Study Of Alcohol Use Disorder Research Articles

Ayurvedic management of Alcohol Use Disorder

Substance use disorders are chronic relapsing disorders, leading to significant impairment in psychosocial functioning. Nicotine and alcohol are most widely consumed psychotropic drugs worldwide. The common use of both increases the risk of noncommunicable diseases to many folds. Conventional therapies have not been able to alter the outcome of these disorders significantly and frequent relapses continue to occur. Hence there is a need to look at complementary and alternate systems of medicine. Ayurveda remains one of the most ancient and yet living traditions practiced widely in India and has a sound philosophical and experiential basis. The planning of an effective adequate management of alcohol use disorder in Ayurveda with the aid of Ahara, Vihara, Achara and Aushadhi depends upon the strength of the disease (Roga) and the stamina of the patient (Rogi). Here is an attempt made to explain a case study of alcohol use disorder with holistic Ayurvedic management.

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Chronic stress and alcohol (ethanol) use are highly interrelated and can change an individual’s behavior through molecular adaptations that do not change the DNA sequence, but instead change gene expression. A recent wealth of research has found that these nongenomic changes can be transmitted across generations, which could partially account for the “missing heritability” observed in genome-wide association studies of alcohol use disorder and other stress-related neuropsychiatric disorders. In this review, we summarize the molecular and behavioral outcomes of nongenomic inheritance of chronic stress and ethanol exposure and the germline mechanisms that could give rise to this heritability. In doing so, we outline the need for further research to: (1) Investigate individual germline mechanisms of paternal, maternal, and biparental nongenomic chronic stress- and ethanol-related inheritance; (2) Synthesize and dissect cross-generational chronic stress and ethanol exposure; (3) Determine cross-generational molecular outcomes of preconception ethanol exposure that contribute to alcohol-related disease risk, using cancer as an example. A detailed understanding of the cross-generational nongenomic effects of stress and/or ethanol will yield novel insight into the impact of ancestral perturbations on disease risk across generations and uncover actionable targets to improve human health.

Modeling the impact of a long-term horizon and multiple treatment episodes on estimates of the cost-effectiveness of alcohol treatment in the United States.

Most clinical studies of alcohol use disorder (AUD) treatment have short follow-up periods, underestimating the full benefits of alcohol treatment. Furthermore, clinical studies only consider one treatment cycle and do not account for the need for multiple episodes to treat a chronic recurrent condition. A validated microsimulation model of the long-term drinking patterns of people with AUD in the United States simulated 10,000 individuals resembling those from a large clinical trial. The model was used to assess the impact of (1) 1-year, 5-year, and lifetime horizon on alcohol treatment cost-effectiveness estimates and (2) no, one, two, four, and unlimited additional treatment episodes on alcohol treatment cost-effectiveness estimates. Model outcomes included healthcare costs, crime costs, labor market productivity, life expectancy, quality-adjusted life years (QALYs), alcohol-related hospitalizations, and deaths. Cost-effectiveness analyses were conducted for two perspectives: a healthcare perspective that included costs from hospitalization and AUD treatment, and a broader societal perspective that also included crime costs and productivity. The incremental cost per additional QALY gained for alcohol treatment compared with no treatment decreased from $55,590 after 1 year to $78 when healthcare costs and QALYs were tracked over the lifetime, that is, treatment became more cost effective. Treatment was cost saving for any time frame when the impacts on crime and labor productivity were also accounted for in a societal perspective. Access to multiple treatment episodes dominated (i.e., it was more effective and less costly) than no-treatment and one-episode scenarios. From a healthcare perspective, incremental costs per additional QALY for increasing from a maximum of two to four treatment episodes was $499 and from four to unlimited episodes was $5049. The unlimited treatment scenario dominated all others from a societal perspective. Results were robust in sensitivity analyses. A long-term perspective and multiple episodes of alcohol treatment improve cost-effectiveness estimates. When societal impacts are included, alcohol treatment is cost saving. Results support the value of alcohol treatment.

RNA alternative splicing impacts the risk for alcohol use disorder

Alcohol use disorder (AUD) is a complex genetic disorder characterized by problems arising from excessive alcohol consumption. Identifying functional genetic variations that contribute to risk for AUD is a major goal. Alternative splicing of RNA mediates the flow of genetic information from DNA to gene expression and expands proteome diversity. We asked whether alternative splicing could be a risk factor for AUD. Herein, we used a Mendelian randomization (MR)-based approach to identify skipped exons (the predominant splicing event in brain) that contribute to AUD risk. Genotypes and RNA-seq data from the CommonMind Consortium were used as the training dataset to develop predictive models linking individual genotypes to exon skipping in the prefrontal cortex. We applied these models to data from the Collaborative Studies on Genetics of Alcoholism to examine the association between the imputed cis-regulated splicing outcome and the AUD-related traits. We identified 27 exon skipping events that were predicted to affect AUD risk; six of these were replicated in the Australian Twin-family Study of Alcohol Use Disorder. Their host genes are DRC1, ELOVL7, LINC00665, NSUN4, SRRM2 and TBC1D5. The genes downstream of these splicing events are enriched in neuroimmune pathways. The MR-inferred impacts of the ELOVL7 skipped exon on AUD risk was further supported in four additional large-scale genome-wide association studies. Additionally, this exon contributed to changes of gray matter volumes in multiple brain regions, including the visual cortex known to be involved in AUD. In conclusion, this study provides strong evidence that RNA alternative splicing impacts the susceptibility to AUD and adds new information on AUD-relevant genes and pathways. Our framework is also applicable to other types of splicing events and to other complex genetic disorders.

Analysis of the Causes, Effects, and Treatment of Alcohol Use Disorder

The number of people with alcohol problems is increasing year by year. There is a trend people of younger ages are even more affected by this issue. Alcohol use disorder is an important issue that contemporary society has started paying attention to, thereby making it one of the key topics of today's research. Researchers have made progress in determining the causes and effects of alcohol use disorder, but there are still gaps in research in certain areas, as well as a lack of unified explanations regarding the issues with cognition that alcohol problems cause. In that sense, studies have been conducted on how alcohol use disorder affects working memory, along with other aspects of cognition. Yet, these studies conclude that additional research is necessary in order to discover how the working memory abilities of people with alcohol use disorder can be increased. In studies of alcohol use disorder causes the physical and emotional aspects, experts note that decision-making processes, positive emotions, and negative experiences are common factors that lead to the disorder. To explore therapy and suggestions to treat alcohol use disorder, this paper examined the literature of negative impact of alcohol use disorders on working memory. The results of the analysis concluded that alcohol use disorder severely affects cognition, especially working memory. Further findings determine that combining behavioral therapy and medications is the best strategy patients can have when they are reluctant to stop using alcohol. The consequences of alcohol use disorder are also provided, including both the physical aspects and the cognitive impacts that affect people’s daily lives.

Advances in neuroimaging studies of alcohol use disorder (AUD).

Alcohol use disorder (AUD) is a worldwide problem and the most common substance use disorder. Chronic alcohol consumption may have negative effects on the body, the mind, the family, and even society. With the progress of current neuroimaging methods, an increasing number of imaging techniques are being used to objectively detect brain impairment induced by alcoholism and serve a vital role in the diagnosis, prognosis, and treatment assessment of AUD. This article organizes and analyzes the research on alcohol dependence concerning the main noninvasive neuroimaging methods, structural magnetic resonance imaging, functional magnetic resonance imaging, and electroencephalography, as well as the most common noninvasive brain stimulation - transcranial magnetic stimulation, and intersperses the article with joint intra- and intergroup studies, providing an outlook on future research directions.

A single-nucleus transcriptomics study of alcohol use disorder in the nucleus accumbens.

Gene expression studies offer promising opportunities to better understand the processes underlying alcohol use disorder (AUD). As cell types differ in their function, gene expression profiles will typically vary across cell types. When studying bulk tissue, failure to account for this cellular diversity has a detrimental impact on the ability to detect disease associations. We therefore assayed the transcriptomes of 32,531 individual nuclei extracted from the nucleus accumbens (NAc) of nine donors with AUD and nine controls (72% male). Our study identified 17 clearly delineated cell types. We detected 26 transcriptome-wide significant differentially expressed genes (DEGs) that mainly involved medium spiny neurons with both D1-type and D2-type dopamine receptors, microglia (MGL) and oligodendrocytes. A higher than expected number of DEGs replicated in an existing single nucleus gene expression study of alcohol dependence in the prefrontal cortex (enrichment ratio 1.91, p value 0.019) with two genes remaining significant after a Bonferroni correction. Our most compelling result involved CD53 in MGL that replicated in the same cell type in the prefrontal cortex and was previously implicated in studies of DNA methylation, bulk gene expression and genetic variants. Several DEGs were previously reported to be associated with AUD (e.g., PER1 and MGAT5). The DEGs for MSN.3 seemed involved in neurodegeneration, disruption of circadian rhythms, alterations in glucose metabolism and changes in synaptic plasticity. For MGL, the DEGs implicated neuroinflammation and immune-related processes and for OLI, disruptions in myelination. This identification of the specific cell-types from which the association signals originate will be key for designing proper follow-up experiments and, eventually, novel clinical interventions.

Examining replicability in addictions research: How to assess and ways forward.

The high rate of statistically significant findings in the sciences that do not replicate in a new sample has been described as a "replication crisis." Few replication attempts have been conducted in studies of alcohol use disorder (AUD), and the best method for determining whether a finding replicates has not been explored. The goal of the current study was to conduct direct replications within a multisite AUD-randomized controlled trial and to test a range of replication metrics. We used data from a large AUD clinical trial (Project Matching Alcoholism Treatments and Client Heterogeneity [Project MATCH], n = 1,726) to simulate direct replication attempts. We examined associations between drinking intensity and negative alcohol-related consequences (Model 1), sex differences in drinking intensity (Model 2), and reductions in drinking following treatment (Model 3). We treated each of the 11 data collection sites as unique studies such that each subsample was treated as an "original" study, and the remaining 10 subsamples were viewed as "replication" studies. Replicability metrics included the consistency of statistical significance, overlapping confidence intervals, and consistency of the direction of the effect. We also tested effect replication and heterogeneity using meta-analysis. We observed between 0% and 100% replicability across the replicability metrics depending on which subsample was treated as the "original" study. Meta-analyses indicated results were more similar across subsamples with no significant heterogeneity for Models 1 and 2. We recommend researchers focus on effect sizes and use meta-analysis to evaluate the level of replicability. We also encourage direct replication attempts and sharing of data and code to facilitate direct replication. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Deriving a Measure of Social Recovery Capital From the Important People and Activities Instrument: Construction and Psychometric Properties.

This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald's ω= 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC.

Perceived racial and social class discrimination and cannabis involvement among Black youth and young adults

BackgroundThe current study examines the association of perceived racial and social class discrimination with cannabis involvement among Black youth and young adults. MethodsThis secondary analysis used data from the Missouri Family Study (MOFAM), a high-risk longitudinal family study of alcohol use disorder, oversampled for Black families. Offspring (n = 806) and their mothers were interviewed by telephone. Cox proportional hazards regression analyzes were used to examine associations of racial and social class discrimination (experienced by offspring and their mothers) with offspring cannabis involvement. Two stages of cannabis involvement were analyzed: timing of 1) initiation and 2) transition from initiation to first cannabis use disorder (CUD) symptom. ResultsThe study found that offspring report of experiencing racial (HR: 1.28, CI: 1.01–1.62) and social class discrimination (HR: 1.45, CI: 1.14–1.84) were associated with cannabis initiation in our fully adjusted model. Mothers’ report of discrimination predicted a lower hazard of cannabis initiation among offspring (HR: 0.79, CI: 0.64–0.98). Offspring social class discrimination (HR: 2.45, CI: 1.71–3.51) predicted an increased hazard of transition from initiation to first CUD symptom, while offspring racial discrimination (HR: 0.57, CI: 0.39–0.85) was associated with lower hazard of transition in our fully adjusted model. ConclusionsAs rates for cannabis use among Black youth are disproportionately rising, there is a critical need to identify pathways to its use among Black youth. These findings suggest racial and social class discrimination may be important targets in efforts to prevent cannabis involvement among Black youth and emerging adults.

Repeated Ethanol Exposure Alters DNA Methylation Status and Dynorphin/Kappa-Opioid Receptor Expression in Nucleus Accumbens of Alcohol-Preferring AA Rats.

Growing evidence suggests that epigenetic mechanisms, such as DNA methylation and demethylation, and histone modifications, are involved in the development of alcohol and drug addiction. However, studies of alcohol use disorder (AUD) that are focused on epigenetic DNA modifications and gene expression changes remain conflicting. Our aim was to study the effect of repeated ethanol consumption on epigenetic regulatory enzymes such as DNA methyltransferase and demethylase enzymes and whether those changes affected dynorphin/kappa-opioid receptor system in the Nucleus Accumbens (NAc). Two groups of male alcohol-preferring Alko Alcohol (AA) rats, rats which are selectively bred for high voluntary alcohol consumption and one group of male Wistar rats were used. The first group of AA rats had access to alcohol (10% ethanol solution) for 90 min on Mondays, Wednesdays and Fridays over a period of 3 weeks to establish a stable baseline of ethanol intake (AA-ethanol). The second group of AA rats (AA-water) and the Wistar rats (Wistar-water) were provided with water. Using qPCR, we found that voluntary alcohol drinking increased Dnmt1, −3a, and −3b mRNA levels and did not affect Tet family transcripts in the AA-ethanol group when compared with AA- and Wistar-water rats. DNMT and TET enzymatic activity measurements showed similar results to qPCR, where DNMT activity was increased in AA-ethanol group compared with AA-water and Wistar-water groups, with no statistically significant difference between groups in TET enzyme activity. In line with previous data, we found an increased percentage of global DNA methylation and hydroxymethylation in the AA-ethanol group compared with control rats. Finally, we investigated changes of selected candidate genes from dynorphin/kappa-opioid receptor system (Pdyn, Kor) and Dnmt3a genes that might be important in AUD-related behaviour. Our gene expression and promoter methylation analysis revealed a significant increase in the mRNA levels of Pdyn, Kor, and Dnmt3a in the AA-ethanol group, however, these changes can only be partially associate with the aberrant DNA methylation in promoter areas of the selected candidate genes. Thus, our findings suggest that the aberrant DNA methylation is rather one of the several mechanisms involved in gene expression regulation in AA rat model.

Dual methylation and hydroxymethylation study of alcohol use disorder.

Using an integrative, multi-tissue design, we sought to characterize methylation and hydroxymethylation changes in blood and brain associated with alcohol use disorder (AUD). First, we used epigenomic deconvolution to perform cell-type-specific methylome-wide association studies within subpopulations of granulocytes/T-cells/B-cells/monocytes in 1132 blood samples. Blood findings were then examined for overlap with AUD-related associations with methylation and hydroxymethylation in 50 human post-mortem brain samples. Follow-up analyses investigated if overlapping findings mediated AUD-associated transcription changes in the same brain samples. Lastly, we replicated our blood findings in an independent sample of 412 individuals and aimed to replicate published alcohol methylation findings using our results. Cell-type-specific analyses in blood identified methylome-wide significant associations in monocytes and T-cells. The monocyte findings were significantly enriched for AUD-related methylation and hydroxymethylation in brain. Hydroxymethylation in specific sites mediated AUD-associated transcription in the same brain samples. As part of the most comprehensive methylation study of AUD to date, this work involved the first cell-type-specific methylation study of AUD conducted in blood, identifying and replicating a finding in DLGAP1 that may be a blood-based biomarker of AUD. In this first study to consider the role of hydroxymethylation in AUD, we found evidence for a novel mechanism for cognitive deficits associated with AUD. Our results suggest promising new avenues for AUD research.

Epigenome-wide association study of alcohol use disorder in five brain regions

Alcohol use disorder (AUD) is closely linked to the brain regions forming the neurocircuitry of addiction. Postmortem human brain tissue enables the direct study of the molecular pathomechanisms of AUD. This study aims to identify these mechanisms by examining differential DNA-methylation between cases with severe AUD (n = 53) and controls (n = 58) using a brain-region-specific approach, in which sample sizes ranged between 46 and 94. Samples of the anterior cingulate cortex (ACC), Brodmann Area 9 (BA9), caudate nucleus (CN), ventral striatum (VS), and putamen (PUT) were investigated. DNA-methylation levels were determined using the Illumina HumanMethylationEPIC Beadchip. Epigenome-wide association analyses were carried out to identify differentially methylated CpG-sites and regions between cases and controls in each brain region. Weighted correlation network analysis (WGCNA), gene-set, and GWAS-enrichment analyses were performed. Two differentially methylated CpG-sites were associated with AUD in the CN, and 18 in VS (q < 0.05). No epigenome-wide significant CpG-sites were found in BA9, ACC, or PUT. Differentially methylated regions associated with AUD case-/control status (q < 0.05) were found in the CN (n = 6), VS (n = 18), and ACC (n = 1). In the VS, the WGCNA-module showing the strongest association with AUD was enriched for immune-related pathways. This study is the first to analyze methylation differences between AUD cases and controls in multiple brain regions and consists of the largest sample to date. Several novel CpG-sites and regions implicated in AUD were identified, providing a first basis to explore epigenetic correlates of AUD.

Gender discrimination and illicit drug use among African American and European American adolescents and emerging adults.

Objective: The present study aimed to characterize the association of perceived gender discrimination and illicit drug use among a sample of African American (AA) and European American (EA) adolescent girls and young women. Method: Data were drawn from a high-risk family study of alcohol use disorder of mothers and their offspring (N = 735). Multinomial regressions were used to examine whether experience of offspring and maternal gender discrimination were associated with offspring illicit drug use (cannabis, cocaine, ecstasy, PCP, opiates, hallucinogens, solvents, sedatives, or inhalants). Outcomes included offspring age of drug use initiation (age ≤ 14) and lifetime heavy drug use (≥ 50 times) of 1 or more illicit substances. Interactions between race and offspring gender discrimination were modeled to assess for race differences. Results: Results revealed that gender discrimination was associated with a greater likelihood of offspring early initiation (relative risk ratio [RRR] = 2.57, 95% CI [1.31, 5.03]) versus later initiation (RRR = 1.33, 95% CI [0.80, 2.24]). Offspring gender discrimination was associated with offspring heavy drug use (RRR = 2.09, 95% CI [1.07, 4.06]) and not associated with moderate/light use (RRR = 1.44, 95% CI [0.86, 2.42]), but post hoc tests revealed no significant group differences. Conclusions: Findings suggest that perceived offspring gender discrimination is associated with early drug use initiation. Gender discrimination, particularly at an early age, has a potential to cause harm, including drug use. Implementation of policies that foster environments that eliminate gender bias and discrimination at an early age should be prioritized. Gender-responsive treatment merits consideration by substance use treatment providers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Recruiting for diversity: a pilot test of recruitment strategies for a national alcohol survey with mail-in genetic data collection.

We assessed the feasibility and acceptability of collecting a saliva sample for DNA through the mail from a national sample of drinkers and examined whether targeted messaging would increase the response rates of Black/African American and Hispanic/Latino participants. We invited respondents from two prior national population surveys to participate in a brief telephone survey regarding recent alcohol use and to mail in a self-administered saliva sample. Blacks/African Americans, Hispanics/Latinos, and Whites had similar rates of consenting to participate. A higher proportion of respondents with a college education and a family history of alcohol problems consented. The differences in participation between respondents receiving targeted and general messaging were not statistically significant. This study provides preliminary evidence for the feasibility of recruiting diverse participants into a genetic study of alcohol use disorder.

Social class discrimination as a predictor of first cigarette use and transition to nicotine use disorder in Black and White youth.

To characterize the association of social class discrimination with the timing of first cigarette use and progression to DSM-IV nicotine dependence (ND) in Black and White youth, examining variation by race, parent vs. youth experiences of discrimination, socioeconomic status (SES), and stage of smoking. Data were drawn from 1461 youth (55.2% Black, 44.8% White; 50.2% female) and mothers in a high-risk family study of alcohol use disorder and related conditions. Cox proportional hazard regression analyses were conducted, using youth's and mother's social class discrimination to predict first cigarette use and progression to ND, stratifying by race. Interactions between discrimination and SES indicators (parental education and household income) were tested. Adjusted models included psychiatric covariates. In the adjusted first cigarette use models, neither youth's nor mother's social class discrimination was asignificant predictor among Black youth, but mother's discrimination was associated with increased risk [HR = 1.53 (1.18-1.99)] among White youth. In the adjusted ND models, mother's discrimination was associated with reduced ND risk for Black youth in middle-income families [HR = 0.29 (CI 0.13-0.63)], but neither youth's nor mother's discrimination predicted transition to ND among White youth. The observed race and smoking stage-specific effects suggest that social class discrimination is more impactful on early stages of smoking for White youth and later stages for Black youth. The robustness of links with mother's discrimination experiences further suggests the importance of considering family-level effects and the need to explore possible mechanisms, such as socialization processes.

Inclusion of Cannabis Users in Alcohol Research Samples: Screening In, Screening Out, and Implications.

Alcohol and cannabis are frequently co-used, as 20-50% of those who drink alcohol report co-using cannabis. This study is based on the argument that alcohol researchers should enroll cannabis users in human laboratory studies of alcohol use disorder (AUD) to strengthen generalizability. This study examines how heavy drinking cannabis users differ from non-cannabis using heavy drinkers. In a community sample of non-treatment-seeking heavy drinkers (n=551, 35% female), cannabis users were identified through: (a) self-reported cannabis use in the past 6months and (b) positive urine toxicology test for tetrahydrocannabinol (THC). Cannabis users, identified as described previously, were compared with non-cannabis users on demographic and clinical characteristics. Those who endorsed cannabis use in the past 6months reported more binge drinking days. Participants who tested positive for THC had higher Alcohol Use Disorder Identification Test scores and more binge drinking days. Younger age and being a tobacco smoker were associated with an increased likelihood of cannabis use in the past 6months, whereas male gender and being a tobacco use were associated with a greater likelihood of testing positive for THC. Individuals with cannabis use disorder (CUD) endorsed more depression and anxiety and had higher AUD symptom counts than cannabis users without CUD. The inclusion of cannabis users in AUD samples allows for increased clinical severity. Excluding cannabis users from AUD studies may limit representativeness and expend unnecessary study resources. Lastly, tobacco use may explain a large portion of the effects of cannabis use on sample characteristics. Alcohol and cannabis are frequently co-used substances. In a sample of non-treatment-seeking heavy drinkers (n=551, 35% female), cannabis users reported higher alcohol use and higher likelihood of tobacco use than non-cannabis users. Including cannabis users in alcohol research studies will improve representativeness and likely increase clinical severity.

Trauma exposure and post-traumatic stress disorder among youth in a high-risk family study: Associations with maternal and paternal alcohol use disorder

This study presents findings regarding the prevalence of trauma exposure and Posttraumatic Stress Disorder (PTSD) based on discrete types of trauma (physical, sexual, witnessed violence, and non-assaultive trauma) among 3404 youth in a family study of Alcohol Use Disorder (AUD). Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were used to examine associations of parent AUD with offspring’s childhood trauma exposure, and with lifetime diagnosis of DSM-IV PTSD among White and Black participants aged 12-35.Of 3404 youth, 59.7% had parents affected by AUD and 78% experienced ≤1 traumatic event before age 18. AUD in one or both parents was associated with physical, sexual, and witnessed violence among Whites. Among African Americans, maternal AUD was associated with sexual assault. The lifetime PTSD rate among youth exposed to childhood trauma was 8.6%, and mother-only AUD was significantly associated with lifetime PTSD among participants in both groups. PTSD among youth in this study were somewhat higher (7.9% to 8.83%) than those found in general population studies of the same demographic (5% to 6.8%). Maternal AUD appears to be a salient risk factor for sexual assault before age 18 among Black and development of lifetime PTSD among White youth.

Recent advances in genetic studies of alcohol use disorders.

Alcohol use disorder (AUD) is a complex genetic disorder with very high heritability. This polygenic disorder not only results in increased morbidity and mortality, it is also a substantial social and economic burden on families and the nation. For past three decades, several genetic studies were conducted to identify genes and pathways associated with AUD. This review aims to summarize past efforts and recent advances in genetic association studies of AUD and related traits. Initial genetic association studies achieved a limted success and suffered from low power due to small sample sizes. AUD is a polygenic trait and data from several thousands individuals was required to identify the genetic factors of small effect sizes. The scenario changed recently with technological advances and significant reduction in cost of the genome wide association analyses (GWAS). This enabled researchers to generate genomic data on mega biobanks and cohorts with access to extensive clinical and non-clinical phenotypes. Public access to data from biobanks and collaborative efforts of researchers lead to identification of several novel loci associated with AUDs and related traits. Efforts are now underway to identify the causal variants under the GWAS loci to identify target genes and biological mechanisms underpining AUDs. Many GWAS variants occur in promoter or enhancer regions of the genes and are involved in regulation of gene expression of causal genes. This, large amounts of "omics" data from projects such as "ENCODE", RoadMap and GTEx is also helping researchers to integrate "multi-omics" data to interpret functional significance of GWAS variants. With current review, we aim to present the recent advances in genetic and molecular studies of AUDs. Recent successes in genetic studies of AUDs will definetely motivate researchers and lead to better therapeutic interventions for this complex disorder.

Alcohol-preferring P rats exhibit aversion-resistant drinking of alcohol adulterated with quinine.

Understanding why some people continue to drink alcohol despite negative consequences and others do not is a central problem in the study of alcohol use disorder (AUD). In this study, we used alcohol-preferring P rats (a strain bred to prefer to drink alcohol, a model for genetic risk for AUD) and Wistar rats (control) to examine drinking despite negative consequences in the form of an aversive bitter taste stimulus produced by quinine. Animals were trained to consume 10% ethanol in a simple Pavlovian conditioning task that paired alcohol access with an auditory stimulus. When the alcohol was adulterated with quinine (0.1g/L), P rats continued to consume alcohol+quinine at the same rate as unadulterated alcohol, despite a demonstrated aversion to quinine-adulterated alcohol when given a choice between adulterated and unadulterated alcohol in the home cage. Conversely, Wistar rats decreased consumption of quinine-adulterated alcohol in the task, but continued to try the alcohol+quinine solution at similar rates to unadulterated alcohol. These results indicate that following about 8 weeks of alcohol consumption, P rats exhibit aversion-resistant drinking. This model could be used in future work to explore how the biological basis of alcohol consumption and genetic risk for excessive drinking lead to drinking that is resistant to devaluation.