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

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

Adverse event reporting and management in psilocybin therapy clinical trials: A systematic review to guide clinical and research protocol development 裸盖菇素治疗临床试验中的不良事件报告和管理：指导临床和研究方案制定的系统综述。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-23 DOI: 10.1016/j.pnpbp.2025.111541

Danielle Bukovsky , Aron Amaev , Jianmeng Song , Shannen Kyte , Edgardo Carmona-Torres , Fumihiko Ueno , Vincenzo Deluca , Antonio P. Strafella , Muhammad I. Husain , Ariel Graff-Guerrero , Philip Gerretsen

Psilocybin, a psychedelic prodrug, has gained renewed interest for its potential to treat various psychiatric disorders, including depression, anxiety, and substance use disorders. While promising, concerns remain regarding its safety profile and the management of potential adverse events (AEs). This systematic review aimed to evaluate the incidence, nature, and severity of adverse events and serious adverse events (SAEs) associated with psilocybin use across diverse clinical populations.

A comprehensive search was conducted across MEDLINE, Embase, and APA PsycInfo via the OVID platform, from database inception to June 5, 2024. A total of 42 clinical studies (N = 1068 participants) met inclusion criteria, all of which reported on AEs and/or SAEs following psilocybin administration. All studies were deemed to have a high risk of bias due to concerns regarding blinding. We synthesized information on common, uncommon, and SAEs, instances of suicidal ideation, methods of measuring AEs, and AEs requiring medical intervention. Reported AEs included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. In rare instances, medical intervention was required. SAEs were reported infrequently in 2 of 42 studies and were limited to participants with underlying depressive disorders (e.g., suicidal behaviour, hospitalization).

Overall, psilocybin appears to have a favourable safety profile when administered in controlled settings. Based on our findings, we provide an outline of commonly reported AEs, uncommon AEs, SAEs, and considerations for future clinical and research protocols.

裸盖菇素是一种致幻前药，因其治疗各种精神疾病的潜力而重新引起人们的兴趣，包括抑郁症、焦虑症和物质使用障碍。尽管前景看好，但对其安全性和潜在不良事件（ae）管理的担忧仍然存在。本系统综述旨在评估不同临床人群中与裸盖菇素使用相关的不良事件和严重不良事件（SAEs）的发生率、性质和严重程度。通过OVID平台对MEDLINE、Embase和APA PsycInfo进行了全面的搜索，从数据库建立到2024年5月6日。共有42项临床研究（N = 1068名受试者）符合纳入标准，所有研究均报告了裸盖菇素给药后的ae和/或sae。由于考虑到盲法，所有的研究都被确定为高偏倚风险。我们综合了常见、不常见和严重不良事件、自杀意念、不良事件测量方法和需要医疗干预的不良事件的信息。报告的不良反应包括头痛、短暂性血压升高和恶心，这些症状通常会自行消退。在极少数情况下，需要进行医疗干预。42项研究中有2项报告了罕见的严重不良事件，并且仅限于有潜在抑郁障碍（如自杀行为、住院）的参与者。总的来说，裸盖菇素在受控环境下似乎具有良好的安全性。基于我们的发现，我们概述了常见的ae、不常见的ae、sae，以及对未来临床和研究方案的考虑1。

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引用次数: 0

Dopamine disruption and autism phenotypes in slc6a3−/− zebrafish: Behavioural and molecular insights slc6a3-/-斑马鱼的多巴胺破坏和自闭症表型：行为和分子的见解。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-14 DOI: 10.1016/j.pnpbp.2025.111528

Wen Li , Xiaocong Zhang , Xiaoyu Niu , Nan Qin , Lulu Kang , Kai Wang , Mingyong Wang

Dopamine plays a crucial role in regulating movement, motivation, attention, and emotions. Disruptions in dopamine metabolism have been linked to various psychiatric disorders, including autism spectrum disorder (ASD). In this study, we generated an slc6a3 knockout zebrafish model using the CRISPR-Cas9 system to investigate the relationship between dopamine dysfunction and autism. Our results revealed that slc6a3 knockout significantly reduced dopamine levels, leading to impaired dopamine synthesis, transport, and metabolism. Behavioural analysis demonstrated that slc6a3−/− zebrafish exhibited decreased motor activity, increased anxiety-like behaviour, and autism-related symptoms, such as impaired social ability and “digging” behaviour. Pharmacological intervention with risperidone and clozapine improved motor function, social interaction, and anxiety levels, with risperidone showing superior effects. Transcriptomic analysis identified significant changes in several nervous system-related genes in slc6a3−/− zebrafish, suggesting that these gene alterations may contribute to the observed behavioural abnormalities. Our study highlights the crucial role of dopamine dysfunction in autism and establishes slc6a3−/− zebrafish as a valuable model for studying autism and screening potential therapeutic drugs.

多巴胺在调节运动、动机、注意力和情绪方面起着至关重要的作用。多巴胺代谢紊乱与各种精神疾病有关，包括自闭症谱系障碍（ASD）。在本研究中，我们利用CRISPR-Cas9系统构建了slc6a3敲除斑马鱼模型，研究多巴胺功能障碍与自闭症之间的关系。我们的研究结果显示，slc6a3敲除显著降低多巴胺水平，导致多巴胺合成、运输和代谢受损。行为分析表明，slc6a3-/-斑马鱼表现出运动活动减少，焦虑样行为增加，以及自闭症相关症状，如社交能力受损和“挖掘”行为。利培酮和氯氮平的药物干预改善了运动功能、社交互动和焦虑水平，其中利培酮表现出更好的效果。转录组学分析发现，slc6a3-/-斑马鱼的几个神经系统相关基因发生了显著变化，表明这些基因改变可能导致观察到的行为异常。我们的研究强调了多巴胺功能障碍在自闭症中的重要作用，并建立了slc6a3-/-斑马鱼作为研究自闭症和筛选潜在治疗药物的有价值的模型。

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引用次数: 0

The possible effect of fentanyl on PTSD 芬太尼对创伤后应激障碍的可能影响。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-10-02 DOI: 10.1016/j.pnpbp.2025.111519

Yehudit O. Weiss Schonberg , Leehe Peled-Avron

Post-traumatic stress disorder (PTSD) is a severe mental health disorder that appears as a result of trauma exposure and adversely affects the daily life and well-being of those who suffer from it. Major risk factors for PTSD include serving as a combat soldier and having traumatic and painful injuries. This review aims to investigate the possible beneficial effects of fentanyl on PTSD, and the possible theoretical mechanisms at the base of these effects. Fentanyl is a powerful analgesic from the opioid family that is often administered in cases of painful injuries, both as a prehospital battlefield treatment and at the hospital. Morphine, another opioid used for analgesia in similar situations, was shown to help both with the prevention and treatment of PTSD. Only a few studies examine the direct influence of fentanyl on PTSD, but there is evidence that indirectly suggests that fentanyl can treat or prevent PTSD via three mediating factors. In this review we suggest three possible hypotheses. In one possible route, the influence of fentanyl on PTSD is mediated by pain relief. Fentanyl was found to effectively reduce pain, and a positive correlation between pain level and PTSD severity was also found. The second route suggests that fentanyl's influence on PTSD is mediated by the activity of the vagus nerve. There is evidence that fentanyl administration results in vagal activity and that the activation of the vagus nerve reduces PTSD levels. A third possible route may be through fentanyl's activation of opioid receptors in limbic region which were found to have protective effects against PTSD. Future research of fentanyl's role in PTSD prevention and treatment is essential, and should account for pre-existing mental health struggles, TBI, delirium, and injury severity.

创伤后应激障碍（PTSD）是一种严重的心理健康障碍，由于创伤暴露而出现，并对患者的日常生活和福祉产生不利影响。创伤后应激障碍的主要风险因素包括作为一名战斗士兵，遭受创伤和痛苦的伤害。本文旨在探讨芬太尼对创伤后应激障碍可能的有益作用，以及这些作用的可能理论机制。芬太尼是阿片类药物家族的一种强效镇痛药，通常用于疼痛损伤的病例，既可作为院前战场治疗，也可在医院使用。吗啡，另一种在类似情况下用于镇痛的阿片类药物，被证明有助于预防和治疗创伤后应激障碍。只有少数研究考察了芬太尼对PTSD的直接影响，但有证据间接表明芬太尼可以通过三个中介因素治疗或预防PTSD。在这篇综述中，我们提出了三种可能的假设。在一种可能的途径中，芬太尼对创伤后应激障碍的影响是通过疼痛缓解介导的。芬太尼能有效减轻疼痛，疼痛程度与创伤后应激障碍严重程度呈正相关。第二种途径表明芬太尼对PTSD的影响是由迷走神经的活动介导的。有证据表明，芬太尼的服用会导致迷走神经活动，迷走神经的激活会降低PTSD的水平。第三种可能的途径是通过芬太尼激活边缘区域的阿片受体，这种受体被发现对创伤后应激障碍有保护作用。芬太尼在PTSD预防和治疗中的作用的未来研究是必不可少的，并且应该考虑到先前存在的精神健康斗争，TBI，谵妄和伤害严重程度。

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引用次数: 0