European Neuropsychopharmacology最新文献_第10页

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。

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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。

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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。

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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。

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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

Three shades of gloom: investigating the genetic background of current depressive symptoms associated with different severity of current stress exposure in a general population 忧郁的三种阴影：在一般人群中调查与当前压力暴露的不同严重程度相关的当前抑郁症状的遗传背景。

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-11-23 DOI: 10.1016/j.euroneuro.2025.11.005

Berta Erdelyi-Hamza , Dora Torok , Nora Eszlari , Gyorgy Bagdy , Gabriella Juhasz , Xenia Gonda

Presence or absence of recent stress preceding emergence of depressive symptoms may play a distinctive role in determining underlying etiological processes, explaining part of the significant heterogeneity characteristic of depression. Separately studying genetic associations of depressive symptoms appearing following, or independently of stress may help disentangle the genetic background of distinct depression subtypes in a general population sample. We included UK Biobank data (application number 1602) of nearly 120,000 subjects, and conducted three separate genome-wide analyses focusing on current depressive symptoms in three groups based on level of stress exposure in the past two years and analysed results from the aspect of neurobiological relationships between genetic variation and brain function. GWAS results were evaluated on SNP and gene-set levels. Heritability estimation revealed 10.4 %, 8.8 % and 5.1 % heritability in major-stress, minor-stress and no-stress groups, respectively. In the no-stress group 22, in the minor-stress group 22, and in the major-stress group 14 SNPs with suggestive significance were identified, with notable differences in the specific genes and processes implicated in the three groups. In the no-stress group marked association with long non-coding and micro-RNA emerged whereas in the major-stress group results implicate involvement of circadian genes and immunological pathways. Our findings reveal marked differences in the genetic underpinnings of depressive symptoms following exposure to different levels of recent stress, arguing that etiological heterogeneity of depression should be considered in both research and clinical applications, and pave the way of distinguishing between subtypes of depression based on the etiological contribution of stress.

在出现抑郁症状之前是否存在近期的压力可能在确定潜在的病因过程中起着独特的作用，部分解释了抑郁症的显著异质性特征。单独研究在压力之后出现的抑郁症状的遗传关联，或独立研究压力可能有助于解开一般人群样本中不同抑郁亚型的遗传背景。我们纳入了近120,000名受试者的UK Biobank数据（申请号1602），并根据过去两年的压力暴露水平，对三组患者当前的抑郁症状进行了三次独立的全基因组分析，并从遗传变异与脑功能之间的神经生物学关系方面分析了结果。GWAS结果在SNP和基因集水平上进行评估。遗传率估计显示，大、小和无应激组的遗传率分别为10.4%、8.8%和5.1%。在无应激组22个、轻度应激组22个和重度应激组中，鉴定出14个具有暗示意义的snp，在三组中涉及的特定基因和过程存在显著差异。在无应激组中，出现了与长链非编码和微rna的显著关联，而在大应激组中，结果暗示了昼夜节律基因和免疫途径的参与。我们的研究结果揭示了暴露于不同水平的近期压力后抑郁症状的遗传基础的显著差异，认为在研究和临床应用中都应考虑抑郁症的病因异质性，并为基于压力的病因贡献区分抑郁症亚型铺平了道路。

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引用次数: 0

Activating β2-adrenergic receptor is a potential cross-disease therapeutic strategy for Alzheimer’s disease, obesity and type 2 diabetes 激活β2-肾上腺素能受体是治疗阿尔茨海默病、肥胖症和2型糖尿病的一种潜在的跨疾病治疗策略

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-11-22 DOI: 10.1016/j.euroneuro.2025.11.006

Ruonan Zhou , Mengli Luo , Jiaxin Lv , Wenbin Shang

引用次数: 0

Reply to the commentary on “Efficacy of pharmacogenetic (PGx)-guided antidepressant treatment on functional outcomes and quality of life in adults with anxiety and affective disorders: A systematic review and meta-analysis” 回复“药物遗传学（PGx）指导的抗抑郁治疗对焦虑和情感障碍成人的功能结局和生活质量的疗效：系统回顾和荟萃分析”的评论。

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-11-22 DOI: 10.1016/j.euroneuro.2025.11.003

Natalia E. Fares-Otero , Monika Budde , Jonathan Laatsch , Mathias Harrer , Teuntje Pelgrim , Alexandra Philipsen , Urs Heilbronner , Eduard Vieta , Roos van Westrhenen , PSY-PGx Consortium

引用次数: 0

Patterns, predictors and outcomes of trajectories for subjective quality of life in patients with early psychosis: 12-year follow-up of the randomized controlled trial on extended early intervention 早期精神病患者主观生活质量轨迹的模式、预测因素和结果：延长早期干预的12年随访随机对照试验

IF 6.7 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2025-11-21 DOI: 10.1016/j.euroneuro.2025.10.006

Ryan Sai Ting Chu , Crystal Nok Yiu Yau , Chris Chit Sze Fung , Vivian Shi Cheng Fung , Janet Hiu Ching Lei , Gabbie Hou Sem Wong , Sherry Kit Wa Chan , Edwin Ho-Ming Lee , Christy Lai-Ming Hui , Eric Yu-Hai Chen , Wing-Chung Chang

Evidence has underscored clinical significance of subjective quality of life (SQoL) as a key therapeutic goal for early psychosis. However, the patterns, predictors and outcomes of SQoL trajectories over long-term follow-up in early psychosis have not been explored. We conducted a 12-year follow-up of the randomized-controlled-trial on extended early intervention for first-episode psychosis with an aim to identify distinct trajectories of the SQoL, their baseline predictors and relationships with 12-year outcomes. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive SQoL trajectories based on 36-Item Short Form Health Survey (SF-36) mental-health component summary scores over 12-year follow-up. Participants who completed SF-36 at three or more time points, including baseline, and 1-, 2-, 3- and 12-year follow-up, were included in the analysis, resulting in 144 patients. Our results identified three distinct trajectories, including high-stable class (36.8 %, n = 53), moderate-improving class (40.3 %, n = 58) and low-stable class (22.9 %, n = 33). Patients in high-stable class had less severe depressive symptoms at baseline than those in moderate-improving class, and less severe positive, negative and depressive symptoms at baseline compared to patients in low-stable class. Additionally, patients with high-stable trajectory exhibited higher rate of personal recovery and lower depressive symptom severity at 12-year follow-up relative to patients with low-stable trajectory. In conclusion, approximately one-fourths of patients displayed consistently poor SQoL over 12 years. Depressive symptoms represent a major determinant of SQoL trajectories, indicating the need to optimize treatment for depression in early psychosis to enhance SQoL outcome.

证据强调了主观生活质量（SQoL）作为早期精神病的关键治疗目标的临床意义。然而，长期随访的早期精神病患者sql轨迹的模式、预测因素和结果尚未得到探讨。我们进行了一项为期12年的随机对照试验，对首发精神病的延长早期干预进行了随访，目的是确定SQoL的不同轨迹、基线预测因子及其与12年预后的关系。评估了病前调整、疾病特征、症状严重程度、功能和治疗概况。在随访12年的36项简短健康调查（SF-36）心理健康成分总结得分基础上，采用潜在生长混合模型推导sql轨迹。在三个或更多时间点完成SF-36的参与者，包括基线，1年，2年，3年和12年的随访，被纳入分析，共有144例患者。我们的研究结果确定了三种不同的轨迹，包括高稳定型（36.8%,n = 53）、中度改善型（40.3%,n = 58）和低稳定型（22.9%,n = 33）。高稳定级患者在基线时抑郁症状的严重程度低于中度改善级患者，在基线时阳性、阴性和抑郁症状的严重程度低于低稳定级患者。此外，在12年的随访中，高稳定轨迹的患者表现出较高的个人恢复率和较低的抑郁症状严重程度。总之，大约四分之一的患者在12年的时间里一直表现出较差的生存质量。抑郁症状是SQoL轨迹的主要决定因素，表明需要优化早期精神病抑郁症的治疗，以提高SQoL结果。

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引用次数: 0