Current View on the Mechanisms of Alcohol-Mediated Toxicity.

Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic pathological conditions. Some of the effects are very well described and explained, but there are still gaps in the explanation of empirically co-founded dysfunction in many alcohol-related conditions. This work focuses on reviewing actual knowledge about the toxic effects of ethanol and its degradation products.

Magnitude and correlates of alcohol use disorder in south Gondar zone, northwest Ethiopia: A community based cross-sectional study.

BACKGROUND: Alcohol use disorder is the major public health problem in low- and middle-income countries that account for up to 70% of alcohol related premature mortality in the region. Therefore, the aim of this study was to assess the magnitude of alcohol use disorder and its associated factors among adult residents in south Gondar zone, Northwest Ethiopia. METHODS: A community-based cross-sectional study was conducted among 848 adult residents of the south Gondar zone from January 13 to February 13, 2020. A multistage sampling technique was used to recruit study participants. We assessed alcohol use disorder (AUD) using the alcohol use disorder identification test (AUDIT). A binary logistic regression model was employed to identify factors associated with AUD. RESULTS: The prevalence of alcohol use disorder over the last 12-months was found to be 23.7% (95% CI: 20.9, 26.7). Being male (AOR = 4.34, 95 CI; 2.800, 6.743), poor social support (AOR = 1.95, 95 CI: 1.098, 3.495), social phobia (AOR = 1.69, 95 CI; 1.117, 2.582), perceived high level of stress (AOR = 2.85, 95 CI; 1.829, 34.469), current cigarette smoking (AOR = 3.06, 95 CI; 1.764, 5.307) and comorbid depression (AOR = 1.81, 95 CI; 1.184, 2.778) were significantly associated with alcohol use disorder. CONCLUSION: The prevalence of alcohol use disorder is high among adult residents of the south Gondar zone and associated with many factors. So, it needs public health attention to decrease the magnitude of alcohol use disorder in Ethiopia.

Perspectives on Mitochondria-ER and Mitochondria-Lipid Droplet Contact in Hepatocytes and Hepatic Lipid Metabolism.

Emerging evidence suggests that mitochondrion-endoplasmic reticulum (ER) and mitochondrion-lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion-ER and mitochondrion-LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion-LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.

Exploring relationships between alcohol consumption, inflammation, and brain structure in a heavy drinking sample.

BACKGROUND: Chronic alcohol consumption is associated with structural brain changes and increased inflammatory signaling throughout the brain and body. Increased inflammation in the brain has been associated with structural damage. Recent studies have also shown that neurofilament light polypeptide (NfL) is released into the systemic circulation following neuronal damage. Although NfL has thus been proposed as a biomarker for neurodegenerative diseases, its connection to alcohol use disorder has not been explored. For this secondary data analysis, we proposed a conceptual model linking alcohol consumption, the pro-inflammatory cytokine IL-6, brain structure, and NfL in heavy drinking participants. METHODS: Of the 182 individuals enrolled in this study, 81 participants had usable data on gray matter (GM) thickness and 80 had usable data on white matter (WM) diffusivity. A subset of participants had NfL (n = 78) and IL-6 (n = 117) data. An estimate of GM thickness was extracted from middle frontal brain regions using FreeSurfer. Estimated mean WM diffusivity values were extracted from Tract Based Spatial Statistics. NfL and IL-6 were measured in blood. Regression models were used to test individual linkages in the conceptual model. Based on significant regression results, we created a simplified conceptual model, which we tested using path analysis. RESULTS: In regressions, negative relationships emerged between GM and both drinks per drinking day (DPDD) (p = 0.018) and NfL (p = 0.004). A positive relationship emerged between WM diffusivity and DPDD (p = 0.033). IL-6 was not significantly associated with alcohol use, GM or WM. The final path model demonstrated adequate fit to the data and showed significant, negative associations between DPDD and middle frontal gyrus (MFG) thickness, and between MFG thickness and NfL, but the association between DPDD and NfL was not significant. CONCLUSIONS: This is the first study to show that heavy drinking is associated with lower GM thickness and higher WM diffusivity and that lower GM thickness is associated with higher circulating NfL. The analyses also show that the effects of drinking do not involve the pro-inflammatory cytokine IL-6.

Negative evaluation of role transitions is associated with perceived stress and alcohol consequences: Examination of the Transitions Overload Model in young adulthood using two years of monthly data.

BACKGROUND: Young adulthood is characterized by transitions into and out of social roles in multiple domains. Consistent with self-medication models of alcohol use, the Transitions Overload Model (J Stud Alcohol Suppl, 14, 2002, 54) hypothesizes that one cause of increased alcohol use during young adulthood may be the stress of navigating simultaneous role transitions. This study examined the simultaneous occurrence of major developmental role transitions in the domains of education, employment, romantic relationships, and residential status and their associations with perceived stress, heavy episodic drinking (HED), and negative alcohol-related consequences. Further, we extended the Transitions Overload Model to explore whether the number of transitions rated as having a negative impact on one's life was related to perceived stress, HED, and alcohol-related consequences. METHODS: A community sample of young adult drinkers (N = 767, 57% women, ages 18 to 25 years) in the Pacific Northwest provided monthly data across 2 years. Multilevel models were used to assess the average (between-person) and month-to-month (within-person) associations of role transitions with perceived stress, HED, and negative alcohol-related consequences. RESULTS: Although having more role transitions was positively associated with HED frequency and alcohol-related consequences at both the between- and within-person (monthly) levels, it was not associated with increased stress. The number of transitions rated as having a negative impact on one's life, however, was positively associated with stress. Thus, rather than the total number of transitions, it is the number of negatively perceived major developmental role transitions that is associated with perceived stress and increased risk for negative alcohol-related consequences. CONCLUSIONS: Contrary to Transitions Overload Model assumptions, more transitions were not a significant predictor of more perceived stress; rather, the evaluation of the transition as negative was associated with stress and negative alcohol-related outcomes. This distinction may help elucidate the etiology of stress and subsequent alcohol consequences and identify individuals at-risk of these effects.

Persistent attention-deficit/hyperactivity disorder predicts socially oriented, but not physical/physiologically oriented, alcohol problems in early adulthood.

BACKGROUND: Although individuals with histories of childhood attention-deficit/hyperactivity disorder (ADHD) report more alcohol-related problems in adulthood than those without ADHD, it is unknown whether there are group differences in certain types of alcohol problems. We tested whether the nature of alcohol problems differed for individuals with and without childhood ADHD, as well as adulthood-persistent ADHD, to facilitate a personalized medicine approach for alcohol problems in this high-risk group. METHODS: Data were drawn from a prospective, observational study. Children diagnosed with ADHD and demographically similar individuals without childhood ADHD were followed prospectively through young adulthood (N = 453; 87.6% male). ADHD symptom persistence was assessed using self-reports and parent reports. Alcohol problems and heavy drinking were assessed repeatedly from 18-30 years old to construct lifetime measures. RESULTS: Full-sample confirmatory factor analyses identified 5 alcohol problem "types:" interpersonal problems/risky behaviors, occupational/academic impairment, impaired control/treatment seeking, tolerance/withdrawal, and drinking to blackout. Latent class analyses of items within each type yielded the best fit for 3-class solutions for all sets of items except blackout drinking, for which 2 classes emerged. Children with ADHD were more likely than those without ADHD to belong to high-risk latent classes for interpersonal problems/risky behaviors, occupational/academic problems, and impaired control (the high-risk class that indexed treatment-seeking behavior). These effects were driven by individuals whose ADHD symptoms persisted into adulthood. Few group differences emerged for tolerance/withdrawal and blackout drinking, except that individuals with only childhood ADHD (no persistence) were more likely to belong to the low-risk groups than those with adulthood-persistent ADHD and without ADHD. CONCLUSIONS: Individuals with ADHD histories whose symptoms persist into adulthood may be more likely to experience socially oriented alcohol problems and impaired control/treatment seeking than individuals without an ADHD history and those with childhood ADHD only. Tailored alcohol prevention and treatment programs may benefit this high-risk population.

The morning after the night before: Alcohol-induced blackouts impair next day recall in sober young adults.

Binge-drinking in adolescents and young adults is a widespread problem, however, an often unreported consequence of binge-drinking behaviour is an alcohol-induced memory blackout (MBO). An MBO is a transient amnesic event resulting from rapid, excessive alcohol consumption. Here, we examine the short-term impact of an alcohol-induced MBO event (testing < 20 hours after blackout) on memory performance in people who have experienced a high volume of MBOs. In addition, we aimed to test the hypothesis that people who experience a high volume of MBOs may have poorer recall than non-blackout controls in either sober or intoxicated states. Three episodic memory paradigms consisting of free recall, serial recall, and depth of encoding tasks, were conducted by a group of alcohol drinkers who had never experienced a memory blackout, and those who reported at least 9 in the preceding 12-months. Studies were completed sober and after alcohol by all participants, and sober but after blackout by the experimental group. Accuracy of recall was assessed with linear mixed effects modelling for all experiments and conditions. Recall rate both before and after alcohol consumption was similar between groups, with poorer recall after drinking alcohol by all participants in all three studies. After blackout, MBO participants showed no significant improvement from their intoxicated state in serial recall and depth of encoding tasks, but an improvement in free recall. Further analysis of these findings revealed that 10 out of 23 participants showed significantly impaired performance after blackout during free recall, extending up to 17 participants in serial recall. In general, alcohol reduced recall rate in both blackout and control participants similarly, but recall following MBO remained poor. Our evidence suggests that alcohol-induced blackouts impair memory functioning the next day, and future research should establish the duration of deficits after an acute alcohol-induced blackout episode.

Stepped Collaborative Care Targeting Posttraumatic Stress Disorder Symptoms and Comorbidity for US Trauma Care Systems: A Randomized Clinical Trial.

Importance: To date, few multisite investigations have evaluated early interventions for injured patients with posttraumatic stress disorder (PTSD) symptoms. Objective: To simultaneously assess the effectiveness and implementation of a brief stepped collaborative care intervention targeting PTSD and comorbidity. Design, Setting, and Participants: A stepped-wedge cluster randomized clinical trial was conducted at 25 US level I trauma centers. Participants included hospitalized survivors of physical injury who underwent a 2-step evaluation for PTSD symptoms. Patients reporting high levels of distress on the PTSD Checklist (PCL-C) were randomized (N = 635) per the stepped-wedge protocol to enhanced usual care control (n = 370) or intervention (n = 265) conditions. The study was conducted from January 4, 2016, through November 2018. Data analysis was performed from November 4, 2019, to December 8, 2020. Interventions: The Trauma Survivors Outcomes and Support collaborative care intervention included proactive injury case management that assisted patients transitioning from hospital inpatient to outpatient and community settings. The intervention also integrated evidence-based pharmacotherapy and psychotherapeutic elements targeting PTSD symptoms and comorbidity. Main Outcomes and Measures: The primary study outcome was PTSD symptoms assessed with the PCL-C at baseline in the surgical ward and at 3, 6, and 12 months postinjury. Secondary outcomes included depressive symptoms, alcohol use, and physical function. Subgroup analyses examined the effect of baseline risk factors for enduring PTSD and quality of protocol implementation on study outcomes. Primary statistical analyses were conducted using the intent-to-treat sample. Results: A total of 327 men (51.5%) were included in analysis; mean (SD) age was 39.0 (14.2) years. The investigation attained follow-up of 75% to 80% of the participants at 3 to 12 months. The intervention lasted a mean (SD) of 122 (132) minutes. Mixed model regression analyses revealed statistically significant changes in PCL-C scores for intervention patients compared with control patients at 6 months (difference, -2.57; 95% CI, -5.12 to -0.03; effect size, 0.18; P < .05) but not 12 months (difference, -1.27; 95% CI, -4.26 to 1.73; effect size, 0.08; P = .35). Subgroup analyses revealed larger PTSD treatment effects for patients with 3 or more baseline risk factors for enduring PTSD and for patients, including firearm injury survivors, treated at trauma centers with good or excellent protocol implementation. Intervention effects for secondary outcomes did not attain statistical significance. Conclusions and Relevance: A brief stepped collaborative care intervention was associated with significant 6-month but not 12-month PTSD symptom reductions. Greater baseline PTSD risk and good or excellent trauma center protocol implementation were associated with larger PTSD treatment effects. Orchestrated efforts targeting policy and funding should systematically incorporate the study findings into national trauma center requirements and verification criteria. Trial Registration: ClinicalTrials.gov Identifier: NCT02655354.

Childhood and Adolescent Bullying Perpetration and Later Substance Use: A Meta-analysis.

CONTEXT: Previous meta-analyses substantially contributed to our understanding of increased drug use risk in bullies but only included research up to 2014 and did not report on other types of substances. OBJECTIVE: To review and meta-analyze existing evidence regarding the prospective association between peer bullying perpetration in childhood and adolescence and later substance use. DATA SOURCES: Electronic databases were searched on March 14, 2019. STUDY SELECTION: We selected peer-reviewed articles and dissertations in English reporting original empirical studies on associations between bullying perpetration in childhood or adolescence and later use of drugs, alcohol, or tobacco. Records were assessed for eligibility independently by 2 authors. DATA EXTRACTION: Data extraction and quality assessment was performed by one author and checked by another author. RESULTS: In total, 215 effects were included from 28 publications, reporting on 22 samples, comprising 28 477 participants. Bullying perpetration was associated positively with all types of substance use (drugs, alcohol, tobacco, and general). The results for combined bullying-victimization were more mixed, with generally weaker effects. LIMITATIONS: Effects were based on a large variability in operationalizations and measures of bullying and substance use, impeding the interpretation of the pooled effect sizes. Although bullying appears to be a risk factor for substance use, no inferences can be made about so-called causal risk factors that can provide the basis for preventive interventions. CONCLUSIONS: There is evidence that adolescents and particularly children who bully their peers have a higher risk of substance use later in life than their nonbullying peers.

Mental health of staff working in intensive care during Covid-19.

BACKGROUND: Staff working in intensive care units (ICUs) have faced significant challenges during the COVID-19 pandemic which have the potential to adversely affect their mental health. AIMS: To identify the rates of probable mental health disorder in staff working in ICUs in nine English hospitals during June and July 2020. METHODS: An anonymized brief web-based survey comprising standardized questionnaires examining depression, anxiety symptoms, symptoms of post-traumatic stress disorder (PTSD), well-being and alcohol use was administered to staff. RESULTS: Seven hundred and nine participants completed the surveys comprising 291 (41%) doctors, 344 (49%) nurses and 74 (10%) other healthcare staff. Over half (59%) reported good well-being; however, 45% met the threshold for probable clinical significance on at least one of the following measures: severe depression (6%), PTSD (40%), severe anxiety (11%) or problem drinking (7%). Thirteen per cent of respondents reported frequent thoughts of being better off dead, or of hurting themselves in the past 2 weeks. Within the sample used in this study, we found that doctors reported better mental health than nurses across a range of measures. CONCLUSIONS: We found substantial rates of probable mental health disorders, and thoughts of self-harm, amongst ICU staff; these difficulties were especially prevalent in nurses. Whilst further work is needed to better understand the real level of clinical need amongst ICU staff, these results indicate the need for a national strategy to protect the mental health, and decrease the risk of functional impairment, of ICU staff whilst they carry out their essential work during COVID-19.

Moderate alcohol consumption is associated with impaired insulin secretion and fasting glucose in non-obese non-diabetic men.

AIMS/INTRODUCTION: A low insulin secretion capacity has been implicated in the high prevalence of non-obese diabetes in East Asians. As alcohol consumption alters insulin and glucose metabolism, we tested the hypothesis that alcohol consumption contributes to impaired insulin secretion and glucose intolerance in lean/normal-weight non-diabetic Japanese men. MATERIALS AND METHODS: This cross-sectional study was undertaken among the residents of Shika town, Japan, between 2011 and 2017. A total of 402 non-diabetic men, including participants with normal fasting plasma glucose (FPG) and impaired FPG (FPG 5.6-6.9 mmol/L), and aged ≥40 years, were examined. FPG, the homeostasis model assessment of insulin secretion capacity (HOMA-B) and alcohol consumption were evaluated and compared between the body mass index (BMI) <25 and BMI ≥25 groups. RESULTS: HOMA-B levels were lower in the BMI <25 group than in the BMI ≥25 group. Alcohol consumption correlated with a low HOMA-B level regardless of BMI, and, thus, the HOMA-B levels of alcohol drinkers were significantly lower in the BMI <25 group. A multivariable logistic regression analysis showed that alcohol consumption, even light-to-moderate consumption (1-25 g/day), was associated with significantly low levels of HOMA-B and impaired FPG in the BMI <25 group. Among participants with impaired FPG, a low level of HOMA-B was observed in alcohol drinkers, but not in non-drinkers. In contrast, light-to-moderate alcohol consumption was not related to HOMA-B or FPG in the BMI ≥25-group. CONCLUSION: Alcohol consumption, even a small amount, might contribute to reductions in HOMA-B levels and impaired FPG in lean/normal-weight Japanese men.

The "Why" of Drinking Matters: A Meta-Analysis of the Association Between Drinking Motives and Drinking Outcomes.

BACKGROUND: Knowledge of how drinking motives are differentially associated with alcohol use (e.g., frequency, quantity) and drinking problems is critical in understanding risky drinking and the development of alcohol use disorder. The purpose of this paper was to use meta-analytic techniques to answer 2 overarching questions: (a) Which types of drinking motives (i.e., enhancement, coping, social, conformity) are most strongly associated with alcohol use and drinking problems? and (b) What are the most likely mechanisms (alcohol use or drinking problems) through which motives may be indirectly associated with outcomes? METHOD: A comprehensive literature search identified 229 studies that met inclusion criteria (254 samples; N = 130,705) with a subset containing longitudinal data (k = 5; N = 6283). Data were analyzed using 2-stage meta-analytic structural equation modeling. RESULTS: Results showed that both enhancement and coping motives were the strongest predictors of drinking problems, but only enhancement motives were the strongest predictor of alcohol use. Enhancement and social motives were indirectly associated with alcohol use through drinking problems and with drinking problems through alcohol use, whereas coping motives were only indirectly associated with alcohol use through drinking problems, although the results differed for cross-sectional and longitudinal data. CONCLUSION: Overall, findings from this meta-analysis provide evidence that drinking motives differentially predict alcohol use outcomes through unique direct and indirect pathways.

Increase in prevalence of current mental disorders in the context of COVID-19: analysis of repeated nationwide cross-sectional surveys.

AIMS: The United Nations warned of COVID-19-related mental health crisis; however, it is unknown whether there is an increase in the prevalence of mental disorders as existing studies lack a reliable baseline analysis or they did not use a diagnostic measure. We aimed to analyse trends in the prevalence of mental disorders prior to and during the COVID-19 pandemic. METHODS: We analysed data from repeated cross-sectional surveys on a representative sample of non-institutionalised Czech adults (18+ years) from both November 2017 (n = 3306; 54% females) and May 2020 (n = 3021; 52% females). We used Mini International Neuropsychiatric Interview (MINI) as the main screening instrument. We calculated descriptive statistics and compared the prevalence of current mood and anxiety disorders, suicide risk and alcohol-related disorders at baseline and right after the first peak of COVID-19 when related lockdown was still in place in CZ. In addition, using logistic regression, we assessed the association between COVID-19-related worries and the presence of mental disorders. RESULTS: The prevalence of those experiencing symptoms of at least one current mental disorder rose from a baseline of 20.02 (95% CI = 18.64; 21.39) in 2017 to 29.63 (95% CI = 27.9; 31.37) in 2020 during the COVID-19 pandemic. The prevalence of both major depressive disorder (3.96, 95% CI = 3.28; 4.62 v. 11.77, 95% CI = 10.56; 12.99); and suicide risk (3.88, 95% CI = 3.21; 4.52 v. 11.88, 95% CI = 10.64; 13.07) tripled and current anxiety disorders almost doubled (7.79, 95% CI = 6.87; 8.7 v. 12.84, 95% CI = 11.6; 14.05). The prevalence of alcohol use disorders in 2020 was approximately the same as in 2017 (10.84, 95% CI = 9.78; 11.89 v. 9.88, 95% CI = 8.74; 10.98); however, there was a significant increase in weekly binge drinking behaviours (4.07% v. 6.39%). Strong worries about both, health or economic consequences of COVID-19, were associated with an increased odds of having a mental disorder (1.63, 95% CI = 1.4; 1.89 and 1.42, 95% CI = 1.23; 1.63 respectively). CONCLUSIONS: This study provides evidence matching concerns that COVID-19-related mental health problems pose a major threat to populations, particularly considering the barriers in service provision posed during lockdown. This finding emphasises an urgent need to scale up mental health promotion and prevention globally.

Practice facilitation to promote evidence-based screening and management of unhealthy alcohol use in primary care: a practice-level randomized controlled trial.

BACKGROUND: Unhealthy alcohol use is the third leading cause of preventable death in the United States. Evidence demonstrates that screening for unhealthy alcohol use and providing persons engaged in risky drinking with brief behavioral and counseling interventions improves health outcomes, collectively termed screening and brief interventions. Medication assisted therapy (MAT) is another effective method for treatment of moderate or severe alcohol use disorder. Yet, primary care clinicians are not regularly screening for or treating unhealthy alcohol use. METHODS AND ANALYSIS: We are initiating a clinic-level randomized controlled trial aimed to evaluate how primary care clinicians can impact unhealthy alcohol use through screening, counseling, and MAT. One hundred and 25 primary care practices in the Virginia Ambulatory Care Outcomes Research Network (ACORN) will be engaged; each will receive practice facilitation to promote screening, counseling, and MAT either at the beginning of the trial or at a 6-month control period start date. For each practice, the intervention includes provision of a practice facilitator, learning collaboratives with three practice champions, and clinic-wide information sessions. Clinics will be enrolled for 6-12 months. After completion of the intervention, we will conduct a mixed methods analysis to identify changes in screening rates, increase in provision of brief counseling and interventions as well as MAT, and the reduction of alcohol intake for patients after practices receive practice facilitation. DISCUSSION: This study offers a systematic process for dissemination and implementation of the evidence-based practice of screening, counseling, and treatment for unhealthy alcohol use. Practices will be asked to implement a process for screening, counseling, and treatment based on their practice characteristics, patient population, and workflow. We propose practice facilitation as a robust and feasible intervention to assist in making changes within the practice. We believe that the process can be replicated and used in a broad range of clinical settings; we anticipate this will be supported by our evaluation of this approach. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT04248023, Registered 5 February 2020.

Heart Rate Variability Reactivity Moderates the Indirect Link Between Child Maltreatment and Young Adult Alcohol Use Problems Via Depressive Symptoms.

BACKGROUND AND OBJECTIVES: Young adults with childhood maltreatment (CM) histories are particularly vulnerable to depressive symptoms and alcohol use problems. Research suggests that maltreated youth may misuse alcohol in part to alleviate depressive symptoms. However, many youths with depressive symptoms exercise self-control and abstain from heavy alcohol use. The present study aimed to examine the influence of heart rate variability reactivity (HRV-R), a psychophysiological biomarker of self-regulation, in the indirect link between CM and alcohol-use problems via depressive symptoms among low socioeconomic-status rural young adults. METHODS: Two waves of data were collected from a community sample of 225 low socioeconomic-status nonmetropolitan young adults (Mage = 21.56, 52.9% female). HRV data were obtained with an electrocardiogram during a social stress task. CM was assessed through the Childhood Trauma Questionnaire. Alcohol use problems were measured using the Alcohol Use Disorders Identification Test. RESULTS: The indirect effect of CM on alcohol use problems via elevated depressive symptoms was positive and significant (α × ß = .159, P < .001). Self-regulation, indicated by high HRV-R (ie, vagal withdrawal), was found to significantly buffer the link between depressive symptoms and alcohol use problems (ß = .193, P = .022). DISCUSSION AND CONCLUSIONS: Adequate self-regulation capacities can protect maltreated youths from self-medicating alcohol use problems. SCIENTIFIC SIGNIFICANCE: This study will advance researchers' understanding of the development of alcohol use problems through unwrapping the risk and protective mechanisms underlying the association between young adults' early life stress and alcohol use behaviors. (Am J Addict 2020;29:141-150).

Pain Severity and Alcohol Use Among Daily Tobacco Cigarette Smokers.

BACKGROUND AND OBJECTIVES: Pain is associated with hazardous alcohol use. Drinkers have reported using alcohol for pain-coping, and negative affect may be a key mechanism in pain-induced motivation to drink. However, no previous study has examined pain severity in relation to alcohol consumption, dependence, and alcohol-related consequences. Moreover, no studies have examined pain-alcohol interrelations among tobacco cigarette smokers. These secondary analyses tested the hypotheses that greater past 4-week pain severity would be positively associated with indices of hazardous drinking (ie, quantity/frequency, harmful use, and dependence), and that the current pain intensity would be positively/indirectly associated with the urge to drink via negative affect. METHODS: Participants included 225 daily smokers (43% female; MCPD = 22) who completed the baseline session for a larger experimental study. RESULTS: Every one-point increase in pain severity was associated with a 47% increased likelihood of hazardous drinking, and pain severity was positively associated with quantity/frequency of alcohol consumption, harmful patterns of drinking, and alcohol dependence level (Ps < .05). Pain intensity was indirectly associated with urge to drink via negative affect (P < .05). CONCLUSIONS: These findings provide initial evidence that smokers with greater pain severity may also report hazardous patterns of alcohol use. SCIENTIFIC SIGNIFICANCE: This is the first study to demonstrate that past 4-week pain severity may be one factor that maintains three conceptually distinct patterns of hazardous drinking among smokers. The current results also provide the first evidence that greater pain intensity may be associated with an increased urge to drink alcohol, via negative affect. (Am J Addict 2020;29:134-140).

Alcohol Use Disorders in Adolescents.

Alcohol use during adolescence is an important and modifiable health risk behavior given the significant acute consequences and long-term impacts on the developing brain. Alcohol is the most common substance used by young adults 12 to 17 years old, with binge drinking, polysubstance use, and co-occurring mental health disorders posing particular concerns in this age group. Physicians can play a crucial role in screening and responding to alcohol use, with targeted brief interventions designed to delay or decrease use.

Alcohol and Hypertension-New Insights and Lingering Controversies.

PURPOSE OF REVIEW: To examine outstanding issues in the relationship of alcohol to hypertension. These include whether the increase in BP with alcohol is causally related, the nature of the relationship in women, the contribution of alcohol-related increases in BP to cardiovascular disease and the aetiology of alcohol-related hypertension. RECENT FINDINGS: Intervention studies and Mendelian randomisation analyses confirm the alcohol-BP relationship is causal. The concept that low-level alcohol intake reduces BP in women is increasingly unsustainable. Alcohol-related hypertension is in the causal pathway between alcohol use and increased risk for several cardiovascular outcomes. The aetiology of alcohol-related hypertension is multifactorial with recent data highlighting the effects of alcohol on the vasoconstrictor 20-HETE and oxidative stress. The high prevalence of both alcohol use and hypertension mandates a careful alcohol history in every patient with elevated BP. Early intervention for excessive alcohol use offers the promise of lower levels of BP and reduced risk of adverse cardiovascular outcomes.

Interoceptive awareness is associated with acute alcohol-induced changes in subjective effects.

Interoception, the sensing of bodily signals, is related to emotional reactivity and may contribute to the pathophysiology of addiction. Evidence is accumulating that individuals with alcohol use disorders and other substance-dependences show altered interoceptive processing, however little is known about the acute effects of alcohol on interoception and how this may influence the perception of drug induced effects. In a double-blind design, fifty (30 females) healthy young participants were given a beverage containing either a low (0.4 g/kg, n = 18) or high (0.6 g/kg, n = 15) alcohol dose or a placebo (n = 17). After alcohol administration, participants completed two interoceptive paradigms, the heart-beat tracking and heart-beat discrimination tasks, both assessing different accuracy and metacognitive measures of interoception. Subjective feelings elicited by alcohol administration were also measured. Participants under the low alcohol dose had lower metacognitive interoceptive awareness on the discrimination task compared to placebo. Participants under alcohol experienced feelings of light-headedness, which were positively associated with increased interoceptive awareness in the cardiac discrimination task. These results provide evidence for a relationship between interoceptive processing and the perception of drug-induced mood changes. This finding, showing how interoceptive awareness of cardiac discrimination contributes to the appraisal of subjective light-headedness generated by alcohol administration, brings novel perspectives to the understanding of drug discrimination and reinforcement mechanisms.