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Long-term clinical recovery and treatment resistance in first-episode psychosis: a 10-year follow-up study. 首发精神病患者的长期临床康复和治疗阻力:一项为期 10 年的随访研究。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-08-22 DOI: 10.1038/s41537-024-00489-7
Kristin Fjelnseth Wold, Isabel Viola Kreis, Gina Åsbø, Camilla Bärthel Flaaten, Line Widing, Magnus Johan Engen, Siv Hege Lyngstad, Erik Johnsen, Torill Ueland, Carmen Simonsen, Ingrid Melle

Illness trajectories in people with first-episode psychosis (FEP) vary significantly over time. Identifying early-course parameters predicting outcomes is essential, but long-term data still needs to be provided. We conducted a 10-year follow-up study of a comprehensive first-episode psychosis (FEP) cohort investigating the prevalence of clinical recovery (CR) and treatment resistance (TR) after ten years, as well as clinical, demographic, and pre-illness predictors of long-term outcomes. 102 participants with FEP DSM-IV Schizophrenia spectrum disorders were recruited within their first year of treatment. The Treatment Response and Resistance in Psychosis Working Group (TRRIP) and the Remission in Schizophrenia Working Group (RSWG) criteria were used to define TR and CR, respectively. At 10-year follow-up, 29 (29%) of the participants were classified as in CR, while 32 (31%) were classified as TR. We also identified a larger middle group (n = 41, 40%) consisting of participants in partial recovery. 7% of all participants had tried Clozapine at the 10-year follow-up. Logistic regression analyses identified insidious onset (OR = 4.16) and baseline disorganized symptoms (OR = 2.96) as significantly associated with an increased risk of developing TR. Good premorbid academic adjustment (OR = 1.60) and acute onset (OR = 3.40) were associated with an increased chance of CR. We identified three long-term outcome groups by using recent consensus definitions. We also identified the potential importance of assessing baseline disorganized symptoms and monitoring patients with insidious onset more closely. Further, the findings suggest that clinicians should pay close attention to early-course parameters and provide adequate treatment to improve long-term outcomes of FEP.

首发精神病(FEP)患者的病情轨迹随着时间的推移而变化很大。确定预测结果的早期病程参数至关重要,但仍需提供长期数据。我们对一个综合性首发精神病(FEP)队列进行了一项为期十年的随访研究,调查十年后临床康复(CR)和治疗阻力(TR)的发生率,以及长期预后的临床、人口学和病前预测因素。102 名患有 FEP DSM-IV 精神分裂症谱系障碍的患者是在接受治疗的第一年内被招募的。精神病治疗反应和抵抗工作组(TRRIP)和精神分裂症缓解工作组(RSWG)的标准分别用于定义TR和CR。在 10 年的随访中,29 名参与者(29%)被归类为 CR,32 名参与者(31%)被归类为 TR。我们还发现了一个较大的中间组(n = 41,40%),由部分康复的参与者组成。在 10 年的随访中,7% 的参与者尝试过氯氮平。逻辑回归分析表明,隐匿起病(OR = 4.16)和基线紊乱症状(OR = 2.96)与罹患 TR 的风险显著相关。病前学习适应良好(OR = 1.60)和急性发病(OR = 3.40)与 CR 发生几率增加有关。通过使用最近达成共识的定义,我们确定了三个长期结果组。我们还发现了评估基线紊乱症状和更密切地监测隐匿性发病患者的潜在重要性。此外,研究结果还表明,临床医生应密切关注早期病程参数,并提供适当的治疗,以改善 FEP 的长期预后。
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引用次数: 0
Prevalence and incidence measures for schizophrenia among commercial health insurance and medicaid enrollees. 商业健康保险和医疗补助参保者中精神分裂症的流行率和发病率测量。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-08-22 DOI: 10.1038/s41537-024-00490-0
Molly T Finnerty, Atif Khan, Kai You, Rui Wang, Gyojeong Gu, Deborah Layman, Qingxian Chen, Noémie Elhadad, Shalmali Joshi, Paul S Appelbaum, Todd Lencz, Sander Markx, Steven A Kushner, Andrey Rzhetsky

Given the chronic nature of schizophrenia, it is important to examine age-specific prevalence and incidence to understand the scope of the burden of schizophrenia across the lifespan. Estimates of lifetime prevalence of schizophrenia have varied widely and have often relied upon community-based data estimates from over two decades ago, while more recent studies have shown considerable promise by leveraging pooled datasets. However, the validity of measures of schizophrenia, particularly new onset schizophrenia, has not been well studied in these large health databases. The current study examines prevalence and validity of incidence measures of new diagnoses of schizophrenia in 2019 using two U.S. administrative health databases: MarketScan, a national database of individuals receiving employer-sponsored commercial insurance (N = 16,365,997), and NYS Medicaid, a large state public insurance program (N = 4,414,153). Our results indicate that the prevalence of schizophrenia is over 10-fold higher, and the incidence two-fold higher, in the NYS Medicaid population compared to the MarketScan database. In addition, prevalence increased over the lifespan in the Medicaid population, but decreased in the employment based MarketScan database beginning in early adulthood. Incident measures of new diagnoses of schizophrenia had excellent validity, with positive predictive values and specificity exceeding 95%, but required a longer lookback period for Medicaid compared to MarketScan. Further work is needed to leverage these findings to develop robust clinical outcome predictors for new onset of schizophrenia within large administrative health data systems.

鉴于精神分裂症的慢性性质,研究特定年龄段的患病率和发病率对于了解精神分裂症对整个生命周期造成的负担范围非常重要。对精神分裂症终生患病率的估计差异很大,而且往往依赖于二十多年前基于社区的数据估计,而最近的研究则通过利用集合数据集显示出了相当大的前景。然而,在这些大型健康数据库中,对精神分裂症(尤其是新发精神分裂症)测量指标的有效性还没有进行过深入研究。本研究利用两个美国行政卫生数据库对 2019 年精神分裂症新诊断发病率测量的流行性和有效性进行了研究:这两个数据库分别是:MarketScan,这是一个关于接受雇主赞助的商业保险的个人的全国性数据库(N = 16,365,997),以及纽约州医疗补助(NYS Medicaid),这是一个大型的州公共保险项目(N = 4,414,153)。我们的研究结果表明,与 MarketScan 数据库相比,纽约州医疗补助人群的精神分裂症患病率高出 10 倍以上,发病率高出 2 倍。此外,在医疗补助人群中,精神分裂症的患病率随年龄增长而增加,但在以就业为基础的 MarketScan 数据库中,患病率则从成年早期开始下降。精神分裂症新诊断的事件测量具有良好的有效性,阳性预测值和特异性均超过 95%,但与 MarketScan 相比,Medicaid 需要更长的回溯期。需要进一步开展工作,利用这些发现在大型健康管理数据系统中开发出稳健的精神分裂症新发临床结果预测指标。
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引用次数: 0
Interaction between BDNF Val66Met polymorphism and mismatch negativity for working memory capacity in schizophrenia. BDNF Val66Met多态性与错配负性对精神分裂症工作记忆能力的相互作用
IF 3 Q2 PSYCHIATRY Pub Date : 2024-08-22 DOI: 10.1038/s41537-024-00493-x
Wenpeng Hou, Xiangqin Qin, Hang Li, Qi Wang, Yushen Ding, Xiongying Chen, Ru Wang, Fang Dong, Qijing Bo, Xianbin Li, Fuchun Zhou, Chuanyue Wang

Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

据报道,脑源性神经营养因子(BDNF)缬氨酸(Val)/蛋氨酸(Met)多态性和错配负性(MMN)振幅都与精神分裂症患者的工作记忆障碍有关。然而,旨在探索这三个因素之间关系的研究明显不足。在这项随机对照双盲试验的二次分析中,我们对这些关系进行了调查。该试验评估了经颅直流电刺激对临床稳定的精神分裂症患者增强工作记忆的疗效,这些患者被随机分为三组:背外侧前额叶皮层刺激组、后顶叶皮层刺激组和假刺激组。经颅直流电刺激与工作记忆任务同时进行,为期五天。我们对 BDNF 基因型、MMN 振幅、工作记忆能力和干扰控制子域进行了评估。54名患者接受了基线评估,48名患者接受了干预后随访。与BDNF Met携带者相比,Val同卵双生者在基线时表现出较少的积极症状和一般症状,工作记忆能力也有所提高。只有 BDNF Val 基因同型携带者的 MMN 振幅与工作记忆能力之间存在相关性。两个 BDNF 基因型组的相关性存在明显差异。此外,在MMN振幅有明显改善的干预组中,BDNF Val同型基因携带者的工作记忆能力比Met基因携带者有更大的提高。这项研究为 MMN 与 BDNF Val/Met 多态性在工作记忆能力方面的相互作用提供了体内证据。由于 MMN 被认为是 N-甲基-D-天冬氨酸受体(NMDAR)功能的生物标志物,这些数据揭示了 BDNF 和 NMDAR 在精神分裂症患者工作记忆方面的复杂相互作用。
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引用次数: 0
Messiah or pariah? Psychosis, science, and finding meaning in lived experience. 救世主还是贱民?精神病、科学以及从生活经验中寻找意义。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-08-05 DOI: 10.1038/s41537-024-00486-w
Carlos A Larrauri
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引用次数: 0
Longitudinal study on hippocampal subfields and glucose metabolism in early psychosis. 早期精神病海马亚区和葡萄糖代谢的纵向研究。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-07-31 DOI: 10.1038/s41537-024-00475-z
Reetta-Liina Armio, Heikki Laurikainen, Tuula Ilonen, Maija Walta, Elina Sormunen, Arvi Tolvanen, Raimo K R Salokangas, Nikolaos Koutsouleris, Lauri Tuominen, Jarmo Hietala

Altered hippocampal morphology and metabolic pathology, but also hippocampal circuit dysfunction, are established phenomena seen in psychotic disorders. Thus, we tested whether hippocampal subfield volume deficits link with deviations in glucose metabolism commonly seen in early psychosis, and whether the glucose parameters or subfield volumes change during follow-up period using one-year longitudinal study design of 78 first-episode psychosis patients (FEP), 48 clinical high-risk patients (CHR) and 83 controls (CTR). We also tested whether hippocampal morphology and glucose metabolism relate to clinical outcome. Hippocampus subfields were segmented with Freesurfer from 3T MRI images and parameters of glucose metabolism were determined in fasting plasma samples. Hippocampal subfield volumes were consistently lower in FEPs, and findings were more robust in non-affective psychoses, with strongest decreases in CA1, molecular layer and hippocampal tail, and in hippocampal tail of CHRs, compared to CTRs. These morphometric differences remained stable at one-year follow-up. Both non-diabetic CHRs and FEPs had worse glucose parameters compared to CTRs at baseline. We found that, insulin levels and insulin resistance increased during the follow-up period only in CHR, effect being largest in the CHRs converting to psychosis, independent of exposure to antipsychotics. The worsening of insulin resistance was associated with deterioration of function and symptoms in CHR. The smaller volume of hippocampal tail was associated with higher plasma insulin and insulin resistance in FEPs, at the one-year follow-up. Our longitudinal study supports the view that temporospatial hippocampal subfield volume deficits are stable near the onset of first psychosis, being more robust in non-affective psychoses, but less prominent in the CHR group. Specific subfield defects were related to worsening glucose metabolism during the progression of psychosis, suggesting that hippocampus is part of the circuits regulating aberrant glucose metabolism in early psychosis. Worsening of glucose metabolism in CHR group was associated with worse clinical outcome measures indicating a need for heightened clinical attention to metabolic problems already in CHR.

海马形态和代谢病理改变以及海马回路功能障碍是精神病性障碍的既定现象。因此,我们通过对 78 名首发精神病患者(FEP)、48 名临床高危患者(CHR)和 83 名对照组(CTR)进行为期一年的纵向研究,检验了海马亚区体积缺陷是否与早期精神病中常见的葡萄糖代谢偏差有关,以及葡萄糖参数或亚区体积在随访期间是否会发生变化。我们还测试了海马形态和葡萄糖代谢是否与临床结果有关。我们使用 Freesurfer 对 3T MRI 图像中的海马子场进行了分割,并对空腹血浆样本中的葡萄糖代谢参数进行了测定。与CTR相比,FEPs患者的海马子野体积一直较低,而非情感性精神病患者的海马子野体积更低,CA1、分子层和海马尾部以及CHRs患者的海马尾部的体积下降幅度最大。这些形态学差异在一年的随访中保持稳定。与基线时的CTR相比,非糖尿病CHR和FEP的血糖参数都更差。我们发现,在随访期间,胰岛素水平和胰岛素抵抗仅在CHR中增加,在转化为精神病的CHR中影响最大,与抗精神病药物的暴露无关。胰岛素抵抗的恶化与CHR功能和症状的恶化有关。在为期一年的随访中,海马尾部较小的体积与FEPs较高的血浆胰岛素和胰岛素抵抗有关。我们的纵向研究支持这样一种观点,即颞叶海马子场体积缺陷在首次精神病发病时较为稳定,在非情感性精神病中更为明显,但在CHR组中不那么突出。在精神病进展过程中,特定的子野缺陷与糖代谢恶化有关,这表明海马是调节早期精神病异常糖代谢回路的一部分。CHR组患者的糖代谢恶化与更差的临床结果测量有关,这表明临床上需要更加关注CHR患者的代谢问题。
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引用次数: 0
Advances in the study of phencyclidine-induced schizophrenia-like animal models and the underlying neural mechanisms. 苯环利定诱导的精神分裂症样动物模型及其潜在神经机制的研究进展。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-07-23 DOI: 10.1038/s41537-024-00485-x
Dabing Li, Qiangwen Pan, Yewei Xiao, Kehui Hu

Schizophrenia (SZ) is a chronic, severe mental disorder with heterogeneous clinical manifestations and unknown etiology. Research on SZ has long been limited by the low reliability of and ambiguous pathogenesis in schizophrenia animal models. Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, rapidly induces both positive and negative symptoms of SZ as well as stable SZ-related cognitive impairment in rodents. However, the neural mechanism underlying PCP-induced SZ-like symptoms is not fully understood. Nondopaminergic pathophysiology, particularly excessive glutamate release induced by NMDAR hypofunction in the prefrontal cortex (PFC), may play a key role in the development of PCP-induced SZ-like symptoms. In this review, we summarize studies on the behavioral and metabolic effects of PCP and the cellular and circuitary targets of PCP in the PFC and hippocampus (HIP). PCP is thought to target the ventral HIP-PFC pathway more strongly than the PFC-VTA pathway and thalamocortical pathway. Systemic PCP administration might preferentially inhibit gamma-aminobutyric acid (GABA) neurons in the vHIP and in turn lead to hippocampal pyramidal cell disinhibition. Excitatory inputs from the HIP may trigger sustained, excessive and pathological PFC pyramidal neuron activation to mediate various SZ-like symptoms. In addition, astrocyte and microglial activation and oxidative stress in the cerebral cortex or hippocampus have been observed in PCP-induced models of SZ. These findings perfect the hypoglutamatergic hypothesis of schizophrenia. However, whether these effects direct the consequences of PCP administration and how about the relationships between these changes induced by PCP remain further elucidation through rigorous, causal and direct experimental evidence.

精神分裂症(SZ)是一种慢性严重精神障碍,临床表现多样,病因不明。长期以来,精神分裂症动物模型的可靠性低、发病机制不明确,限制了对 SZ 的研究。苯环利定(PCP)是一种非竞争性的 N-甲基-D-天冬氨酸受体(NMDAR)拮抗剂,能迅速诱导啮齿类动物出现 SZ 的阳性和阴性症状以及稳定的 SZ 相关认知障碍。然而,五氯苯酚诱发类似 SZ 症状的神经机制尚未完全明了。非多巴胺能病理生理学,特别是前额叶皮质(PFC)中 NMDAR 功能减退所诱发的谷氨酸过度释放,可能在 PCP 诱导的 SZ 类症状的发展过程中起着关键作用。在本综述中,我们总结了有关五氯苯酚的行为和代谢效应以及五氯苯酚在前额叶皮质和海马(HIP)中的细胞和环路靶点的研究。人们认为五氯苯酚对腹侧 HIP-PFC 通路的靶向作用强于 PFC-VTA 通路和丘脑皮层通路。全身服用五氯苯酚可能会优先抑制 vHIP 中的γ-氨基丁酸(GABA)神经元,进而导致海马锥体细胞失抑制。来自 HIP 的兴奋性输入可能会引发持续、过度和病理性的 PFC 锥体神经元激活,从而介导各种类似 SZ 的症状。此外,在五氯苯酚诱导的 SZ 模型中还观察到大脑皮层或海马的星形胶质细胞和小胶质细胞活化和氧化应激。这些发现完善了精神分裂症的低谷氨酸能假说。然而,这些效应是否是服用五氯苯酚的直接后果,以及五氯苯酚诱导的这些变化之间的关系如何,仍有待通过严格、因果和直接的实验证据来进一步阐明。
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引用次数: 0
Exploration on the potential efficacy and mechanism of methyl salicylate glycosides in the treatment of schizophrenia based on bioinformatics, molecular docking and dynamics simulation. 基于生物信息学、分子对接和动力学模拟,探讨水杨酸甲酯苷治疗精神分裂症的潜在疗效和机制。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-07-17 DOI: 10.1038/s41537-024-00484-y
Xiuhuan Wang, Jiamu Ma, Ying Dong, Xueyang Ren, Ruoming Li, Guigang Yang, Gaimei She, Yunlong Tan, Song Chen

The etiological and therapeutic complexities of schizophrenia (SCZ) persist, prompting exploration of anti-inflammatory therapy as a potential treatment approach. Methyl salicylate glycosides (MSGs), possessing a structural parent nucleus akin to aspirin, are being investigated for their therapeutic potential in schizophrenia. Utilizing bioinformation mining, network pharmacology, molecular docking and dynamics simulation, the potential value and mechanism of MSGs (including MSTG-A, MSTG-B, and Gaultherin) in the treatment of SCZ, as well as the underlying pathogenesis of the disorder, were examined. 581 differentially expressed genes related to SCZ were identified in patients and healthy individuals, with 349 up-regulated genes and 232 down-regulated genes. 29 core targets were characterized by protein-protein interaction (PPI) network, with the top 10 core targets being BDNF, VEGFA, PVALB, KCNA1, GRIN2A, ATP2B2, KCNA2, APOE, PPARGC1A and SCN1A. The pathogenesis of SCZ primarily involves cAMP signaling, neurodegenerative diseases and other pathways, as well as regulation of ion transmembrane transport. Molecular docking analysis revealed that the three candidates exhibited binding activity with certain targets with binding affinities ranging from -4.7 to -109.2 kcal/mol. MSTG-A, MSTG-B and Gaultherin show promise for use in the treatment of SCZ, potentially through their ability to modulate the expression of multiple genes involved in synaptic structure and function, ion transport, energy metabolism. Molecular dynamics simulation revealed good binding abilities between MSTG-A, MSTG-B, Gaultherin and ATP2B2. It suggests new avenues for further investigation in this area.

精神分裂症(SCZ)的病因和治疗仍然十分复杂,这促使人们探索抗炎疗法作为一种潜在的治疗方法。水杨酸甲酯苷(MSGs)具有类似阿司匹林的结构母核,目前正在研究其治疗精神分裂症的潜力。利用生物信息挖掘、网络药理学、分子对接和动力学模拟,研究了MSGs(包括MSTG-A、MSTG-B和Gaultherin)治疗SCZ的潜在价值和机制,以及该疾病的潜在发病机制。在患者和健康人中发现了 581 个与 SCZ 相关的差异表达基因,其中 349 个基因上调,232 个基因下调。通过蛋白-蛋白相互作用(PPI)网络确定了29个核心靶点,其中前10个核心靶点分别是BDNF、VEGFA、PVALB、KCNA1、GRIN2A、ATP2B2、KCNA2、APOE、PPARGC1A和SCN1A。SCZ 的发病机制主要涉及 cAMP 信号传导、神经退行性疾病和其他途径,以及离子跨膜转运的调控。分子对接分析表明,三种候选化合物与某些靶点具有结合活性,结合亲和力在-4.7至-109.2 kcal/mol之间。MSTG-A、MSTG-B和Gaultherin有望用于治疗SCZ,这可能是由于它们能够调节涉及突触结构和功能、离子转运、能量代谢的多个基因的表达。分子动力学模拟揭示了 MSTG-A、MSTG-B、Gaultherin 和 ATP2B2 之间良好的结合能力。这为该领域的进一步研究提供了新的途径。
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引用次数: 0
A neural modeling approach to study mechanisms underlying the heterogeneity of visual spatial frequency sensitivity in schizophrenia. 研究精神分裂症患者视觉空间频率敏感性异质性机制的神经建模方法。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-07-16 DOI: 10.1038/s41537-024-00480-2
Caroline Dugan, Basilis Zikopoulos, Arash Yazdanbakhsh

Patients with schizophrenia exhibit abnormalities in spatial frequency sensitivity, and it is believed that these abnormalities indicate more widespread dysfunction and dysregulation of bottom-up processing. The early visual system, including the first-order Lateral Geniculate Nucleus of the thalamus (LGN) and the primary visual cortex (V1), are key contributors to spatial frequency sensitivity. Medicated and unmedicated patients with schizophrenia exhibit contrasting changes in spatial frequency sensitivity, thus making it a useful probe for examining potential effects of the disorder and antipsychotic medications in neural processing. We constructed a parameterized, rate-based neural model of on-center/off-surround neurons in the early visual system to investigate the impacts of changes to the excitatory and inhibitory receptive field subfields. By incorporating changes in both the excitatory and inhibitory subfields that are associated with pathophysiological findings in schizophrenia, the model successfully replicated perceptual data from behavioral/functional studies involving medicated and unmedicated patients. Among several plausible mechanisms, our results highlight the dampening of excitation and/or increase in the spread and strength of the inhibitory subfield in medicated patients and the contrasting decreased spread and strength of inhibition in unmedicated patients. Given that the model was successful at replicating results from perceptual data under a variety of conditions, these elements of the receptive field may be useful markers for the imbalances seen in patients with schizophrenia.

精神分裂症患者在空间频率敏感性方面表现出异常,人们认为这些异常表明自下而上的处理过程出现了更广泛的功能障碍和失调。早期视觉系统,包括丘脑第一阶外侧膝状核(LGN)和初级视觉皮层(V1),是空间频率敏感性的关键因素。服药和未服药的精神分裂症患者在空间频率敏感性上表现出截然不同的变化,因此空间频率敏感性是研究精神分裂症和抗精神病药物对神经处理的潜在影响的有用探针。我们构建了一个参数化的、基于速率的早期视觉系统中心/非环绕神经元神经模型,以研究兴奋性和抑制性感受野子场变化的影响。通过将与精神分裂症病理生理发现相关的兴奋和抑制子场的变化纳入模型,该模型成功地复制了涉及服药和未服药患者的行为/功能研究中的感知数据。在几种似是而非的机制中,我们的研究结果突出表明,服药患者的兴奋减弱和/或抑制子场的扩散和强度增加,而未服药患者的抑制扩散和强度则相反地减弱。鉴于该模型成功地复制了各种条件下感知数据的结果,这些感受野元素可能是精神分裂症患者失衡的有用标记。
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引用次数: 0
Elevated serum kynurenic acid in individuals with first-episode psychosis and insufficient response to antipsychotics. 首发精神病患者血清犬尿酸升高且对抗抑郁药反应不足。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-07-10 DOI: 10.1038/s41537-024-00483-z
Alex Hatzimanolis, Stefania Foteli, Lida-Alkisti Xenaki, Mirjana Selakovic, Stefanos Dimitrakopoulos, Ilias Vlachos, Ioannis Kosteletos, Rigas-Filippos Soldatos, Maria Gazouli, Stylianos Chatzipanagiotou, Nikos Stefanis

The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.

色氨酸代谢犬尿氨酸途径(KP)可被增强的炎症反应激活,并被认为与精神分裂症的病理生理学有关。然而,几乎没有证据表明 KP 在精神疾病的早期病程中失调。我们旨在研究 KP 在首发精神病患者(FEP)中潜在的免疫介导的高活性以及与症状严重程度和治疗反应结果的关系。研究人员对104名抗精神病药物无效的FEP患者和80名健康对照组(HC)进行了血清免疫测定,以测量外周炎症细胞因子(IL-1β、IL-10、TNF-a)、KP限速酶(IDO/TDO)和犬尿酸(KYNA)代谢物的水平。在入院时和接受抗精神病药物治疗 4 周后,采用阳性和阴性综合征量表 (PANSS) 和全球功能评估量表 (GAF) 评估精神病理学和功能状况。与HC相比,FEP患者在抗精神病药物治疗前后的细胞因子和KP成分水平均大幅升高。在FEP患者中观察到促炎性IL-1β和KYNA水平之间存在明显的正相关,而在HC患者中则没有发现。重要的是,患者内部分析表明,基线 KYNA 水平较高的患者会出现更严重的阴性症状,随访时的临床改善程度也较差。这些研究结果表明,KP在早期精神病中上调,可能是通过诱导IL-1β依赖性途径,而外周KYNA升高可能是FEP患者对抗精神病药物无反应的一个有希望的指标。
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引用次数: 0
A systematic review of structural and functional magnetic resonance imaging studies on the neurobiology of depressive symptoms in schizophrenia spectrum disorders. 关于精神分裂症谱系障碍抑郁症状神经生物学的结构和功能磁共振成像研究的系统回顾。
IF 3 Q2 PSYCHIATRY Pub Date : 2024-07-04 DOI: 10.1038/s41537-024-00478-w
Julia Gallucci, Maria T Secara, Oliver Chen, Lindsay D Oliver, Brett D M Jones, Tulip Marawi, George Foussias, Aristotle N Voineskos, Colin Hawco

Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond "total score" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.

精神分裂症谱系障碍(SSD)患者的抑郁症状会对自杀倾向、预后和生活质量产生负面影响。尽管如此,有效的治疗方法仍然有限,这主要是因为人们对精神分裂症谱系障碍抑郁症状的神经机制仍然知之甚少。我们进行了一项系统性综述,旨在概述使用神经影像技术调查 SSD 患者抑郁症状神经相关因素的研究。我们检索了从开始到 2023 年 6 月 19 日的 MEDLINE、PsycINFO、EMBASE、Web of Science 和 Cochrane Library 数据库。具体而言,我们重点关注结构性和功能性磁共振成像(MRI),包括:(1)测量大脑形态的 T1 加权成像;(2)评估白质完整性的弥散加权成像;或(3)测量大脑功能的 T2* 加权成像。我们的搜索共获得 33 篇文章;14 项结构性 MRI 研究、18 项功能性 (f)MRI 研究和 1 项多模态 fMRI/MRI 研究。综述研究表明,SSD 和重度抑郁障碍在抑郁症状的神经生物学方面存在潜在的共性,尤其是在皮层下和额叶脑区,但这种解释的可信度有限。综述强调了我们在了解 SSD 抑郁症神经生物学方面存在明显的知识空白,其特点是研究方法不一致,而且很少有研究对抑郁症状的成像指标进行检查。研究结果的不一致性强调了对 SSD 抑郁症神经生物学进行更直接、更全面研究的必要性。未来的研究应超越 "总分 "抑郁指标,采用更细致的评估方法,考虑不同的子域。这可以揭示独特的神经生物学特征,并为研究针对 SSD 抑郁症的治疗方法提供信息。
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引用次数: 0
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Schizophrenia (Heidelberg, Germany)
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