Associations Between Smoking, Alcohol Consumption, Physical Activity and Depression in Middle-Aged Premenopausal and Postmenopausal Women

Background: Changes in lifestyle factors are known to affect mood. However, there is insufficient evidence supporting the association between smoking, alcohol consumption, physical activity and depression in middle-aged women who are likely to experience rapid hormonal changes.Methods: We used a nationwide database of medical records in South Korea. 901,721 premenopausal and 943,710 postmenopausal women aged 40 years or older included in this study. Information on smoking, alcohol consumption, physical activity was identified from health examination data and followed up for the occurrence of depression using claims data.Results: Compared with never-smokers, ex-smokers and current smokers among premenopausal and postmenopausal women showed an increased risk of depression in a dose-dependent manner (aHR 1.13 for ex-smokers; aHR 1.23 for current smokers). Compared with non-drinkers, mild drinkers showed a decreased risk of depression (aHR 0.98 for premenopausal women; aHR 0.95 for postmenopausal women), and heavy drinkers showed an increased risk of depression both among premenopausal (aHR 1.20) and postmenopausal women (aHR 1.05). The risk of depression due to smoking and heavy alcohol consumption was higher in premenopausal women than in postmenopausal women. Compared with those who had not engaged in regular physical activity, those who had engaged showed a decreased risk of depression both among premenopausal (aHR 0.96) and postmenopausal women (aHR 0.95).Conclusions: Smoking and heavy alcohol consumption increased the risk of depression, and the increased risk was prominent in premenopausal than in postmenopausal women. Regular physical activity decreased the risk of depression both in premenopausal and postmenopausal women.

Abdominal pain and cirrhosis at diagnosis of hemochromatosis: Analysis of 219 referred probands with HFE p.C282Y homozygosity and a literature review

Background In hemochromatosis, causes of abdominal pain and its associations with cirrhosis are poorly understood. Methods We retrospectively compared characteristics of referred hemochromatosis probands with HFE p.C282Y homozygosity with/without biopsy-proven cirrhosis: sex, age, diabetes, heavy alcohol consumption, abdominal pain/tenderness, hepatomegaly, splenomegaly, non-alcoholic fatty liver disease, chronic viral hepatitis, ascites, transferrin saturation (TS), serum ferritin (SF), and iron removed by phlebotomy (QFe). We performed logistic regression on cirrhosis using characteristics identified in univariate comparisons. We performed computerized and manual searches to identify hemochromatosis case series and compiled prevalence data on cirrhosis and abdominal pain and causes of abdominal pain. Results Of 219 probands, 57.1% were men. Mean age was 48±13 y. In 22 probands with cirrhosis, proportions of men, mean age, prevalences of heavy alcohol consumption, abdominal pain, abdominal tenderness, hepatomegaly, splenomegaly, and chronic viral hepatitis, and median TS, SF, and QFe were significantly greater than in probands without cirrhosis. Regression analysis revealed three associations with cirrhosis: abdominal pain (p = 0.0292; odds ratio 9.8 (95% CI: 1.2, 76.9)); chronic viral hepatitis (p = 0.0153; 11.5 (95% CI: 1.6, 83.3)); and QFe (p = 0.0009; 1.2 (95% CI: 1.1, 1.3)). Of eight probands with abdominal pain, five had cirrhosis and four had diabetes. One proband each with abdominal pain had heavy alcohol consumption, chronic viral hepatitis B, hepatic sarcoidosis, hepatocellular carcinoma, and chronic cholecystitis, cholelithiasis, and sigmoid diverticulitis. Abdominal pain was alleviated after phlebotomy alone in four probands. In 12 previous reports (1935–2011), there was a negative correlation of cirrhosis prevalence and publication year (p = 0.0033). In 11 previous reports (1935–1996), a positive association of abdominal pain prevalence and publication year was not significant (p = 0.0802). Conclusions Abdominal pain, chronic viral hepatitis, and QFe are significantly associated with cirrhosis in referred hemochromatosis probands with HFE p.C282Y homozygosity. Iron-related and non-iron-related factors contribute to the occurrence of abdominal pain.

Alcohol Use Intensity Decreases in Response to Successful Smoking Cessation Therapy

Smokers frequently drink heavily. However, the effectiveness of smoking cessation therapy for those with comorbid alcohol abuse is unclear, and the content of smoking cessation programs often does not address comorbid alcohol consumption. In order to achieve a better understanding of the relationship between changes in rate of smoking to the change in intensity of alcohol consumption, and the necessity for alcohol-specific programming for dual users, we quantified cigarette and alcohol consumption in 39 subjects undergoing a 3-month contingency management smoking cessation program using recently developed DNA methylation tools. Intake alcohol consumption, as quantified by the Alcohol T Score (ATS), was highly correlated with cg05575921 smoking intensity (adjusted R2 = 0.49) with 19 of the 39 subjects having ATS scores indicative of Heavy Alcohol Consumption. After 90 days of smoking cessation therapy, ATS values decreased with the change in ATS score being highly correlated with change in cg05575921 smoking intensity (adjusted R2 = 0.60), regardless of whether or not the subject managed to completely quit smoking. We conclude that alcohol consumption significantly decreases in response to successful smoking cessation. Further studies to determine whether targeted therapy focused on comorbid alcohol use increases the success of smoking cessation in those with dual use should be explored.

Increased Visit-to-Visit Liver Enzyme Variability Is Associated with Incident Diabetes: A Community-Based 12-Year Prospective Cohort Study

Background: Fatty liver and/or increased liver enzyme values have been reported to be associated with incident diabetes. We sought to determine whether increased visit-to-visit liver enzyme variability is associated with incident diabetes.Methods: Study participants were recruited from the Korean Genome and Epidemiologic Study (KoGES). A total of 4,151 people aged 40 to 69 years was recruited and tested every 2 years for up to 12 years. Visit-to-visit aspartate aminotransferase (AST) and alanine aminotransferase (ALT) variability was evaluated in first the 6-year period through the use of various variability measurements: standard deviation (SD), average successive variability, coefficient of variation (CV), and variation independent of mean (VIM). Oral glucose tolerance test was performed at every visit.Results: During the 6-year follow‐up appointments, 13.0% (538/4,151) of people developed incident diabetes. Visit-to-visit AST variability was associated with an increased risk of diabetes independent of conventional risk factors for diabetes (hazard ratio per 1-SD increment [95% confidence interval]: 1.06 [1.00 to 1.11], 1.12 [1.04 to 1.21], and 1.13 [1.04 to 1.22] for SD, CV, and VIM, respectively; all P<0.05); however, no such associations were observed in the visit-to-visit ALT variability. According to alcohol consumption status, both AST and ALT variability were independent predictors for incident diabetes in subjects with heavy alcohol consumption; however, neither AST nor ALT variability was associated with diabetes risk in subjects who did not drink alcohol heavily.Conclusion: Visit-to-visit liver enzyme variability is an independent predictor of incident diabetes. Such association was more evident in those who consumed significant amounts of alcohol.

IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis

Background Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this study is to explore the potential benefits of the IL-1β antibody, canakinumab, in the treatment of AH. Methods This is a multicentre, double-blind, randomised placebo-controlled trial. Participants will be diagnosed with AH using clinical criteria. Liver biopsy will then confirm that all histological features of AH are present. Up to 58 participants will be recruited into two groups from 15 centres in the UK. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is the difference between groups in the proportion of patients demonstrating histological improvement and will compare histological appearances at baseline with appearances at 28 days to assign a category of “improved” or “not improved”. Patients with evidence of ongoing disease activity will receive a second infusion of canakinumab or placebo. Participants will be followed up for 90 days. Secondary outcomes include mortality and change in MELD score at 90 days. Discussion This phase II study will explore the benefits of the IL-1β antibody, canakinumab, in the treatment of AH to provide proof of concept that inhibition of IL-1β signalling may improve histology and survival for patients with AH. Trial registration EudraCT 2017-003724-79. Prospectively registered on 13 April 2018.

Heavy alcohol consumption before and after negative life events in late mid-life: longitudinal latent trajectory analyses

BackgroundPeople who experience negative life events report more heavy alcohol consumption compared with people without these experiences, but little is known about patterns of change within this group. This study aims to identify trajectories of heavy alcohol consumption before and after experiencing either divorce, or severe illness or death in the family. Furthermore, the aim is to examine characteristics of individuals belonging to each trajectory.MethodsLongitudinal study of public sector employees from the Finnish Retirement and Aging Study with up to 5 years of annual follow-ups (n=6783; eligible sample n=1393). Divorce and severe illness or death in the family represented negative life events. Heavy alcohol consumption was categorised as >14 units/week.ResultsBased on latent trajectory analysis, three trajectories of heavy drinking were identified both for divorce and for severe illness or death in the family: ‘No heavy drinking’ (82% illness/death, 75% divorce), ‘Constant heavy drinking’ (10% illness/death, 13% divorce) and ‘Decreasing heavy drinking’ (7% illness/death, 12% divorce). Constant heavy drinkers surrounding illness or death in the family were more likely to be men, report depression and anxiety and to smoke than those with no heavy drinking. Constant heavy drinkers surrounding divorce were also more likely to be men and to report depression compared with those with no heavy drinking.ConclusionsMost older workers who experience divorce or severe illness or death in the family have stable drinking patterns regarding heavy alcohol consumption, that is, most do not initiate or stop heavy drinking.

Post-traumatic stress disorder among persons with HIV who engage in heavy alcohol consumption in southwestern Uganda

Background We aimed to describe the prevalence of PTSD symptoms and its associated factors in persons living with HIV (PLWH) in Uganda who engage in heavy alcohol use. Methods We analyzed baseline data from the Drinkers Intervention to Prevent Tuberculosis study which enrolls PLWH with latent tuberculosis who engage in heavy alcohol consumption. Using the primary care Post Traumatic Stress Disorder (PTSD) screening scale from the DSM-5 (PC-PTSD-5), probable PTSD was defined as reporting ≥3 of 5 assessed symptoms. We conducted the Alcohol Use Disorders Identification Test-Consumption and assessed demographics, smoking, symptoms of depression, and spirituality/religiosity. Results Of 421 participants enrolled from 2018 through 2020, the majority (68.2%) were male, median age was 40 years (interquartile range [IQR]: 32–47), and median AUDIT-C score was 6 [IQR: 4–8]. Half (50.1%) of the participants reported ever experiencing a traumatic event, and 20.7% reported ≥3 symptoms of PTSD. The most commonly reported PTSD symptoms in the past 1 month in the entire sample were avoidance (28.3%), nightmares (27.3%), and being constantly on guard (21.6%). In multivariable logistic regression analyses, level of alcohol use was not associated with probable PTSD (adjusted odds ratio [AOR] for each AUDIT-C point: (1.02; 95% CI: 0.92–1.14; p = 0.69); however, lifetime smoking (AOR 1.89; 95% CI: 1.10–3.24) and reporting symptoms of depression (AOR 1.89; 95% CI: 1.04–3.44) were independently associated with probable PTSD. Conclusions and recommendations A history of traumatic events and probable PTSD were frequently reported among persons who engage in heavy drinking, living with HIV in Uganda. Level of alcohol use was not associated with probable PTSD in this sample of PLWH with heavy alcohol use, however other behavioral and mental health factors were associated with probable PTSD. These data highlight the high prevalence of PTSD in this group, and the need for screening and interventions for PTSD and mental health problems.

Genetic underpinnings of the transition from alcohol consumption to alcohol use disorder: shared and unique genetic architectures in a cross-ancestry sample

Recent GWAS of alcohol-related traits have uncovered key differences in the underlying genetic architectures of alcohol consumption and alcohol use disorder (AUD), with the two traits having opposite genetic correlations with psychiatric disorders. Understanding the genetic factors that underlie the transition from heavy drinking to AUD has important theoretical and clinical implications. We utilized longitudinal data from the cross-ancestry Million Veteran Program sample to identify 1) novel loci associated with AUD and alcohol consumption [measured by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)] and 2) genetic variants with direct effects on AUD not mediated through alcohol consumption. We identified 26 loci associated with AUD, including 5 ancestry-specific and 6 novel loci and 22 loci associated with AUDIT-C, including 3 ancestry-specific and 8 novel loci. In secondary GWAS that excluded individuals who report abstinence, we identify 7 additional loci for AUD and 8 additional loci for AUDIT-C. We demonstrate that, although the heterogeneity of the abstinent group biases the GWAS findings, unique variance between alcohol consumption and disorder remains after the group is excluded. Finally, using mediation analysis, we identified a set of variants with effects on AUD that are not mediated through alcohol consumption. The distinct genetic architectures of alcohol consumption and AUD suggest different biological contributions to the traits. Genetic variants with direct effects on AUD are potentially relevant to understanding the transition from heavy alcohol consumption to AUD and targets for translational prevention and treatment efforts.

Prevalence of alcohol use among women of reproductive age in Canada

Introduction Reporting on alcohol use among women of reproductive age in Canada addresses a major gap in evidence. Methods We assessed the prevalence of weekly and heavy alcohol consumption among women aged 15 to 54 years by sociodemographic characteristics, province of residence and concurrent use of other substance(s) using data from the 2019 Canadian Community Health Survey. Results Of the target population, 30.5% reported weekly and 18.3% reported heavy alcohol consumption in the past year. Prevalence varied by sociodemographic characteristics, province and substance use. The most notable and significant differences were to do with cannabis use and smoking. Conclusion This information can guide health care providers in assessing alcohol consumption and in promoting low-risk alcohol drinking to prevent alcohol exposure during pregnancy.

Epigenetic Analyses of Alcohol Consumption in Combustible and Non-Combustible Nicotine Product Users

Alcohol and tobacco use are highly comorbid and exacerbate the associated morbidity and mortality of either substance alone. However, the relationship of alcohol consumption to the various forms of nicotine-containing products is not well understood. To improve this understanding, we examined the relationship of alcohol consumption to nicotine product use using self-report, cotinine, and two epigenetic biomarkers specific for smoking (cg05575921) and drinking (Alcohol T Scores (ATS)) in n = 424 subjects. Cigarette users had significantly higher ATS values than the other groups (p < 2.2 × 10−16). Using the objective biomarkers, the intensity of nicotine and alcohol consumption was correlated in both the cigarette and smokeless users (R = −0.66, p = 3.1 × 10−14; R2 = 0.61, p = 1.97 × 10−4). Building upon this idea, we used the objective nicotine biomarkers and age to build and test a Balanced Random Forest classification model for heavy alcohol consumption (ATS > 2.35). The model performed well with an AUC of 0.962, 89.3% sensitivity, and 85% specificity. We conclude that those who use non-combustible nicotine products drink significantly less than smokers, and cigarette and smokeless users drink more with heavier nicotine use. These findings further highlight the lack of informativeness of self-reported alcohol consumption and suggest given the public and private health burden of alcoholism, further research into whether using non-combustible nicotine products as a mode of treatment for dual users should be considered.