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Is it possible to find reliable biomarkers to diagnose suicide risk? 是否有可能找到可靠的生物标志物来诊断自杀风险?
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1017/neu.2023.8
Leo Sher
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引用次数: 0
Obstetric complications and clinical presentation in first episode of psychosis. 精神病首发的产科并发症与临床表现。
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1017/neu.2023.9
Norma Verdolini, Gisela Mezquida, Isabel Valli, Clemente Garcia-Rizo, Manuel Cuesta, Eduard Vieta, Miquel Bioque, Antonio Lobo, Ana González-Pinto, Laura Pina-Camacho, Iluminada Corripio, Marina Garriga, Inmaculada Baeza, Laura Martínez-Sadurní, Byron Bitanihirwe, Mary Cannon, Miquel Bernardo

Objective: Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs.

Methods: Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis-Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia.

Results: Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use.

Conclusions: Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation.

目的:精神障碍表现出复杂的病因,包括遗传和环境因素。在后者中,产科并发症(OCs)作为危险因素已被广泛研究,但尚不清楚OCs如何与精神障碍的异质性表现相关联。我们评估了与OCs存在相关的首发精神病(FEP)个体的临床表型。方法:采用Lewis-Murray量表对277例FEP患者的OCs进行评估,并根据时间和产科事件的特征将数据分为三个亚量表,即:妊娠并发症、胎儿生长发育异常和分娩困难。我们还考虑了另外两组:妊娠期间的任何并发症和所有的OCs。采用精神分裂症阳性和阴性症状量表对患者进行临床评价。结果:总OCs和分娩困难与更严重的精神病理有关,并且在年龄、性别、创伤经历、抗精神病药物剂量和大麻使用共变后,这一点仍然显著。结论:我们的研究结果强调了OCs与精神病临床表现的相关性。描述OCs发生的时间对于理解临床表现的异质性至关重要。
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引用次数: 1
Major neurocognitive psychosis: a novel schizophrenia endophenotype class that is based on machine learning and resembles Kraepelin's and Bleuler's conceptions. 重度神经认知精神病:一种基于机器学习的新型精神分裂症内表型类,类似于Kraepelin和Bleuler的概念。
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1017/neu.2022.32
Michael Maes

The purpose of this study is to describe how to use the precision nomothetic psychiatry approach to (a) delineate the associations between schizophrenia symptom domains, including negative symptoms, psychosis, hostility, excitation, mannerism, formal thought disorders, psychomotor retardation (PHEMFP), and cognitive dysfunctions and neuroimmunotoxic and neuro-oxidative pathways and (b) create a new endophenotype class based on these features. We show that all symptom domains (negative and PHEMFP) may be used to derive a single latent trait called overall severity of schizophrenia (OSOS). In addition, neurocognitive test results may be used to extract a general cognitive decline (G-CoDe) index, based on executive function, attention, semantic and episodic memory, and delayed recall scores. According to partial least squares analysis, the impacts of adverse outcome pathways (AOPs) on OSOS are partially mediated by increasing G-CoDe severity. The AOPs include neurotoxic cytokines and chemokines, oxidative damage to proteins and lipids, IgA responses to neurotoxic tryptophan catabolites, breakdown of the vascular and paracellular pathways with translocation of Gram-negative bacteria, and insufficient protection through lowered antioxidant levels and impairments in the innate immune system. Unsupervised machine learning identified a new schizophrenia endophenotype class, named major neurocognitive psychosis (MNP), which is characterised by increased negative symptoms and PHEMFP, G-CoDe and the above-mentioned AOPs. Based on these pathways and phenome features, MNP is a distinct endophenotype class which is qualitatively different from simple psychosis (SP). It is impossible to draw any valid conclusions from research on schizophrenia that ignores the MNP and SP distinctions.

本研究的目的是描述如何使用精确的精神病学方法来(a)描述精神分裂症症状域之间的关联,包括阴性症状、精神病、敌意、兴奋、行为举止、形式思维障碍、精神运动迟缓(PHEMFP)、认知功能障碍和神经免疫毒性和神经氧化途径;(b)基于这些特征创建一个新的内表型类别。我们表明,所有症状域(阴性和PHEMFP)可用于得出一个单一的潜在特征,称为精神分裂症的总体严重程度(OSOS)。此外,神经认知测试结果可用于提取基于执行功能、注意力、语义和情景记忆以及延迟回忆分数的一般认知衰退(G-CoDe)指数。根据偏最小二乘分析,不良结局通路(AOPs)对OSOS的影响部分由G-CoDe严重程度的增加介导。AOPs包括神经毒性细胞因子和趋化因子,对蛋白质和脂质的氧化损伤,IgA对神经毒性色氨酸分解代谢物的反应,革兰氏阴性菌易位导致血管和细胞旁通路的破坏,以及由于抗氧化水平降低和先天免疫系统损伤而导致的保护不足。无监督机器学习确定了一种新的精神分裂症内表型类型,称为主要神经认知精神病(MNP),其特征是阴性症状增加,PHEMFP, G-CoDe和上述AOPs。基于这些途径和表型特征,MNP是一个不同于单纯精神病(SP)的独特的内表型类型。如果忽视MNP和SP的区别,就不可能从精神分裂症的研究中得出任何有效的结论。
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引用次数: 5
A comparative study of retinal layer changes among patients with schizophrenia and healthy controls. 精神分裂症患者与健康对照者视网膜层变化的比较研究。
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1017/neu.2022.35
Abhilaksh Kango, Sandeep Grover, Vishali Gupta, Swapnajeet Sahoo, Ritu Nehra

Aim: This study aimed to evaluate the retinal nerve fibre layer changes among different group of patients with schizophrenia and compare it with healthy controls by using swept-source optical coherence tomography.

Methodology: Patients with first-episode schizophrenia (n = 21) in remission (n = 35) or with treatment-resistant schizophrenia (TRS) (n = 35) and 36 healthy controls were evaluated for retinal thickness.

Results: Patients with psychotic illnesses had significantly lower sub-foveal choroidal thickness (effect size 0.84-0.86), when compared to the healthy controls. When patients with first-episode schizophrenia were compared with patients with TRS, TRS patients had significant lower sub-foveal choroidal thickness (left eye) when the various confounders (such as age, gender, duration of treatment, smoking, current medications, body mass index, waist circumference, blood pressure, fasting glucose, HbA1c, presence or absence of metabolic syndrome) were taken into account. When the patients with TRS were compared with healthy controls, initially significant differences were observed for the macular volume (left and right) and the ganglion cell thickness (right eye) but these differences disappeared after controlling for the various covariates.

Conclusions: Compared to healthy controls, patients with schizophrenia, psychotic illnesses have thinning of the retina, especially in the sub-foveal choroidal thickness.

目的:应用扫描源光学相干断层扫描技术,观察不同组精神分裂症患者视网膜神经纤维层的变化,并与健康对照进行比较。方法:对首发精神分裂症(n = 21)缓解期(n = 35)或难治性精神分裂症(TRS)患者(n = 35)和36名健康对照进行视网膜厚度评估。结果:与健康对照相比,精神病患者的中央凹下脉络膜厚度显著降低(效应值0.84-0.86)。当将首发精神分裂症患者与TRS患者进行比较时,考虑到各种混杂因素(如年龄、性别、治疗持续时间、吸烟、当前药物、体重指数、腰围、血压、空腹血糖、糖化血红蛋白、有无代谢综合征),TRS患者的中央窝下脉膜厚度(左眼)明显较低。当TRS患者与健康对照组比较时,最初在黄斑体积(左右)和神经节细胞厚度(右眼)上观察到显著差异,但在控制了各种协变量后,这些差异消失了。结论:与健康对照相比,精神分裂症、精神病患者视网膜变薄,特别是在中央凹下脉络膜厚度。
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引用次数: 3
Gut microbiota alterations in stable outpatients with schizophrenia: findings from a case-control study. 稳定的精神分裂症门诊患者肠道微生物群的改变:一项病例对照研究的结果。
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1017/neu.2022.38
Błażej Misiak, Patryk Piotrowski, Agnieszka Cyran, Krzysztof Kowalski, Jerzy Samochowiec, Marcin Jabłoński, Piotr Plichta, Łukasz Łaczmański, Paulina Żebrowska, Dorota Kujawa, Igor Łoniewski, Mariusz Kaczmarczyk

Objective: The pathogenesis of schizophrenia is multidimensional and intensively studied. The gut-brain axis disturbances might play a significant role in the development of schizophrenia.

Methods: We compared the gut microbiota of 53 individuals with schizophrenia and 58 healthy controls, using the 16S rRNA sequencing method. Individuals with schizophrenia were assessed using the following scales: the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Social and Occupational Functioning Assessment Scale and the Repeatable Battery for the Assessment of Neuropsychological Status.

Results: No significant between-group differences in α-diversity measures were observed. Increased abundance of Lactobacillales (order level), Bacilli (class level) and Actinobacteriota (phylum level) were found in individuals with schizophrenia regardless of potential confounding factors, and using two independent analytical approaches (the distance-based redundancy analysis and the generalised linear model analysis). Additionally, significant correlations between various bacterial taxa (the Bacteroidia class, the Actinobacteriota phylum, the Bacteroidota phylum, the Coriobacteriales order and the Coriobacteria class) and clinical manifestation (the severity of negative symptoms, performance of language abilities, social and occupational functioning) were observed.

Conclusions: The present study indicates that gut microbiota alterations are present in European patients with schizophrenia. The abundance of certain bacterial taxa might be associated with the severity of negative symptoms, cognitive performance and general functioning. Nonetheless, additional studies are needed before the translation of our results into clinical practice.

目的:对精神分裂症的发病机制进行了多方面的深入研究。肠脑轴紊乱可能在精神分裂症的发展中起重要作用。方法:采用16S rRNA测序方法,对53例精神分裂症患者和58例健康对照者的肠道菌群进行比较。采用以下量表对精神分裂症患者进行评估:阳性和阴性综合征量表、精神分裂症卡尔加里抑郁量表、社会和职业功能评估量表和神经心理状态评估可重复电池。结果:各组间α-多样性指标无显著差异。无论潜在的混淆因素如何,在精神分裂症患者中发现乳酸杆菌(目水平)、芽胞杆菌(纲水平)和放线菌(门水平)的丰度增加,并使用两种独立的分析方法(基于距离的冗余分析和广义线性模型分析)。此外,各种细菌分类群(拟杆菌纲、放线菌纲、拟杆菌纲、科氏杆菌纲和科氏杆菌纲)与临床表现(阴性症状的严重程度、语言能力的表现、社会和职业功能)之间存在显著相关性。结论:目前的研究表明,欧洲精神分裂症患者存在肠道菌群改变。某些细菌分类群的丰度可能与阴性症状的严重程度、认知能力和一般功能有关。尽管如此,在将我们的结果转化为临床实践之前,还需要进行更多的研究。
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引用次数: 2
Dynamic impedance is correlated with static impedance and seizure quality parameters in bifrontal electroconvulsive therapy. 在双额电惊厥治疗中,动态阻抗与静态阻抗和癫痫发作质量参数相关。
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1017/neu.2023.10
Jan Exner, Gunnar Deuring, Erich Seifritz, Annette Beatrix Brühl

Background: To evoke a therapeutically effective seizure, electrical stimulation in electroconvulsive therapy (ECT) has to overcome the combined resistivity of scalp, skull and other tissues. Static impedances are measured prior to stimulation using high-frequency electrical alternating pulses, dynamic impedances during passage of the stimulation current. Static impedance can partially be influenced by skin preparation techniques. Earlier studies showed a correlation between dynamic and static impedance in bitemporal and right unilateral ECT.

Objective: This study aims at assessing the correlation of dynamic and static impedance with patient characteristics and seizure quality criteria in bifrontal ECT.

Methods: We performed a cross-sectional single-centre retrospective analysis of ECT treatments at the Psychiatric University Hospital Zurich between May 2012 and March 2020 and used linear mixed-effects regression models in 78 patients with a total of 1757 ECT sessions.

Results: Dynamic and static impedance were strongly correlated. Dynamic impedance was significantly correlated with age and higher in women. Energy set and factors positively (caffeine) and negatively (propofol) affecting seizure at the neuronal level were not associated with dynamic impedance. For secondary outcomes, dynamic impedance was significantly related to Maximum Sustained Power and Average Seizure Energy Index. Other seizure quality criteria showed no significant correlation with dynamic impedance.

Conclusion: Aiming for low static impedance might reduce dynamic impedance, which is correlated with positive seizure quality parameters. Therefore, good skin preparation to achieve low static impedance is recommended.

背景:为了引起治疗上有效的癫痫发作,电痉挛疗法(ECT)中的电刺激必须克服头皮、颅骨和其他组织的综合电阻率。在使用高频电脉冲刺激之前测量静态阻抗,在刺激电流通过期间测量动态阻抗。静电阻抗可以部分地受到皮肤制备技术的影响。早期的研究表明,在双颞和右单侧电痉挛中动态和静态阻抗之间存在相关性。目的:本研究旨在评估双额电痉挛中动态和静态阻抗与患者特征和癫痫发作质量标准的相关性。方法:我们对苏黎世精神病学大学医院2012年5月至2020年3月期间的ECT治疗进行了横断面单中心回顾性分析,并对78名患者进行了1757次ECT治疗,使用线性混合效应回归模型。结果:动态阻抗与静态阻抗相关性强。动态阻抗与年龄显著相关,女性较高。在神经元水平上,能量设置和影响癫痫发作的积极因素(咖啡因)和消极因素(异丙酚)与动态阻抗无关。对于次要结果,动态阻抗与最大持续功率和平均发作能量指数显著相关。其他癫痫发作质量标准与动态阻抗无显著相关性。结论:以低静态阻抗为目标可降低动态阻抗,动态阻抗与癫痫发作质量参数呈正相关。因此,建议进行良好的皮肤准备以达到低静态阻抗。
{"title":"Dynamic impedance is correlated with static impedance and seizure quality parameters in bifrontal electroconvulsive therapy.","authors":"Jan Exner,&nbsp;Gunnar Deuring,&nbsp;Erich Seifritz,&nbsp;Annette Beatrix Brühl","doi":"10.1017/neu.2023.10","DOIUrl":"https://doi.org/10.1017/neu.2023.10","url":null,"abstract":"<p><strong>Background: </strong>To evoke a therapeutically effective seizure, electrical stimulation in electroconvulsive therapy (ECT) has to overcome the combined resistivity of scalp, skull and other tissues. Static impedances are measured prior to stimulation using high-frequency electrical alternating pulses, dynamic impedances during passage of the stimulation current. Static impedance can partially be influenced by skin preparation techniques. Earlier studies showed a correlation between dynamic and static impedance in bitemporal and right unilateral ECT.</p><p><strong>Objective: </strong>This study aims at assessing the correlation of dynamic and static impedance with patient characteristics and seizure quality criteria in bifrontal ECT.</p><p><strong>Methods: </strong>We performed a cross-sectional single-centre retrospective analysis of ECT treatments at the Psychiatric University Hospital Zurich between May 2012 and March 2020 and used linear mixed-effects regression models in 78 patients with a total of 1757 ECT sessions.</p><p><strong>Results: </strong>Dynamic and static impedance were strongly correlated. Dynamic impedance was significantly correlated with age and higher in women. Energy set and factors positively (caffeine) and negatively (propofol) affecting seizure at the neuronal level were not associated with dynamic impedance. For secondary outcomes, dynamic impedance was significantly related to Maximum Sustained Power and Average Seizure Energy Index. Other seizure quality criteria showed no significant correlation with dynamic impedance.</p><p><strong>Conclusion: </strong>Aiming for low static impedance might reduce dynamic impedance, which is correlated with positive seizure quality parameters. Therefore, good skin preparation to achieve low static impedance is recommended.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Serum s100b protein levels as a neuroinflammatory biomarker of acutely relapsed paranoid schizophrenia patients. 血清s100b蛋白水平作为急性复发偏执型精神分裂症患者的神经炎症生物标志物
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1017/neu.2022.37
Armando L Morera-Fumero, Estefania Diaz-Mesa, Lourdes Fernandez-Lopez, Pedro Abreu-Gonzalez, Manuel S Henry-Benitez

Objective: The s100b inflammatory protein is involved in schizophrenia pathophysiology. We aim at studying the evolution of the s100b serum levels in acutely relapsed paranoid schizophrenia patients at three different time points (admission, discharge and 3 months after hospital discharge 3MAHD).

Methods: Twenty-three paranoid schizophrenia inpatients meeting DSM-IV criteria participated in the research. Twenty-three healthy subjects matched by age, gender and season acted as the control group. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Serum s100b levels were determined at 12:00 and 24:00 h with an enzyme-linked immunoassay kit.

Results: Patients had significant higher serum s100b levels at admission and discharge (12:00 h) than the group of healthy subjects. At admission and discharge, s100b serum levels at 24 h had decreased compared to the 24:00 h s100b levels of the healthy subjects. At 3MAHD patients and healthy subjects had similar levels of serum s100b protein. Positive and negative PANSS scores decreased significantly between admission and discharge. Positive and negative PANSS scores decreased between discharge and 3MAHD, but these changes had no statistical significance.

Conclusions: Our study confirms that the acute inflammatory response produced in acutely relapsed patients is reversed after 3 month of hospital discharge. The variations of serum s100b concentrations when the patients suffer from an acute relapse may be a useful predictor of disease evolution.

目的:炎性蛋白s100b参与精神分裂症的病理生理。我们旨在研究急性复发型偏执型精神分裂症患者在三个不同时间点(入院、出院和出院后3个月)血清s100b水平的变化。方法:23例符合DSM-IV标准的偏执型精神分裂症住院患者参与研究。23名按年龄、性别、季节相匹配的健康受试者作为对照组。采用阳性和阴性综合征量表(PANSS)进行精神病理检查。在12:00和24:00 h用酶联免疫测定试剂盒检测血清s100b水平。结果:患者入院和出院时(12:00 h)血清s100b水平明显高于健康对照组。入院和出院时,24 h血清s100b水平较健康受试者24时s100b水平有所下降。3MAHD患者和健康受试者血清s100b蛋白水平相似。PANSS阳性和阴性评分在入院和出院期间显著下降。PANSS阳性和阴性评分在出院和3MAHD期间均有所下降,但变化无统计学意义。结论:我们的研究证实,急性复发患者的急性炎症反应在出院3个月后得到逆转。患者急性复发时血清s100b浓度的变化可能是疾病演变的有用预测因子。
{"title":"Serum s100b protein levels as a neuroinflammatory biomarker of acutely relapsed paranoid schizophrenia patients.","authors":"Armando L Morera-Fumero,&nbsp;Estefania Diaz-Mesa,&nbsp;Lourdes Fernandez-Lopez,&nbsp;Pedro Abreu-Gonzalez,&nbsp;Manuel S Henry-Benitez","doi":"10.1017/neu.2022.37","DOIUrl":"https://doi.org/10.1017/neu.2022.37","url":null,"abstract":"<p><strong>Objective: </strong>The s100b inflammatory protein is involved in schizophrenia pathophysiology. We aim at studying the evolution of the s100b serum levels in acutely relapsed paranoid schizophrenia patients at three different time points (admission, discharge and 3 months after hospital discharge 3MAHD).</p><p><strong>Methods: </strong>Twenty-three paranoid schizophrenia inpatients meeting DSM-IV criteria participated in the research. Twenty-three healthy subjects matched by age, gender and season acted as the control group. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Serum s100b levels were determined at 12:00 and 24:00 h with an enzyme-linked immunoassay kit.</p><p><strong>Results: </strong>Patients had significant higher serum s100b levels at admission and discharge (12:00 h) than the group of healthy subjects. At admission and discharge, s100b serum levels at 24 h had decreased compared to the 24:00 h s100b levels of the healthy subjects. At 3MAHD patients and healthy subjects had similar levels of serum s100b protein. Positive and negative PANSS scores decreased significantly between admission and discharge. Positive and negative PANSS scores decreased between discharge and 3MAHD, but these changes had no statistical significance.</p><p><strong>Conclusions: </strong>Our study confirms that the acute inflammatory response produced in acutely relapsed patients is reversed after 3 month of hospital discharge. The variations of serum s100b concentrations when the patients suffer from an acute relapse may be a useful predictor of disease evolution.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9890210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 3
Distributed Genetic Effects of the Corpus Callosum Subregions Suggest Links to Neuropsychiatric Disorders and Related Traits 胼胝体亚区的分布遗传效应表明与神经精神障碍和相关特征有关
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-05-14 DOI: 10.1101/2023.05.13.23289938
M. Campbell, S. Dalvie, A. Shadrin, D. van der Meer, K. O’Connell, O. Frei, O. Andreassen, Dan J Stein, J. Rokicki
Background: The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remains largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions, and the genetic overlap with psychiatric disorders. Methods: We applied multivariate GWAS to genetic and T1-weighted MRI data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid posterior, central, mid anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine SNP-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits. Results: We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 x 10-8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid anterior, 29 in the central, 7 in the mid posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 x 10-6). LDSC estimated the heritability of CC to (h2SNP=0.38, SE=0.03), and subregions ranging from 0.22 (SE=0.02) to 0.37 (SE=0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg=-0.09, SE=0.03; p=5.9 x 10-3) and drinks consumed per week (rg=-0.09, SE=0.02; p=4.8 x 10-4), and volume of the mid anterior subregion with BD (rg=-0.12, SE=0.02; p=2.5 x 10-4), major depressive disorder (rg=-0.12, SE=0.04; p=3.6 x 10-3), drinks consumed per week (rg=-0.13, SE=0.04; p=1.8 x 10-3) and cannabis use (rg=-0.09, SE=0.03; p=8.4 x 10-3). Conclusions: Our results demonstrate that the CC has a polygenic architecture implicating multiple genes, and show that CC subregion volumes are heritable. We found distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialization. Significant genetic correlation between volumes of the CC and bipolar disorder, drinks per week, major depressive disorder and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.
背景:胼胝体(CC)是一种具有高遗传性的大脑结构,在精神疾病中具有潜在作用。然而,CC的遗传结构以及与精神疾病的遗传联系在很大程度上仍不清楚。我们研究了CC体积及其亚区的遗传结构,以及与精神疾病的遗传重叠。方法:我们将多变量GWAS应用于英国生物库40894名个体的遗传和T1加权MRI数据,旨在促进基因发现,并评估FreeSurfer 7.1获得的CC五个亚区(后部、中后部、中部、中前部和前部)体积的多效性效应。多变量GWAS结合所有子区域运行,相关变量共同变化。使用MAGMA进行基因集富集分析。连锁不平衡评分回归(LDSC)用于确定基于SNP的CC总体积及其亚区体积的遗传力,以及它们与相关精神特征的遗传相关性。结果:我们确定了70个独立的基因座,这些基因座在CC的五个亚区具有分布效应(p<5×10-8)。此外,我们在前部亚区确定了33个重要位点,23个在前部中部,29个在中部,7个在后部,56个在后部亚区。基因集分析显示,156个重要基因对CC亚区的体积有贡献(p<2.6 x 10-6)。LDSC估计CC的遗传力为(h2SNP=0.38,SE=0.03),亚区的遗传力范围为0.22(SE=0.02)至0.37(SE=0.03)。我们发现总CC容量与双相情感障碍(BD,rg=0.09,SE=0.03;p=5.9 x 10-3)和每周饮酒量(rg-0.09,SE=0.02;p=4.8 x 10-4)之间存在显著的遗传相关性,重度抑郁障碍(rg=0.12,SE=0.04;p=3.6 x 10-3)、每周饮酒量(rg=0.13,SE=0.4;p=1.8 x 10-3。结论:我们的结果表明CC具有涉及多个基因的多基因结构,并表明CC亚区体积是可遗传的。我们发现不同的遗传因素参与了前部和后部亚区的发育,这与它们不同的功能专门化一致。CC量和双相情感障碍、每周饮酒量、重度抑郁障碍和大麻消费亚区域量与精神特征之间存在显著的遗传相关性,值得注意,值得进一步研究。
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引用次数: 1
Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors: effects of in vitro cannabidiol administration. T和B淋巴细胞大麻素1型和2型受体在严重抑郁和自杀行为中的作用:体外施用大麻素的影响。
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-04-25 DOI: 10.1101/2023.04.19.23288847
Michael Maes, M. Rachayon, K. Jirakran, A. Sughondhabirom, A. Almulla, P. Sodsai
Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD) (Maes et al., 1990-1993). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2. Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2 and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 mug/mL, 1.0 mug/mL or 10.0 mug/mL CBD. We found that CB2+ was significantly higher in CD20+ than CD3+ and CD4+, and CD8+ cells. Stimulation with anti-CD3/CD8 beads increases the number of CB2-bearing CD3+, CD4+, and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterized by lowered basal FoxP3+CB1+% and higher CD20+CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety, and current suicidal behaviors) is explained by CD20+CB2+% (positively) and CD3+CB2+% (inversely). All 5 immune cell populations were significantly increased by 10 mug/mL CBD administration. In conclusion, reductions in FoxP3+CB1+% and CD3+/CD4+CB2+% contribute to deficits in immune homeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.
早期的流式细胞术研究揭示了严重抑郁障碍(MDD)中的T细胞活化(Maes等人,1990-1993)。MDD的特征是免疫炎症反应系统(IRS)和补偿免疫调节系统(CIRS)的激活,包括T调节(Treg)细胞的缺陷。本研究检测了MDD中携带大麻素1型(CB1)和2型(CB2)受体的T/B淋巴细胞的数量,以及体外施用大麻素二醇(CBD)对CB1/CB2的影响。使用流式细胞术,我们在5种条件下测定了19名健康对照和29名MDD患者的CD20+CB2+、CD3+CB2+,CD4+CB2+和CD8+CB2以及FoxP3+CB1+细胞的百分比:基线,用抗CD3/CD28刺激或不加0.1、1.0或10.0。我们发现CD20+中的CB2+显著高于CD3+、CD4+和CD8+细胞。用抗CD3/CD8珠的刺激增加了携带CD3+、CD4+和CD8+细胞的CB2以及携带FoxP3+细胞的CB1的数量。CD4+CB2+减少的数量与IRS谱(包括M1巨噬细胞、T辅助细胞-(Th)-1和Th-17表型)之间存在负相关。MDD的特征是基础FoxP3+CB1+%降低和CD20+CB2+%升高。33.2%的抑郁现象(包括抑郁、焦虑和当前自杀行为的严重程度)的差异由CD20+CB2+%(阳性)和CD3+CB2++%(阴性)解释。所有5个免疫细胞群均通过10mug/mL CBD给药显著增加。总之,FoxP3+CB1+%和CD3+/CD4+CB2+%的减少有助于MDD免疫稳态的缺陷,而CD20+CB2++%的增加可能通过激活T非依赖性体液免疫来促进MDD的病理生理学。
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引用次数: 1
Regional spectral ratios as potential neural markers to identify mild cognitive impairment related to Alzheimer's disease. 区域谱比作为识别阿尔茨海默病相关轻度认知障碍的潜在神经标志物。
IF 3.8 4区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1017/neu.2022.18
Tien-Wen Lee, Gerald Tramontano

Objective: Alzheimer's disease (AD) has prolonged asymptomatic or mild symptomatic periods. Given that there is an increase in treatment options and that early intervention could modify the disease course, it is desirable to devise biological indices that may differentiate AD and nonAD at mild cognitive impairment (MCI) stage.

Methods: Based on two well-acknowledged observations of background slowing (attenuation in alpha power and enhancement in theta and delta powers) and early involvement of posterior cingulate cortex (PCC, a neural hub of default-mode network), this study devised novel neural markers, namely, spectral ratios of alpha1 to delta and alpha1 to theta in the PCC.

Results: We analysed 46 MCI patients, with 22 ADMCI and 24 nonADMCI who were matched in age, education, and global cognitive capability. Concordant with the prediction, the regional spectral ratios were lower in the ADMCI group, suggesting its clinical application potential.

Conclusion: Previous research has verified that neural markers derived from clinical electroencephalography may be informative in differentiating AD from other neurological conditions. We believe that the spectral ratios in the neural hubs that show early pathological changes can enrich the instrumental assessment of brain dysfunctions at the MCI (or pre-clinical) stage.

目的:阿尔茨海默病(AD)具有较长的无症状期或轻度症状期。考虑到治疗选择的增加和早期干预可以改变疾病进程,设计可以区分轻度认知障碍(MCI)阶段AD和非AD的生物学指标是必要的。方法:基于两个公认的背景变慢(α功率衰减,θ和δ功率增强)和早期累及后扣带皮层(PCC,默认模式网络的神经中枢)的观察结果,本研究设计了新的神经标记,即在PCC中α 1与δ和α 1与θ的频谱比。结果:我们分析了46例MCI患者,其中22例ADMCI患者和24例非ADMCI患者,他们在年龄、教育程度和全球认知能力方面相匹配。与预测一致,ADMCI组的区域谱比较低,提示其临床应用潜力。结论:已有研究证实,临床脑电图神经标记物可用于区分AD与其他神经系统疾病。我们认为,显示早期病理变化的神经中枢的频谱比可以丰富MCI(或临床前)阶段脑功能障碍的工具评估。
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引用次数: 2
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Acta Neuropsychiatrica
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