Showing papers in "Alcoholism: Clinical and Experimental Research in 2021"

Changes in Alcohol Use and Drinking Context due to the COVID-19 Pandemic: A Multimethod Study of College Student Drinkers.

Abstract: BACKGROUND: In spring 2020, U.S. universities closed campuses to limit the transmission of COVID-19, resulting in an abrupt change in residence, reductions in social interaction, and in many cases, movement away from a heavy drinking culture. The present mixed-methods study explores COVID-19-related changes in college student drinking. We characterize concomitant changes in social and location drinking contexts and describe reasons attributed to changes in drinking. METHODS: We conducted two studies of the impact of the COVID-19 pandemic on drinking behavior, drinking context, and reasons for both increases and decreases in consumption among college students. Study 1 (qualitative) included 18 heavy-drinking college students (Mage = 20.2; 56% female) who completed semi-structured interviews. Study 2 (quantitative) included 312 current and former college students who reported use of alcohol and cannabis (Mage = 21.3; 62% female) and who completed an online survey. RESULTS: In both studies, COVID-19-related increases in drinking frequency were accompanied by decreases in quantity, heavy drinking, and drunkenness. Yet, in Study 2, although heavier drinkers reduced their drinking, among non-heavy drinkers several indices of consumption increased or remained stable . Both studies also provided evidence of reductions in social drinking with friends and roommates and at parties and increased drinking with family. Participants confirmed that their drinking decreased due to reduced social opportunities and/or settings, limited access to alcohol, and reasons related to health and self-discipline. Increases were attributed to greater opportunity (more time) and boredom and to a lesser extent, lower perceived risk of harm and to cope with distress. CONCLUSION: This study documents COVID-19-related changes in drinking among college student drinkers that were attributable to changes in context, particularly a shift away from heavy drinking with peers to lighter drinking with family. Given the continued threat of COVID-19, it is imperative for researchers, administrators, and parents to understand these trends as they may have lasting effects on college student drinking behaviors.

Is the COVID-19 Pandemic a High-Risk Period for College Student Alcohol Use? A Comparison of Three Spring Semesters.

Abstract: BACKGROUND: There has been widespread concern that the COVID-19 pandemic may be a high-risk time for alcohol use among heavy drinking populations such as college students. Initial efforts to evaluate changes in college drinking have not yet accounted for typical drinking patterns within a semester. METHODS: To fill this gap, we evaluated how college student drinking patterns changed with the onset of restrictions related to the COVID-19 pandemic during spring 2020 relative to spring 2018 and 2019. Participants were 1,365 college students aged 19 and older, including 895 students who reported past-month alcohol use. Daily drinking data were extracted from an online Timeline Followback survey. RESULTS: Negative binomial hurdle models revealed that, with the onset of the COVID-19 pandemic in spring 2020, college student drinkers did not increase their drinking frequency as was typical in late spring semester, and the number of drinks per occasion declined substantially (28% reduction), greater than the change observed from early to late spring 2018 (3% reduction) or spring 2019 (8% increase). This reduction in drinking quantity in spring 2020 was larger for college student drinkers who moved residences because of the pandemic (49% reduction) than students who did not move (21% reduction). Perceptions in pandemic-related changes in drinking also revealed that 83.5% of college student drinkers self-reported that their drinking stayed the same or decreased. CONCLUSIONS: Findings suggest that, on average, college students drank less-not more-during the onset of the COVID-19 pandemic and highlight the importance of living situation in college student drinking behavior. More research is needed to assess alcohol use in other universities, as this information could be utilized in norms-based interventions to further reduce drinking in students who remain at risk.

Stigmatization of people with alcohol use disorders: An updated systematic review of population studies.

Abstract: BACKGROUND We summarize research on the public stigmatization of persons with alcohol use disorder (AUD) in comparison with other mental health conditions and embed the results into a conceptual framework of the stigma process. METHODS We conducted a systematic search using Embase, MEDLINE, PubMed and PsycINFO (via Ovid), and Web of Science for population-based studies on the public stigma in AUD and at least 1 other mental health condition, published between October 1, 2010 and December 20, 2020, thus including all studies published since the last systematic review on this topic. The study is registered with PROSPERO (registration number: CRD42020173054). RESULTS We identified 20,561 records, of which 24 met the inclusion criteria, reporting results from 16 unique studies conducted in 9 different countries. Compared to substance-unrelated mental disorders, persons with AUD were generally less likely to be considered mentally ill, while they were perceived as being more dangerous and responsible for their condition. Further, the public desire for social distance was consistently higher for people with AUD. We found no consistent differences in the public stigma toward persons with AUD in comparison with other substance use disorders. CONCLUSION The stigmatization of persons with AUD remains comparatively high and is distinct from that of other substance-unrelated disorders.

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

Abstract: 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.

COVID-19 impacts on drinking and mental health in emerging adults: Longitudinal changes and moderation by economic disruption and sex.

Abstract: BACKGROUND: There are significant concerns that the COVID-19 pandemic may have negative effects on substance use and mental health, but most studies to date are cross-sectional. In a sample of emerging adults, over a two-week period during the pandemic, the current study examined: (1) changes in drinking-related outcomes, depression, anxiety, and posttraumatic stress disorder and (2) differences in changes by sex and income loss. The intra-pandemic measures were compared to pre-pandemic measures. METHODS: Participants were 473 emerging adults (Mage = 23.84; 41.7% male) in an existing longitudinal study on alcohol misuse who were assessed from June 17 to July 1, 2020, during acute public health restrictions in Ontario, Canada. These intra-pandemic data were matched to participant pre-pandemic reports, collected an average of 5 months earlier. Assessments included validated measures of drinking, alcohol-related consequences, and mental health indicators. RESULTS: Longitudinal analyses revealed significant decreases in heavy drinking and adverse alcohol consequences, with no moderation by sex or income loss, but with substantial heterogeneity in changes. Significant increases in continuous measures of depression and anxiety were present, both of which were moderated by sex. Females reported significantly larger increases in depression and anxiety. Income loss >50% was significantly associated with increases in depression. CONCLUSIONS: During the initial phase of the pandemic, reductions in heavy drinking and alcohol consequences were present in this sample of emerging adults, perhaps due to restrictions on socializing. In contrast, there was an increase in internalizing symptoms , especially in females, highlighting disparities in the mental health impacts of the pandemic.

Network Meta-Analysis on the Mechanisms Underlying Alcohol Augmentation of COVID-19 Pathologies.

Abstract: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a worldwide crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients present with fever in the early phase, with some progressing to a hyperinflammatory phase. Ethanol (EtOH) exposure may lead to systemic inflammation. Network meta-analysis was conducted to examine possible relationships between EtOH consumption and COVID-19 pathologies. METHODS: Molecules affected by EtOH exposure were identified by analysis with QIAGEN Knowledge Base. Molecules affected by COVID-19 were identified from studies in MEDLINE, bioRxiv, and medRxiv reporting gene expression profiles in COVID-19 patients, QIAGEN Coronavirus Network Explorer, and analysis of the RNA-sequencing data of autopsied lungs of COVID-19 patients retrieved from the GEO database. Network meta-analysis was then conducted on these molecules using QIAGEN Ingenuity Pathway Analysis (IPA). RESULTS: Twenty-eight studies reporting significant gene expression changes in COVID-19 patients were identified. One RNA-sequencing dataset on autopsied lungs of COVID-19 patients was retrieved from GEO. Our network meta-analysis suggests that EtOH exposure may augment the effects of SARS-CoV-2 infection on hepatic fibrosis signaling pathway, cellular metabolism and homeostasis, inflammation, and neuroinflammation. EtOH may also enhance the activity of key mediators including cytokines, such as IL-1s, IL-6, and TNF, and transcription factors, such as JUN and STAT, while inhibiting the activity of anti-inflammatory mediators including glucocorticoid receptor. Furthermore, IL-1s, IL-6, TNF, JUN, and STAT were mapped to 10 pathways predicted to associate with SARS-CoV-2 proteins, including HMGB1, IL-1, and IL-6 signaling pathways. CONCLUSIONS: Our meta-analyses demonstrate that EtOH exposure may augment SARS-CoV-2-induced inflammation by altering the activity of key inflammatory mediators. Our findings suggest that it is important for clinicians to caution patients about the risk of alcohol consumption, which has increased during the COVID-19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.

Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes

Abstract: BACKGROUND Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. METHODS Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. RESULTS Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. CONCLUSIONS High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans.

Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front-Loading and Robust Compulsive-Like Alcohol Drinking in Male and Female C57BL/6J Mice.

Abstract: Background Current models of compulsive-like quinine-adulterated alcohol (QuA) drinking in mice, if improved, could be more useful for uncovering the neural mechanisms of compulsive-like alcohol drinking. The purpose of these experiments was to further characterize and improve the validity of a model of compulsive-like QuA drinking in C57BL/6J mice. We sought to determine whether compulsive-like alcohol drinking could be achieved following 2 or 3 weeks of Drinking-in-the-Dark (DID), whether it provides evidence for a robust model of compulsive-like alcohol drinking by inclusion of a water control group and use of a highly concentrated QuA solution, whether repeated QuA exposures alter compulsive-like drinking, and whether there are sex differences in compulsive-like alcohol drinking. Methods Male and Female C57BL/6J mice were allowed free access to either 20% alcohol or tap water for 2 hours each day for approximately 3 weeks. After 2 or 3 weeks, the mice were given QuA (500 μM) and the effect of repeated QuA drinking sessions on compulsive-like alcohol drinking was assessed. 3-minute front-loading, 2 hour binge-drinking, and blood alcohol concentrations were determined. Results Compulsive-like QuA drinking was achieved after 3 weeks, but not 2 weeks, of daily alcohol access as determined by alcohol history mice consuming significantly more QuA than water history mice and drinking statistically nondifferent amounts of QuA than nonadulterated alcohol at baseline. Thirty-minute front-loading of QuA revealed that alcohol history mice front-loaded significantly more QuA than water history mice, but still found the QuA solution aversive. Repeated QuA exposures did not alter these patterns, compulsive-like drinking did not differ by sex, and BACs for QuA drinking were at the level of a binge. Conclusions These data suggest that compulsive-like QuA drinking can be robustly achieved following 3 weeks of DID and male and female C57BL/6J mice do not differ in compulsive-like alcohol drinking.

Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta-analysis.

Abstract: Author(s): Hahn, Judith A; Murnane, Pamela M; Vittinghoff, Eric; Muyindike, Winnie R; Emenyonu, Nneka I; Fatch, Robin; Chamie, Gabriel; Haberer, Jessica E; Francis, Joel M; Kapiga, Saidi; Jacobson, Karen; Myers, Bronwyn; Couture, Marie Claude; DiClemente, Ralph J; Brown, Jennifer L; So-Armah, Kaku; Sulkowski, Mark; Marcus, Gregory M; Woolf-King, Sarah; Cook, Robert L; Richards, Veronica L; Molina, Patricia; Ferguson, Tekeda; Welsh, David; Piano, Mariann R; Phillips, Shane A; Stewart, Scott; Afshar, Majid; Page, Kimberly; McGinnis, Kathleen; Fiellin, David A; Justice, Amy C; Bryant, Kendall; Saitz, Richard | Abstract: BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8nng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8nng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

Comparison of the Diagnostic Value of Phosphatidylethanol and Carbohydrate-Deficient Transferrin as Biomarkers of Alcohol Consumption.

Abstract: BACKGROUND The aim of this study was to compare the results of Phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT) in blood as biomarkers of alcohol consumption in a large clinical cohort and to evaluate concentrations in relation to age and sex. METHODS Results of PEth 16:0/18:1 in blood and CDT in serum were included, together with information of age and sex, which were extracted from a clinical chemistry database containing samples mostly from patients of primary care physicians and social care institutions. PEth concentrations were determined using Ultra Performance Convergence chromatography mass spectrometer. CDT was quantified by electrophoretic Capillary System. CDT values ≥ 1.7 %-units and PEth values ≥ 0.31 µmol/L were considered to indicate heavy alcohol consumption. RESULTS Samples from 6705 patients were included. The median age was 54.5 years, and 34 % were females. Only 47 % of the patients with PEth ≥ 0.31 µmol/L had increased CDT ≥ 1.7 %-units examined in the same specimen (Cohen's kappa was 0.43, p < 0.001). Patients above 50 years had significantly higher concentrations for both CDT (1.0 %-units vs. 0.9 %-units, p < 0.001) and PEth (0.340 µmol/L vs. 0.200 µmol/L, p < 0.001) compared with younger patients. Concentrations of CDT were significantly higher in males compared with females (p = 0.002), while no significant sex differences were seen for PEth (p = 0.465). CONCLUSIONS A high fraction of the patients had PEth values above the suggested cutoff for heavy drinking and normal CDT values, verifying the superior sensitivity of PEth compared with CDT. The effect of age seems to be minor for both markers. Higher concentrations of CDT, but not PEth, were seen in males, indicating that PEth, as opposed to CDT, might be formed equally in men and women. Therefore, the bias due to sex is possibly present only for CDT, not for PEth.

Trends in US Alcohol Consumption Frequency During the First Wave of the SARS-CoV-2 Pandemic.

Abstract: BACKGROUND: The SARS-CoV-2 pandemic created disruptions and stressors which may have influenced alcohol consumption frequency trends. Varying COVID-19 health burden and alcohol policies may have contributed to different consumption trends between states. The aim of this study is to assess trends in alcohol consumption and moderation by state of residence. METHODS: We examined trends in adult drinking days, during the first wave of the pandemic (March 10 to June 8) using longitudinal data from the Understanding America Study (N = 6,172 unique participants; N = 28,059 observations). Because state mandates were responsive to disease burden, we modeled the interaction of time by COVID-19 burden, defined as whether the state had the median (or higher) daily incidence of COVID-19 cases on the survey date, and state random effects. We controlled for individual sociodemographics, perceived personal/familial COVID-19 burden, mental health symptomology, and risk avoidance. RESULTS: Drinking days increased throughout the duration (incidence risk ratio [IRR] for drinking per increase in one calendar day = 1.003, 95% CI 1.001, 1.004); trends were heterogeneous by disease burden, with individuals living in states with lower COVID-19 burden increasing (IRR = 1.005, 95% CI 1.003, 1.007) faster than those living in states with higher COVID-19 burden (IRR = 1.000, 95% CI 0.998, 1.002). Trends were heterogeneous between states, but there was no evidence of systematic geographic clustering of state trends. CONCLUSIONS: Drinking days increased during the first months of the COVID-19 pandemic, particularly among residents of states with lower disease burden.

Sex-Dependent Alcohol Instrumentalization Goals in Non-Addicted Alcohol Consumers versus Patients with Alcohol Use Disorder: Longitudinal Change and Outcome Prediction

Abstract: BACKGROUND: Alcohol can be instrumentalized to achieve goals that without the drug would either not be achievable or would be so only with considerably more workload. While an understanding of the neurobiological mechanisms of alcohol instrumentalization is emerging, little information is available concerning instrumentalization goals in controlled consumers and how these goals change during the development of an alcohol use disorder (AUD). METHODS: We surveyed instrumentalization goals in 103 male and 78 female inpatients with AUD (before / after onset of the disorder) and compared them with the goals of 124 male and 96 female age-matched non-addicted controls. We also investigated whether instrumentalization goals predict 24-month alcohol-related hospital readmissions in the patients using a false discovery rate (FDR) approach. RESULTS: Separately for both sexes, the most frequently (>25%) self-reported alcohol instrumentalization goals in patients were "stress coping," "craving for alcohol," and "reduction of anxiety and / or depressive mood" and in controls "facilitation of social interaction." Relative to controls, and in a sex-dependent manner, patients with AUD reported the goals "facilitation of social interaction" and "search for a partner" significantly less frequently and "reduction of anxiety and / or depressive mood," "stress coping," "improvement of sexual activity," "improvement of concentration," "euphoria," and "craving for alcohol" more frequently. During the transition to addiction, many of the instrumentalization goals changed significantly, some in a sex-dependent manner. In female AUD patients, a goal of "euphoria" nominally predicted a lower risk of alcohol-related readmission, although not significantly when FDR corrected. CONCLUSIONS: We identified cross-sectional and intra-individual differences in instrumentalization goals that support the assumption that the onset of an AUD coincides with a shift in instrumentalization goals from prosocial instrumentalization toward the self-management of aversive mental states.

Evolution of the Physical Phenotype of Fetal Alcohol Spectrum Disorders from Childhood through Adolescence.

Abstract: Background This paper reports findings from the first longitudinal study on the evolution of the physical phenotypes of fetal alcohol syndrome (FAS) and partial FAS (PFAS) from early childhood through adolescence. Methods The sample consisted of 155 children (78 males and 77 females) born to women recruited at an antenatal clinic serving a Cape Coloured (mixed ancestry) population in Cape Town, South Africa. Two expert FASD dysmorphologists, blind regarding prenatal alcohol exposure, independently evaluated each child's growth and dysmorphology at 4 clinics conducted over an 11-year period. Case conferences were held to reach consensus regarding which children had FAS or PFAS growth and physical features using the Revised Institute of Medicine (2005) guidelines. Results The prevalence of the physical phenotype was stable across the 4 ages for about half of the children with FAS and about one-third of those with PFAS but more variable for the others. Test-retest reliability was substantial for the FAS phenotype, but poorer for PFAS. Two distinct patterns were seen: a "strong phenotype" that was consistently identified and a less consistent one in which dysmorphic features and/or anthropometric deficits fluctuated or diminished with age. The physical phenotype was most apparent during early childhood and least apparent during puberty, due to differences in timing of the growth spurt and the evolving adult face. Short palpebral features and small head circumference diminished with age, flat philtrum fluctuated, while thin vermilion and weight and height restriction were stable. Conclusions Key facial features that characterize FASD in early childhood diminish or evolve in some individuals, making diagnostic examinations that rely on these characteristics most sensitive during early childhood and school age. Moreover, puberty poses classification problems due to variability in timing of the growth spurt. Given that several features and small head circumference diminished with age, many individuals would be misdiagnosed if only examined at a later age.

Diagnostic Accuracy of Biomarkers of Alcohol Use in Patients With Liver Disease: A Systematic Review.

Abstract: Background and aims Alcohol-related liver disease is the most frequent cause of cirrhosis and a major indication for liver transplantation. Several alcohol use biomarkers have been developed in recent years and are already in use in several centers. However, in patients with liver disease their diagnostic performance might be influenced by altered biomarker formation by hepatic damage, altered excretion by kidney dysfunction and diuretics use, and altered deposition in hair and nails. We systematically reviewed studies on the diagnostic accuracy of biomarkers of alcohol use in patients with liver disease and performed a detailed study quality assessment. Methods A structured search in PubMed/Medline/Embase databases was performed for relevant studies, published until April 28, 2019. The risk of bias and applicability concerns was assessed according to the adapted quality assessment of diagnostic accuracy studies-2 (QUADAS-2) checklist. Results Twelve out of 6,449 studies met inclusion criteria. Urinary ethyl glucuronide and urinary ethyl sulfate showed high sensitivity (70 to 89 and 73 to 82%, respectively) and specificity (93 to 99 and 86 to 89%, respectively) for assessing any amount of alcohol use in the past days. Serum carbohydrate-deficient transferrin showed low sensitivity but higher specificity (40 to 79 and 57 to 99%, respectively) to detect excessive alcohol use in the past weeks. Whole blood phosphatidylethanol showed high sensitivity and specificity (73 to 100 and 90 to 96%, respectively) to detect any amount of alcohol use in the previous weeks. Scalp hair ethyl glucuronide showed high sensitivity (85 to 100%) and specificity (97 to 100%) for detecting chronic excessive alcohol use in the past 3 to 6 months. Main limitations of the current evidence are the lack of an absolute gold standard to assess alcohol use, heterogeneous study populations, and the paucity of studies. Conclusions Urinary and scalp hair ethyl glucuronide are currently the most validated alcohol use biomarkers in patients with liver disease with good diagnostic accuracies. Phosphatidylethanol is a highly promising alcohol use biomarker, but so far less validated in liver patients. Alcohol use biomarkers can complement each other regarding diagnostic time window. More validation studies on alcohol use biomarkers in patients with liver disease are needed.

Increased Toll-like Receptor-MyD88-NFκB-Proinflammatory neuroimmune signaling in the orbitofrontal cortex of humans with alcohol use disorder.

Abstract: Background Many brain disorders, including alcohol use disorder (AUD), are associated with induction of multiple proinflammatory genes. One aspect of proinflammatory signaling is progressive increases in expression across cells and induction of other innate immune genes. High-mobility group box 1 (HMGB1) heteromers contribute to amplification by potentiating multiple proinflammatory responses, including Toll-like receptors (TLRs). TLR signaling recruits coupling proteins linked to nuclear transcription factors that induce proinflammatory cytokines and chemokines and their respective receptors. We tested the hypothesis that AUD induction of TLR expression increases levels of proinflammatory genes and cellular signaling cascades in association with neurodegeneration in the orbitofrontal cortex (OFC). Methods Postmortem human OFC tissue samples (n = 10) from males diagnosed with AUD were compared to age-matched moderate drinking controls (CON). Neuroimmune signaling molecules were assessed using immunohistochemistry for protein and reverse transcription polymerase chain reaction for messenger RNA (mRNA). Results In the AUD OFC, we report induction of the endogenous TLR agonist HMGB1 as well as all TLRs assessed (i.e., TLR2-TLR9) except TLR1. This was accompanied by increased expression of the TLR adaptor protein myeloid differentiation primary response 88 (MyD88), activation of the proinflammatory nuclear transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and downstream induction of proinflammatory cytokines, chemokines, and their corresponding receptors. Several of these proinflammatory signaling markers are expressed in glia and neurons. The induction of HMGB1-TLR-MyD88-NFκB proinflammatory signaling pathways correlates with neurodegeneration (i.e., Fluoro-Jade B), lifetime alcohol consumption, and age of drinking onset. Conclusion These data implicate the induction of HMGB1-TLR-MyD88-NFκB cascades through coordinated glial and neuronal signaling as contributors to the neurodegeneration seen in the postmortem human OFC of individuals with AUD.

Clinical and Neural Correlates of Reward and Relief Drinking.

Abstract: Background Alcohol use disorder (AUD) is heterogenous. One approach to parsing this heterogeneity is to phenotype individuals by their underlying motivation to drink, specifically drinking for reward (i.e., positive reinforcement) or for relief (i.e., negative reinforcement/normalizing). Reward- versus relief-motivated behavior is thought to be associated with a shift from ventral to dorsal striatal (DS) signaling. The present study examined whether reward and relief drinking were differentially associated with other clinical characteristics and with alcohol cue-elicited activation of the ventral and dorsal striatum. Methods Non-treatment-seeking heavy drinkers (N = 184; 61 female, 123 male) completed the UCLA Reward, Relief, Habit Drinking Scale (RRHDS) and the Reasons for Heavy Drinking Questionnaire (RHDQ), to categorize drinking motivation. Measures of alcohol use, alcohol problems, mood, and craving were also collected. A subset of participants (N = 45; 17 female, 28 male) also completed a functional neuroimaging alcohol cue reactivity task. Results RRHDS-designated relief/habit drinkers scored lower than reward drinkers on the RHDQ Reinforcement subscale (p = 0.04) and higher on the RHDQ Normalizing subscale (p = 0.004). Relief/habit drinkers also demonstrated greater AUD severity on a host of clinical measures. Relief/habit drinkers displayed higher cue-elicited DS activation compared with reward drinkers (p = 0.04), while ventral striatal cue-elicited activation did not significantly differ between groups. Conclusions Our findings support and extend the differentiation of reward from relief/habit-motivated drinking and suggest that differences in DS response to conditioned alcohol cues may underlie this distinction. Elucidating neurobiological and clinical differences between these subtypes may facilitate treatment matching and precision medicine for AUD.

Balancing the story of fetal alcohol spectrum disorder: A narrative review of the literature on strengths.

Abstract: For many years, researchers have explored the complex challenges experienced by individuals with fetal alcohol spectrum disorder (FASD). This research has been important for documenting the brain- and body-based impacts of prenatal alcohol exposure and the psychosocial vulnerabilities and environmental adversities frequently associated with FASD. It has also supported advocacy efforts and highlighted the necessity of providing FASD services and supports. However, with the focus on deficits and needs, there is a considerable gap in the literature on the strengths and successes of individuals with FASD. The lack of strengths-based FASD research has likely perpetuated the stress and stigma experienced by individuals with FASD and their families. Thus, there is a critical need to shift the direction of the field. Here we provide a narrative review of the literature on strengths in FASD. Our goals are to: (1) understand the state of strengths-based research related to individuals with FASD across the lifespan, and (2) describe positive characteristics, talents, and abilities of individuals with FASD that may be cultivated to promote their fulfillment and well-being. We identified a total of 19 studies, most of which were conducted to explore the lived experiences of adults with FASD. This preliminary but critical body of evidence highlights the intrinsic strengths of individuals with FASD, including strong self-awareness, receptiveness to support, capacity for human connection, perseverance through challenges, and hope for the future. Despite the importance of this emerging evidence, appraisal of the literature indicates a need for more intentional, methodologically rigorous, participatory, and theory-driven research in this area. Findings from this study, including the identified gaps in the literature, can be used to inform research, practice, and policy to meaningfully advance the field of FASD and promote positive outcomes in this population.

Effects of prenatal alcohol exposure on cognitive and behavioral development: Findings from a hierarchical meta-analysis of data from six prospective longitudinal U.S. cohorts

Abstract: BACKGROUND Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, individual participant meta-analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller samples. METHODS Meta-analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores. RESULTS The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle-class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent- and teacher-reported behavior problems and not significant for sustained attention. In a meta-analysis of five aspects of executive function, the strongest effect was on set-shifting. CONCLUSIONS The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle-class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition-learning/memory and set-shifting-that are particularly affected by PAE, and one, sustained attention, which is apparently spared.

Epigenetic Clock Analysis in Children With Fetal Alcohol Spectrum Disorder.

Abstract: Background Fetal alcohol spectrum disorder (FASD) is characterized by severe clinical impairment, considerable social burden, and high mortality and morbidity, which are due to various malformations, sepsis, and cancer. As > 50% of deaths from FASD occur during the first year of life, we hypothesized that there is the acceleration of biological aging in FASD. Several recent studies have established genome-wide DNA methylation (DNAm) profiles as "epigenetic clocks" that can estimate biological aging, and FASD has been associated with differential DNAm patterns. Therefore, we tested this hypothesis using epigenetic clocks. Methods We investigated five DNAm-based measures of epigenetic age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and telomere length (DNAmTL) using four independent publicly available DNAm datasets; two datasets were derived from buccal epithelium, and the other two datasets were derived from peripheral blood. Results Compared to controls, children with FASD exhibited an acceleration of GrimAge in one buccal and two blood datasets. No significant difference was found in other DNAm ages and DNAmTL. Meta-analyses showed a significant acceleration of GrimAge in the blood samples but not in the buccal samples. Conclusions This study provides novel evidence regarding accelerated epigenetic aging in children with FASD.

Prevalence of fetal alcohol spectrum disorder in Greater Manchester, UK: An active case ascertainment study

Abstract: Background: Despite high levels of prenatal alcohol exposure in the UK, evidence on the prevalence of fetal alcohol spectrum disorders (FASD) is lacking. This paper reports on FASD prevalence in a small sample of children in primary school. Methods: A two-phase active case ascertainment study was conducted in three mainstream primary schools in Greater Manchester, UK. Schools were located in areas that ranged from relatively deprived to relatively affluent. Initial screening of children aged 8-9 years used pre-specified criteria for elevated FASD risk (small for age; special educational needs; currently/previously in care; significant social/emotional/mental health symptoms). Screen positive children were invited for detailed ascertainment of FASD using gold standard measures including medical history, facial dysmorphology, neurological impairment, executive function and behavioural difficulties. Results: Of 220 eligible children, 50 (23%) screened positive and 12% (26/220) proceeded to phase-two assessment. Twenty had a developmental disorder, of which, four had FASD and four were assessed as possible FASD. The crude prevalence rate of FASD in these schools was 1.8% (95%CI: 1.0%,3.4%) and when including possible cases was 3.6% (2.1%,6.3%). None of these children had previously identified with a developmental diagnosis. Conclusions: FASD was found to be common in these schools, but limitations to the sampling restrict inferences to a population prevalence. Most of these children’s needs had not previously been identified.

Abstinence Among Alcohol Use Disorder Patients During the COVID-19 Pandemic: Insights From Spain.

Abstract: BACKGROUND: Patients with alcohol use disorder (AUD) are likely to suffer disproportionate harms related to the COVID-19 pandemic and related policy measures. While many surveys have been conducted, most are focused on drinking changes in the general population and validation with biological markers is lacking. METHOD: We performed a retrospective cohort study among patients with AUD attending a urine drug screening program. With mixed-effects logistic regression models, we assessed the probability of screening positive for ethyl glucuronide according to patients' main clinical characteristics and time of analysis (either prior to or after a lockdown was implemented in Spain). RESULTS: A total of 362 patients provided 2,040 urine samples (1,295 prior to lockdown, 745 during lockdown). The mean age of participants was 52.0 years (SD 12.6), and 69.2% were men. Of the 43% of patients tested for other drugs 22% screened positive. After adjusting for all covariates, the odds of screening positive for ethyl glucuronide during lockdown almost doubled (OR = 1.99, 95% CI 1.20 to 3.33, p = 0.008). Other significant covariates included testing positive for other drugs (OR = 10.79, 95% CI 4.60 to 26.97) and length of treatment (OR = 0.59, 95% CI 0.47 to 0.74). CONCLUSIONS: Our data support an association between the lockdown due to COVID-19 and increased alcohol use in patients with AUD. Thus, addiction healthcare systems could face significant challenges ahead. In light of these findings, it is essential to evaluate prospectively how patients with AUD are affected by the pandemic and how health systems respond to their needs.

Microglia Phenotypes Following the Induction of Alcohol Dependence in Adolescent Rats.

Abstract: Background Activation of the innate immune system may play a role in the development of alcohol use disorders (AUDs), which often originate with adolescent alcohol abuse. A key player in the innate immune system is microglia, the activation of which occurs along a spectrum from proinflammatory, or M1-like, to anti-inflammatory, or M2-like, phenotypes. Methods Adolescent, male rats were gavaged with ethanol (EtOH) or isocaloric control diet every 8 hours for 4 days and then sacrificed at 0, 2, 7, and 14 days later. Microglia were isolated from the entorhinal cortex and hippocampus by Percoll gradient centrifugation, labeled with surface antigens for activation, and analyzed by flow cytometry. Polarization states of microglia, defined as CD11b+ CD45low cells, were determined by the expression of M1 surface markers, major histocompatibility complex (MHC) II, CD32, and CD86, and M2 surface marker, CD206 (mannose receptor). Cytokine gene expression was measured by reverse transcriptase polymerase chain reaction. Results Isolated cells were a highly enriched population (>95% pure) of microglia/macrophages according to CD11b immunoreactivity. EtOH rats showed the most dramatic increases in microglia activation markers CD11b and CD45, and M1 (MHC-II) and M2 (CD206) markers at T2, when additional M1 markers CD86 and CD32 were also increased. Surprisingly, proinflammatory gene expression of CCL2, IL-1β, IL-6, and TNF-α generally was decreased at all time points in EtOH rats except for IL-6 which was increased at T0 and TNF-α which was not changed at T0 in either region. Simultaneously, BDNF expression was increased at T2 and T7, while IGF1 and TGF-β gene expression was decreased. Arginase was also increased at T0 in hippocampus, but not changed by alcohol otherwise. Conclusions These data show that microglia phenotype after alcohol dependence is not a simple M1 or M2 classification, though more indicators of an anti-inflammatory phenotype were observed. Determining microglia phenotype is critical for understanding their role in the development of AUDs.

Repetitive blast mild traumatic brain injury increases ethanol sensitivity in male mice and risky drinking behavior in male combat veterans.

Abstract: Background Mild traumatic brain injury (mTBI) is common in civilians and highly prevalent among military service members. mTBI can increase health risk behaviors (e.g., sensation seeking, impulsivity) and addiction risk (e.g., for alcohol use disorder (AUD)), but how mTBI and substance use might interact to promote addiction risk remains poorly understood. Likewise, potential differences in single vs. repetitive mTBI in relation to alcohol use/abuse have not been previously examined. Methods Here, we examined how a history of single (1×) or repetitive (3×) blast exposure (blast-mTBI) affects ethanol (EtOH)-induced behavioral and physiological outcomes using an established mouse model of blast-mTBI. To investigate potential translational relevance, we also examined self-report responses to the Alcohol Use Disorders Identification Test-Consumption questions (AUDIT-C), a widely used measure to identify potential hazardous drinking and AUD, and used a novel unsupervised machine learning approach to investigate whether a history of blast-mTBI affected drinking behaviors in Iraq/Afghanistan Veterans. Results Both single and repetitive blast-mTBI in mice increased the sedative properties of EtOH (with no change in tolerance or metabolism), but only repetitive blast potentiated EtOH-induced locomotor stimulation and shifted EtOH intake patterns. Specifically, mice exposed to repetitive blasts showed increased consumption "front-loading" (e.g., a higher rate of consumption during an initial 2-h acute phase of a 24-h alcohol access period and decreased total daily intake) during an intermittent 2-bottle choice condition. Examination of AUDIT-C scores in Iraq/Afghanistan Veterans revealed an optimal 3-cluster solution: "low" (low intake and low frequency), "frequent" (low intake and high frequency), and "risky" (high intake and high frequency), where Veterans with a history of blast-mTBI displayed a shift in cluster assignment from "frequent" to "risky," as compared to Veterans who were deployed to Iraq/Afghanistan but had no lifetime history of TBI. Conclusions Together, these results offer new insight into how blast-mTBI may give increase AUD risk and highlight the increased potential for adverse health risk behaviors following repetitive blast-mTBI.

A cascade of care for alcohol use disorder: Using 2015-2019 National Survey on Drug Use and Health data to identify gaps in past 12-month care.

Abstract: Background Although effective treatments exist, alcohol use disorder (AUD) is undertreated. We used a cascade of care framework to understand gaps in care for persons with AUD. Methods Using 2015-2019 National Survey on Drug Use and Health data, we evaluated the following steps in the cascade of care: (1) adult prevalence of AUD; (2) proportion of adults with AUD who utilized health care in the past 12 months; (3) proportion with AUD screened about their alcohol use; (4) proportion with AUD who received a brief intervention about their alcohol misuse; (5) proportion with AUD who received information about treatment for alcohol misuse; and (6) proportion with AUD who received treatment. Analyses were stratified by AUD severity. Results Of the 214,505 persons included in the sample, the weighted prevalence of AUD was 7.8% (95% CI 7.6-8.0%). Cascades of care showed the majority of individuals with AUD utilized health care in the past 12 months [81.4% (95% CI 80.7-82.1%)] and were screened about alcohol use [69.9% (95% CI 68.9-70.8%)]. However, only a minority of individuals received subsequent steps of care, including 11.6% (95% CI 11.0-12.2%) who reported receiving a brief intervention, 5.1% (95% CI 4.6-5.6%) who were referred to treatment, and 5.8% (95% CI 5.4-6.3%) who received treatment. Similar patterns were observed when cascades of care were stratified by AUD severity. Conclusions Persons with AUD commonly utilize health care and are often screened about alcohol use, but few receive treatment. Healthcare settings-particularly primary care settings-represent a prime opportunity to implement AUD treatment to improve outcomes in this high-risk population.

Alterations in connectivity of the bed nucleus of the stria terminalis during early abstinence in individuals with alcohol use disorder

Abstract: Background For individuals with Alcohol Use Disorder (AUD), long-term recovery is difficult in part due to symptoms of anxiety that occur during early abstinence and can trigger relapse Research in rodent models of AUD has identified the bed nucleus of the stria terminalis (BNST), a small, sexually dimorphic, subcortical region, as critical for regulating anxiety-like behaviors during abstinence, particularly in female mice Furthermore, prolonged alcohol use and subsequent abstinence alter BNST afferent and efferent connections to other brain regions To our knowledge, however, no studies of early abstinence have investigated BNST structural connectivity in humans during abstinence; this study addresses that gap Methods Nineteen participants with AUD currently in early abstinence and 20 healthy controls completed a diffusion tensor imaging (DTI) scan BNST structural connectivity was evaluated using probabilistic tractography A linear mixed model was used to test between-groups differences in BNST network connectivity Exploratory analyses were conducted to test for correlations between BNST connectivity and alcohol use severity and anxiety within the abstinence group Sex was included as a factor for all analyses Results The BNST showed stronger structural connectivity with the BNST network in early abstinence women than in control women, which was not seen in men Women also showed region-specific differences, with stronger BNST-hypothalamus structural connectivity but weaker vmPFC-BNST structural connectivity than men Exploratory analyses also demonstrated a relationship between alcohol use severity and vmPFC-BNST structural connectivity that was moderated by sex Conclusions This study is the first to demonstrate BNST structural connectivity differences in early abstinence and revealed key sex differences The sex-specific differences in BNST structural connectivity during early abstinence could underlie known sex differences in abstinence symptoms and relapse risk and help to inform potential sex-specific treatments

Increased Synaptic Strength and mGlu2/3 Receptor Plasticity on Mouse Prefrontal Cortex Intratelencephalic Pyramidal Cells Following Intermittent Access to Ethanol.

Abstract: Background The medial prefrontal cortex (PFC) is crucial for regulating craving and alcohol seeking in alcohol use disorder (AUD) patients and alcohol seeking in animal models. Maladaptive changes in volitional ethanol (EtOH) intake have been associated with PFC function, yet synaptic adaptations within PFC have not been consistently detected in voluntary drinking rodent models. At least 80% of the neurons in PFC are glutamatergic pyramidal cells. Pyramidal cells provide the predominant cortical output to several brain regions relevant to AUD, including structures within the telencephalon (IT: e.g., basal ganglia, amygdala, other neocortical regions) and outside the telencephalon (ET: e.g., lateral hypothalamus, midbrain monoaminergic structures, thalamus). Methods In addition to their anatomical distinctions, studies from several laboratories have revealed that prefrontal cortical IT and ET pyramidal cells may be differentiated by specific electrophysiological parameters. These distinguishable parameters make it possible to readily classify pyramidal cells into separable subtypes. Here, we employed and validated the hyperpolarization sag ratio as a diagnostic proxy for separating ET (type A) and IT (type B) neurons. We recorded from deep-layer prelimbic PFC pyramidal cells of mice 1 day after 4 to 5 weeks of intermittent access (IA) EtOH exposure. Results Membrane properties were not altered by IA EtOH, but excitatory postsynaptic strength onto IT type B neurons was selectively enhanced in slices from IA EtOH mice. The increased excitatory drive was accompanied by enhanced mGlu2/3 receptor plasticity on IT type B neurons, providing a potential translational approach to mitigate cognitive and motivational changes to PFC function related to binge drinking. Conclusions Together, these studies provide insight into the specific PFC neurocircuits altered by voluntary drinking. In addition, the findings provide an additional rationale for developing compounds that potentiate mGlu2 and/or mGlu3 receptor function as potential treatments for AUD.

Ecological Momentary Assessment of Alcohol Consumption and Its Concordance with Transdermal Alcohol Detection and Timeline Follow‐Back Self‐report Among Adults Experiencing Homelessness

Abstract: Background Studies of alcohol use presume valid assessment measures. To evaluate this presumption, we examined the concordance of alcohol use as measured by ecological momentary assessment (EMA) self-reports, transdermal alcohol concentration readings via the Secure Continuous Remote Alcohol Monitor (SCRAM), and retrospective self-reports via the Timeline Follow-Back (TLFB) among adults experiencing homelessness. Methods Forty-nine adults who reported alcohol misuse (mean age = 47, SD = 9; 57% Black; 82% men) were recruited from a homeless shelter. For 4 weeks, alcohol use was assessed: (i) 5 times or more per day by EMA, (ii) every 30 minutes by a SCRAM device worn on the ankle, and (iii) by TLFB for the past month at the end of the study period. There were 1,389 days of observations of alcohol use and alcohol use intensity for 49 participants. Results EMA and SCRAM alcohol use data agreed on 73% of days, with an interrater agreement Kappa = 0.46. A multilevel analysis of concordance of 3 measures for alcohol use yielded statistically significant correlations of 0.40 (day level) and 0.63 (person level) between EMA and SCRAM. Alcohol use was detected on 49, 38, and 33% of days by EMA, SCRAM, and TLFB, respectively. For alcohol use intensity, EMA and SCRAM resulted in statistically significant correlations of 0.46 (day level) and 0.78 (person level). The concordance of TLFB with either EMA or SCRAM was weak, especially at the day level. Conclusions This is the first study to examine concordance of alcohol use estimates using EMA, SCRAM, and TLFB methods in adults experiencing homelessness. EMA is a valid approach to quantifying alcohol use, especially given its relatively low cost, low participant burden, and ease of use. Furthermore, any stigma associated with wearing the SCRAM or reporting alcohol use in person may be attenuated by using EMA, which may be appealing for use in studies of stigmatized and underserved populations.

Does the Combination Matter? Examining the Influence of Alcohol and Cannabis Product Combinations on Simultaneous Use and Consequences in Daily Life

Abstract: BACKGROUND Alcohol and marijuana/cannabis are frequently used simultaneously (i.e., SAM use). SAM use is complex, and the ways in which alcohol and cannabis are simultaneously used may reveal differential effects. The purpose of this study was to examine day-level effects of distinct alcohol and cannabis product combinations on simultaneous use and consequences on that day. METHODS College student SAM users (N = 274; 50% women; Mage = 19.82 years) were recruited to complete 54 days of data collection, including 5 repeated daily surveys each day. We identified 12 distinct product combinations reported during SAM-use days. We tested 4 reference groups, with one reflecting the most common use pattern and 3 potentially risky use patterns. We considered 3 outcomes (negative consequences, number of drinks, and number of cannabis uses) and used generalized linear mixed-effects models disentangling within- from between-person effects in all analyses. RESULTS Using multiple products (≥2) of alcohol was consistently linked to higher odds of experiencing a negative consequence. Combining beer with only one cannabis product (leaf or concentrate) was consistently associated with lower odds of a consequence. Combining cannabis with multiple alcohol products was associated with heavier alcohol consumption. Using dual cannabis products also was associated with heavier cannabis consumption, but this pattern was not significantly different than using concentrate only on a given day. CONCLUSION This is the first study to examine day-level influences of distinct alcohol and cannabis product combinations on consumption and consequences among young adult SAM users. Findings suggest that mixing alcohol products confers greater risk for negative consequences and heavier consumption, whereas there is little difference in cannabis consumption when using concentrate only vs. 2 cannabis products on a given day, except for concentrate + beer. Our findings support existing protective strategies of not mixing alcohol products and avoiding use of cannabis concentrate for SAM use as well.

Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study.

Abstract: Background Posttraumatic stress disorder (PTSD) often co-occurs with alcohol consumption (AC) and alcohol use disorder (AUD). However, it is unknown whether the same etiologic influences that underlie PTSD co-occurring with AUD are those that underlie PTSD and AC individually. Methods This study used large-scale genome-wide association study (GWAS) data to test whether PTSD and drinks per week [DPW]/AUD are causally related to one another, and, if so, whether PTSD precedes DPW/AUD and/or vice versa. We used Mendelian Randomization methods to analyze European ancestry GWAS summary statistics from the Psychiatric Genomics Consortium (PGC; PTSD), GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN; DPW), and the Million Veteran Program (MVP; AUD). Results PTSD exerted a potentially causal effect on AUD (β = 0.039, SE = 0.014, p = 0.005), but not on DPW (β = 0.002, SE = 0.003, p = 0.414). Additionally, neither DPW (β = 0.019, SE = 0.041, p = 0.637) nor AUD (β = 8.87 × 10-4 , SE = 0.001, p = 0.441) exerted a causal effect on PTSD. Conclusions These findings are consistent with the self-medication model, in which individuals misuse alcohol to cope with aversive trauma-related symptoms. These findings extend latent analysis and molecular findings of shared and correlated risk between PTSD and alcohol phenotypes. Given the health behaviors associated with these phenotypes, these findings are important in that they suggest groups to prioritize for prevention efforts. Further, they provide a rationale for future preclinical and clinical studies examining the biological mechanisms by which PTSD may impact AUD.

Maternal choline supplementation in a rat model of periconceptional alcohol exposure: Impacts on the fetus and placenta

Abstract: Maternal choline supplementation in rats can ameliorate specific neurological and behavioral abnormalities caused by alcohol exposure during pregnancy. We aimed to test whether choline supplementation could ameliorate fetal growth restriction and molecular changes in the placenta associated with periconceptional ethanol exposure in the rat. Sprague-Dawley dams were given either 12.5% ethanol (PCE) or 0% ethanol (Con) in a liquid diet from 4 days prior to 4 days after conception. At day 5 of pregnancy, dams were either placed on a standard chow (1.6 g choline/kg chow) or an intermediate chow (2.6 g choline/kg chow). On day 10 of pregnancy, a subset of the intermediate dams were placed on a chow further supplemented with choline (7.2 g choline/kg chow), resulting in 6 groups. Fetuses and placentas were collected on day 20 of pregnancy for analysis. Choline supplementation resulted in increased fetal weight at late gestation, ameliorating the deficits due to PCE. This was most pronounced in litters on a standard chow during pregnancy. Choline also increased fetal liver weight and decreased fetal brain:liver ratio, independent of alcohol exposure. Placental weight was reduced as choline levels in the chow increased, particularly in female placentas. This resulted in a greater ratio of fetal:placental weight, suggesting increased placental efficiency. Global DNA methylation in the placenta was altered in a sex-specific manner by both PCE and choline. However, the increased glycogen deposition in female placentas, previously reported in this PCE model, was not prevented by choline supplementation. Our results suggest that choline has the potential to ameliorate fetal growth restriction associated with PCE and improve placental efficiency following prenatal alcohol exposure. Our study highlights the importance of maternal nutrition in moderating the severity of adverse fetal and placental outcomes that may arise from prenatal alcohol exposure around the time of conception.