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未用药首发精神分裂症患者皮质下功能连接梯度紊乱及抗精神病药物治疗后的正常化效应。

Disrupted subcortical functional connectome gradient in drug-naïve first-episode schizophrenia and the normalization effects after antipsychotic treatment.

机构信息

Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China.

出版信息

Neuropsychopharmacology. 2023 Apr;48(5):789-796. doi: 10.1038/s41386-022-01512-0. Epub 2022 Dec 10.

Abstract

Antipsychotics are thought to improve schizophrenia symptoms through the antagonism of dopamine D2 receptors, which are abundant mainly in subcortical regions. By introducing functional gradient, a novel approach to identify hierarchy alterations by capturing the similarity of whole brain fucntional connectivity (FC) profiles between two voxels, the present study aimed to characterize how the subcortical gradient is associated with treatment effects and response in first-episode schizophrenia in vivo. Two independent samples of first-episode schizophrenia (FES) patients with matched healthy controls (HC) were obtained: the discovery dataset included 71 patients (FES) and 64 HC at baseline, and patients were re-scanned after either 6 weeks (FES N = 33) or 12 months (FES N = 57) of antipsychotic treatment, of which 19 patients finished both 6-week and 12-month evaluation. The validation dataset included 22 patients and 24 HC at baseline and patients were re-scanned after 6 weeks. Gradient metrics were calculated using BrainSpace Toolbox. Voxel-based gradient values were generated and group-averaged gradient values were further extracted across all voxels (global), three systems (thalamus, limbic and striatum) and their subcortical subfields. The comparisons were conducted separately between FES and HC for investigating illness effects, and between FES/FES and FES for treatment effects. Correlational analyses were then conducted between the longitudinal gradient alterations and the improvement of clinical ratings. Before treatment, schizophrenia patients exhibited an expanded range of global gradient scores compared to HC which indicated functional segregation within subcortical systems. The increased gradient in limbic system and decreased gradient in thalamic and striatal system contributed to the baseline abnormalities and led to the disruption of the subcortical functional integration. After treatment, these disruptions were normalized and the longitudinal changes of gradient scores in limbic system were significantly associated with symptom improvement. Similar illness and treatment effects were also observed in the validation dataset. By measuring functional hierarchy of subcortical organization, our findings provide a novel imaging marker that is sensitive to treatment effects and may make a promising indicator of treatment response in schizophrenia.

摘要

抗精神病药物被认为通过拮抗多巴胺 D2 受体来改善精神分裂症症状,多巴胺 D2 受体主要存在于皮质下区域。本研究通过引入功能梯度,这是一种通过捕获两个体素之间全脑功能连接 (FC) 谱的相似性来识别层次结构改变的新方法,旨在描述皮质下梯度如何与首发精神分裂症患者的治疗效果和反应相关。本研究获得了两个独立的首发精神分裂症 (FES) 患者与匹配的健康对照组 (HC) 的样本:发现数据集包括 71 名患者(FES)和 64 名 HC 在基线时,患者在接受抗精神病药物治疗 6 周(FES N=33)或 12 个月(FES N=57)后重新扫描,其中 19 名患者完成了 6 周和 12 个月的评估。验证数据集包括 22 名患者和 24 名 HC 在基线时,患者在 6 周后重新扫描。使用 BrainSpace 工具包计算梯度指标。生成基于体素的梯度值,并进一步从所有体素(全局)、三个系统(丘脑、边缘系统和纹状体)及其皮质下亚区提取体素的平均梯度值。分别在 FES 和 HC 之间进行比较,以研究疾病效应,在 FES/FES 和 FES 之间进行比较,以研究治疗效应。然后进行纵向梯度变化与临床评分改善之间的相关性分析。在治疗前,与 HC 相比,精神分裂症患者的全局梯度评分范围扩大,表明皮质下系统内的功能分离。边缘系统的梯度增加和丘脑和纹状体系统的梯度降低导致了基线异常,并导致皮质下功能整合的破坏。治疗后,这些破坏得到了纠正,边缘系统梯度评分的纵向变化与症状改善显著相关。在验证数据集也观察到了类似的疾病和治疗效果。通过测量皮质下组织的功能层次结构,我们的研究结果提供了一种新的成像标志物,对治疗效果敏感,可能成为精神分裂症治疗反应的有前途的指标。

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