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Background: Marijuana and alcohol are both substances that, when used during pregnancy, may have profound effects on the developing fetus. There is evidence to suggest that both drugs have the capacity to affect working memory, one function of the hippocampal formation; however, there is a paucity of data on how perinatal exposure to alcohol or cannabis impacts the process of adult neurogenesis. Methods: This systematic review examines immunohistochemical data from adult rat and mouse models that assess perinatal alcohol or perinatal marijuana exposure. A comprehensive list of search terms was designed and used to search 3 separate databases. All results were imported to Mendeley and screened by 2 authors. Consensus was reached on a set of final papers that met the inclusion criteria, and their results were summarized. Results: Twelve papers were identified as relevant, 10 of which pertained to the effects of perinatal alcohol on the adult hippocampus, and 2 pertained to the effects of perinatal marijuana on the adult hippocampus. Cellular proliferation in the dentate gyrus was not affected in adult rats and mice exposed to alcohol perinatally. In general, perinatal alcohol exposure did not have a significant and reliable effect on the maturation and survival of adult born granule neurons in the dentate gyrus. In contrast, interneuron numbers appear to be reduced in the dentate gyrus of adult rats and mice exposed perinatally to alcohol. Perinatal marijuana exposure was also found to reduce inhibitory interneuron numbers in the dentate gyrus. Conclusions: Perinatal alcohol exposure and perinatal marijuana exposure both act on inhibitory interneurons in the hippocampal formation of adult rats. These findings suggest simultaneous perinatal alcohol and marijuana exposure (SAM) may have a dramatic impact on inhibitory processes in the dentate gyrus. [ABSTRACT FROM AUTHOR]

Background We examined differences in response to self-reported alcohol use items by survey mode, whether self-report differences were the result of modality effects or self-selection, and whether these differences varied across the treatment and control arms of a preventative intervention trial. Methods Data from an existing alcohol prevention trial were used to estimate the effect of survey modality on adolescent's self-reported alcohol use at ages 17 to 18. Estimates were derived from regression models controlling for self-reported alcohol use during 8th grade, measured using a single survey modality, as well as time invariant selection factors. Results No statistically significant survey modality effects were found. No differential effects of survey modality were observed by assigned intervention group. Conclusions We provide initial evidence that adolescent alcohol prevention trials may use multiple survey modalities when necessary to increase response rates without harming interpretation of intervention effects. [ABSTRACT FROM AUTHOR]

Aims: Venue capacity has been proposed as a factor associated with increased number of violent incidents on‐premises, though no specific research has demonstrated this association, and instead has tended to focus on the relationship between crowding and aggression. The aim of current paper is to investigate the association between venue capacity and the number of violent incidents on‐premises. Methods: Venue capacity data (the maximum capacity listed on the liquor license) were obtained for all venues in central Melbourne from 2010 until 2016. These data were then matched with police‐recorded on‐premises assaults that occurred within high‐alcohol hours (Friday and Saturday 8 pm–6 am) inside the venue. Results: Analyses were conducted on 5729 venue‐years (yearly assault counts per venue, per year) across central Melbourne. Compared with venues that have a maximum capacity of between 0 and 100 patrons, venues with higher capacities have increasingly more recorded assaults. Venues with maximum capacities between 501 and 1000 are 6.1 times more likely to have an assault recorded compared with venues with a maximum capacity between 0 and 100. Further, each additional high‐alcohol hour that a venue can be open for is associated with a 72% increase in the number of recorded assaults. Conclusions: Greater venue capacity was found to be strongly associated with an increased risk of violent incidents for any given venue. This was further exacerbated by late‐night trading which substantially adds to the risk of assaults inside the venue. [ABSTRACT FROM AUTHOR]

Background: The overall prevalence of U.S. young adult alcohol use has decreased, but little is known about historical change in related behaviors such as simultaneous alcohol and marijuana (SAM) use that may increase alcohol‐related risks and societal costs. The purpose of this paper was to examine historical change in SAM use prevalence among U.S. young adult alcohol users from 1977 to 2016, and consider the extent to which observed historical change in SAM use among alcohol users reflects co‐occurring change in marijuana use during these years. Methods: Data on past 12‐month alcohol, marijuana, and SAM use at up to 6 modal ages (19/20, 21/22, 23/24, 25/26, 27/28, and 29/30) were collected from 11,789 individuals (45.0% men) participating in the Monitoring the Future panel study. Annual prevalence estimates within modal age group were obtained; historical SAM use trends among alcohol and marijuana users were estimated. Results: From 2014 to 2016, SAM use was reported by approximately 30% of alcohol users aged 19/20 and 21/22, and 20 to 25% of alcohol users aged 23/24 through 29/30. Since the mid‐1990s, age‐specific historical trends in SAM use prevalence among alcohol users followed 1 of 4 patterns: significant increase followed by oscillating increases/decreases (at modal age 19/20), consistent and significant increases (at modal ages 21/22, 23/24, and 25/26), stability followed by increase (at modal ages 27/28), or stability (at modal ages 29/30). In contrast, SAM use trends among marijuana users primarily reflected stability, with some evidence of a decrease across time at modal ages 19/20 and 23/24. Historical change in SAM prevalence among alcohol users was strongly and positively correlated with changes in overall marijuana use prevalence. Conclusions: A growing proportion of early and mid‐young adult alcohol users reported SAM use, with the highest risk among those in the early years of young adulthood. Young adult SAM use may continue to increase in proportion to the degree that young adult marijuana use continues to increase. This paper examined historical change in simultaneous alcohol and marijuana (SAM) use prevalence among U.S. young adult alcohol users from 1977‐2016. While the overall prevalence of U.S. young adult alcohol use has decreased, a growing proportion of early and mid‐young adult alcohol users reported SAM use, with the highest risk among those in the early years of young adulthood. Young adult SAM use may continue to increase in proportion to the degree that young adult marijuana use continues to increase. [ABSTRACT FROM AUTHOR]

Background: We recently showed that alcohol and cannabis can interact prenatally, and in a recent review paper, we identified parvalbumin‐positive (PV) interneurons in the hippocampus as a potential point of convergence for these teratogens. Methods: A 2 (Ethanol [EtOH], Air) × 2 (tetrahydrocannabinol [THC], Vehicle) design was used to expose pregnant Sprague‐Dawley rats to either EtOH or air, in addition to either THC or the inhalant vehicle solution, during gestational days 5–20. Immunohistochemistry was performed to detect PV interneurons in 1 male and 1 female pup from each litter at postnatal day 70. Results: Significant between‐group and subregion‐specific effects were found in the dorsal cornu ammonis 1 (CA1) subfield and the ventral dentate gyrus (DG). In the dorsal CA1 subfield, there was an increase in the number of PV interneurons in both the EtOH and EtOH +THC groups, but a decrease with THC alone. There were fewer changes in interneuron numbers overall in the DG, though there was a sex difference, with a decrease in the number of PV interneurons in the THC‐exposed group in males. There was also a greater cell layer volume in the DG in the EtOH +THC group than the control group, and in the CA1 region in the EtOH group compared to the control and THC groups. Conclusions: Prenatal exposure to alcohol and THC differentially affects parvalbumin‐positive interneuron numbers in the hippocampus, indicating that both individual and combined exposure can impact the balance of excitation and inhibition in a structure critically involved in learning and memory processes. [ABSTRACT FROM AUTHOR]

Background: Among American Indians/Alaskan Natives (AI/ANs), suicides are disproportionately high among those younger than 40 years of age. This paper examines suicide and alcohol intoxication (postmortem BAC ≥ 0.08 g/dl) by age among Whites and AI/ANs to better understand the reasons for the high rate of suicide among AI/ANs for those younger than 40. Methods: Data come from the restricted 2003 to 2016 National Violent Death Reporting System (NVDRS), with postmortem information on 79,150 White and AI/AN suicide decedents of both genders who had a BAC test in 32 states of the United States. Results: Among Whites, 39.3% of decedents legally intoxicated are younger than 40 years of age, while among AI/ANs the proportion is 72.9% (p < 0.001). Multivariable logistic regression with data divided by age shows that in the 18 to 39 age group, AI/ANs are about 2 times more likely than Whites to have a postmortem BAC ≥ 0.08. Veteran status compared to nonveteran, and history of alcohol problems prior to suicide were also associated with BAC ≥ 0.08. Suicide methods other than by firearm and a report of the presence of 2 or more suicide precipitating circumstances were protective against BAC ≥ 0.08. Results for the age group 40 years of age and older mirror those for the younger group with 1 exception: Race/ethnicity was not associated with BAC level. Conclusions: The proportion of suicide decedents with a BAC ≥ 0.08 is higher among AI/ANs than Whites, especially among those 18 to 39 years of age. However, acute alcohol intoxication does not fully explain differences in suicide age structure between AI/ANs and Whites. [ABSTRACT FROM AUTHOR]

Background Low levels of alcohol responses (low LRs) are genetically influenced phenotypes that are identified before alcohol dependence and predict future heavy drinking and alcohol problems. A recent paper described 13 LR-related blood oxygen level-dependent ( BOLD) response contrast patterns observed during an emotional face recognition task that might reflect cognitive processes contributing to LR and that might themselves predict adverse alcohol outcomes ( Paulus et al., Biol Psychiatry 2012; 72: 848). This paper evaluates the predictive implications of those functional magnetic resonance imaging (f MRI) patterns. Methods Of 120 subjects from Paulus and colleagues (2012), 114 (57 low and high LRs; ~50% females) were interviewed 5 years later at age 25. Correlations between baseline f MRI patterns and alcohol-related outcomes were evaluated, and regression analyses were used to determine if BOLD response contrasts incremented over LR in predicting outcomes. Results Baseline f MRI patterns in 5 of 13 baseline regions of interest correlated with adverse outcomes. Such patterns in insular regions, particularly the left anterior insula, and the right frontal gyrus, added to LR in predicting alcohol problems. The relationships remained robust when exact binomial procedures were used, but, reflecting the small sample size, it was not possible to adequately consider Bonferroni corrections. Conclusions The data suggest that f MRI BOLD response contrasts predicted heavier drinking and alcohol problems 5 years later, even after considering baseline low LRs. Future work will focus on whether f MRI results can predict outcomes in larger samples and among young nondrinkers, as well as how the imaging results increase understanding of the processes through which LR operates. [ABSTRACT FROM AUTHOR]

Background Marijuana policies are rapidly evolving. In the United States, recreational use of marijuana is now legal in 4 states and medical marijuana is legal in 23 states. Research evaluating such policies has focused primarily on how policies affect issues of price, access to, use, and consequences of marijuana. Due to potential spillover effects, researchers also need to examine how marijuana policies may impact use and consequences of alcohol. Methods The current paper is a critical review of articles evaluating alcohol outcomes associated with marijuana decriminalization, medical marijuana legalization, and nonmedical or recreational marijuana legalization. We identified articles and reports through (1) online searches of EBSCO host database including Academic Search Premier, Econlit, Legal Collection, Medline, PsycARTICLES, and Psyc INFO, as well as PubMed and Google Scholar databases; (2) review of additional articles cited in papers identified through electronic searches; and (3) targeted searches of state and local government records regarding marijuana law implementation. We reviewed studies with respect to their data sources and sample characteristics, methodology, and the margin of alcohol and marijuana use, timing of policy change, and the aspects of laws examined. Results The extant literature provides some evidence for both substitution (i.e., more liberal marijuana policies related to less alcohol use as marijuana becomes a substitute) and complementary (i.e., more liberal marijuana policies related to increases in both marijuana and alcohol use) relationships in the context of liberalization of marijuana policies in the United States. Conclusions Impact of more liberal marijuana policies on alcohol use is complex, and likely depends on specific aspects of policy implementation, including how long the policy has been in place. Furthermore, evaluation of marijuana policy effects on alcohol use may be sensitive to the age group studied and the margin of alcohol use examined. Design of policy evaluation research requires careful consideration of these issues. [ABSTRACT FROM AUTHOR]

Background Although most people are aware of government guidelines for alcohol consumption, few have accurate knowledge of these and fewer still use these guidelines to monitor their drinking. Most people also lack accurate knowledge of the alcohol content of the drinks they consume. The aim of the study reported here was to examine whether or not personalized feedback on alcohol consumption based on performance in a drink-pouring task and self-reported alcohol intake would improve university students' knowledge of alcohol consumption guidelines and reduce their alcohol intake. Methods A quasi-randomized control trial with a 2-month follow-up was conducted with 200 students aged 18 to 37 in the south of England. Participants were allocated to a 'pour + feedback' group that completed a drink-pouring task and received personalized feedback, a 'pour only' group that completed the drink-pouring task but did not receive feedback, and a control group. Results At follow-up, participants in the 'pour + feedback' group had significantly better knowledge of government guidelines, and significantly lower weekly alcohol intake when compared to the 'control' and 'pour only' groups. Conclusions Further refinement of the drink-pouring intervention and feedback is reported in this paper, and assessment of their impact in various populations may lead to better understanding of which elements of personalized feedback have the greatest influence on young people's alcohol use. [ABSTRACT FROM AUTHOR]

Background Alcohol-related blackouts ( ARBs) are reported by ~50% of drinkers. While much is known about the prevalence of ARBs in young adults and their cross-sectional correlates, there are few prospective studies regarding their trajectories over time during mid-adolescence. This paper reports latent trajectory classes of ARBs between age 15 and 19, along with predictors of those patterns. Methods Latent class growth analysis ( LCGA) was used to evaluate the pattern of occurrence of ARBs across 4 time points for 1,402 drinking adolescents from the Avon Longitudinal Study of Parents and Children ( ALSPAC). Multinomial regression analyses evaluated age-15 demography, substance-related items, externalizing characteristics, and estimated peer substance use as predictors of latent class membership. Results ARBs were reported at age 15 in 30% and at age 19 in 74% of these subjects. Four latent trajectory classes were identified: Class 1 (5.1%) reported no blackouts; for Class 2 (29.5%), ARBs rapidly increased with age; for Class 3 (44.9%), blackouts slowly increased; and for Class 4 (20.5%), ARBs were consistently reported. Using Class 2 (rapid increasers) as the reference, predictors of class membership included female sex, higher drinking quantities, smoking, externalizing characteristics, and estimated peer substance involvement (pseudo R2 = 0.22). Conclusions ARBs were common and repetitive in these young subjects, and predictors of their trajectories over time involved multiple domains representing diverse characteristics. [ABSTRACT FROM AUTHOR]

Background The instantaneous rate of change of alcohol exposure (slope) may contribute to changes in measures of brain function following administration of alcohol that are usually attributed to breath alcohol concentration ( BrAC) acting alone. To test this proposition, a 2-session experiment was designed in which carefully prescribed, constant-slope trajectories of BrAC intersected at the same exposure level and time since the exposure began. This paper presents the methods and limitations of the experimental design. Methods Individualized intravenous infusion rate profiles of 6% ethanol (EtOH) that achieved the constant-slope trajectories for an individual were precomputed using a physiologically based pharmacokinetic model. Adjusting the parameters of the model allowed each infusion profile to account for the subject's EtOH distribution and elimination kinetics. Sessions were conducted in randomized order and made no use of feedback of BrAC measurements obtained during the session to modify the precalculated infusion profiles. In one session, an individual's time course of exposure, BrAC( t), was prescribed to rise at a constant rate of 6.0 mg% per minute until it reached 68 mg% and then descend at −1.0 mg% per minute; in the other, to rise at a rate of 3.0 mg% per minute. The 2 exposure trajectories were designed to intersect at a BrAC ( t = 20 minutes) = 60 mg% at an experimental time of 20 minutes. Results Intersection points for 54 of 61 subjects were within prescribed deviations (range of ±3 mg% and ±4 minutes from the nominal intersection point). Conclusions Results confirmed the feasibility of applying the novel methods for achieving the intended time courses of the BrAC, with technical problems limiting success to 90% of the individuals tested. [ABSTRACT FROM AUTHOR]

Background: California is the largest alcohol market in the United States. In 2005 alone, Californians consumed almost 14 billion alcoholic drinks, which contributed to many severe and potentially fatal alcohol-related illnesses and conditions. Alcohol use also causes violent and nonviolent crimes, as well as injuries and traffic collisions. While several studies have estimated the magnitude and cost of these problems nationally and others have analyzed underage drinking costs, no overall cost estimate at the state level currently exists for California. We present the first comprehensive estimate of the cost of alcohol consumption in California. Methods: For each category of alcohol-related problems, we estimated fatal and nonfatal cases attributable to alcohol use. We multiplied alcohol-attributable cases by estimated costs per case to obtain total costs for each problem. Our estimates are presented in 2 sections, the economic costs, estimated using a human capital approach, and quality-of-life costs estimated using a quality adjusted life year framework. Results: Alcohol consumption in California led to an estimated 9,439 deaths and 921,929 alcohol-related problems, such as crime and injury in 2005. The economic cost of these problems is estimated at between $35.4 billion and $42.2 billion. Our main estimate is $38.5 billion, of which $5.4 billion was for medical and mental health spending, $25.3 billion in work losses, and $7.8 billion in criminal justice spending, property damage and public program costs. In addition, alcohol is responsible for severe reductions in individuals’ quality of life in California. We estimate that the disability caused by injury, the personal anguish of violent crime victims, and the life years lost to fatality are the largest costs imposed by alcohol. The total value for this reduced quality of life in California is between $30.3 billion and $60.0 billion. Our main estimate for quality-of-life costs is $48.8 billion. Conclusions: In light of the associated substantial illness, injuries, death, and high cost to society, alcohol consumption in California needs serious attention. In addition, the methods developed in this paper can be expanded to estimate the cost of alcohol in other states. [ABSTRACT FROM AUTHOR]

Background: In light of the inconsistent evidence associating acculturation with drinking outcomes among Latinos in the United States, the current paper comprehensively reviews the literature on this topic. Methods: Studies were eligible for review if they (1) were published in a refereed journal, (2) were published in English, (3) sampled Latino/Hispanic adults aged 18+, (4) examined self-reported drinking behavior, alcohol-related problems, and/or alcohol abuse/dependence, and (5) reported original results or unique analyses from a larger dataset. The review includes only studies using composite scales of acculturation. Studies were identified via electronic databases (i.e., PSYCHINFO, ETOH, and PUBMED) using search terms, and combinations thereof, including “acculturat*,”“alcohol*,”“Latino,” and “Hispanic.” This search was supplemented by recursive checking and author searches. Thirty-two articles were identified and coded on methodological characteristics; results from 24 disaggregating genders and using appropriate outcomes were summarized. Results: Higher acculturation was very consistently associated with higher odds of drinking among women, even controlling for demographic covariates. The evidence for women also suggested associations between higher acculturation and heavier drinking on other outcomes, including total volume, drinking frequency, typical quantity, heavy/problem drinking, drinking problems, and abuse/dependence, despite some null results. Relationships were weaker and ambiguous among men. Some evidence suggested that highly acculturated men are (compared with peers low on acculturation) more prone to drink, and perhaps as a result, can show higher consumption and problems. However, results also implied that, among male drinkers, higher acculturation may be associated with a lighter drinking pattern. Important study limitations were identified, including low power, aggregation of nondrinkers with drinkers, restrictive sampling, measurement issues, and analytical issues. Conclusions: The pattern of results suggests important associations between acculturation and drinking outcomes—particularly for women—but conclusions are tempered by serious methodological limitations. The review urges further research, particularly large-scale, longitudinal studies, addressing these limitations. [ABSTRACT FROM AUTHOR]

Background: The decision among young people to drink is complex and reflects multiple domains of influence. This paper applies the results from a previous test of an externalizing-based model predicting heavy drinking and alcohol problems in the probands from the San Diego Prospective Study to evaluate how similar characteristics relate to the decision to drink in their offspring. Methods: Data were generated from multiple sources for 152 offspring with a mean age of 17.2 years. Information on the family histories, personal alcohol and other substance use, socioeconomic stratum, the child’s gestational problems, and additional characteristics were gathered from face-to-face interviews with a parent approximately every 5 years between their mid-20s and mid-40s. Data regarding the drinking status and additional variables applicable to the offspring were extracted from the 25-year (T25) epoch of the family evaluations using data supplied directly by the offspring. The relationships of variables to the drinking status in that generation were determined through correlations, regression analyses, and an AMOS-based structural equation model (SEM). Results: Significant correlations to the drinking status in offspring were observed for age, but not for sex. Using age-adjusted backgrounds and data supplied by the offspring at T25, the most robust correlations to the drinking status were seen for a disinhibition measure, peer drinking, expectations of the effects of alcohol, and the history of having worked outside the home. When placed into an SEM, the former 3 variables performed in a manner similar to that observed in the original probands in the prediction of the drinking status, in a model with good fit characteristics. Conclusions: These data from a prospective study support the importance of similar domains across 2 generations in characterizing age-appropriate alcohol-related outcomes. [ABSTRACT FROM AUTHOR]

Background: This second of a pair of papers investigates the effects of a moderate dose of alcohol and staying up late on driving simulation performance and simple visual reaction time (RT) at a known circadian phase in well-rested young adults. Methods: Twenty-nine adults (9 males), ages 21 to 25 years, spent 1 week on an at-home stabilization schedule of 8.5 to 9 hours, followed by 3 nonconsecutive nights in-lab: adaptation, placebo, and alcohol. Performance task practice occurred on 3 occasions before the study. Alcohol (vodka; 0.54 g/kg men; 0.49 g/kg women mixed with tonic) was consumed over 30 minutes ending 1 hour before normal bedtime; the same quantity of beverage was given on placebo. Driving simulation (with drive-only and dual-task drive and subtract components) and psychomotor vigilance task (PVT) testing occurred before and after alcohol/placebo ingestion. Breath alcohol concentration (BrAC) readings were taken before all test sessions. Saliva samples were taken approximately every 30 minutes to determine circadian phase. Results: Driving simulation and PVT variables significantly deteriorated with increasing time awake. Driving simulator lane variability was worse with alcohol compared with placebo at 15.5 hours awake. No PVT variable showed an effect of alcohol. Conclusions: Driving simulation performance deteriorated with extended waking and with alcohol; driving was most impaired at the peak alcohol level. The PVT, less complex than the driving simulation, did not show effects of alcohol, a finding consistent with previous literature that disruptive effects of low alcohol concentrations increase with task complexity. Overall, simulated driving performance is significantly impaired late at night when even a moderate dose of alcohol is consumed. [ABSTRACT FROM AUTHOR]

Background: Many alcohol treatment outcome studies exclude some patients with particular problems, such as psychiatric disorders, noncompliance, and homelessness. Such criteria may increase the likelihood of a study being successfully conducted, but may also have the unintended consequence of reducing a study's ability to comply with National Institutes of Health guidelines for inclusion of racial minorities, women, and children in treatment research. Methods and Results: This paper examined this issue empirically using 5 prior studies of treatment systems enrolling over 100,000 alcohol patients. Widely used eligibility criteria in the alcohol treatment field typically exclude between one-fifth to one-third of patients from enrolling in research. Under several eligibility criteria, most notably those for drug use and social/residential instability, women and African-American patients are substantially more likely to be excluded than are men and non–African-American patients, respectively. Conclusions: In designing treatment studies with many eligibility criteria, researchers may therefore inadvertently be thwarting their own good faith efforts to ensure that a range of vulnerable populations are able to participate in research. We analyze the implications of this dilemma for the generalizability of treatment results and for research design, and provide data that may help researchers working in different treatment systems estimate the impact of various eligibility criteria. [ABSTRACT FROM AUTHOR]

Background: Tracking the dynamic course of human alcoholism brain pathology can be accomplished only through naturalistic study and without opportunity for experimental manipulation. Development of an animal model of alcohol-induced brain damage, in which animals consume large amounts of alcohol following cycles of alcohol access and deprivation and are examined regularly with neuroimaging methods, would enable hypothesis testing focused on the degree, nature, and factors resulting in alcohol-induced brain damage and the prospects for recovery or relapse. Methods: We report the results of longitudinal magnetic resonance imaging (MRI) studies of the effects of free-choice chronic alcohol intake on the brains of 2 cohorts of selectively bred alcohol-preferring (P) rats. In the companion paper, we described the MRI acquisition and analysis methods, delineation of brain regions, and growth patterns in total brain and selective structures of the control rats in the present study. Both cohorts were studied as adults for about 1 year and consumed high doses of alcohol for most of the study duration. The paradigm involved a 3-bottle choice with 0, 15 (or 20%), and 30% (or 40%) alcohol available in several different exposure schemes: continuous exposure, cycles of 2 weeks on followed by 2 weeks off alcohol, and binge drinking in the dark. Results: Brain structures of the adult P rats in both the alcohol-exposed and the water control conditions showed significant growth, which was attenuated in a few measures in the alcohol-exposed groups. The region with the greatest demonstrable effect was the corpus callosum, measured on midsagittal images. Conclusion: The P rats showed an age–alcohol interaction different from humans, in that normal growth in selective brain regions that continues in adult rats was retarded. [ABSTRACT FROM AUTHOR]

Background : The mesolimbic/mesoeortical dopamine pathway mediates the rewarding effects of ethanol and other drugs of abuse like cocaine and opiates. Dopaminergic neurons of the ventral tegmental area (VTA) arc the cells of origin of the mesolimbic/mesocortical dopamine pathway. Ethanol's rewarding properties result from its ability to excite dopaminergic cell bodies in the VTA which results in increased dopamine release in the nucleus accumbens. Many recent papers have speculated that ethanol excitation of dopaminergic VTA neurons is indirect, either that ethanol acts on GABAergic or other interneurons, which in turn modulate the activity of dopaminergic VTA neurons, or that ethanol modulates the action of neurotransmitter-gated ion channels in the VTA. Methods : VTA neurons were acutely dissociated and plated onto a cover slip in an electrophysiological recording chamber. These neurons generated spontaneous action potentials which could be measured with cell attached loose patch recording. The dissociation procedure truncated the dendritic trees, severed synaptic contacts and widely dispersed these neurons. Dopamine (10-50 nM) and ethanol (20-120 mM) were bath applied and their effects on firing rate were measured. After some experiments, plated cells were fixed and processed for immunostaining of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Results : All neurons met electrophysiological criteria previously established for dopaminergic VTA neurons. Dopamine inhibited all VTA neurons tested, indicating the presence of dopamine autoreceptors. All neurons identified as dopaminergic by these electrophysiological and pharmacological criteria, and that were processed for immunohistochemistry, stained positive for tyrosine hydroxylase immunoreactivity. All acutely dissociated VTA neurons, identified as dopaminergic by electrophysiological, pharmacological and immunohistochemical criteria, were robustly excited by behaviorally relevant concentrations of ethanol. The ethanol-induced excitation was concentration-dependent. Conclusions : These data provide strong evidence that ethanol directly excites dopaminergic VTA neurons, 21s this excitation still occurs in the absence of input from surrounding neurons. [ABSTRACT FROM AUTHOR]

Pathological fibrogenesis in the liver is mediated by activated stellate cells. These cells have a myofibroblastic phenotype with the ability to proliferate and synthesize large quantities of extracellular matrix coniponents. A number of factors have been proposed to initiate and perpetuate the fibrogenic process in stellate cells, including inflammatory cytokines, alterations in the extracellular matrix, growth factors, and oxidative stress. Some recent research has focused on the intracellular signaling pathways that are stimulated by these factors in stellate cells. including mitogen-activated protein kinases, phosphatidylinositol 3-kinase, focal adhesion kinase, and protein kinase C. This paper will summarize the experimental evidence that implicates these pathways in stellate cell activation, focusing on the effects of exposure to platelet-derived growth factor, tumor necrosis factor-α, and fibronectin. Implications for alcohol-induced hepatic fibrosis and future directions for research will also be discussed. [ABSTRACT FROM AUTHOR]

This paper endeavored to determine (1) if early onset of regular tobacco use is as predictive of drug use and depressive disorders as it is of alcohol use disorders; and (2) if a biological commonality, as measured by a family history of alcoholism and both early onset and severity of disease, among all three disorders can be evidenced in a large nationally representative sample. Prevalences of lifetime drug use, drug abuse and dependence, and major depressive disorders, as well as indices of their severity, were compared among smoking groups defined by age at onset of regular tobacco use and among nonsmokers. Linear logistic regression analyses, controlling for important covariates, including a family history positive for alcoholism, were conducted to assess the relationship between age at smoking onset and drug use, abuse and dependence, as well as depressive disorders. Both objectives were met. Moreover, results suggest that smoking may play an equally, if not even more, insidious role than drinking in the use and development of dependence on illicit substances and depression. [ABSTRACT FROM AUTHOR]

Background: We examined the influence of interindividual differences in alcohol use on the intraindividual associations of drinking occurrence with interpersonal behaviors, affect, and perceptions of others during naturally occurring social interactions. Methods: For 14 consecutive days, 219 psychology freshmen (55% female; Mage = 20.7 years, SD = 2.18) recorded their behaviors, affect, and perceptions in social interactions soon after an interpersonal event occurred. Interpersonal behaviors and perceptions were assessed in terms of dominance–submissiveness and agreeableness–quarrelsomeness. Participants also reported the number of alcoholic drinks consumed within 3 hours of each interaction. We considered the intraindividual associations of (i) having a drinking episode and (ii) the number of drinks during an episode with behaviors, affect, and perceptions and examined interindividual differences in drinking frequency and intensity during social interactions as potential moderators of these associations. Results: Social drinking frequency and intensity moderated the associations between drinking episode and behaviors, affect, and perceptions in social interactions. During a drinking episode, more frequent social drinkers perceived others as more dominant than less frequent social drinkers. During a drinking episode in which more alcohol was consumed than usual, more frequent social drinkers also reported behaving more dominantly and experiencing less pleasant affect. Conclusions: As more frequent social drinkers had different interpersonal responses to drinking than less frequent social drinkers, including when they had consumed larger amounts of alcohol than usual, our results suggest a differential susceptibility to the effects of alcohol during naturally occurring social interactions among drinkers with varying drinking frequency. [ABSTRACT FROM AUTHOR]

Human and animal studies have clearly demonstrated that alcohol is both a physical and behavioral teratogen and that heavy prenatal alcohol exposure can lead to a distinct pattern of birth defects termed the fetal alcohol syndrome. Underlying the behavioral and cognitive anomalies seen in fetal alcohol syndrome are alterations in brain structure and/or function. This paper reviews the literature examining brain anomalies attributable to prenatal alcohol exposure, beginning with a survey of autopsy studies and leading up to current findings using magnetic resonance imaging and positron emission tomography studies. Autopsy reports clearly illustrate the wide and devastating influence alcohol has on the developing brain, although for the most part no specific pattern of brain malformation has been identified. More recent magnetic resonance imaging studies, particularly when combined with quantitative analysis, have indicated that specific brain areas-such as the basal ganglia, the corpus callo-sum, and parts of the cerebellum-might be especially susceptible to alcohol's teratogenic effects. Further studies using functional brain imaging techniques may provide even more information about the unique effects prenatal alcohol exposure has on the developing brain. Discovering specific areas of the brain that are affected by alcohol may allow clinicians and researchers to look for patterns of vulnerable regions in the brain, thereby helping in the future detection of children who are prenatally exposed to alcohol. [ABSTRACT FROM AUTHOR]

Based on findings from an ethnographic analysis of an assembly plant in a large manufacturing industry, this paper delineates a conceptual framework for 'minimization' that proposes to explain the interactional processes leading to systemized weakening of alcohol problem awareness and action in the unionized workplace. In the course of 50 semi-structured interviews and observations with union representatives and management, the role of the first-line supervisor emerged as pivotal to minimization. Individual case studies from the ethnography and responses from a survey sample of 1000 employees are used to illustrate how goals and processes of the workplace culture impede forthright action and clear lines of decision making on alcohol issues. [ABSTRACT FROM AUTHOR]

Attempting to account for greater alcohol consumption among women, social scientists have argued that traditional gender roles and gender-role attitudes concerning the division of labor in the family have provided women with a moral or cultural protection against heavier drinking but that the 'breakdown' of this protection has allowed for greater alcohol use. This paper assesses the breakdown argument using data from two representative samples: a sample of 12,069 young adults in the United States and a sample of 1,367 employed men and women in metropolitan Detroit. Our analysis indicates that among young women the nontraditional role of employment and nontraditional gender-role attitudes concerning responsibilities for household labor and child care are associated with greater alcohol consumption. However, among the employed, our analysis indicates that it is not nontraditional women and traditional men but rather traditional women and nontraditional men who have greater alcohol use-it is the women and men who believe that they have substantial obligations at home and who have intense competition at the workplace that consume a greater quantity of alcohol. [ABSTRACT FROM AUTHOR]

This paper examines the effect on drinking behavior of chronic strains deriving from on-going work circumstances, and intermittent strains deriving from transitions imposed by life events: unemployment; economic strain; and stress experience (e.g., death in the family, serious illness, etc.). The respondent's personal resources for coping with these life strains are also examined by way of three measures of alienation: the sense of powerlessness, self-esteem, and social integration. The interaction of situational strains and individual alienation is a primary focus. Regression and covariance analyses, using a sample of some 500 male respondents, indicate that (1) unemployment in itself is of relatively little consequence, (2) powerlessness is the most consistent predictor of alcohol use and abuse, and (3) the combination of stress experience and high powerlessness typifies those who are most vulnerable to high drinking quantity and drinking problems. [ABSTRACT FROM AUTHOR]

The major metabolic product of ethanol is acetaldehyde. It is highly reactive with proteins. In situ this modification is significant enough to generate an antibody response. Whether an effector cellular immune response can be generated against these acetaldehyde modified adducts on syngeneic cells is not known. In this paper we have demonstrated in the murine system that acetaldehyde modified splenic cells can generate cytotoxic T lymphocytes (CTL). These CTL are specific for the acetaldehyde modified syngeneic cells, and not acetaldehyde modified allogeneic cells. The ability of the CTL to lyse specific targets is dependent on the formation of stable acetaldehyde adducts. Cold target inhibition studies reveal that modified syngeneic cells can inhibit lysis as effectively as unmodified cells. Therefore, the present study lends support to the hypothesis that acetaldehyde modified cells can generate a cellular immune response and may do so in pathologic states. [ABSTRACT FROM AUTHOR]

Fetal alcohol syndrome (FAS) is a major known cause of fetal malformations and mental retardation. Prevention/intervention of FAS can only be achieved with identification of the mechanisms by which alcohol induces birth defects. The purpose of this paper is to discuss the data on possible mechanisms of FAS, and to give a number of suggestions for future research areas. [ABSTRACT FROM AUTHOR]

Prenatal exposure to alcohol can cause a variety of behavioral disturbances later in life. Many of the reports in animals of the behavioral teratogenic effects of alcohol have focused on assessing younger animals. The purpose of this paper is to review some of the longer lasting behavioral consequences of gestational alcohol exposure in animals. It is not meant as a comprehensive review, but rather focuses on selected studies. It is concluded that prenatal alcohol exposure does have long lasting effects, although some of these might only occur under challenging or stressful circumstances. It is hypothesized that as the animal matures compensatory mechanisms or strategies develop to compensate for these dysfunctions. Thus, behavioral problems may only be detected when these compensatory systems break down, either as a result of stress, because of complex testing procedures, or old age. [ABSTRACT FROM AUTHOR]

We describe two subtypes of transient potassium current, IA, found in two identified cells within the nervous system of Aplysia. These subtypes of IA are differentially sensitive to ethanol, since the decay of current is significantly slowed in the presence of ethanol in one cell, while IA is unaffected by ethanol at the same concentrations in the other cell. In this paper, we examine a number of parameters including temperature sensitivity of these different IAS. While both currents fulfill the criteria for being called IA, they are significantly different with respect to the kinetics of activation and inactivation, as well as recovery from inactivation. They do not differ significantly in the temperature sensitivity of a number of measured parameters, suggesting that ethanol and temperature do not act as a common locus; e.g., by affecting a bulk lipid membrane fluidity. In light of recent work describing the molecular biology of channels underlying IA, it is reasonable to assume that these IA subtypes reflect different underlying channels. This system may be useful for understanding the relationship of channel structure and function to ethanol action. [ABSTRACT FROM AUTHOR]

Background: High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol. Methods: We obtained information from the UK Biobank on approximately 500,000 participants aged 40–70 years at baseline assessment in 2006–2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis. Results: Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89–2.17) for all causes, 1.89 (1.69–2.12) for any cancer, 1.87 (1.61–2.17) for any circulatory disease, and 9.40 (7.00–12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment. Conclusions: People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality. [ABSTRACT FROM AUTHOR]

Background and aims: For most treatment‐seeking patients with severe Alcohol Use Disorder (AUD), abstinence is the clinically indicated goal. Existing AUD motivation scales are non‐specific about treatment consumption goals, which limit their effectiveness. Desires and mental imagery are relevant in the motivation for AUD treatment engagement. The Motivational Thought Frequency Scale for an abstinence goal (MTF‐A) was adapted from the MTF for controlled drinking (MTF‐CD). This study psychometrically evaluated the MTF‐A in an alcohol‐dependent sample engaged in treatment with a goal of abstinence. To enhance the clinical utility of the scale, a secondary aim was to evaluate a psychometrically equivalent short version of the MTF‐A. Method: A sample N of 329 treatment‐seeking patients with AUD (mean age of 44.44 years, SD = 11.89 years, 72% male) who were undertaking a cognitive behavioral treatment (CBT) program for abstinence completed the Motivational Thought Frequency Scale for Abstinence (MTF‐A) and the Severity of Alcohol Dependence Questionnaire (SADQ). The MTF‐A measured motivation for abstinence through four factors: intensity, self‐efficacy imagery, incentives imagery, and availability. Confirmatory factor analyses (CFAs) were conducted to examine factor structure and model fit. Cronbach's alpha assessed internal consistency. Predictive validity was determined by logistic regression predicting first‐session treatment non‐attendance and alcohol consumption between baseline assessment and commencement of treatment, controlling for potential confounds. Results: A four‐factor structure provided the best fit for the MTF‐A, compared with one‐ and three‐factor models. A shortened 9‐item MTF‐A scale (S‐MTF‐A) provided better fit than the 13‐item MTF‐A scale. Both MTF‐A and S‐MTF‐A displayed good internal consistency. Although both MTF‐A and S‐MTF‐A successfully predicted first‐session treatment non‐attendance, neither predicted alcohol consumption between the baseline assessment and commencement of treatment. Conclusions: The model fit of the four‐factor, 9‐item S‐MTF‐A was superior to the original 13‐item MTF‐A. Both scales were predictive of participation of AUD treatment. Desires and mental imagery play an important role in AUD treatment motivation. [ABSTRACT FROM AUTHOR]

Background: Simultaneous use of alcohol and cannabis to enhance each other's effect can cause potential harm. Time trends are diverging in adolescent use of alcohol, which is declining, and cannabis, which is increasing among certain subgroups. However, little is known about trends in their simultaneous and non‐simultaneous use. Racial and socioeconomic disparities are emerging in cannabis use, which may portend consequences to public health. Methods: The 2000 to 2020 Monitoring the Future surveys included approximately 38,000 U.S. 12th‐grade students with information on simultaneous use and pertinent demographic factors. A 5‐level alcohol/cannabis measure included past‐year simultaneous use (i.e., alcohol and cannabis use at the same time), non‐simultaneous alcohol and cannabis use, alcohol‐use‐only, cannabis‐use‐only, and no use. Multinomial logistic regressions estimated associations (adjusted relative risk ratios; aRRR) with time period (2000 to 2004, 2005 to 2009, 2010 to 2014, 2015 to 2020). Models were adjusted and included interactions with sex, race/ethnicity, and parental education. Results: Between 2000 and 2020, simultaneous alcohol/cannabis use among 12th graders decreased from 24.4% to 18.7%. From 2015 to 2020 compared to 2000 to 2004, the odds of simultaneous use (adjusted relative risk ratio (aRRR) vs. no use = 0.57, 95% CI [0.50, 0.66]) and alcohol‐use‐only (aRRR = 0.55, 95% CI [0.49, 0.61]) decreased, while cannabis‐use‐only odds increased (aRRR = 2.59, 95% CI [1.87, 3.59]). Notably, the prevalence of cannabis‐use‐only more than doubled from 2011 to 2019. The odds of simultaneous use, alcohol‐use‐only, and non‐simultaneous use of alcohol and cannabis declined more rapidly among males than females, whereas the odds for cannabis‐use‐only increased faster for females than males. Increases in cannabis‐use‐only were faster for non‐white adolescents. Conclusion: Simultaneous use of alcohol and cannabis is declining among U.S. adolescents, but the decline is slower among females than males. Declines in simultaneous use are largely concomitant with historical declines in alcohol use, indicating that a continued focus on reducing alcohol use among adolescents and young adults has extended benefits to other adolescent substance use. However, cannabis use without any reported past‐year alcohol use more than doubled in the last decade, a concerning trend. [ABSTRACT FROM AUTHOR]

Background: Adults experiencing homelessness have much higher rates of alcohol misuse than housed individuals. This study describes the development and preliminary effectiveness of a smartphone‐based, just‐in‐time adaptive intervention (JITAI) to reduce alcohol use among adults experiencing homelessness. Methods: We conducted a pilot trial (N = 41; mean age [SD] = 45.2 [11.5]; 19.5% women) of the Smart‐T Alcohol JITAI where participants completed brief ecological momentary assessments (EMAs) each day, received personalized treatment messages following each EMA, and accessed on‐demand intervention content for 4 weeks. The prediction algorithm and treatment messages were developed based on an independent but similar sample as part of the trial. We examined three drinking outcomes: daily drinking (yes/no), drinks per day, and heavy episodic drinking, controlling for scores on the Alcohol Use Disorders Identification Test (AUDIT) at baseline, age, and sex using quadratic growth curve models. Results: Over the 4‐week period, participants showed a decline in all alcohol use outcomes. Participants also reported high levels of satisfaction with the JITAI. Conclusions: Use of the Smart‐T Alcohol JITAI was well received and provided encouraging evidence that it may reduce any drinking, drinks per day, and heavy episodic drinking among adults experiencing homelessness. [ABSTRACT FROM AUTHOR]

Background: While consumption of alcohol does not often begin until early adolescence, young children are highly capable of internalizing normative information through observational learning. We used a longitudinal multiple‐informant family study to examine the impact of exposure to mothers' and fathers' drinking on young children's normative perceptions of who drinks alcohol. Methods: Three hundred twenty‐nine children (4 to 6 years old at baseline [Mage 4.78 (SD = 0.725)], 51% girls) completed the Dutch electronic appropriate beverage task [eABT] where they attributed alcoholic beverages to a variety of persons depicted in an illustrated scenario. Their parents completed an online survey that included information on alcohol use and exposure. Results: Children more frequently exposed to their mothers' drinking provided females shown in the eABT illustrations with alcohol significantly more often than children less frequently exposed to mothers' drinking. There was no effect of mother's exposure on providing males in the eABT with alcoholic beverages. Similarly, children more frequently exposed to their fathers' drinking provided fathers with alcoholic beverages significantly more often than children less frequently exposed to their fathers' drinking. There was no effect of father's exposure on providing the females with alcoholic beverages, nor was there an effect of father's exposure on providing "other males" with alcohol. These patterns held after adjusting for age and sex. Conclusions: This study demonstrates that there are gender‐specific effects of exposure to parents' (particularly mothers') drinking on young children's perceptions of person‐specific drinking norms. The findings provide unique evidence in a young population group of effects on an understudied dimension of alcohol‐related perceptions with implications for future drinking behavior. [ABSTRACT FROM AUTHOR]

Background: Alcohol withdrawal is a key component of severe alcohol use disorder. Animal models of alcohol withdrawal tend to focus on traditional anxiety/stress tests. While these have been essential to advancing our understanding of the biology of alcohol withdrawal, abrupt cessation of drinking following heavy alcohol consumption can also trigger withdrawal‐related affective states that impact responses to a variety of life events and stressors. To this end, we show that behaviors in a variety of tasks that differ in task demand and intensity are altered during withdrawal in male and female mice after voluntary alcohol access. Methods: Male and female miceunderwent six weeks of intermittent two‐bottle choice alcohol exposure followed by behavioral tests. The tests included—Home cage: low‐stress baseline environment to measure spontaneous natural behaviors; Open field: anxiety‐inducing bright novel environment; Looming disc: arena with a protective hut where mice are exposed to a series of discs that mimic an overhead advancing predator, and Robogator‐simulated predator task: forced foraging behavioral choice in the presence of an advancing robot predator that "attacks" when mice are near a food pellet in a large open arena. Results: A history of alcohol exposure impacted behaviors in these tasks in a sex‐dependent manner. In the home cage, alcohol induced reductions in digging and heightened stress coping through an increase in grooming time. In males, increased rearing yielded greater vigilance/exploration in a familiar environment. The open‐field test revealed an anxiety phenotype in both male and female mice exposed to alcohol. Male mice showed no behavioral alterations to the looming disc task, while females exposed to alcohol showed greater escape responses than water controls, indicative of active stress‐response behaviors. In males, the Robogator task revealed a hesitant/avoidant phenotype in alcohol‐exposed mice under greater task demands. Conclusions: Few drugs show robust evidence of efficacy in clinical trials for alcohol withdrawal. Understanding how withdrawal alters a variety of behaviors in both males and females that are linked to stress coping can increase our understanding of alcohol misuse and aid in developing better medications for treating individuals with AUD. [ABSTRACT FROM AUTHOR]

Background: Evidence implicates sleep/circadian factors in alcohol use, suggesting the existence of a 24‐h rhythm in alcohol craving, which may vary by individual differences in sleep factors and alcohol use frequency. This study sought to (1) replicate prior findings of a 24‐h rhythm in alcohol craving, and (2) examine whether individual differences in sleep timing, sleep duration, or alcohol use frequency are related to differences in the timing of the peak of the craving rhythm (i.e., the acrophase) or magnitude of fluctuation of the rhythm (i.e., amplitude). Finally, whether such associations varied by sex or racial identity was explored. Methods: Two‐hundred fifteen adult drinkers (21 to 35 years of age, 72% male, 66% self‐identified as White) completed a baseline assessment of alcohol use frequency and then smartphone reports of alcohol craving intensity six times a day across 10 days. Sleep timing was also recorded each morning of the 10‐day period. Multilevel cosinor analysis was used to test the presence of a 24‐h rhythm and to estimate acrophase and amplitude. Results: Multilevel cosinor analysis revealed a 24‐h rhythm in alcohol craving. Individual differences in sleep timing or sleep duration did not predict rhythm acrophase or amplitude. However, alcohol use frequency moderated this rhythm wherein individuals who used alcohol more frequently in the 30 days prior to beginning the study had higher mean levels of craving and greater rhythm amplitudes (i.e., greater rhythmic fluctuations). Associations did not vary by sex or racial identity. Conclusions: Results show that alcohol craving exhibits a systematic rhythm over the course of the 24 h and that the frequency of alcohol use may be relevant to the shape of this rhythm. Consideration of daily rhythms in alcohol craving may further our understanding of the mechanisms that drive alcohol use. [ABSTRACT FROM AUTHOR]

Background: Growing evidence indicates that sleep characteristics predict future substance use and related problems. However, most prior studies assessed a limited range of sleep characteristics, studied a narrow age span, and included few follow‐up assessments. Here, we used six annual assessments from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study, which spans adolescence and young adulthood with an accelerated longitudinal design, to examine whether multiple sleep characteristics in any year predict alcohol and cannabis use the following year. Methods: The sample included 831 NCANDA participants (423 females; baseline age 12–21 years). Sleep variables included circadian preference, sleep quality, daytime sleepiness, the timing of midsleep (weekday/weekend), and sleep duration (weekday/weekend). Using generalized linear mixed models (logistic for cannabis; ordinal for binge severity), we tested whether each repeatedly measured sleep characteristic (years 0–4) predicted substance use (alcohol binge severity or cannabis use) the following year (years 1–5), covarying for age, sex, race, visit, parental education, and previous year's substance use. Results: Greater eveningness, more daytime sleepiness, later weekend sleep timing, and shorter sleep duration (weekday/weekend) all predicted more severe alcohol binge drinking the following year. Only greater eveningness predicted a greater likelihood of any cannabis use the following year. Post‐hoc stratified exploratory analyses indicated that some associations (e.g., greater eveningness and shorter weekend sleep duration) predicted binge severity only in female participants, and that middle/high school versus post‐high school adolescents were more vulnerable to sleep‐related risk for cannabis use. Conclusions: Our findings support the relevance of multiple sleep/circadian characteristics in the risk for future alcohol binge severity and cannabis use. Preliminary findings suggest that these risk factors vary based on developmental stage and sex. Results underscore a need for greater attention to sleep/circadian characteristics as potential risk factors for substance use in youth and may inform new avenues to prevention and intervention. [ABSTRACT FROM AUTHOR]

Background: Little research has considered the importance of a person's attitude toward heavy drinking when evaluated against other well‐known predictors of alcohol use and related harm including drinking motives and drinker identity. The current study aimed to evaluate whether one's favorable attitude toward heavy drinking is a unique predictor of prospectively assessed drinking‐related outcomes when considered against descriptive and injunctive norms, drinking intentions, drinking motives, and drinker identity. Methods: Participants in the current study comprised mandated students (n = 374; 54% male) who violated a campus alcohol policy and received a brief intervention (eCHECKUP TO GO). Analyses included the use of negative binomial regression to examine baseline predictors— attitude toward heavy drinking, perceived descriptive and injunctive norms, drinking intentions, drinking motives, and drinker identity—of prospective alcohol use outcomes and alcohol‐related problems 1 month later. Results: We found that one's attitude toward heavy drinking remains a significant predictor of binge frequency, peak drinking, and alcohol‐related problems when accounting for norms, intentions, motives, and identity. Conclusions: This study has important theoretical and intervention implications. Indeed, the finding that one's attitude toward heavy drinking remains a significant predictor of alcohol‐related outcomes when intentions are included in the model has implications within the theory of planned behavior. Furthermore, attitude toward heavy drinking has predictive utility when considered against descriptive and injunctive norms, drinking motives, and drinker identity. These findings contribute to a growing literature suggesting that attitudes could be an important intervention target when the goal is to change drinking behavior. One's attitude toward heavy drinking is an important determinant of alcohol use and associated problems but more work is needed to look at the predictive utility of ones attitude toward heavy drinking in the context of other well known predictors of alcohol use and problems. This work suggests that ones attitude toward heavy drinking is a significant and positive predictor of prospective alcohol use when compared to social norms, drinking motives, and drinker identity. [ABSTRACT FROM AUTHOR]

Background: While drinking alcohol, one must choose between the immediate rewarding effects and the delayed reward of a healthier lifestyle. Individuals differ in their devaluation of a delayed reward based on the time required to receive it, i.e., delay discounting (DD). Previous studies have shown that adolescents discount more steeply than adults and that steeper DD is associated with heavier alcohol use in both groups. Methods: In a large‐scale longitudinal study, we investigated whether higher rates of DD are an antecedent or a consequence of alcohol use during adolescent development. As part of the IMAGEN project, 2220 adolescents completed the Monetary Choice Questionnaire as a DD measure, the Alcohol Use Disorders Identification Test, and the Timeline Follow Back interview at ages 14, 16, 18, and 22. Bivariate latent growth curve models were applied to investigate the relationship between DD and drinking. To explore the consequences of drinking, we computed the cumulative alcohol consumption and correlated it with the development of discounting. A subsample of 221 participants completed an intertemporal choice task (iTeCh) during functional magnetic resonance imaging at ages 14, 16, and 18. Repeated‐measures ANOVA was used to differentiate between high‐risk and low‐risk drinkers on the development of neural processing during intertemporal choices. Results: Overall, high rates of DD at age 14 predicted a greater increase in drinking over 8 years. In contrast, on average, moderate alcohol use did not affect DD from ages 14 to 22. Of note, we found indicators for less brain activity in top‐down control areas during intertemporal choices in the participants who drank more. Conclusions: Steep DD was shown to be a predictor rather than a consequence of alcohol use in low‐level drinking adolescents. Important considerations for future longitudinal studies are the sampling strategies to be used and the reliability of the assessments. [ABSTRACT FROM AUTHOR]

Progression of chronic infections to end‐stage diseases and poor treatment results are frequently associated with alcohol abuse. Alcohol metabolism suppresses innate and adaptive immunity leading to increased viral load and its spread. In case of hepatotropic infections, viruses accelerate alcohol‐induced hepatitis and liver fibrosis, thereby promoting end‐stage outcomes, including cirrhosis and hepatocellular carcinoma (HCC). In this review, we concentrate on several unexplored aspects of these phenomena, which illustrate the combined effects of viral/bacterial infections and alcohol in disease development. We review alcohol‐induced alterations implicated in immunometabolism as a central mechanism impacting metabolic homeostasis and viral pathogenesis in Simian immunodeficiency virus/human immunodeficiency virus infection. Furthermore, in hepatocytes, both HIV infection and alcohol activate oxidative stress to cause lysosomal dysfunction and leakage and apoptotic cell death, thereby increasing hepatotoxicity. In addition, we discuss the mechanisms of hepatocellular carcinoma and tumor signaling in hepatitis C virus infection. Finally, we analyze studies that review and describe the immune derangements in hepatotropic viral infections focusing on the development of novel targets and strategies to restore effective immunocompetency in alcohol‐associated liver disease. In conclusion, alcohol exacerbates the pathogenesis of viral infections, contributing to a chronic course and poor outcomes, but the mechanisms behind these events are virus specific and depend on virus–alcohol interactions, which differ among the various infections. [ABSTRACT FROM AUTHOR]

Background: Long‐term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle‐bound microRNAs (EV‐miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease. Methods: In this study, we profiled the plasma EV‐miRNA content by miRNA‐Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking. Results: We identified a list of up‐ and downregulated EV‐miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR‐155, miR‐154, miR‐34c, miR‐450a, and miR‐204 led to increased production of the inflammatory cytokines TNFα or IL‐6 in peripheral blood mononuclear cells after stimulation. Conclusion: This exploratory study identified several EV‐miRNAs that could serve as biomarkers of long‐term alcohol drinking and provide a mechanism to explain alcohol‐induced peripheral inflammation. [ABSTRACT FROM AUTHOR]

Background: Heightened behavioral impulsivity has been advocated as a preexisting risk factor for the development of alcohol use disorder (AUD). Nonetheless, studies investigating impulsivity in adolescent/young adult at‐risk drinkers—who are at increased risk of developing AUD—report mixed findings. This may be due to methodological limitations related to definitions of at‐risk drinking, the retrospective assessment of alcohol intake, and/or the relatively modest sample size of some studies. Methods: Healthy individuals (N = 814, Mage = 22.50) completed online surveys and a measure of choice impulsivity. Of these, a number of participants also undertook an online measure of response inhibition (n = 627, Mage = 22.66), and a further subgroup submitted real‐time alcohol consumption information for a period of 21 days using an app (n = 543, Mage = 22.96). Differences in behavioral impulsivity were assessed as a function of various at‐risk alcohol intake categories. Hierarchical multiple regression was employed to determine whether impulsivity predicted alcohol use in the form of a continuous index comprising variables related to intake and consequences of use. Results: Significantly greater impulsivity was not evident in heavy, standard binge, high binge, harmful, or hazardous alcohol drinkers as compared to controls, regardless of the criteria employed to categorize these at‐risk drinkers. Neither choice impulsivity nor reduced response inhibition significantly predicted the alcohol use index. Conclusions: While results could be attributed to the online nature of this research, it is possible that more sensitive measures of behavioral impulsivity are required when assessing nondependent drinkers. [ABSTRACT FROM AUTHOR]

Background: Binge drinking is a dichotomous variable that allows researchers to sort students into categories based upon a specific threshold of consumption, commonly 4 (females) or 5 (males) drinks. Crossing the binge threshold increases the risk of negative alcohol-related consequences. The use of such thresholds has played a vital role in the study of college drinking. While extremely valuable, the dichotomous nature of binge drinking variables removes information about how heavily students actually drink, leaving the characterization of college drinking incomplete. The present study examined patterns of alcohol use beyond the binge threshold. Methods: The data set consisted of self-reported 2-week drinking histories from 10,424 first-semester freshmen at 14 schools across the United States during the fall of 2003. The number of students who reached the 4+/5+ binge-drinking threshold was calculated, as was the number who reached 2 times (8+/10+ drinks) or 3 times (12+/15+ drinks) the binge threshold. Logistic regression analyses were used to explore gender differences and to assess whether frequent binge drinkers (3+ binges per 2 weeks) were more likely than infrequent binge drinkers (1–2 binges per 2 weeks) to reach high peak levels of consumption. Results: Roughly 1 of 5 males consumed 10+ drinks and 1 of 10 females consumed 8+ drinks, twice the binge threshold, at least once in the previous 2 weeks. Gender differences were observed at every drinking level and were particularly large at higher peak levels. Frequent binge drinkers were more likely than infrequent binge drinkers to consume 2 or 3 times the binge threshold. Discussion: A surprisingly large percentage of students, particularly males, drink at peak levels well beyond the binge threshold. Such findings suggest that schools might make additional progress in the battle against alcohol misuse by focusing on extreme drinking practices in addition to binge drinking per se. [ABSTRACT FROM AUTHOR]

BACKGROUND:: The level of response (LR) to alcohol is a genetically-influenced phenotype related to the alcoholism risk. Usually measured by evaluating psychological and physiological changes that follow the administration of alcohol, the heritability of LR is estimated to be between 0.4 and 0.6, and efforts are being made to find genes related to this phenotype. This paper presents data from a family-based genome with linkage analysis focusing on alcohol challenge determinants of LR.METHODS:: The subjects were 18-to-29-year-old sibling pairs with at least one parent who was alcohol-dependent and who had experience with alcohol but were not yet alcohol-dependent themselves. Both members of the sibling pairs were given oral alcohol challenges (0.75-0.90 ml/kg of ethanol for females and males, respectively), with LR established using the Subjective High Assessment Scale (SHAS) and changes in body sway (BS) repeatedly over a 3.5-hr. period. Blood samples from siblings and at least one parent were genotyped using 811 microsatellite markers, with results evaluated using several related variance component approaches as implemented in SOLAR for continuous traits. In addition, association was tested using single nucleotide polymorphisms (SNPs) within the KCNMA1, HTR7 and SLC18A2 genes that may relate to a finding on chromosome 10.RESULTS:: Data were generated from 238 sib-pairs representing 365 individuals (41.6% were males) from 165 families. The most consistent results across methods and samples were observed for SHAS on chromosome 10 between 120 and 140 cM (with a maximum LOD score of 2.6 at 122 cM), and a second region of possible interest at 173 cM (LOD = 1.2). Statistical analysis with the KCNMA1, HTR7 and SLC18A2 genes, which lie in the support region of interest revealed no evidence for association after correction for multiple comparisons.CONCLUSIONS:: These evaluations from the largest known alcohol challenge-based genetic study to date highlight the potential importance of genes on chromosome 10 as possible contributors to the low LR to alcohol as a risk factor for alcoholism. [ABSTRACT FROM AUTHOR]

Acute consumption of ethanol results in reversible changes in learning and memory whereas chronic ethanol consumption of six or more months produces permanent deficits and neural damage in rodents. The goal of the current paper was determine whether shorter durations of chronic ethanol ingestion in mice would produce long-term deficits in learning and memory after the cessation of ethanol. We first examined the effects of four and eight weeks of 20% ethanol followed by a three week withdrawal period on learning and memory in mice. We determined that three weeks after eight, but not four, weeks of 20% ethanol consumption resulted in deficits in learning and long-term memory (seven days) in T-maze footshock avoidance and Greek Cross brightness discrimination, step-down passive avoidance and shuttlebox active avoidance. Short-term memory (1 hr) was not affected. The deficit was not related to changes in thiamine status, caloric intake, or nonmnemonic factors, such as, activity or footshock sensitivity. Lastly, we examined if the mice recovered after longer durations of withdrawal. After eight weeks of ethanol, we compared mice after three and 12 weeks of withdrawal. Mice that had been off ethanol for both three and 12 weeks were impaired in T-maze footshock avoidance compared to the controls. The current results indicate that a duration of ethanol consumption as short as eight weeks produces deficits in learning and memory that are present 12 weeks after withdrawal. [ABSTRACT FROM AUTHOR]

Background: Low levels of response (low LR) to alcohol predict heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies of emotion processing have shown that low LR individuals exhibit lower activation in task‐related brain regions following both placebo and alcohol administration, but these studies did not examine functional brain networks that might contribute to the phenomena. The current study expands upon the earlier results by evaluating whether functional connectivity differences between the amygdala and other brain regions modulated by emotional face processing are associated with LR. Based on prior findings, we hypothesized that low LR is related to lower functional connectivity in fronto‐amygdalar functional circuits, which underlie the processing of emotional stimuli. Methods: Secondary analyses were conducted on data from a double‐blind, placebo‐controlled, within‐subjects, cross‐over study in 108 18‐to‐25‐year‐old low and high LR sex‐matched pairs without alcohol use disorder at baseline. Participants performed modified emotional faces processing tasks after receiving placebo or approximately 0.7 ml/kg of ethanol. Psychophysiological interaction analyses examined functional connectivity between left and right amygdalae and related brain circuits using LR‐by‐alcohol general linear models. The data included 54 sex‐matched pairs with 216 fMRI scans comprising alcohol and placebo conditions. Results: Compared with individuals with high LR, low LR subjects demonstrated lower functional connectivity between the amygdala and the frontal lobes, insula, and parietal regions, while processing angry and happy faces. Interactions showed lower connectivity following alcohol in low LR and higher connectivity in high LR groups. Conclusions: Low LR individuals demonstrated lower functional connectivity in response both to placebo and a modest dose of ethanol. Attenuated connectivity among low LR individuals when processing emotional faces may contribute to an impaired ability to recognize alcohol intoxication in social situations and to appraise angry and happy emotions irrespective of whether alcohol is consumed. [ABSTRACT FROM AUTHOR]

Background: The majority of adolescents and young adults (AYA) who use cannabis also use alcohol. Although cannabis use is increasing in the United States (US), it is not known whether the increase contributes to either increased co‐use of alcohol and cannabis (e.g., complementarity) or replacement of alcohol with cannabis (e.g., substitution). The current study estimated the prevalence of alcohol use by cannabis use status among US AYA ages 12 to 25 in 2018 and trends in alcohol use by cannabis use status from 2002 to 2018. Methods: Data were drawn from the 2002 to 2018 National Survey on Drug Use and Health public use data files. The analytic sample included AYA ages 12 to 25 (2018 sample, n = 26,924; total combined sample 2002 to 2018, n = 576,053). Linear and logistic regression models were used to estimate past‐month alcohol use, daily alcohol use, and average quantity of alcohol consumed among AYA with and without past‐month cannabis use from 2002 to 2018. Results: In 2018, any alcohol use and daily alcohol use were significantly more common among AYA who used cannabis use than those who did not use cannabis. Overall, any alcohol use, daily alcohol use, and average drinks per day declined from 2002 to 2018 among AYA irrespective of recent cannabis use. However, the decline in any alcohol use, daily alcohol use, and average alcohol drinks per day was more rapid among AYA who used cannabis (daily and nondaily) than those who did not use cannabis. The rate of decline in average alcohol drinks per day was also higher among AYA with daily compared to nondaily cannabis use. Conclusions: Even with declines in alcohol use over time, drinking is much more common among AYA who report cannabis than those without recent cannabis use, which is consistent with complementarity. Yet, because the decline in alcohol use has been more rapid among AYA who use cannabis, there is also evidence of substitution. Thus, the current data on alcohol and cannabis use are consistent with both complementarity and substitution. However, these relationships may change as cannabis legalization expands over time. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the association between APOE genotype and alcohol use. Although some of these studies have reported outcomes associated with a history of drinking, none have examined alcohol‐seeking behavior. In addition, no preclinical studies have examined alcohol use as a function of APOE genotype with or without traumatic brain injury. Methods: Male and female human APOE3‐ and APOE4‐targeted replacement (TR) mice were used to assess voluntary alcohol seeking longitudinally using a 2‐bottle choice paradigm conducted within the automated IntelliCage system prior to and following repeated mild TBI (rmTBI). Following an acquisition phase in which the concentration of ethanol (EtOH) was increased to 12%, a variety of drinking paradigms that included extended alcohol access (EAA1 and EAA2), alcohol deprivation effect (ADE), limited access drinking in the dark (DID), and progressive ratio (PR) were used to assess alcohol‐seeking behavior. Additional behavioral tasks were performed to measure cognitive function and anxiety‐like behavior. Results: All groups readily consumed increasing concentrations of EtOH (4–12%) during the acquisition phase. During the EAA1 period (12% EtOH), there was a significant genotype effect in both males and females for EtOH preference. Following a 3‐week abstinence period, mice received sham or rmTBI resulting in a genotype‐ and sex‐independent main effect of rmTBI on the recovery of righting reflex and a main effect of rmTBI on spontaneous home‐cage activity in females only. Reintroduction of 12% EtOH (EAA2) resulted in a significant effect genotype for alcohol preference in males with APOE4 mice displaying increased preference and motivation for alcohol compared with APOE3 mice independent of TBI while in females, there was a significant genotype × TBI interaction under the ADE and DID paradigms. Finally, there was a main effect of rmTBI on increased risk‐seeking behavior in both sexes, but no effect on spatial learning or cognitive flexibility. Conclusion: These results suggest that sex and APOE genotype play a significant role in alcohol consumption and may subsequently influence long‐term recovery following traumatic brain insults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Alcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol‐induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear. Microglia are uniquely positioned to sense and respond to central nervous system insult, and are now understood to exhibit innate immune memory, or "priming," altering their future functional responses based on prior exposures. In alcohol use disorders (AUDs), the role of microglia is debated. Whereas microglial activation can be pathogenic, contributing to neuroinflammation, tissue damage, and behavioral changes, or protective, it can also engage protective functions, providing support and mediating the resolution of damage. Understanding the role of microglia in adolescent AUDs is complicated by the fact that microglia are thought to be involved in developmental processes such as synaptic refinement and myelination, which underlie the functional maturation of multiple brain systems in adolescence. Thus, the role microglia play in the impact of alcohol use in adolescence is likely multifaceted. Long‐term sequelae may be due to a failure to recover from EtOH‐induced tissue damage, altered neurodevelopmental trajectories, and/or persistent changes to microglial responsivity and function. Here, we review critically the literature surrounding the effects of alcohol on microglia in models of adolescent alcohol misuse. We attempt to disentangle what is known about microglia from other neuroimmune effectors, to which we apply recent discoveries on the role of microglia in development and plasticity. Considered altogether, these studies challenge assumptions that proinflammatory microglia drive addiction. Alcohol priming microglia and thereby perturbing their homeostatic roles in neurodevelopment, especially during critical periods of plasticity such as adolescence, may have more serious implications for the neuropathogenesis of AUDs in adolescents. [ABSTRACT FROM AUTHOR]