355 adults aged 50-80 years. These sequences were used to compute the portion of adulthood spent separated/divorced and the number of episodes of divorce. These variables were used as predictors in logistic regressions predicting unhealthy alcohol use, while also controlling for current marital status. Results: We found that the number of episodes of separation/divorce increased the odds of drinking ≥5 days/week and binge drinking (≥6 drinks/occasion for women; ≥8 drinks/occasion for men), whereas the portion of adulthood spent divorced was not associated with drinking frequency or binge drinking. Some nuances by gender were also noted. Conclusions: Recurrent transitions into separation/divorce over adulthood appears to increase risk of unhealthy alcohol use in mid to later life beyond the risks associated with current marital status.

Analysis of Ohio Advanced Practice Registered Nurses' Rate of Prescribing Naltrexone for Patients With Alcohol Use Disorder Since Elimination of the X-Waiver.

BACKGROUND: Alcohol use disorder (AUD) is common and deadly. Naltrexone is a treatment for AUD. Previous research examined factors that predict Ohio Advanced Practice Registered Nurses' (APRNs) utilization of naltrexone to treat AUD. Inclusion criteria included APRNs' endorsing receipt of the X-waiver, a designation indicating providers' receipt of substance use disorder education. In 2023, the X-waiver was eliminated. The purpose of this study was to replicate the previous research design in respondents without an X-waiver and compare findings. AIMS: The aims of this study were three-fold: (1) assess whether race, age, practice setting, years in practice, or work experience with an addiction specialist physician predicted prescription of naltrexone for AUD, (2) assess whether the goal of abstinence or reduced alcohol use as desired treatment affected the likelihood of naltrexone prescription for AUD, and (3) compare differences between the answers in the current respondent group without X-waiver and the previous study's X-waivered respondents. METHOD: All Ohio APRNs were sent surveys. Eighty-eight responses were included in analysis. Descriptive statistics, logistic regression, and chi-square results were reported. RESULTS: Work experience with an addiction specialist physician was negatively associated with prescribing naltrexone for AUD. Respondents from the previous study of X-waivered APRNs were significantly more likely to prescribe naltrexone for reduced alcohol consumption as a treatment outcome than the respondents in this study. CONCLUSION: The recent policy change eliminating the X-waiver provides important context for research, adding to the substance use disorder literature.

ChatGPT-4: Alcohol use disorder responses.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) is characterized by low levels of engagement with effective treatments. Enhancing awareness of AUD treatments and how to navigate the treatment system is crucial. Many individuals use online sources (e.g. search engines) for answers to health-related questions; web-based results include a mix of high- and low-quality information. Artificial intelligence may improve access to quality health information by providing concise, high-quality responses to complex health-related questions. This study evaluated the quality of ChatGPT-4 responses to AUD-related queries. METHOD: A comprehensive list of 64 AUD-related questions was developed through a combination of Google Trends analysis and expert consultation. ChatGPT-4 was prompted with each question, followed by a request to provide 3-5 peer-reviewed scientific citations supporting each response. Responses were evaluated for whether they were evidence-based, provided a referral and provided supporting documentation. RESULTS: ChatGPT-4 responded to all AUD-related queries, with 92.2% (59/64) of responses being fully evidence-based. Although only 12.5% (8/64) of responses included referrals to external resources, all responses (100%; 5/5) to location-specific ('near me') queries directed individuals to appropriate resources like the NIAAA Treatment Navigator. Most (85.9%; 55/64) responses to the follow-up question provided supporting documentation. CONCLUSIONS: ChatGPT-4 responds to alcohol use disorder-related questions with evidence-based information and supporting documentation. ChatGPT-4 could be promoted as a reasonable resource for those looking online for alcohol use disorder-related information.

Mobility and sexually transmitted infections: Exploring intersectional axes of alcohol consumption and risky sexual behavior among Indian men.

OBJECTIVE: Studies in India and other low-income countries find an inconsistent association between mobility/migration and sexually transmitted infections (STIs) among men. This study comprehensively examined the association between mobility and STIs among men in India. It also assessed heterogeneous associations of mobility, alcohol consumption, and risky sexual behavior with STIs using interaction analysis. METHODS: We utilized a sample of 71,128 sexually active men aged 15-54 years from the 2019-21 National Family Health Survey-5. Binary logistic regression models were employed to study the associations. RESULTS: Among the study participants, 16% were mobile and away from home for a month or more in the last 12 months. Around 29% of men reported alcohol consumption and 6% had risky sexual behavior (sexual intercourse with a non-marital/non-cohabitating partner). Regression results suggest that mobility (AOR: 1.41, 95% CI: 1.29-1.55 [short-duration]; AOR: 1.95, 95% CI: 1.77-2.13 [long-duration]) and alcohol consumption (AOR: 1.32, 95% CI: 1.24-1.40) were significantly associated with an increased risk of STIs, even after controlling for socio-demographic covariates. Interaction analysis further reveals that mobile men who consumed alcohol and engaged in risky sexual behavior had a significantly higher likelihood of contracting an STI-twice as high in cases of short-duration mobility and three times higher in cases of long-duration mobility. CONCLUSION: Our study indicates that both short and long-duration mobility are significantly associated with an increased risk of STIs among men. Alcohol consumption and risky sexual behavior further exacerbate the risk of STIs in mobile men. Initiatives for STI/HIV prevention among men must pay particular attention to temporary mobile men for both short and long durations.

Identifying and responding to fetal alcohol spectrum disorder in child and family health: Lessons from an exploratory mixed methods study.

INTRODUCTION: Developmental outcomes for children and young people with fetal alcohol spectrum disorder (FASD) are optimised if their needs are identified early. Yet, health workers miss vital opportunities to identify and respond to FASD due to a lack of support, knowledge and skills. METHODS: Through surveys and interviews, our study investigated what child and family health workers in an Australian metropolitan local health district understand, already do and want to learn about FASD. RESULTS: The study provided evidence of low FASD knowledge and confidence and a lack of referral options with some workers 'patching together' care planning in a 'referral black hole'. Qualitative data provided insight into how skilled clinicians engage families in FASD assessment and negotiate gaps in clinical knowledge. DISCUSSION AND CONCLUSIONS: Health workers in this study requested high-quality training and the development of FASD practice guidelines to improve role clarity and clinical impact when working with FASD populations.

One-Year Follow-Up: Schema Therapy for Patients With Borderline Personality Disorder and Comorbid Alcohol Use Disorder.

This article describes the 1-year follow-up of a study into the effectiveness of Schema Therapy (ST) for borderline personality disorder (BPD) and comorbid alcohol use disorder (AUD). In the original study, 20 of these patients participated in a multiple baseline case series design study. The results of the original study were promising (a significant decrease of BPD and AUD symptoms). The present study is aimed at examining the longer term benefits of ST for BPD and comorbid AUD. One year after the cessation of the investigational therapy, 17 of the original participants agreed to participate in this follow-up study. T- or Wilcoxon signed rank tests were performed to compare 1-year follow-up to start of therapy (baseline). The results suggest that the main therapeutic improvements were generally preserved at 1-year follow-up. These findings add to the idea that integrated ST for BPD and comorbid AUD might be effective, also in the long term. A randomized clinical trial is indicated to substantiate this idea.

Effects of voluntary chronic intermittent access to ethanol on the behavioral performance in adult C57BL/6 J mice.

BACKGROUND: Chronic alcohol drinking increases the risk of alcohol use disorders, causing various neurological disorders. However, the impact of different ethanol levels on a spectrum of behaviors during chronic drinking remains unclear. In this study, we established an intermittent access to ethanol in a two-bottle choice (IA2BC) procedure to explore the dose-dependent effects of ethanol on the behavioral performance of C57BL/6 J mice. METHODS: Adult male C57BL/6 J mice were provided voluntary access to different ethanol concentrations (0 %, 5 %, 10 %, and 20 % ethanol) under a 12-week IA2BC paradigm. A battery of behavioral tests was administered to assess alterations in pain threshold, anxiety-like behaviors, locomotor activity, motor coordination, and cognition. Ethanol consumption and preference were monitored during each session. Moreover, the liver, heart, and lung tissues were examined using pathological microscopy. RESULTS: The average (standard deviation) ethanol consumption of mice under the IA2BC paradigm increased dose-dependently to 5.1 (0.2), 8.7 (0.7), and 15.9 (0.8) g/kg/24 h with 5 %, 10 %, and 20 % ethanol, respectively. However, there is no significant difference in ethanol preference among all the ethanol groups. Chronic ethanol drinking caused hyperalgesia, cognitive impairment, and motor incoordination, but caused no changes in body temperature, locomotor activity, or anxiety-like behaviors. Minor histopathological alterations in the liver were detected; however, no major abnormal pathology was observed in the heart or lungs. CONCLUSION: These findings clarify the link between ethanol dosage and behavioral changes in mice over a 12-week IA2BC paradigm, thereby bridging the knowledge gap regarding the effects of chronic ethanol drinking on neurological disorders.

Risk Factors of Alcohol Use Disorders Among Inpatients with Schizophrenia: An Institutional-Based Cross-sectional Survey.

Objective: This study aimed to elucidate the risk factors associated with alcohol use disorders (AUDs) among inpatients with schizophrenia at a specialized mental hospital in Baoding city, China. Methods: This cross-sectional survey comprised 301 comorbid patients. Three binary logistic regression models were used to investigate the factors linked to AUDs in patients with schizophrenia. Propensity score matching analysis was conducted to validate inconsistent variables identified by the regression models. Results: Significant differences were observed between the comorbid and non-comorbid groups concerning sex (P < .001), disposition (P = .049), smoking habits (P < .001), place of residence (P = .010), family relationships (P = .002), family history of mental disorders (P = .008), history of alcoholism (P = .003), onset latency (P = .005), impulsivity (P < .001), suicide or self-injury history (P < .001), and obvious aggressive behavior (P < .001) in univariate analyses. The area under the curve values for the three regression models were 0.83 (P < .001), 0.80 (P < .001), and 0.81 (P < .001), respectively. Binary logistic regression and propensity score matching analyses indicated that introverted disposition, smoking, acute onset, impulsivity, and suicide or self-injury history were independent risk factors associated with AUDs in inpatients with schizophrenia with an odds ratio of > 1. Conclusion: Introverted disposition, smoking, acute onset, impulsivity, and suicide or self-injury history were independently associated with the AUDs in inpatients with schizophrenia. Future studies should prioritize longitudinal studies to discern the evolving dynamics of potential confounding risk factors.

Alcohol-related stigma within the UK veterinary profession.

BACKGROUND: Veterinarians have poorer mental health and have higher levels of alcohol consumption compared to the general population. This study aimed to explore perceptions and experiences of problem drinking within the veterinary profession in the UK. METHODS: Online semi-structured interviews were completed with multidisciplined practising veterinarians in the UK. The data were analysed using reflexive thematic analysis. RESULTS: Seventeen veterinarians were recruited. The participants were predominantly female (n = 15, 88%). Seven participants (41%) reported personal experience of problem drinking. Four main themes were identified: a normalised culture of drinking, the impact of drinking on mental health and suicide risk, perceptions and attitudes towards problem drinking, and impacts of formal intervention. Drinking to cope was normalised and widespread among veterinarians. Problem drinking was reported to negatively impact mental health and provoke high self-stigma. Both alcohol-related stigma and fear of involvement from the Royal College of Veterinary Surgeons (RCVS) were barriers to help-seeking. LIMITATIONS: No other veterinary professionals or participants with lived experience of RCVS investigation for problem drinking were included. CONCLUSION: Alcohol-related stigma and fear of RCVS involvement reduce veterinary help-seeking for problem drinking, which may have a negative effect on veterinarians' mental health.

Default mode network aberrance in subjects of alcohol and opioid use disorders during working memory task: An exploratory EEG microstates study.

Background: Aberrance in switching from default mode network (DMN) to fronto-parietal network (FPN) is proposed to underlie working memory deficits in subjects with substance use disorders, which can be studied using neuro-imaging techniques during cognitive tasks. The current study used EEG to investigate pre-stimulus microstates during the performance of Sternberg's working memory task in subjects with substance use disorders. Methods: 128-channel EEG was acquired and processed in ten age and gender-matched subjects, each with alcohol use disorder, opioid use disorder, and controls while they performed Sternberg's task. Behavioral parameters, pre-stimulus EEG microstate, and underlying sources were analyzed and compared between subjects with substance use disorders and controls. Results: Both alcohol and opioid use disorder subjects had significantly lower accuracy (P < 0.01), while reaction times were significantly higher only in subjects of alcohol use disorder compared to controls (P < 0.01) and opioid use disorder (P < 0.01), reflecting working memory deficits of varying degrees in subjects with substance use disorders. Pre-stimulus EEG microstate revealed four topographic Maps 1-4: subjects of alcohol and opioid use disorder showing significantly lower mean duration of Map 3 (visual processing) and Map 2 (saliency and DMN switching), respectively, compared to controls (P < 0.05). Conclusion: Reduced mean durations in Map 3 and 2 in subjects of alcohol and opioid use disorder can underlie their poorer performance in Sternberg's task. Furthermore, cortical sources revealed higher activity in both groups of substance use disorders in the parahippocampal gyrus- a hub of DMN; superior and middle temporal gyri associated with impulsivity; and insula that maintains balance between executive reflective system and impulsive system. EEG microstates can be used to envisage neural underpinnings implicated for working memory deficits in subjects of alcohol and opioid use disorders, reflected by aberrant switching between neural networks and information processing mechanisms.

Alcohol use disorder research in India: An update.

Background: Despite alcohol use being a risk factor for numerous health-related conditions and alcohol use disorder (AUD) recognized as a disease, there was limited research in India until 2010. This narrative review aims to evaluate AUD-related research in India from 2010 to July 2023. Methods: A PubMed search used key terms for AUD in India after 2010. Indian and international journals with regional significance that publish alcohol-related research were searched by each author individually. These were then collated, and duplicates were removed. In addition, we also conducted a gray literature search on focused areas related to AUD. Results: The alcohol-related research in India after 2010 focused on diverse areas associated with alcohol use. Some areas of research have received more attention than others. Two major epidemiological surveys conducted in the past decade reveal that around 5% have a problematic alcohol use pattern. Factors associated with alcohol use, like genetic, neurobiological, psychological, and sociocultural, were studied. The studies focused on the clinical profile of AUD, including their correlates, such as craving, withdrawal, alcohol-related harm, and comorbid psychiatric and medical illnesses. During this period, minimal research was conducted to understand AUD's laboratory biomarkers, course, and prognosis. While there was a focus on generating evidence for different psychological interventions for alcohol dependence in management-related research, pharmacological studies centered on anticraving agents like baclofen. Research on noninvasive brain stimulation, such as rTMS, has shown preliminary usefulness in treating alcohol dependence. Very little research has been conducted regarding alcohol policy. Conclusion: In the past decade, Indian research on alcohol has focused on diverse areas. Epidemiological and psychological management-related research received maximum attention. Considering the magnitude of the alcohol-related burden, it is essential to prioritize research to other less studied areas like pharmacological management of alcohol dependence and alcohol policy.

Irresponsibility Stereotypes Exacerbate Effects of Sexual Violence on Cisgender Bisexual Women's Coping Drinking Motives.

OBJECTIVE: Bisexual women experience disparities in alcohol use outcomes compared to both lesbian and heterosexual women. Bisexual women also experience higher rates of sexual violence (SV) and alcohol use following SV. We examined whether coping drinking motives mediate the link between adult SV severity and alcohol use and whether dimensions of binegativity (i.e., hostility, instability, irresponsibility) moderate the effects of SV. METHOD: The sample consisted of 355 young (ages 18-35) cisgender bisexual women drinkers (Mage=25.8, 84.2% White) recruited via MTurk. Measures included: Sexual Experiences Survey-Short Form Victimization (Koss et al., 2007), Anti-Bisexual Experiences Scale (Brewster & Moradi, 2010), Modified Drinking Motives Questionnaire-Revised (Grant et al., 2007), and Alcohol Use Disorders Identification Test Consumption subscale (Babor et al., 2001). The PROCESS macro for SPSS was used. RESULTS: There was an interaction between SV severity and irresponsibility stereotypes in predicting coping motives. SV severity related to greater coping motives at mean and high, but not low, levels of irresponsibility stereotypes. Indirect effects of SV severity on alcohol use via coping motives were significant at mean and high, but not low, levels of irresponsibility stereotypes. Hostility and instability dimensions of binegativity did not interact with SV severity in predicting coping motives. CONCLUSIONS: Results identified SV severity and irresponsibility stereotypes as compounding experiences that may explain greater alcohol use. Bisexual women exposed to this dimension of binegativity may be particularly vulnerable to drink alcohol to cope with distress following SV. Interventions for alcohol use may be enhanced by helping bisexual women cope with SV-related distress and irresponsibility stereotypes.

An Integrative Model of Alcohol-Facilitated Intimate Partner Aggression Perpetration in Sexual and Gender Diverse Couples.

OBJECTIVE: Sexual and gender diverse (SGD) individuals are at heightened risk for intimate partner aggression (IPA) perpetration relative to their heterosexual and cisgender peers. Alcohol is a well-established cause of IPA perpetration in cisgender, heterosexual couples; however, minimal research has investigated the alcohol-IPA perpetration link in SGD couples. The relative lack of work in this area is a major barrier to addressing this health disparity. SGD individuals experience unique stressors related to their and/or their partner's intersecting minoritized identities that are critical to understanding alcohol-IPA etiology and informing culturally affirming intervention programming. METHOD: We advance prior work by members of the authorship team (see Parrott et al., 2023a; Shorey et al., 2019) to propose an integrative theoretical model that invokes (1) the I3 Model to organize risk and resilience factors at the individual and dyadic level, and (2) Alcohol Myopia Theory to explain the mechanism by which proximal alcohol use facilitates IPA as a function of individual differences in those factors. RESULTS: This integrative model provides a framework to understand how the confluence of stigma, minority stressors, proximal alcohol use, and other factors contribute to IPA perpetration in SGD couples. DISCUSSION: Application of this integrative model has potential to facilitate more rigorous research (e.g., intensive longitudinal designs, dyadic analysis) focused on putative risk and resilience factors across the social ecology. Further, the model provides guidance for intervention development by identifying how individual (e.g., minority stress), relationship (e.g., relationship functioning), and structural factors (e.g., SGD stigma) interactively contribute to alcohol-facilitated IPA perpetration.

Greater ventral striatal functional connectivity in cigarette smokers relative to non-smokers across a spectrum of alcohol consumption.

Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing. Although the high comorbidity of cigarette smoking with drinking behaviors may collectively affect brain activity, there could be independent effects of smoking in alcohol use disorder that impact brain function and behavior. We hypothesized that smoking status, independent of alcohol use, would be associated with aberrations of nucleus accumbens functional connectivity to brain regions that facilitate reward processing, salience attribution, and inhibitory control. Resting state functional magnetic resonance imaging data from thirty-one nonsmokers and nineteen smoking individuals were analyzed using seed-based correlations of the bilateral accumbens with all other brain voxels. Statistical models accounted for drinks consumed per week. The smoking group demonstrated significantly higher functional connectivity between the left accumbens and the bilateral insula and anterior cingulate cortex, as well as hyperconnectivity between the right accumbens and the insula. Confirmatory analyses using the insula and cingulate clusters generated from the original analysis as seed regions reproduced the hyperconnectivity in smokers between the bilateral insular regions and the accumbens. In conclusion, smoking status had distinct effects on neural activity; hyperconnectivity between the accumbens and insula in smokers may reflect enhanced encoding of the reinforcing effects of smoking and greater orientation toward smoking-associated stimuli.

Substance Use Among Illinois Farmers.

BACKGROUND:  People in agriculture face unique stressors and occupational hazards, and relatively little is known about substance use in this population. The purpose of this study was to describe substance use among farmers in Illinois. METHODS:  We conducted a mail survey of Illinois farmers that included the Brief ASSIST to assess substance use for lifetime and past three-month use of ten different substances. The survey also included questions about farming characteristics, mental health, stress, coping, social support, and demographic characteristics. We used chi-square and non-parametric tests to assess group differences. RESULTS:  Alcohol, tobacco, cannabis, and sedatives were most reported as used for a lifetime and in the past three months. About three-quarters of the sample had recently used alcohol. Recent tobacco use was associated with not being married, less education, and less concern about climate-related farm stress. Recent sedative use was associated with greater concern about isolation-related farm stress. People who reported multiple substance use were at a greater risk for suicide and were more likely to meet the criteria for generalized anxiety disorder. None of the participants reported recent use of cocaine, heroin, inhalants, or hallucinogens. CONCLUSION:  Specific social and cultural aspects of farming and farm communities may contribute to substance use among people working in agriculture. Future research can help to better understand this intersection and make recommendations for programs and resources to promote adaptive coping strategies.

Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C).

INTRODUCTION: Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy. METHODS: Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self-report (≥40 g/day of ethanol), physician-reported history of problematic alcohol use, and anti-craving medication prescription via population-based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression. RESULTS: Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician-reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty-three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted-odds ratio 1.69, 95% confidence interval 1.32-2.17) and patients were over-represented for cirrhosis (45.1% vs. 25.6% in no-risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2-year survival (adjusted-hazard ratio 1.98, 95% confidence interval 0.84-4.63) after DAA therapy were not associated with risky alcohol use. DISCUSSION AND CONCLUSIONS: Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under-recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this.

The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels.

BACKGROUND: Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients. METHODS: Thirty-nine male and female AUD patients were grouped by normal [≥71 µg/dL (Group 1, number (n) = 26)] and low [<71 µg/dL (Group 2, n = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers. RESULTS: Group 2 females exhibited lower LTDH than Group 2 males (p = 0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (p = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (p = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (R2 = 0.633, p = 0.037). CONCLUSION: Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.

Modelling alcohol consumption in rodents using two-bottle choice home cage drinking and optional lickometry-based microstructural analysis.

Two-bottle choice home cage drinking is one of the most widely used paradigms to study ethanol consumption in rodents. In its simplest form, animals are provided with access to two drinking bottles, one of which contains regular tap water and the other ethanol, for 24 hr/day with daily intake measured via change in bottle weight over the 24 hr period. Consequently, this approach requires no specialized laboratory equipment. While such ease of implementation is likely the greatest contributor to its widespread adoption by preclinical alcohol researchers, the resolution of drinking data acquired using this approach is limited by the number of times the researcher measures bottle weight (e.g., once daily). However, the desire to examine drinking patterns in the context of overall intake, pharmacological interventions, and neuronal manipulations has prompted the development of home cage lickometer systems that can acquire data at the level of individual licks. Although a number of these systems have been developed recently, the open-source system, LIQ HD, has garnered significant attention in the field for its affordability and user friendliness. Although exciting, this system was designed for use in mice. Here, we review appropriate procedures for standard and lickometer-equipped two-bottle choice home cage drinking. We also introduce methods for adapting the LIQ HD system to rats including hardware modifications to accommodate larger cage size and a redesigned 3D printed bottle holder compatible with standard off-the-shelf drinking bottles. Using this approach, researchers can examine daily drinking patterns in addition to levels of intake in many rats in parallel thereby increasing the resolution of acquired data with minimal investment in additional resources. These methods provide researchers with the flexibility to use either standard bottles or a lickometer-equipped apparatus to interrogate the neurobiological mechanisms underlying alcohol drinking depending on their precise experimental needs.