Pub Date : 2024-09-06DOI: 10.1016/j.alcohol.2024.09.002
Ilknur Dursun, Nur Damla Korkmaz, Sinem Firtina, Muhammed Salih Erkoyuncu, Fahri Akbas, Birsen Elibol
Early developmental exposure to alcohol has been implicated in adverse effects on the brain, often associated with the onset of neurodevelopmental disorders. Moreover, maternal alcohol consumption during pregnancy has been linked to the manifestation of mental health disorders, such as depression and anxiety, in subsequent generations. These mood disturbances may be attributed to alterations in protein expressions related to depression and anxiety within the hippocampus. While the precise mechanisms remain elusive, it is likely that pre- and postnatal exposure to alcohol induces changes in hippocampus, potentially through epigenetic modifications. The FKBP5 gene, known to modulate the stress response, is particularly relevant in this context. We postulate that alcohol-induced methylation of the FKBP5 gene disrupts HPA axis function, thereby prompting individuals to anxiety-like and depressive-like behaviors. To investigate this hypothesis, female C57BL/6 pups were subjected to early alcohol exposure via intubation with ethanol mixed in artificial milk from Postnatal Day 3 to Day 20. The intubation control pups were subjected to the same procedures without ethanol or milk, and a non-intubated control group included. Anxiety-like and depressive-like behaviors were assessed using the open field test, plus maze test, forced swim test, and tail suspension test when the pups reached 3 months of age. For epigenetic analysis of the FKBP5 gene, genomic DNA was isolated from hippocampal tissues and subjected to bisulfite conversion to distinguish methylated and unmethylated cytosines. Then, methylation-specific PCR was performed to assess methylation levels. Pups exposed to early postnatal alcohol exhibited increased levels of depression-like behavior and susceptibility to anxiety-like behavior during adolescence, as verified by behavioral assessments. Methylation profiling revealed higher rates of methylation within the stress-associated gene FKBP5 in both the early postnatal alcohol-exposed cohort (13.82%) and the intubation control group (3.93%), in contrast to the control cohort devoid of stress or alcohol exposure. These findings suggest a potential epigenetic mechanism underlying the observed behavioral alterations, implicating FKBP5 methylation as a candidate mediator of the increased vulnerability to mood disorders following early postnatal alcohol exposure.
{"title":"Exploring epigenetic modification of the stress-related FKBP5 gene in mice exposed to alcohol during early postnatal development.","authors":"Ilknur Dursun, Nur Damla Korkmaz, Sinem Firtina, Muhammed Salih Erkoyuncu, Fahri Akbas, Birsen Elibol","doi":"10.1016/j.alcohol.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.09.002","url":null,"abstract":"<p><p>Early developmental exposure to alcohol has been implicated in adverse effects on the brain, often associated with the onset of neurodevelopmental disorders. Moreover, maternal alcohol consumption during pregnancy has been linked to the manifestation of mental health disorders, such as depression and anxiety, in subsequent generations. These mood disturbances may be attributed to alterations in protein expressions related to depression and anxiety within the hippocampus. While the precise mechanisms remain elusive, it is likely that pre- and postnatal exposure to alcohol induces changes in hippocampus, potentially through epigenetic modifications. The FKBP5 gene, known to modulate the stress response, is particularly relevant in this context. We postulate that alcohol-induced methylation of the FKBP5 gene disrupts HPA axis function, thereby prompting individuals to anxiety-like and depressive-like behaviors. To investigate this hypothesis, female C57BL/6 pups were subjected to early alcohol exposure via intubation with ethanol mixed in artificial milk from Postnatal Day 3 to Day 20. The intubation control pups were subjected to the same procedures without ethanol or milk, and a non-intubated control group included. Anxiety-like and depressive-like behaviors were assessed using the open field test, plus maze test, forced swim test, and tail suspension test when the pups reached 3 months of age. For epigenetic analysis of the FKBP5 gene, genomic DNA was isolated from hippocampal tissues and subjected to bisulfite conversion to distinguish methylated and unmethylated cytosines. Then, methylation-specific PCR was performed to assess methylation levels. Pups exposed to early postnatal alcohol exhibited increased levels of depression-like behavior and susceptibility to anxiety-like behavior during adolescence, as verified by behavioral assessments. Methylation profiling revealed higher rates of methylation within the stress-associated gene FKBP5 in both the early postnatal alcohol-exposed cohort (13.82%) and the intubation control group (3.93%), in contrast to the control cohort devoid of stress or alcohol exposure. These findings suggest a potential epigenetic mechanism underlying the observed behavioral alterations, implicating FKBP5 methylation as a candidate mediator of the increased vulnerability to mood disorders following early postnatal alcohol exposure.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1016/j.alcohol.2024.09.001
Tse-Ang Lee, Hongjoo J Lee, Regina A Mangieri, Rueben Gonzales, Heba Ajmal, Tanya Hutter
The unclear mechanisms of ethanol metabolism in the brain highlight the need for a deeper understanding of its metabolic pathways. This study used in vivo microdialysis to simultaneously sample ethanol and its metabolites, acetaldehyde and acetate, in the rat striatum following self-administration of ethanol, emphasizing the natural oral exposure route. To enhance the self-administration, rats underwent two-bottle-choice and limited access training. Dialysate samples, collected every 10 minutes for 2.5 hours, were analyzed using gas chromatography with flame ionization detection (GC-FID). The measured time courses of dialysate concentrations of ethanol, acetaldehyde, and acetate provided insights into dynamics of ethanol metabolism. Notably, in a subject with low ethanol consumption (0.29 g/kg), the concentration of acetaldehyde remained below the limit of detection throughout the experiment. However, the acetate concentration was clearly increased after ethanol consumption in this subject and was comparable to that of other rats with higher ethanol consumption. Compared with focusing only on peak values in the time-courses of concentrations of ethanol and its metabolites, calculating areas under curves provided better models of the relationships between ethanol intake and individual ethanol metabolites, as indicated by the r-square values for the linear regressions. This approach of using the area under the curve accounts for both the amplitude and duration of the concentration profiles, reducing the impact of variations in individual drinking patterns. In vivo microdialysis enables concurrent sampling of brain metabolites during oral ethanol administration, contributing insights into metabolite dynamics. To our knowledge, this paper is the first to report measurement of all three analytes in the brain following self-administration of ethanol. Future studies will explore regional variations and dynamics post-ethanol dependence, further advancing our understanding of ethanol metabolism in the brain.
乙醇在大脑中的代谢机制尚不清楚,因此需要更深入地了解其代谢途径。本研究采用体内微透析法,在大鼠自我给药乙醇后,同时对其纹状体中的乙醇及其代谢物乙醛和乙酸盐进行采样,强调自然的口服暴露途径。为了增强大鼠的自我给药能力,对大鼠进行了双瓶选择和有限接触训练。在 2.5 小时内,每隔 10 分钟收集一次透析液样本,并使用火焰离子化检测气相色谱法(GC-FID)进行分析。通过测量透析液中乙醇、乙醛和乙酸盐浓度的时间过程,可以了解乙醇代谢的动态变化。值得注意的是,在一个乙醇消耗量较低(0.29 克/千克)的受试者身上,乙醛的浓度在整个实验过程中都保持在检测限以下。然而,该实验对象在摄入乙醇后乙酸盐浓度明显升高,与其他乙醇摄入量较高的大鼠的乙酸盐浓度相当。与只关注乙醇及其代谢物浓度时间序列的峰值相比,计算曲线下面积能更好地模拟乙醇摄入量与单个乙醇代谢物之间的关系,这一点可以从线性回归的 r 平方值中看出。这种使用曲线下面积的方法同时考虑了浓度曲线的振幅和持续时间,减少了个人饮酒模式变化的影响。体内微透析法可在口服乙醇期间对脑代谢物进行同步采样,有助于深入了解代谢物的动态变化。据我们所知,本文首次报道了自我给药乙醇后大脑中所有三种分析物的测量结果。未来的研究将探索乙醇依赖后的区域变化和动态变化,进一步加深我们对乙醇在大脑中代谢的了解。
{"title":"Time-course concentration of ethanol, acetaldehyde and acetate in rat brain dialysate following alcohol self-administration.","authors":"Tse-Ang Lee, Hongjoo J Lee, Regina A Mangieri, Rueben Gonzales, Heba Ajmal, Tanya Hutter","doi":"10.1016/j.alcohol.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.09.001","url":null,"abstract":"<p><p>The unclear mechanisms of ethanol metabolism in the brain highlight the need for a deeper understanding of its metabolic pathways. This study used in vivo microdialysis to simultaneously sample ethanol and its metabolites, acetaldehyde and acetate, in the rat striatum following self-administration of ethanol, emphasizing the natural oral exposure route. To enhance the self-administration, rats underwent two-bottle-choice and limited access training. Dialysate samples, collected every 10 minutes for 2.5 hours, were analyzed using gas chromatography with flame ionization detection (GC-FID). The measured time courses of dialysate concentrations of ethanol, acetaldehyde, and acetate provided insights into dynamics of ethanol metabolism. Notably, in a subject with low ethanol consumption (0.29 g/kg), the concentration of acetaldehyde remained below the limit of detection throughout the experiment. However, the acetate concentration was clearly increased after ethanol consumption in this subject and was comparable to that of other rats with higher ethanol consumption. Compared with focusing only on peak values in the time-courses of concentrations of ethanol and its metabolites, calculating areas under curves provided better models of the relationships between ethanol intake and individual ethanol metabolites, as indicated by the r-square values for the linear regressions. This approach of using the area under the curve accounts for both the amplitude and duration of the concentration profiles, reducing the impact of variations in individual drinking patterns. In vivo microdialysis enables concurrent sampling of brain metabolites during oral ethanol administration, contributing insights into metabolite dynamics. To our knowledge, this paper is the first to report measurement of all three analytes in the brain following self-administration of ethanol. Future studies will explore regional variations and dynamics post-ethanol dependence, further advancing our understanding of ethanol metabolism in the brain.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.alcohol.2024.08.004
Hye Jean Yoon, Marie A Doyle, Megan E Altemus, Rishik Bethi, Sofia H Lago, Danny G Winder, Erin S Calipari
Understanding sex differences in disease prevalence is critical to public health, particularly in the context of alcohol use disorder (AUD). The goal of this study was to understand sex differences in ethanol drinking behavior and define the precise conditions under which sex differences emerge. Consistent with prior work, C57BL/6J females drank more than males under continuous access two-bottle choice conditions. However, using ethanol self-administration - where an operant response results in access to an ethanol sipper for a fixed time period - we found no sex differences in operant response rates or ethanol consumption (volume per body weight consumed, as well as lick behavior). This remained true across a wide range of parameters including acquisition, when the ethanol sipper access period was manipulated, and when the concentration of the ethanol available was scaled. The only sex differences observed were in total ethanol consumption, which was explained by differences in body weight between males and females, rather than by sex differences in motivation to drink. Using dimensionality reduction approaches, we found that drinking behavior in the operant context did not cluster by sex, but rather clustered by high and low drinking phenotypes. Interestingly, these high and low drinking phenotypes in the operant context showed no correlation with those same categorizations in the home cage context within the same animals. These data underscore the complexity of sex differences in ethanol consumption, highlighting the important role that drinking conditions/context plays in the expression of these differences.
{"title":"Operant ethanol self-administration behaviors do not predict sex differences in continuous access home cage drinking.","authors":"Hye Jean Yoon, Marie A Doyle, Megan E Altemus, Rishik Bethi, Sofia H Lago, Danny G Winder, Erin S Calipari","doi":"10.1016/j.alcohol.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.08.004","url":null,"abstract":"<p><p>Understanding sex differences in disease prevalence is critical to public health, particularly in the context of alcohol use disorder (AUD). The goal of this study was to understand sex differences in ethanol drinking behavior and define the precise conditions under which sex differences emerge. Consistent with prior work, C57BL/6J females drank more than males under continuous access two-bottle choice conditions. However, using ethanol self-administration - where an operant response results in access to an ethanol sipper for a fixed time period - we found no sex differences in operant response rates or ethanol consumption (volume per body weight consumed, as well as lick behavior). This remained true across a wide range of parameters including acquisition, when the ethanol sipper access period was manipulated, and when the concentration of the ethanol available was scaled. The only sex differences observed were in total ethanol consumption, which was explained by differences in body weight between males and females, rather than by sex differences in motivation to drink. Using dimensionality reduction approaches, we found that drinking behavior in the operant context did not cluster by sex, but rather clustered by high and low drinking phenotypes. Interestingly, these high and low drinking phenotypes in the operant context showed no correlation with those same categorizations in the home cage context within the same animals. These data underscore the complexity of sex differences in ethanol consumption, highlighting the important role that drinking conditions/context plays in the expression of these differences.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-27DOI: 10.1016/j.alcohol.2024.08.005
Ayushi Jain, Michael R Wellner, Jing Peng, Jianing Ma, Kenneth D Allen, Chelsey McShane, Mitchell L Ramsey, Khalid Mumtaz, Sean G Kelly, Lanla F Conteh, Robert Kirkpatrick, Lindsay A Sobotka
Introduction: Alcohol related liver disease (ALD) affects diverse communities with individual and social characteristics that can impact outcomes. The Social Vulnerability Index (SVI) assigns a score between 0 and 1, where higher scores represent an increased risk of social vulnerability. We sought to assess the impact of SVI on outcomes of patients hospitalized with ALD with access to social support services.
Methods and materials: Hospitalizations for ALD at our institution between March and August 2019 were reviewed. All patients were assigned an SVI score based on their residential census tract. Per our standard practice, patients were screened by care coordinators to identify needs for rehabilitation counseling, and care coordination after discharge. Demographics, hepatic decompensation, critical care needs, readmission, and mortality were compared.
Results: Among 73 patients admitted for alcoholic hepatitis, 32 had a low SVI and 42 had a high SVI. African American patients were more likely to have a higher SVI (35% vs 0%, p=<0.001). No significant difference in outcomes based on SVI was noted. There were 393 patients admitted for alcoholic cirrhosis including 166 with a low SVI and 227 with a high SVI. Patients that were African American (23.6% vs 5.5%, p=<0.001) or disabled (41.4% vs 29.5%, p=0.008) had a higher SVI. No significant difference in outcomes based on SVI was noted.
Conclusion: Most patients admitted for ALD had a high SVI; however, SVI did not impact hospitalization outcomes.
导言:酒精相关肝病(ALD)影响着不同的社区,其个人和社会特征都会对治疗效果产生影响。社会脆弱性指数(SVI)在 0 到 1 之间打分,分数越高,社会脆弱性风险越大。我们试图评估 SVI 对获得社会支持服务的 ALD 住院患者预后的影响:我们对本机构 2019 年 3 月至 8 月期间因 ALD 住院的患者进行了回顾。所有患者均根据其居住人口普查区进行了 SVI 评分。根据我们的标准做法,护理协调员对患者进行筛查,以确定出院后的康复咨询和护理协调需求。对患者的人口统计学、肝功能失代偿、重症监护需求、再入院情况和死亡率进行了比较:在因酒精性肝炎入院的 73 名患者中,32 人的 SVI 值较低,42 人的 SVI 值较高。非裔美国患者更有可能具有较高的 SVI(35% vs 0%,p=结论:大多数因酒精性肝病入院的患者 SVI 值较高,但 SVI 值并不影响住院治疗效果。
{"title":"Impact of Social Vulnerability Index on Patients with Alcohol-Related Liver Disease.","authors":"Ayushi Jain, Michael R Wellner, Jing Peng, Jianing Ma, Kenneth D Allen, Chelsey McShane, Mitchell L Ramsey, Khalid Mumtaz, Sean G Kelly, Lanla F Conteh, Robert Kirkpatrick, Lindsay A Sobotka","doi":"10.1016/j.alcohol.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.08.005","url":null,"abstract":"<p><strong>Introduction: </strong>Alcohol related liver disease (ALD) affects diverse communities with individual and social characteristics that can impact outcomes. The Social Vulnerability Index (SVI) assigns a score between 0 and 1, where higher scores represent an increased risk of social vulnerability. We sought to assess the impact of SVI on outcomes of patients hospitalized with ALD with access to social support services.</p><p><strong>Methods and materials: </strong>Hospitalizations for ALD at our institution between March and August 2019 were reviewed. All patients were assigned an SVI score based on their residential census tract. Per our standard practice, patients were screened by care coordinators to identify needs for rehabilitation counseling, and care coordination after discharge. Demographics, hepatic decompensation, critical care needs, readmission, and mortality were compared.</p><p><strong>Results: </strong>Among 73 patients admitted for alcoholic hepatitis, 32 had a low SVI and 42 had a high SVI. African American patients were more likely to have a higher SVI (35% vs 0%, p=<0.001). No significant difference in outcomes based on SVI was noted. There were 393 patients admitted for alcoholic cirrhosis including 166 with a low SVI and 227 with a high SVI. Patients that were African American (23.6% vs 5.5%, p=<0.001) or disabled (41.4% vs 29.5%, p=0.008) had a higher SVI. No significant difference in outcomes based on SVI was noted.</p><p><strong>Conclusion: </strong>Most patients admitted for ALD had a high SVI; however, SVI did not impact hospitalization outcomes.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.alcohol.2024.07.009
Benneth Ben-Azu, Pere-Ebi Y Toloyai, Adaeze Adebesin, Vivian O Ojiokor, Olusegun G Adebayo, Aliance Romain Fokoua, Goodes E Moke, Elo J Ejukolemu, Ife-Oluwa O Akpojevughe, Abdulkareem M Abdulkadir, Ephraim Okwuchi
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2g/kg, oral gavage) every other day, alongside daily morin (50 and 100mg/kg) or fluoxetine (10mg/kg) from days 8-21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal-cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin prevented TNF-α, and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.
{"title":"Alcohol-exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin.","authors":"Benneth Ben-Azu, Pere-Ebi Y Toloyai, Adaeze Adebesin, Vivian O Ojiokor, Olusegun G Adebayo, Aliance Romain Fokoua, Goodes E Moke, Elo J Ejukolemu, Ife-Oluwa O Akpojevughe, Abdulkareem M Abdulkadir, Ephraim Okwuchi","doi":"10.1016/j.alcohol.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.07.009","url":null,"abstract":"<p><p>Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2g/kg, oral gavage) every other day, alongside daily morin (50 and 100mg/kg) or fluoxetine (10mg/kg) from days 8-21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal-cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin prevented TNF-α, and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1016/j.alcohol.2024.07.008
Celia Antuña-Camblor, Gabriel Esteller Collado, Joel Juarros-Basterretxea, Roger Muñoz-Navarro, Francisco Javier Rodríguez-Díaz
Background: Epidemiological studies reveal a high prevalence of alcohol use and comorbidity rates with emotional disorders. This study aims to explore the possible mediational effect of stress-coping strategies on the relationship between symptoms of emotional disorders and problematic alcohol use.
Methods: The sample included 1014 participants (33.82% male, 66.17% female) aged 18 to 75 years (M = 33.0, SD = 15.15). Three mediation analyzes were carried out, for depressive, anxious and somatization symptomatology measured with the LSB-50 in which they acted as an independent variable, the coping strategies of the CSQ as a mediating variable and the problematic alcohol use, measured with AUDIT, as a dependent variable. Additionally, sex, age, educational level, and socioeconomic status were entered as covariates.
Results: In all the models, problematic alcohol use was mediated by Problem-Solving Focus and Open Emotional Expression. However, while in depressive symptoms was a fully mediation, in anxious and somatization symptomatology was partially mediated.
Conclusions: The similarities found may be due to shared variance between emotional disorders. Interventions focused on Problem-Solving Focus could improve the emotional symptoms and the problematic alcohol use.
{"title":"Coping-strategies as a mediator between emotional disorders and problematic alcohol use.","authors":"Celia Antuña-Camblor, Gabriel Esteller Collado, Joel Juarros-Basterretxea, Roger Muñoz-Navarro, Francisco Javier Rodríguez-Díaz","doi":"10.1016/j.alcohol.2024.07.008","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.07.008","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies reveal a high prevalence of alcohol use and comorbidity rates with emotional disorders. This study aims to explore the possible mediational effect of stress-coping strategies on the relationship between symptoms of emotional disorders and problematic alcohol use.</p><p><strong>Methods: </strong>The sample included 1014 participants (33.82% male, 66.17% female) aged 18 to 75 years (M = 33.0, SD = 15.15). Three mediation analyzes were carried out, for depressive, anxious and somatization symptomatology measured with the LSB-50 in which they acted as an independent variable, the coping strategies of the CSQ as a mediating variable and the problematic alcohol use, measured with AUDIT, as a dependent variable. Additionally, sex, age, educational level, and socioeconomic status were entered as covariates.</p><p><strong>Results: </strong>In all the models, problematic alcohol use was mediated by Problem-Solving Focus and Open Emotional Expression. However, while in depressive symptoms was a fully mediation, in anxious and somatization symptomatology was partially mediated.</p><p><strong>Conclusions: </strong>The similarities found may be due to shared variance between emotional disorders. Interventions focused on Problem-Solving Focus could improve the emotional symptoms and the problematic alcohol use.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27DOI: 10.1016/j.alcohol.2024.04.006
Nathan A Sollenberger, Logan R Cummings, Josefina Freitag, Elisa M Trucco, Sthefany Gomez, Melanie Giraldo, Gabriela Muse, Aaron T Mattfeld, Dana L McMakin
Negative reinforcement is proposed to mediate associations between sleep and alcohol use, especially among people with depression and/or anxiety symptoms. Worse sleep (e.g., shorter duration, less efficiency, more irregular timing) exacerbates negative emotions, which alcohol may temporarily relieve. Not yet examined, we propose sleep indirectly impacts early stages of alcohol use via differences in negative reinforcement learning (NRL), since sleep impacts emotion, reward response, and learning. The current study aimed to replicate associations between sleep and alcohol use, test associations with NRL, and examine indirect associations between sleep health and alcohol use via NRL among 60 underage college students (ages 18-20 years, 77% female) varying in depression and anxiety symptoms. Participants wore Fitbit smartwatches and completed daily diaries measuring sleep and substance use for ∼14 days before completing two computer tasks assessing social (SNRL) and monetary (MNRL) negative reinforcement learning. Robust generalized linear models tested direct associations within the proposed model. SNRL performance was positively associated with alcohol use, but no other associations were observed. Statistical mediation models failed to indicate indirect effects of sleep on alcohol use via SNRL or MNRL performance. Post-hoc exploratory models examining depression and anxiety symptoms as moderators of direct associations indicated several interactions. Positive associations between sleep timing variability and alcohol use were weakened at higher anxiety symptom severity and stronger at higher depression symptom severity. The positive association between SNRL performance and alcohol use was also stronger at higher depression symptom severity. Among students with elevated depression symptoms, variable sleep timing and stronger SNRL performance were independently associated with more alcohol use, but indirect effects were not supported. Future research should replicate findings, confirm causality of interactions, and examine sleep timing and behavioral responses to negative social stimuli as targets for improving alcohol-related outcomes among underage college students with elevated depressive symptoms.
{"title":"Associations between sleep health, negative reinforcement learning, and alcohol use among South Florida college students with elevated internalizing symptoms.","authors":"Nathan A Sollenberger, Logan R Cummings, Josefina Freitag, Elisa M Trucco, Sthefany Gomez, Melanie Giraldo, Gabriela Muse, Aaron T Mattfeld, Dana L McMakin","doi":"10.1016/j.alcohol.2024.04.006","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.04.006","url":null,"abstract":"<p><p>Negative reinforcement is proposed to mediate associations between sleep and alcohol use, especially among people with depression and/or anxiety symptoms. Worse sleep (e.g., shorter duration, less efficiency, more irregular timing) exacerbates negative emotions, which alcohol may temporarily relieve. Not yet examined, we propose sleep indirectly impacts early stages of alcohol use via differences in negative reinforcement learning (NRL), since sleep impacts emotion, reward response, and learning. The current study aimed to replicate associations between sleep and alcohol use, test associations with NRL, and examine indirect associations between sleep health and alcohol use via NRL among 60 underage college students (ages 18-20 years, 77% female) varying in depression and anxiety symptoms. Participants wore Fitbit smartwatches and completed daily diaries measuring sleep and substance use for ∼14 days before completing two computer tasks assessing social (SNRL) and monetary (MNRL) negative reinforcement learning. Robust generalized linear models tested direct associations within the proposed model. SNRL performance was positively associated with alcohol use, but no other associations were observed. Statistical mediation models failed to indicate indirect effects of sleep on alcohol use via SNRL or MNRL performance. Post-hoc exploratory models examining depression and anxiety symptoms as moderators of direct associations indicated several interactions. Positive associations between sleep timing variability and alcohol use were weakened at higher anxiety symptom severity and stronger at higher depression symptom severity. The positive association between SNRL performance and alcohol use was also stronger at higher depression symptom severity. Among students with elevated depression symptoms, variable sleep timing and stronger SNRL performance were independently associated with more alcohol use, but indirect effects were not supported. Future research should replicate findings, confirm causality of interactions, and examine sleep timing and behavioral responses to negative social stimuli as targets for improving alcohol-related outcomes among underage college students with elevated depressive symptoms.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Substance use continues to be recognized as one of the major health and social issues in the Caribbean. This study focusses on the risks and consequences of adolescent school student's exposure to alcohol and prevention strategies. Participants were selected from the age group of 13 to 19 years old, who are attending Secondary School. Five schools were chosen according to the prevalence of alcohol. Students were purposively selected from each school based on the recommendations from the school social workers. Students completed the Adolescent Drug Involvement Scale (ADIS) to understand the extent of involvement in alcohol use. The study recommends that there is a need for effective parenting where training in awareness, skills, and techniques around engaging young adolescent students with age-appropriate information on alcohol abuse can be disbursed and reinforced as they enter various stages of their development.
{"title":"EFFECTS OF ALCOHOL AND ITS PREVENTION STRATEGIES ON ADOLESCENT SCHOOL STUDENTS.","authors":"Emmanuel Janagan Johnson, Jessica Evangelin Emmanuel Janagan","doi":"10.1016/j.alcohol.2024.03.009","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.03.009","url":null,"abstract":"<p><p>Substance use continues to be recognized as one of the major health and social issues in the Caribbean. This study focusses on the risks and consequences of adolescent school student's exposure to alcohol and prevention strategies. Participants were selected from the age group of 13 to 19 years old, who are attending Secondary School. Five schools were chosen according to the prevalence of alcohol. Students were purposively selected from each school based on the recommendations from the school social workers. Students completed the Adolescent Drug Involvement Scale (ADIS) to understand the extent of involvement in alcohol use. The study recommends that there is a need for effective parenting where training in awareness, skills, and techniques around engaging young adolescent students with age-appropriate information on alcohol abuse can be disbursed and reinforced as they enter various stages of their development.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-12DOI: 10.1016/j.alcohol.2024.03.007
S Washburn, K Nation, T Cudd, M Stanton, C Goodlett
In rodent models of fetal alcohol spectrum disorders (FASD), cognitive deficits are implicated in impaired T-maze spatial reversal learning. Rat studies have indicated supplemental administration of choline during the developmental period of alcohol exposure can ameliorate spatial reversal deficits. This study tested whether beneficial effects of prenatal choline supplementation could be confirmed in a sheep model of binge exposure in the first trimester equivalent. Two hypotheses were tested: 1) alcohol exposure would produce deficits in reversal of a T-maze position discrimination; and 2) gestational dietary supplementation of choline would ameliorate those deficits. Mated ewes were assigned to one of seven groups-a normal control (NC) group or one of six infusion treatment groups: saline control (SC; isotonic saline), saline control plus choline (SC-CH; isotonic saline plus choline, 10 mg/kg administered orally throughout each day of gestation), binge alcohol (BA; 1.75 g/kg alcohol per infusion day), binge alcohol plus choline (BA-CH; 1.75 g/kg/day alcohol plus choline), heavy binge alcohol (HBA; 2.5 g/kg/day alcohol), or heavy binge alcohol plus choline (HBA-CH; 2.5 g/kg/day alcohol plus choline). The alcohol infusions modeled a weekend binge drinking pattern over the first trimester-equivalent (gestational day 4-41). T-maze training began at 12 weeks of age, with daily sessions occurring 5 days/week. Lambs were given five days of habituation training, followed by five days of position discrimination training (3 trials per daily session, intertrial interval of 3 hours, reinforced side randomly assigned across subjects). Lambs were then given 10 days of training on the reversal task. There was no difference among groups during acquisition. Alcohol impaired reversal learning, and choline supplementation mitigated these deficits in the HBA-CH group. These results suggest that maternal dietary choline supplementation can ameliorate or prevent some impairments of executive function in a sheep model of FASD.
{"title":"Gestational choline supplementation ameliorates T-maze reversal learning deficits induced by first trimester binge alcohol exposure in weanling lambs.","authors":"S Washburn, K Nation, T Cudd, M Stanton, C Goodlett","doi":"10.1016/j.alcohol.2024.03.007","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.03.007","url":null,"abstract":"<p><p>In rodent models of fetal alcohol spectrum disorders (FASD), cognitive deficits are implicated in impaired T-maze spatial reversal learning. Rat studies have indicated supplemental administration of choline during the developmental period of alcohol exposure can ameliorate spatial reversal deficits. This study tested whether beneficial effects of prenatal choline supplementation could be confirmed in a sheep model of binge exposure in the first trimester equivalent. Two hypotheses were tested: 1) alcohol exposure would produce deficits in reversal of a T-maze position discrimination; and 2) gestational dietary supplementation of choline would ameliorate those deficits. Mated ewes were assigned to one of seven groups-a normal control (NC) group or one of six infusion treatment groups: saline control (SC; isotonic saline), saline control plus choline (SC-CH; isotonic saline plus choline, 10 mg/kg administered orally throughout each day of gestation), binge alcohol (BA; 1.75 g/kg alcohol per infusion day), binge alcohol plus choline (BA-CH; 1.75 g/kg/day alcohol plus choline), heavy binge alcohol (HBA; 2.5 g/kg/day alcohol), or heavy binge alcohol plus choline (HBA-CH; 2.5 g/kg/day alcohol plus choline). The alcohol infusions modeled a weekend binge drinking pattern over the first trimester-equivalent (gestational day 4-41). T-maze training began at 12 weeks of age, with daily sessions occurring 5 days/week. Lambs were given five days of habituation training, followed by five days of position discrimination training (3 trials per daily session, intertrial interval of 3 hours, reinforced side randomly assigned across subjects). Lambs were then given 10 days of training on the reversal task. There was no difference among groups during acquisition. Alcohol impaired reversal learning, and choline supplementation mitigated these deficits in the HBA-CH group. These results suggest that maternal dietary choline supplementation can ameliorate or prevent some impairments of executive function in a sheep model of FASD.</p>","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-08DOI: 10.1016/j.alcohol.2024.03.004
Rigina Skeva, Caroline Jay, Steve Pettifer, Lynsey Gregg
{"title":"Alcohol Treatment Preferences and the Acceptability of Virtual Reality Therapy for Treating Alcohol Misuse in Adult Drinkers.","authors":"Rigina Skeva, Caroline Jay, Steve Pettifer, Lynsey Gregg","doi":"10.1016/j.alcohol.2024.03.004","DOIUrl":"https://doi.org/10.1016/j.alcohol.2024.03.004","url":null,"abstract":"","PeriodicalId":93864,"journal":{"name":"Alcohol (Fayetteville, N.Y.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}