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A growing body of evidence indicates the existence of abnormal local and long-range functional connection patterns in patients with alcohol use disorder (AUD). However, it has yet to be established whether AUD is associated with abnormal interhemispheric and intrahemispheric functional connection patterns. In the present study, we analysed resting-state functional magnetic resonance imaging data from 55 individuals with AUD and 32 healthy nonalcohol users. For each subject, whole-brain functional connectivity density (FCD) was decomposed into ipsilateral and contralateral parts. Correlation analysis was performed between abnormal FCD and a range of clinical measurements in the AUD group. Compared with healthy controls, the AUD group exhibited a reduced global FCD in the anterior and middle cingulate gyri, prefrontal cortex and thalamus, along with an enhanced global FCD in the temporal, parietal and occipital cortices. Abnormal interhemispheric and intrahemispheric FCD patterns were also detected in the AUD group. Furthermore, abnormal global, contralateral and ipsilateral FCD data were correlated with the mean amount of pure alcohol and the severity of alcohol addiction in the AUD group. Collectively, our findings indicate that global, interhemispheric and intrahemispheric FCD may represent a robust method to detect abnormal functional connection patterns in AUD; this may help us to identify the neural substrates and therapeutic targets of AUD., (© 2024 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Alcohol-associated hepatitis is an acute manifestation of alcohol-associated liver disease (ALD) and is associated with 30%-40% mortality at 28 days. Abstinence and corticosteroids are the mainstays of treatment, but the latter only improves short-term mortality, so new and improved therapies remain an unmet need., Aims: The aim was to review the pathophysiology of alcohol-associated hepatitis and how various targets can be used by current and emerging therapies as treatment., Methods: A thorough literature review was conducted on acute alcohol-associated hepatitis, current therapies and therapies under investigation., Results: With the increasing prevalence of alcohol use disorder and ALD, the burden of alcohol-associated hepatitis is also expected to rise. The current understanding of alcohol-associated hepatitis pathophysiology has led to clinical trials of several therapies involving IL-1 antagonism, modification of the gut microbiome and liver regeneration., Conclusions: Corticosteroid therapy for alcohol-associated hepatitis is restricted in its applicability and has limited efficacy. Developing multidisciplinary, patient-centred care models based on digital health technologies, in combination with continued discovery of novel therapies using multiomics data and computational biology techniques will be necessary to tackle the increasing burden of alcohol-associated hepatitis., (© 2022 John Wiley & Sons Ltd.)

The escalating burden of lifestyle‐related diseases stands as a critical global public health challenge, contributing substantially to the prevalence of chronic conditions and a large portion of premature mortality. Despite this, concise evidence‐based lifestyle interventions targeting physical inactivity, nutrition, alcohol and smoking continue to be underutilised. Although good evidence exists for addressing the four lifestyle‐related risk factors independently, rarely do these present in isolation. Evidence is lacking regarding how to integrate interventions targeting multiple risk factors. Consequently, this paper aims to provide an overview of the evidence for delivering multiple interventions in primary healthcare settings. Different lifestyle factors are inter‐related, with decisions around ordering of the delivery of multiple lifestyle interventions an important consideration. There is evidence supporting the effectiveness of addressing some lifestyle factors simultaneously (e.g., physical activity and nutrition), although smoking cessation may be delivered best in a sequential approach. While the World Health Organisation highlights four key lifestyle factors (nutrition, physical activity, alcohol and smoking), incorporating additional elements such as sleep, mental well‐being and social connectedness offers a holistic framework for promoting well‐being. Despite the presentation of multiple behaviour risk factors being commonplace in healthcare settings, the evidence (outlined in the paper) for how best to deliver interventions to address this is limited, with further research and subsequent clinical guidance required. In order to address the barriers to delivering lifestyle interventions in primary care, innovation will be required. The use of non‐medical personnel, social prescribers and health coaches has the potential to alleviate time constraints, whilst mounting evidence exists for group consultations for addressing lifestyle‐related non‐communicable diseases (NCDs). If the challenges to implementation can be addressed, and if healthcare systems can adapt for the promotion of healthy lifestyles, the impact of NCDs can be mitigated. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic-assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4-12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5-MeO-DMT. Primarily, 5-MeO-DMT is able to induce mystical experiences and ego-dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood-related comorbidities consistent with the negative reinforcement and self-medication paradigms. In addition, preliminary evidence indicates that 5-MeO-DMT modulates neural oscillations that might subserve ego-dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5-MeO-DMT is characterized by neuroplasticity, anti-inflammation, 5-HT 2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood-related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action., (© 2024 The Author. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Problems associated with alcohol use are multidimensional with psychiatric, psychological, physical, and social aspects, which makes it challenging to choose appropriate assessment scales. However, there has been no systematic evaluation of existing alcohol scales. Methods: A systematic literature search was conducted for articles that assessed the psychometric properties of scales for alcohol use disorder on March 19, 2023, using Medline, EMBASE, and PsycINFO. Only scales whose original development papers were cited more than 20 times were included. The methodological quality and psychometric properties of the scales were evaluated using COnsensus‐based Standards for the selection of health Measurement INstruments. The overall rating of the scales were assessed with a score ranging from 0 to 18. Results: In total, 314 studies and 40 scales were identified. These scales differ widely in measurement methods, target populations, and psychometric properties. The overall mean score was 6.3, and only the following three scales received >9 points suggesting a moderate level of evidence: Alcohol Use Disorders Identification Test (AUDIT), Alcohol Dependence Scale (ADS), and Short Alcohol Dependence Data Questionnaire (SADD). Measurement error and responsiveness were not evaluated or reported in the included scales. Conclusions: Although the AUDIT, ADS, and SADD were rated the highest among the 40 scales, they showed, at most, a moderate level of evidence. These findings underscore the need to accumulate further evidence to assure the quality of the scales. It may be advisable to select and combine scales to meet the purpose of the assessment. [ABSTRACT FROM AUTHOR]

This paper documents a longitudinal crisis of midlife among the inhabitants of rich nations. Yet middle‐aged citizens in our datasets are close to their peak earnings, have typically experienced little or no illness, reside in some of the safest countries in the world, and live in the most prosperous era in human history. This is paradoxical and troubling. The finding is consistent, however, with the prediction—one little‐known to economists—of Elliott Jaques (1965). Our analysis does not rest on elementary cross‐sectional analysis. Instead, the paper uses panel and through‐time data on, in total, approximately 500,000 individuals. It checks that the key results are not due to cohort effects. Nor do we rely on simple life satisfaction measures. The paper shows that there are approximately quadratic hill‐shaped patterns in data on midlife suicide, sleeping problems, alcohol dependence, concentration difficulties, memory problems, intense job strain, disabling headaches, suicidal feelings, and extreme depression. We believe that the seriousness of this societal problem has not been grasped by the affluent world's policy‐makers. This paper is part of the Economica 100 Series. Economica, the LSE "house journal" is now 100 years old. To commemorate this achievement, we are publishing 100 papers by former students, as well as current and former faculty. Andrew Oswald is Professor of Economics and Behavioural Science at the University of Warwick. He was previously a Senior Research Fellow at the LSE. [ABSTRACT FROM AUTHOR]

Background: Electroencephalography (EEG)-based electrophysiological techniques have made progress in diagnosing and treating alcohol dependence in recent years., Aims: The article reviews the latest literature in this field., Materials and Methods: Alcohol dependence, which is common and prone to relapsing, poses a serious threat to individuals, families, and society. At present, the objective detection methods for alcohol dependence in clinic are not enough. As electrophysiological techniques developed in psychiatry, some researches on EEG-based monitoring methods are of great significance in the diagnosis and treatment of alcohol dependence., Discussion: As electrophysiological techniques developed in psychiatry, some researches on EEG-based monitoring methods such as resting electroencephalography (REEG), event-related potentials (ERP), event-related oscillations (ERO), and polysomnography (PSG), was reported., Conclusion: In this paper, the status of electrophysiological researches on EEG in alcoholics are reviewed in detail., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Patient and public involvement and co‐production are widely used, but nevertheless contested concepts in applied health research. There is much confusion about what they are, how they might be undertaken and how they relate to each other. There are distinct challenges and particular gaps in public involvement in alcohol research, especially when the study focus is on health matters other than alcohol dependence. Objective: To explore how patient and public involvement and co‐production have been interpreted and applied within a multi‐disciplinary research programme in the development of a complex intervention on alcohol and medicine use in community pharmacies. Design: The paper presents the authors' critical reflection on a grounded example of how public involvement concepts have been translated into practice in the intervention development phase of a publicly funded research programme, noting its impact on the programme to date. Discussion: Co‐production adds another layer of complexity in the development of a complex intervention. The research planning requirements for publicly funded research circumscribe the possibilities for co‐production, including impacting on the possibility of stability and continuity over time. [ABSTRACT FROM AUTHOR]

Abstract: Aim: In this review, the author focused on anticraving therapy for alcohol use disorder (AUD) defined by DMS‐5. A comprehensive review was carried out on the available published papers on anticraving drugs for treating AUD patients. Methods: The author described all drugs with anticraving benefits for treating AUD patients approved by the Food and Drug Administration of the United States (US FDA) and European Medicines Agency of the European Union. Then, the commonly prescribed anticraving drugs and those under development were also described. Results: The US FDA‐approved anticraving drugs included acamprosate and naltrexone, and those approved by European Medicines Agency were gamma‐hydroxybutyrate and nalmefene. The author also highlighted topiramate, gabapentin, ondansetron, LY196044, ifenprodil, varenicline, ABT‐436, mifepristone, citicoline, and baclofen. The putative mechanisms of action of and the use in clinical practice of those anticraving drugs were also described. Conclusion: Although slowly developing, the field of anticraving drugs is getting into shape as a promising entity of a pharmaceutical class of drugs. Then, the author addressed on the underused issues of those recommended, and suggested anticraving drugs by the practice guideline of the American Psychiatric Association. The author urges that clinicians should be more “adventurous” in prescribing those promising drugs because benefits of those anticraving drugs are far‐outweighing the possible side effects of anticraving drugs, or the harms of untreated AUD itself. [ABSTRACT FROM AUTHOR]

Background: The development of alcohol dependence is associated with significant morbidity and mortality. For the majority of affected people the most appropriate goal, in terms of drinking behaviour, is abstinence from alcohol. Psychosocial intervention is the mainstay of the treatment but adjuvant pharmacotherapy is also available and its use recommended., Aim: To provide an updated analysis of current and potential pharmacotherapeutic options for the management of alcohol dependence. In addition, factors predictive of therapeutic outcome, including compliance and pharmacogenetics, and the current barriers to treatment, including doctors' unwillingness to prescribe these agents, will be explored., Methods: Relevant papers were selected for review following extensive, language- and date-unrestricted, electronic and manual searches of the literature., Results: Acamprosate and naltrexone have a substantial evidence base for overall efficacy, safety and cost-effectiveness while the risks associated with the use of disulfiram are well-known and can be minimised with appropriate patient selection and supervision. Acamprosate can be used safely in patients with liver disease and in those with comorbid mental health issues and co-occurring drug-related problems. A number of other agents are being investigated for potential use for this indication including: baclofen, topiramate and metadoxine., Conclusion: Pharmacotherapy for alcohol dependence has been shown to be moderately efficacious with few safety concerns, but it is substantially underutilised. Concerted efforts must be made to remove the barriers to treatment in order to optimise the management of people with this condition., (© 2017 John Wiley & Sons Ltd.)

Introduction: We sought to characterize social and structural drivers of HIV vulnerability for transgender women (TGW) in Zimbabwe, where TGW are not legally recognized, and explore differences in vulnerability by feminine presentation. Methods: A secondary analysis was conducted with a sub‐sample of participants recruited from a 2019 respondent‐driven sampling survey that comprised men who have sex with men, TGW and genderqueer individuals assigned male sex at birth, from two cities in Zimbabwe. Survey questionnaires captured information related to socio‐demographics, sexual and substance use behaviours, and social and structural barriers to HIV services. Secondary analyses were restricted to participants who identified as female, transfemale or transwomen (236/1538) and were unweighted. Descriptive statistics were used to calculate sample estimates and chi‐square and Fisher's exact tests were used to assess differences in vulnerability by feminine presentation. Results: Among 236 TGW, almost half (45.3%) presented as feminine in the 6 months preceding the survey and 8.5% had ever used hormones to affirm their gender identities. Median age among TGW was 23 years (interquartile range: 20–26). Feminine presenting TGW in our sample had higher prevalence of arrest (15.9% vs. 3.9%), rejection by family/friends (38.3% vs. 14.0%), employment termination (11.2% vs. 3.9%), employment refusal (14.0% vs. 3.9%), denial of healthcare (16.8% vs. 2.3%), physical, sexual or verbal harassment or abuse (59.8% vs. 34.1%), alcohol dependence (32.7% vs. 12.4%), recent transactional sex with a male or TGW partner (30.8% vs. 13.3%) and recent non‐injection drug use (38.3% vs. 20.2%) than non‐feminine presenting TGW (all p‐value <0.05). Conclusions: Findings suggest that TGW, particularly feminine presenting TGW, experience social and structural inequities which may contribute to HIV vulnerability. Interventions aimed at addressing inequities, including trans competency training for providers and gender‐affirming, psychosocial and legal support services for TGW, might mitigate risk. [ABSTRACT FROM AUTHOR]

This paper shows that the quadratic shape of the Engel curve for alcohol is induced by preference heterogeneity between drinkers and abstainers in a Japanese data set. With controlling the heterogeneity, it is shown that the Engel curve for alcohol slopes monotonically downwards for drinkers, and that the probability of being a drinker is an increasing function of total expenditure. These two relationships generate a quadratic shape for the Engel curve for alcohol. Other goods in this data set appear to have nearly linear Engel curves, so if the alcohol Engel curve for drinkers is also linear, then after controlling for this preference heterogeneity the rank of this demand system would be two. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Based on data from the 1988 Alcohol Supplement of the National Health Interview Survey, Mullahy and Sindelar (1996) (M&S) find, for both men and women, that alcohol abuse results in reduced employment and increased unemployment. The estimates from which they drew these interferences were obtained via the instrumental variables (IV) method, which was implemented in order to account for the potential endogeneity of problem drinking. Though these IV estimates qualitatively supported the prior expectation that problem drinking damages individuals' labour market prospects, they were not found to be statistically significant. The present paper revisits this research and offers a estimation method which, in addition to accounting for endogeneity, explicitly allows for the inherent non-linearity of the underlying regression structure. The new method is applied to the same data and variable specifications as those used by M&S for the male subpopulation. Consistent with their results, problem drinking is found to have a positive effect on the probability of unemployment and negative effect on the likelihood of being employed. Unlike their result, however, the latter estimate is statistically significant. An appealing feature of the new method is that it accommodates the likely possibility that alcohol abuse effects are heterogeneous with respect to the observed and unobserved characteristics of individuals in the population. To illustrate this fact, abuse effects are computed for two widely differing subgroups of the population. The large differential between the estimated effects for these two subpopulations demonstrates the potential importance of accounting for heterogeneity. [ABSTRACT FROM AUTHOR]

Tolerance occurs when, following an initial experience with a substance, more of the substance is required subsequently to induce identical behavioral effects. Tolerance is not well‐understood, and numerous researchers have turned to model organisms, particularly Drosophila melanogaster, to unravel its mechanisms. Flies have high translational relevance for human alcohol responses, and there is substantial overlap in disease‐causing genes between flies and humans, including those associated with Alcohol Use Disorder. Numerous Drosophila tolerance mutants have been described; however, approaches used to identify and characterize these mutants have varied across time and labs and have mostly disregarded any impact of initial resistance/sensitivity to ethanol on subsequent tolerance development. Here, we analyzed our own, as well as data published by other labs to uncover an inverse correlation between initial ethanol resistance and tolerance phenotypes. This inverse correlation suggests that initial resistance phenotypes can explain many 'perceived' tolerance phenotypes, thus classifying such mutants as 'secondary' tolerance mutants. Additionally, we show that tolerance should be measured as a relative increase in time to sedation between an initial and second exposure rather than an absolute change in time to sedation. Finally, based on our analysis, we provide a method for using a linear regression equation to assess the residuals of potential tolerance mutants. These residuals provide predictive insight into the likelihood of a mutant being a 'primary' tolerance mutant, where a tolerance phenotype is not solely a consequence of initial resistance, and we offer a framework for understanding the relationship between initial resistance and tolerance. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) and related health conditions result from a complex interaction of genetic, neural and environmental factors, with differential impacts across the lifespan. From its inception, the Collaborative Study on the Genetics of Alcoholism (COGA) has focused on the importance of brain function as it relates to the risk and consequences of alcohol use and AUD, through the examination of noninvasively recorded brain electrical activity and neuropsychological tests. COGA's sophisticated neurophysiological and neuropsychological measures, together with rich longitudinal, multi‐modal family data, have allowed us to disentangle brain‐related risk and resilience factors from the consequences of prolonged and heavy alcohol use in the context of genomic and social‐environmental influences over the lifespan. COGA has led the field in identifying genetic variation associated with brain functioning, which has advanced the understanding of how genomic risk affects AUD and related disorders. To date, the COGA study has amassed brain function data on over 9871 participants, 7837 with data at more than one time point, and with notable diversity in terms of age (from 7 to 97), gender (52% female), and self‐reported race and ethnicity (28% Black, 9% Hispanic). These data are available to the research community through several mechanisms, including directly through the NIAAA, through dbGAP, and in collaboration with COGA investigators. In this review, we provide an overview of COGA's data collection methods and specific brain function measures assessed, and showcase the utility, significance, and contributions these data have made to our understanding of AUD and related disorders, highlighting COGA research findings. [ABSTRACT FROM AUTHOR]

Alcohol Use Disorder is a complex genetic disorder, involving genetic, neural, and environmental factors, and their interactions. The Collaborative Study on the Genetics of Alcoholism (COGA) has been investigating these factors and identified putative alcohol use disorder risk genes through genome‐wide association studies. In this review, we describe advances made by COGA in elucidating the functional changes induced by alcohol use disorder risk genes using multimodal approaches with human cell lines and brain tissue. These studies involve investigating gene regulation in lymphoblastoid cells from COGA participants and in post‐mortem brain tissues. High throughput reporter assays are being used to identify single nucleotide polymorphisms in which alternate alleles differ in driving gene expression. Specific single nucleotide polymorphisms (both coding or noncoding) have been modeled using induced pluripotent stem cells derived from COGA participants to evaluate the effects of genetic variants on transcriptomics, neuronal excitability, synaptic physiology, and the response to ethanol in human neurons from individuals with and without alcohol use disorder. We provide a perspective on future studies, such as using polygenic risk scores and populations of induced pluripotent stem cell‐derived neurons to identify signaling pathways related with responses to alcohol. Starting with genes or loci associated with alcohol use disorder, COGA has demonstrated that integration of multimodal data within COGA participants and functional studies can reveal mechanisms linking genomic variants with alcohol use disorder, and potential targets for future treatments. [ABSTRACT FROM AUTHOR]

The collaborative study on the genetics of alcoholism (COGA) is a multi‐site, multidisciplinary project with the goal of identifying how genes are involved in alcohol use disorder and related outcomes, and characterizing how genetic risk unfolds across development and in conjunction with the environment and brain function. COGA is a multi‐generational family‐based study in which probands were recruited through alcohol treatment centers, along with a set of community comparison families. Nearly 18,000 individuals from >2200 families have been assessed over a period of over 30 years with a rich phenotypic battery that includes semi‐structured psychiatric interviews and questionnaire measures, along with DNA collection and electrophysiological data on a large subset. Participants range in age from 7 to 97, with many having longitudinal assessments, providing a valuable opportunity to study alcohol use and problems across the lifespan. Here we provide an overview of data collection methods for the COGA sample, and details about sample characteristics and comorbidity. We also review key research findings that have emerged from analyses of the COGA data. COGA data are available broadly to researchers, and we hope this overview will encourage further collaboration and use of these data to advance the field. [ABSTRACT FROM AUTHOR]

This review describes the genetic approaches and results from the family‐based Collaborative Study on the Genetics of Alcoholism (COGA). COGA was designed during the linkage era to identify genes affecting the risk for alcohol use disorder (AUD) and related problems, and was among the first AUD‐focused studies to subsequently adopt a genome‐wide association (GWAS) approach. COGA's family‐based structure, multimodal assessment with gold‐standard clinical and neurophysiological data, and the availability of prospective longitudinal phenotyping continues to provide insights into the etiology of AUD and related disorders. These include investigations of genetic risk and trajectories of substance use and use disorders, phenome‐wide association studies of loci of interest, and investigations of pleiotropy, social genomics, genetic nurture, and within‐family comparisons. COGA is one of the few AUD genetics projects that includes a substantial number of participants of African ancestry. The sharing of data and biospecimens has been a cornerstone of the COGA project, and COGA is a key contributor to large‐scale GWAS consortia. COGA's wealth of publicly available genetic and extensive phenotyping data continues to provide a unique and adaptable resource for our understanding of the genetic etiology of AUD and related traits. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to develop a Service Capacity Index for Substance Use Disorders (SCI‐SUD) that would reflect the capacity of national health systems to provide treatment for alcohol and drug use disorders, in terms of the proportion of available service elements in a given country from a theoretical maximum. Methods: Data were collected through the WHO Global Survey on Progress with Sustainable Development Goals (SDG) Health Target 3.5, conducted between December 2019 and July 2020 to produce the SCI‐SUD, based on 378 variables overall. Results: The SCI‐SUD was directly derived for 145 countries. We used multiple imputation to produce comparable SCI‐SUD estimates for countries that did not submit data (40 countries) or had very high level of missingness (9 countries). The final SCI‐SUD demonstrates considerable consistency and internal stability and is strongly associated with the macro‐level economic, healthcare‐related and epidemiologic (such as prevalence rates) variables. Conclusion: The presented methodology represents a step forward in monitoring the global situation in regard to the development of treatment systems for SU disorders, however, further work is warranted to improve the external validity of the measure (e.g., in‐depth data generation in countries) and ensure its feasibility for regular reporting (e.g., reducing the number of variables). [ABSTRACT FROM AUTHOR]

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole‐brain, voxel‐based, multi‐tissue mega‐analytic approach, thereby extending our recent surface‐based region of interest findings on a nearly matching sample using a complementary methodological approach. T1‐weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel‐based morphometry. The effects of group, sex, group‐by‐sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group‐by‐sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group‐by‐sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo‐occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD. [ABSTRACT FROM AUTHOR]

Eugenics in most western countries in the first four decades of the 20th century was based on the idea that genes control most human phenotypic traits, everything from physical features such as polydactyly and eye colour to physiological conditions such as the A-B-O blood groups to mental and personality traits such as 'feeblemindedness,' alcoholism and pauperism. In assessing the development of the eugenics movement-its rise and decline between 1900 and 1950-it is important to recognise that its naïve assumptions and often flawed methodologies were openly criticised at the time by scientists and nonscientists alike. This paper will present a brief overview of the critiques launched against eugenicists' claims, particularly criticisms of the American school led by Charles B. Davenport. Davenport's approach to eugenics will be contrasted to his British counterpart, Karl Pearson, founder and first editor of the Annals of Eugenics. It was not the case that nearly everyone in the early 20th century accepted eugenic conclusions as the latest, cutting-edge science. There are lessons from this historical approach for dealing with similar naïve claims about genetics today. [ABSTRACT FROM AUTHOR]

This paper develops dialogue between geographers’ engagement with emotion, embodiment and affect, and geographical research on alcohol, drinking and drunkenness. In doing so, we focus on the long-running ‘moral panic’ relating to alcohol-related violence, disorder and drunken behaviour in urban public space. We argue there has been an ontological and epistemological impasse in ‘alcohol studies’ between approaches that have considered the biological, physiological and psychological impacts of alcohol consumption and those focused on social and cultural practices. While there has been an artificial separation, and hence under-theorisation of the relationships between emotions, embodiment, affect and everyday uses of alcohol, we develop an argument that signals the possibilities of a more nuanced and sophisticated approach. We present empirical research from the UK and offer theoretical, methodological and policy-relevant conclusions. [ABSTRACT FROM AUTHOR]

Parametric linkage analysis of simultaneous mapping of the two disease loci of a qualitative trait governed by a two-locus model has been shown to provide greater power in detecting linkage than standard lod-score analysis that maps a single disease locus. Despite its great potential for power gains, two-locus parametric analysis has not been used routinely in disease gene mapping. due to the computational intensity of currently available methods and programs. In this paper, we propose a Markov chain Monte Carlo (MCMC) method for performing lod-score analysis of qualitative traits governed by two-locus models. This method obtains lod-score estimates that can be arbitrarily close to their corresponding exact values. The algorithm implementing this MCMC method is linear in the number of markers. This feature enables us to perform two-locus analysis mapping each trait to a set of markers, instead of just to a single marker. We analyzed an alcohol dependence dataset composed of 105 pedigrees with various sizes and various degrees of missingness in the observed marker and disease data. The estimates from our MCMC procedure match up well with the lod scores from exact analysis, but it took much less time for the MCMC procedure to obtain the results. We also performed a simulation study to investigate power gains with additional markers. Our results indicate that an additional marker on each map can provide a great deal more information for linkage measured in terms of the magnitude of lod scores.

Interval-specific congenic strains (ISCS) allow fine mapping of a quantitative trait locus (QTL), narrowing its confidence interval by an order of magnitude or more. In earlier work, we mapped four QTL specifying differential ethanol sensitivity, assessed by loss of righting reflex because of ethanol (LORE), in the inbred long-sleep (ILS) and inbred short-sleep (ISS) strains, accounting for approximately 50% of the genetic variance for this trait. Subsequently, we generated reciprocal congenic strains in which each full QTL interval from ILS was bred onto the ISS background and vice versa. An earlier paper reported construction and results of the ISCS on the ISS background; here, we describe this process and report results on the ILS background. We developed multiple ISCS for each Lore QTL in which the QTL interval was broken into a number of smaller intervals. For each of the four QTL regions (chromosomes 1, 2, 11 and 15), we were successful in reducing the intervals significantly. Multiple, positive strains were overlapped to generate a single, reduced interval. Subsequently, this reduced region was overlaid on previous reductions from the ISS background congenics, resulting in substantial reductions in all QTL regions by approximately 75% from the initial mapping study. Genes with sequence or expression polymorphisms in the reduced intervals are potential candidates; evidence for these is presented. Genetic background effects can be important in detection of single QTL; combining this information with the generation of congenics on both backgrounds, as described here, is a powerful approach for fine mapping QTL. [ABSTRACT FROM AUTHOR]

A number of philosophers have argued that alcoholics should receive lower priority for liver transplantations because they are morally responsible for their medical conditions. In this paper, I argue that this conclusion is false. Moral responsibility should not be used as a criterion for the allocation of medical resources. The reason I advance goes further than the technical problem of assessing moral responsibility. The deeper problem is that using moral responsibility as an allocation criterion undermines the functioning of medicine. [ABSTRACT FROM AUTHOR]

This paper explores Drueulu women's engagement in an organized collectivity during the late 1980s and early 1990s. I focus particularly on the Drueulu Women's Group, a group affiliated to the umbrella Catholic organization, mouvement féminin vers un Souriant Village Mé1anésien (mfSVM), to illustrate how these women mobilized cultural elements, including customary bonds, religious affiliation, and maternal relations, to assert their agency and empowerment. To move beyond a given and unchanging representation of Lifouan men and women means bringing to the fore multiple changing identities which are negotiated in different times and places. This does not mean privileging localism over national commonalities. By examining a 1990 protest march against alcohol abuse by men, I attest to the various articulations of women's concerns, customary linkages, and denominational affiliation which informed women's agenda at the village level. I then consider how these configurations were articulated in the 1992 annual general assembly of the mfSVM when 200 women gathered in Drueulu from all over the country for the twentieth anniversary of the movement. In the wider social settings here examined, the ubiquitous metaphorical use of maternal tropes gained strategic efficacy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Drugs of abuse, including alcohol, increase dopamine in the mesocorticolimbic system via actions on dopamine neurons in the ventral tegmental area (VTA). Increased dopamine transmission can activate inhibitory G protein signalling pathways in VTA dopamine neurons, including those controlled by GABAB and D2 receptors. Members of the R7 subfamily of regulator of G protein signalling (RGS) proteins can regulate inhibitory G protein signalling, but their influence on VTA dopamine neurons is unclear. Here, we investigated the influence of RGS6, an R7 RGS family memberthat has been implicated in the regulation of alcohol consumption in mice, on inhibitory G protein signalling in VTA dopamine neurons. Experimental Approach: We used molecular, electrophysiological and genetic approaches to probe the impact of RGS6 on inhibitory G protein signalling in VTA dopamine neurons and on binge‐like alcohol consumption in mice. Key Results: RGS6 is expressed in adult mouse VTA dopamine neurons and it modulates inhibitory G protein signalling in a receptor‐dependent manner, tempering D2 receptor‐induced somatodendritic currents and accelerating deactivation of synaptically evoked GABAB receptor‐dependent responses. RGS6−/− mice exhibit diminished binge‐like alcohol consumption, a phenotype replicated in female (but not male) mice lacking RGS6 selectively in VTA dopamine neurons. Conclusions and Implications: RGS6 negatively regulates GABAB‐ and D2 receptor‐dependent inhibitory G protein signalling pathways in mouse VTA dopamine neurons and exerts a sex‐dependent positive influence on binge‐like alcohol consumption in adult mice. As such, RGS6 may represent a new diagnostic and/or therapeutic target for alcohol use disorder. [ABSTRACT FROM AUTHOR]

Background and Purpose: A major problem managing alcohol use disorder is the high vulnerability to relapse, even after long periods of abstinence. Chronic alcohol use dysregulates stress responsivity, rendering this system hyporesponsive and making individuals vulnerable to relapse. Orexin (hypocretin) plays a role in diverse physiological processes, including stress. Orexin neurons in the hypothalamus, project to the infralimbic cortex. This study asked does infralimbic cortex orexin transmission play a significant role in stress‐induced reinstatement of alcohol‐seeking behaviour in alcohol‐dependent rats. Experimental Approach: Male and female rats were trained to self‐administer 10% alcohol (3 weeks) and then made dependent via chronic intermittent alcohol vapour exposure. Following extinction (5 days·week−1 at 8 h abstinence for 10 sessions), rats received an intra‐ infralimbic cortex microinfusion of the OX1/2 antagonist TCS 1102 (15 μg/0.5 μl per side) and then tested for footshock stress‐induced reinstatement of alcohol seeking. In a separate cohort, orexin regulation of infralimbic cortex neuronal activity at the time of reinstatement was investigated using ex vivo electrophysiology. Key Results: TCS 1102 prevented reinstatement in dependent animals only. Moreover, Hcrtr mRNA expression in the hypothalamus and Hcrtr1/2 in the infralimbic cortex increased in alcohol‐dependent animals at the time of testing. Dependence dampened basal orexin/OX receptor influence over infralimbic cortex GABAergic synapses (using TCS 1102) allow for greater stimulated orexin effects. Conclusion and Implications: Infralimbic cortex transmission is implicate in stress‐induced reinstatement of alcohol‐seeking behaviour in subjects with a history of alcohol dependence and show maladaptive recruitment of infralimbic cortex transmission by alcohol dependence. [ABSTRACT FROM AUTHOR]

The association between deprivation and accidental dwelling fire injuries was examined in Merseyside which has a high proportion of deprived areas. For the years 2006 to 2016, over half of the accidental dwelling fire injuries in Merseyside occurred in deprived areas, and almost three quarters of alcohol and drug related accidental dwelling fire injuries occurred in such areas. In particular, we examine the relationship between the established accidental dwelling fire injury risk factors of old age, disability and alcohol and drug consumption and the level of deprivation. There were strong correlations between deprivation and the overall number of fire injuries, and between deprivation and fire injuries relating to alcohol/drug consumption, disability/mobility related fire injuries, and fire injuries sustained by those aged 65+. [ABSTRACT FROM AUTHOR]

Background: Although alcohol use disorder is a complex human pathology, the use of animal models represents an opportunity to study some aspects of this pathology. One of the most used paradigms to study the voluntary alcohol consumption in rodents is operant self‐administration (OSA). Aims: In order to facilitate the performance of this paradigm, we aim to describe some critical steps of OSA under a saccharin‐fading procedure. Material & Methods: We used 40 male Wistar rats to study the process of acquiring the operant response through a saccharin‐fading procedure under a fixed ratio (FR1) schedule of reinforcement. Next, we analyze the alcohol introduction and concentration increase, the effect of an alcohol deprivation, and the analogy between this paradigm with the Drinking in the Dark‐Multiple Scheduled Access paradigm. Results: During alcohol concentration increase, animals reduced their lever presses in accordance with the increase in alcohol concentration. On the contrary, the consumption measured in g·kg−1 BW showed a great stability. The lever presses pattern within operant session changes with the introduction of different alcohol concentrations: at higher alcohol concentrations, animals tended to accumulate most of their presses in the initial period of the session. Discussion: We show the utility of fading with low concentrations of saccharin and the evolution of the operant response through the different concentrations of alcohol. Conclusion: Taken together, our results aimed to dissect the acquisition and maintenance of OSA behavior as well as other related variables, to facilitate the understanding and performance of this paradigm. [ABSTRACT FROM AUTHOR]

Introduction: Young adults with perinatally acquired HIV (YA‐PHIV) are facing transitions to adult life. This study assessed health risk behaviours (including substance use), mental health, quality of life (QOL) and HIV treatment outcomes of Thai YA‐PHIV. Methods: A cross‐sectional study was conducted in Thai YA‐PHIV aged 18–25 years who were enrolled in a prospective cohort study at five tertiary paediatric HIV care centres in Thailand. Study data were obtained through face‐to‐face interviews from November 2020 to July 2021. Assessments were performed for alcohol use (Alcohol Use Disorders Identification Test; AUDIT), smoking (Fagerstrom Test for Nicotine Dependence), drug/substance use (Drug Abuse Screening Test; DAST‐10), depression (Patient Health Questionnaire for Adolescents; PHQ‐A), anxiety (Generalized Anxiety Disorder; GAD‐7) and QOL (World Health Organization QOL Brief‐Thai). HIV treatment outcomes were extracted from the National AIDS Program database. Results: Of 355 YA‐PHIV, 163 (46%) were males: their median age was 21.7 (interquartile range, IQR 20.2–23.5) years. There were 203 YA‐PHIV (58%) who reported ever having sex; 141 (40%) were sexually active in the past 6 months, of whom 86 (61%) reported 100% condom use. Overall, 49 (14%) met the criteria for harmful alcohol use; 28 (7.9%) were alcohol dependent. Sixty (17%) were current smokers and 37 (11%) used drugs/substances. The frequency of moderate up to severe symptoms for depression was 18% and for anxiety was 9.7%. Their overall QOL was good in 180 (51%), moderate in 168 (47%) and poor in five (1.4%). There were 49 YA‐PHIV (14%) with CD4 <200 cells/mm3 and 85 (24%) with virologic non‐suppression (HIV‐RNA >200 copies/ml). On multivariate analyses, the highest education at the primary to high school or vocational school levels (adjusted odds ratio [aOR] 2.02, 95% CI 1.40–3.95, p 0.04), harmful alcohol use (aOR 2.48, 95% CI 1.24–4.99, p 0.01), alcohol dependence (aOR 3.54, 95% CI 1.51–8.31, p <0.01) and lifetime suicidal attempt (aOR 2.66, 95% CI 1.11–6.35, p 0.03) were associated with non‐suppression. Conclusions: Regular screening for alcohol use and mental health, including suicidality, would be useful to identify YA‐PHIV who need more intensive psychosocial support or referral services to ensure they can achieve and maintain a high QOL into adult life. [ABSTRACT FROM AUTHOR]

Background: Housing insecurity is prevalent among emergency department (ED) patients. Despite a surge of interest in screening for patients' social needs including housing insecurity, little research has examined ED social needs interventions. We worked together with government and community partners to develop and pilot test a homelessness prevention intervention targeted to ED patients with drug or unhealthy alcohol use. Methods: We approached randomly sampled patients at an urban public hospital ED, May to August 2019. Adult patients were eligible if they were medically stable, not incarcerated, spoke English, had unhealthy alcohol or any drug use, and were not currently homeless but screened positive for risk of future homelessness using a previously developed risk screening tool. Participants received a three‐part intervention: (1) brief counseling and referral to treatment for substance use delivered through a preexisting ED program; (2) referral to Homebase, an evidence‐based community homelessness prevention program; and (3) up to three troubleshooting phone calls by study staff. Participants completed surveys at baseline and 6 months. Results: Of 2183 patients screened, 51 were eligible and 40 (78.4%) participated; one later withdrew, leaving 39 participants. Participants were diverse in age, gender, race, and ethnicity. Of the 32 participants reached at 6 months, most said it was very or extremely helpful to talk to someone about their housing situation (n = 23, 71.9%) at the baseline ED visit. Thirteen (40.6%) said their housing situation had improved in the past 6 months and 16 (50.0%) said it had not changed. Twenty participants (62.5%) had made contact with a Homebase office. Participants shared ideas of how to improve the intervention. Conclusions: This pilot intervention was feasible and well received by participants though it required a large amount of screening to identify potentially eligible patients. Our findings will inform a larger future trial and may be informative for others seeking to develop similar interventions. [ABSTRACT FROM AUTHOR]

Background: At‐risk youth may be defined as a diverse group of young people in unstable life circumstances, who are currently experiencing or are at risk of developing one or more serious problems. At‐risk youth are often very unlikely to seek out help for themselves within the established venues, as their adverse developmental trajectories have installed a lack of trust in authorities such as child protection agencies and social workers. To help this population, a number of outreach programmes have been established seeking to help the young people on an ad hoc basis, meaning that the interventions are designed to fit the individual needs of each young person rather than as a one‐size‐fits‐all treatment model. The intervention in this review is targeted outreach work which may be (but does not have to be) multicomponent programmes in which outreach may be combined with other services. Objectives: The main objective of this review was to answer the following research questions: What are the effects of outreach programmes on problem/high‐risk behaviour of young people between 8 and 25 years of age living in OECD countries? Are they less likely to experience an adverse outcome such as school failure or drop‐out, runaway and homelessness, substance and/or alcohol abuse, unemployment, long‐term poverty, delinquency and more serious criminal behaviour? Search Methods: We identified relevant studies through electronic searches of bibliographic databases, governmental and grey literature repositories, hand search in specific targeted journals, citation tracking, and Internet search engines. The database searches were carried out in September 2020 and other resources were searched in October and November 2021. We searched to identify both published and unpublished literature, and reference lists of included studies and relevant reviews were searched. Selection Criteria: The intervention was targeted outreach work which may have been combined with other services. Young people between 8 and 25 years of age living in OECD countries, who either have experienced or is at‐risk of experiencing an adverse outcome were eligible. Our primary focus was on measures of problem/high‐risk behaviour and a secondary focus was on social and emotional outcomes. All study designs that used a well‐defined control group were eligible for inclusion. Studies that utilised qualitative approaches were not included. Data Collection and Analysis: The total number of potentially relevant studies constituted 17,659 hits. A total of 16 studies (17 different interventions) met the inclusion criteria. Only five studies could be used in the data synthesis. Eight studies could not be used in the data synthesis as they were judged to have critical risk of bias and, in accordance with the protocol, were excluded from the meta‐analysis on the basis that they would be more likely to mislead than inform. Two studies (three interventions) did not provide enough information enabling us to calculate an effect size and standard error, and one study did not provide enough information to assess risk of bias. Meta‐analysis of all outcomes were conducted on each conceptual outcome separately. All analyses were inverse variance weighted using random effects statistical models incorporating both the sampling variance and between study variance components into the study level weights. Random effects weighted mean effect sizes were calculated using 95% confidence intervals. Too few studies were included to carry out any sensitivity analyses. Main Results: Four of the five studies used for meta analysis were from the USA and one was from Canada. The timespan in which included studies were carried out was 32 years, from 1985 to 2017; on average the intervention year was 2005. The average number of participants in the analysed interventions was 116, ranging from 30 to 346 and the average number of controls was 81, ranging from 32 to 321. At most, the results from two studies could be pooled in a single meta‐analysis. It was only possible to pool the outcomes drug (other than marijuana) use, marijuana use and alcohol use each at two different time points (one and 3 months follow up). At 1 month follow up the weighted averages varied between zero and 0.05 and at 3 months follow up between −0.17 and 0.07. None of them were statistically significant. In addition, a number of other outcomes were reported in a single study only. Authors' Conclusions: Overall, there were too few studies included in any of the meta‐analyses in order for us to draw any conclusion concerning the effectiveness of outreach. The vast majority of studies were undertaken in the USA. The dominance of the USA as the main country in which outreach interventions meeting our inclusion criteria have been evaluated using rigorous methods and within our specific parameters clearly limits the generalisability of the findings. None of the studies, however, was considered to be of overall high quality in our risk of bias assessment and the process of excluding studies with critical risk of bias from the meta‐analysis applied in this review left us with only five of a total of 16 possible studies to synthesise. Further, because too few studies reported results on the same type of outcome at most two studies could be combined in a particular meta‐analysis. Given the limited number of rigorous studies available from countries other than the USA, it would be natural to consider conducting a series of randomised controlled trials evaluating the effectiveness of outreach for at‐risk youth in countries outside the USA. The trial(s) should be designed, conducted and reported according to methodological criteria for rigour in respect of internal and external validity to achieve robust results and preferably reporting a larger number of outcomes. [ABSTRACT FROM AUTHOR]

Aims: Previous studies have suggested an increased risk of developing schizophrenia later in life in children with autism spectrum disorder (ASD). This study aims to investigate the diagnosis stability and the potential predictors for progression to schizophrenia in ASD. Methods: We recruited 11 170 adolescents (10–19 years) and young adults (20–29 years) with ASD between 2001 and 2010. They were followed up to the end of 2011 to identify newly diagnosed schizophrenia. The Kaplan–Meier method and Cox regression with age as a time scale were employed to estimate incidence rates and the significance of candidate predictors. Results: The progression rate from ASD to schizophrenia was 10.26% for 10 years of follow‐up. Among 860 progressors, 580 (67.44%) occurred within the first 3 years after a diagnosis of ASD. The identified predictors were age (reported as hazard ratio with 95% confidence interval: 1.13; 1.11–1.15), depressive disorder (1.36; 1.09–1.69), alcohol use disorder (3.05; 2.14–4.35), substance use disorder (1.91; 1.18–3.09), cluster A personality disorder (2.95; 1.79–4.84), cluster B personality disorder (1.86; 1.05–3.28), and a family history of schizophrenia (2.12; 1.65–2.74). Conclusion: More than two‐thirds of the progressors developed schizophrenia within the first 3 years. Demographic characteristics, physical and psychiatric comorbidities, and psychiatric family history were significant predictors of progression. [ABSTRACT FROM AUTHOR]

Background: In Spain, the perceived professional quality of life among veterinarians has not been explored. Methods: Veterinarians were invited to complete an online questionnaire in which they answered the ProfessionalQuality of Life scale, theMedical Outcomes Study Social Support Survey and the Warwick-Edinburgh Mental Well-Being Scale. Participants were asked whether they were receiving psychological therapy or were taking anxiolytics, hypnotics or antidepressant medication. Alcohol consumption was measured using the Alcohol Use Disorders Identification Test and nicotine dependence was assessed using the Fagerström test; participants were asked whether they took illegal drugs. Results: The study sample comprised a total of 602 veterinarians, most of whom reported average levels of compassion satisfaction, secondary stress trauma and burnout. Emotional support andmental wellbeing influenced participants' professional quality of life. The percentage of veterinarians in psychological therapy and/or taking anxiolytics was higher than in the general population. Conclusions: A considerable number of clinical veterinarians in Spain may be suffering from work-related stress. Our study identifies salary, emotional support and mental wellbeing as important factors that affect the professional quality of life. Interventions to improve veterinary clinicians' professional quality of life should therefore focus on these factors. [ABSTRACT FROM AUTHOR]

This is linked to Bang et al papers. To view these articles visit https://doi.org/10.1111/apt.14243 and https://doi.org/10.1111/apt.14281. [ABSTRACT FROM AUTHOR]

Mu opioid receptors (MORs) are expressed in the dorsal striatum, a brain region that mediates goal‐directed (via the dorsomedial striatum) and habitual (via the dorsolateral striatum, DLS) behaviours. Our previous work indicates that glutamate transmission is depressed when MORs are activated in the dorsal striatum, inducing MOR‐mediated long‐term synaptic depression (MOR‐LTD) or short‐term depression (MOR‐STD), depending on the input. In the DLS, MOR‐LTD is produced by MORs on anterior insular cortex (AIC) inputs and MOR‐STD occurs at thalamic inputs, suggesting input‐specific MOR plasticity mechanisms. Here, we evaluated the mechanisms of induction of MOR‐LTD and MOR‐STD in the DLS using pharmacology and optogenetics combined with patch‐clamp electrophysiology. We found that cAMP/PKA signalling and protein synthesis are necessary for MOR‐LTD expression, similar to previous studies of cannabinoid‐mediated LTD in DLS. MOR‐STD does not utilize these same mechanisms. We also demonstrated that cannabinoid‐LTD occurs at AIC inputs to DLS. However, while cannabinoid‐LTD requires mTOR signalling in DLS, MOR‐LTD does not. We characterized the role of presynaptic HCN1 channels in MOR‐LTD induction as HCN1 channels expressed in AIC are necessary for MOR‐LTD expression in the DLS. These results suggest a mechanism in which MOR activation requires HCN1 to induce MOR‐LTD, suggesting a new target for pharmacological modulation of synaptic plasticity, providing new opportunities to develop novel drugs to treat alcohol and opioid use disorders. Key points: Mu opioid receptor‐mediated long‐term depression at anterior insular cortex inputs to dorsolateral striatum involves presynaptic cAMP/PKA signalling and protein translation, similar to known mechanisms of cannabinoid long‐term depression.Dorsal striatal cannabinoid long‐term depression also occurs at anterior insular cortex inputs to the dorsolateral striatum. Dorsal striatal cannabinoid long‐term depression requires mTOR signalling, similar to hippocampal cannabinoid long‐term depression, but dorsal striatal mu opioid long‐term depression does not require mTOR signalling.Mu opioid long‐term depression requires presynaptic HCN1 channels at anterior insular cortex inputs to dorsolateral striatum. [ABSTRACT FROM AUTHOR]

Alcohol consumption affects motor behavior and motor control. Both acute and chronic alcohol abuse have been extensively investigated; however, the therapeutic efficacy of alcohol on some movement disorders, such as myoclonus‐dystonia or essential tremor, still does not have a plausible mechanistic explanation. Yet, there are surprisingly few systematic trials with known GABAergic drugs mimicking the effect of alcohol on neurotransmission. In this brief survey, we aim to summarize the effects of EtOH on striatal function, providing an overview of its cellular and synaptic actions in a 'circuit‐centered' view. In addition, we will review both experimental and clinical evidence, in the attempt to provide a plausible mechanistic explanation for alcohol‐responsive movement disorders, with particular emphasis on dystonia. Different hypotheses emerge, which may provide a rationale for the utilization of drugs that mimic alcohol effects, predicting potential drug repositioning. [ABSTRACT FROM AUTHOR]

We estimate the effects of legalized recreational marijuana on entry into the foster‐care system. Exploiting state‐level variation in legalization and its timing, we estimate that legalization decreases foster‐care placements by at least 10%, with larger effects in years after legalization, and for admissions for reasons of parental drug and alcohol abuse, physical abuse, neglect, and parental incarceration. Our findings imply that legalization may have important consequences for child welfare, and that substitution toward marijuana from other substances can be an important part of how legalization affects admissions. [ABSTRACT FROM AUTHOR]

Aims: Individuals with substance use disorders (SUD) have higher risk of developing pain disorders. This study aimed to investigate the risk of major psychiatric disorders (MPD), SUD, and pain disorders among their offspring. Methods: This study used data from the Taiwan National Health Research Database. The case cohort included participants who had a parent diagnosed with SUD. The matched control cohort was offspring of parents without any SUD or major psychiatric disorder (MPD). Poisson regression was applied to estimate the risk of MPD, SUD, and pain disorder between case and control cohorts. Results: We recruited 13,840 cases and 138,400 matched controls. After adjusting for demographic characteristics and family history of psychiatric disorder, the offspring of parents with SUD had higher risk for bipolar disorder (reported as risk ratio with 95% confidence interval: 2.48, 1.79–3.43), depressive disorder (2.22, 1.94–2.52), SUD (2.53, 2.18–2.92), and alcohol use disorder (1.43, 1.16–1.76) than controls. With adjustments of demographic characteristics, individual MPD, and family history of psychiatric disorder, they also presented higher risk than controls for several pain disorders, including migraine (1.43, 1.15–1.78), fibromyalgia (1.21, 1.03–1.42), dorsopathies (1.20, 1.06–1.37), dysmenorrhea (1.16, 1.04–1.29), irritable bowel syndrome (1.26, 1.11–1.43), and dyspepsia (1.14, 1.02–1.27). Conclusions: Clinicians should be aware of the influence of parental SUD on the elevated risk for MPD, SUD, and pain disorders in their offspring. [ABSTRACT FROM AUTHOR]

Aim: Alcoholism is the most prevalent substance use disorder in Japan; the estimated number of patients and high‐risk drinkers is in the millions. Although studies in the West have shown that cognitive behavioral therapy (CBT) is one of the most effective treatment strategies for alcoholic patients, there is a dearth of efficacy studies of CBT‐based intervention for those patients in the non‐Western setting. The aim of this study is to investigate the efficacy of a 12‐session CBT‐based relapse prevention program for Japanese alcoholic patients. Methods: Forty‐eight alcoholic patients (M = 36, F = 12) who were admitted to an addiction treatment unit were randomly allocated either to a 12‐session relapse prevention (RP) program (n = 24) or a 12‐session psychoeducation (PE) program (n = 24). Both treatment programs were conducted in a group format once a week for 12 weeks. Other aspects of inpatient treatment (group meetings, etc) were the same in both groups. Self‐rating scales, which measure behavioral and cognitive coping, coping response, self‐efficacy, and cognition of drinking, were administered at pretreatment, mid‐treatment, and posttreatment periods. The proportion of participants who relapsed at 3 and 6 months after discharge was evaluated. Results: Both RP and PE groups showed significant improvement in self‐efficacy and cognition of drinking at posttreatment. However, there were no significant differences in the self‐rating scales between both groups. In addition, there were no significant differences in relapse rate at 3 and 6 months after discharge between both groups. Conclusions: The 12‐session CBT‐based relapse prevention program and the psychoeducation program may be equally efficacious for alcoholic patients. Several factors that influenced the results are discussed. [ABSTRACT FROM AUTHOR]

We present a case of a 60‐year‐old female with a history of liver cirrhosis, alcohol abuse, and chronic venous insufficiency who presented with maggot‐infested wounds on her legs, bilateral buttocks, and groin area. Two sets of blood cultures grew Wohlfahrtiimonas chitiniclastica. She underwent wound debridement and treatment with cefazolin. [ABSTRACT FROM AUTHOR]

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega‐analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case‐ and control‐only sites led to the inadvertent learning of site‐effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary‐based feature selection leveraging leave‐one‐site‐out cross‐validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test‐set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi‐site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD. [ABSTRACT FROM AUTHOR]

Background and Purpose: The current study was designed to: (i) examine whether functional interactions occur between receptors known to regulate alcohol self-administration; and (ii) characterize relapse to alcohol seeking following abstinence.Experimental Approach: The selective cannabinoid CB(1) receptor antagonist SR141716A (0.03-1.0 mg.kg(-1) i.p.) resulted in a dose-dependent reduction in ethanol self-administration in ethanol-preferring Indiana-preferring rats. SR141716A was then co-administered with either the selective glutamate metabotropic glutamate 5 (mGlu(5)) receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) or the selective adenosine A(2A) receptor antagonist SCH58261.Key Results: When administered at individually sub-threshold doses, a combination of SR141716A (0.1 mg.kg(-1)) and SCH58261 (0.5 mg.kg(-1) i.p.) produced a reduction (28%) in ethanol self-administration. Combinations of threshold doses of SR141716A (0.3 mg.kg(-1)) and SCH58261 (2.0 mg.kg(-1), i.p.) caused an essentially additive reduction (68%) in alcohol self-administration. A combination of individually sub-threshold doses of CB(1) and mGlu(5) receptor antagonists did not affect alcohol self-administration; however, combined threshold doses of SR141716A (0.3 mg.kg(-1)) and MTEP (1.0 mg.kg(-1) i.p.) did reduce ethanol self-administration markedly (80%). Cue-conditioned alcohol seeking was attenuated by pretreatment with MTEP (1.0 mg.kg(-1)) co-administered with SR141716A (0.3 mg.kg(-1) i.p.). In contrast, SCH58261 (2.0 mg.kg(-1)) co-administered with SR141716A (0.3 mg.kg(-1) i.p.) did not reduce cue-conditioned alcohol seeking.Conclusions and Implications: Adenosine A(2A) and cannabinoid CB(1) receptors regulated alcohol self-administration additively, but combined low-dose antagonism of these receptors did not prevent cue-conditioned alcohol seeking after abstinence. In contrast, combined low-dose antagonism of mGlu(5) and CB(1) receptors did prevent relapse-like alcohol seeking after abstinence, suggesting a prominent role for mGlu(5) receptors in this paradigm. [ABSTRACT FROM AUTHOR]

The article offers information about the issue of intoxicated mistakes of self-defense in England and Wales. The criminal law considers several cases where an intoxicated individual attacked someone in a mistaken belief that the victim was about to attack. There are inconsistencies of the law which deals with intoxicated acts of aggression and mistakes about self-defense. An example of the murder case and the impact on criminal liability are discussed.

Consuming cannabis in combination with alcohol is common among Australian cannabis users. This paper investigates whether the economic relationship between cannabis and alcohol is affected by the manner in which these two substances are used. Our results indicate that cannabis and alcohol are economic complements for all cannabis users, but this relationship is stronger for cannabis users who tend to use alcohol and cannabis together, whom we refer to as polysubstance users. Separate analysis by gender suggests that cannabis consumption by polysubstance and non-polysubstance using males is more responsive to changes in the full price of alcohol than their female counterparts. [ABSTRACT FROM AUTHOR]

Although a number of international diet and lifestyle guidelines during pregnancy (DLGP) exist in the literature, contextualization to low‐ and middle‐income settings is less common. The aim of this study was to present the Lebanese DLGP and to describe the process followed for their development. A mixed‐method approach was used including a review and synthesis of existing international DLGP and a consensus building nominal group technique (NGT) with a multidisciplinary group of experts (n = 11). During the meeting, participants identified the themes of the guidelines, formulated the wording of each themes' guideline and translated the guidelines to the Arabic language. Consensus was defined as an agreement of 80%. Reviewing the literature, a list of 17 main topics were found to be common themes for the DLGP. For the Lebanese DLGP, participants in the NGT meeting selected seven themes from this list: gestational weight gain, diet diversity, hydration, food safety, harmful foods, physical activity and breastfeeding. In addition, the group formulated three themes based on merging/modifying existing themes: supplementation, alcohol and smoking and religious fasting. Two context‐specific new themes emerged: wellbeing and nutrition resilience. For each of the identified themes, the group agreed upon the wording of its guidelines and description. This study is the first from the Eastern Mediterranean Region to develop through consensus building, context and culture‐specific dietary and lifestyle guidelines for pregnant women. Putting maternal nutrition at the heart of tackling malnutrition and its detrimental health outcomes is a core investment for a better maternal and child health. [ABSTRACT FROM AUTHOR]

Introduction: Mental health disorders may negatively impact HIV outcomes, such as viral suppression (VS) and antiretroviral (ART) adherence among people with HIV (PWH) with hazardous alcohol use. This study evaluates the longitudinal association between depression, anxiety symptoms, VS and complete ART adherence among ART clients with hazardous alcohol use in Vietnam; and examines alcohol dependence as a modifier in this association. Methods: This was a secondary data analysis of a trial for hazardous drinking ART clients in Thai Nguyen, Vietnam. From March 2016 to May 2018, 440 ART clients with an Alcohol Use Disorders Identification Test‐Concise (AUDIT‐C) score ≥4 for men and ≥3 for women were enrolled. Individuals were randomized to either a combined intervention, a brief intervention or a standard of care. Data on sociodemographics, depression, anxiety symptoms, alcohol use, VS and ART adherence were collected at baseline, three, six, and twelve months. Generalized estimating equation models controlling for intervention exposure were used to estimate time‐lagged associations. Risk ratios were estimated using Poisson regression with robust variance estimation. Results: The mean age of participants was 40.2. The majority was male (96.8%), had at least some secondary school education (85.0%) and had a history of injection drug use (80.9%). No overall effect of depression and anxiety symptoms on VS was observed. When stratified by time, increased anxiety symptoms at six months were associated with VS at 12 months (adjusted risk ratio (aRR) = 1.09; 95% CI 1.02 to 1.17). An increase in depression or anxiety symptoms was associated with a decreased probability of complete ART adherence (depression symptoms: aRR = 0.95; 95% CI: 0.91 to 0.99; anxiety symptoms: aRR = 0.93; 85% CI: 0.88 to 0.99). The negative effects of anxiety symptoms on ART adherence were stronger among participants with alcohol dependence, compared to those without. Conclusions: Depression and anxiety symptoms had no overall effect on VS, although they were associated with a lower probability of complete ART adherence. Interventions focusing on mental healthcare for PWH with hazardous alcohol use are needed, and integration of mental healthcare and alcohol reduction should be implemented in HIV primary care settings. [ABSTRACT FROM AUTHOR]

Objectives: Diverse instruments are used to measure problem gambling and Gambling Disorder intervention outcomes. The 2004 Banff consensus agreement proposed necessary features for reporting gambling treatment efficacy. To address the challenge of including these features in a single instrument, a process was initiated to develop the Gambling Disorder Identification Test (GDIT), as an instrument analogous to the Alcohol Use Disorders Identification Test and the Drug Use Disorders Identification Test. Methods: Gambling experts from 10 countries participated in an international two‐round Delphi (n = 61; n = 30), rating 30 items proposed for inclusion in the GDIT. Gambling researchers and clinicians from several countries participated in three consensus meetings (n = 10; n = 4; n = 3). User feedback was obtained from individuals with experience of problem gambling (n = 12) and from treatment‐seekers with Gambling Disorder (n = 8). Results: Ten items fulfilled Delphi consensus criteria for inclusion in the GDIT (M ≥ 7 on a scale of 1–9 in the second round). Item‐related issues were addressed, and four more items were added to conform to the Banff agreement recommendations, yielding a final draft version of the GDIT with 14 items in three domains: gambling behavior, gambling symptoms and negative consequences. Conclusions: This study established preliminary construct and face validity for the GDIT. [ABSTRACT FROM AUTHOR]

This paper focuses on the specific problem of alcoholism in the husband/father member of the family. Disturbed personality and decompensation hypotheses were not supported by the data. Systems theory alone is inadequate to conceptualize the inconsistency of the alcoholic, and his impact on the family. A combination of systems theory and Hill's (1949) crisis theory was suggested as one view of the alcoholic marriage. Therapeutic implications were derived from this combined theoretical perspective, and were briefly discussed. [ABSTRACT FROM AUTHOR]