Orlagh Keating, Ruth H. Brown, Renate Kuenssberg, Sarah Driscoll, Stewart McDougall, Suzanne O'Rourke
Fetal alcohol exposure is a growing public health concern. However, ascertaining its true extent remains challenging as maternal self-reports may lack validity. Increasingly, interest has turned to more objective measures of prenatal alcohol use (PAU) of which one, meconium, is recognized as a valuable tool. This review assesses both the international prevalence of PAU obtained using meconium biomarkers in general maternity populations and, when feasible, the level of agreement between meconium biomarkers and self-reported PAU. A systematic literature search for studies reporting the prevalence of PAU, as determined by meconium biomarker testing, was conducted using multiple electronic databases from 1990 to 2023. Seventeen studies were identified for inclusion and evaluated for methodological quality. Using fatty acid ethyl esters (FAEEs) meconium biomarkers, PAU prevalence varied from 2.4% to 44%. Rates based on EtG (ethyl glucuronide) analysis ranged from 0% to 16.3%, and EtS (ethyl sulfate) analysis from 7.8% to 16.7%. Studies were of moderate quality with high heterogeneity. Prevalence rates based on self-report data ranged from 0% to 46.4%. When reported, none of the reviewed studies identified agreement between meconium-based and self-report-based PAU prevalence rates. Using both self-reports to detect early pregnancy alcohol use, and meconium biomarkers to detect the occurrence of alcohol use later in pregnancy, may provide a more complete picture of PAU prevalence. Furthermore, research is warranted to develop stringent guidance on the ascertainment, storage, analysis, and reporting required in this field.
{"title":"The international prevalence of prenatal alcohol use obtained via meconium biomarkers: A systematic literature review","authors":"Orlagh Keating, Ruth H. Brown, Renate Kuenssberg, Sarah Driscoll, Stewart McDougall, Suzanne O'Rourke","doi":"10.1111/acer.15410","DOIUrl":"10.1111/acer.15410","url":null,"abstract":"<p>Fetal alcohol exposure is a growing public health concern. However, ascertaining its true extent remains challenging as maternal self-reports may lack validity. Increasingly, interest has turned to more objective measures of prenatal alcohol use (PAU) of which one, meconium, is recognized as a valuable tool. This review assesses both the international prevalence of PAU obtained using meconium biomarkers in general maternity populations and, when feasible, the level of agreement between meconium biomarkers and self-reported PAU. A systematic literature search for studies reporting the prevalence of PAU, as determined by meconium biomarker testing, was conducted using multiple electronic databases from 1990 to 2023. Seventeen studies were identified for inclusion and evaluated for methodological quality. Using fatty acid ethyl esters (FAEEs) meconium biomarkers, PAU prevalence varied from 2.4% to 44%. Rates based on EtG (ethyl glucuronide) analysis ranged from 0% to 16.3%, and EtS (ethyl sulfate) analysis from 7.8% to 16.7%. Studies were of moderate quality with high heterogeneity. Prevalence rates based on self-report data ranged from 0% to 46.4%. When reported, none of the reviewed studies identified agreement between meconium-based and self-report-based PAU prevalence rates. Using both self-reports to detect early pregnancy alcohol use, and meconium biomarkers to detect the occurrence of alcohol use later in pregnancy, may provide a more complete picture of PAU prevalence. Furthermore, research is warranted to develop stringent guidance on the ascertainment, storage, analysis, and reporting required in this field.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1657-1676"},"PeriodicalIF":3.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily D. K. Sullivan, Carol A. Dannenhoffer, Elizabeth B. Sutherland, Elena M. Vidrascu, Alexander Gómez-A, Charlotte A. Boettiger, Donita L. Robinson
Background
Alcohol is commonly consumed by adolescents in a binge-like pattern, which can lead to long-lasting cognitive deficits, including reduced behavioral flexibility. We and others have determined that adolescent intermittent ethanol (AIE) exposure leads to increased number of perineuronal net (PNN) numbers in brain regions that are important for behavioral flexibility. However, whether altered neurochemistry stemming from AIE exposure plays a significant role in reduced behavioral flexibility is unknown.
Methods
We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning.
Results
We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part through changes in PV and PNN fluorescent measures in the AIC.
Conclusions
This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.
{"title":"Effects of adolescent intermittent ethanol exposure on cortical perineuronal net and parvalbumin expression in adulthood mediate behavioral inflexibility","authors":"Emily D. K. Sullivan, Carol A. Dannenhoffer, Elizabeth B. Sutherland, Elena M. Vidrascu, Alexander Gómez-A, Charlotte A. Boettiger, Donita L. Robinson","doi":"10.1111/acer.15395","DOIUrl":"10.1111/acer.15395","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol is commonly consumed by adolescents in a binge-like pattern, which can lead to long-lasting cognitive deficits, including reduced behavioral flexibility. We and others have determined that adolescent intermittent ethanol (AIE) exposure leads to increased number of perineuronal net (PNN) numbers in brain regions that are important for behavioral flexibility. However, whether altered neurochemistry stemming from AIE exposure plays a significant role in reduced behavioral flexibility is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part <i>through</i> changes in PV and PNN fluorescent measures in the AIC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1507-1518"},"PeriodicalIF":3.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790159","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}
Karine Gallopel-Morvan, Quentin Duche, Jacques François Diouf, Sophie Lacoste-Badie, Olivier Droulers, Romain Moirand, Elise Bannier
<div> <section> <h3> Background</h3> <p>Although the World Health Organization recommends visible and clear warning labels about the risks of alcohol consumption on containers and advertising, many of the currently used labels are too small to be visible. This study investigated the brain activity (using fMRI) and alcohol consumption intentions of French young men exposed to two warning formats displayed on alcoholic beverage advertisements: a small Text-only Alcohol Warning (TAW) currently used in many countries, and a larger text-and-picture alcohol warning (PAW).</p> </section> <section> <h3> Methods</h3> <p>Seventy-four eligible 18–25-year-old male drinkers completed a face-to-face individual visit with a physician expert in addiction medicine. This was followed by the fMRI session during which they viewed 288 stimuli [96 alcohol advertisements with TAWs, the same 96 advertisements with PAWs, and 96 water advertisements (controls)] for 3 s each. If the advertisement made participants want (“yes”)/do not want (“no”) to consume the product, they pressed the corresponding button (self-report responses). The number of “yes” responses was compared between advertisement types with a paired sample <i>t</i>-test. Whole-brain and region-of-interest (ROI) analyses of the fMRI data were performed.</p> </section> <section> <h3> Results</h3> <p>Whole-brain BOLD fMRI highlighted contrasting effects of PAWs and TAWs. Compared with TAWs, PAWs elicited more activation in the precuneus, angular gyrus, occipital, frontal and temporal areas, and less activation in the nucleus accumbens, ventral tegmental areas, and putamen areas (regions of the reward circuit). The ROI analysis confirmed less activation in the reward circuit (left and right ventral tegmental areas, left and right nucleus accumbens) when viewing PAWs than TAWs. Analysis of the self-report responses indicated that the desire to consume the advertised alcohol product was lower when PAWs were viewed (compared with TAWs) (<i>T</i> = 8.18, <i>p</i> < 10<sup>−11</sup>).</p> </section> <section> <h3> Conclusions</h3> <p>This is the first fMRI study to assess the effect of different alcohol warning formats. Our findings show that compared with TAWs, stronger PAWs in advertisements elicited less activity in key regions of the reward system. This suggests that the effects may influence the desire to consume alcohol products (self-report response analysis). These results could help policymakers who are interested in developing more effective labeling measures that target young people.</p> </
{"title":"Impact of text-only versus large text-and-picture alcohol warning formats: A functional magnetic resonance imaging study in French young male drinkers","authors":"Karine Gallopel-Morvan, Quentin Duche, Jacques François Diouf, Sophie Lacoste-Badie, Olivier Droulers, Romain Moirand, Elise Bannier","doi":"10.1111/acer.15389","DOIUrl":"10.1111/acer.15389","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although the World Health Organization recommends visible and clear warning labels about the risks of alcohol consumption on containers and advertising, many of the currently used labels are too small to be visible. This study investigated the brain activity (using fMRI) and alcohol consumption intentions of French young men exposed to two warning formats displayed on alcoholic beverage advertisements: a small Text-only Alcohol Warning (TAW) currently used in many countries, and a larger text-and-picture alcohol warning (PAW).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventy-four eligible 18–25-year-old male drinkers completed a face-to-face individual visit with a physician expert in addiction medicine. This was followed by the fMRI session during which they viewed 288 stimuli [96 alcohol advertisements with TAWs, the same 96 advertisements with PAWs, and 96 water advertisements (controls)] for 3 s each. If the advertisement made participants want (“yes”)/do not want (“no”) to consume the product, they pressed the corresponding button (self-report responses). The number of “yes” responses was compared between advertisement types with a paired sample <i>t</i>-test. Whole-brain and region-of-interest (ROI) analyses of the fMRI data were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Whole-brain BOLD fMRI highlighted contrasting effects of PAWs and TAWs. Compared with TAWs, PAWs elicited more activation in the precuneus, angular gyrus, occipital, frontal and temporal areas, and less activation in the nucleus accumbens, ventral tegmental areas, and putamen areas (regions of the reward circuit). The ROI analysis confirmed less activation in the reward circuit (left and right ventral tegmental areas, left and right nucleus accumbens) when viewing PAWs than TAWs. Analysis of the self-report responses indicated that the desire to consume the advertised alcohol product was lower when PAWs were viewed (compared with TAWs) (<i>T</i> = 8.18, <i>p</i> < 10<sup>−11</sup>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first fMRI study to assess the effect of different alcohol warning formats. Our findings show that compared with TAWs, stronger PAWs in advertisements elicited less activity in key regions of the reward system. This suggests that the effects may influence the desire to consume alcohol products (self-report response analysis). These results could help policymakers who are interested in developing more effective labeling measures that target young people.</p>\u0000 </","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1610-1620"},"PeriodicalIF":3.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joshua Jaeger, Lara Osterburg, Maria Stein, Miranda Germann, Sara A. Lustenberger, Alexander Wopfner, Niklaus Denier, Tobias Bracht, Franz Moggi, Leila M. Soravia
Background
Alcohol use disorder (AUD) and depression are highly prevalent and tied to significant psychological, physiological, social and economic consequences. Their co-occurrence presents a complex clinical challenge, as the impact of antidepressant medication on AUD outcomes remains equivocal. In this multicenter, longitudinal study we investigated the relationship between antidepressant medication and changes in depression symptoms and alcohol use in AUD patients.
Methods
We analyzed data from 153 detoxified AUD patients who attended a 12-week residential treatment program between 2015 and 2019. Within a mediation analysis, adopting a bootstrapping approach and a quasi-Bayesian framework, we estimated the total, direct, and mediated effects of antidepressants on the percentage of days abstinent to assess the role of changes in depression symptoms as a mediating factor.
Results
The mediation analysis revealed a dual impact pathway model with a negative direct effect of antidepressants on abstinence (p = 0.004) and a positive indirect effect, mediated through the reduction of depression symptoms (p = 0.002).
Conclusions
The findings of the mediation analysis show that patients treated with antidepressants and whose depression symptoms do not improve over time show more relapses, while patients treated with antidepressants who achieve a reduction in depression symptoms show fewer relapses over time. Thus, to optimize treatment outcome, depression symptoms should be vigilantly monitored when antidepressants are prescribed during AUD treatment.
{"title":"Antidepressants and alcohol use disorder: A multicenter study on the mediating role of depression symptom changes","authors":"Joshua Jaeger, Lara Osterburg, Maria Stein, Miranda Germann, Sara A. Lustenberger, Alexander Wopfner, Niklaus Denier, Tobias Bracht, Franz Moggi, Leila M. Soravia","doi":"10.1111/acer.15386","DOIUrl":"10.1111/acer.15386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorder (AUD) and depression are highly prevalent and tied to significant psychological, physiological, social and economic consequences. Their co-occurrence presents a complex clinical challenge, as the impact of antidepressant medication on AUD outcomes remains equivocal. In this multicenter, longitudinal study we investigated the relationship between antidepressant medication and changes in depression symptoms and alcohol use in AUD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 153 detoxified AUD patients who attended a 12-week residential treatment program between 2015 and 2019. Within a mediation analysis, adopting a bootstrapping approach and a quasi-Bayesian framework, we estimated the total, direct, and mediated effects of antidepressants on the percentage of days abstinent to assess the role of changes in depression symptoms as a mediating factor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mediation analysis revealed a dual impact pathway model with a negative direct effect of antidepressants on abstinence (<i>p</i> = 0.004) and a positive indirect effect, mediated through the reduction of depression symptoms (<i>p</i> = 0.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings of the mediation analysis show that patients treated with antidepressants and whose depression symptoms do not improve over time show more relapses, while patients treated with antidepressants who achieve a reduction in depression symptoms show fewer relapses over time. Thus, to optimize treatment outcome, depression symptoms should be vigilantly monitored when antidepressants are prescribed during AUD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1577-1585"},"PeriodicalIF":3.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha Lucenell Chéry, Todd K. O'Buckley, Giorgia Boero, Irina Balan, A. Leslie Morrow
Background
Neuroimmune dysfunction in alcohol use disorder (AUD) is associated with activation of myeloid differentiation primary response 88 (MyD88)-dependent Toll-like receptors (TLR) resulting in overexpression of the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). MCP-1 overexpression in the brain is linked to anxiety, higher alcohol intake, neuronal death, and activation of microglia observed in AUD. The neurosteroid [3α,5α][3-hydroxypregnan-20-one (3α,5α-THP) has been reported as an inhibitor of MyD88-dependent TLR activation and MCP-1 overexpression in mouse and human macrophages and the brain of alcohol-preferring (P) rats.
Methods
We investigated how 3α,5α-THP regulates MCP-1 expression at the cellular level in P rat nucleus accumbens (NAc) and central amygdala (CeA). We focused on neurons, microglia, and astrocytes, examining the individual voxel density of MCP-1, neuronal marker NeuN, microglial marker IBA1, astrocytic marker GFAP, and their shared voxel density, defined as intersection. Ethanol-naïve male and female P rats were perfused 1 h after IP injections of 15 mg/kg of 3α,5α-THP, or vehicle. The NAc and CeA were imaged using confocal microscopy following double-immunofluorescence staining for MCP-1 with NeuN, IBA1, and GFAP, respectively.
Results
MCP-1 intersected with NeuN predominantly and IBA1/GFAP negligibly. 3α,5α-THP reduced MCP-1 expression in NeuN-labeled cells by 38.27 ± 28.09% in male and 56.11 ± 21.46% in female NAc, also 37.99 ± 19.53% in male and 54.96 ± 30.58% in female CeA. In females, 3α,5α-THP reduced the MCP-1 within IBA1 and GFAP-labeled voxels in the NAc and CeA. Conversely, in males, 3α,5α-THP did not significantly alter the MCP-1 within IBA1 in NAc or with GFAP in the CeA. Furthermore, 3α,5α-THP decreased levels of IBA1 in both regions and sexes with no impact on GFAP or NeuN levels. Secondary analysis performed on data normalized to % control values indicated that no significant sex differences were present.
Conclusions
These data suggest that 3α,5α-THP inhibits neuronal MCP-1 expression and decreases the proliferation of microglia in P rats. These results increase our understanding of potential mechanisms for 3α,5α-THP modulation of ethanol consumption.
{"title":"Neurosteroid [3α,5α]3-hydroxypregnan-20-one inhibition of chemokine monocyte chemoattractant protein-1 in alcohol-preferring rat brain neurons, microglia, and astroglia","authors":"Samantha Lucenell Chéry, Todd K. O'Buckley, Giorgia Boero, Irina Balan, A. Leslie Morrow","doi":"10.1111/acer.15404","DOIUrl":"10.1111/acer.15404","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroimmune dysfunction in alcohol use disorder (AUD) is associated with activation of myeloid differentiation primary response 88 (MyD88)-dependent Toll-like receptors (TLR) resulting in overexpression of the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). MCP-1 overexpression in the brain is linked to anxiety, higher alcohol intake, neuronal death, and activation of microglia observed in AUD. The neurosteroid [3α,5α][3-hydroxypregnan-20-one (3α,5α-THP) has been reported as an inhibitor of MyD88-dependent TLR activation and MCP-1 overexpression in mouse and human macrophages and the brain of alcohol-preferring (P) rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated how 3α,5α-THP regulates MCP-1 expression at the cellular level in P rat nucleus accumbens (NAc) and central amygdala (CeA). We focused on neurons, microglia, and astrocytes, examining the individual voxel density of MCP-1, neuronal marker NeuN, microglial marker IBA1, astrocytic marker GFAP, and their shared voxel density, defined as intersection. Ethanol-naïve male and female P rats were perfused 1 h after IP injections of 15 mg/kg of 3α,5α-THP, or vehicle. The NAc and CeA were imaged using confocal microscopy following double-immunofluorescence staining for MCP-1 with NeuN, IBA1, and GFAP, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MCP-1 intersected with NeuN predominantly and IBA1/GFAP negligibly. 3α,5α-THP reduced MCP-1 expression in NeuN-labeled cells by 38.27 ± 28.09% in male and 56.11 ± 21.46% in female NAc, also 37.99 ± 19.53% in male and 54.96 ± 30.58% in female CeA. In females, 3α,5α-THP reduced the MCP-1 within IBA1 and GFAP-labeled voxels in the NAc and CeA. Conversely, in males, 3α,5α-THP did not significantly alter the MCP-1 within IBA1 in NAc or with GFAP in the CeA. Furthermore, 3α,5α-THP decreased levels of IBA1 in both regions and sexes with no impact on GFAP or NeuN levels. Secondary analysis performed on data normalized to % control values indicated that no significant sex differences were present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data suggest that 3α,5α-THP inhibits neuronal MCP-1 expression and decreases the proliferation of microglia in P rats. These results increase our understanding of potential mechanisms for 3α,5α-THP modulation of ethanol consumption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1693-1703"},"PeriodicalIF":3.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592252","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}
{"title":"Articles of Public Interest","authors":"","doi":"10.1111/acer.15405","DOIUrl":"10.1111/acer.15405","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 7","pages":"1208"},"PeriodicalIF":3.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565280","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}
Benedict R. H. Turner, Poppy I Jenkinson, Marc Huttman, Benjamin H. Mullish
Alcohol is the most widely abused substance in the world, the leading source of mortality in 15–49-year-olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long-term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re-defined as a manifestation of sickness behavior secondary to alcohol-induced inflammation, using the Bradford-Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol-exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well-characterized cascade of systemic inflammation, additionally activating toll-like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol-related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol-mediated inflammation, research into gut permeability and the gut microbiome may be an exciting future therapeutic avenue to prevent alcohol hangover and other alcohol-related diseases.
{"title":"Inflammation, oxidative stress and gut microbiome perturbation: A narrative review of mechanisms and treatment of the alcohol hangover","authors":"Benedict R. H. Turner, Poppy I Jenkinson, Marc Huttman, Benjamin H. Mullish","doi":"10.1111/acer.15396","DOIUrl":"10.1111/acer.15396","url":null,"abstract":"<p>Alcohol is the most widely abused substance in the world, the leading source of mortality in 15–49-year-olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long-term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re-defined as a manifestation of sickness behavior secondary to alcohol-induced inflammation, using the Bradford-Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol-exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well-characterized cascade of systemic inflammation, additionally activating toll-like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol-related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol-mediated inflammation, research into gut permeability and the gut microbiome may be an exciting future therapeutic avenue to prevent alcohol hangover and other alcohol-related diseases.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1451-1465"},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ReJoyce Green, Anna E. Kirkland, Brittney D. Browning, Pamela L. Ferguson, Kevin M. Gray, Lindsay M. Squeglia
Background
Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options.
Methods
This preliminary study examined the effect of N-acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non-treatment-seeking adolescents (17.6–19.9 years old, 55% female) who use alcohol heavily. In a randomized cross-over design, participants completed three fMRI sessions: baseline and after a 10-day course of N-acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non-alcohol beverage cues after N-acetylcysteine versus placebo, with a secondary outcome of self-reported subjective craving.
Results
In the full sample (n = 31), there was no effect of N-acetylcysteine versus placebo on neural alcohol reactivity (ps ≥ 0.49; s = 0.00–0.07) or self-reported acute alcohol craving (p = 0.18, = 0.06). However, N-acetylcysteine did reduce self-reported generalized alcohol craving (p = 0.03, = 0.15). In a subsample of youth who met criteria for past-year alcohol use disorder (n = 19), results remained unchanged.
Conclusions
N-acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.
背景：酒精渴求与问题性饮酒有关；因此，能够调节酒精渴求的药物疗法备受关注。N-乙酰半胱氨酸是一种非处方抗氧化剂，是治疗青少年饮酒的一种候选药物疗法，具有影响渴求的潜力。使用功能性磁共振成像（fMRI）的线索反应范式可以确定与渴求有关的神经区域，并作为新型药物治疗方案的筛选工具：这项初步研究考察了 N-乙酰半胱氨酸对 31 名不寻求治疗的酗酒青少年（17.6-19.9 岁，55% 为女性）的酒精线索神经反应和主观渴求的影响。在随机交叉设计中，受试者完成了三次 fMRI 治疗：基线期和服用 N-乙酰半胱氨酸（1200 毫克，每天两次）和匹配安慰剂的 10 天疗程后。主要结果是服用 N-乙酰半胱氨酸和安慰剂后对酒精和非酒精饮料线索的神经反应，次要结果是自我报告的主观渴望：在全样本（n = 31）中，N-乙酰半胱氨酸与安慰剂相比对神经酒精反应性（ps ≥ 0.49; η p 2 $$ {upeta_{mathrm{p}}^2 $ s = 0.00-0.07）或自我报告的急性酒精渴求（p = 0.18, η p 2 $$ {upeta_{mathrm{p}}^2 $$ = 0.06）没有影响。）然而，N-乙酰半胱氨酸确实会降低自我报告的普遍酒精渴求（p = 0.03, η p 2 $$ {upeta_{mathrm{p}}^2 $$ = 0.15）。在符合过去一年酒精使用障碍标准的青少年子样本（n = 19）中，结果保持不变：结论：N-乙酰半胱氨酸可能不会改变神经对酒精线索的反应或急性渴求；但是，它可能会减少大量饮酒的青少年对酒精的主观渴求。
{"title":"Effect of N-acetylcysteine on neural alcohol cue reactivity and craving in adolescents who drink heavily: A preliminary randomized clinical trial","authors":"ReJoyce Green, Anna E. Kirkland, Brittney D. Browning, Pamela L. Ferguson, Kevin M. Gray, Lindsay M. Squeglia","doi":"10.1111/acer.15402","DOIUrl":"10.1111/acer.15402","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. <i>N</i>-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This preliminary study examined the effect of <i>N</i>-acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non-treatment-seeking adolescents (17.6–19.9 years old, 55% female) who use alcohol heavily. In a randomized cross-over design, participants completed three fMRI sessions: baseline and after a 10-day course of <i>N</i>-acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non-alcohol beverage cues after <i>N</i>-acetylcysteine versus placebo, with a secondary outcome of self-reported subjective craving.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the full sample (<i>n</i> = 31), there was no effect of <i>N</i>-acetylcysteine versus placebo on neural alcohol reactivity (<i>p</i>s ≥ 0.49; <span></span><math></math>s = 0.00–0.07) or self-reported acute alcohol craving (<i>p</i> = 0.18, <span></span><math></math> = 0.06). However, <i>N</i>-acetylcysteine did reduce self-reported generalized alcohol craving (<i>p</i> = 0.03, <span></span><math></math> = 0.15). In a subsample of youth who met criteria for past-year alcohol use disorder (<i>n</i> = 19), results remained unchanged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>N</i>-acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1772-1783"},"PeriodicalIF":3.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499793","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}
Zhihong Yang, Hui Gao, Jing Ma, Nathan A. Liang, Sophia P. Liang, Nazmul Huda, Yanchao Jiang, Themis Thoudam, Wanzhu Tu, Jing Su, Maggie Hesler, Kristina Chandler, Suthat Liangpunsakul
Background
Excessive alcohol consumption has a multifaceted impact on the body's metabolic pathways and organ systems. The objectives of this study were to characterize global metabolomic changes and identify specific pathways that are altered in individuals with excessive alcohol use.
Methods
This exploratory study included 22 healthy controls with no known history of excessive alcohol use and 38 patients identified as using alcohol excessively. A Fibrosis-4 score was used to determine the risk of underlying alcohol-associated liver disease among the excessive drinkers.
Results
We found significantly altered urinary and serum metabolites among excessive drinkers, affecting various metabolic pathways including the metabolism of lipids, amino acids and peptides, cofactors and vitamins, carbohydrates, and nucleotides. Levels of two steroid hormones—5alpha-androstan-3beta,17beta-diol disulfate and androstenediol (3beta,17beta) disulfate—were significantly higher in both the serum and urine samples of excessive drinkers. These elevated levels may be associated with a higher risk of liver fibrosis in individuals with excessive alcohol use.
Conclusion
Alcohol consumption leads to marked alterations in multiple metabolic pathways, highlighting the systemic impact of alcohol on various tissues and organ systems. These findings provide a foundation for future mechanistic studies aimed at elucidating alcohol-induced changes in these metabolic pathways and their implications.
{"title":"Unique urine and serum metabolomic signature in patients with excessive alcohol use: An exploratory study","authors":"Zhihong Yang, Hui Gao, Jing Ma, Nathan A. Liang, Sophia P. Liang, Nazmul Huda, Yanchao Jiang, Themis Thoudam, Wanzhu Tu, Jing Su, Maggie Hesler, Kristina Chandler, Suthat Liangpunsakul","doi":"10.1111/acer.15398","DOIUrl":"10.1111/acer.15398","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Excessive alcohol consumption has a multifaceted impact on the body's metabolic pathways and organ systems. The objectives of this study were to characterize global metabolomic changes and identify specific pathways that are altered in individuals with excessive alcohol use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This exploratory study included 22 healthy controls with no known history of excessive alcohol use and 38 patients identified as using alcohol excessively. A Fibrosis-4 score was used to determine the risk of underlying alcohol-associated liver disease among the excessive drinkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found significantly altered urinary and serum metabolites among excessive drinkers, affecting various metabolic pathways including the metabolism of lipids, amino acids and peptides, cofactors and vitamins, carbohydrates, and nucleotides. Levels of two steroid hormones—5alpha-androstan-3beta,17beta-diol disulfate and androstenediol (3beta,17beta) disulfate—were significantly higher in both the serum and urine samples of excessive drinkers. These elevated levels may be associated with a higher risk of liver fibrosis in individuals with excessive alcohol use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Alcohol consumption leads to marked alterations in multiple metabolic pathways, highlighting the systemic impact of alcohol on various tissues and organ systems. These findings provide a foundation for future mechanistic studies aimed at elucidating alcohol-induced changes in these metabolic pathways and their implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1519-1528"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478087","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}
Giovanni Deiana, Ruinan Sun, Jie Huang, Valerio Napolioni, Roberto Ciccocioppo
{"title":"Infection burden and ALDH2 rs671, East Asian genetic diversity: A reply","authors":"Giovanni Deiana, Ruinan Sun, Jie Huang, Valerio Napolioni, Roberto Ciccocioppo","doi":"10.1111/acer.15403","DOIUrl":"10.1111/acer.15403","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1812-1813"},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473178","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号