European Neuropsychopharmacology最新文献_第9页

Sodium benzoate treatment linked to increased glutathione levels and improved positive and negative symptoms, global function, and quality of life in patients with clozapine-resistant schizophrenia: secondary analysis of a randomized clinical trial 苯甲酸钠治疗与增加谷胱甘肽水平、改善阳性和阴性症状、整体功能和氯氮平抵抗性精神分裂症患者的生活质量有关：一项随机临床试验的二次分析

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-12-15 DOI: 10.1016/j.euroneuro.2025.11.010

Chieh-Hsin Lin , Hsien-Yuan Lane

Oxidative stress is implicated in schizophrenia. Glutathione (GSH), a crucial endogenous antioxidant, is usually reduced in individuals with schizophrenia. GSH and its precursor, N-acetyl cysteine, have demonstrated potential as adjunctive treatment for schizophrenia; however, their effectiveness appears inconsistent, possibly because of their limited ability to penetrate the blood-brain barrier (BBB). Administration of sodium benzoate, capable of crossing BBB, enhanced GSH capacity and antipsychotic-like activity in animals. Further, adjunctive benzoate therapy improved clinical and functional outcomes in patients with schizophrenia, including clozapine-resistant schizophrenia (CRS). Whether sodium benzoate can also boost GSH to exert its therapeutic efficacy for schizophrenia deserves elucidation. This secondary analysis used data from a double-blind trial, in which 60 patients with CRS were randomized to receive addon treatment of sodium benzoate (n = 40) or placebo (n = 20) for 6 weeks. Clinical and functional assessments were conducted bi-weekly. Plasma levels of GSH were assayed at baseline and endpoint. As a result, six-week treatment of sodium benzoate was linked to increased GSH levels than placebo. Among the 40 benzoate receivers, the changes in GSH levels were correlated with the improvements in positive symptoms, negative symptoms, quality of life, and global function. In comparison, among placebo recipients, GSH changes were not associated with any changes in clinical or functional variables. The findings suggest that benzoate treatment may be related with elevation in GSH levels in CRS patients and improvement in functional outcomes as well as positive and negative symptoms. Longer-term studies in other populations are necessary in the future.

氧化应激与精神分裂症有关。谷胱甘肽（GSH）是一种重要的内源性抗氧化剂，在精神分裂症患者中通常会减少。谷胱甘肽及其前体n -乙酰半胱氨酸已被证明具有作为精神分裂症辅助治疗的潜力；然而，它们的效果似乎不一致，可能是因为它们穿透血脑屏障（BBB）的能力有限。能穿过血脑屏障的苯甲酸钠在动物体内增强谷胱甘肽能力和抗精神病样活性。此外，辅助苯甲酸酯治疗改善了精神分裂症患者的临床和功能结局，包括氯氮平抵抗性精神分裂症（CRS）。苯甲酸钠是否也能促进谷胱甘肽的分泌，从而发挥其治疗精神分裂症的作用，值得进一步研究。这项二次分析使用了一项双盲试验的数据，在该试验中，60名CRS患者随机接受6周的苯甲酸钠（n = 40）或安慰剂（n = 20）的附加治疗。临床和功能评估每两周进行一次。在基线和终点检测血浆谷胱甘肽水平。结果，六周的苯甲酸钠治疗与安慰剂相比，GSH水平升高有关。在40名苯甲酯受体中，GSH水平的变化与阳性症状、阴性症状、生活质量和整体功能的改善相关。相比之下，在安慰剂接受者中，谷胱甘肽的变化与临床或功能变量的任何变化无关。研究结果表明，苯甲酯治疗可能与CRS患者谷胱甘肽水平升高、功能结局以及阳性和阴性症状的改善有关。未来有必要对其他人群进行长期研究。

{"title":"Sodium benzoate treatment linked to increased glutathione levels and improved positive and negative symptoms, global function, and quality of life in patients with clozapine-resistant schizophrenia: secondary analysis of a randomized clinical trial","authors":"Chieh-Hsin Lin , Hsien-Yuan Lane","doi":"10.1016/j.euroneuro.2025.11.010","DOIUrl":"10.1016/j.euroneuro.2025.11.010","url":null,"abstract":"<div><div>Oxidative stress is implicated in schizophrenia. Glutathione (GSH), a crucial endogenous antioxidant, is usually reduced in individuals with schizophrenia. GSH and its precursor, N-acetyl cysteine, have demonstrated potential as adjunctive treatment for schizophrenia; however, their effectiveness appears inconsistent, possibly because of their limited ability to penetrate the blood-brain barrier (BBB). Administration of sodium benzoate, capable of crossing BBB, enhanced GSH capacity and antipsychotic-like activity in animals. Further, adjunctive benzoate therapy improved clinical and functional outcomes in patients with schizophrenia, including clozapine-resistant schizophrenia (CRS). Whether sodium benzoate can also boost GSH to exert its therapeutic efficacy for schizophrenia deserves elucidation. This secondary analysis used data from a double-blind trial, in which 60 patients with CRS were randomized to receive addon treatment of sodium benzoate (n = 40) or placebo (n = 20) for 6 weeks. Clinical and functional assessments were conducted bi-weekly. Plasma levels of GSH were assayed at baseline and endpoint. As a result, six-week treatment of sodium benzoate was linked to increased GSH levels than placebo. Among the 40 benzoate receivers, the changes in GSH levels were correlated with the improvements in positive symptoms, negative symptoms, quality of life, and global function. In comparison, among placebo recipients, GSH changes were not associated with any changes in clinical or functional variables. The findings suggest that benzoate treatment may be related with elevation in GSH levels in CRS patients and improvement in functional outcomes as well as positive and negative symptoms. Longer-term studies in other populations are necessary in the future.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112733"},"PeriodicalIF":6.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767508","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}

引用次数: 0

Different effect of adverse childhood experiences on white matter microstructure in major depression and bipolar disorder: moderating role of genetic liability 童年不良经历对重度抑郁症和双相情感障碍白质微观结构的不同影响：遗传倾向的调节作用

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-12-13 DOI: 10.1016/j.euroneuro.2025.11.011

Marco Paolini , Laura Raffaelli , Valentina Bettonagli , Cristina Lorenzi , Sara Spadini , Beatrice Bravi , Lidia Fortaner-Uyà , Giulia Gulino , Chiara Fabbri , Alessandro Serretti , Raffaella Zanardi , Cristina Colombo , Francesco Benedetti , Sara Poletti

Adverse childhood experiences (ACEs) are risk factors for both major depressive (MDD) and bipolar disorder. ACEs have been associated with white matter (WM) alterations, but whether they have different effects in MDD and BD remains unclear. Polygenic risk scores (PRS) allow for an individual estimation of genetic liabilities for most psychiatric conditions. The aim of the present study was to characterize the effect of ACEs on WM microstructure in MDD and BD, testing a possible differential effect between the two diagnoses and investigating whether genetic liabilities might modulate this relation. 260 depressed inpatients (140 MDD and 120 BD, mean age 49.29 ± 10.60, F = 161) underwent 3T MRI scan and ACEs evaluation. MDD and BD PRS were calculated in a subset of patients. Significant ACEs x diagnosis interactions were found for several DTI metrics. Single group analyses showed widespread detrimental effects of ACEs on WM integrity in BD, and less pronounced effects in MDD. Significant moderating effect of BD PRS in the whole sample and in MDD specifically were found for the relation between ACEs, fractional anisotropy and radial diffusivity, with bipolar-like relations for higher values of BD PRS. The differential effect of ACEs on WM microstructure in the two diagnostic groups points towards putative differential pathophysiological routes through which childhood maltreatment affects the two conditions, while the identification of a BD PRS moderation on the whole sample and in MDD specifically sheds light on the causal relation between ACEs, diagnostic phenotype and DTI metrics, and provides a possible tool to disentangle MDD heterogeneity.

不良童年经历（ace）是重度抑郁症（MDD）和双相情感障碍的危险因素。ace与白质（WM）改变有关，但它们对重度抑郁症和双相障碍是否有不同的影响尚不清楚。多基因风险评分（PRS）允许对大多数精神疾病的遗传责任进行个体估计。本研究的目的是表征ace对MDD和BD中WM微观结构的影响，测试两种诊断之间可能的差异效应，并研究遗传负荷是否可能调节这种关系。260例住院抑郁症患者（重度抑郁症140例，双相抑郁症120例，平均年龄49.29±10.60岁，F = 161）行3T MRI扫描和ace评估。计算一部分患者的MDD和BD PRS。在几个DTI指标中发现了显著的ace与诊断的相互作用。单组分析显示，ace对BD患者的WM完整性有广泛的有害影响，而对MDD患者的影响不太明显。在整个样本中，特别是在MDD中，BD PRS对ace、分数各向异性和径向扩散率之间的关系有显著的调节作用，在更高的BD PRS值时呈双极样关系。在两个诊断组中，ace对WM微观结构的不同影响指向了儿童虐待影响这两种情况的可能的不同病理生理途径，而在整个样本和MDD中发现的BD PRS调节作用特别揭示了ace、诊断表型和DTI指标之间的因果关系，并提供了一种可能的工具来解决MDD的异质性。

{"title":"Different effect of adverse childhood experiences on white matter microstructure in major depression and bipolar disorder: moderating role of genetic liability","authors":"Marco Paolini , Laura Raffaelli , Valentina Bettonagli , Cristina Lorenzi , Sara Spadini , Beatrice Bravi , Lidia Fortaner-Uyà , Giulia Gulino , Chiara Fabbri , Alessandro Serretti , Raffaella Zanardi , Cristina Colombo , Francesco Benedetti , Sara Poletti","doi":"10.1016/j.euroneuro.2025.11.011","DOIUrl":"10.1016/j.euroneuro.2025.11.011","url":null,"abstract":"<div><div>Adverse childhood experiences (ACEs) are risk factors for both major depressive (MDD) and bipolar disorder. ACEs have been associated with white matter (WM) alterations, but whether they have different effects in MDD and BD remains unclear. Polygenic risk scores (PRS) allow for an individual estimation of genetic liabilities for most psychiatric conditions. The aim of the present study was to characterize the effect of ACEs on WM microstructure in MDD and BD, testing a possible differential effect between the two diagnoses and investigating whether genetic liabilities might modulate this relation. 260 depressed inpatients (140 MDD and 120 BD, mean age 49.29 ± 10.60, <em>F</em> = 161) underwent 3T MRI scan and ACEs evaluation. MDD and BD PRS were calculated in a subset of patients. Significant ACEs x diagnosis interactions were found for several DTI metrics. Single group analyses showed widespread detrimental effects of ACEs on WM integrity in BD, and less pronounced effects in MDD. Significant moderating effect of BD PRS in the whole sample and in MDD specifically were found for the relation between ACEs, fractional anisotropy and radial diffusivity, with bipolar-like relations for higher values of BD PRS. The differential effect of ACEs on WM microstructure in the two diagnostic groups points towards putative differential pathophysiological routes through which childhood maltreatment affects the two conditions, while the identification of a BD PRS moderation on the whole sample and in MDD specifically sheds light on the causal relation between ACEs, diagnostic phenotype and DTI metrics, and provides a possible tool to disentangle MDD heterogeneity.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112734"},"PeriodicalIF":6.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750305","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}

引用次数: 0

Are cell type-specific methylation profiles the missing link in ADHD epigenetics? 细胞类型特异性甲基化谱是ADHD表观遗传学中缺失的环节吗？

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-12-13 DOI: 10.1016/j.euroneuro.2025.11.013

Guilherme Lima Ferreira Neves, Guilherme Nobre Nogueira

引用次数: 0

Dynamic functional network connectivity impairment in bipolar disorder and its relationship with global functioning 双相情感障碍的动态功能网络连接障碍及其与整体功能的关系

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-12-13 DOI: 10.1016/j.euroneuro.2025.11.015

Daniele Olivo , Alessandro Miola , Francesco Folena Comini , Nicolò Trevisan , Giovanni Librizzi , Tommaso Toffanin , Renzo Manara , Fabio Sambataro

Abnormal functional connectivity (FC) has been consistently associated with bipolar disorders (BD). Classical FC analyses assume stationarity of brain interactions, although connectivity actually varies over time. Here, we examined alterations in dynamic functional network connectivity (dFNC) in BD, their associations with symptom severity and global functioning, and potential differences between bipolar disorder type I (BD1) and type II (BD2).

In this case-control study, we investigated dFNC in 57 patients with BD (29 BD1, 28 BD2) and 43 healthy controls (HCs). Most patients were euthymic at scanning (∼86 %), with only a minority showing residual depressive or hypomanic/mixed symptoms. Resting-state fMRI data were decomposed with spatially constrained independent component analysis and analyzed using a sliding-window approach. Meta-state metrics—number of meta-states, transitions, total distance, and span—were derived and compared across groups. Correlations with clinical measures and Global Assessment of Functioning (GAF) scores were tested. Dynamic metrics (number of meta-states, state transitions, and total distance) were reduced in BD relative to HCs, with the greatest reduction in BD1, followed by BD2. State span did not differ between groups. Across the BD sample, higher GAF scores were positively associated with greater dynamic fluidity, whereas no significant associations emerged with standard symptom scales.

In conclusion, BD is characterized by a graded disruption of the spatio-temporal dynamics of large-scale brain networks, most pronounced in BD1. Reduced neural flexibility is linked to poorer global functioning, suggesting that dFNC meta-state metrics may provide clinically relevant markers of illness burden in bipolar disorder.

功能连接异常（FC）一直与双相情感障碍（BD）相关。经典的FC分析假设大脑相互作用是平稳的，尽管连通性实际上随着时间的推移而变化。在这里，我们研究了双相情感障碍中动态功能网络连接（dFNC）的改变，它们与症状严重程度和整体功能的关系，以及I型双相情感障碍（BD1）和II型双相情感障碍（BD2）之间的潜在差异。在这项病例对照研究中，我们调查了57例BD患者（29例BD1, 28例BD2）和43例健康对照（hc）的dFNC。大多数患者在扫描时心境良好（约86%），只有少数患者表现出残留的抑郁或轻躁/混合症状。静息状态fMRI数据采用空间约束独立分量分析进行分解，并采用滑动窗口方法进行分析。元状态度量——元状态的数量、转换、总距离和跨度——被导出并跨组进行比较。测试了与临床测量和总体功能评估（GAF）评分的相关性。动态指标（元状态数量、状态转换和总距离）在BD中相对于hcc减少，其中BD1减少最多，其次是BD2。各组之间的状态跨度没有差异。在BD样本中，较高的GAF分数与较高的动态流动性呈正相关，而与标准症状量表没有显著关联。总之，BD的特征是大尺度脑网络时空动态的逐步中断，在BD1中最为明显。神经灵活性降低与整体功能较差有关，表明dFNC元状态指标可能提供双相情感障碍疾病负担的临床相关标记。

{"title":"Dynamic functional network connectivity impairment in bipolar disorder and its relationship with global functioning","authors":"Daniele Olivo , Alessandro Miola , Francesco Folena Comini , Nicolò Trevisan , Giovanni Librizzi , Tommaso Toffanin , Renzo Manara , Fabio Sambataro","doi":"10.1016/j.euroneuro.2025.11.015","DOIUrl":"10.1016/j.euroneuro.2025.11.015","url":null,"abstract":"<div><div>Abnormal functional connectivity (FC) has been consistently associated with bipolar disorders (BD). Classical FC analyses assume stationarity of brain interactions, although connectivity actually varies over time. Here, we examined alterations in dynamic functional network connectivity (dFNC) in BD, their associations with symptom severity and global functioning, and potential differences between bipolar disorder type I (BD1) and type II (BD2).</div><div>In this case-control study, we investigated dFNC in 57 patients with BD (29 BD1, 28 BD2) and 43 healthy controls (HCs). Most patients were euthymic at scanning (∼86 %), with only a minority showing residual depressive or hypomanic/mixed symptoms. Resting-state fMRI data were decomposed with spatially constrained independent component analysis and analyzed using a sliding-window approach. Meta-state metrics—number of meta-states, transitions, total distance, and span—were derived and compared across groups. Correlations with clinical measures and Global Assessment of Functioning (GAF) scores were tested. Dynamic metrics (number of meta-states, state transitions, and total distance) were reduced in BD relative to HCs, with the greatest reduction in BD1, followed by BD2. State span did not differ between groups. Across the BD sample, higher GAF scores were positively associated with greater dynamic fluidity, whereas no significant associations emerged with standard symptom scales.</div><div>In conclusion, BD is characterized by a graded disruption of the spatio-temporal dynamics of large-scale brain networks, most pronounced in BD1. Reduced neural flexibility is linked to poorer global functioning, suggesting that dFNC meta-state metrics may provide clinically relevant markers of illness burden in bipolar disorder.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112738"},"PeriodicalIF":6.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750304","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}

引用次数: 0

Association between tirzepatide use and risk of mortality, hospitalization, and suicidal behavior in patients with schizophrenia spectrum disorders: A one-year retrospective cohort study of 3618 patients 精神分裂症谱系障碍患者使用替西帕肽与死亡、住院和自杀行为风险之间的关系：一项为期一年的3618例患者回顾性队列研究

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-12-12 DOI: 10.1016/j.euroneuro.2025.11.016

Ting-Hui Liu , Chia-Hsuan Hsu , Jheng-Yan Wu , Po-Yu Huang , Chih-Cheng Chang , Chih-Cheng Lai

This study aimed to evaluate the real-world effectiveness and psychiatric safety of tirzepatide among adults with schizophrenia spectrum disorders, focusing on the risks of mortality, hospitalization, and suicidal behavior. Based on the electronic health records from the TriNetX Global Collaborative Network, adults with schizophrenia spectrum disorders who initiated tirzepatide on or before June 1, 2024, were included. Tirzepatide users were propensity score–matched 1:1 to nonusers based on demographic and clinical variables. The primary outcome was a composite of all-cause mortality, hospitalization, and suicidal behavior evaluated between 30 and 365 days after the index date. Secondary outcomes included each component separately. Cox proportional hazards models and Kaplan–Meier estimators were used to estimate associations. Subgroup and sensitivity analyses were performed. Overall, a total of 1809 matched pairs were included. Tirzepatide use was associated with lower risk of the composite outcome (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.55–0.79), as well as all-cause mortality (HR, 0.18; 95 % CI, 0.06–0.51), hospitalization (HR, 0.75; 95 % CI, 0.61–0.92), and suicidal behavior (HR, 0.43; 95 % CI, 0.27–0.70). Risk reduction was generally consistent across subgroups. Control outcome analyses supported internal validity. In conclusion, tirzepatide use in patients with schizophrenia spectrum disorders is associated with improved clinical outcomes, including reduced risks of mortality, hospitalization, and suicidal behavior. These findings support the integration of tirzepatide into metabolic management strategies for this high-risk population, offering benefits for glycemic control and potentially for psychiatric outcomes.

本研究旨在评估替西帕肽在精神分裂症谱系障碍成人患者中的实际有效性和精神病学安全性，重点关注其死亡率、住院率和自杀行为的风险。根据TriNetX全球协作网络的电子健康记录，纳入了在2024年6月1日或之前开始使用替西帕肽的精神分裂症谱系障碍成年人。根据人口统计学和临床变量，替西肽使用者与非使用者的倾向评分匹配为1:1。主要结局是指标日期后30至365天内评估的全因死亡率、住院率和自杀行为的综合结果。次要结局分别包括每个成分。使用Cox比例风险模型和Kaplan-Meier估计器来估计相关性。进行亚组分析和敏感性分析。总共纳入了1809对匹配的配对。使用替西帕肽与综合结局（危险比[HR]， 0.66； 95%可信区间[CI]， 0.55-0.79）、全因死亡率（危险比，0.18;95% CI, 0.06-0.51）、住院（危险比，0.75;95% CI, 0.61-0.92）和自杀行为（危险比，0.43;95% CI, 0.27-0.70）的风险较低相关。风险降低在各个亚组中总体上是一致的。对照结果分析支持内部效度。总之，在精神分裂症谱系障碍患者中使用替西帕肽可改善临床结果，包括降低死亡、住院和自杀行为的风险。这些发现支持将替西帕肽整合到这一高危人群的代谢管理策略中，为血糖控制和潜在的精神预后提供益处。

{"title":"Association between tirzepatide use and risk of mortality, hospitalization, and suicidal behavior in patients with schizophrenia spectrum disorders: A one-year retrospective cohort study of 3618 patients","authors":"Ting-Hui Liu , Chia-Hsuan Hsu , Jheng-Yan Wu , Po-Yu Huang , Chih-Cheng Chang , Chih-Cheng Lai","doi":"10.1016/j.euroneuro.2025.11.016","DOIUrl":"10.1016/j.euroneuro.2025.11.016","url":null,"abstract":"<div><div>This study aimed to evaluate the real-world effectiveness and psychiatric safety of tirzepatide among adults with schizophrenia spectrum disorders, focusing on the risks of mortality, hospitalization, and suicidal behavior. Based on the electronic health records from the TriNetX Global Collaborative Network, adults with schizophrenia spectrum disorders who initiated tirzepatide on or before June 1, 2024, were included. Tirzepatide users were propensity score–matched 1:1 to nonusers based on demographic and clinical variables. The primary outcome was a composite of all-cause mortality, hospitalization, and suicidal behavior evaluated between 30 and 365 days after the index date. Secondary outcomes included each component separately. Cox proportional hazards models and Kaplan–Meier estimators were used to estimate associations. Subgroup and sensitivity analyses were performed. Overall, a total of 1809 matched pairs were included. Tirzepatide use was associated with lower risk of the composite outcome (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.55–0.79), as well as all-cause mortality (HR, 0.18; 95 % CI, 0.06–0.51), hospitalization (HR, 0.75; 95 % CI, 0.61–0.92), and suicidal behavior (HR, 0.43; 95 % CI, 0.27–0.70). Risk reduction was generally consistent across subgroups. Control outcome analyses supported internal validity. In conclusion, tirzepatide use in patients with schizophrenia spectrum disorders is associated with improved clinical outcomes, including reduced risks of mortality, hospitalization, and suicidal behavior. These findings support the integration of tirzepatide into metabolic management strategies for this high-risk population, offering benefits for glycemic control and potentially for psychiatric outcomes.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"103 ","pages":"Article 112739"},"PeriodicalIF":6.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145719036","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}

引用次数: 0

Psychedelics: The pathway to implementation in the European healthcare systems 致幻剂：在欧洲医疗保健系统实施的途径。

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-12-03 DOI: 10.1016/j.euroneuro.2025.11.007

Gerhard Gründer , Lea J. Mertens , Moritz Spangemacher , Andreas Meyer-Lindenberg , Henrik Jungaberle

The integration of psychedelic therapies into European healthcare is a nuanced process that involves not only obtaining European Medicines Agency (EMA) approval but also successfully navigating Health Technology Assessment (HTA) evaluations across member states. After EMA approval, which focuses on the safety, efficacy, and quality of the therapeutic, HTA agencies assess these therapies for their “added therapeutic value,” considering factors like cost-effectiveness, clinical outcomes, and overall societal impact. Each country's HTA, including the UK’s National Institute for Health and Care Excellence (NICE), Germany’s Institute for Quality and Efficiency in Health Care (IQWiG), and France’s Haute Autorité de Santé (HAS), plays a pivotal role in determining reimbursement and access to these treatments. An added challenge is that HTA bodies in Europe often require active comparator studies rather than just placebo controls to establish a treatment’s advantage over existing standard of care – a particular hurdle for psychedelic-assisted therapies, where controlled trials against active comparators are almost completely lacking. Furthermore, psychedelics are typically integrated with psychotherapy, adding complexity to HTA evaluations, as few frameworks currently assess the value of combination therapies within healthcare systems. Creating a standardized HTA approach or a unified European guideline for such novel treatments could promote equitable access across countries, helping to overcome the discrepancies in market access and patient reach across Europe.

将迷幻疗法整合到欧洲医疗保健中是一个微妙的过程，不仅需要获得欧洲药品管理局（EMA）的批准，还需要成功地通过成员国的健康技术评估（HTA）评估。在EMA批准后，主要关注治疗的安全性、有效性和质量，HTA机构评估这些治疗的“附加治疗价值”，考虑成本效益、临床结果和整体社会影响等因素。每个国家的HTA，包括英国的国家卫生和护理卓越研究所（NICE）、德国的卫生保健质量和效率研究所（IQWiG）和法国的高级医疗机构（HAS），在决定这些治疗的报销和获得方面发挥着关键作用。一个额外的挑战是，欧洲的HTA机构经常需要主动比较研究，而不仅仅是安慰剂对照，以确定一种治疗方法比现有的标准治疗方法更有优势——这对迷幻剂辅助治疗来说是一个特别的障碍，在这种治疗中，几乎完全缺乏针对主动比较的对照试验。此外，致幻剂通常与心理治疗相结合，增加了HTA评估的复杂性，因为目前很少有框架评估医疗保健系统中联合治疗的价值。为这种新疗法制定标准化的HTA方法或统一的欧洲指南可以促进各国之间的公平获取，帮助克服欧洲各地市场准入和患者覆盖范围的差异。

{"title":"Psychedelics: The pathway to implementation in the European healthcare systems","authors":"Gerhard Gründer , Lea J. Mertens , Moritz Spangemacher , Andreas Meyer-Lindenberg , Henrik Jungaberle","doi":"10.1016/j.euroneuro.2025.11.007","DOIUrl":"10.1016/j.euroneuro.2025.11.007","url":null,"abstract":"<div><div>The integration of psychedelic therapies into European healthcare is a nuanced process that involves not only obtaining European Medicines Agency (EMA) approval but also successfully navigating Health Technology Assessment (HTA) evaluations across member states. After EMA approval, which focuses on the safety, efficacy, and quality of the therapeutic, HTA agencies assess these therapies for their “added therapeutic value,” considering factors like cost-effectiveness, clinical outcomes, and overall societal impact. Each country's HTA, including the UK’s National Institute for Health and Care Excellence (NICE), Germany’s Institute for Quality and Efficiency in Health Care (IQWiG), and France’s Haute Autorité de Santé (HAS), plays a pivotal role in determining reimbursement and access to these treatments. An added challenge is that HTA bodies in Europe often require active comparator studies rather than just placebo controls to establish a treatment’s advantage over existing standard of care – a particular hurdle for psychedelic-assisted therapies, where controlled trials against active comparators are almost completely lacking. Furthermore, psychedelics are typically integrated with psychotherapy, adding complexity to HTA evaluations, as few frameworks currently assess the value of combination therapies within healthcare systems. Creating a standardized HTA approach or a unified European guideline for such novel treatments could promote equitable access across countries, helping to overcome the discrepancies in market access and patient reach across Europe.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 41-48"},"PeriodicalIF":6.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667683","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}

引用次数: 0

The effect of switching antipsychotics to aripiprazole versus paliperidone on weight/cardiometabolic parameters: 18-month follow-up findings from the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST) 将抗精神病药物转换为阿立哌唑与帕利哌酮对体重/心脏代谢参数的影响：来自欧洲精神分裂症长效抗精神病药物试验（EULAST）的18个月随访结果。

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-12-03 DOI: 10.1016/j.euroneuro.2025.11.014

Nini de Boer , Zara Vučko , Derek IJ. Koster , Marte van der Horst , Michael Davidson , Wiepke Cahn , Jurjen J. Luykx

Antipsychotic-induced weight gain (AiWG) is a common, burdensome adverse effect. Switching to antipsychotics with lower metabolic risks, such as aripiprazole, is recommended, but long-term data is limited. Long-acting injectables (LAIs) may offer metabolic benefits over oral formulations, yet evidence is inconsistent. We compared long-term effects of switching to aripiprazole versus paliperidone on bodyweight, considering administration route and smoking. To that end, we analyzed data from 241 participants (mean age = 31.0; 32 % female) in the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST), a multicentre, open-label, randomized trial. Participants received aripiprazole (n = 119) or paliperidone (n = 122), orally or as LAIs. Bodyweight was assessed over 18 months. Secondary outcomes included changes in BMI and cardiometabolic parameters. Both groups showed progressive weight gain: over 18 months, body weight increased by 4.7 kgs (95 % CI 3.0–6.5). Weight gain was 4.5 kgs with aripiprazole (95 % CI 2.1–7.0) and 4.9 kgs with paliperidone (95 % CI 2.3–7.4). Clinically significant weight gain (≥5 %) occurred in 41.1 % and 58.7 % of users, respectively (NNH = 5; p = 0.06). Weight gain was more pronounced among participants receiving LAIs (difference of 5.57 kgs; 95 % CI: 0.8–10.4; p = 0.02). Smoking was associated with greater weight gain (+2.3 kgs; 95 % CI: 0.9–3.6; p = 0.001). In conclusion, switching to aripiprazole or paliperidone did not prevent AiWG and LAIs showed no metabolic advantage relative to oral counterparts. The association between smoking and increased weight gain suggests smoking may represent a modifiable risk factor, warranting further investigation of smoking cessation as a potential intervention in AiWG management.

抗精神病药物引起的体重增加（AiWG）是一种常见的、沉重的不良反应。建议改用代谢风险较低的抗精神病药物，如阿立哌唑，但长期数据有限。长效注射剂（LAIs）可能比口服制剂提供代谢益处，但证据不一致。考虑给药途径和吸烟，我们比较了阿立哌唑和帕利哌酮对体重的长期影响。为此，我们分析了来自欧洲精神分裂症长效抗精神病药物试验（EULAST）的241名参与者（平均年龄31.0岁，32%为女性）的数据，这是一项多中心、开放标签、随机试验。参与者服用阿立哌唑（n = 119）或帕利哌酮（n = 122），口服或作为LAIs。体重评估持续了18个月。次要结局包括BMI和心脏代谢参数的变化。两组均表现出进行性体重增加：18个月后，体重增加4.7公斤（95% CI 3.0-6.5）。阿立哌唑组体重增加4.5公斤（95% CI 2.1-7.0），帕利潘酮组体重增加4.9公斤（95% CI 2.3-7.4）。临床显著体重增加（≥5%）分别发生在41.1%和58.7%的使用者中（NNH = 5; p = 0.06）。接受LAIs的参与者体重增加更为明显（差异为5.57公斤；95% CI: 0.8-10.4; p = 0.02）。吸烟与体重增加较多相关（+2.3 kg; 95% CI: 0.9-3.6; p = 0.001）。综上所述，改用阿立哌唑或帕利哌酮并不能预防AiWG，与口服同类药物相比，LAIs没有代谢优势。吸烟与体重增加之间的联系表明，吸烟可能是一个可改变的危险因素，因此有必要进一步研究戒烟作为AiWG管理的潜在干预措施。

{"title":"The effect of switching antipsychotics to aripiprazole versus paliperidone on weight/cardiometabolic parameters: 18-month follow-up findings from the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST)","authors":"Nini de Boer , Zara Vučko , Derek IJ. Koster , Marte van der Horst , Michael Davidson , Wiepke Cahn , Jurjen J. Luykx","doi":"10.1016/j.euroneuro.2025.11.014","DOIUrl":"10.1016/j.euroneuro.2025.11.014","url":null,"abstract":"<div><div>Antipsychotic-induced weight gain (AiWG) is a common, burdensome adverse effect. Switching to antipsychotics with lower metabolic risks, such as aripiprazole, is recommended, but long-term data is limited. Long-acting injectables (LAIs) may offer metabolic benefits over oral formulations, yet evidence is inconsistent. We compared long-term effects of switching to aripiprazole versus paliperidone on bodyweight, considering administration route and smoking. To that end, we analyzed data from 241 participants (mean age = 31.0; 32 % female) in the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST), a multicentre, open-label, randomized trial. Participants received aripiprazole (<em>n</em> = 119) or paliperidone (<em>n</em> = 122), orally or as LAIs. Bodyweight was assessed over 18 months. Secondary outcomes included changes in BMI and cardiometabolic parameters. Both groups showed progressive weight gain: over 18 months, body weight increased by 4.7 kgs (95 % CI 3.0–6.5). Weight gain was 4.5 kgs with aripiprazole (95 % CI 2.1–7.0) and 4.9 kgs with paliperidone (95 % CI 2.3–7.4). Clinically significant weight gain (≥5 %) occurred in 41.1 % and 58.7 % of users, respectively (NNH = 5; <em>p</em> = 0.06). Weight gain was more pronounced among participants receiving LAIs (difference of 5.57 kgs; 95 % CI: 0.8–10.4; <em>p</em> = 0.02). Smoking was associated with greater weight gain (+2.3 kgs; 95 % CI: 0.9–3.6; <em>p</em> = 0.001). In conclusion, switching to aripiprazole or paliperidone did not prevent AiWG and LAIs showed no metabolic advantage relative to oral counterparts. The association between smoking and increased weight gain suggests smoking may represent a modifiable risk factor, warranting further investigation of smoking cessation as a potential intervention in AiWG management.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 49-57"},"PeriodicalIF":6.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676738","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}

引用次数: 0

Exploring clozapine dose adjustment strategy in acute-phase reaction of inflammation based on free drug concentrations and Kpuu 基于游离药物浓度和Kpuu的炎症急性期反应氯氮平剂量调整策略探讨

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-11-26 DOI: 10.1016/j.euroneuro.2025.10.007

Yang Han , Jing Guo , Gaoyu Wang , Fan Wang , Wenyan Wang

引用次数: 0

Default mode network integrity across neuropsychiatric disorders and its relation to social dysfunction: A normative modelling approach 神经精神障碍的默认模式网络完整性及其与社会功能障碍的关系：一种规范的建模方法

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-11-26 DOI: 10.1016/j.euroneuro.2025.11.002

Simon Braak , Marianne Oldehinkel , Maarten Mennes , Tanja Su , Yolande Pijnenburg , Celso Arango , José Luis Ayuso-Mateos , Nic van der Wee , Gerard R. Dawson , Hugh M. Marston , Christian F. Beckmann , Martien J.H. Kas , Brenda W.J.H. Penninx

Structural and functional default mode network (DMN) alterations are common in neuropsychiatric disorders and may contribute transdiagnostically to social dysfunction. Normative modelling enables assessment of DMN alterations at the individual level. This study investigates whether individual deviations in cortical thickness, surface area, and between-network functional connectivity of the DMN differ between schizophrenia (SZ), major depressive disorder (MDD), Alzheimer’s disease (AD), and healthy controls (HC), and whether these deviations transdiagnostically relate to social dysfunction. Social dysfunction was assessed using a composite score from the Social Functioning Scale and De Jong-Gierveld Loneliness scale. Structural MRI data was collected for 329 participants (SZ=86, MDD=44, AD=82, HC=117) and resting-state fMRI data for 317 participants. Individual deviation scores of DMN integrity were computed by adapting existing normative models of cortical thickness (N = 58,836), surface area (N = 43,524), and between-network functional connectivity (N = 21,515). Extreme deviations were quantified using a z-threshold of ±1.96. DMN deviation scores were not transdiagnostically associated with social dysfunction across the sample (ps>0.05). AD patients had more extreme negative deviations in DMN cortical thickness than all other groups (ps<0.0001; z = -4.14 to -6.34) and fewer extreme positive deviations in DMN surface area relative to SZ and HC (ps<0.05; z = 2.10 to 2.71). For between-network functional connectivity of the DMN, AD and SZ patients had more extreme negative deviations than MDD and HC (ps<0.05; z = -2.09 to -3.54). To conclude, normative modelling reveals differences in individual deviations of DMN integrity between neuropsychiatric groups, but these deviations do not transdiagnostically relate to social dysfunction.

结构和功能默认模式网络（DMN）的改变在神经精神疾病中很常见，并可能导致社会功能障碍。规范建模可以在个人层面上评估DMN的变化。本研究探讨了精神分裂症（SZ）、重度抑郁症（MDD）、阿尔茨海默病（AD）和健康对照组（HC）在DMN皮质厚度、表面积和网络间功能连接方面的个体偏差是否存在差异，以及这些偏差是否与社会功能障碍相关。使用社会功能量表和De Jong-Gierveld孤独量表的综合评分来评估社会功能障碍。收集329名参与者（SZ=86， MDD=44， AD=82， HC=117）的结构MRI数据和317名参与者的静息状态fMRI数据。通过采用现有的皮质厚度（N = 58,836）、表面积（N = 43,524）和网络间功能连通性（N = 21,515）的规范模型，计算DMN完整性的个体偏差评分。极值偏差采用±1.96的z阈值进行量化。在整个样本中，DMN偏差评分与社交功能障碍没有跨诊断相关性（ps>0.05）。AD患者DMN皮质厚度的极端负向偏差高于其他各组（ps<0.0001; z = -4.14 ~ -6.34）， DMN表面积的极端正向偏差低于SZ和HC （ps<0.05; z = 2.10 ~ 2.71）。对于DMN的网络间功能连通性，AD和SZ患者比MDD和HC患者有更极端的负偏差（ps<0.05; z = -2.09 ~ -3.54）。综上所述，规范模型揭示了神经精神组之间DMN完整性个体偏差的差异，但这些偏差与社会功能障碍无关。

{"title":"Default mode network integrity across neuropsychiatric disorders and its relation to social dysfunction: A normative modelling approach","authors":"Simon Braak , Marianne Oldehinkel , Maarten Mennes , Tanja Su , Yolande Pijnenburg , Celso Arango , José Luis Ayuso-Mateos , Nic van der Wee , Gerard R. Dawson , Hugh M. Marston , Christian F. Beckmann , Martien J.H. Kas , Brenda W.J.H. Penninx","doi":"10.1016/j.euroneuro.2025.11.002","DOIUrl":"10.1016/j.euroneuro.2025.11.002","url":null,"abstract":"<div><div>Structural and functional default mode network (DMN) alterations are common in neuropsychiatric disorders and may contribute transdiagnostically to social dysfunction. Normative modelling enables assessment of DMN alterations at the individual level. This study investigates whether individual deviations in cortical thickness, surface area, and between-network functional connectivity of the DMN differ between schizophrenia (SZ), major depressive disorder (MDD), Alzheimer’s disease (AD), and healthy controls (HC), and whether these deviations transdiagnostically relate to social dysfunction. Social dysfunction was assessed using a composite score from the Social Functioning Scale and De Jong-Gierveld Loneliness scale. Structural MRI data was collected for 329 participants (SZ=86, MDD=44, AD=82, HC=117) and resting-state fMRI data for 317 participants. Individual deviation scores of DMN integrity were computed by adapting existing normative models of cortical thickness (<em>N</em> = 58,836), surface area (<em>N</em> = 43,524), and between-network functional connectivity (<em>N</em> = 21,515). Extreme deviations were quantified using a z-threshold of ±1.96. DMN deviation scores were not transdiagnostically associated with social dysfunction across the sample (<em>ps</em>>0.05). AD patients had more extreme negative deviations in DMN cortical thickness than all other groups (<em>ps<</em>0.0001; <em>z</em> = -4.14 to -6.34) and fewer extreme positive deviations in DMN surface area relative to SZ and HC (<em>ps</em><0.05; <em>z</em> = 2.10 to 2.71). For between-network functional connectivity of the DMN, AD and SZ patients had more extreme negative deviations than MDD and HC (<em>ps</em><0.05; <em>z</em> = -2.09 to -3.54). To conclude, normative modelling reveals differences in individual deviations of DMN integrity between neuropsychiatric groups, but these deviations do not transdiagnostically relate to social dysfunction.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"102 ","pages":"Pages 28-38"},"PeriodicalIF":6.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616607","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}

引用次数: 0

Corrigendum to “Does bipolar disorder accelerate cellular aging? A systematic review and meta-analysis of telomere length” [European Neuropsychopharmacology; 2025;99:21-30] “双相情感障碍会加速细胞衰老吗？”端粒长度的系统回顾和荟萃分析[欧洲神经精神药理学；2025年;99:21-30]

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-11-25 DOI: 10.1016/j.euroneuro.2025.11.004

Simge Uzman Ozbek , Kerime Akyol , Emre Bora

引用次数: 0