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精神分裂症伴严重阴性症状的神经免疫方面:疾病表型的新诊断标志物。

Neuro-Immune Aspects of Schizophrenia with Severe Negative Symptoms: New Diagnostic Markers of Disease Phenotype.

机构信息

Head of the Laboratory of Molecular Immunology and Virology; National Research Center "Kurchatov Institute", 1 Akademika Kurchatova Square, Moscow, 123182, Russia; Leading Researcher, Laboratory of Clinical Immunology; Federal Research and Clinical Center of Physical-Chemical Medicine.

Associate Professor, Senior Researcher; National Research Nuclear University MEPhI, 31 Kashirskoe Shosse, Moscow, 115409, Russia; Department Head; Alekseev Psychiatric Clinical Hospital No.1, Moscow Department of Health, 2 Zagorodnoe Shosse, Moscow, 117152, Russia; Leading Researcher, Institute for Advanced Brain Research; Lomonosov Moscow State University, 27/1 Lomonosov Avenue, Moscow, 119192, Russia.

出版信息

Sovrem Tekhnologii Med. 2021;13(6):24-33. doi: 10.17691/stm2021.13.6.03. Epub 2021 Dec 28.

Abstract

UNLABELLED

was to analyze the immune-inflammatory profile of patients with paranoid schizophrenia and relate it to the severity of negative symptoms and the MRI data in order to identify biomarkers of schizophrenia severity, search for new approaches to therapy, and control its effectiveness.

MATERIALS AND METHODS

The main group included 51 patients with paranoid schizophrenia, the control group - 30 healthy subjects. Patients underwent MRI scans and immunological studies, which included an assessment of natural and adaptive immunity, the systemic level of key pro-inflammatory and anti-inflammatory cytokines, and other markers of inflammation.

RESULTS

Disorders of immunity and immunoinflammatory profile in patients with paranoid schizophrenia with severe negative symptoms were revealed for the first time: in the presence of severe negative symptoms (>15 points according to the NSA-4 scale), the levels of humoral immunity factors, cytokines IL-10 and IL-12p40 and neurotrophin NGF were increased as well as the markers of systemic inflammation. Morphometric changes in the brain, typical for patients with schizophrenia, and also specific for patients with severe negative symptoms, were determined. The data analysis revealed correlations between the immune changes with structural changes in some of the brain areas, including the frontal cortex and hippocampus. Associations were found between the levels of anti-inflammatory IL-10, IL-12p40 cytokines and morphometric parameters of the brain, specific only for schizophrenic patients with severe negative symptoms.

CONCLUSION

The interdisciplinary approach, combining brain morphometry with in-depth immunological and clinical studies, made it possible to determine neurobiological, immune, and neurocognitive markers of paranoid schizophrenia with severe negative symptoms. The results are important for further deciphering the pathogenesis of schizophrenia and its subtypes, as well as for the search for new approaches to the treatment of severe forms of the disease.

摘要

目的

分析偏执型精神分裂症患者的免疫炎症特征,并将其与阴性症状严重程度及 MRI 数据相关联,以确定精神分裂症严重程度的生物标志物,寻找新的治疗方法,并控制其疗效。

材料和方法

主要组包括 51 例偏执型精神分裂症患者,对照组包括 30 例健康受试者。患者接受 MRI 扫描和免疫研究,包括评估自然和适应性免疫、系统性关键促炎和抗炎细胞因子水平以及其他炎症标志物。

结果

首次发现伴有严重阴性症状(根据 NSA-4 量表>15 分)的偏执型精神分裂症患者存在免疫和免疫炎症特征障碍:体液免疫因子水平升高,细胞因子 IL-10 和 IL-12p40 以及神经营养因子 NGF 增加,同时还存在全身炎症标志物。确定了精神分裂症患者特有的脑形态计量学变化,以及特定于严重阴性症状患者的变化。数据分析显示,免疫变化与某些脑区(包括额叶皮质和海马体)的结构变化之间存在相关性。发现抗炎细胞因子 IL-10、IL-12p40 水平与仅在严重阴性症状的精神分裂症患者中特定的脑形态计量学参数之间存在关联。

结论

将脑形态计量学与深入的免疫和临床研究相结合的跨学科方法,使确定伴有严重阴性症状的偏执型精神分裂症的神经生物学、免疫和神经认知标志物成为可能。这些结果对于进一步解析精神分裂症及其亚型的发病机制以及寻找严重疾病形式的新治疗方法具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/313f/8858398/267cad3c4778/STM-13-6-03-f1.jpg

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