Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献_第9页

Correlation of auditory network hyperconnectivity with P3a amplitude and set-shifting in individuals with autism spectrum disorder 自闭症谱系障碍患者听觉网络超连通性与P3a振幅和集移位的相关性

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-11-03 DOI: 10.1016/j.pnpbp.2025.111552

Yi-Ling Chien , Chi Chen , Ming Hsien Hsieh , Susan Shur-Fen Gau

Backgrounds

Individuals with autism spectrum disorder (ASD) exhibit aberrant intrinsic connectivity and altered mismatch negativity responses. Both mismatch negativity and intrinsic connectivity are associated with pre-attentive mechanisms. However, the potential link between mismatch negativity and alterations in intrinsic connectivity in ASD has not been thoroughly explored. This study aimed to investigate the resting-state functional connectivity of the auditory network in ASD and examine its association with mismatch negativity and set-shifting performance.

Methods

This study recruited 75 ASD participants and 50 neurotypical controls (NAC). All participants underwent clinical assessments, mismatch negativity on the oddball paradigm, and resting-state functional MRI. We compared the resting-state brain connectivity of the auditory network between ASD and NAC using independent component analysis. We then examined correlations between this connectivity, mismatch negativity, and executive function measured by the Intra-Extra Dimensional Set Shift task (IED).

Results

The ASD group demonstrated resting-state hyperconnectivity between the auditory network and the regions of the posterior cingulate gyrus, left inferior frontal gyrus, right angular gyrus, and right caudate/thalamus. In ASD, the connectivity between the auditory network and the left inferior frontal gyrus was positively correlated with higher P3a amplitude and a greater number of completed stages on the IED task, indicating enhanced cognitive flexibility.

Conclusion

Findings suggest heightened functional connectivity between the auditory network and various brain regions in ASD. Specifically, connectivity to the left inferior frontal gyrus at rest may predict enhanced attention reorientation and cognitive flexibility in autistic individuals. Further research is warranted to elucidate these relationships.

背景：自闭症谱系障碍（ASD）个体表现出异常的内在连通性和改变的错配负性反应。失配消极性和内在连通性都与注意前机制有关。然而，失配负性与ASD内在连通性改变之间的潜在联系尚未得到充分探讨。本研究旨在探讨ASD患者静息状态听觉网络的功能连通性，并探讨其与失配负性和集移表现的关系。方法：本研究招募75名ASD参与者和50名神经正常对照组（NAC）。所有参与者都进行了临床评估，在古怪范式上进行了失配阴性，并进行了静息状态功能MRI。我们使用独立分量分析比较了ASD和NAC的静息状态听觉网络连接。然后，我们研究了这种连通性、错配负性和执行功能之间的相关性，这些关系是通过内部额外维度集合转移任务（IED）测量的。结果：ASD组静息状态下听觉网络与扣带回后区、左侧额下回、右侧角回和右侧尾状/丘脑区域之间存在超连通性。在ASD中，听觉网络与左侧额下回之间的连通性与更高的P3a振幅和更多的IED任务完成阶段呈正相关，表明认知灵活性增强。结论：研究结果表明，ASD患者听觉网络与大脑各区域之间的功能连通性增强。具体来说，休息时与左额下回的连通性可能预示着自闭症患者注意力重新定向和认知灵活性的增强。需要进一步的研究来阐明这些关系。

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引用次数: 0

Global and regional morphometric similarity in insomnia with objective short sleep duration 客观睡眠时间短的失眠症的整体和局部形态学相似性。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-11-03 DOI: 10.1016/j.pnpbp.2025.111551

Zhangwei Lv , Haobo Zhang , Yuhan Fan , Yuanyuan Chen , Yuxian Wei , Xu Lei

Insomnia disorder is a heterogeneous psychiatric condition characterized by differences in psychological traits and neurobiological mechanisms, necessitating precise phenotyping for targeted interventions. This clinical control study, part of a two-year multicenter research project, examined differences in sleep parameters, psychological characteristics, and morphometric similarity (MS) patterns between insomnia phenotypes classified by objective total sleep time (oTST). The study enrolled 997 adult patients with insomnia disorder, of whom 270 underwent MRI scanning. Participants were categorized into insomnia with objective normal sleep duration (INSD) and insomnia with objective short sleep duration (ISSD) based on oTST measured using a wearable forehead sleep recorder. Primary outcomes included sleep parameters (e.g., wake after sleep onset and rapid eye movement percentage), psychological characteristics (e.g., rumination), and MS patterns assessed through MS mapping. Results showed that the ISSD phenotype showed shorter wake after sleep onset, lower eye movement sleep (REM) percentage, and higher non-REM stage 2 percentage, whereas the INSD phenotype exhibited greater sleep perception bias and more fragmented sleep. Additionally, ISSD showed higher global MS and distinct regional MS patterns, including lower MS in the right middle temporal gyrus and higher MS in the right postcentral gyrus. It also exhibited decoupling with the visual network and de-differentiation with the ventral attention and default mode networks. These findings reveal distinct neurobiological mechanisms underlying insomnia phenotypes and highlight the need for phenotype-based interventions.

失眠是一种异质性精神疾病，其特点是心理特征和神经生物学机制的差异，需要精确的表型来进行有针对性的干预。这项临床对照研究是一项为期两年的多中心研究项目的一部分，研究了按客观总睡眠时间（oTST）分类的失眠表型之间睡眠参数、心理特征和形态相似性（MS）模式的差异。该研究招募了997名患有失眠症的成年患者，其中270人接受了核磁共振扫描。参与者被分为客观正常睡眠时间失眠（INSD）和客观短睡眠时间失眠（ISSD），基于使用可穿戴式前额睡眠记录仪测量的oTST。主要结局包括睡眠参数（如入睡后醒来和快速眼动百分比）、心理特征（如反刍）和通过质谱图评估的质谱模式。结果表明，ISSD表型表现为睡眠后觉醒时间较短，眼动睡眠（REM）比例较低，非REM第二阶段（N2）比例较高，而INSD表型表现为更大的睡眠感知偏差和更多的碎片化睡眠。此外，ISSD表现出更高的整体质谱和明显的区域质谱模式，包括右侧颞中回低质谱和右侧中央后回高质谱。它还表现出与视觉网络的解耦和与腹侧注意网络和默认模式网络的去分化。这些发现揭示了失眠表型背后的独特神经生物学机制，并强调了基于表型干预的必要性。

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引用次数: 0

Distinct functional profiles of partial agonist antipsychotics in cAMP and β-arrestin signaling mechanisms of dopamine D2 and D3 receptors in vitro 部分激动剂抗精神病药物在体外多巴胺D2和D3受体cAMP和β-抑制素信号传导机制中的独特功能特征。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-11-03 DOI: 10.1016/j.pnpbp.2025.111554

Katalin Domány-Kovács, Sándor Kolok, Dalma Kurkó, Zsófia Bekes, Ferenc Horti, Amrita Bobok, József Nagy, Zoltán Kapui , Balázs Lendvai, András Visegrády, Béla Kiss

Aripiprazole, brexpiprazole and cariprazine represent a new generation of atypical antipsychotics with partial agonist activity at dopamine D₂ and D₃ receptors. So far, the functional activity of these partial agonists has mainly been studied at G-protein-dependent cyclic adenosine monophosphate (cAMP) signaling pathways of D₂ and D₃ receptors. While their effects at D₂ receptor-mediated β-arrestin translocation were relatively well characterized the comparative investigation at D₃-dependent β-arrestin translocation is still largely missing. Moreover, antagonism of these partial agonists either at D₂ or D₃ receptors has not been studied at multiple cellular signaling pathways. In this study, we compared the agonist and antagonist features of aripiprazole, brexpiprazole, cariprazine on dopamine receptor-mediated cAMP and β-arrestin pathways in multiple cell lines expressing recombinant human D₂ or D₃ receptors using homogeneous time-resolved fluorescence and luminescent enzyme fragment complementation technologies. We demonstrated that the three partial agonists display qualitatively similar functional profile at D₂ receptor-mediated cAMP and β-arrestin pathways. While cariprazine showed partial agonism and partial antagonism at D₃ receptor-mediated β-arrestin translocation, aripiprazole and brexpiprazole displayed only weak or no agonist but potent antagonist activity. These data suggest differentiated mechanism of action of cariprazine at the D₃ receptor signaling compared to aripiprazole and brexpiprazole.

阿立哌唑、brexpiprazole和cariprazine是新一代具有多巴胺D2和D3受体部分激动剂活性的非典型抗精神病药物。到目前为止，这些部分激动剂的功能活性主要研究于D2和D3受体的g蛋白依赖性环腺苷单磷酸（cAMP）信号通路。虽然它们在D2受体介导的β-阻滞蛋白易位中的作用已经得到了较好的表征，但对d3依赖性β-阻滞蛋白易位的比较研究仍在很大程度上缺失。此外，这些部分激动剂对D2或D3受体的拮抗作用尚未在多种细胞信号通路中得到研究。在本研究中，我们采用均匀时间分辨荧光和发光酶片段互补技术，比较了阿立哌唑、brexpiprazole和cariprazine在表达重组人D2或D3受体的多种细胞系中对多巴胺受体介导的cAMP和β-阻滞素通路的激动剂和拮抗剂特性。我们证明了这三种部分激动剂在D2受体介导的cAMP和β-阻滞素途径上表现出质量相似的功能特征。在D3受体介导的β-抑制素易位中，卡吡嗪表现出部分激动作用和部分拮抗作用，而阿立哌唑和brexpiprazole表现出微弱或无激动作用，但具有强拮抗作用。这些数据表明，与阿立哌唑和brexpiprazole相比，cariprazine对D3受体信号的作用机制是不同的。

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引用次数: 0

Clozapine mitigates MK-801-induced mismatch negativity impairment in a rat electroencephalography study: relevance for schizophrenia drug development 氯氮平减轻大鼠脑电图研究中mk -801诱导的错配负性损伤：与精神分裂症药物开发的相关性

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-11-02 DOI: 10.1016/j.pnpbp.2025.111555

Florian W. Adraoui , Maëlle Violas , Geoffrey Viardot , Kenza Hettak , Samuel Tugler , Eric Delpy , Anne Maurin , Philippe L'Hostis , Christophe Drieu La Rochelle , Kevin Carvalho

Treating people with schizophrenia still represents a major challenge for neuropsychiatric drug development companies. While available atypical antipsychotics are mainly effective on positive symptoms of schizophrenia, their effects on cognitive and social-cognitive deficits remain insufficient and poorly characterized. For instance, a modest improvement of cognitive functions has been described following clozapine treatment. Nevertheless, it remains unclear whether this outcome is due to a direct effect on the neural circuits underlying cognition or to an indirect effect mediated by an overall reduction in positive symptoms. To address this question, we sought to measure mismatch negativity (MMN) responses in telemetered rats. MMN constitutes an electroencephalography-based biomarker of sensory, pre-attentional and predictive coding processes, functions whose disruptions highly influence certain aspects of patients' cognitive symptoms. MMN was measured under N-methyl-d-aspartate receptor (NMDAr) pharmacological inhibition by MK-801 (dizocilpine), a model based on the glutamatergic hypothesis of schizophrenia, and we tested whether clozapine could improve MMN under this condition or not. We found that MK-801 dose-dependently reduced the MMN peak amplitude in rats, aligning with the MMN response deficit seen in schizophrenia patients. Strikingly, clozapine was able to mitigate this electrophysiological deficit, an unprecedented observation that has the potential to inspire new treatment strategies aimed towards unaddressed schizophrenia symptoms.

治疗精神分裂症患者仍然是神经精神药物开发公司面临的主要挑战。虽然现有的非典型抗精神病药物主要对精神分裂症的阳性症状有效，但它们对认知和社会认知缺陷的影响仍然不足，而且特征不明确。例如，氯氮平治疗后认知功能有适度改善。然而，尚不清楚这一结果是由于对认知基础神经回路的直接影响，还是由于阳性症状总体减少介导的间接影响。为了解决这个问题，我们试图测量遥测大鼠的错配负性（MMN）反应。MMN是一种基于脑电图的感觉、注意前和预测编码过程的生物标志物，这些功能的中断严重影响患者认知症状的某些方面。基于谷氨酸能假说的精神分裂症模型MK-801（二唑西平）在n -甲基-d-天冬氨酸受体（NMDAr）药理抑制下测定MMN，并检验氯氮平是否能改善这种情况下的MMN。我们发现MK-801剂量依赖性地降低了大鼠的MMN峰值幅度，这与精神分裂症患者的MMN反应缺陷一致。引人注目的是，氯氮平能够减轻这种电生理缺陷，这是一个前所未有的观察结果，有可能激发针对未解决的精神分裂症症状的新治疗策略。

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引用次数: 0

Adult hippocampal neurogenesis and temporal lobe epilepsy: A potential key to understanding cognitive deficit 成人海马神经发生和颞叶癫痫：理解认知缺陷的潜在关键。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-11-02 DOI: 10.1016/j.pnpbp.2025.111553

Rúbia Aparecida Fernandes , Matheus Silva de Oliveira , Olagide Wagner de Castro , Victor Rodrigues Santos

Contrary to a prevailing dogma in twentieth-century neuroscience, emerging evidence suggests that the generation of new neurons continues throughout life, contributing significantly to crucial life functions owing to their robust ability to enhance neuroplasticity. Hippocampal neurogenesis occurs in the subgranular layer of the dentate gyrus, a region characterized by a specific microenvironment conducive to the proliferation of neuronal cells. A substantial body of evidence supports the belief that this phenomenon impacts various functions, including learning, emotional responses, and the formation of new memories. Diseases affecting these areas can significantly disrupt cognition and general behavior. For instance, in mesial temporal lobe epilepsy, aberrant neurogenesis has been observed, leading to increased cell proliferation, altered patterns of cellular integration, errors in information processing, and the formation of abnormal synaptic connections and transmissions. These abnormalities have the potential to generate epileptic seizures, underscoring the profound impact of these diseases on cognitive functions. Conversely, the chronic recurrence of seizures, can result in chronic recurrence of seizures, which can lead to a persistent reduction of neurogenesis in the epileptic brain. This reduction directly impacts various learning processes and the formation of hippocampus-dependent declarative memory. The mechanisms behind these processes remain fully elucidated and involve the delicate balance between neuronal excitation and inhibition, directly influencing brain performance and potentially leading to a decline in cognitive functions. For example, of this are the genetic and epigenetic factors that have been found to significantly influence the etiology of temporal lobe epilepsy, particularly in relation to the processes of neurogenesis. In mesial temporal lobe epilepsy, this condition stands out as one of the most severe disorders affecting the well-being of epileptic patients. While memory is highlighted as one of the most affected functions, it is not the sole cognitive function compromised by this comorbidity. The alterations can extend from language to executive and spatial functions.

与20世纪神经科学的主流教条相反，新出现的证据表明，新神经元的产生贯穿整个生命，由于其增强神经可塑性的强大能力，对关键的生命功能做出了重大贡献。海马神经发生发生在齿状回的亚颗粒层，该区域具有有利于神经元细胞增殖的特定微环境。大量证据支持这一观点，即这种现象会影响各种功能，包括学习、情绪反应和新记忆的形成。影响这些区域的疾病会严重破坏认知和一般行为。例如，在内侧颞叶癫痫中，观察到异常的神经发生，导致细胞增殖增加，细胞整合模式改变，信息处理错误，以及异常突触连接和传输的形成。这些异常有可能产生癫痫发作，强调这些疾病对认知功能的深远影响。相反，癫痫发作的慢性复发可导致癫痫发作的慢性复发，这可导致癫痫大脑中神经发生的持续减少。这种减少直接影响各种学习过程和海马体依赖性陈述性记忆的形成。这些过程背后的机制仍未完全阐明，涉及神经元兴奋和抑制之间的微妙平衡，直接影响大脑的表现，并可能导致认知功能的下降。例如，遗传和表观遗传因素已被发现显著影响颞叶癫痫的病因学，特别是与神经发生过程有关。在内侧颞叶癫痫中，这种情况是影响癫痫患者健康的最严重疾病之一。虽然记忆被强调为最受影响的功能之一，但它并不是受这种共病影响的唯一认知功能。这种改变可以从语言扩展到执行和空间功能。

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引用次数: 0

Association between long-term stimulant treatment and the functional brain response to methylphenidate in adolescents and adults with attention-deficit/hyperactivity disorder 青少年和成人注意缺陷/多动障碍患者长期兴奋剂治疗与脑功能对哌甲酯的反应之间的关系

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-29 DOI: 10.1016/j.pnpbp.2025.111545

Zarah van der Pal , Liesbeth Reneman , Henk J.M.M. Mutsaerts , Antonia Kaiser , Marco A. Bottelier , Hilde M. Geurts , Anouk Schrantee

Background

Stimulant medication is commonly used by children and adolescents with attention-deficit/hyperactivity disorder (ADHD), however its long-lasting effects on the developing brain remain unclear. In a previous randomized controlled trial (RCT) we found that short-term stimulant treatment influences the functional brain response to an acute methylphenidate-challenge in an age-dependent manner, in line with animal studies suggesting persisting effects on brain development.

Methods

In this 4-year naturalistic follow-up of the initial RCT, we investigated the long-term age-dependent effects of stimulant treatment on the functional brain response to methylphenidate in male children and adults with ADHD (n = 56; adolescents aged 10–17 years, adults aged 23–43 years). At baseline and 4-year follow-up, we used pharmacological MRI to estimate relative cerebral blood flow (rCBF) before a single-dose methylphenidate-challenge (resting rCBF) and the rCBF-response to a single-dose methylphenidate-challenge. Linear mixed models were constructed to evaluate the effect of stimulant medication use, age and visit on resting rCBF and rCBF-response.

Results

We found no evidence for long-term age-dependent effects of stimulant treatment, suggesting that our previously identified short-term effects may be transient. We did identify age-dependent associations between rCBF-response in the medial prefrontal cortex and stimulant treatment, which were already present before treatment initiation but were unrelated to ADHD symptom severity. Moreover, rCBF-response was associated with dopamine D1 receptor distributions in adolescents only.

Conclusions

The identified age-dependent associations may potentially be mediated by changes in dopamine- and noradrenaline-related functioning, and may hold predictive value for extent of stimulant medication use after ADHD diagnosis in children and adolescents.

兴奋剂药物通常用于患有注意力缺陷/多动障碍（ADHD）的儿童和青少年，但其对发育中的大脑的长期影响尚不清楚。在之前的一项随机对照试验（RCT）中，我们发现短期兴奋剂治疗会以年龄依赖的方式影响大脑对急性哌甲酯攻击的功能性反应，这与动物研究表明对大脑发育的持续影响一致。方法在最初的随机对照试验的4年自然随访中，我们研究了兴奋剂治疗对ADHD男性儿童和成人对哌甲酯的功能性脑反应的长期年龄依赖性影响（n = 56； 10-17岁的青少年，23-43岁的成年人）。在基线和4年随访中，我们使用药理学MRI来评估单剂量哌甲酯刺激前的相对脑血流量（rCBF）（静息rCBF）和单剂量哌甲酯刺激后的rCBF反应。建立线性混合模型评价兴奋剂使用、年龄和就诊对静息rCBF和rCBF反应的影响。结果：我们没有发现兴奋剂治疗的长期年龄依赖效应的证据，这表明我们之前确定的短期效应可能是短暂的。我们确实确定了内侧前额叶皮层rcbf反应与兴奋剂治疗之间的年龄依赖性关联，这种关联在治疗开始前就已经存在，但与ADHD症状严重程度无关。此外，rcbf反应仅与青少年的多巴胺D1受体分布有关。结论所确定的年龄依赖性关联可能由多巴胺和去甲肾上腺素相关功能的变化介导，并可能对儿童和青少年ADHD诊断后兴奋剂药物使用程度具有预测价值。

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引用次数: 0

Thalamocortical structural connectivity with sleep oscillatory coupling in insomnia disorder 失眠障碍的丘脑皮质结构连通性与睡眠振荡耦合

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-28 DOI: 10.1016/j.pnpbp.2025.111544

Ziqiang Shao , Zhe Du , Suping Cai , Jiayi Liu , Xumeng Zhao , Dahua Yu , Xiaona Sheng , Yifei Zhu , Kai Yuan

Background

Thalamocortical interactions play a critical role in sleep oscillatory activities. However, in individuals with insomnia disorder (ID), the structural organization of these circuits, their relationship with sleep oscillatory coupling, and their potential modulation by repetitive transcranial magnetic stimulation (rTMS) remain unclear.

Methods

In Study 1, we recruited 62 ID patients and 62 healthy controls and assessed white matter tract strength between thalamic subregions and cortical areas using probabilistic tractography. In Study 2, we administered 20 sessions of 1 Hz rTMS (active vs. sham) and evaluated changes in thalamocortical connectivity and sleep oscillations measured via polysomnography.

Results

Abnormal thalamic structural connectivity was observed in tracts projecting to the left prefrontal cortex (PFC) and bilateral sensory cortex (SC). Following treatment, significant alterations in tract strength were detected between the right thalamus and both the PFC and SC, accompanied by improvements in slow wave (SW)-spindle coupling. Furthermore, changes in right thalamus–PFC tract strength were correlated with improved subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI; r = 0.6143; 95 % CI, 0.24 to 0.83, p = 0.004), and right thalamus–SC tract strength was associated with SW–spindle coupling (post-rTMS: r = −0.59; 95 % CI, −0.83 to −0.17, p = 0.011).

Conclusion

These findings advance our understanding of the role of subdivided thalamocortical circuits and sleep oscillatory coupling in the pathophysiology of ID and suggest that rTMS can modulate these pathways, with concomitant improvements in PSQI.

背景丘脑皮质相互作用在睡眠振荡活动中起关键作用。然而，在失眠障碍（ID）个体中，这些电路的结构组织、它们与睡眠振荡耦合的关系以及它们通过重复经颅磁刺激（rTMS）的电位调节尚不清楚。方法在研究1中，我们招募了62名ID患者和62名健康对照者，使用概率束造影评估丘脑亚区和皮层区域之间的白质束强度。在研究2中，我们进行了20次1 Hz rTMS（活动与假），并通过多导睡眠图测量了丘脑皮质连通性和睡眠振荡的变化。结果在左侧前额叶皮层（PFC）和双侧感觉皮层（SC）上可见丘脑结构连通性异常。治疗后，在右丘脑与PFC和SC之间检测到束强度的显著变化，并伴有慢波-纺锤体耦合的改善。此外，右丘脑-前额皮质束强度的变化与主观睡眠质量的改善相关（匹兹堡睡眠质量指数，PSQI; r = 0.6143; 95% CI， 0.24至0.83,p = 0.004），右丘脑-前额皮质束强度与sw -纺锤体耦合相关（rtms后：r = - 0.59; 95% CI, - 0.83至- 0.17,p = 0.011）。结论这些发现促进了我们对细分丘脑皮质回路和睡眠振荡耦合在ID病理生理中的作用的理解，并表明rTMS可以调节这些通路，同时改善PSQI。

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引用次数: 0

Profiling small extracellular vesicles microRNAs and their expressions in EVs-depleted plasma as biomarkers for distinguishing schizophrenia 分析细胞外小泡microrna及其在ev -贫血浆中的表达，作为区分精神分裂症的生物标志物。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-27 DOI: 10.1016/j.pnpbp.2025.111543

Bao-Yu Chen , Jin-Jia Lin , Huai-Hsuan Tseng , Chih-Chun Huang , Po-See Chen , Chia-Hsuan Li , Chi-Yu Yao , Tzu-Yun Wang , Fong-Lin Jang , Sheng-Hsiang Lin

In schizophrenia (SZ), significant alterations in microRNAs (miRNAs) regulation and the underlying mechanisms of post-transcriptional modification have been observed. Extracellular vesicles (EVs) encapsulate miRNAs, protecting them from degradation and enabling long-range intercellular communication. While profiling sEV-derived miRNAs (sEV-miRNAs) is essential for understanding sEV-mediated signaling, examining sEV-associated miRNAs in EVs-depleted (dEV) plasma is equally important for evaluating their selectivity and potential roles in systemic physiological regulation. To investigate the hypothesis that specific miRNAs are selectively enriched in small EVs (sEVs), we compared sEV-miRNAs expression profiles between SZ patients and nonpsychotic controls (NC). We then conducted a side-by-side comparison of candidate sEV-associated miRNA expressions in dEV plasma. In the screening set (N = 24), five aberrantly expressed sEV-miRNAs (miR-23a, miR-103a, miR-182, miR-450b, and miR-4433b) were selected for further validation. In the validation set (N = 139), miR-23a, miR-103a, and miR-450b were highly expressed in SZ patients' sEVs, they were less expressed in dEV plasma. This could indicate miRNAs may play various roles in signal transduction based on their origin and distribution. An optimal marker panel (sEV-miR-103a, sEV-miR-450b, and dEV-miR-450b) was established to differentiate SZ patients from NC, yielding an area under the curve (AUC) of 0.988 and an accuracy of 0.935. In the 10-fold cross-validation model, AUC was 0.930, and accuracy was 0.887. Enrichment analysis showed that dysregulated sEV-associated miRNAs are involved in neurobiological and immune pathways in SZ. These findings support a link between SZ and altered posttranscriptional regulation mediated by specific sEV-miRNAs, highlighting their potential as therapeutic targets.

在精神分裂症（SZ）中，已经观察到microRNAs （miRNAs）调控的显著改变和转录后修饰的潜在机制。细胞外囊泡（EVs）封装mirna，保护它们免受降解并实现细胞间的远程通信。虽然分析sev衍生的mirna （sev - mirna）对于理解sev介导的信号传导至关重要，但在ev -贫（dEV）血浆中检测sev相关的mirna对于评估其选择性和在全身生理调节中的潜在作用同样重要。为了研究特定mirna在小ev （sev）中选择性富集的假设，我们比较了SZ患者和非精神病对照组（NC）的sev - mirna表达谱。然后，我们对dEV血浆中候选sev相关mirna的表达进行了并排比较。在筛选集（N = 24）中，选择5个异常表达的sev - mirna （miR-23a, miR-103a, miR-182， miR-450b和miR-4433b）进行进一步验证。在验证集（N = 139）中，miR-23a、miR-103a和miR-450b在SZ患者的sev中高表达，在dEV血浆中低表达。这可能表明mirna可能根据其起源和分布在信号转导中发挥多种作用。建立最佳标记面板（sEV-miR-103a、sEV-miR-450b和dEV-miR-450b）来区分SZ患者和NC患者，曲线下面积（AUC）为0.988，准确度为0.935。在10倍交叉验证模型中，AUC为0.930，准确率为0.887。富集分析表明，sev相关的mirna失调参与了SZ的神经生物学和免疫途径。这些发现支持SZ与特定sev - mirna介导的转录后调控改变之间的联系，突出了它们作为治疗靶点的潜力。

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引用次数: 0

Targeting neurochemical and immune dysregulation in schizophrenia: From molecular mechanisms to emerging therapeutic strategies 针对精神分裂症的神经化学和免疫失调：从分子机制到新兴的治疗策略。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-24 DOI: 10.1016/j.pnpbp.2025.111535

Aastha Datta , Himani Rana, Shareen Singh , Thakur Gurjeet Singh

Schizophrenia is a multifaceted neuropsychiatric condition marked by a diverse array of symptoms, which can be categorized into positive, negative, and cognitive deficits. The underlying pathophysiology of this disorder is complex, involving a variety of mechanisms such as the dysregulation of neurotransmitter systems, neuroinflammatory responses, and neuronal dysfunction induced by oxidative stress. These interrelated processes lead to synaptic and neuronal impairments, which ultimately result in the clinical manifestations observed in patients with schizophrenia. The challenge of elucidating the molecular mechanisms that contribute to schizophrenia is significant, given the disorder's intricate and multifactorial characteristics. Neuroinflammatory pathways, such as those involving NF-κB, MAPK/ERK, kynurenine pathway and the activation of the NLRP3 inflammasome, play a significant role in promoting oxidative stress, synaptic dysfunction, and neuronal injury, which in turn aggravate cognitive and negative symptoms associated with schizophrenia. Although current pharmacological treatments primarily focus on dopamine and glutamate systems, their limited effectiveness in alleviating cognitive and negative symptoms highlights the necessity for a deeper mechanistic understanding of the disorder at the molecular level. Progress in neurobiological research, particularly concerning inflammatory pathways, mitochondrial dysfunction, and synaptic plasticity, is essential for the development of more targeted and effective therapeutic strategies for schizophrenia. This review underscores the critical need for a deeper understanding of molecular insights and treatment methodologies in the context of schizophrenia.

精神分裂症是一种多方面的神经精神疾病，以各种各样的症状为特征，可分为阳性、阴性和认知缺陷。这种疾病的潜在病理生理是复杂的，涉及多种机制，如神经递质系统失调、神经炎症反应和氧化应激诱导的神经元功能障碍。这些相互关联的过程导致突触和神经元损伤，最终导致在精神分裂症患者中观察到的临床表现。鉴于精神分裂症的复杂和多因素特征，阐明导致精神分裂症的分子机制的挑战是重大的。神经炎症通路，如涉及NF-κB、MAPK/ERK、犬尿氨酸通路和NLRP3炎性体激活的神经炎症通路，在促进氧化应激、突触功能障碍和神经元损伤中发挥重要作用，从而加重精神分裂症相关的认知和阴性症状。虽然目前的药物治疗主要集中在多巴胺和谷氨酸系统，但它们在缓解认知和阴性症状方面的有限效果突出了在分子水平上对该疾病进行更深入的机制理解的必要性。神经生物学研究的进展，特别是关于炎症途径、线粒体功能障碍和突触可塑性的研究，对于开发更有针对性和更有效的精神分裂症治疗策略至关重要。这篇综述强调了在精神分裂症的背景下，对分子见解和治疗方法有更深入的了解的迫切需要。

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引用次数: 0

Cognitive electroencephalographic potentials evoked by words as markers of the severity of the pathology and resistance to treatment in obsessive-compulsive disorder. 词语诱发的认知脑电图电位作为强迫症病理严重程度和治疗抵抗的标志。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-24 DOI: 10.1016/j.pnpbp.2025.111530

Issa Wassouf , Nicolas Vibert , Julien Dampuré , Damien Doolub , Ghina Harika-Germaneau , Nicolas Langbour , Nematollah Jaafari

Patients suffering from obsessive-compulsive disorder (OCD) show an attentional bias towards pathology-related words. Electroencephalographic cognitive potentials were used to investigate how patients responded to words related to their obsessions and compulsions. Forty OCD patients with various levels of severity and treatment-resistance were included to assess links between word-evoked potentials and patients' clinical variables, and compared with 40 control participants. The P200 component evoked by both neutral and pathology-related words was greater in patients than in controls, suggesting that patients were more attentive overall. In the N400 time window, pathology-related words evoked less negative potentials than neutral words in OCD patients, suggesting that pathology-related words were particularly familiar to them and permanently pre-activated in their mental lexicon. Finally, correlations were detected between pathology severity and the profile of word-evoked potentials in the N400 time window, and between the patients' treatment resistance and the amplitude of late word-evoked positive potentials (P600).

患有强迫症（OCD）的患者表现出对病理相关词汇的注意偏倚。使用脑电图认知电位来调查患者对与他们的强迫和强迫有关的词语的反应。本研究选取了40名不同严重程度和治疗抵抗程度的强迫症患者，以评估词诱发电位与患者临床变量之间的联系，并与40名对照受试者进行比较。中性词和病理相关词诱发的P200成分在患者中比对照组更大，表明患者总体上更专注。在N400时间窗内，病理相关词诱发的负性电位低于中性词，说明病理相关词在强迫症患者的心理词汇中特别熟悉，并被永久预激活。最后，我们发现病理严重程度与N400时间窗内的单词诱发电位分布、患者的治疗抵抗与晚期单词诱发正电位振幅之间存在相关性（P600）。

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引用次数: 0