Alcoholism, clinical and experimental research最新文献

{"title":"Adolescent Intermittent Ethanol Increases the Sensitivity to the Reinforcing Properties of Ethanol and the Expression of Select Cholinergic and Dopaminergic Genes within the Posterior Ventral Tegmental Area.","authors":"Sheketha R Hauser, Christopher P Knight, William A Truitt, Robert Aaron Waeiss, Ian S Holt, Gustavo B Carvajal, Richard L Bell, Zachary A Rodd","doi":"10.1111/acer.14150","DOIUrl":"10.1111/acer.14150","url":null,"abstract":"<p><strong>Background: </strong>Although not legally allowed to consume alcohol, adolescents account for 11% of all alcohol use in the United States and approximately 90% of adolescent intake is in the form of an alcohol binge. The adolescent intermittent ethanol (AIE) model developed by the NADIA consortium produces binge-like EtOH exposure episodes. The current experiment examined the effects of AIE on the reinforcing properties of EtOH and genetic expression of cholinergic and dopaminergic factors within the posterior ventral tegmental area (pVTA) in Wistar male and female rats and in male alcohol-preferring (P) rats.</p><p><strong>Methods: </strong>Rats were exposed to the AIE or water during adolescence, and all testing occurred during adulthood. Wistar control and AIE rats were randomly assigned to groups that self-administered 0 to 200 mg% EtOH. Male P rats self-administered 0 to 100 mg%.</p><p><strong>Results: </strong>The data indicated that exposure to AIE in both Wistar male and female rats (and male P rats) resulted in a significant leftward shift in dose-response curve for EtOH self-administration into the pVTA. TaqMan array indicated that AIE exposure had divergent effects on the expression of nicotinic receptors (increased a7, reduction in a4 and a5). There were also sex-specific effects of AIE on gene expression; male only reduction in D3 receptors.</p><p><strong>Conclusion: </strong>Binge-like EtOH exposure during adolescence enhances the sensitivity to the reinforcing properties of EtOH during adulthood which could be part of biological sequelae that are the basis for the deleterious effects of adolescent alcohol consumption on the rate of alcoholism during adulthood.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72533608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Hormone and Alcoholic Fatty Liver: The Developmental Input.","authors":"Arturo Hernandez","doi":"10.1111/acer.14145","DOIUrl":"https://doi.org/10.1111/acer.14145","url":null,"abstract":"The liver is a main target of thyroid hormones (TH), which can regulate the expression of multiple genes in this tissue, most notably, those associated with the metabolism and physiology of lipids. Systemic TH status is associated with biochemical parameters dependent on liver function, including cholesterol level. For this reason, the liver is considered a desirable therapeutic target for tissue-specific thyromimetic action. This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.14145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37398361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specifically Sized Hyaluronan (35 kDa) Prevents Ethanol-Induced Disruption of Epithelial Tight Junctions Through a layilin-Dependent Mechanism in Caco-2 Cells.","authors":"Damien A Bellos,&nbsp;Dhara Sharma,&nbsp;Megan R McMullen,&nbsp;Jeanette Wat,&nbsp;Paramananda Saikia,&nbsp;Carol A de la Motte,&nbsp;Laura E Nagy","doi":"10.1111/acer.14140","DOIUrl":"https://doi.org/10.1111/acer.14140","url":null,"abstract":"BACKGROUND Specific-sized species of the carbohydrate hyaluronan elicit a variety of cellular responses mediating tissue integrity and repair, as well as regulating inflammatory responses. Orally provided hyaluronan with an average molecular weight of 35kDa (HA35) protects mice from short term ethanol-induced liver injury. This protection was associated with maintenance of the co-localization of zonula occludins-1 (ZO-1) and occludin at tight junctions in the proximal colon. However, it is not known whether HA35 also protects other regions of the intestine or whether protection is due to a direct and/or indirect interaction of HA35 with the intestinal epithelium. METHODS Female C57BL/6J mice were fed an ethanol containing diet or pair-fed control diet (4 days) and treated with or without HA35 via daily gavage during the last 3 days of ethanol feeding. Intestinal morphology and tight junction integrity was assessed. Differentiated Caco-2 cells were transfected or not with scrambled siRNA or siRNA targeting layilin, a hyaluronan receptor. Caco-2 cells were treated with or without HA35 prior to challenge with ethanol. Localization of tight junction proteins, FITC-dextran permeability and transepithelial electrical resistance (TEER) were evaluated. RESULTS While short-term ethanol did not result in any apparent changes in the gross morphology of the intestine, co-localization of ZO-1 and occludin at tight junctions was decreased in proximal and distal colon. HA35 prevented these effects of ethanol. In differentiated Caco-2 cells, ethanol decreased the localization of ZO-1 and occludin at tight junctions and increased permeability of FITC-dextran. At higher concentrations, ethanol also decreased TEER. Pre-treatment with HA35 prevented these changes. When the hyaluronan receptor Layilin was knocked down in Caco-2 cells, HA35 no longer protected cells from ethanol-induced loss of tight junctions. CONCLUSION Taken together, these data indicate that HA35 interacts with Layilin on intestinal epithelial cells and maintains intestinal tight junction integrity during short-term ethanol exposure. This article is protected by copyright. All rights reserved.","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.14140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37363400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergent Evidence From Humans and Drosophila melanogaster Implicates the Transcription Factor MEF2B/Mef2 in Alcohol Sensitivity.","authors":"Rebecca E Schmitt, Brandon C Shell, Kristen M Lee, Keith L Shelton, Laura D Mathies, Alexis C Edwards, Mike Grotewiel","doi":"10.1111/acer.14138","DOIUrl":"10.1111/acer.14138","url":null,"abstract":"<p><strong>Background: </strong>Self-Rating of the Effects of Alcohol (SRE) measures level of response to ethanol (EtOH) in humans. Interestingly, there is a positive relationship between the SRE and risk for abusing alcohol, suggesting mechanistic connections between SRE and alcohol abuse.</p><p><strong>Methods: </strong>To identify candidate genes with a role in SRE and alcohol-related behavior more generally, we coupled human genetic analyses with studies in Drosophila melanogaster. We first performed a gene-based analysis of Genomewide association studies (GWAS) summary statistics for SRE in the Avon Longitudinal Study of Parents and Children sample. Based on prior findings in humans, orthology to fly genes, and the availability of genetic reagents, we selected a subset of these genes for studies on EtOH behavior in Drosophila.</p><p><strong>Results: </strong>We found 37 genes with nominal associations in our SRE GWAS. We explored the role of 6 orthologous genes in Drosophila EtOH sedation and rapid tolerance. We found that the transcription factor Mef2 is required for normal EtOH sedation in flies. Pan-neuronal expression of 2 independent Mef2 RNAi transgenes significantly reduced Mef2 expression and made flies resistant to EtOH sedation. Additionally, flies with multiple independent mutant alleles of Mef2 were also resistant to EtOH sedation, confirming a role for Mef2 in this behavior. Altered expression of Mef2 did not change EtOH rapid tolerance or cause a net change in internal EtOH concentrations.</p><p><strong>Conclusions: </strong>Our studies indicate that MEF2B influences SRE in humans and that Mef2 impacts EtOH sedation in Drosophila.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721962/pdf/nihms-1038089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37090786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol Effects on Colon Epithelium are Time-Dependent.","authors":"Faraz Bishehsari, Lijuan Zhang, Robin M Voigt, Natalie Maltby, Bita Semsarieh, Eyas Zorub, Maliha Shaikh, Sherry Wilber, Andrew R Armstrong, Seyed Sina Mirbagheri, Nailliw Z Preite, Peter Song, Alessia Stornetta, Silvia Balbo, Christopher B Forsyth, Ali Keshavarzian","doi":"10.1111/acer.14141","DOIUrl":"10.1111/acer.14141","url":null,"abstract":"<p><strong>Background: </strong>Alcohol intake increases the risk of developing colon cancer. Circadian disruption promotes alcohol's effect on colon carcinogenesis through unknown mechanisms. Alcohol's metabolites induce DNA damage, an early step in carcinogenesis. We assessed the effect of time of alcohol consumption on markers of tissue damage in the colonic epithelium.</p><p><strong>Methods: </strong>Mice were treated by alcohol or phosphate-buffered saline (PBS), at 4-hour intervals for 3 days, and their colons were analyzed for (i) proliferation (Ki67) and antiapoptosis (Bcl-2) markers, (ii) DNA damage (γ-H2AX), and (iii) the major acetaldehyde (AcH)-DNA adduct, N² -ethylidene-dG. To model circadian disruption, mice were shifted once weekly for 12 h and then were sacrificed at 4-hour intervals. Samples of mice with a dysfunctional molecular clock were analyzed. The dynamics of DNA damage repair from AcH treatment as well as role of xeroderma pigmentosum, complementation group A (XPA) in their repair were studied in vitro.</p><p><strong>Results: </strong>Proliferation and survival of colonic epithelium have daily rhythmicity. Alcohol induced colonic epithelium proliferation in a time-dependent manner, with a stronger effect during the light/rest period. Alcohol-associated DNA damage also occurred more when alcohol was given at light. Levels of DNA adduct did not vary by time, suggesting rather lower repair efficiency during the light versus dark. XPA gene expression, a key excision repair gene, was time-dependent, peaking at the beginning of the dark. XPA knockout colon epithelial cells were inefficient in repair of the DNA damage induced by alcohol's metabolite.</p><p><strong>Conclusions: </strong>Time of day of alcohol intake may be an important determinant of colon tissue damage and carcinogenicity.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722020/pdf/nihms-1038080.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37363401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discriminative Stimulus Effects and Metabolism of Ethanol in Rhesus Monkeys.","authors":"Daicia C Allen, Kathleen A Grant","doi":"10.1111/acer.14142","DOIUrl":"10.1111/acer.14142","url":null,"abstract":"<p><strong>Background: </strong>Animal models are an essential feature of drug and pharmacotherapy development for treating alcohol use disorders (AUDs). The rhesus macaque is a robust animal model for many aspects of AUDs particularly in exploiting individual differences in oral self-administration of ethanol (EtOH), endocrine orchestration of stress response, and menstrual cycle characteristics. However, the clearance rates of EtOH have not been reported in this species, and the GABA_A and N-methyl-D-aspartate (NMDA) receptor involvement in EtOH's discriminative stimulus effects has not been fully characterized.</p><p><strong>Methods: </strong>EtOH clearance rates following 2 doses of EtOH on separate days (0.5 and 1.0 g/kg, i.g.) were determined in 8 young adult male rhesus macaques. The EtOH was given by nasogastric gavage, and repeated blood samples were taken over 5 hours without sedation. Next, all subjects were trained on a 2-choice 1.0 g/kg EtOH (i.g.) versus water discrimination with a 60-minutes pretreatment period to capture peak blood EtOH concentration (BEC). Substitution testing was conducted with GABA_A ligands pentobarbital (i.g. and i.m.) and midazolam (i.g.), as well as NMDA antagonist MK-801 (i.m.).</p><p><strong>Results: </strong>Peak BECs were 34 and 87 mg/dl for 0.5 and 1.0 g/kg doses, respectively, and occurred at 66 and 87 minutes following gavage. All GABA_A and NMDA ligands tested resulted in responding on the EtOH-appropriate lever with the potency ranking of MK-801 (ED₅₀ : 0.017 mg/kg) > midazolam (ED₅₀ : 1.6 mg/kg) > pentobarbital (ED₅₀ : 3.7 mg/kg) > EtOH (ED₅₀ : 700 mg/kg, or 0.7 g/kg) in these subjects.</p><p><strong>Conclusions: </strong>These results suggest that the compound discriminative stimulus effects of EtOH are highly consistent across species, providing further support for the rhesus macaque as strong model for pharmacotherapy development for AUD.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721990/pdf/nihms-1038079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37363402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte-Neuron Lactate Shuttle in the Brain.","authors":"Daniel Lindberg,&nbsp;Ada Man Choi Ho,&nbsp;Lee Peyton,&nbsp;Doo-Sup Choi","doi":"10.1111/acer.14137","DOIUrl":"10.1111/acer.14137","url":null,"abstract":"<p><strong>Background: </strong>Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones.</p><p><strong>Methods: </strong>We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs.</p><p><strong>Results: </strong>Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs.</p><p><strong>Conclusion: </strong>CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.14137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37367320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social and Situational Party Characteristics Associated With High-Intensity Alcohol Use Among Youth and Young Adults.","authors":"Melissa J Cox,&nbsp;Kathleen L Egan,&nbsp;Cynthia K Suerken,&nbsp;Beth A Reboussin,&nbsp;Eunyoung Y Song,&nbsp;Kimberly G Wagoner,&nbsp;Mark Wolfson","doi":"10.1111/acer.14143","DOIUrl":"https://doi.org/10.1111/acer.14143","url":null,"abstract":"<p><strong>Background: </strong>Rates of high-intensity drinking, which is alcohol consumption that exceeds standard heavy drinking levels, have increased in recent years and peak in young adulthood. To identify modifiable environmental targets for prevention of high-intensity drinking, we identified characteristics of parties attended by youth and young adults that were associated with high-intensity drinking and the consequences of this excessive form of drinking.</p><p><strong>Methods: </strong>Data are from 15- to 20-year-old participants in an online survey (n = 2,442; 55.4% female, 74.8% White) who resided in 24 communities across 7 states that were a part of a community randomized intervention trial to reduce the incidence and consequences of underage drinking parties. We used multinomial logistic regression to predict level of drinking by 6 party characteristics (size, location, age and gender composition, supervision, others' drinking behavior), and to predict 6 consequences (hangover, not remember event, passed out, punished by parents, broke something/got in fight, and sex against will) from level of drinking. We tested study hypotheses in 2 models, one that used a single binge drinking threshold (below binge vs. at or above binge level) and one that additionally used a high-intensity drinking level (below binge, 1 to 2 times binge, 2+ times binge level).</p><p><strong>Results: </strong>We found that larger party size and a mostly male composition were unique predictors of high-intensity drinking when compared to those who consumed 1 to 2 times the binge drinking level. Odds of passing out, not remembering the drinking event, breaking/damaging property, or getting in a fight were more than double for high-intensity drinkers compared to standard binge level drinkers.</p><p><strong>Conclusions: </strong>Results from this study indicate there are unique precursors and consequences of high-intensity alcohol consumption among youth and young adults. These environmental factors associated with high-risk drinking contexts can be used to develop prevention strategies to mitigate the harms associated with excessive alcohol consumption.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/acer.14143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41188118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent Changes in Stress-Regulatory Genes in Pregnant Women or Children Exposed Prenatally to Alcohol.","authors":"Dipak K Sarkar, Omkaram Gangisetty, Jeffrey R Wozniak, Judith K Eckerle, Michael K Georgieff, Tatiana M Foroud, Leah Wetherill, Wladimir Wertelecki, Christina D Chambers, Edward Riley, Natalya Zymak-Zakutnya, Lyubov Yevtushok","doi":"10.1111/acer.14148","DOIUrl":"10.1111/acer.14148","url":null,"abstract":"<p><strong>Background: </strong>We have recently shown that binge or heavy levels of alcohol drinking increase deoxyribonucleic acid (DNA) methylation and reduce gene expression of proopiomelanocortin (POMC) and period 2 (PER2) in adult human subjects (Gangisetty et al., Alcohol Clin Exp Res, 43, 2019, 212). One hypothesis would be that methylation of these 2 genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of prenatal alcohol exposure (PAE). Results of the present study provided some support for this hypothesis.</p><p><strong>Methods: </strong>We conducted a series of studies to determine DNA methylation changes in stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) using biological samples from 3 separate cohorts of patients: (i) pregnant women who consumed moderate-to-high levels of alcohol or low/unexposed controls, (ii) children with PAE and non-alcohol-exposed controls, and (iii) children with PAE treated with or without choline.</p><p><strong>Results: </strong>We found pregnant women who consumed moderate-to-high levels of alcohol and gave birth to PAE children had higher DNA methylation of POMC and PER2. PAE children also had increased methylation of POMC and PER2. The differences in the gene methylation of PER2 and POMC between PAE and controls did not differ by maternal smoking status. PAE children had increased levels of stress hormone cortisol and adrenocorticotropic hormone. Choline supplementation reduced DNA hypermethylation and increased expression of POMC and PER2 in children with PAE.</p><p><strong>Conclusions: </strong>These data suggest that PAE significantly elevates DNA methylation of POMC and PER2 and increases levels of stress hormones. Furthermore, these results suggest the possibility that measuring DNA methylation levels of PER2 and POMC in biological samples from pregnant women or from children may be useful for identification of a woman or a child with PAE.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73492947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Drinking and Cortical Thickness in Younger Adult Drinkers: Findings From the Human Connectome Project.","authors":"Vanessa L Morris, Max M Owens, Sabrina K Syan, Tashia D Petker, Lawrence H Sweet, Assaf Oshri, James MacKillop, Michael Amlung","doi":"10.1111/acer.14147","DOIUrl":"10.1111/acer.14147","url":null,"abstract":"<p><strong>Background: </strong>Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol-related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences.</p><p><strong>Methods: </strong>This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; M_age  = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting).</p><p><strong>Results: </strong>Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow-up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men.</p><p><strong>Conclusions: </strong>This study adds to the understanding of brain correlates of alcohol use in a large, gender-balanced sample of younger adults. Although the cross-sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations.</p>","PeriodicalId":7410,"journal":{"name":"Alcoholism, clinical and experimental research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721970/pdf/nihms-1040196.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40451511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}