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Action prediction in psychosis. 精神病患者的行动预测。
Q2 PSYCHIATRY Pub Date : 2024-01-10 DOI: 10.1038/s41537-023-00429-x
Noemi Montobbio, Enrico Zingarelli, Federica Folesani, Mariacarla Memeo, Enrico Croce, Andrea Cavallo, Luigi Grassi, Luciano Fadiga, Stefano Panzeri, Martino Belvederi Murri, Cristina Becchio

Aberrant motor-sensory predictive functions have been linked to symptoms of psychosis, particularly reduced attenuation of self-generated sensations and misattribution of self-generated actions. Building on the parallels between prediction of self- and other-generated actions, this study aims to investigate whether individuals with psychosis also demonstrate abnormal perceptions and predictions of others' actions. Patients with psychosis and matched controls completed a two-alternative object size discrimination task. In each trial, they observed reaching actions towards a small and a large object, with varying levels of temporal occlusion ranging from 10% to 80% of movement duration. Their task was to predict the size of the object that would be grasped. We employed a novel analytic approach to examine how object size information was encoded and read out across progressive levels of occlusion with single-trial resolution. Patients with psychosis exhibited an overall pattern of reduced and discontinuous evidence integration relative to controls, characterized by a period of null integration up to 20% of movement duration, during which they did not read any size information. Surprisingly, this drop in accuracy in the initial integration period was not accompanied by a reduction in confidence. Difficulties in action prediction were correlated with the severity of negative symptoms and impaired functioning in social relationships.

异常的运动感觉预测功能与精神病的症状有关,尤其是对自我产生的感觉的衰减和对自我产生的行动的错误归因。基于对自身和他人动作的预测之间的相似性,本研究旨在探讨精神病患者是否也会表现出对他人动作的异常感知和预测。精神病患者和匹配的对照组完成了一项双备选物体大小辨别任务。在每次试验中,他们观察了向一个小物体和一个大物体伸手的动作,时间闭塞程度从动作持续时间的 10% 到 80% 不等。他们的任务是预测将要抓住的物体的大小。我们采用了一种新颖的分析方法来研究物体大小信息是如何在单次试验分辨率下通过渐进的闭塞水平进行编码和读出的。与对照组相比,精神病患者表现出证据整合减少和不连续的整体模式,其特点是整合无效期长达运动持续时间的 20%,在此期间他们没有读出任何尺寸信息。令人惊讶的是,最初整合期准确率的下降并没有伴随着信心的降低。动作预测的困难与消极症状的严重程度和社会关系功能的受损程度相关。
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引用次数: 0
OXTR polymorphisms associated with severity and treatment responses of schizophrenia. 与精神分裂症严重程度和治疗反应相关的 OXTR 多态性。
Q2 PSYCHIATRY Pub Date : 2024-01-06 DOI: 10.1038/s41537-023-00413-5
Xue Lv, Yue-Sen Hou, Zhao-Hui Zhang, Wei-Hua Yue

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = -0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.

精神分裂症特定症状的产生机制尚不清楚,而基因研究使我们有可能从根本上探讨这些问题。考虑到催产素系统与精神分裂症患者明显受损的社会功能之间的关联,我们假设催产素受体基因(OXTR)可能与精神分裂症症状的严重程度和对抗抑郁药的反应有关,并进行了这项探索性定位研究。我们的研究共包括 2363 名精神分裂症患者(男性 1181 人,女性 1182 人),他们被随机分配到 7 个抗精神病药物治疗组,接受为期 6 周的抗精神病药物单药治疗。对他们的血液 DNA 进行了 OXTR 多态性基因分型。他们的症状严重程度由阳性和阴性综合征量表(PANSS)进行评估,并将得分转化为七个因子(阳性、混乱、阴性症状冷漠/逃避、阴性症状表达缺失、敌意、焦虑和抑郁)。计算 PANSS 评分从基线到第 6 周的百分比变化,以量化抗精神病药物反应。我们发现,OXTR 多态性与总体症状(rs237899,β = 1.669,p = 0.019)、敌意症状(rs237899,β = 0.427,p = 0.044)和焦虑症状(rs13316193,β = -0.197,p = 0.038)的严重程度有名义上的相关性。至于治疗反应,OXTR 多态性与负性症状冷漠/逃避的改善有一定关系(rs2268490,β = 2.235,p = 0.0499)。在对多态性进行统计校正后,未发现严重程度或对治疗的反应与 OXTR 多态性之间存在关联。总之,我们的研究结果表明,OXTR 基因与精神分裂症症状的严重程度和改善之间可能存在名义上的显著关联。鉴于本研究的探索性质,这些关联表明了 OXTR 基因在精神分裂症病理中的作用,并可能有助于进一步阐明精神分裂症特定症状的机制,以及开发对特定症状更有效的抗精神病药物。
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引用次数: 0
Sex differences in autonomic adverse effects related to antipsychotic treatment and associated hormone profiles. 与抗精神病治疗相关的自律神经不良反应的性别差异及相关激素谱。
Q2 PSYCHIATRY Pub Date : 2024-01-06 DOI: 10.1038/s41537-023-00430-4
Ingrid T Johansen, Nils Eiel Steen, Linn Rødevand, Synve H Lunding, Gabriela Hjell, Monica B E G Ormerod, Ingrid Agartz, Ingrid Melle, Trine V Lagerberg, Mari Nerhus, Ole A Andreassen

Autonomic adverse effects of antipsychotic drugs (APs) cause clinical challenges, but few studies have investigated sex differences and their underlying biological pathways. Sex-specific regulation of relevant hormones could be involved. We investigated sex differences in autonomic adverse effects related to olanzapine, quetiapine, risperidone, and aripiprazole, and the role of hormones related to APs. Patients with severe mental disorders (N = 1318) were included and grouped based on AP monotherapy: olanzapine (N = 364), quetiapine (N = 211), risperidone (N = 102), aripiprazole (N = 138), and no AP (N = 503). Autonomic symptoms from the Udvalg for Kliniske Undersøgelser (UKU) side effect scale was analyzed with logistic regression, adjusting for age, diagnosis, and polypharmacy. Further, we analyzed associations between autonomic symptoms and hormones related to APs. We found associations between autonomic adverse effects and APs, with sex-specific risk for palpitations/tachycardia associated with hormonal changes related to APs. Results showed increased salivation associated with aripiprazole, reduced salivation with quetiapine, and nausea/vomiting and palpitations/tachycardia with olanzapine, and higher risk of nausea/vomiting, diarrhea, constipation, polyuria/polydipsia, and palpitations/tachycardia in females. Significant sex x AP interaction was found for palpitations/tachycardia, with higher risk in risperidone-treated males, which was associated with different hormone profiles of prolactin, cortisol, and insulin. Our findings implicate a role of several hormones in the sex-specific autonomic adverse effects related to APs.

抗精神病药物(APs)的自主神经不良反应给临床带来了挑战,但很少有研究对性别差异及其潜在的生物学途径进行调查。这可能与相关激素的性别特异性调节有关。我们研究了与奥氮平、喹硫平、利培酮和阿立哌唑相关的自主神经不良反应的性别差异,以及与抗精神病药物相关的激素的作用。研究纳入了严重精神障碍患者(N = 1318),并根据 AP 单一疗法进行分组:奥氮平(N = 364)、喹硫平(N = 211)、利培酮(N = 102)、阿立哌唑(N = 138)和无 AP(N = 503)。通过逻辑回归分析了Udvalg for Kliniske Undersøgelser (UKU) 副作用量表中的自主神经症状,并对年龄、诊断和多重用药进行了调整。此外,我们还分析了自律神经症状和与 APs 相关的激素之间的关联。我们发现自律神经不良反应与 APs 之间存在关联,其中心悸/心动过速的性别特异性风险与 APs 相关的激素变化有关。结果显示,阿立哌唑会导致流涎增加,喹硫平会导致流涎减少,奥氮平会导致恶心/呕吐和心悸/心动过速,而女性出现恶心/呕吐、腹泻、便秘、多尿/多尿、心悸/心动过速的风险更高。在心悸/心动过速方面发现了显著的性别 x AP交互作用,利培酮治疗的男性风险更高,这与催乳素、皮质醇和胰岛素的不同激素谱有关。我们的研究结果表明,在与 APs 相关的特定性别自律神经不良反应中,多种激素发挥了作用。
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引用次数: 0
Non-prescribing of clozapine for outpatients with schizophrenia in real-world settings: The clinicians' perspectives. 在现实环境中,精神分裂症门诊患者不使用氯氮平:临床医生的观点。
Q2 PSYCHIATRY Pub Date : 2023-12-22 DOI: 10.1038/s41537-023-00423-3
Michelle Iris Jakobsen, Stephen Fitzgerald Austin, Ole Jakob Storebø, Jimmi Nielsen, Erik Simonsen

Clozapine is the gold standard for treating treatment-resistant schizophrenia although continuously underutilized. Previous surveys of clinicians have found that some of the most frequently cited barriers to clozapine prescribing are related to the blood-monitoring requirements. However, these surveys tend to explore general perspectives and may not reflect the true impact of different barriers in real-world outpatient settings. This study aimed to explore this issue. First, by surveying the clinicians responsible for the treatment of 39 clozapine-eligible, yet clozapine-naive, outpatients with schizophrenia. Then, based on the survey results, explanatory interviews with the participating psychiatrists were conducted and analyzed thematically. The most frequently cited reason for non-prescribing of clozapine was the expected non-compliance with blood-monitoring requirements; however, overall stability and/or severe mental illness was chosen as the most important reason in most patient-cases. The qualitative analysis highlighted the combined impact of standard clinical practice, personal experiences, and organizational constraints on clozapine utility.

氯氮平是治疗耐药性精神分裂症的金标准,但一直未得到充分利用。此前对临床医生进行的调查发现,氯氮平处方中最常被提及的一些障碍与血液监测要求有关。然而,这些调查倾向于探讨一般观点,可能无法反映不同障碍在实际门诊环境中的真实影响。本研究旨在探讨这一问题。首先,调查了负责治疗 39 名符合氯氮平治疗条件但未服用氯氮平的门诊精神分裂症患者的临床医生。然后,根据调查结果对参与调查的精神科医生进行解释性访谈,并进行专题分析。不开具氯氮平处方的最常见原因是预期不符合血液监测要求;然而,在大多数患者病例中,整体稳定性和/或严重精神疾病被选为最重要的原因。定性分析强调了标准临床实践、个人经历和组织限制对氯氮平使用的综合影响。
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引用次数: 0
Intra- and inter-individual cognitive variability in schizophrenia and bipolar spectrum disorder: an investigation across multiple cognitive domains. 精神分裂症和双相情感谱系障碍的个体内和个体间认知变异:跨多个认知领域的研究。
Q2 PSYCHIATRY Pub Date : 2023-12-18 DOI: 10.1038/s41537-023-00414-4
Beathe Haatveit, Lars T Westlye, Anja Vaskinn, Camilla Bärthel Flaaten, Christine Mohn, Thomas Bjella, Linn Sofie Sæther, Kjetil Sundet, Ingrid Melle, Ole A Andreassen, Dag Alnæs, Torill Ueland

There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC, n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.

精神分裂症(SZ)和双相情感障碍(BD)患者的认知存在很大的异质性。更多地了解认知能力变异的程度和临床相关性,可以提高我们对认知障碍的理解。我们使用双广义线性模型(DGLMs)研究了 SZ(905 人)和 BD 谱系障碍(522 人)患者与健康对照组(1170 人)在 22 个变量上的认知平均值和变异性差异。分析显示,90%的变量存在明显的病例对照差异。与健康对照组相比,在精细运动速度、心理处理速度和抑制控制(SZ 和 BD)以及言语学习、记忆和智力功能(SZ)方面,患者在不同测试中表现出更大的个体内(主体内)变异性和更大的个体间(主体间)变异性。我们发现,在 SZ 中,个体内部和个体之间(抑制控制和速度功能)的变异性越大,其功能越低,负面症状越多。在记忆和智力功能的单项测量中,个体间的差异性还与紊乱和阳性症状以及抗抑郁药物的使用有关。在 BD 中,受试者内部与症状严重程度没有关联。然而,个体间更大的变异性(主要是抑制控制和加速功能)与功能低下、更多的消极和紊乱症状、更早的发病年龄、更长的病程以及更多的药物使用有关。这些结果突显出,与对照组相比,患者在各个认知领域的个体差异更大。我们有必要进一步研究认知功能个体差异的原因和相关因素。
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引用次数: 0
Patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia: mediation effects of potentially harmful behavior, affiliate stigma, and social support. 中国精神分裂症患者家庭照顾者的残疾和照顾者负担:潜在有害行为、附属污名和社会支持的中介作用
Q2 PSYCHIATRY Pub Date : 2023-12-01 DOI: 10.1038/s41537-023-00418-0
Dan Qiu, Yilu Li, Qiuyan Wu, Yanni An, Zixuan Tang, Shuiyuan Xiao

Evidence on the associations between patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia is lacking. This study aimed at explore the underlying mechanisms between patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia. A cross-sectional study was carried out in four Chinese cities (Wuhan, Changsha, Guangzhou, and Shenzhen), between April, 2021 and March, 2022. A total of 493 patients and their family caregivers were invited to report related data. The Zarit burden interview, WHODAS 2.0, the Potentially harmful behavior scale, the Affiliate Stigma Scale, and the Multidimensional Scale of perceived social support were used to collect data. Linear regression analysis and bootstrapping analysis were conducted. The adjusted regression results showed that patients' disability (B = 0.616; 95% CI: 0.479-0.753), potentially harmful behavior on caregivers (B = 0.474; 95% CI: 0.232-0.716), and caregiver's low social support (B = -0.079; 95% CI: -0.158- -0.002), high level of affiliate stigma (B = 13.045; 95% CI: 10.227-15.864) were associated with higher level of caregiver burden (p < 0.05). In the mediation model, the direct path from patient's disability to caregiver burden (B = 0.428, β = 0.371, p < 0.001) was significant and positive. Patient's disability was indirectly associated with caregiver burden through patient's potentially harmful behavior, caregiver's affiliate stigma, and social support, the standardized regression coefficients ranged from 0.026-0.049 (p < 0.05). Patient's potentially harmful behavior, caregiver's affiliate stigma, and social support mediated the relationship between patients' disability and caregiver burden. Future intervention studies designed to target these three factors may be beneficial for family caregivers of persons living with schizophrenia.

中国精神分裂症患者家庭照顾者的残疾与照顾者负担之间的关系尚缺乏证据。本研究旨在探讨中国精神分裂症患者家庭照顾者残疾与照顾者负担之间的潜在机制。在2021年4月至2022年3月期间,在中国四个城市(武汉、长沙、广州和深圳)进行了横断面研究。共邀请493名患者及其家庭照顾者报告相关数据。采用Zarit负担访谈、WHODAS 2.0、潜在有害行为量表、附属污名量表和感知社会支持多维量表收集数据。进行了线性回归分析和自举分析。调整后的回归结果显示,患者的残疾程度(B = 0.616;95% CI: 0.479-0.753),对照顾者的潜在有害行为(B = 0.474;95% CI: 0.232-0.716),照顾者社会支持低(B = -0.079;95% CI: -0.158- -0.002),高水平的附属柱头(B = 13.045;95% CI: 10.227-15.864)与较高水平的照顾者负担相关(p
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引用次数: 0
Slower clozapine titration is associated with delayed onset of clozapine-induced fever among Japanese patients with schizophrenia. 在日本精神分裂症患者中,较慢的氯氮平滴定与氯氮平诱发的发烧延迟发作有关。
IF 3 Q2 PSYCHIATRY Pub Date : 2023-11-20 DOI: 10.1038/s41537-023-00412-6
Yuki Kikuchi, Yuji Yada, Yuji Otsuka, Fumiaki Ito, Hiroaki Tanifuji, Hiroshi Komatsu, Hiroaki Tomita

Clozapine-induced fever marks the beginning of its inflammatory and potentially life-threatening adverse effects, such as myocarditis. We retrospectively analyzed the correlation between clozapine titration rate and fever onset date in 254 Japanese patients, including 55 with treatment-resistant schizophrenia who developed clozapine-induced fever. Pearson's product-moment correlation indicated a significant delay in the fever onset date with slower titration. Most fever onset cases occurred within 4 weeks, even with slow titration. Therefore, clinicians should remain vigilant in monitoring clozapine-induced fever within 4 weeks of clozapine initiation, regardless of the titration rate.

氯氮平引起的发热标志着其炎症和潜在危及生命的不良反应的开始,如心肌炎。我们回顾性分析了254名日本患者氯氮平滴定率与发热发病日期的相关性,其中包括55名出现氯氮平诱发发热的难治性精神分裂症患者。皮尔逊积差相关性表明,随着滴定速度的减慢,发烧发病日期明显延迟。大多数发热病例发生在4周内,即使滴定缓慢。因此,临床医生应保持警惕,在氯氮平开始使用后4周内监测氯氮平引起的发热,无论滴定率如何。
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引用次数: 0
Fronto-striato-thalamic circuit connectivity and neuromelanin in schizophrenia: an fMRI and neuromelanin-MRI study. 精神分裂症患者的额纹状体-丘脑回路连接和神经松弛素:功能磁共振成像和神经松弛蛋白MRI研究。
IF 3 Q2 PSYCHIATRY Pub Date : 2023-11-10 DOI: 10.1038/s41537-023-00410-8
Sunah Choi, Minah Kim, Taekwan Kim, Eun-Jung Choi, Jungha Lee, Sun-Young Moon, Sang Soo Cho, Jongho Lee, Jun Soo Kwon

Changes in dopamine and fronto-striato-thalamic (FST) circuit functional connectivity are prominent in schizophrenia. Dopamine is thought to underlie connectivity changes, but experimental evidence for this hypothesis is lacking. Previous studies examined the association in some of the connections using positron emission tomography (PET) and functional MRI (fMRI); however, PET has disadvantages in scanning patients, such as invasiveness. Excessive dopamine induces neuromelanin (NM) accumulation, and NM-MRI is suggested as a noninvasive proxy measure of dopamine function. We aimed to investigate the association between NM and FST circuit connectivity at the network level in patients with schizophrenia. We analysed substantia nigra NM-MRI and resting-state fMRI data from 29 schizophrenia patients and 63 age- and sex-matched healthy controls (HCs). We identified the FST subnetwork with abnormal connectivity found in schizophrenia patients compared to that of HCs and investigated the relationship between constituting connectivity and NM-MRI signal. We found a higher NM signal (t = -2.12, p = 0.037) and a hypoconnected FST subnetwork (FWER-corrected p = 0.014) in schizophrenia patients than in HCs. In the hypoconnected subnetwork of schizophrenia patients, lower left supplementary motor area-left caudate connectivity was associated with a higher NM signal (β = -0.38, p = 0.042). We demonstrated the association between NM and FST circuit connectivity. Considering that the NM-MRI signal reflects dopamine function, our results suggest that dopamine underlies changes in FST circuit connectivity, which supports the dopamine hypothesis. In addition, this study reveals implications for the future use of NM-MRI in investigations of the dopamine system.

多巴胺和额纹状体-丘脑(FST)回路功能连接的变化在精神分裂症中很突出。多巴胺被认为是连接变化的基础,但缺乏这一假设的实验证据。先前的研究使用正电子发射断层扫描(PET)和功能性MRI(fMRI)检查了一些连接中的相关性;然而,PET在扫描患者时有缺点,例如侵入性。过量的多巴胺会诱导神经松弛素(NM)的积累,NM-MRI被认为是多巴胺功能的非侵入性替代指标。我们旨在研究精神分裂症患者网络水平上NM和FST电路连接之间的关系。我们分析了29名精神分裂症患者和63名年龄和性别匹配的健康对照(HC)的黑质NM-MRI和静息态fMRI数据。我们确定了在精神分裂症患者中发现的与HC相比具有异常连接的FST子网络,并研究了构成连接与NM-MRI信号之间的关系。我们发现NM信号(t = -2.12,p = 0.037)和次连接FST子网络(FWER校正p = 0.014)。在精神分裂症患者的低连接子网络中,左下补充运动区-左尾状连接与较高的NM信号(β = -0.38,p = 0.042)。我们证明了NM和FST电路连接性之间的关联。考虑到NM-MRI信号反映了多巴胺功能,我们的研究结果表明,多巴胺是FST电路连接变化的基础,这支持了多巴胺假说。此外,本研究揭示了NM-MRI在多巴胺系统研究中的未来应用。
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引用次数: 0
Symptomatic, functional and quality of life measures of remission in 194 outpatients with schizophrenia followed naturalistically in a 6-month, non-interventional study of aripiprazole once-monthly. 194名门诊精神分裂症患者的症状、功能和生活质量缓解指标,对阿立哌唑进行了为期6个月的非干预性研究,每月一次。
Q2 PSYCHIATRY Pub Date : 2023-11-08 DOI: 10.1038/s41537-023-00405-5
Christoph U Correll, Andreas Brieden, Wolfgang Janetzky

An important goal in the treatment of patients with schizophrenia is remission in various domains, i.e., of symptoms, psychosocial functioning and subjective well-being. We undertook a post hoc analysis of pre-stabilized outpatients with schizophrenia and complete outcome data who had been enrolled in a 6-month non-interventional study of aripiprazole once-monthly (AOM) at 75 German sites. Key outcomes were (i) symptomatic remission (cross-sectional Andreasen et al. criteria (≤mild positive and negative key symptoms on the Brief Psychiatric Rating Scale (BPRS))); (ii) functional remission (Global Assessment of Functioning (GAF) scale score >70), and (iii) subjective well-being remission (WHO-5 scale score ≥13) at week 24. Of 242 enrolled patients, 194 (80.2%) (age = 43.9 ± 15.3 years; 51.5% male, illness duration = 14.0 ± 12.0 years) with complete data were analyzed. While 61.3% of the patients achieved symptomatic remission and 76.8% achieved remission regarding subjective well-being, only 24.7% achieved psychosocial functioning remission at 6 months. Remission rates were similar for men and women and across strata of disease duration with, on average, less remission in patients with longer illness duration. Correlations of improvements on the BPRS and GAF were weak, with the weakest correlation between the BPRS depressive mood item and the GAF scale, but similarly high correlation between BPRS subscales or the BPRS depressive mood item and subjective well-being. These findings suggest that while treatment with AOM can lead to symptomatic remission and remission regarding subjective well-being, additional interventions such as psychosocial therapy or supported employment and education may be necessary to achieve functional remission.

精神分裂症患者治疗的一个重要目标是在各个领域得到缓解,即症状、心理社会功能和主观幸福感。我们对在75个德国地点进行了为期6个月的阿立哌唑非介入性研究的精神分裂症预稳定门诊患者和完整的结果数据进行了事后分析。关键结果是(i)症状缓解(Andreasen等人的横断面标准(≤简要精神病评定量表(BPRS)中的轻度阳性和阴性关键症状);(ii)功能缓解(全球功能评估(GAF)量表得分>70),以及(iii)第24周的主观幸福感缓解(WHO-5量表得分≥13)。在242名入选患者中,194名(80.2%)(年龄 = 43.9 ± 15.3年;51.5%男性,患病时间 = 14 ± 12.0年)。61.3%的患者在主观幸福感方面实现了症状缓解,76.8%的患者在6个月时实现了心理社会功能缓解。男性和女性的缓解率相似,不同疾病持续时间的患者的缓解率平均较低。BPRS和GAF改善的相关性较弱,其中BPRS抑郁情绪项目与GAF量表之间的相关性最弱,但BPRS分量表或BPRS抑郁心情项目与主观幸福感之间的相关性相似。这些发现表明,虽然AOM治疗可以导致症状缓解和主观幸福感缓解,但可能需要额外的干预措施,如心理社会治疗或支持就业和教育,以实现功能缓解。
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引用次数: 0
Capsaicin alleviates neuronal apoptosis and schizophrenia-like behavioral abnormalities induced by early life stress. 辣椒素可减轻早期生活压力引起的神经元凋亡和精神分裂症样行为异常。
Q2 PSYCHIATRY Pub Date : 2023-11-07 DOI: 10.1038/s41537-023-00406-4
Shilin Xu, Keke Hao, Ying Xiong, Rui Xu, Huan Huang, Huiling Wang

Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.

早期生活压力(ELS)与精神分裂症的后期发展有关。在啮齿类动物模型中,母体分离(MS)应激可能诱导神经元凋亡和精神分裂症样行为。尽管TRPV1激动剂辣椒素(CAP)已被报道可减少中枢神经系统的细胞凋亡,但其在MS模型中的作用尚不清楚。Wistar大鼠幼崽在出生后24小时的MS(PND9)用作ELS。成年期雄性大鼠为研究对象。帽(1 mg/kg/天)腹膜内注射预处理1周,并在测试期间继续。行为测试包括开放视野、新物体识别、巴恩斯迷宫测试和脉冲前抑制(PPI)测试。与对照组相比,MS大鼠表现出类似精神分裂症症状的行为缺陷和认知障碍。与对照组相比,MS降低了额相关皮层(FrA)和海马CA1、CA3和齿状回(DG)区域TRPV1的表达,导致促凋亡蛋白(BAX、Caspase3、Cleaved-Caspase3)增加和抗凋亡蛋白(Bcl-2)减少。与对照组相比,MS组FrA、CA1、CA3和DG中NeuN++TUNEL+细胞的数量增加。多发性硬化症的神经元和行为障碍通过CAP治疗得以逆转。暴露于ELS可能导致神经元凋亡增加和认知功能受损,成年后前额叶皮层和海马中TRPV1的表达减少。持续低剂量给予CAP可改善神经元凋亡和认知功能。我们的研究结果为辣椒或CAP作为膳食补充剂逆转治疗精神分裂症的未来临床试验提供了证据。
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引用次数: 0
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Schizophrenia (Heidelberg, Germany)
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