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Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis 影响哌唑嗪治疗PTSD患者噩梦和失眠疗效的因素——系统回顾和meta-回归分析。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2025.111253
Thaís Pereira Mendes , Brunno Guimarães Pereira , Evandro Silva Freire Coutinho , Marina S. Melani , Thomas C. Neylan , William Berger
Posttraumatic stress disorder (PTSD) is a debilitating condition affecting 5.7 % of the global population in their lifetime. There is a strong association between trauma-related nightmares and insomnia with higher rates of physical illness, mental distress, and suicide among PTSD patients. Prazosin, an α1-adrenergic antagonist, has shown mixed results in treating these sleep disturbances. This study aims to evaluate the effect of prazosin compared to placebo on insomnia, nightmares, and global PTSD symptoms, and to examine variables that might influence this effect. We conducted a meta-analysis and a novel meta-regression analysis of randomized clinical trials (RCTs) comparing prazosin to placebo in samples of patients with PTSD. Data sources were MEDLINE, EMBASE, Scopus, ISI Web of Science, and PTSD Pubs. Examined variables were age, gender, military/civilian status, prazosin dose, treatment duration, baseline symptom severity, use of antidepressants, use of benzodiazepines (BDZ), prevalence of depression, and alcohol use disorder. Ten RCTs with 648 patients were included. Analysis revealed prazosin significantly improved insomnia (SMD = −0.654, p = 0.043) and nightmares (SMD = −0.641, p = 0.025), but not overall PTSD symptoms (SMD = −0.428, p = 0.077). Unexpectedly, higher BDZ use was associated with greater improvement in insomnia (β = −0.046; p = 0.01) and PTSD severity (β = −0.037; p = 0.004). These findings suggest that prazosin effectively reduces insomnia and nightmares in PTSD patients. Benzodiazepine co-administration seems to enhance prazosin's efficacy, suggesting that the addition of prazosin might allow for a reduction of BDZ doses in these patients. Further research should empirically test the efficacy of prazosin alone versus prazosin combined with BDZ to confirm these findings.
创伤后应激障碍(PTSD)是一种使人衰弱的疾病,影响全球5.7% %的人口。在创伤后应激障碍患者中,与创伤相关的噩梦和失眠与较高的身体疾病、精神痛苦和自杀率之间存在着密切的联系。吡唑嗪是一种α - 1肾上腺素能拮抗剂,在治疗这些睡眠障碍方面显示出好坏参半的结果。本研究旨在评估哌唑嗪与安慰剂相比对失眠、噩梦和整体创伤后应激障碍症状的影响,并检查可能影响这种影响的变量。我们对PTSD患者样本中吡唑嗪与安慰剂的随机临床试验(rct)进行了荟萃分析和新颖的荟萃回归分析。数据来源为MEDLINE、EMBASE、Scopus、ISI Web of Science和PTSD bars。检查的变量包括年龄、性别、军人/平民身份、吡唑嗪剂量、治疗持续时间、基线症状严重程度、抗抑郁药的使用、苯二氮卓类药物(BDZ)的使用、抑郁症的患病率和酒精使用障碍。纳入10项随机对照试验,共648例患者。分析显示哌唑嗪显著改善失眠(SMD = -0.654,p = 0.043)和噩梦(SMD = -0.641,p = 0.025),而不是整体PTSD症状(SMD = -0.428,p = 0.077)。出乎意料的是,更多的BDZ使用与失眠的改善有关(β = -0.046;p = 0.01)和PTSD严重程度(β = -0.037; = 0.004页)。这些发现表明,哌唑嗪能有效减少PTSD患者的失眠和噩梦。苯二氮卓类药物的联合使用似乎增强了普拉唑嗪的疗效,这表明普拉唑嗪的加入可能会减少这些患者的BDZ剂量。进一步的研究应通过实证检验普拉唑嗪单独与普拉唑嗪联合BDZ的疗效,以证实这些发现。
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引用次数: 0
Chemistry to cognition: Therapeutic potential of (m-CF3-PhSe)2 targeting rats' striatum dopamine proteins in amphetamine dependence. 认知化学:(m-CF3-PhSe)2靶向大鼠纹状体多巴胺蛋白对苯丙胺依赖的治疗潜力。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 Epub Date: 2024-12-26 DOI: 10.1016/j.pnpbp.2024.111238
Mustafa Munir Mustafa Dahleh, Sabrina Grendene Muller, Isabella Pregardier Klann, Luiza Souza Marques, Jéssica Leandra da Rosa, Murilo Barboza Fontoura, Marilise Escobar Burger, Cristina Wayne Nogueira, Marina Prigol, Silvana Peterini Boeira, Hecson Jesser Segat

Amphetamine (AMPH) abuse represents a major global public health issue, highlighting the urgent need for effective therapeutic interventions to manage addiction caused by this psychostimulant. This study aimed to assess the potential of m-trifluoromethyl-diphenyldiselenide [(m-CF3-PhSe)2] in preventing the addictive effects induced by AMPH through targeting dopamine metabolism proteins. (m-CF3-PhSe)2 is of interest due to its demonstrated efficacy in mitigating opioid abuse, establishing it as a promising candidate for addiction treatment research. Initially, in silico studies examined the affinity of AMPH and (m-CF3-PhSe)2 for dopamine 1, 2, and 3 receptors (D1R, D2R, D3R), and dopamine transporter (DAT). In our experimental design, male Wistar rats were divided into four groups: I) Control; II) (m-CF3-PhSe)2; III) AMPH; IV) (m-CF3-PhSe)2 + AMPH. Animals were administered (m-CF3-PhSe)2 (0.1 mg/kg, by gavage) or canola oil (vehicle) 30 min before AMPH (4.0 mg/kg, i.p.) administration. Drug administration occurred for 8 days in the conditioned place preference (CPP) paradigm. Twenty-four hours after the last CPP conditioning section, preference for the drug-compartment was assessed, with anxiety-related effects and working memory were evaluated using the Y-maze test. Finally, animals were euthanized for striatal dissection to quantify D1R, D2R, D3R, and DAT levels in western blot. In silico findings suggest that (m-CF3-PhSe)2 may prevent AMPH activation in DAT, interacting with Asp46 and Phe319, preventing possible addictive effects of AMPH in DAT. In vivo results showed that (m-CF3-PhSe)2 attenuated AMPH effects, reducing preference for the drug-compartment in CPP test. Furthermore, (m-CF3-PhSe)2 prevented AMPH-induced anxiogenic effects in the elevated plus maze (EPM) test, similarly to light/dark test. No differences in locomotion or working memory were observed among the experimental groups in the Y-maze test. Ex vivo western blot analyses of the entire striatum indicates that (m-CF3-PhSe)2 prevented the AMPH-induced increase in D1R levels and decrease in D2R and DAT levels, with no changes in D3R levels. Overall, our study suggests that (m-CF3-PhSe)2 may interact with DAT sites similarly to AMPH, reducing drug-compartment preference and anxiogenic behaviors while maintaining dopaminergic metabolism proteins in the striatum, a key region involved in the onset and perpetuation of addiction.

滥用安非他明(AMPH)是一个重大的全球公共卫生问题,突出表明迫切需要有效的治疗干预措施来控制这种精神兴奋剂引起的成瘾。本研究旨在评估间三氟甲基二苯二烯[(m-CF3-PhSe)2]通过靶向多巴胺代谢蛋白预防AMPH诱导的成瘾性效应的潜力。(m-CF3-PhSe)2因其在减轻阿片类药物滥用方面的功效而引起人们的兴趣,使其成为成瘾治疗研究的有希望的候选药物。最初,计算机研究检测了AMPH和(m-CF3-PhSe)2对多巴胺1、2和3受体(D1R、D2R、D3R)和多巴胺转运蛋白(DAT)的亲和力。在我们的实验设计中,雄性Wistar大鼠分为四组:1)对照组;(二)(m-CF3-PhSe) 2;3)两栖的;(四)(m-CF3-PhSe) 2 + 两栖的。动物在AMPH(4.0 mg/kg, i.p.)给药前30 min给药(m-CF3-PhSe)2(0.1 mg/kg,灌胃)或菜籽油(载药)。在条件位置偏好(CPP)模式下,给药时间为8 天。最后一次CPP条件反射24小时后,评估药物室的偏好,使用y迷宫测试评估焦虑相关效应和工作记忆。最后,对动物实施安乐死,解剖纹状体,用western blot方法量化D1R、D2R、D3R和DAT水平。计算机实验结果表明(m-CF3-PhSe)2可能通过与Asp46和Phe319相互作用,阻止AMPH在DAT中的可能的成瘾性作用,从而阻止AMPH在DAT中的激活。体内实验结果显示(m-CF3-PhSe)2减弱了AMPH效应,降低了CPP试验中对药物室的偏好。此外,(m-CF3-PhSe)2在升高加迷宫(EPM)试验中阻止了amph诱导的焦虑效应,类似于光/暗试验。在y型迷宫测试中,各组小鼠在运动和工作记忆方面均无差异。整个纹状体的体外western blot分析表明,(m-CF3-PhSe)2阻止了amph诱导的D1R水平的升高和D2R和DAT水平的降低,而D3R水平没有变化。总的来说,我们的研究表明,(m-CF3-PhSe)2可能与与AMPH相似的DAT位点相互作用,减少药物室偏好和焦虑行为,同时维持纹状体中的多巴胺能代谢蛋白,纹状体是参与成瘾发生和持续的关键区域。
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引用次数: 0
Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review. 裸盖菇素作为抗抑郁药的临床和临床前证据。叙述性评论
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 Epub Date: 2025-01-06 DOI: 10.1016/j.pnpbp.2025.111249
Ines Erkizia-Santamaría, Igor Horrillo, J Javier Meana, Jorge E Ortega

In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance. Several preclinical studies have also been carried out to determine the long-term mechanism of action of this drug. In this sense, preclinical studies in naïve animals as well as in animal models of disease have shown somewhat discrepant results in conventional tests for assessment of depression- and anxiety-like phenotype in response to psilocybin, but overall suggest positive outcomes. Additionally, several valuable assays in rodent models have been developed over the years to elucidate the neurochemical correlates of serotonin 2A receptor (5HT2AR) activation in the brain, primary molecular target of psilocin. This review aims to provide a general overview of the current and most recent literature in the therapeutic potential of psilocybin through a description of clinical trials of psilocybin-assisted psychotherapy, and to showcase the scene in the up-to-date preclinical research. A detailed description of preclinical rodent models and experimental approaches that have been used to study the neurobiological and behavioural actions of psilocybin is provided, and potential therapeutic mechanisms of action are discussed.

在快速发展的致幻剂研究领域,裸盖菇素(及其活性代谢物裸盖菇素)已被认为是寻找神经精神疾病新疗法的有希望的候选者。临床试验表明,裸盖菇素在改善抑郁和焦虑症状方面具有巨大、快速和持久的作用。安全性被认为是有利的,毒性低,耐受性好。一些临床前研究也已进行,以确定该药物的长期作用机制。从这个意义上说,naïve动物和疾病动物模型的临床前研究显示,在评估裸盖菇素对抑郁和焦虑样表型的传统测试中,结果有些不同,但总体上显示出积极的结果。此外,多年来在啮齿动物模型中进行了一些有价值的实验,以阐明大脑中5 -羟色胺2 A受体(5HT2AR)激活的神经化学相关关系,这是psilocin的主要分子靶点。本综述旨在通过对裸盖菇素辅助心理治疗的临床试验的描述,对裸盖菇素治疗潜力的当前和最新文献进行概述,并展示最新临床前研究的场景。详细描述了用于研究裸盖菇素神经生物学和行为作用的临床前啮齿动物模型和实验方法,并讨论了潜在的治疗作用机制。
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引用次数: 0
The entorhinal cortex and cognitive impairment in schizophrenia: A comprehensive review 精神分裂症患者的内嗅皮质与认知障碍:一项综合综述。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111218
Kun Li , Liju Qian , Chenchen Zhang , Jiajia Zhang , Chuang Xue , Yuebing Zhang , Wei Deng
Schizophrenia, a severe mental illness characterized by cognitive impairment and olfactory dysfunction, remains an enigma with its pathological mechanism yet to be fully elucidated. The entorhinal cortex, a pivotal structure involved in numerous neural loop circuits related to olfaction, cognition, and emotion, has garnered significant attention due to its structural and functional abnormalities, which have been implicated in the pathogenesis of schizophrenia. This review focuses on the abnormal structural and functional changes in the entorhinal cortex in schizophrenia patients, as evidenced by neuroimaging, cellular biology, and genetic studies. These changes are posited to play a crucial role in the pathogenesis of cognitive impairment in schizophrenia. Furthermore, this review explores the various intervention strategies targeting the entorhinal cortex in current treatment modalities and proposes potential directions for future research endeavors, thereby providing a novel perspective on unraveling the complexity of neural mechanisms underlying schizophrenia and developing innovative therapeutic approaches for schizophrenia.
精神分裂症是一种以认知障碍和嗅觉功能障碍为特征的严重精神疾病,其病理机制仍是一个未解之谜。内嗅皮层是一个涉及许多与嗅觉、认知和情感相关的神经回路的关键结构,由于其结构和功能异常而引起了极大的关注,这与精神分裂症的发病机制有关。本文综述了神经影像学、细胞生物学和遗传学研究证明的精神分裂症患者内嗅皮层结构和功能的异常变化。这些变化被认为在精神分裂症认知障碍的发病机制中起着至关重要的作用。此外,本文还探讨了目前针对内嗅皮层的各种干预策略,并提出了未来研究的潜在方向,从而为揭示精神分裂症神经机制的复杂性和开发精神分裂症的创新治疗方法提供了一个新的视角。
{"title":"The entorhinal cortex and cognitive impairment in schizophrenia: A comprehensive review","authors":"Kun Li ,&nbsp;Liju Qian ,&nbsp;Chenchen Zhang ,&nbsp;Jiajia Zhang ,&nbsp;Chuang Xue ,&nbsp;Yuebing Zhang ,&nbsp;Wei Deng","doi":"10.1016/j.pnpbp.2024.111218","DOIUrl":"10.1016/j.pnpbp.2024.111218","url":null,"abstract":"<div><div>Schizophrenia, a severe mental illness characterized by cognitive impairment and olfactory dysfunction, remains an enigma with its pathological mechanism yet to be fully elucidated. The entorhinal cortex, a pivotal structure involved in numerous neural loop circuits related to olfaction, cognition, and emotion, has garnered significant attention due to its structural and functional abnormalities, which have been implicated in the pathogenesis of schizophrenia. This review focuses on the abnormal structural and functional changes in the entorhinal cortex in schizophrenia patients, as evidenced by neuroimaging, cellular biology, and genetic studies. These changes are posited to play a crucial role in the pathogenesis of cognitive impairment in schizophrenia. Furthermore, this review explores the various intervention strategies targeting the entorhinal cortex in current treatment modalities and proposes potential directions for future research endeavors, thereby providing a novel perspective on unraveling the complexity of neural mechanisms underlying schizophrenia and developing innovative therapeutic approaches for schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111218"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822896","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
Adiponectin, resistin, interleukin-4 and TGF-β2 levels in treatment resistant schizophrenia patients 治疗难治性精神分裂症患者的脂联素、抵抗素、白介素-4和TGF-β2水平。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111221
Andreas Karampas , George Leontaritis , Georgios Markozannes , Alexandros Asimakopoulos , Dimitra T. Archimandriti , Polyxeni Spyrou , Georgios Georgiou , Marios Plakoutsis , Konstantinos Kotsis , Paraskevi V. Voulgari , Petros Petrikis

Background

The aim of the present study was to measure adiponectin, resistin, interleukin-4 and TGF-β levels in first episode, treatment resistant patients with schizophrenia.

Methods

In total, fifty-three treatment-resistant patients were included in the study. In subgroups of these patients, we measured Interleukin-4 (IL-4), Tumor Growth Factor-β2 (TGF-β2), adiponectin and resistin levels at three different timepoints: in the drug-naïve state, after two rounds of treatment with different antipsychotic drugs for a total of 16 weeks and, after clozapine treatment for 12 weeks.

Results

TGF-β2 and adiponectin levels decreased after treatment with olanzapine and risperidone, while resistin and IL-4 levels did not differ significantly.Comparing the levels of the aforementioned cytokines before the initiation and after clozapine treatment, we found an even greater decrease in adiponectin levels while resistin and IL-4 levels significantly increased and TGF-β2 levels did not differ significantly.

Conclusions

We report elevated resistin and IL-4 levels and decreased adiponectin levels in first-episode, treatment resistant schizophrenia patients after clozapine treatment. These findings may be at least partly due to the anti-inflammatory action of clozapine, although sub-clinical metabolic disturbances may also have played a role as far as resistin and adiponectin are concerned. In a subgroup of these patients we report reduced TGF-β2 and adiponectin levels after two unsuccessful trials with risperidone and olanzapine comparing them with the ones of the same subgroup in the drug-naïve phase.
背景:本研究的目的是测定首次发作、治疗抵抗的精神分裂症患者的脂联素、抵抗素、白细胞介素-4和TGF-β水平。方法:共纳入53例治疗耐药患者。在这些患者的亚组中,我们测量了三个不同时间点的白细胞介素-4 (IL-4)、肿瘤生长因子-β2 (TGF-β2)、脂联素和抵抗素水平:在drug-naïve状态下,在两轮不同抗精神病药物治疗后共16 周,在氯氮平治疗后12 周。结果:奥氮平、利培酮治疗后TGF-β2、脂联素水平降低,抵抗素、IL-4水平差异无统计学意义。对比氯氮平治疗前后上述细胞因子水平,我们发现脂联素水平下降幅度更大,而抵抗素和IL-4水平显著升高,TGF-β2水平无显著差异。结论:我们报告了氯氮平治疗后首次发作的难治性精神分裂症患者抵抗素和IL-4水平升高,脂联素水平降低。这些发现可能至少部分是由于氯氮平的抗炎作用,尽管亚临床代谢紊乱也可能在抵抗素和脂联素方面起作用。在这些患者的一个亚组中,我们报告了在使用利培酮和奥氮平进行两次不成功的试验后,与drug-naïve期的同一亚组比较,TGF-β2和脂联素水平降低。
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引用次数: 0
Systemic heterogeneity in autism spectrum disorder revealed by individualized structural covariance network analysis 个体化结构协方差网络分析揭示自闭症谱系障碍的系统异质性。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111224
Qiuyue Zhang , Xi Yang , Jianfeng Qiu , Weizhao Lu

Background and purpose

Autism spectrum disorder (ASD) is clinically heterogeneous, and resent neuroimaging studies have shown the presence of brain structural heterogeneity in ASD. However, there is currently a lack of evidence for systemic level brain structural heterogeneity. This study aimed to reveal the heterogeneity of brain structural changes at the systemic level in ASD patients through individual differential structural covariance network (IDSCN) analysis.

Materials and methods

We included 803 neurotypical controls (NCs) and 650 ASD patients from 24 sites and the corresponding structural magnetic resonance and clinical data. 516 ASD patients were used as training group, and 134 ASD patients were selected as an independent validation group. In the training group, we constructed IDSCN for each ASD patient, identified differentiated structural covariance edges, and resolved systemic heterogeneity using K-means clustering algorithm. We then conducted statistical analyses on the demographical and clinical data of the ASD subgroups, and performed correlation analyses between structural covariance edges and clinical profiles within each ASD subgroup. We also tested the reliability of the IDSCN in the validation group.

Results

The results of the training and validation groups were similar, revealing two subtypes of ASD, with 17 brain connections showing differences between the two subtypes. There were differences in clinical profiles between the two subgroups in restricted repetitive behavior score from autism diagnostic interview-revised (ADI_RRB_TOTAL), total score of autism diagnostic observation schedule (ADOS), social interaction score from ADOS and stereotyped behaviors score from ADOS. In both datasets, we also found a significant correlation between ADI_RRB_TOTAL scale and the Z-score for edges between the bilateral ventral tegmental area (VTA) and between the left VTA and right substantia nigra pars compacta.

Conclusion

ASD exhibited brain structural heterogeneity at the systemic level, mainly involving nucleus in the subcortical regions and brainstem, which can affect RRB in ASD patients. The two subtypes discovered in this study have the potential to be applied in precise diagnosis and treatment of the disorder.
背景与目的:自闭症谱系障碍(Autism spectrum disorder, ASD)具有临床异质性,近期神经影像学研究显示ASD患者存在脑结构异质性。然而,目前缺乏系统性水平脑结构异质性的证据。本研究旨在通过个体差异结构协方差网络(IDSCN)分析,揭示ASD患者脑结构变化在系统水平上的异质性。材料和方法:我们纳入了来自24个部位的803例神经正常对照(nc)和650例ASD患者,并收集了相应的结构磁共振和临床资料。516例ASD患者作为训练组,134例ASD患者作为独立验证组。在训练组中,我们为每个ASD患者构建了IDSCN,识别了差异化的结构协方差边缘,并使用K-means聚类算法解决了系统异质性。然后,我们对ASD亚组的人口学和临床资料进行统计分析,并对每个ASD亚组的结构协方差边缘与临床资料进行相关性分析。我们还在验证组中测试了IDSCN的可靠性。结果:训练组和验证组的结果相似,揭示了ASD的两种亚型,17个脑连接显示了两种亚型之间的差异。两亚组在自闭症诊断访谈修正版限制性重复行为评分(ADI_RRB_TOTAL)、自闭症诊断观察量表总分(ADOS)、社交互动评分(ADOS)和刻板印象行为评分(ADOS)的临床特征上存在差异。在这两个数据集中,我们还发现ADI_RRB_TOTAL量表与双侧腹侧被盖区(VTA)之间以及左侧VTA与右侧致密黑质之间边缘的Z-score之间存在显著相关性。结论:ASD在系统水平上表现出大脑结构的异质性,主要累及皮质下核和脑干,这可能影响ASD患者的RRB。本研究中发现的两种亚型有可能应用于该疾病的精确诊断和治疗。
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引用次数: 0
Natural polyphenols as therapeutic candidates for mitigating neuropsychiatric symptoms in post-traumatic stress disorder: Evidence from preclinical studies 天然多酚作为减轻创伤后应激障碍神经精神症状的治疗候选者:来自临床前研究的证据
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111230
Payman Raise-Abdullahi , Mehrnaz Rezvani , Fatemeh Yousefi , Sadaf Rahmani , Morvarid Meamar , Ehsan Raeis-Abdollahi , Abbas Ali Vafaei , Hamed Rashidipour , Ali Rashidy-Pour
Post-traumatic stress disorder (PTSD) is a challenging mental health condition that affects millions of people worldwide after they experience traumatic events. The current medications often do not fully address the wide range of PTSD symptoms or the underlying brain mechanisms, prompting the need to explore new treatments. Polyphenols, which are natural compounds found in many plant-based foods, have gained interest due to their brain-protective, anti-inflammatory, and antioxidant benefits. This review looks at how polyphenols might help treat PTSD by influencing important brain pathways related to the disorder. We explored how polyphenols affect the stress-response system, fear-related memories, brain chemicals, and inflammation. Specifically, we discuss how compounds like resveratrol, curcumin, green tea extract, and quercetin can balance stress hormones, help reduce fear memories, regulate brain chemicals, and decrease brain inflammation. Studies with animals have provided insights into how these compounds might work to ease PTSD symptoms. Based on the preclinical studies, the present review suggests that polyphenols could be a valuable addition or alternative to current PTSD treatments. However, more research is needed to confirm these findings and to determine the best ways to use polyphenols in treating PTSD.
创伤后应激障碍(PTSD)是一种具有挑战性的精神健康状况,在经历创伤性事件后影响着全世界数百万人。目前的药物往往不能完全解决创伤后应激障碍的广泛症状或潜在的大脑机制,这促使人们需要探索新的治疗方法。多酚是一种存在于许多植物性食物中的天然化合物,由于其对大脑的保护、抗炎和抗氧化作用而引起了人们的兴趣。这篇综述着眼于多酚如何通过影响与PTSD相关的重要脑通路来帮助治疗PTSD。我们探索了多酚如何影响压力反应系统、与恐惧相关的记忆、大脑化学物质和炎症。具体来说,我们讨论了像白藜芦醇、姜黄素、绿茶提取物和槲皮素这样的化合物如何平衡压力激素,帮助减少恐惧记忆,调节大脑化学物质,减少大脑炎症。对动物的研究为这些化合物如何缓解创伤后应激障碍症状提供了见解。基于临床前研究,目前的综述表明,多酚可能是目前PTSD治疗的一种有价值的补充或替代方法。然而,需要更多的研究来证实这些发现,并确定使用多酚治疗创伤后应激障碍的最佳方法。
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引用次数: 0
Alterations in white matter microstructure in bipolar disorder patients with and without psychosis 双相情感障碍伴和不伴精神病患者白质微结构的改变。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111229
Xiuli Wang , Xipeng Long , Bochao Cheng , Yuan Cao , Di Kong , Baolin Wu , Hongsheng Xie , Ziru Zhao , Neil Roberts , Nenghan Zhang , Zhiyun Jia

Objective

The overlap of affective disturbance and psychosis considerably makes it complex to determine the etiology of bipolar disorder (BD) and develop targeted interventions. The present study aimed to determine the white matter microstructural alterations that distinguish between BD with psychosis (BDP) and BD with no psychosis (BDNP) to identify patients who may specifically benefit from appropriately effective treatments.

Methods

Diffusion-weighted magnetic resonance images were acquired from 38 participants with BDP, 52 participants with BDNP and 70 healthy controls (HCs). The indices of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were computed and compared among the three groups via tract-based spatial statistics (TBSS).

Results

Analysis of covariance (ANCOVA) revealed the main effects of group on the FA, MD and RD values of the forceps minor (FMI) of the corpus callosum, right anterior thalamic radiation (ATR), and left corticospinal tract (CST). Post hoc analysis revealed that BDP patients had lower FA value in the FMI than HCs did, as well as lower FA and higher RD values in the FMI than BDNP patients did, whereas BDNP patients had lower FA and MD values in the right ATR, as well as higher FA and lower RD values in the left CST than HCs did.

Conclusion

These findings provide further insights into the specific neurobiological mechanisms that underlie the presence of psychosis in BD patients and represent potential objective biomarkers for differentiating between BDP and BDNP.
目的:情感障碍与精神疾病的重叠使得确定双相情感障碍(BD)的病因和制定有针对性的干预措施变得非常复杂。本研究旨在确定区分双相障碍合并精神病(BDP)和双相障碍合并非精神病(BDNP)的白质微结构改变,以确定可能从适当有效治疗中获益的患者。方法:对38例BDP患者、52例BDNP患者和70例健康对照(hc)进行弥散加权磁共振成像。采用基于束的空间统计方法(TBSS)计算并比较各组的分数各向异性(FA)、平均扩散系数(MD)、径向扩散系数(RD)和轴向扩散系数(AD)。结果:协方差分析(ANCOVA)揭示了各组对胼胝体小腹(FMI) FA、MD和RD值、右侧丘脑前辐射(ATR)和左侧皮质脊髓束(CST)的主要影响。事后分析显示,BDP患者在FMI的FA值低于hcc患者,FMI的FA值低于BDNP患者,FMI的RD值高于BDNP患者,而BDNP患者在右侧ATR的FA和MD值低于hcc患者,左侧CST的FA和RD值高于hcc患者。结论:这些发现进一步揭示了BD患者精神病存在的特定神经生物学机制,并为区分BDP和BDNP提供了潜在的客观生物标志物。
{"title":"Alterations in white matter microstructure in bipolar disorder patients with and without psychosis","authors":"Xiuli Wang ,&nbsp;Xipeng Long ,&nbsp;Bochao Cheng ,&nbsp;Yuan Cao ,&nbsp;Di Kong ,&nbsp;Baolin Wu ,&nbsp;Hongsheng Xie ,&nbsp;Ziru Zhao ,&nbsp;Neil Roberts ,&nbsp;Nenghan Zhang ,&nbsp;Zhiyun Jia","doi":"10.1016/j.pnpbp.2024.111229","DOIUrl":"10.1016/j.pnpbp.2024.111229","url":null,"abstract":"<div><h3>Objective</h3><div>The overlap of affective disturbance and psychosis considerably makes it complex to determine the etiology of bipolar disorder (BD) and develop targeted interventions. The present study aimed to determine the white matter microstructural alterations that distinguish between BD with psychosis (BDP) and BD with no psychosis (BDNP) to identify patients who may specifically benefit from appropriately effective treatments.</div></div><div><h3>Methods</h3><div>Diffusion-weighted magnetic resonance images were acquired from 38 participants with BDP, 52 participants with BDNP and 70 healthy controls (HCs). The indices of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were computed and compared among the three groups via tract-based spatial statistics (TBSS).</div></div><div><h3>Results</h3><div>Analysis of covariance (ANCOVA) revealed the main effects of group on the FA, MD and RD values of the forceps minor (FMI) of the corpus callosum, right anterior thalamic radiation (ATR), and left corticospinal tract (CST). Post hoc analysis revealed that BDP patients had lower FA value in the FMI than HCs did, as well as lower FA and higher RD values in the FMI than BDNP patients did, whereas BDNP patients had lower FA and MD values in the right ATR, as well as higher FA and lower RD values in the left CST than HCs did.</div></div><div><h3>Conclusion</h3><div>These findings provide further insights into the specific neurobiological mechanisms that underlie the presence of psychosis in BD patients and represent potential objective biomarkers for differentiating between BDP and BDNP.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111229"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883652","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
Abnormal ReHo and ALFF values in drug-naïve depressed patients with suicidal ideation or attempts: Evidence from the REST-meta-MDD consortium drug-naïve有自杀意念或企图的抑郁症患者ReHo和ALFF值异常:来自REST-meta-MDD联盟的证据
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111210
Guowei Luo , Jian Zhou , Luyu Liu , Xinran Song , Min Peng , Xiangyang Zhang , the REST-meta-MDD Consortium

Background

The assessment of suicide risk in patients with major depressive disorder (MDD) is somewhat subjective in clinical diagnosis and may lead to diagnostic bias and serious consequences. Therefore, the aim of this study was to determine whether MDD patients with suicidal ideation or suicide attempts exhibited local brain functional synchrony and spontaneous activity intensity, thus providing certain imaging basis for suicide assessment.

Methods

This study was conducted using ReHo and ALFF analyses on 213 first episode drug-naïve MDD patients from the REST-meta-MDD consortium. All patients were categorized into MDD with SI or SA group and MDD without SI and SA. A voxel-based two-sample t-test was then used to identify brain regions with significant differences in ReHo or ALFF values. Finally, Reho or ALFF values of those brain regions in MDD with SI or SA group were extracted for correlation analysis with suicide severity.

Results

Compared with MDD patients without SI or SA, MDD patients with SI or SA had increased ReHo in the triangular part of left inferior frontal gyrus, orbital part of right inferior frontal gyrus and right precuneus gyrus, and increased ALFF in the middle occipital gyrus. All of these brain region characteristics were positively correlated with suicide severity on the HAMD 3th item score and HAMD 9th item score.

Conclusion

Our findings suggest that abnormalities of regional spontaneous brain activity were found in IFG, precuneus gyrus, and MOG among MDD patients with suicidal thoughts or attempts, which provides a reliable imaging basis for identifying and preventing suicide.
背景:重度抑郁障碍(MDD)患者自杀风险评估在临床诊断中存在一定的主观性,可能导致诊断偏差和严重后果。因此,本研究的目的是确定有自杀意念或自杀企图的MDD患者是否表现出局部脑功能同步性和自发活动强度,从而为自杀评估提供一定的影像学依据。方法:本研究对来自REST-meta-MDD联盟的213例首发drug-naïve MDD患者进行ReHo和ALFF分析。将所有患者分为伴有SI或SA的MDD组和不伴有SI和SA的MDD组。然后使用基于体素的双样本t检验来识别ReHo或ALFF值存在显著差异的大脑区域。最后提取MDD合并SI或SA组脑区Reho或ALFF值与自杀严重程度的相关性分析。结果:与未伴SI或SA的MDD患者相比,伴SI或SA的MDD患者左侧额下回三角区、右侧额下回眶区和右侧楔前回的ReHo升高,枕中回ALFF升高。这些脑区特征与自杀严重程度在HAMD第3项和第9项得分上呈显著正相关。结论:我们的研究结果提示MDD患者有自杀念头或企图时,IFG、楔前回、MOG等区域自发性脑活动出现异常,为识别和预防自杀提供了可靠的影像学依据。
{"title":"Abnormal ReHo and ALFF values in drug-naïve depressed patients with suicidal ideation or attempts: Evidence from the REST-meta-MDD consortium","authors":"Guowei Luo ,&nbsp;Jian Zhou ,&nbsp;Luyu Liu ,&nbsp;Xinran Song ,&nbsp;Min Peng ,&nbsp;Xiangyang Zhang ,&nbsp;the REST-meta-MDD Consortium","doi":"10.1016/j.pnpbp.2024.111210","DOIUrl":"10.1016/j.pnpbp.2024.111210","url":null,"abstract":"<div><h3>Background</h3><div>The assessment of suicide risk in patients with major depressive disorder (MDD) is somewhat subjective in clinical diagnosis and may lead to diagnostic bias and serious consequences. Therefore, the aim of this study was to determine whether MDD patients with suicidal ideation or suicide attempts exhibited local brain functional synchrony and spontaneous activity intensity, thus providing certain imaging basis for suicide assessment.</div></div><div><h3>Methods</h3><div>This study was conducted using ReHo and ALFF analyses on 213 first episode drug-naïve MDD patients from the REST-meta-MDD consortium. All patients were categorized into MDD with SI or SA group and MDD without SI and SA. A voxel-based two-sample <em>t</em>-test was then used to identify brain regions with significant differences in ReHo or ALFF values. Finally, Reho or ALFF values of those brain regions in MDD with SI or SA group were extracted for correlation analysis with suicide severity.</div></div><div><h3>Results</h3><div>Compared with MDD patients without SI or SA, MDD patients with SI or SA had increased ReHo in the triangular part of left inferior frontal gyrus, orbital part of right inferior frontal gyrus and right precuneus gyrus, and increased ALFF in the middle occipital gyrus. All of these brain region characteristics were positively correlated with suicide severity on the HAMD 3th item score and HAMD 9th item score.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that abnormalities of regional spontaneous brain activity were found in IFG, precuneus gyrus, and MOG among MDD patients with suicidal thoughts or attempts, which provides a reliable imaging basis for identifying and preventing suicide.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111210"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781676","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
Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy. 比较迷幻药和二甲双胍作为帕金森痴呆症的神经保护剂:对证据和疗效的系统回顾。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 Epub Date: 2024-09-30 DOI: 10.1016/j.pnpbp.2024.111155
Randall D Ordovich-Clarkson, Maurice Jabbour, Daniel Arteaga Pelayo, Daniel Lara, Sebastian La Croix, Macie Mumman, Shoshanah Stukas, Reagan Anderson, David Meraz, Anthony Bangura, Brooklyn Anderson, Luke Bamrud, Caleb Blake

Background & aim: Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD.

Methods: The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects.

Results: The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation.

Conclusion: Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.

背景和目的:帕金森病(PD)的治疗方法基本未变,主要侧重于通过激活多巴胺能通路来缓解症状。目前,还没有经证实的预防帕金森病的方法。本系统综述旨在比较两种不同的化合物--二甲双胍(MTF)和迷幻药--作为预防帕金森氏症的潜在疗法:作者进行了一项系统性综述,重点关注在细胞和动物模型上测试这两种化合物的主要研究,以确定它们是否具有任何神经保护或神经可塑性作用:综述结果发现,MTF 可通过多种机制阻止帕金森病等疾病的发展,包括减少线粒体水平的氧化应激,从而减少与 α-突触核蛋白相关的损伤。另一方面,迷幻药可能会通过激活血清素能通路,特别是激活 5-HT2A 受体,增加受损神经元的修复,最终增加脑源性神经营养因子(BDNF)的释放,减少α-突触核蛋白的积累:本研究的意义包括需要进一步研究MTF的标签外使用,以及进一步研究5-羟色胺能化合物,如治疗和预防神经退行性疾病的迷幻药。
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引用次数: 0
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Progress in Neuro-Psychopharmacology & Biological Psychiatry
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