Pub Date : 2024-11-28DOI: 10.1016/j.euroneuro.2024.11.005
Meritxell González-Campos , Helena Andreu , Oscar De Juan , Luis Olivier , Gerard Anmella
{"title":"Valproate's impact on future generations — A call for stricter guidelines for maternal and paternal use","authors":"Meritxell González-Campos , Helena Andreu , Oscar De Juan , Luis Olivier , Gerard Anmella","doi":"10.1016/j.euroneuro.2024.11.005","DOIUrl":"10.1016/j.euroneuro.2024.11.005","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"91 ","pages":"Pages 50-51"},"PeriodicalIF":6.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.euroneuro.2024.11.004
Cristina Ruiz-Rull , María José Jaén-Moreno , Gloria Isabel del Pozo , Cristina Camacho-Rodríguez , Marta Rodríguez-López , Fernando Rico-Villademoros , José Luis Otero-Ferrer , Nuria Feu , Micaela Reyes-López , Rosa M. Fiestas , David Laguna-Muñoz , Ana Jiménez-Peinado , David Mannino , Eduard Vieta , Fernando Sarramea
{"title":"Corrigendum to “Lung function decline in people with serious mental illness: A call to action” [European Neuropsychopharmacology (2024) 41-46/ ENP-24-342]","authors":"Cristina Ruiz-Rull , María José Jaén-Moreno , Gloria Isabel del Pozo , Cristina Camacho-Rodríguez , Marta Rodríguez-López , Fernando Rico-Villademoros , José Luis Otero-Ferrer , Nuria Feu , Micaela Reyes-López , Rosa M. Fiestas , David Laguna-Muñoz , Ana Jiménez-Peinado , David Mannino , Eduard Vieta , Fernando Sarramea","doi":"10.1016/j.euroneuro.2024.11.004","DOIUrl":"10.1016/j.euroneuro.2024.11.004","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Page 79"},"PeriodicalIF":6.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1016/j.euroneuro.2024.10.007
Alejandro de la Torre-Luque , Jose Luis Ayuso-Mateos
{"title":"The need for specific mental health interventions for the prevention of suicide in postpandemic times","authors":"Alejandro de la Torre-Luque , Jose Luis Ayuso-Mateos","doi":"10.1016/j.euroneuro.2024.10.007","DOIUrl":"10.1016/j.euroneuro.2024.10.007","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 77-78"},"PeriodicalIF":6.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.euroneuro.2024.10.006
Guido Cammà , Monika P. Verdouw , Pim B. van der Meer , Lucianne Groenink , Albert Batalla
Interest in cannabinoids’ therapeutic potential in mental health is growing, supported by evidence of the involvement of the endocannabinoid system in psychiatric disorders such as anxiety, depression, and addiction. While the major cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have been more extensively researched, approximately 120 minor cannabinoids from the cannabis plant have been identified. Although some displayed promising pharmacological profiles, research on their application for psychiatric disorders is fragmented. This systematic review evaluates, for the first time, both preclinical and clinical studies exploring minor cannabinoids’ therapeutic potential in psychiatric disorders.
22 preclinical studies and one clinical study were included, investigating various minor cannabinoids in substance use disorders, anxiety disorders, depressive disorders, trauma and stressor-related disorders, psychotic disorders, neurodevelopmental disorders, and eating disorders. Despite the heterogeneous results and the moderate to high risk of bias in several articles, certain compounds demonstrate promise for further investigation. Δ8-tetrahydrocannabidivarin (Δ8‐THCV) exhibited potential for nicotine addiction; Δ9-tetrahydrocannabidivarin (Δ9‐THCV) for psychotic-like symptoms; cannabidiolic acid methyl ester (CBDA-ME) alleviated anxiety and depression-like symptoms, and cannabidivarin (CBDV) autism spectrum disorder-like symptoms.
{"title":"Therapeutic potential of minor cannabinoids in psychiatric disorders: A systematic review","authors":"Guido Cammà , Monika P. Verdouw , Pim B. van der Meer , Lucianne Groenink , Albert Batalla","doi":"10.1016/j.euroneuro.2024.10.006","DOIUrl":"10.1016/j.euroneuro.2024.10.006","url":null,"abstract":"<div><div>Interest in cannabinoids’ therapeutic potential in mental health is growing, supported by evidence of the involvement of the endocannabinoid system in psychiatric disorders such as anxiety, depression, and addiction. While the major cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have been more extensively researched, approximately 120 minor cannabinoids from the cannabis plant have been identified. Although some displayed promising pharmacological profiles, research on their application for psychiatric disorders is fragmented. This systematic review evaluates, for the first time, both preclinical and clinical studies exploring minor cannabinoids’ therapeutic potential in psychiatric disorders.</div><div>22 preclinical studies and one clinical study were included, investigating various minor cannabinoids in substance use disorders, anxiety disorders, depressive disorders, trauma and stressor-related disorders, psychotic disorders, neurodevelopmental disorders, and eating disorders. Despite the heterogeneous results and the moderate to high risk of bias in several articles, certain compounds demonstrate promise for further investigation. Δ8-tetrahydrocannabidivarin (Δ8‐THCV) exhibited potential for nicotine addiction; Δ9-tetrahydrocannabidivarin (Δ9‐THCV) for psychotic-like symptoms; cannabidiolic acid methyl ester (CBDA-ME) alleviated anxiety and depression-like symptoms, and cannabidivarin (CBDV) autism spectrum disorder-like symptoms.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"91 ","pages":"Pages 9-24"},"PeriodicalIF":6.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.euroneuro.2024.10.009
Heidi Ka Ying Lo , Joe Kwun Nam Chan , Corine Sau Man Wong , Ka Fai Chung , Christoph U Correll , Marco Solmi , Lawrence W Baum , Thuan Quoc Thach , Pak Chung Sham , Wing Chung Chang
Depression is associated with premature mortality, but evidence is mainly derived from Western countries. Very limited research has evaluated shortened lifespan in depression using life-years-lost (LYLs), a recently developed mortality metric taking into account the illness onset for life expectancy estimation. Temporal trends of differential mortality gap are understudied. This population-based cohort study, which utilized a territory-wide medical-record database of public inpatient and outpatient healthcare services in Hong Kong, evaluated the extent of premature mortality in 126,573 individuals with depression (persons-years=1,139,073) between January 2002 and December 2021 regarding the standardized mortality ratio (SMR) and excess LYLs. Trends in annual SMRs over 20 years were assessed by joinpoint analyses. The results showed that individuals with depression exhibited significantly higher all-cause (SMR=1.84 [95% CI=1.82–1.88]), natural-cause (1.69 [1.66–1.72]), and unnatural-cause (5.24 [4.97–5.51]) mortality rates than the general population. Suicide-specific SMR was markedly elevated (7.92 [7.47–8.38]), particularly in the 15–34 year-olds (12.75 [10.87–14.79]). Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Excess LYLs extended to men (5.67 years, 95% CI = 5.45–5.90) and women (4.06 years, 95% CI = 3.89–4.23). Overall and natural-cause mortality rates improved over time, but unnatural-cause and suicide-related mortality gaps persisted. Taken together, this study indicates that depression is associated with increased premature mortality and reduced lifespan in a predominantly Chinese population, mainly attributed to natural causes. Relative suicide-specific mortality is substantially elevated, especially among young people. The pronounced mortality gap underscores an urgent need for effective interventions targeting improved physical health and suicide risk reduction in individuals with depression.
{"title":"Excess mortality and life-years lost in people diagnosed with depression: A 20-year population-based cohort study of 126,573 depressed individuals followed for 1,139,073 persons-years","authors":"Heidi Ka Ying Lo , Joe Kwun Nam Chan , Corine Sau Man Wong , Ka Fai Chung , Christoph U Correll , Marco Solmi , Lawrence W Baum , Thuan Quoc Thach , Pak Chung Sham , Wing Chung Chang","doi":"10.1016/j.euroneuro.2024.10.009","DOIUrl":"10.1016/j.euroneuro.2024.10.009","url":null,"abstract":"<div><div>Depression is associated with premature mortality, but evidence is mainly derived from Western countries. Very limited research has evaluated shortened lifespan in depression using life-years-lost (LYLs), a recently developed mortality metric taking into account the illness onset for life expectancy estimation. Temporal trends of differential mortality gap are understudied. This population-based cohort study, which utilized a territory-wide medical-record database of public inpatient and outpatient healthcare services in Hong Kong, evaluated the extent of premature mortality in 126,573 individuals with depression (persons-years=1,139,073) between January 2002 and December 2021 regarding the standardized mortality ratio (SMR) and excess LYLs. Trends in annual SMRs over 20 years were assessed by joinpoint analyses. The results showed that individuals with depression exhibited significantly higher all-cause (SMR=1.84 [95% CI=1.82–1.88]), natural-cause (1.69 [1.66–1.72]), and unnatural-cause (5.24 [4.97–5.51]) mortality rates than the general population. Suicide-specific SMR was markedly elevated (7.92 [7.47–8.38]), particularly in the 15–34 year-olds (12.75 [10.87–14.79]). Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Excess LYLs extended to men (5.67 years, 95% CI = 5.45–5.90) and women (4.06 years, 95% CI = 3.89–4.23). Overall and natural-cause mortality rates improved over time, but unnatural-cause and suicide-related mortality gaps persisted. Taken together, this study indicates that depression is associated with increased premature mortality and reduced lifespan in a predominantly Chinese population, mainly attributed to natural causes. Relative suicide-specific mortality is substantially elevated, especially among young people. The pronounced mortality gap underscores an urgent need for effective interventions targeting improved physical health and suicide risk reduction in individuals with depression.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"91 ","pages":"Pages 1-8"},"PeriodicalIF":6.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.euroneuro.2024.10.003
Jurjen J. Luykx , Caroline T.A. Moermond , Lisa Page , Unax Lertxundi , Christiaan H. Vinkers
Despite the multifaceted negative influences of psychotropic medications on the environment, an overview of such effects and of actions to curtail them is currently lacking. We therefore summarized the most relevant literature on what we refer to as Environmentally Conscious Psychopharmacotherapy (ECP), i.e., prescribing the most appropriate psychotropic medications for patients while at the same time considering the wellbeing of the planet. In our literature appraisal we identified viable actions at the levels of industry, physicians, pharmacists, patients, and policymakers that can reduce the environmental hazards associated with psychotropics. We divided these actions into the following categories: careful treatment selection, curtailing overprescribing, adequate disposal of medication by users, and transparent reporting of environmental risk. For each of these categories, we give examples of practices are in line with ECP, which in turn has the potential to reduce the impact of psychotropic medication prescribing practices on the environment. We note that many such practices result in co-benefits for patients, prescribers and the environment. On the other hand, evidence on environmental impact is lacking for several factors related to these medications, e.g., geographical region of manufacturing, duration of use, pharmacological vs. non-pharmaceutical treatment options, and ecotoxicological data. We conclude that general as well as disorder-specific considerations for clinicians prescribing psychotropics already carry the potential to limit the environmental burden associated with these agents. Future research aimed at filling the knowledge gaps we identified is likely to substantially advance ECP in the near future.
{"title":"Environmentally conscious psychopharmacotherapy: Practice recommendations for psychiatrists","authors":"Jurjen J. Luykx , Caroline T.A. Moermond , Lisa Page , Unax Lertxundi , Christiaan H. Vinkers","doi":"10.1016/j.euroneuro.2024.10.003","DOIUrl":"10.1016/j.euroneuro.2024.10.003","url":null,"abstract":"<div><div>Despite the multifaceted negative influences of psychotropic medications on the environment, an overview of such effects and of actions to curtail them is currently lacking. We therefore summarized the most relevant literature on what we refer to as Environmentally Conscious Psychopharmacotherapy (ECP), i.e., prescribing the most appropriate psychotropic medications for patients while at the same time considering the wellbeing of the planet. In our literature appraisal we identified viable actions at the levels of industry, physicians, pharmacists, patients, and policymakers that can reduce the environmental hazards associated with psychotropics. We divided these actions into the following categories: careful treatment selection, curtailing overprescribing, adequate disposal of medication by users, and transparent reporting of environmental risk. For each of these categories, we give examples of practices are in line with ECP, which in turn has the potential to reduce the impact of psychotropic medication prescribing practices on the environment. We note that many such practices result in co-benefits for patients, prescribers and the environment. On the other hand, evidence on environmental impact is lacking for several factors related to these medications, e.g., geographical region of manufacturing, duration of use, pharmacological vs. non-pharmaceutical treatment options, and ecotoxicological data. We conclude that general as well as disorder-specific considerations for clinicians prescribing psychotropics already carry the potential to limit the environmental burden associated with these agents. Future research aimed at filling the knowledge gaps we identified is likely to substantially advance ECP in the near future.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 71-76"},"PeriodicalIF":6.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-08DOI: 10.1016/j.euroneuro.2024.10.011
Károly Mirnics
{"title":"Fetal Fentanyl Syndrome – Only the “tip of the iceberg”?","authors":"Károly Mirnics","doi":"10.1016/j.euroneuro.2024.10.011","DOIUrl":"10.1016/j.euroneuro.2024.10.011","url":null,"abstract":"","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 69-70"},"PeriodicalIF":6.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1016/j.euroneuro.2024.10.002
Mojtaba Oraki Kohshour , Urs Heilbronner , Thorsten Mueller , Moritz Rossner , Sergi Papiol , Thomas G. Schulze
MicroRNAs (miRNAs) have the potential to affect drug metabolism, and some drugs affect cellular miRNA expression. miRNAs are found inside extracellular vesicles (EVs), and the profile of these EV-miRNAs can change across different diseases and disease states. Consequently, in recent years EV-miRNAs have attracted increasing attention as possible non-invasive biomarkers. For example, analyzing the miRNA expression profile of brain-derived EVs in blood may allow us to non-invasively assess miRNA dysregulation and thus to gain knowledge about the pathophysiology of psychiatric disorders and identify potential new predictive targets. We searched PubMed for all studies related to the effects of psychiatric medications on EV-miRNAs and identified 14 relevant articles. Taken together, findings indicate that certain EV-miRNAs may be targets for psychiatric medications and that antipsychotics such as olanzapine and antidepressants such as fluoxetine may alter the expression levels of particular EV-miRNAs. If confirmed and replicated, these findings may lead to the suggested miRNA profiles being used as pharmacodynamic biomarkers. However, heterogeneities and uncertainties remain regarding the role of EV-miRNAs in psychiatric disorders and their interaction with neuronal gene expression and drugs. This minireview summarizes some of the findings on the effects of psychiatric medications on EV-miRNAs and describes the potential role of EV-miRNAs as pharmacodynamic biomarkers for psychiatric disorders.
{"title":"The microRNA profile of brain-derived extracellular vesicles: A promising step forward in developing pharmacodynamic biomarkers for psychiatric disorders","authors":"Mojtaba Oraki Kohshour , Urs Heilbronner , Thorsten Mueller , Moritz Rossner , Sergi Papiol , Thomas G. Schulze","doi":"10.1016/j.euroneuro.2024.10.002","DOIUrl":"10.1016/j.euroneuro.2024.10.002","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) have the potential to affect drug metabolism, and some drugs affect cellular miRNA expression. miRNAs are found inside extracellular vesicles (EVs), and the profile of these EV-miRNAs can change across different diseases and disease states. Consequently, in recent years EV-miRNAs have attracted increasing attention as possible non-invasive biomarkers. For example, analyzing the miRNA expression profile of brain-derived EVs in blood may allow us to non-invasively assess miRNA dysregulation and thus to gain knowledge about the pathophysiology of psychiatric disorders and identify potential new predictive targets. We searched PubMed for all studies related to the effects of psychiatric medications on EV-miRNAs and identified 14 relevant articles. Taken together, findings indicate that certain EV-miRNAs may be targets for psychiatric medications and that antipsychotics such as olanzapine and antidepressants such as fluoxetine may alter the expression levels of particular EV-miRNAs. If confirmed and replicated, these findings may lead to the suggested miRNA profiles being used as pharmacodynamic biomarkers. However, heterogeneities and uncertainties remain regarding the role of EV-miRNAs in psychiatric disorders and their interaction with neuronal gene expression and drugs. This minireview summarizes some of the findings on the effects of psychiatric medications on EV-miRNAs and describes the potential role of EV-miRNAs as pharmacodynamic biomarkers for psychiatric disorders.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 62-68"},"PeriodicalIF":6.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1016/j.euroneuro.2024.10.001
Agueda Castro-Quintas , Helena Palma-Gudiel , Elisenda Eixarch , Nerea San Martín González , Simone Röh , Susann Sauer , Monika Rex-Haffner , Jose Luis Monteserin-Garcia , Lorena de la Fuente-Tomás , Fatima Crispi , Maria Paz Garcia Portilla , Elisabeth B. Binder , Lourdes Fañanas
Maternal stress during pregnancy can impact offspring health, increasing the risk of neuropsychiatric disorders. The human placenta plays a crucial role in understanding this effect, influencing fetal programming as it connects maternal and fetal circulation. Our hypothesis centers on maternal stress influencing children's outcomes through placental DNA methylation, targeting three cortisol-regulating genes: NR3C1, FKBP5, and HSD11B2.
In this pilot study, chorionic villi and maternal decidua placental layers from 45 mother-infant dyads (divided into two groups based on high/low maternal stress exposure) were analyzed for DNA methylation at the genes of interest via targeted bisulfite sequencing. Pregnant women provided four saliva samples throughout a day for cortisol determinations and were assessed for the presence of depressive symptoms at each of the three trimesters of pregnancy. Newborns underwent neurodevelopmental assessments and salivary cortisol evaluations at 7 weeks.
Increased maternal diurnal cortisol levels in the first trimester of pregnancy was significantly associated with elevated DNA methylation at exon 1D of the NR3C1 gene and lower DNA methylation at intron 7 of the FKBP5 gene, both in chorionic villi samples. Elevated DNA methylation at introns 1 and 7 of FKBP5 in the maternal decidua were strongly linked to an anticipated delivery. DNA methylation at the HSD11B2 promoter region was uniformly low across all placental samples. No associations with newborn neurodevelopment were found.
These results emphasize the importance of exploring layer-specific methylation differences at distinct pregnancy stages, highlighting the complex interplay between maternal stress, placental epigenetic modifications, and fetal development throughout the prenatal period.
孕期母体的压力会影响后代的健康，增加患神经精神疾病的风险。人类胎盘在了解这种影响方面起着至关重要的作用，它连接着母体和胎儿的血液循环，影响着胎儿的发育。我们的假说集中于母体压力通过胎盘 DNA 甲基化影响儿童的结果，目标是三个皮质醇调节基因：NR3C1、FKBP5 和 HSD11B2。在这项试验性研究中，通过靶向亚硫酸氢盐测序分析了45对母婴（根据母婴压力暴露程度分为高/低两组）的绒毛和母体蜕膜胎盘层中相关基因的DNA甲基化情况。孕妇每天提供四份唾液样本用于皮质醇测定，并在怀孕三个月的每个阶段对是否存在抑郁症状进行评估。新生儿在 7 周时接受神经发育评估和唾液皮质醇评估。在绒毛样本中，妊娠头三个月母体昼夜皮质醇水平的升高与NR3C1基因外显子1D的DNA甲基化升高和FKBP5基因内含子7的DNA甲基化降低有显著关联。母体蜕膜中 FKBP5 基因内含子 1 和 7 的 DNA 甲基化升高与预产期密切相关。在所有胎盘样本中，HSD11B2 启动子区域的 DNA 甲基化程度都很低。没有发现与新生儿神经发育有关的关联。这些结果强调了在不同妊娠阶段探索特定层甲基化差异的重要性，突出了整个产前期间母体压力、胎盘表观遗传修饰和胎儿发育之间复杂的相互作用。
{"title":"Placental epigenetic signatures of maternal distress in glucocorticoid-related genes and newborn outcomes: A study of Spanish primiparous women","authors":"Agueda Castro-Quintas , Helena Palma-Gudiel , Elisenda Eixarch , Nerea San Martín González , Simone Röh , Susann Sauer , Monika Rex-Haffner , Jose Luis Monteserin-Garcia , Lorena de la Fuente-Tomás , Fatima Crispi , Maria Paz Garcia Portilla , Elisabeth B. Binder , Lourdes Fañanas","doi":"10.1016/j.euroneuro.2024.10.001","DOIUrl":"10.1016/j.euroneuro.2024.10.001","url":null,"abstract":"<div><div>Maternal stress during pregnancy can impact offspring health, increasing the risk of neuropsychiatric disorders. The human placenta plays a crucial role in understanding this effect, influencing fetal programming as it connects maternal and fetal circulation. Our hypothesis centers on maternal stress influencing children's outcomes through placental DNA methylation, targeting three cortisol-regulating genes: <em>NR3C1, FKBP5</em>, and <em>HSD11B2</em>.</div><div>In this pilot study, chorionic villi and maternal decidua placental layers from 45 mother-infant dyads (divided into two groups based on high/low maternal stress exposure) were analyzed for DNA methylation at the genes of interest via targeted bisulfite sequencing. Pregnant women provided four saliva samples throughout a day for cortisol determinations and were assessed for the presence of depressive symptoms at each of the three trimesters of pregnancy. Newborns underwent neurodevelopmental assessments and salivary cortisol evaluations at 7 weeks.</div><div>Increased maternal diurnal cortisol levels in the first trimester of pregnancy was significantly associated with elevated DNA methylation at exon 1D of the <em>NR3C1</em> gene and lower DNA methylation at intron 7 of the <em>FKBP5</em> gene, both in chorionic villi samples. Elevated DNA methylation at introns 1 and 7 of <em>FKBP5</em> in the maternal decidua were strongly linked to an anticipated delivery. DNA methylation at the <em>HSD11B2</em> promoter region was uniformly low across all placental samples. No associations with newborn neurodevelopment were found.</div><div>These results emphasize the importance of exploring layer-specific methylation differences at distinct pregnancy stages, highlighting the complex interplay between maternal stress, placental epigenetic modifications, and fetal development throughout the prenatal period.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 36-47"},"PeriodicalIF":6.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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