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Excitation/inhibition imbalance in schizophrenia: a meta-analysis of inhibitory and excitatory TMS-EMG paradigms. 精神分裂症的兴奋/抑制失衡:抑制性和兴奋性 TMS-EMG 范例的荟萃分析。
Q2 PSYCHIATRY Pub Date : 2024-06-15 DOI: 10.1038/s41537-024-00476-y
Orsolya Lányi, Boróka Koleszár, Alexander Schulze Wenning, David Balogh, Marie Anne Engh, András Attila Horváth, Péter Fehérvari, Péter Hegyi, Zsolt Molnár, Zsolt Unoka, Gábor Csukly

Cortical excitation-inhibition (E/I) imbalance is a potential model for the pathophysiology of schizophrenia. Previous research using transcranial magnetic stimulation (TMS) and electromyography (EMG) has suggested inhibitory deficits in schizophrenia. In this meta-analysis we assessed the reliability and clinical potential of TMS-EMG paradigms in schizophrenia following the methodological recommendations of the PRISMA guideline and the Cochrane Handbook. The search was conducted in three databases in November 2022. Included articles reported Short-Interval Intracortical Inhibition (SICI), Intracortical Facilitation (ICF), Long-Interval Intracortical Inhibition (LICI) and Cortical Silent Period (CSP) in patients with schizophrenia and healthy controls. Meta-analyses were conducted using a random-effects model. Subgroup analysis and meta-regressions were used to assess heterogeneity. Results of 36 studies revealed a robust inhibitory deficit in schizophrenia with a significant decrease in SICI (Cohen's d: 0.62). A trend-level association was found between SICI and antipsychotic medication. Our findings support the E/I imbalance hypothesis in schizophrenia and suggest that SICI may be a potential pathophysiological characteristic of the disorder.

皮层兴奋-抑制(E/I)失衡是精神分裂症病理生理学的一个潜在模型。此前使用经颅磁刺激(TMS)和肌电图(EMG)进行的研究表明,精神分裂症患者存在抑制功能障碍。在这项荟萃分析中,我们按照 PRISMA 指南和 Cochrane 手册的方法学建议,评估了 TMS-EMG 范式在精神分裂症中的可靠性和临床潜力。该研究于 2022 年 11 月在三个数据库中进行了检索。纳入的文章报告了精神分裂症患者和健康对照组的短时皮质内抑制(SICI)、皮质内促进(ICF)、长时皮质内抑制(LICI)和皮质静默期(CSP)。元分析采用随机效应模型进行。分组分析和元回归用于评估异质性。36 项研究的结果表明,精神分裂症患者存在严重的抑制缺陷,SICI 显著下降(Cohen's d:0.62)。SICI与抗精神病药物之间存在趋势性关联。我们的研究结果支持精神分裂症的E/I失衡假说,并表明SICI可能是精神分裂症的一个潜在病理生理特征。
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引用次数: 0
Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia. PLA2G4A 的拷贝数缺失会影响精神分裂症的易感性和临床表型。
Pub Date : 2024-05-30 DOI: 10.1038/s41537-024-00474-0
Zibo Gao, Xinru Guo, Zhouyang Sun, Songyu Wu, Qianyi Wang, Qianlong Huang, Wei Bai, Changgui Kou

Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia.

磷脂酶 A2(PLA2)超家族被认为通过影响细胞膜的脂质平衡参与了精神分裂症的发病机制。我们假设 PLA2 基因拷贝数变异(CNV)可能会影响 PLA2 酶的表达,并与精神分裂症风险相关。这项研究表明,在发现阶段,PLA2G6拷贝数的增加以及PLA2G3、PLA2G4A、PLA2G4F和PLA2G12F的缺失与精神分裂症风险的增加有关。在公开数据集中检测到了涉及六个 PLA2 基因的 CNV 片段,其中包括两个 PLA2G4A 基因特有的缺失片段。随后,在由 806 人组成的验证组中再次证实了 PLA2G4A 基因缺失与精神分裂症易感性之间的关系。PLA2G4A 基因缺失与男性患者的思维贫乏症状和女性患者的色情妄想症状之间存在明显的相关性。此外,酶联免疫吸附试验结果表明,与正常基因型和拷贝数重复基因型的患者相比,PLA2G4A缺失基因型患者的外周血细胞膜PLA2(cPLA2)水平明显下降。这些数据表明,PLA2G4A 基因功能拷贝数缺失通过降低 cPLA2 的表达与精神分裂症的患病风险和临床表型有关,而 cPLA2 的表达可能是精神分裂症易感性的一个指标。
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引用次数: 0
Multimodal fusion of brain signals for robust prediction of psychosis transition. 多模态融合大脑信号,稳健预测精神病转变。
Pub Date : 2024-05-21 DOI: 10.1038/s41537-024-00464-2
Jenna M Reinen, Pablo Polosecki, Eduardo Castro, Cheryl M Corcoran, Guillermo A Cecchi, Tiziano Colibazzi

The prospective study of youths at clinical high risk (CHR) for psychosis, including neuroimaging, can identify neural signatures predictive of psychosis outcomes using algorithms that integrate complex information. Here, to identify risk and psychosis conversion, we implemented multiple kernel learning (MKL), a multimodal machine learning approach allowing patterns from each modality to inform each other. Baseline multimodal scans (n = 74, 11 converters) included structural, resting-state functional imaging, and diffusion-weighted data. Multimodal MKL outperformed unimodal models (AUC = 0.73 vs. 0.66 in predicting conversion). Moreover, patterns learned by MKL were robust to training set variations, suggesting it can identify cross-modality redundancies and synergies to stabilize the predictive pattern. We identified many predictors consistent with the literature, including frontal cortices, cingulate, thalamus, and striatum. This highlights the advantage of methods that leverage the complex pathophysiology of psychosis.

对处于精神病临床高风险(CHR)的青少年进行前瞻性研究,包括神经影像学研究,可以利用整合复杂信息的算法识别预测精神病结果的神经特征。在这里,为了识别风险和精神病转换,我们采用了多核学习(MKL),这是一种多模态机器学习方法,可以让每种模态的模式相互借鉴。基线多模态扫描(n = 74,11 名转换者)包括结构、静息态功能成像和弥散加权数据。多模态 MKL 的表现优于单模态模型(预测转换的 AUC = 0.73 对 0.66)。此外,MKL 学习到的模式对训练集的变化具有鲁棒性,这表明它可以识别跨模态冗余和协同作用,从而稳定预测模式。我们发现了许多与文献一致的预测因子,包括额叶皮层、扣带回、丘脑和纹状体。这凸显了利用精神病复杂病理生理学的方法的优势。
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引用次数: 0
The contribution of prosody to machine classification of schizophrenia. 前奏对精神分裂症机器分类的贡献。
Pub Date : 2024-05-18 DOI: 10.1038/s41537-024-00463-3
Tomer Ben Moshe, Ido Ziv, Nachum Dershowitz, Kfir Bar

We show how acoustic prosodic features, such as pitch and gaps, can be used computationally for detecting symptoms of schizophrenia from a single spoken response. We compare the individual contributions of acoustic and previously-employed text modalities to the algorithmic determination whether the speaker has schizophrenia. Our classification results clearly show that we can extract relevant acoustic features better than those textual ones. We find that, when combined with those acoustic features, textual features improve classification only slightly.

我们展示了如何通过计算利用声学前音特征(如音高和间隙)从单个口语应答中检测出精神分裂症的症状。我们比较了声学模态和以前使用的文本模态对算法判断说话者是否患有精神分裂症的各自贡献。我们的分类结果清楚地表明,我们能比文字模式更好地提取相关的声学特征。我们发现,当与这些声学特征相结合时,文本特征只能稍微改善分类效果。
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引用次数: 0
Combination of UGT1A1 polymorphism and baseline plasma bilirubin levels in predicting the risk of antipsychotic-induced dyslipidemia in schizophrenia patients. 结合 UGT1A1 多态性和血浆胆红素基线水平预测精神分裂症患者因抗精神病药引起血脂异常的风险。
Pub Date : 2024-05-17 DOI: 10.1038/s41537-024-00473-1
Chenquan Lin, Shuangyang Zhang, Ping Yang, Bikui Zhang, Wenbin Guo, Renrong Wu, Yong Liu, Jianjian Wang, Haishan Wu, Hualin Cai

The prolonged usage of atypical antipsychotic drugs (AAPD) among individuals with schizophrenia often leads to metabolic side effects such as dyslipidemia. These effects not only limit one's selection of AAPD but also significantly reduce compliance and quality of life of patients. Recent studies suggest that bilirubin plays a crucial role in maintaining lipid homeostasis and may be a potential pre-treatment biomarker for individuals with dyslipidemia. The present study included 644 schizophrenia patients from two centers. Demographic and clinical characteristics were collected at baseline and 4 weeks after admission to investigate the correlation between metabolites, episodes, usage of AAPDs, and occurrence of dyslipidemia. Besides, we explored the combined predictive value of genotypes and baseline bilirubin for dyslipidemia by employing multiple PCR targeted capture techniques to sequence two pathways: bilirubin metabolism-related genes and lipid metabolism-related genes. Our results indicated that there existed a negative correlation between the changes in bilirubin levels and triglyceride (TG) levels in patients with schizophrenia. Among three types of bilirubin, direct bilirubin in the baseline (DBIL-bl) proved to be the most effective in predicting dyslipidemia in the ROC analysis (AUC = 0.627, p < 0.001). Furthermore, the odds ratio from multinomial logistic regression analysis showed that UGT1A1*6 was a protective factor for dyslipidemia (ß = -12.868, p < 0.001). The combination of baseline DBIL and UGT1A1*6 significantly improved the performance in predicting dyslipidemia (AUC = 0.939, p < 0.001). Schizophrenia patients with UGT1A1*6 mutation and a certain level of baseline bilirubin may be more resistant to dyslipidemia and have more selections for AAPD than other patients.

精神分裂症患者长期服用非典型抗精神病药物(AAPD)往往会导致血脂异常等代谢副作用。这些副作用不仅限制了患者对非典型抗精神病药物的选择,还大大降低了患者的依从性和生活质量。最近的研究表明,胆红素在维持血脂平衡方面起着至关重要的作用,可能成为血脂异常患者治疗前的潜在生物标志物。本研究纳入了来自两个中心的 644 名精神分裂症患者。我们收集了基线和入院 4 周后的人口统计学和临床特征,以研究代谢物、发作、AAPDs 的使用和血脂异常发生之间的相关性。此外,我们还采用多种 PCR 靶向捕获技术,对胆红素代谢相关基因和脂质代谢相关基因两条通路进行测序,探讨了基因型和基线胆红素对血脂异常的综合预测价值。结果表明,精神分裂症患者胆红素水平的变化与甘油三酯(TG)水平之间存在负相关。在三种胆红素中,基线直接胆红素(DBIL-bl)在 ROC 分析中被证明是预测血脂异常最有效的指标(AUC = 0.627,p<0.05)。
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引用次数: 0
Bridging cholinergic signalling and inflammation in schizophrenia. 连接精神分裂症中的胆碱能信号和炎症
Pub Date : 2024-05-11 DOI: 10.1038/s41537-024-00472-2
Christine N Metz, Michael Brines, Valentin A Pavlov
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引用次数: 0
Author Correction: The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study. 作者更正:具有突出阴性症状的精神分裂症患者的网络特征:一项多模态融合研究。
Pub Date : 2024-04-08 DOI: 10.1038/s41537-024-00467-z
Li Kong, Yao Zhang, Xu-Ming Wu, Xiao-Xiao Wang, Hai-Su Wu, Shuai-Biao Li, Min-Yi Chu, Yi Wang, Simon S Y Lui, Qin-Yu Lv, Zheng-Hui Yi, Raymond C K Chan
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引用次数: 0
Visualizing threat and trustworthiness prior beliefs in face perception in high versus low paranoia. 在高度偏执狂和低度偏执狂的人脸感知中,将威胁和可信度先验信念可视化。
Pub Date : 2024-03-20 DOI: 10.1038/s41537-024-00459-z
Antonia Bott, Hanna C Steer, Julian L Faße, Tania M Lincoln

Predictive processing accounts of psychosis conceptualize delusions as overly strong learned expectations (prior beliefs) that shape cognition and perception. Paranoia, the most prevalent form of delusions, involves threat prior beliefs that are inherently social. Here, we investigated whether paranoia is related to overly strong threat prior beliefs in face perception. Participants with subclinical levels of high (n = 109) versus low (n = 111) paranoia viewed face stimuli paired with written descriptions of threatening versus trustworthy behaviors, thereby activating their threat versus trustworthiness prior beliefs. Subsequently, they completed an established social-psychological reverse correlation image classification (RCIC) paradigm. This paradigm used participants' responses to randomly varying face stimuli to generate individual classification images (ICIs) that intend to visualize either facial prior belief (threat vs. trust). An independent sample (n = 76) rated these ICIs as more threatening in the threat compared to the trust condition, validating the causal effect of prior beliefs on face perception. Contrary to expectations derived from predictive processing accounts, there was no evidence for a main effect of paranoia. This finding suggests that paranoia was not related to stronger threat prior beliefs that directly affected face perception, challenging the assumption that paranoid beliefs operate on a perceptual level.

精神病的预测加工理论将妄想概念化为影响认知和感知的过于强烈的习得性预期(先验信念)。妄想症是妄想症中最常见的一种,它涉及到具有内在社会性的威胁先验信念。在此,我们研究了妄想症是否与人脸感知中过于强烈的威胁先验信念有关。亚临床水平的高度(n = 109)和低度(n = 111)偏执狂被试观看了与威胁性和可信性行为的书面描述配对的人脸刺激,从而激活了他们的威胁性和可信性先验信念。随后,他们完成了一个成熟的社会心理学反向相关图像分类(RCIC)范式。该范式利用被试对随机变化的面部刺激的反应来生成个体分类图像(ICIs),目的是将面部先验信念(威胁与信任)形象化。独立样本(n = 76)将这些 ICIs 评为威胁条件下比信任条件下更具威胁性,从而验证了先验信念对人脸感知的因果效应。与根据预测处理理论得出的预期相反,没有证据表明偏执狂会产生主效应。这一发现表明,偏执狂与直接影响人脸感知的更强的威胁先验信念无关,这对偏执狂信念在感知层面发挥作用的假设提出了质疑。
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引用次数: 0
Mapping the landscape: a bibliometric analysis of resting-state fMRI research on schizophrenia over the past 25 years. 绘制图景:对过去 25 年精神分裂症静息态 fMRI 研究的文献计量分析。
Pub Date : 2024-03-15 DOI: 10.1038/s41537-024-00456-2
Linhan Fu, Remilai Aximu, Guoshu Zhao, Yayuan Chen, Zuhao Sun, Hui Xue, Shaoying Wang, Nannan Zhang, Zhihui Zhang, Minghuan Lei, Ying Zhai, Jinglei Xu, Jie Sun, Juanwei Ma, Feng Liu

Schizophrenia, a multifaceted mental disorder characterized by disturbances in thought, perception, and emotion, has been extensively investigated through resting-state fMRI, uncovering changes in spontaneous brain activity among those affected. However, a bibliometric examination regarding publication trends in resting-state fMRI studies related to schizophrenia is lacking. This study obtained relevant publications from the Web of Science Core Collection spanning the period from 1998 to 2022. Data extracted from these publications included information on countries/regions, institutions, authors, journals, and keywords. The collected data underwent analysis and visualization using VOSviewer software. The primary analyses included examination of international and institutional collaborations, authorship patterns, co-citation analyses of authors and journals, as well as exploration of keyword co-occurrence and temporal trend networks. A total of 859 publications were retrieved, indicating an overall growth trend from 1998 to 2022. China and the United States emerged as the leading contributors in both publication outputs and citations, with Central South University and the University of New Mexico being identified as the most productive institutions. Vince D. Calhoun had the highest number of publications and citation counts, while Karl J. Friston was recognized as the most influential author based on co-citations. Key journals such as Neuroimage, Schizophrenia Research, Schizophrenia Bulletin, and Biological Psychiatry played pivotal roles in advancing this field. Recent popular keywords included support vector machine, antipsychotic medication, transcranial magnetic stimulation, and related terms. This study systematically synthesizes the historical development, current status, and future trends in resting-state fMRI research in schizophrenia, offering valuable insights for future research directions.

精神分裂症是一种以思维、感知和情感障碍为特征的多发性精神障碍,人们通过静息态 fMRI 对精神分裂症进行了广泛的研究,发现了患者大脑自发活动的变化。然而,有关精神分裂症静息态 fMRI 研究发表趋势的文献计量学研究尚属空白。本研究从科学网核心藏书中获取了1998年至2022年期间的相关出版物。从这些出版物中提取的数据包括国家/地区、机构、作者、期刊和关键词等信息。收集到的数据使用 VOSviewer 软件进行了分析和可视化。主要分析包括对国际和机构合作、作者身份模式、作者和期刊的共同引用分析,以及对关键词共同出现和时间趋势网络的探索。共检索到 859 篇出版物,显示出从 1998 年到 2022 年的总体增长趋势。中国和美国在出版物产出和引文方面均居领先地位,中南大学和新墨西哥大学被认为是产出最高的机构。Vince D. Calhoun 的论文数量和引用次数均居首位,而 Karl J. Friston 则根据共同引用次数被评为最具影响力的作者。神经影像》(Neuroimage)、《精神分裂症研究》(Schizophrenia Research)、《精神分裂症公报》(Schizophrenia Bulletin)和《生物精神病学》(Biological Psychiatry)等重要期刊在推动这一领域的发展方面发挥了关键作用。最近流行的关键词包括支持向量机、抗精神病药物、经颅磁刺激和相关术语。本研究系统地总结了精神分裂症静息态 fMRI 研究的历史发展、现状和未来趋势,为未来的研究方向提供了宝贵的见解。
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引用次数: 0
Relationship between social cognition and premorbid adjustment in psychosis: a systematic review. 精神病患者的社会认知与病前适应之间的关系:系统性综述。
Pub Date : 2024-03-15 DOI: 10.1038/s41537-023-00428-y
P Punsoda-Puche, A Barajas, M Mamano-Grande, A Jiménez-Lafuente, S Ochoa

This systematic review provides a comprehensive overview of the association between premorbid adjustment and social cognition in people with psychotic spectrum disorder. Obtaining evidence of this association will facilitate early detection and intervention before the onset of psychosis. Literature searches were conducted in Scopus, PubMed and PsycINFO. Studies were eligible if they included patients with a psychotic disorder or at a high-risk state; social cognition and premorbid adjustment were measured; and the relationship between premorbid adjustment and social cognition was analysed. The authors independently extracted data from all included articles, and discrepancies were resolved through discussion. Literature searches were conducted in Scopus, PubMed and PsycINFO. Studies were eligible if they included patients with a psychotic disorder or at a high-risk state; social cognition and premorbid adjustment were measured; and the relationship between premorbid adjustment and social cognition was analysed. The authors independently extracted data from all included articles, and discrepancies were resolved through discussion. Of 229 studies identified, 23 met the inclusion criteria. Different methods of assessment were used to measure premorbid adjustment, such as the Premorbid Adjustment Scale or premorbid IQ, among others. Social cognition was assessed as a global measure or by domains using different instruments. A total of 16 articles found a relationship between social cognition (or its domains) and premorbid adjustment: general social cognition (n = 3); Theory of Mind (n  = 12); Emotional Recognition and Social Knowledge (n  = 1). This review shows evidence of a significant relationship between social cognition and premorbid adjustment, specifically between Theory of Mind and premorbid adjustment. Social cognition deficits may already appear in phases prior to the onset of psychosis, so an early individualized intervention with stimulating experiences in people with poor premorbid adjustment can be relevant for prevention. We recommend some future directions, such as carrying out longitudinal studies with people at high-risk of psychosis, a meta-analysis study, broadening the concept of premorbid adjustment, and a consensual assessment of social cognition and premorbid adjustment variables. PROSPERO registration number: CRD42022333886.

本系统综述全面概述了精神病谱系障碍患者病前适应与社会认知之间的关联。获得这种关联的证据将有助于在精神病发作前进行早期检测和干预。我们在 Scopus、PubMed 和 PsycINFO 中进行了文献检索。符合条件的研究包括:精神病患者或处于高危状态的患者;测量社会认知和病前适应;分析病前适应与社会认知之间的关系。作者从所有纳入的文章中独立提取数据,并通过讨论解决差异。文献检索在 Scopus、PubMed 和 PsycINFO 中进行。符合条件的研究包括:纳入了患有精神障碍或处于高危状态的患者;测量了社会认知和病前适应;分析了病前适应与社会认知之间的关系。作者从所有纳入的文章中独立提取数据,并通过讨论解决差异。在确定的 229 项研究中,有 23 项符合纳入标准。研究采用了不同的评估方法来衡量病前适应情况,如病前适应量表或病前智商等。对社会认知的评估则是采用不同的工具进行整体或分域测量。共有 16 篇文章发现了社会认知(或其领域)与病前适应之间的关系:一般社会认知(3 篇);心智理论(12 篇);情感识别和社会知识(1 篇)。本综述显示,有证据表明社会认知与病前适应之间存在显著关系,特别是心智理论与病前适应之间的关系。社会认知缺陷可能已经出现在精神病发病前的阶段,因此对病前适应不良者进行早期个体化干预,提供刺激性体验,对预防精神病有重要意义。我们建议了一些未来的研究方向,例如对精神病高危人群进行纵向研究、荟萃分析研究、拓宽病前适应性的概念,以及对社会认知和病前适应性变量进行一致评估。PROSPERO 注册号:CRD42022333886。
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引用次数: 0
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Schizophrenia (Heidelberg, Germany)
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