Showing papers in "Alcoholism: Clinical and Experimental Research in 2018"

Trends in Adult Alcohol Use and Binge Drinking in the Early 21st-Century United States: A Meta-Analysis of 6 National Survey Series.

Abstract: Background Recent trends in alcoholic liver disease, alcohol-related emergency room admissions, and alcohol use disorder prevalence as measured by general-population surveys have raised concerns about rising alcohol-related morbidity and mortality in the United States. In contrast, upward trends in per capita alcohol consumption have been comparatively modest. Methods To resolve these discordant observations, we sought to examine trends in the prevalence of alcohol use and binge drinking from 6 regularly or periodically administered national surveys using a meta-analytic approach. Annual or periodic prevalence estimates for past-12-month or past-30-day alcohol use and binge drinking were estimated for available time points between the years 2000 and 2016. Estimates were combined in a random-effects regression model in which prevalence was modeled as a log-linear function of time to obtain meta-analytic trend estimates for the full population and by sex, race, age, and educational attainment. Results Meta-analysis-derived estimates of average annual percentage increase in the prevalence of alcohol use and binge drinking were 0.30% per year (95% CI: 0.22%, 0.38%) and 0.72% per year (95% CI: 0.46%, 0.98%), respectively. There was substantial between-survey heterogeneity among trend estimates, although there was notable consistency in the degree to which trends have impacted various demographic groups. For example, most surveys found that the changes in prevalence for alcohol use and binge drinking were large and positive for ages 50 to 64 and 65 and up, and smaller, negative, or nonsignificant for ages 18 to 29. Conclusions Significant increases in the prevalence of alcohol use and of binge drinking over the past 10 to 15 years were observed, but not for all demographic groups. However, the increase in binge drinking among middle-aged and older adults is substantial and may be driving increasing rates of alcohol-related morbidity and mortality.

Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review.

Abstract: Alcohol use disorders (AUDs) are complex traits, meaning that variations in many genes contribute to the risk, as does the environment. Although the total genetic contribution to risk is substantial, most individual variations make only very small contributions. By far the strongest contributors are functional variations in 2 genes involved in alcohol (ethanol [EtOH]) metabolism. A functional variant in alcohol dehydrogenase 1B (ADH1B) is protective in people of European and Asian descent, and a different functional variant in the same gene is protective in those of African descent. A strongly protective variant in aldehyde dehydrogenase 2 (ALDH2) is essentially only found in Asians. This highlights the need to study a wide range of populations. The likely mechanism of protection against heavy drinking and AUDs in both cases is alteration in the rate of metabolism of EtOH that at least transiently elevates acetaldehyde. Other ADH and ALDH variants, including functional variations in ADH1C, have also been implicated in affecting drinking behavior and risk for alcoholism. The pattern of linkage disequilibrium in the ADH region and the differences among populations complicate analyses, particularly of regulatory variants. This critical review focuses upon the ADH and ALDH genes as they affect AUDs.

Trends in Alcohol‐Related Emergency Department Visits in the United States: Results from the Nationwide Emergency Department Sample, 2006 to 2014

Abstract: Background Acute alcohol consumption and chronic alcohol consumption increase the burden placed on emergency departments (EDs) by contributing to injury and disease. Whether the prevalence of alcohol-related ED visits in the United States has changed in recent years is unknown. The purpose of this study was to examine trends in ED visits involving acute and chronic alcohol consumption in the United States by age and sex between 2006 and 2014. Methods Data from the Nationwide Emergency Department Sample (NEDS), the largest all-payer ED database in the United States involving 945 hospitals in 33 states and Washington, DC, were analyzed to assess changes in prevalence and rates of ED visits involving acute and chronic alcohol consumption by age and sex over time among persons aged ≥12 between 2006 and 2014. Results Between 2006 and 2014, the number of ED visits involving alcohol consumption increased 61.6%, from 3,080,214 to 4,976,136. The rate increased 47% from 1,223 to 1,802 per 100,000 population and the total cost of such visits increased 272% from $4.1 billion to $15.3 billion. The number of acute alcohol-related ED visits increased 51.5% from 1,801,006 to 2,728,313 and the rate increased 40% from 720.9 to 1,009.6 per 100,000 population. The number chronic alcohol-related visits increased 75.7% from 1,279,208 to 2,247,823 and the rate increased 57.9% from 502.2 to 792.9 per 100,000. The annual percentage change in rates of all alcohol-related ED visits was larger for females than for males (5.3% vs. 4.0%). Other drug involvement increased the likelihood of admission for inpatient treatment. Conclusions Alcohol consumption contributed to an increasing number of ED visits in the United States between 2006 and 2014, especially among females. Increased utilization of evidence-based interventions is needed.

Alcohol and Opioid Use, Co-Use, and Chronic Pain in the Context of the Opioid Epidemic: A Critical Review

Abstract: The dramatic increase in opioid misuse, opioid use disorder (OUD), and opioid-related overdose deaths in the United States has led to public outcry, policy statements, and funding initiatives. Meanwhile, alcohol misuse and alcohol use disorder (AUD) are a highly prevalent public health problem associated with considerable individual and societal costs. This study provides a critical review of alcohol and opioid misuse, including issues of prevalence, morbidity, and societal costs. We also review research on interactions between alcohol and opioid use, the influence of opioids and alcohol on AUD and OUD treatment outcomes, respectively, the role of pain in the co-use of alcohol and opioids, and treatment of comorbid OUD and AUD. Heavy drinking, opioid misuse, and chronic pain individually represent significant public health problems. Few studies have examined co-use of alcohol and opioids, but available data suggest that co-use is common and likely contributes to opioid overdose-related morbidity and mortality. Co-use of opioids and alcohol is related to worse outcomes in treatment for either substance. Finally, chronic pain frequently co-occurs with use (and co-use) of alcohol and opioids. Opioid use and alcohol use are also likely to complicate the treatment of chronic pain. Research on the interactions between alcohol and opioids, as well as treatment of the comorbid disorders is lacking. Currently, most alcohol research excludes patients with OUD and there is lack of measurement in both AUD and OUD research in relation to pain-related functioning. Research in those with chronic pain often assesses opioid use, but rarely assesses alcohol use or AUD. New research to examine the nexus of alcohol, opioids, and pain, as well as their treatment, is critically needed.

Meta-analysis of the association of alcohol-related social media use with alcohol consumption and alcohol-related problems in adolescents and young adults

Abstract: Despite the pervasive use of social media by young adults, there is comparatively little known about whether, and how, engagement in social media influences this group's drinking patterns and risk of alcohol-related problems. We examined the relations between young adults' alcohol-related social media engagement (defined as the posting, liking, commenting, and viewing of alcohol-related social media content) and their drinking behavior and problems. We conducted a systematic review and meta-analysis of studies evaluating the association of alcohol consumption and alcohol-related problems with alcohol-related social media engagement. Summary baseline variables regarding the social media platform used (e.g., Facebook and Twitter), social media measures assessed (e.g., number of alcohol photographs posted), alcohol measures (e.g., Alcohol Use Disorders Identification Test and Timeline Follow back Interview), and the number of time points at which data were collected were extracted from each published study. We used the Q statistic to examine heterogeneity in the correlations between alcohol-related social media engagement and both drinking behavior and alcohol-related problems. Because there was significant heterogeneity, we used a random-effects model to evaluate the difference from zero of the weighted aggregate correlations. We used metaregression with study characteristics as moderators to test for moderators of the observed heterogeneity. Following screening, 19 articles met inclusion criteria for the meta-analysis. The primary findings indicated a statistically significant relationship and moderate effect sizes between alcohol-related social media engagement and both alcohol consumption (r = 0.36, 95% CI: 0.29 to 0.44, p < 0.001) and alcohol-related problems (r = 0.37, 95% CI: 0.21 to 0.51, p < 0.001). There was significant heterogeneity among studies. Two significant predictors of heterogeneity were (i) whether there was joint measurement of alcohol-related social media engagement and drinking behavior or these were measured on different occasions and (ii) whether measurements were taken by self-report or observation of social media engagement. We found moderate-sized effects across the 19 studies: Greater alcohol-related social media engagement was correlated with both greater self-reported drinking and alcohol-related problems. Further research to determine the causal direction of these associations could provide opportunities for social media-based interventions with young drinkers aimed at reducing alcohol consumption and alcohol-related adverse consequences.

Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

Abstract: Background We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function. Methods Sixty-nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months. Results Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory. Conclusions This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory.

Beyond Abstinence: Changes in Indices of Quality of Life with Time in Recovery in a Nationally Representative Sample of U.S. Adults.

Abstract: Background Alcohol and other drug (AOD) treatment and recovery research typically have focused narrowly on changes in alcohol/drug use (e.g., "percent days abstinent") with little attention on changes in functioning or well-being. Furthermore, little is known about whether and when such changes may occur, and for whom, as people progress in recovery. Greater knowledge would improve understanding of recovery milestones and points of vulnerability and growth. Methods National, probability-based, cross-sectional sample of U.S. adults who screened positive to the question, "Did you used to have a problem with alcohol or drugs but no longer do?" (Response = 63.4% from 39,809; final weighted sample n = 2,002). Linear, spline, and quadratic regressions tested relationships between time in recovery and 5 measures of well-being: quality of life, happiness, self-esteem, recovery capital, and psychological distress, over 2 temporal horizons: the first 40 years and the first 5 years, after resolving an AOD problem and tested moderators (sex, race, primary substance) of effects. Locally Weighted Scatterplot Smoothing regression was used to explore turning points. Results In general, in the 40-year horizon there were initially steep increases in indices of well-being (and steep drops in distress), during the first 6 years, followed by shallower increases. In the 5-year horizon, significant drops in self-esteem and happiness were observed initially during the first year followed by increases. Moderator analyses examining primary substance found that compared to alcohol and cannabis, those with opioid or other drugs (e.g., stimulants) had substantially lower recovery capital in the early years; mixed race/native Americans tended to exhibit poorer well-being compared to White people; and women consistently reported lower indices of well-being over time than men. Conclusions Recovery from AOD problems is associated with dynamic monotonic improvements in indices of well-being with the exception of the first year where self-esteem and happiness initially decrease, before improving. In early recovery, women, certain racial/ethnic groups, and those suffering from opioid and stimulant-related problems appear to face ongoing challenges that suggest a need for greater assistance.

Sex Differences in Binge-Like and Aversion-Resistant Alcohol Drinking in C57BL/6J Mice.

Abstract: Background Alcohol use disorder is characterized by compulsive alcohol intake, or drinking despite negative consequences. Previous studies have shown that female rodents have a heightened vulnerability to drug use across different stages of the addictive cycle, but no previous studies have studied females in a model of aversion-resistant alcohol intake. Here, we investigated sex differences in binge-like and aversion-resistant alcohol drinking in C57BL/6J mice using a modified drinking-in-the-dark (DID) paradigm. Methods In Experiment 1, 24-hour aversion to quinine (0, 100, or 250 μM) was assessed. In Experiment 2, male and female adult C57BL/6J mice consumed 15% ethanol (EtOH) or water in a 2-bottle limited-access DID paradigm for 2 h/d for 15 days. The EtOH was next adulterated with quinine (0, 100, or 250 μM) over 3 consecutive drinking sessions to test aversion-resistant intake. In Experiment 3, intake of quinine-adulterated (100 μM) EtOH was assessed across all 15 drinking sessions. Results Quinine was equally aversive to both sexes in Experiment 1. In Experiment 2, female mice consumed significantly more alcohol than male mice during the final 6 drinking sessions. Levels of aversion-resistant intake did not differ between the sexes. In Experiment 3, quinine suppressed consumption in all mice, though females drank significantly more on the final 2 sessions. Conclusions The results of this study demonstrate that while female mice escalate and consume more EtOH than males, both sexes exhibit similar levels of aversion-resistant drinking. These results inform our understanding of how sex interacts with vulnerability for addiction and argue for the inclusion of females in more studies of aversion-resistant alcohol drinking.

Simultaneous Alcohol and Marijuana Use Among Young Adult Drinkers: Age-Specific Changes in Prevalence from 1977 to 2016.

Abstract: Background The overall prevalence of US 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 US 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 (450% 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

Drinking Risk Level Reductions Associated with Improvements in Physical Health and Quality of Life Among Individuals with Alcohol Use Disorder.

Abstract: BACKGROUND Abstinence and no heavy drinking days are currently the only Food and Drug Administration-approved end points in clinical trials for alcohol use disorder (AUD). Many individuals who fail to meet these criteria may substantially reduce their drinking during treatment, and most individuals with AUD prefer drinking reduction goals. One- and two-level reductions in World Health Organization (WHO) drinking risk levels have been proposed as alternative end points that reflect reduced drinking and are associated with reductions in drinking consequences, improvements in mental health, and reduced risk of developing alcohol dependence. The current study examined the association between WHO drinking risk level reductions and improvements in physical health and quality of life in a sample of individuals with alcohol dependence. METHODS Secondary data analysis of individuals with alcohol dependence (n = 1,142) enrolled in the longitudinal, prospective COMBINE study, a multi site randomized placebo-controlled clinical trial, examining the association between reductions in WHO drinking risk levels and change in blood pressure, liver enzyme levels, and self-reported quality of life following treatment for alcohol dependence. RESULTS One- and two-level reductions in WHO drinking risk level during treatment were associated with significant reductions in systolic blood pressure (p < 0.001), improvements in liver enzyme levels (all p < 0.01), and significantly better quality of life (p < 0.001). CONCLUSIONS One- and two-level reductions in WHO drinking risk levels predicted significant improvements in markers of physical health and quality of life, suggesting that the WHO drinking risk level reduction could be a meaningful surrogate marker of improvements in how a person "feels and functions" following treatment for alcohol dependence. The WHO drinking risk levels could be useful in medical practice for identifying drinking reduction targets that correspond with clinically significant improvements in health and quality of life.

Age of alcohol initiation and progression to binge drinking in adolescence: a prospective cohort study

Abstract: Background: Early alcohol initiation is common and has been associated with the development of alcohol problems. Yet, past research on the association of age of initiation with later problem drinking has produced inconsistent findings. Using prospective data from the Australian Parental Supply of Alcohol Longitudinal Study cohort, this study examined age of alcohol initiation, and of first drunkenness, and associations with subsequent drinking in adolescence. Methods: A total of 1,673 parent–child dyads recruited through Australian secondary schools completed annual surveys for 5 years (grades 7 to 11). Limiting the sample to those adolescents who had initiated alcohol use by age 17 (n = 839), multinomial logistic regression models were used to examine associations between (i) age of initiation to alcohol use (consuming at least 1 full serve) and (ii) age of first drunkenness, and 2 outcomes: (i) binge drinking (consuming >4 standard drinks on a single occasion), and (ii) the total number of alcoholic drinks consumed in the past year, adjusted for a range of potential child, parent, family, and peer covariates. Results: Fifty percent of adolescents reported alcohol use and 36% reported bingeing at wave 5 (mean age 16.9 years), and the mean age of initiation to alcohol use for drinkers was 15.1 years. Age of initiation was significantly associated with binge drinking and total quantity of alcohol consumed in unadjusted and adjusted models. Age of first drunkenness was associated with total quantity of alcohol consumed in unadjusted models but not adjusted models and was not associated with subsequent bingeing. Conclusions: Initiating alcohol use earlier in adolescence is associated with an increased risk of binge drinking and higher quantity of consumption in late secondary school, supporting an argument for delaying alcohol initiation for as long as possible to reduce the risk for problematic use in later adolescence and the alcohol‐related harms that may accompany this use.

Daily Patterns of Marijuana and Alcohol Co-Use Among Individuals with Alcohol and Cannabis Use Disorders.

Abstract: Author(s): Metrik, Jane; Gunn, Rachel L; Jackson, Kristina M; Sokolovsky, Alexander W; Borsari, Brian | Abstract: BACKGROUND:The study aims were to examine daily associations between marijuana and alcohol use and the extent to which the association differs as a function of cannabis use disorder (CUD) and/or alcohol use disorder (AUD) diagnosis. METHODS:Timeline Followback interview data was collected in a study of veterans (N = 127) recruited from a Veterans Affairs hospital who reported at least 1 day of co-use of marijuana and alcohol in the past 180 days (22,860 observations). Participants reported 40% marijuana use days, 28% drinking days, with 37% meeting DSM-5 criteria for CUD, 40% for AUD, and 15% for both. Use of marijuana on a given day was used to predict a 3-level gender-adjusted drinking variable (heavy: ≥5 (men)/4 (women) drinks; moderate: 1 to 4/3 drinks; or none: 0 drinks). A categorical 4-level variable (no diagnosis, AUD, CUD, or both) was tested as a moderator of the marijuana-alcohol relationship. RESULTS:Multilevel modeling analyses demonstrated that participants were more likely to drink heavily compared to moderately (OR = 2.34) and moderately compared to not drinking (OR = 1.61) on marijuana use days relative to nonuse days. On marijuana use days, those with AUD and those with AUD + CUD were more likely to drink heavily (OR = 1.91; OR = 2.51, respectively), but those with CUD were less likely to drink heavily (OR = 0.32) compared to moderately, nonsignificant differences between any versus moderate drinking in interaction models. CONCLUSIONS:Heavy drinking occurs on days when marijuana is also used. This association is particularly evident in individuals diagnosed with both AUD and CUD and AUDs alone but not in those with only CUDs. Findings suggest that alcohol interventions may need to specifically address marijuana use as a risk factor for heavy drinking and AUD.

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial assessing Efficacy and Safety.

Abstract: Background: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT®), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD).

A Critical Review and Meta-Analysis of the Associations Between Acculturation and Alcohol Use Outcomes Among Hispanic Americans.

Abstract: Acculturation has been studied as one key sociocultural determinant that helps explain ethnic disparities in alcohol use outcomes among Hispanic Americans. Primary studies and other systematic reviews have found between-study inconsistencies regarding the extent to which acculturation is associated with alcohol use outcomes among Hispanic Americans. To better examine whether acculturation is distinctly linked to drinker status, drinking frequency, volume, intensity, binge drinking, and hazardous alcohol use/drinking problems, and to identify individual and methodological factors that moderate these associations, we conducted a comprehensive research synthesis. A systematic review was conducted on research pertaining to the associations between acculturation and alcohol use among Hispanics. We included 88 independent study samples (N = 68,282) coded from 68 manuscripts published in 1987 to 2017. Standard and robust variance estimation (RVE) meta-analyses were conducted to calculate the correlations between acculturation and overall alcohol use. We also conducted a series of analyses to examine the weighted mean correlations between acculturation and 6 specific drinking outcomes. We found a statistically significant correlation between acculturation and overall alcohol use (r = 0.09, p < 0.001). Acculturation was associated with drinker status (r = 0.10, p < 0.001), drinking intensity (r = 0.09, p = 0.001), binge drinking (r = 0.05, p = 0.006), and hazardous alcohol use/drinking problems (r = 0.06, p = 0.006), but not drinking frequency (r = 0.02, p = 0.56) or volume (r = 0.01, p = 0.73). Gender, acculturation dimension, acculturation domain, age group, and sampling settings were found to explain between-study variability in some of these associations. Findings show small relations between acculturation and various alcohol use outcomes, but the effects are relatively more robust among Hispanic women, adults, and when studies measured U.S. cultural orientation, linguistic acculturation, and behavioral practices.

Ovarian Hormones Contribute to High Levels of Binge-Like Drinking by Female Mice.

Abstract: Background Recently, the incidence of binge drinking by women has increased. Binge drinking is detrimental to women's health, yet the biological mechanisms that promote excessive drinking by women are not well understood. One method of assessing binge-like ethanol (EtOH) consumption in mice is the drinking in the dark (DID) test, in which mice drink sufficient EtOH to achieve intoxication. In this study, we directly compared male, female, and ovariectomized (OVX) mice for DID and tested whether 17β-estradiol (E2) contributes to DID. We also measured whether DID varies throughout the estrous cycle and whether repeated intermittent DID impacts the estrous cycle. Methods Male, female, and OVX C57BL/6J mice were tested for DID for 2 hours per day on days 1 to 3 and for 4 hours on day 4 using a single bottle containing 20% EtOH. To measure the effects of E2 on DID, OVX mice were treated with estradiol benzoate (EB) or vehicle daily starting 2 weeks prior to the drinking test and throughout the DID procedure. In a separate group of experiments, EtOH consumption and estrous cycle phase were measured in freely cycling mice that were drinking EtOH or water 5 days per week for 2 or 6 weeks. Results Female mice consumed more EtOH than male and OVX mice. Treatment with EB increased EtOH consumption by OVX mice compared with vehicle-treated controls. However, EtOH intake did not vary across the estrous cycle, nor did long-term DID alter the estrous cycle. Conclusions These results demonstrate that ovarian hormones, specifically E2, contribute to increased EtOH consumption by female mice in the DID test. Although ovarian hormones contribute to this behavior, EtOH consumption is not affected by estrous cycle phase in freely cycling mice. This study provides a framework for understanding the factors that contribute to binge drinking in females.

The Lieber-DeCarli Diet—A Flagship Model for Experimental Alcoholic Liver Disease

Abstract: Alcoholic liver disease (ALD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. Understanding the pathophysiology and successful treatment for ALD is closely associated with the suitability of the animal model, which fully reflects all aspects of the pathogenesis and typical histological findings. This study reviews one of the most widely used experimental models of ALD in rodents-the Lieber-DeCarli (LDC) liquid diet. It is an easy, accurate, reliable, and inexpensive model to study the pathogenesis of early stages of ALD. Here, we discuss the historical background and provide an overview of the advantages and disadvantages of the classical LDC as well as modified "second-hit" models. We also provide a comprehensive protocol for the application of the LDC diet to perform it successfully, reliably, and reproducibly in mice.

Effects of Long-Term Alcohol Drinking on the Dopamine D2 Receptor: Gene Expression and Heteroreceptor Complexes in the Striatum in Rats.

Abstract: Background Reduced dopamine D2 receptor (D2R) ligand binding has repeatedly been demonstrated in the striatum of humans with alcohol use disorder (AUD). The attenuated D2R binding has been suggested to reflect a reduced D2R density, which in turn has been proposed to drive craving and relapse. However, results from rodent studies addressing the effects of alcohol drinking on D2R density have been inconsistent. Methods A validated alcohol drinking model (intermittent access to 20% alcohol) in Wistar rats was used to study the effects of voluntary alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age-matched alcohol-naive control rats. Reverse transcriptase quantitative PCR was used to quantify isoform-specific Drd2 gene expression levels. Using bisulfite pyrosequencing, DNA methylation levels of a regulatory region of the Drd2 gene were determined. In situ proximity ligation assay was used to measure densities of D2R receptor complexes: D2R-D2R, adenosine A2A receptor (A2AR)-D2R, and sigma1 receptor (sigma1R)-D2R. Results Long-term voluntary alcohol drinking significantly reduced mRNA levels of the long D2R isoform in the nucleus accumbens (NAc) but did not alter CpG methylation levels in the analyzed sequence of the Drd2 gene. Alcohol drinking also reduced the striatal density of D2R-D2R homoreceptor complexes, increased the density of A2AR-D2R heteroreceptor complexes in the NAc shell and the dorsal striatum, and decreased the density of sigma1R-D2R heteroreceptor complexes in the dorsal striatum. Conclusions The present results on long-term alcohol drinking might reflect reduced D2R levels through reductions in D2R-D2R homoreceptor complexes and gene expression. Furthermore, based on antagonistic interactions between A2AR and D2R, an increased density of A2AR-D2R heteroreceptor complexes might indicate a reduced affinity and signaling of the D2R population within the complex. Hence, both reduced striatal D2R levels and reduced D2R protomer affinity within the striatal A2AR-D2R complex might underlie reduced D2R radioligand binding in humans with AUD. This supports the hypothesis of a hypodopaminergic system in AUD and suggests the A2AR-D2R heteroreceptor complex as a potential novel treatment target.

A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity.

Abstract: Attributes of alcohol sensitivity are present before alcohol use disorders (AUDs) develop, they predict those adverse alcohol outcomes, are familial in nature, and many are heritable. Whether measured by alcohol challenges or retrospective reports of numbers of drinks required for effects, alcohol sensitivity reflects multiple phenotypes, including low levels of alcohol response and alcohol-related stimulation. Identification of genes that contribute to alcohol sensitivity could help identify individuals carrying risks for AUDs through their alcohol responses for whom early intervention might mitigate their vulnerability. Such genes could also improve understanding of biological underpinnings of AUDs, which could lead to new treatment approaches. However, the existing literature points to a wide range of genetic mechanisms that might contribute to alcohol responses, and few such genetic findings have been widely replicated. This critical review describes the potential impact of the diverse methods used to study sensitivity on the diversity of genetic findings that have been reported, places the genetic variants mentioned in the literature into broader categories rather than isolated results, and offers suggestions regarding how to advance the field by interpreting findings in light of the methods used to select research subjects and to measure alcohol sensitivity. To date, the most promising results have been for GABA, glutamate, opioid, dopamine, serotonin, and cholinergic system genes. The more gene variants that can be identified as contributors to sensitivity the better future gene screening platforms or polygenic scores are likely to be.

Regional Brain Volume Changes in Alcohol-Dependent Individuals During Short-Term and Long-Term Abstinence.

Abstract: Background Widespread brain atrophy in alcohol-dependent individuals (ALC) has been consistently documented in pathological and magnetic resonance imaging (MRI) studies. Longitudinal MRI studies have shown that the regional brain volume losses in ALC are partially reversible during abstinence from alcohol. The goal of this study was to determine volume reductions in cortical and subcortical regions functionally important to substance use behavior and their changes during short-term (1 week to 1 month) and long-term abstinence (1 to 7 months) from alcohol. The regions of interest (ROIs) were as follows: anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), insula, amygdala, and hippocampus. Methods A total of 85 unique ALC were assessed at 1 week (n = 65), 1 month (n = 82), and 7 months (n = 36) of abstinence. In addition, 17 light/nondrinking healthy controls (CON) were assessed at baseline and follow-up over a 10-month interval. Regional brain volumes were derived from FreeSurfer. Cross-sectional statistical analyses using 1-way analysis of variance or Fisher's exact test were applied to identify group differences. Longitudinal statistical analyses using linear mixed models were applied to identify regional volume increases and nonlinear volume recovery trajectories. Results We demonstrated significant regional volume reductions in ACC, DLPFC, and hippocampus. Older age was associated with smaller DLPFC and OFC, and higher average monthly drinking over 1 year prior to study was associated with smaller OFC. We also demonstrated significant volume increases of all ROIs except amygdala in ALC and significant nonlinear volume recovery trajectories of DLPFC, OFC, and insula. Conclusions Results showed significant volume reductions in key regions of the executive control, salience, and emotion networks in ALC at entry into treatment and significant volume increases during short-term and long-term abstinence that were nonlinear over the entire abstinence period for the DLPFC, OFC, and insula. This gray matter plasticity during alcohol abstinence may have important neurobiological and neurocognitive implications in ALC, and it may contribute to an individual's ability to maintain abstinence from alcohol at different phases.

A Clinical Trial with Combined Transcranial Direct Current Stimulation and Attentional Bias Modification in Alcohol‐Dependent Patients

Abstract: Modifying attentional processes with attentional bias modification (ABM) might be a relevant add-on to treatment in addiction. This study investigated whether influencing cortical plasticity with transcranial direct current stimulation (tDCS) could increase training effects. tDCS could also help alcohol-dependent patients to overcome craving and reduce relapse, independent of training. These approaches were combined to investigate effects in the treatment of alcoholism. Ninety-eight patients (analytical sample = 83) were randomly assigned to 4 groups in a 2-by-2 factorial design. Patients received 4 sessions of ABM (control or real training) combined with 2 mA tDCS (active: 20 minutes or sham: 30 seconds) over the left dorsolateral prefrontal cortex. Alcohol bias and craving were assessed, and treatment outcome was measured as relapse after 1 year. Attentional bias scores indicated that during the training only the group with active tDCS and real ABM displayed an overall avoidance bias (p 0.2). However, effects on relapse after active tDCS were in the expected direction. There was no evidence of a beneficial effect of tDCS or ABM or the combination. Whether the absence of effect was due to issues with the outcome measurements (e.g., lack of craving, high dropout, and unreliable measurements) or aspects of the intervention should be further investigated. [Abstract copyright: © 2018 The Authors Alcoholism: Clinical & Experimental Research published by Wiley Periodicals, Inc. on behalf of Research Society on Alcoholism.]

Differences in the Synthesis and Elimination of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 After Acute Doses of Alcohol

Abstract: Background The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers. Methods A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in 15 minutes. Blood and breath samples were collected before, at various times up to 360 minutes postconsumption, and 2, 4, 7, 11, and 14 days after alcohol consumption. Initial rates of PEth synthesis, 360 minutes area under the PEth pharmacokinetic curves (AUCs), and elimination half-lives were determined. Results (i) Nonzero PEth levels were observed before alcohol dosing for most participants, despite 7 days of alcohol use monitoring; (ii) 0.4 and 0.8 g/kg doses of alcohol produced proportional increases in PEth levels in all but 1 participant; (iii) the initial rate of synthesis of both PEth homologues did not differ between the 2 doses, but was greater for PEth 16:0/18:2 than PEth 16:0/18:1 at both doses; (iv) the mean AUC of both PEth homologues was higher at 0.8 g/kg than at 0.4 g/kg; (v) the mean AUC of 16:0/18:2 was greater than that of PEth 16:0/18:1 at both alcohol doses; (vi) the mean half-life of PEth 16:0/18:1 was longer than that of PEth 16:0/18:2 (7.8 ± 3.3 [SD] days and 6.4 ± 5.0 [SD] days, respectively); and (vii) there were no sex differences in PEth 16:0/18:1 or 16:0/18:2 pharmacokinetics. Conclusions The results of this study support the use of PEth 16:0/18:1 and 16:0/18:2 as biomarkers for alcohol consumption. Because of consistent pharmacokinetic differences, the levels of these 2 PEth homologues may provide more information regarding the quantity and recentness of alcohol consumption than either alone.

Stress, Motivation, and the Gut-Brain Axis: A Focus on the Ghrelin System and Alcohol Use Disorder

Abstract: Since its discovery, the gut hormone, ghrelin, has been implicated in diverse functional roles in the central nervous system. Central and peripheral interactions between ghrelin and other hormones, including the stress-response hormone cortisol, govern complex behavioral responses to external cues and internal states. By acting at ventral tegmental area dopaminergic projections and other areas involved in reward processing, ghrelin can induce both general and directed motivation for rewards, including craving for alcohol and other alcohol-seeking behaviors. Stress-induced increases in cortisol seem to increase ghrelin in the periphery, suggesting a pathway by which ghrelin influences how stressful life events trigger motivation for rewards. However, in some states, ghrelin may be protective against the anxiogenic effects of stressors. This critical review brings together a dynamic and growing literature, that is, at times inconsistent, on the relationships between ghrelin, central reward-motivation pathways, and central and peripheral stress responses, with a special focus on its emerging role in the context of alcohol use disorder.

How Do Self-Assessment of Alexithymia and Sensitivity to Bodily Sensations Relate to Alcohol Consumption?

Abstract: BACKGROUND: Alexithymia describes an abnormality of emotional experience that is commonly expressed among individuals with addiction and alcohol abuse disorders. Alexithymic individuals are characterized by difficulties in identifying and describing their emotions. This impairment is linked to the development and maintenance of addiction. Moreover, an emergent theory suggests alexithymia is itself secondary to a failure of interoception (sensitivity to internal bodily signals, including physiological arousal states). METHODS: The present study tested for hypothesized contributory roles of alexithymia and dysfunctional interoception in the expression of binge drinking. Alexithymia, subjective sensitivity to bodily sensations, and alcohol consumption scores were quantified using the Toronto Alexithymia Scale, the Body Perception Questionnaire and the Alcohol Use Questionnaire respectively, in a normative sample (N=600). Regression and bootstrapping mediation analyses were used to test the hypothesis that alexithymia mediated the association between sensitivity to bodily sensations and alcohol consumption. RESULTS: Alexithymia was positively correlated with sensitivity to bodily sensations and with alcohol consumption. Mediation analysis revealed that alexithymia, and more precisely, difficulty in identifying feelings, mediated the relationship between sensitivity to bodily sensations and alcohol consumption, such that the predictive effect of sensitivity to bodily sensations on alcohol intake became non-significant when controlling for alexithymia. CONCLUSIONS: These results indicate that alexithymia is associated with subjective hypersensitivity to bodily sensations. Moreover, our findings support the theoretical proposal that alexithymia is an expression of impaired processing of bodily sensations including physiological arousal, which underpin the development of maladaptive coping strategies, including alcohol use disorders. Our observations extend a growing literature emphasizing the importance of interoception and alexithymia in addiction, which can inform the development of new therapeutic strategies. This article is protected by copyright. All rights reserved.

Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice.

Abstract: Background Chronic alcohol intake leads to long-lasting changes in reward- and stress-related neuronal circuitry. The nucleus accumbens (NAc) is an integral component of this circuitry. Here, we investigate the effects of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) on neuronal activity in the NAc and binge-like drinking. Methods C57BL/6J mice were stereotaxically injected with AAV2 hSyn-HA hM3Dq, -hM4Di, or -eGFP bilaterally into NAc [core + shell, core or shell]. We measured clozapine-n-oxide (CNO)-induced changes in NAc activity and assessed binge-like ethanol (EtOH) or tastant/fluid intake in a limited access Drinking in the Dark (DID) schedule. Results We found that CNO increased NAc firing in hM3Dq positive cells and decreased firing in hM4Di cells, confirming the efficacy of these channels to alter neuronal activity both spatially and temporally. Increasing NAc core + shell activity decreased binge-like drinking without altering intake of other tastants. Increasing activity specifically in the NAc core reduced binge-like drinking, and decreasing activity in the NAc core increased drinking. Manipulation of NAc shell activity did not alter DID. Thus, we find that increasing activity in the entire NAc, or just the NAc core is sufficient to decrease binge drinking. Conclusions We conclude that the reduction in EtOH drinking is not due to general malaise, altered perception of taste, or reduced calorie-seeking. Furthermore, we provide the first evidence for bidirectional control of NAc core and binge-like drinking. These findings could have promising implications for treatment.

Reduction in Nonabstinent WHO Drinking Risk Levels and Change in Risk for Liver Disease and Positive AUDIT-C Scores: Prospective 3-Year Follow-Up Results in the U.S. General Population.

Abstract: Background Abstinence is often the treatment aim for alcohol use disorders (AUD), but this may deter individuals who prefer drinking reduction goals from entering treatment, and be an overly restrictive end point in alcohol clinical trials. Nonabstinent drinking reductions that predict improvement in how individuals feel or function may be useful clinical trial outcomes, for example, reductions in the 4-category World Health Organization (WHO) drinking risk levels. To investigate the clinical relevance of these reductions, we examined their relationship with 2 outcomes of interest to medical providers: liver disease, and positive scores on an alcohol screening measure. Methods Current drinkers in a U.S. national survey (n = 21,925) were interviewed in 2001 to 2002 (Wave 1) and re-interviewed 3 years later (Wave 2). WHO drinking risk levels, liver disease, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) were assessed at both waves. Adjusted odds ratios (aORs) were used to indicate the association of change in WHO drinking risk levels with Wave 2 liver disease and AUDIT-C scores. Results Wave 1 very-high-risk drinkers who reduced 1, 2, or 3 WHO drinking risk levels had significantly lower odds of Wave 2 liver disease (aORs = 0.34, 0.23, 0.17) and positive AUDIT-C scores (aORs = 0.27, 0.09, 0.03). Wave 1 high-risk drinkers who reduced 1 or 2 WHO risk levels had significantly lower odds of positive AUDIT-C scores (aORs = 0.61, 0.25). Adjusting for alcohol dependence or AUDIT-C scoring variations did not affect results. Conclusions In the highest-risk drinkers, reductions in WHO drinking risk levels predicted lower likelihood of liver disease and positive AUDIT-C scores. Results add to findings that reductions in the 4-category WHO drinking risk levels are a meaningful indicator of how individuals feel and function, and could serve as nonabstinent end points in clinical trials. Results also connect the WHO risk drinking levels to commonly used alcohol screening questions, which may be more familiar to healthcare providers.

Affective Disturbances During Withdrawal from Chronic Intermittent Ethanol Inhalation in C57BL/6J and DBA/2J Male Mice

Abstract: Background Alcohol use disorders are characterized by a complex behavioral symptomatology, which includes the loss of control over alcohol consumption and the emergence of a negative affective state when alcohol is not consumed. Some of these symptoms can be recapitulated in rodent models, for instance following chronic intermittent ethanol (EtOH; CIE) vapor inhalation. However, the detection of negative affect in mice withdrawn from CIE has proven challenging and variable between strains. This study aimed to detect reliable indices of negative emotionality in CIE-exposed C57BL/6J (C57) and DBA/2J (DBA) mice. Males were used because they are known to escalate their voluntary EtOH consumption upon CIE exposure, which is hypothesized to be driven by negative reinforcement (relief from negative affect). Methods Adult male mice were exposed to 4 to 6 weeks of CIE and were evaluated 3 to 10 days into withdrawal in the social approach, novelty-suppressed feeding, digging, marble burying, and bottle brush tests. Results Withdrawal from CIE decreased sociability in DBA mice but not in C57 mice. Conversely, hyponeophagia was exacerbated by CIE in C57 mice but not in DBA mice. Withdrawal from CIE robustly increased digging activity in both strains, even in the absence of marbles. Aggressive responses to bottle brush attacks were elevated in both C57 and DBA mice following CIE exposure, but CIE had an opposite effect on defensive responses in the 2 strains (increase in C57 vs. decrease in DBA). Conclusions Our results indicate that withdrawal from CIE elicits negative emotionality in both C57 and DBA mice, but different tests need to be used to measure the anxiogenic-like effects of withdrawal in each strain. Increased digging activity and irritability-like behavior represent novel indices of affective dysfunction associated with withdrawal from CIE in both mouse strains. Our findings enrich the characterization of the affective symptomatology of protracted withdrawal from CIE in mice.

Outlet Type, Access to Alcohol, and Violent Crime.

Abstract: BACKGROUND While there are overwhelming data supporting the association between alcohol outlet density and violent crime, there remain conflicting findings about whether on- or off-premise outlets have a stronger association. This inconsistency may be in part a result of the methods used to calculate alcohol outlet density and violent crime. This analysis uses routine activity theory and spatial access methods to study the association between access to alcohol outlets and violent crime, including type of outlet and type of crime in Baltimore, MD. METHODS The data in this analysis include alcohol outlets from 2016 (n = 1,204), violent crimes from 2012 to 2016 (n = 51,006), and markers of social disorganization, including owner-occupied housing, median annual household income, drug arrests, and population density. The analysis used linear regression to determine the association between access to alcohol outlets and violent crime exposure. RESULTS Each 10% increase in alcohol outlet access was associated with a 4.2% increase in violent crime exposure (β = 0.43, 95% CI 0.33, 0.52, p < 0.001). A 10% increase in access to off-premise outlets (4.4%, β = 0.45, 95% CI 0.33, 0.57, p < 0.001) and LBD-7 outlets (combined off- and on-premise outlets; 4.2%, β = 0.43, 95% CI 0.33, 0.52, p < 0.001) had a greater association with violent crime than on-premise outlets (3.0%, β = 0.31, 95% CI 0.20, 0.41, p < 0.001). CONCLUSIONS Access to outlets that allow for off-site consumption had a greater association with violent crime than outlets that only permit on-site consumption. The lack of effective measures to keep order in and around off-premise outlets could attract or multiply violent crime.

Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population

Abstract: Background Alcohol use (both quantity and dependence) is moderately heritable, and genomewide association studies (GWAS) have identified risk genes in European, African, and Asian populations. The most reproducibly identified risk genes affect alcohol metabolism. Well-known functional variants at the gene encoding alcohol dehydrogenase B and other alcohol dehydrogenases affect risk in European and African ancestry populations. Similarly, variants mapped to these same genes and a well-known null variant that maps to the gene that encodes aldehyde dehydrogenase 2 (ALDH2) also affect risk in various Asian populations. In this study, we completed the first GWAS for 3 traits related to alcohol use in a Thai population recruited initially for studies of methamphetamine dependence. Methods All subjects were evaluated with the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). A total of 1,045 subjects were available for analysis. Three traits were analyzed: flushing, maximum number of alcoholic beverages consumed in any lifetime 24-hour period ("MAXDRINKS"), and DSM-IV alcohol dependence criterion count. We also conducted a pleiotropy analysis with major depression, the only other psychiatric trait where summary statistics from a large-scale Asian-population GWAS are available. Results All 3 traits showed genomewide significant association with variants near ALDH2, with significance ranging from 2.01 × 10-14 (for flushing; lead single nucleotide polymorphism (SNP) PTPN11* rs143894582) to pmeta = 5.80 × 10-10 (for alcohol dependence criterion count; lead SNP rs149212747). These lead SNPs flank rs671 and span a region of over a megabase, illustrating the need for prior biological information in identifying the actual effect SNP, rs671. We also identified significant pleiotropy between major depression and flushing. Conclusions These results are consistent with prior findings in Asian populations and add new information regarding alcohol use-depression pleiotropy.

Remote Alcohol Monitoring to Facilitate Incentive-Based Treatment for Alcohol Use Disorder: A Randomized Trial.

Abstract: BACKGROUND The delivery of monetary incentives contingent on verified abstinence is an effective treatment for alcohol use disorder. However, technological barriers to accurate, frequent biochemical verification of alcohol abstinence have limited the dissemination of this technique. METHODS In the present randomized parallel trial, we employed a breathalyzer that allows remote, user-verified collection of a breath alcohol sample, text messaging, and reloadable debit cards for remote delivery of incentives to evaluate a contingency management treatment for alcohol use disorder that can be delivered with no in-person contact. Treatment-seeking participants with alcohol use disorder (n = 40) were recruited from the community and randomized to either a contingent or a noncontingent group (n = 20 each). The contingent group received nearly immediate monetary incentives each day they remotely provided negative breathalyzer samples. The noncontingent group received matched monetary payments each day they successfully provided samples independent of alcohol content. Groups were not masked as awareness of group contingencies was an essential intervention component. RESULTS The primary outcome of the intent-to-treat analyses (analyzed n = 40) was percent days abstinent as measured by the remote breathalyzer samples. Abstinence rates in the contingent group were 85%, which was significantly higher than the 38% recorded in the noncontingent group, corresponding to an odds ratio of 9.4 (95% CI = 4.0 to 22.2). Breathalyzer collection adherence rates were over 95%, and participant ratings of acceptability were also high. CONCLUSIONS These results support the efficacy, acceptability, and feasibility of this remotely deliverable abstinence reinforcement incentive intervention for the initiation and near-term maintenance of abstinence from alcohol in adults with alcohol use disorder. Due to low provider and participant burden, this procedure has the potential for broad dissemination.

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies.

Abstract: Prenatal alcohol exposure results in cognitive, behavioral, and neurological deficits in offspring. There is an urgent need for safe and effective treatments to overcome these effects. Maternal choline supplementation has been identified as a potential intervention. Our objective was to review preclinical and clinical studies using choline supplementation in known cases of fetal alcohol exposure to determine its effectiveness in ameliorating deficits in offspring. A systematic search of 6 electronic databases was conducted and studies selected by reviewing titles/abstracts against specific inclusion/exclusion criteria. Study characteristics, population demographics, alcohol exposure, and intervention methods were tabulated, and quality of reporting was assessed. Data on cognitive, behavioral, and neurological outcomes were extracted and tabulated. Quantitative analysis was performed to determine treatment effects for individual study outcomes. A total of 189 studies were retrieved following duplicate removal. Of these, 22 studies (2 randomized controlled trials, 2 prospective cohort studies, and 18 preclinical studies) met the full inclusion/exclusion criteria. Choline interventions were administered at different times relative to alcohol exposure, impacting on their success to prevent deficits for specific outcomes. Only 1 clinical study showed significant improvements in information processing in 6-month-old infants from mothers treated with choline during pregnancy. Preclinical studies showed significant amelioration of deficits due to prenatal alcohol exposure across a wide variety of outcomes, including epigenetic/molecular changes, gross motor, memory, and executive function. This review suggests that choline supplementation has the potential to ameliorate specific behavioral, neurological, and cognitive deficits in offspring caused by fetal alcohol exposure, at least in preclinical studies. As only 1 clinical study has shown benefit, we recommend more clinical trials be undertaken to assess the effectiveness of choline in preventing deficits across a wider range of cognitive domains in children.