Alcohol and alcoholism最新文献

Cytochrome P450 (CYPs) superfamily of enzymes metabolize thousands of endogenous and exogenous substrates including ethanol. Results: Cytochrome P4502E1 (CYP2E1) is involved in ethanol metabolism as part of the so-called microsomal ethanol metabolizing system, in the metabolism of fatty acids and some drugs such as acetaminophen and isoniazid, and in the activation of a variety of procarcinogens (PCs). Chronic ethanol consumption induces CYP2E1 which may result in an enhanced metabolism of these drugs to their toxic intermediates, and in the generation of carcinogens. In addition, ethanol oxidation increases and is associated with the generation of reactive oxygen species (ROS). This oxidative stress is an important driver for the development of alcohol-associated liver disease (AALD) and alcohol-mediated cancer (AMC). ROS may bind directly to proteins and to DNA. ROS may also lead to lipid peroxidation (LPO) with the generation of LPO products. These LPO products may bind to DNA forming etheno-DNA adducts. Cell culture studies as well as animal experiments have shown that CYP2E1 knock-out animals or the inhibition of CYP2E1 by chemicals results in a significant improvement of liver histology. CYP2E1 is also involved in pathogenesis of hepatic steatosis and fibrosis. More recent studies in patients with AALD have demonstrated an improvement of serum transaminase activities when CYP2E1 was inhibited by clomethiazole. In addition to its role in the generation of ROS, CYP2E1 also enhances the activation of PCs and decreases the level of retinol and retinoic acid in the liver. Conclusion: Inhibition of CYP2E1 may improve AALD and may inhibit AMC.

Introduction: Empirical evidence of the buffering effect of social capital and its underlying psychosocial mechanisms on socio-economic inequalities in alcohol use disorder (AUD) symptoms is limited. As socio-economic disadvantages often go together with deficits in resources and considering social capital's beneficial effects on health, we hypothesized a stronger buffering (at high scores) and a cumulative disadvantaged effect (at low scores) of social capital on AUD symptoms among people reporting higher socio-economic disadvantage compared with their more advantaged counterparts. Additionally, we investigated whether this moderation effect was associated with drinking motives.

Method: Three-hundred and sixty-five young adults participated in a cross-sectional online questionnaire measuring all model variables. First, we tested a moderation model, including AUD symptoms (DV), perceived socio-economic disadvantage (IV), and social capital (moderator). Secondly, we tested a moderated mediation model, additionally including drinking motives as mediators of the moderation effect tested in the first model.

Results: In the case of high social capital, young adults reporting higher socio-economic disadvantage reported fewer AUD symptoms than their advantaged counterparts, which was associated with their lower endorsement of coping, enhancement, and social motives. When social capital was low, those reporting higher socio-economic disadvantages showed higher AUD symptoms than their advantaged counterparts, which was associated with their higher endorsement of coping motives only.

Conclusion: Social capital can buffer (at high levels) or aggravate (at low levels) socio-economic inequalities in AUD symptoms, and drinking for coping, enhancement, and social motives may explain why this happens.

Aims: Magnetic resonance imaging (MRI) studies have identified brain structural predictors of treatment response in individuals with alcohol use disorder (AUD) but with varying findings and primarily in male veterans. The present study investigated cortical surface area and thickness (CT) as predictors of brief intervention response in community-based adults with AUD.

Methods: Sixty-five non-treatment-seeking adults with AUD (44.6% male, aged 33.2 ± 1.3 years) underwent an MRI and received a brief intervention comprising personalized feedback and motivational interviewing, with follow-up ~6-8 weeks later to quantify changes in drinks/week (DPW), the primary outcome. Eighteen bilateral a priori regions of interest (ROIs) were used to predict DPW at follow-up, adjusting for baseline drinking. Significant predictors were examined with secondary outcomes, percent drinking and heavy drinking days, and in relation to out-of-scanner measures of impulsivity and comorbidities.

Results: Participants exhibited significant decreases in alcohol consumption in response to the brief intervention. Eight bilateral CT ROIs in the frontal, temporal, and occipital lobes, most notably medial orbitofrontal, middle temporal, and lateral occipital gyri, predicted DPW; however, only three predicted the secondary outcomes. Significant associations were observed between CT in frontal and occipital regions and impulsivity (delay discounting, lack of premeditation), executive functioning, anxiety, and stress.

Conclusions: Thinner frontal, temporal, and occipital ROIs predicted poorer brief intervention response, with notable overlap with brain regions previously implicated in AUD. Clarifying whether these regions reflect premorbid or acquired differences and, if the latter, the potential for recovery of cortical gray matter following drinking reductions are future priorities.

Background: Gabapentin, an anticonvulsant medication, has been proposed as a treatment for alcohol use disorder (AUD). A multisite study tested gabapentin enacarbil extended-release (GE-XR; 600 mg/twice a day), a prodrug formulation, combined with a computerized behavioral intervention, for AUD. In this multisite trial, the gabapentin GE-XR group did not differ significantly from placebo on the primary outcome of percent of subjects with no heavy drinking days. Despite the null findings, there is considerable interest in using machine learning methods to identify responders to GE-XR. The present study applies interaction tree machine learning methods to identify positive and iatrogenic (i.e. individuals who responded better to placebo than to GE-XR) treatment responders in the trial.

Methods: Baseline characteristics taken from the multisite trial were examined as potential moderators of treatment response using qualitative interaction trees (QUINT; N = 338; 223 M/115F). QUINT models are an exploratory decision tree approach that iteratively splits the data into leaves based on predictor variables to maximize a specific criterion.

Results: Analyses identified key factors that are associated with the efficacy (or iatrogenic effects) of GE-XR for AUD. Such factors are baseline drinking levels, motivation for change, confidence in their ability to reach drinking goals (i.e. self-efficacy), cognitive impulsivity, and baseline anxiety levels.

Conclusion: Baseline drinking levels and anxiety levels may be associated with the protracted withdrawal syndrome, previously implicated in the clinical response to gabapentin. However, these analyses underscore motivation for change and self-efficacy as predictors of clinical response to GE-XR, suggesting these established constructs should receive further attention in gabapentin research and clinical practice. Multiple studies using different machine learning methods are valuable as these novel analytic tools are applied to medication development for AUD.

To understand the need for addiction treatment across the spectrum of adult age, this study evaluated the age of individuals with alcohol/substance use disorder (N = 541) who sought treatment in a local center in Rhode Island. Data extracted from the community showed a need for clinical research to support future addiction medicine that is age-inclusive (e.g. including older adults in clinical trials).

Aims: This study compared individuals with hazardous alcohol consumption who used the web-based intervention "Ohne Alkohol mit Nathalie" (OAMN) with individuals who relied exclusively on traditional support to enhance the understanding of OAMN user characteristics.

Methods: A cross-sectional online survey included 2460 treatment-seeking participants with Alcohol Use Disorders Identification Test scores ≥8 indicating hazardous alcohol use. The OAMN group (n = 1825) included individuals who had used OAMN programs, while the non-OAMN group (n = 635) relied exclusively on traditional support. Analyses compared sociodemographic characteristics, psychiatric comorbidities, the extent to which OAMN was used as a standalone or complementary tool, alcohol consumption, and abstinence motives.

Results: Both groups were predominantly female and highly educated, but these characteristics were more pronounced among OAMN users. About one-third of OAMN users relied exclusively on the examined intervention, while two-thirds combined it with other forms of support. Non-OAMN users exhibited higher psychiatric comorbidities and had higher Alcohol Use Disorders Identification Test scores. Intrinsic motives were key drivers for abstinence in both groups, while these motives were more pronounced among OAMN users and extrinsic motives were more frequently reported by non-OAMN users.

Conclusion: These findings show that OAMN primarily attracts well-educated women and that it's used as both a standalone and complementary intervention. OAMN users were more likely to report intrinsic motives such as improving well-being and autonomy as key drivers for abstinence and less likely to report extrinsic motives such as external expectations and fear. These insights enhance understanding of the characteristics and abstinence motives of individuals engaging with OAMN.

Aims: The goal of the present study was to determine the effect of prior experience with ethanol drinking and changes in session duration on the acquisition and maintenance of operant ethanol self-administration.

Methods: Adult male and female Long-Evans rats were trained to operantly self-administer ethanol. A subset of rats underwent 3 weeks of intermittent-access two-bottle choice drinking in the home cage prior to operant training. Controls were given access to two bottles of water. Once fully trained in 30-min operant sessions, the session duration was reduced to 15 min for all rats. Differences between 30- and 15-min sessions were also assessed in a separate group of rats trained to self-administer sucrose.

Results: No differences were observed in acquisition rates, the magnitude of responding for ethanol, or total ethanol consumed between rats allowed to drink ethanol in the home cage and those that remained ethanol naïve prior to operant training. A significant decrease in appetitive and consummatory behaviors was observed in rats trained to lever press for either ethanol or sucrose when session length was reduced from 30 to 15 min. Assessment of within-session drinking patterns suggests that this is driven primarily by missed drinking opportunities occurring during the second half of 30-min sessions.

Conclusions: These data suggest that prior short-term home cage ethanol drinking offers little advantage as an initiation procedure over no initiation procedure at all. Moreover, reducing operant session duration from 30-min to 15-min has the potential to decrease, rather than increase, levels of ethanol intake.

Aims: We described the age-specific trajectories of total alcohol consumption and the consumption of different types of beverages among adult Norwegian women as they age, and how these relate to education, lifestyle, and health-related factors.

Methods: This study included 76 382 women aged 31-70 years who participated in at least two of the three Norwegian Women and Cancer (NOWAC) study surveys conducted in 1991-97, 1998-2003, and 2004-11. Group-based trajectory modeling was used to identify the trajectories of self-reported alcohol consumption. Multinomial regression models were used to fit the adjusted odds ratios (ORs) of the associations between education, lifestyle, health-related factors, and the trajectory membership. Analysis was stratified into two subcohorts: women aged 31-49 years and women aged 50-70 years at enrolment.

Results: Five different trajectories of total alcohol consumption were identified among the two subcohorts: non-drinker stable (12.5%-23.6%), low stable (66.3%-60.1%), light increasing or light unstable (17.8%-12.1%), moderate to high or light to high (2.8%-2.7%), and high to moderate or moderate decreasing (.6%-1.4%). Trajectories were resembled by those of wine consumption. Compared to low stable drinkers, women who sustained or increased their total alcohol consumption showed higher ORs for higher education level, excellent self-rated health, former or current smoking status, and a body mass index (BMI) below 25 kg/m2.

Conclusion: While most women in this study maintained stable low-light levels of alcohol consumption, certain groups-such as women with higher education and better health-were more likely to increase their drinking with age. Women can particularly increase their drinking around the retirement age. The increasing trends of total alcohol consumption were reflected by those of wine. These findings provide information into groups and beverages that could be targeted in alcohol-reducing interventions.

Aims and methods: Hazardous alcohol use poses an increasing public health issue worldwide and it manifests as excessive consumption (acute or chronic), which may lead to addiction. The risk of alcohol-related pathologies correlates with the patterns of intake and increases with the amount of alcohol consumed. While the effects of alcohol consumption on ischemic stroke and ischemic heart disease are well documented, the impact on venous thromboembolism is less clear. Conflicting studies have reported that alcohol may be a risk factor for, or have a protective role against venous thromboembolism. Our narrative review aimed to assess the risk of unusual-site venous thrombosis in individuals with hazardous alcohol use, as it may stem from alcohol-related organ damage (e.g. liver cirrhosis, pancreatitis) as well as provide some suggestions for physicians.

Results: There appears to be a correlation between hazardous alcohol use and unusual-site thrombosis, though the underlying mechanisms are largely still unknown.

Conclusion: In subjects with hazardous alcohol use complicated by alcohol-related organ damage, physicians should be vigilant for potential thrombotic symptoms, and be prepared to diagnose and promptly initiate appropriate anticoagulation therapy.