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Ever since 2018 France has been the only country to approve the gamma aminobutyric acid type B (GABA-B) receptor agonist baclofen for alcohol dependence. This authorization follows a ten-year period of intensive off-label use during which baclofen was used in doses of up to 300 and even 400mg per day to support the gradual reduction of alcohol consumption in patients suffering from alcohol dependence. However, in international clinical trials, baclofen has mainly been studied to support the maintenance of abstinence. The French use of baclofen was therefore somewhat atypical as it paved the way for drug-supported approaches to reducing alcohol consumption, even before nalmefene was marketed. In line with this specific use of baclofen, approval was granted only for alcohol reduction support. However, a recent Cochrane systematic review and meta-analysis by Agabio et al. found significant efficacy only for abstinence maintenance, while no significant effect was found on alcohol reduction outcomes and no dose-response relationship was identified in the analyses. The safety of baclofen was judged to be good. Based on these substantial new results, the Société française d'alcoologie (SFA) now considers that baclofen should also be approved for the maintenance of abstinence. The extension of approval should not lead to the removal of the initial indication or the possibility of using high doses, as some patients have found this therapeutic regimen particularly useful for them. France, which has been a open skies national laboratory on the use of baclofen in alcohol dependence for over ten years, should let this original therapeutic option available to patients. However, it should update the regulatory framework defining the main conditions of access to treatment for patients based on the latest and highest scientific evidence.
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CONTEXT: Alcohol-related health problems represent a significant public health concern, and it is imperative for the healthcare team to accurately perceive and detect these issues to provide appropriate care. The objective of this survey was to evaluate the knowledge, practices, and educational background of healthcare professionals in the field of alcohol-related health concerns, aiming to identify their information requirements. METHODS: This study employs a cross-sectional descriptive survey methodology, in which data were gathered through a digital questionnaire designed for healthcare professionals (including those in medical, paramedical, and medico-social professions) working in addictology services as well as other relevant services across France and its overseas departments. RESULTS: A total of 611 questionnaires were deemed usable for analysis. A considerable percentage of participants reported their knowledge and skills to be insufficient or very insufficient, with rates of 33 % and 36 %, respectively. Moreover, a significant proportion of respondents (≈ 28 %) stated that they had received no education in addictology. Our results highlight differences in levels of knowledge and competence among the various healthcare settings, notably with lower reported levels of satisfaction in hospital settings (public and private), private practice, and in Harm Reduction Centers. Furthermore, certain professions reported unsatisfactory levels of skills and knowledge in alcohol-related issues, particularly support staff, pharmacists, expert patients, administrative staff, and social workers. These findings suggest the need to enhance knowledge and skills by tailoring interventions according to the specific healthcare settings and professions. Additionally, the priority themes and channels for disseminating information varied depending on age, region, and professional category. CONCLUSION: This survey reveals a low level of knowledge, practice, and education in addictology, emphasizing the critical need for training. The importance of training extends not only to the priority topics addressed but also to the channels used for dissemination, all while customizing them to suit the age, professional category, structure, and region of healthcare professionals.
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Severe Alcoholic Hepatitis (sAH) is an acute form of liver injury caused by chronic and heavy alcohol drinking. A one-month corticosteroids course is the only sAH reference treatment, and its interactions with the Gut Microbiota (GM), which is a key contributor to liver injury, remain unknown. To evaluate the evolution of the GM in sAH patients, we retrospectively investigated the composition of the GM of 27 sAH patients at the Amiens University Hospital before (D0) and after (D7) a 7-day corticotherapy course using fecal metagenomics sequencing. We also quantified fecal Short-Chain Fatty Acids (SCFA) and fecal and serum Bile Acids (BA), as well as serum Lipopolysaccharide-Binding Protein (LBP). Overall, the community and taxonomical analyses did not reveal any GM evolution between D0 and D7, nor did the SCFA profiles analysis. However, in serum but not fecal samples, the ratio of glyco-conjugated to tauro-conjugated BA was significantly reduced at D7, independently of the response to treatment, while two BA were enriched in non-responder patients. LBP concentration significantly diminished between D0 and D7, which may indicate an improvement of the gut barrier. The stability of the GM of sAH is interesting in the perspective of new treatments based on GM modulation.
There is a gap in the understanding of the effects of corticosteroids on the gut microbiota of severe alcoholic hepatitis patients.In this study, the composition of the Gut Microbiota of sAH patients treated with prednisolone remains unchanged after 7 days of prednisolone treatment.Short-Chain Fatty Acid profiles are not impacted by the treatment, while Bile Acids profiles change in serum but not in stool samples.Responders and non-responders show different lipopolysaccharide-binding protein serum concentration evolution across time, as well as distinct Bile Acid profiles.
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Ácidos y Sales Biliares , Heces , Microbioma Gastrointestinal , Hepatitis Alcohólica , Prednisolona , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Hepatitis Alcohólica/tratamiento farmacológico , Hepatitis Alcohólica/sangre , Masculino , Heces/microbiología , Heces/química , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/metabolismo , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Prednisolona/administración & dosificación , Adulto , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/sangre , Proteínas Portadoras/genética , Proteínas Portadoras/sangre , Proteínas de Fase Aguda/metabolismo , Glicoproteínas de Membrana/sangre , Glicoproteínas de Membrana/genética , Anciano , MetagenómicaRESUMEN
The use of psilocybin to treat alcohol use disorder is very promising, but the mechanisms of action remain poorly understood. We combined behavioral, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal psilocybin or directly within the nucleus accumbens core or the ventral tegmental area. Transcripts from the dopaminergic system were quantified in the nucleus accumbens and prefrontal cortex. Psilocybin significantly reduced (50%) ethanol self-administration when injected 4 hours before the session either intraperitoneally (1mg/kg) or directly within the left nucleus accumbens (0.15µg) but not the right nucleus accumbens or the left ventral tegmental area. The effect of intraperitoneal injection of psilocybin was prevented by intra left nucleus accumbens injection of 0.3µg of the 5-HT2AR antagonist ketanserin. In rats that self-administered ethanol but not in those self-administering saccharin, dopamine D2 receptor mRNA were increased in both the nucleus accumbens and the prefrontal cortex by psilocybin, while D1R mRNA was increased only in the prefrontal cortex. As in humans, psilocybin reduced ethanol self-administration in rats through the 5-HT2AR within the left nucleus accumbens possibly through increased D2R expression. Our results open unexpected perspectives regarding the hemispheric lateralization of psychedelic effects.
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Alcohol use disorder (AUD) is a public health issue that affects millions of people worldwide leading to physical, mental and socio-economic consequences. While current treatments for AUD have provided relief to individuals, their effectiveness on the long term is often limited, leaving a number of affected individuals without sustainable solutions. In this review, we aim to explore two emerging approaches for AUD: psychedelics and epigenetic drugs (i.e., epidrugs). By examining preclinical studies, different animal species and procedures, we delve into the potential benefits of each of these treatments in terms of addictive behaviors (alcohol drinking and seeking, motivation to drink alcohol and prevention of relapse). Because psychedelics and epidrugs may share common and complementary mechanisms of action, there is an exciting opportunity for exploring synergies between these approaches and their parallel effectiveness in treating AUD and the diverse associated psychiatric conditions.
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Alcoholismo , Epigénesis Genética , Alucinógenos , Animales , Humanos , Alcoholismo/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Epigénesis Genética/efectos de los fármacos , Alucinógenos/uso terapéuticoRESUMEN
AIMS: up to 80% of patients with alcohol use disorder display cognitive impairments. Some studies have suggested that alcohol-related cognitive impairments could be worsened by hepatic damage. The primary objective of this study was to compare mean scores on the Brief Evaluation of Alcohol-Related Neurocognitive Impairments measure between alcohol use disorder patients with (CIR+) or without cirrhosis (CIR-). METHODS: we conducted a prospective case-control study in a hepatology department of a university hospital. All patients were assessed using the Evaluation of Alcohol-Related Neuropsychological Impairments test. RESULTS: a total of 82 patients (50 CIR+, 32 CIR-) were included in this study. CIR- patients were significantly younger than CIR+ patients (respectively, 45.5 ± 6.8 vs 60.1 ± 9.0; P < .0001). After adjusting for age and educational level, the mean Evaluation of Alcohol-Related Neuropsychological Impairments total scores in the CIR+ group were significantly lower than in the group of CIR- patients (14.1 ± 0.7 vs 7.8 ± 0.4, respectively, P < .0001). The mean subscores on delayed verbal memory, alphabetical ordination, alternating verbal fluency, visuospatial abilities, and ataxia subtests were also significantly lower in the CIR+ than in the CIR- group (respectively, 1.9 ± 0.2 vs 2.8 ± 0.2; 1.8 ± 0.2 vs 2.7 ± 0.2; 2.2 ± 0.2 vs 3.6 ± 0.2; 0.7 ± 0.2 vs 1.6 ± 0.2; 0.7 ± 0.2 vs 3.1 ± 0.2; P < .0001 for all comparisons). CONCLUSIONS: in the present study, alcohol use disorder patients with cirrhosis presented more severe cognitive impairments than those without cirrhosis. Longitudinal studies are needed to investigate how cirrhosis can influence cognitive impairments.
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Alcoholismo , Disfunción Cognitiva , Humanos , Alcoholismo/complicaciones , Alcoholismo/psicología , Estudios de Casos y Controles , Pruebas Neuropsicológicas , Disfunción Cognitiva/complicaciones , Cirrosis Hepática/complicaciones , CogniciónRESUMEN
Background: Many patients admitted to general emergency departments (EDs) have a pattern of drinking that could lead to future alcohol-related complications. However, it is often difficult to screen these patients in the context of emergency. The aim of this study is to analyze whether reasons for admission could help to screen patients who have an unhealthy alcohol use. Method: Patients were recruited among six public hospital ED in France, between 2012 and 2014. During a one-month period in each hospital, anonymous questionnaires including sociodemographic questions, AUDIT-C and RAPS4-QF were administered to each patients visiting the ED. The reason for admission of each patient was noted at the end of their questionnaire by the ED practitioner. Results: Ten thousand Four hundred twenty-one patients were included in the analysis. Patients who came to the ED for injuries and mental disorders were more likely to report unhealthy alcohol use than non-harmful use or no use. Among male patients under 65 years old admitted to the ED for a mental disorder, 24.2% drank more than four drinks (40 g ethanol) in typical day at least four time a week in the last 12 months. Among these patients, 79.7% reported daily or almost daily heavy episodic drinking (HED, 60 g ethanol), and all were positive on the RAPS4-QF. Conclusion: This study highlights that unhealthy alcohol use is frequent among ED patients and particularly among those who come for injuries or mental disorders. Men under 65 years old with a mental disorder require special attention because of their increased prevalence of daily or almost daily HED.
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Alcohol Use Disorder (AUD) is a psychiatric condition characterized by chronic and excessive drinking despite negative consequences on overall health and social or occupational functioning. There are currently limited treatment options available for AUD, and the effects size and the response rates to these treatments are often low to moderate. The World Health Organization has identified the development of medications to treat AUD as one of its 24 priorities. This past decade was marked by a renewed interest in psychedelic use in psychiatry. At the centre of this renaissance, ketamine, an atypical psychedelic already used in the treatment of major depression, is an NMDA receptor antagonist that exists as a racemic compound made of two enantiomers, S-ketamine, and R-ketamine. Each form can be metabolized into different metabolites, some of which having antidepressant properties. In this article, we review both clinical and preclinical studies on ketamine and its metabolites in the treatment of AUD. Preclinical as well as clinical studies have revealed that ketamine is effective in reducing withdrawal symptoms and alcohol craving. Convergent data showed that antidepressant properties of ketamine largely contribute to the decreased likelihood of alcohol relapse, especially in patients undergoing ketamine-assisted psychotherapies. Its effectiveness is believed to be linked with its ability to regulate the glutamatergic pathway, enhance neuroplasticity, rewire brain resting state network functional connectivity and decrease depressive-like states. However, it remains to further investigate (i) why strong differences exist between male and female responses in preclinical studies and (ii) the respective roles of each of the metabolites in the ketamine effects in both genders. Interestingly, current studies are also focusing on ketamine addiction and the comorbidity between alcohol addiction and depression occurring more frequently in females.
Title: Intérêt et mécanismes d'action de la kétamine dans le traitement de l'addiction à l'alcool Revue des études cliniques et précliniques. Abstract: Le Trouble de l'Usage d'Alcool (TUA) est une maladie psychiatrique caractérisée par une consommation chronique et excessive d'alcool malgré des conséquences négatives sur la santé et le fonctionnement social ou professionnel. Les options de traitements du TUA sont actuellement limitées et les tailles d'effet et taux de réponse à ces traitements sont souvent faibles à modérés. L'Organisation Mondiale de la Santé a identifié le développement des médicaments pour traiter le TUA comme l'une de ses 24 priorités. Cette dernière décennie a été marquée par un intérêt renouvelé pour l'utilisation de psychédéliques en psychiatrie. La kétamine, un psychédélique atypique déjà utilisé dans le traitement de la dépression majeure, est au centre de cette renaissance. Cet antagoniste des récepteurs NMDA existe sous deux formes énantiomères, la S-kétamine et la R-kétamine, qui peuvent être métabolisées en différents dérivés, dont certains ont montré des propriétés antidépressives. Cet article de revue vise à faire le bilan des études cliniques et précliniques sur l'utilisation de la kétamine et de ses métabolites dans le traitement du TUA. L'ensemble de ces études montre que la kétamine est efficace pour réduire les symptômes de sevrage et les envies irrépressibles d'alcool. Les propriétés antidépressives avérées de la kétamine contribuent à la diminution du risque de rechute dans le mésusage d'alcool, notamment chez les patients suivant des psychothérapies. Son efficacité est supposée être liée à sa capacité à réguler la voie glutamatergique, à améliorer la neuroplasticité, à réorganiser la connectivité fonctionnelle des réseaux d'état de repos (resting state networks) du cerveau et à réduire les états dépressifs. Bien que ces premiers résultats soient prometteurs, la mise en évidence de différences importantes entre les sexes, et la méconnaissance du rôle de chacun des métabolites dans les effets observés justifient la poursuite des recherches précliniques pour mieux comprendre comment agissent véritablement la kétamine et ses métabolites sur le TUA. En clinique, les études récentes s'intéressent désormais à la dépendance à la kétamine et à la dépression comorbide, ainsi qu'à l'influence du sexe, une comorbidité plus forte entre la dépendance à l'alcool et la dépression semblant exister chez la femme.
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Alcoholismo , Trastorno Depresivo Mayor , Alucinógenos , Ketamina , Humanos , Masculino , Femenino , Ketamina/farmacología , Ketamina/uso terapéutico , Alcoholismo/tratamiento farmacológico , Alucinógenos/uso terapéutico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Etanol/uso terapéuticoRESUMEN
Background: Binge drinking (BD) among students is a frequent alcohol consumption pattern that produces adverse consequences. A widely discussed difficulty in the scientific community is defining and characterizing BD patterns. This study aimed to find homogenous drinking groups and then provide a new tool, based on a model that includes several key factors of BD, to assess the severity of BD regardless of the individual's gender. Methods: Using the learning sample (N1 = 1,271), a K-means clustering algorithm and a partial proportional odds model (PPOM) were used to isolate drinking and behavioral key factors, create homogenous groups of drinkers, and estimate the probability of belonging to these groups. Robustness of our findings were evaluated with Two validations samples (N2 = 2,310, N3 = 120) of French university students (aged 18-25 years) were anonymously investigated via demographic and alcohol consumption questionnaires (AUDIT, AUQ, Alcohol Purchase Task for behavioral economic indices). Results: The K-means revealed four homogeneous groups, based on drinking profiles: low-risk, hazardous, binge, and high-intensity BD. The PPOM generated the probability of each participant, self-identified as either male or female, to belong to one of these groups. Our results were confirmed in two validation samples, and we observed differences between the 4 drinking groups in terms of consumption consequences and behavioral economic demand indices. Conclusion: Our model reveals a progressive severity in the drinking pattern and its consequences and may better characterize binge drinking among university student samples. This model provides a new tool for assessing the severity of binge drinking and illustrates that frequency of drinking behavior and particularly drunkenness are central features of a binge drinking model.
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ALCOHOL CONSUMPTION AND HIGH BLOOD PRESSURE. Cardiovascular disease is the second leading cause of alcohol-attributable mortality after cancer. The impact of alcohol consumption on blood pressure and the risk of cardiovascular pathologies are still largely underestimated by the general population and health professionals. However, numerous studies have demonstrated a dose-dependent increase in blood pressure, even at consumption levels close to the consumption guidelines (two drinks i.e. 20g per day). The alleged protective effects of low consumption levels are not confirmed, even in women. The binge drinking pattern has a particularly strong impact on blood pressure. The increase in blood pressure due to alcohol is reversible after reduction of consumption. Several pathophysiological mechanisms have been proposed to explain the hypertensive effects of alcohol. The screening of alcohol consumption by health professionals remains largely insufficient, especially in France, even in hypertensive subjects, although intervention is effective. It seems particularly important to reinforce the training of health professionals and the screening of alcohol consumption for primary prevention and also for secondary prevention when hypertension is already established. Scientific societies and federations should reinforce communication on the risks associated with alcohol consumption.
CONSOMMATION D'ALCOOL ET HYPERTENSION ARTÉRIELLE. Les pathologies cardiovasculaires sont la deuxième cause de mortalité attribuable à l'alcool, après les cancers. L'impact de la consommation d'alcool sur la pression artérielle et le risque de pathologies cardiovasculaires semble encore largement sous-estimé dans la population générale et par les professionnels de santé. Pourtant, de très nombreuses études ont démontré l'augmentation de la pression artérielle, dose-dépendante, même à des niveaux de consommation proches des repères de consommation (deux verres, soit 20 g/j). Les effets prétendument protecteurs des faibles niveaux de consommation ne sont pas confirmés, même chez les femmes. Le profil de consommation de type « binge drinking ¼ a un impact particulièrement important sur la pression artérielle. L'augmentation de la pression artérielle due à l'alcool est réversible après diminution de la consommation. Plusieurs mécanismes physiopathologiques ont été proposés pour expliquer les effets hypertenseurs de l'alcool. Le repérage de la consommation d'alcool par les professionnels de santé reste largement insuffisant, notamment en France, même chez les sujets hypertendus alors qu'une intervention est efficace. Il apparaît particulièrement important de renforcer la formation des professionnels de santé et le repérage de la consommation d'alcool à des fins de prévention primaire mais aussi secondaire lorsque l'hypertension est déjà installée. Les sociétés savantes et fédérations devraient renforcer la communication sur les risques liés à la consommation d'alcool.
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Enfermedades Cardiovasculares , Hipertensión , Humanos , Femenino , Hipertensión/epidemiología , Hipertensión/etiología , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Presión Sanguínea , Enfermedades Cardiovasculares/complicaciones , EtanolRESUMEN
Studies on the genetic factors involved in binge drinking (BD) and its associated traits are very rare. The aim of this cross-sectional study was to investigate differences in the association between impulsivity, emotion regulation and BD in a sample of young adults according to the rs6265/Val66Met variant in the brain-derived neurotrophic factor (BDNF) gene, a well-known candidate gene in alcohol use disorders. We recruited 226 university students (112 women), aged between 18 and 25 years old, from two centers in France. The participants completed measures related to alcohol consumption, depression severity, state anxiety levels, impulsivity (UPPS-P), and difficulties in emotion regulation [Difficulty in Emotion Regulation Scale (DERS)]. The relationship between the BD score and the clinical characteristics in the BDNF genotype groups was assessed by partial correlation analyses and moderation analyses. The partial correlation analyses showed that, in the Val/Val genotype group, the BD score was positively related to UPPS-P Lack of Premeditation and Sensation Seeking scores. In the Met carriers group, the BD score was positively related to UPPS-P Positive Urgency, lack of Premeditation, lack of Perseverance and Sensation Seeking scores and to Clarity score of the DERS. Moreover, the BD score was positively associated with depression severity and state anxiety scores. The moderation analyses revealed that BDNF Val/Met genotype moderated the relationship between several clinical variables and BD. The results of the present study support the hypothesis of common and specific vulnerability factors regarding impulsivity and emotion regulation difficulties associated with BD according to this BDNF rs6265 polymorphism.
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Alcoholismo , Consumo Excesivo de Bebidas Alcohólicas , Adolescente , Adulto , Femenino , Humanos , Adulto Joven , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Consumo Excesivo de Bebidas Alcohólicas/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Estudios Transversales , Emociones , Genotipo , Conducta Impulsiva/fisiología , Polimorfismo de Nucleótido Simple/genética , Estudiantes , Universidades , MasculinoRESUMEN
Introduction: Clinical studies on the effectiveness of Baclofen in alcohol use disorder (AUD) yielded mixed results possibly because of differential effects of the enantiomers and sex-related differences. Here we examined the effect of the different Baclofen enantiomers on alcohol intake and on evoked dopamine release in the core of the nucleus accumbens (NAcc) in male and female Long Evans rats. Methods: Rats were trained to chronically self-administer 20% alcohol solution in daily binge drinking sessions and were treated with the different forms of Baclofen [RS(±), R(+) and S(-)]. The effects on the evoked dopamine release within the core of the nucleus accumbens were measured in brain slices from the same animals and the alcohol naïve animals using the fast scan cyclic voltammetry technique. Results: RS(±)-Baclofen reduced alcohol intake regardless of sex but more females were non-responders to the treatment. R(+)-Baclofen also reduced alcohol intake regardless of sex but females were less sensitive than males. S(-)-Baclofen did not have any effect on average but in some individuals, especially in the females, it did increase alcohol intake by at least 100%. There were no sex differences in Baclofen pharmacokinetic but a strong negative correlation was found in females with a paradoxical effect of increased alcohol intake with higher blood Baclofen concentration. Chronic alcohol intake reduced the sensitivity to the effect of Baclofen on evoked dopamine release and S(-)-Baclofen increased dopamine release specifically in females. Discussion: Our results demonstrate a sex-dependent effect of the different forms of Baclofen with no or negative effects (meaning an increase in alcohol self-administration) in subgroup of females that could be linked to a differential effect on dopamine release and should warrant future clinical studies on alcohol use disorder pharmacotherapy that will deeply analyze sex difference.
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Binge drinking (BD) is a harmful behavior for health and is a predictive factor for the development of alcohol addiction. Weak decision-making (DM) capacities could play a role in the vulnerability to BD which in turn would lead to DM impairments, thus perpetuating BD. Longitudinal preclinical studies are however lacking and necessary to understand this complex relationship. Both DM and BD are influenced by sex and involve dopamine release in the core of the nucleus accumbens, a central mechanism regulated by dopamine D2/3 autoreceptors. In this context, we used an operant self-administration procedure of BD in male and female rats, and longitudinally assessed DM capacity, memory and anxiety-like behavior. To better understand the mechanisms potentially involved in the relationship between DM and BD, ex vivo dopamine transmission was assessed short term after the end of the binge exposure in the core of the nucleus accumbens (NAc) using the fast-scan cyclic voltammetry (FSCV) technique and the D2/3 agonist quinpirole. We found important basal sex differences in DM, with female rats showing better performances at baseline. Choice processes were impaired exclusively in males after BD history, associated with a decrease in impulse control in both sexes, while memory and anxiety-like behavior were not affected. Our neurobiological results demonstrate that BD did not affect basal dopamine signaling in the NAc core, regardless of the sex, but reveal changes in the sensitivity to the inhibitory effects of quinpirole in females. DM impairments were neither associated with changes in basal dopamine signaling nor pre-synaptic D2 activity. Overall, our findings show that BD affects both DM processes and dopamine transmission in the core of the NAc in a sex-related manner, further suggesting that these effects may play a role in the vicious cycle leading to BD perpetuation and the early onset of AUD. Our results may inform novel strategies for therapeutic and prevention interventions.
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Binge drinking (BD) in young adults/adolescents can lead to cognitive deficits in the adult probably through neuroinflammation and epigenetic. However, the mode of action of alcohol during the initial exposure is less known while it may be the origin of the deficits seen in adults. Recent studies in adolescent rat hippocampus revealed that loss of memory occurred since the very first exposure to BD with similar mechanisms than those highlighted for longer alcohol exposure. Thus, initiation to BD in the young is responsible for cognitive deficits that will be probably entertained by repeated BD behavior. These kind of data may serve to reinforce the prevention campaigns towards the young population who practice BD.
Title: Alcoolisation chez les jeunes - Neuroinflammation et épigénétique à l'origine des pertes de mémoire dès les premiers épisodes de binge drinking. Abstract: La pratique du binge drinking (BD) se caractérise par l'alternance répétée d'épisodes d'alcoolisation rapide et massive, dans le but d'atteindre l'ivresse, et de périodes d'abstinence. Une telle modalité de consommation d'alcool est communément rencontrée chez les jeunes. Elle entraîne des déficits cognitifs en impliquant probablement des processus neuroinflammatoires et épigénétiques. Toutefois, le mode d'action de l'alcool au cours des expositions initiales de type BD, est peu connu. Il pourrait pourtant être à l'origine de ces déficits cognitifs à long terme. Des études récentes, réalisées chez le rat adolescent, révèlent que la perte de mémoire se produit dès les premiers BD, avec des mécanismes similaires à ceux d'une exposition plus longue. L'initiation au BD chez le jeune serait donc responsable de déficits qui seront probablement entretenus par la répétition de cette pratique. Ces données originales devraient permettre de renforcer les campagnes de prévention auprès de la jeune population qui pratique le BD.
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Consumo Excesivo de Bebidas Alcohólicas , Etanol , Ratas , Animales , Etanol/toxicidad , Consumo Excesivo de Bebidas Alcohólicas/psicología , Enfermedades Neuroinflamatorias , Cognición , Epigénesis GenéticaRESUMEN
AIMS: To assess recovery of alcohol-related neuropsychological deficits in a group of patients with pure severe alcohol use disorder (AUD) during a detoxification program using the Brief Evaluation of Alcohol-Related Neuropsychological Impairment (BEARNI) test. METHODS: Thirty-two patients with severe AUD using DSM-IV criteria (24 men, mean age = 45.5 ± 6.8 years old) were assessed using the BEARNI 8 ± 2 days after alcohol cessation (T1) and then were reassessed within 18 ± 2 days after alcohol cessation (T2). The primary study endpoint was the number of patients initially impaired at T1 who recovered cognitive functions at T2 assessment. RESULTS: At T1, 59% (n = 19) patients with pure severe AUD had at least one impaired cognitive function assessed by the BEARNI. At T2, 63% of the patients with AUD with deficits at T1 had normal BEARNI cognitive scores (χ2 = 7.7, P = 0.005); specifically, the percentages of participants with normal subtest scores were 63% on memory (χ2 = 12.4, P = 0.0004), 100% on verbal fluency (χ2 = 16; P = <0.0001), 60% on alphabetical span (χ2 = 12.8; P = 0.0003) and 67% on visuospatial (χ2 = 15, P = 0.0001). CONCLUSIONS: The cognitive impairments of two-thirds of patients with pure AUD included in the present study recovered within 18 days of abstinence, earlier than reported in previous studies.
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Alcoholismo , Trastornos del Conocimiento , Disfunción Cognitiva , Masculino , Humanos , Adulto , Persona de Mediana Edad , Alcoholismo/terapia , Alcoholismo/psicología , Trastornos del Conocimiento/psicología , Cognición , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: The aim of the present study was to assess the frequency and clinical correlates of users of an Internet drug forum who changed their alcohol use during the March-May 2020 COVID-19 lockdown in France. METHODS: An anonymous Internet-based cross-sectional survey during the COVID-19 lockdown was used via messages on a French Internet drug forum. Participants reported any increase in their alcohol consumption during the lockdown. Alcohol craving and depressive/anxiety symptoms were assessed using the Obsessive and Compulsive Drinking scale (OCDS) and Hospital Anxiety and Depression scale (HADS). RESULTS: Of 1310 respondents, 974 (79% of 1270) participants reported alcohol use before lockdown. During the lockdown, 405 participants (41.6%; IC95 (38.5-44.7)) reported an increase. Odds of an increase in alcohol consumption was higher for those with HADS scores higher than 7 (aOR: 2.19; p = 0.00002), OCDS scores greater than 7 (aOR: 3.50; p < 0.001), and daily psychostimulant use (aOR: 1.85; p = 0.002). CONCLUSIONS: Users of an Internet drug forum who reported high levels of depressive symptoms, high levels of alcohol craving, and the use of psychostimulants were more likely to increase alcohol consumption during a COVID-19 lockdown.
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Alcoholismo , COVID-19 , Humanos , Alcoholismo/epidemiología , Alcoholismo/diagnóstico , COVID-19/epidemiología , Estudios Transversales , Control de Enfermedades Transmisibles , Consumo de Bebidas Alcohólicas/epidemiología , InternetRESUMEN
Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or delirium tremens (DT). In addition, we suggest that AW favors the occurrence of Wernicke's encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments.
RESUMEN
In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10-3 ) and UCHL1 (p = 0.036) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10-3 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.
Asunto(s)
Alcoholismo , Síndrome de Abstinencia a Sustancias , Animales , Ratas , Proteínas de Neurofilamentos , Proteína Ácida Fibrilar de la Glía , Ubiquitina Tiolesterasa , Proyectos Piloto , Estudios de Cohortes , Ratas Wistar , Biomarcadores , EncéfaloRESUMEN
Alcohol-related liver disease is the most prevalent chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. However, the knowledge on mechanisms by which alcohol consumption leads to cancer progression and its aggressiveness is limited. Better understanding of the clinical features and the mechanisms of alcohol-induced HCC are of critical importance for prevention and the development of novel treatments. Early stage Huh-7 and advanced SNU449 liver cancer cell lines were subjected to chronic alcohol exposure (CAE), at different doses for 6 months followed by 1-month alcohol withdrawal period. ADH activity and ALDH expression were much lower in SNU449 compared with Huh-7 cells and at the 270 mM dose, CAE decreased cell viability by about 50% and 80%, respectively, in Huh-7 and SNU449 cells but induced mortality only in Huh-7 cells. Thus, Huh-7 may be more vulnerable to ethanol toxicity because of the higher levels of acetaldehyde. CAE induced a dose-dependent increase in cell migration and invasion and also in the expression of cancer stem cells markers (CD133, CD44, CD90). CAE in Huh-7 cells selectively activated ERK1/2 and inhibited GSK3ß signaling pathways. Most of the changes induced by CAE were reversed after alcohol withdrawal. Interestingly, we confirmed the increase in CD133 mRNA levels in the tumoral tissue of patients with ethanol-related HCC compared to other HCC etiologies. Our results may explain the benefits observed in epidemiological studies showing a significant increase of overall survival in abstinent compared with non-abstinent patients.
Asunto(s)
Alcoholismo , Carcinoma Hepatocelular , Neoplasias Hepáticas , Síndrome de Abstinencia a Sustancias , Alcoholismo/complicaciones , Alcoholismo/genética , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Etanol/toxicidad , Humanos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismoRESUMEN
RATIONALE: Binge drinking during adolescence impairs learning and memory on the long term, and many studies suggest a role of neuroinflammation. However, whether neuroinflammation occurs after the very first exposures to alcohol remains unclear, while initial alcohol exposure impairs learning for several days in male rats. OBJECTIVES: To investigate the role of neuroinflammation in the effects of only two binge-like episodes on learning and on neuronal plasticity in adolescent male rat hippocampus. METHODS: Animals received two ethanol i.p. injections (3 g/kg) 9 h apart. Forty-eight hours later, we recorded long-term depression (LTD) and potentiation (LTP) in CA1 area of hippocampus slices. In isolated CA1, we measured immunolabelings for microglial activation and Toll-like receptor 4 (TLR4) and mRNA levels for several cytokines. RESULTS: Forty-eight hours after the two binges, rats performed worse than control rats in novel object recognition, LTD was reduced, LTP was increased, and excitatory neurotransmission was more sensitive to an antagonist of the GluN2B subunit of the NMDA receptor. Exposure to ethanol with minocycline or indomethacin, two anti-inflammatory drugs, or with a TLR4 antagonist, prevented all effects of ethanol. Immunolabelings at 48 h showed a reduction of neuronal TLR4 that was prevented by minocycline pretreatment, while microglial reactivity was undetected and inflammatory cytokines mRNA levels were unchanged. CONCLUSION: Two binge-like ethanol exposures during adolescence in rat involved neuroinflammation leading to changes in TLR4 expression and in GluN2B functioning inducing disturbances in synaptic plasticity and cognitive deficits. Anti-inflammatory drugs are good candidates to prevent brain function and memory deficits induced by few binge-drinking episodes.