The Role of Stress-Immune-Connectome Disruption in Mechanisms of Chinese Early Schizophrenia Spectrum

应激-免疫-连接体破坏在中国早期精神分裂症谱系机制中的作用

• 批准号: 10057388
• 负责人: L Elliot Elliot Hong
• 金额: $ 20万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2023-08-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057388
• 关键词: Activities of Daily Living; Acute; Age; Antipsychotic Agents; Behavioral; Biological; Biological Markers; Brain; Brain Diseases; Cerebrum; China; Chinese People; Chronic; Chronic stress; Clinical; Clinical Immunology; Cognitive deficits; Collaborations; Data; Deterioration; Disease; Disease Progression; Etiology; Evaluation; Functional disorder; Future; Genes; Heterogeneity; Hippocampus (Brain); Hospitalization; Hospitals; Hydrocortisone; Image; Imaging Device; Immune; Immune response; Immunologic Markers; Immunologic Tests; Impairment; Inflammatory; Inflammatory Response; Kynurenic Acid; Laboratories; Light; Link; Longitudinal Studies; Measures; Mental Health; Mental disorders; Metabolic; Methods; Modernization; Multimodal Imaging; Neurosecretory Systems; Onset of illness; Outcome; Outcome Measure; Outcome Study; Pathway interactions; Patient Recruitments; Patients; Pharmaceutical Preparations; Play; Prevention; Protocols documentation; Psychological Stress; Psychoses; Recovery; Relapse; Research; Role; Sampling; Schizophrenia; Series; Stress; Stress Tests; Structure; Symptoms; System; Testing; Thick; Work; acute stress; allostatic load; base; biological adaptation to stress; brain circuitry; connectome; connectome data; cytokine; disorder risk; experience; experimental study; follow-up; frontal lobe; functional outcomes; gray matter; indexing; neuroimaging; novel; predictive marker; prenatal; prevent; recruit; relating to nervous system; resilience; response; schizophrenia-spectrum disorder; sex; therapeutic target; white matter

Project Summary / Abstract The advent of non-invasive connectivity-oriented neuroimaging methods has shed new light onto the inner workings of the brain. The brain's functional and structural connectome play key roles in regulating the pathways from genes to neural systems to mental illnesses. Along these pathways, we hypothesize that abnormal activity in the innate stress-immune pathways has a major contribution to the brain connectome disruption in early stage of schizophrenia spectrum disorder and to its clinical consequence. The project proposes to extend the Connectome Project in Mental Illness to characterize brain circuitry and its relation to stress-immune axis dysfunction in early stage of schizophrenia spectrum disorder in China. We propose a longitudinal study in a large sample of patients that aims to overcome the heterogeneity in the relationship between mental illness and stress-immune-connectome axis, a well-recognized barrier to advancing research and treatment. We will recruit 500 patients with schizophrenia spectrum disorders within five years of disease onset. They will be assessed using modern chronic stress and acute psychological stress laboratory paradigms to define the stress biomarkers at baseline. The patients will be compared with 250 age and sex matched healthy controls. The collaboration leverages the clinical stress research expertise by the U.S. partner and the the clinical immunology research expertise in schizophrenia by the Chinese partner. The proposed study also builds on our ongoing work using acute and chronic stress paradigms to understand how stress is linked to brain structural and functional connectome in schizophrenia spectrum disorders. This novel proposition in U.S. and Chinese mental health research field is strongly supported by preliminary data. The ability to apply the cutting edge connectome protocol using the advanced research designated scanner in Beijing will also enhance our ability to use multimodal imaging tools to aid biologically based heterogeneity reduction. Together, this study will generate actionable strategies to treat and prevent brain connectome deterioration and facilitate clinical recovery after psychosis onset.

项目总结/摘要 非侵入性的连接导向的神经成像方法的出现， 大脑的运作大脑的功能性和结构性连接体在调节大脑的活动中起着关键作用。 从基因到神经系统再到精神疾病沿着这些途径，我们假设， 先天性应激免疫通路的异常活动对大脑连接体有重要作用 精神分裂症谱系障碍早期阶段的中断及其临床后果。项目 建议扩展精神疾病中的连接组项目，以表征大脑回路及其与 精神分裂症谱系障碍早期应激免疫轴功能异常我们提出了一个 在大样本患者中进行的纵向研究，旨在克服关系中的异质性 精神疾病和压力免疫连接体轴之间的联系，这是一个公认的推进研究的障碍 和治疗。我们将招募500名患病五年内患有精神分裂症谱系障碍的患者 发病他们将使用现代慢性应激和急性心理应激实验室范式进行评估 以确定基线时的压力生物标志物。将患者与250名年龄和性别匹配的患者进行比较 健康对照该合作利用了美国合作伙伴和美国合作伙伴的临床压力研究专业知识。 中方合作伙伴在精神分裂症临床免疫学研究方面的专业知识。拟议的研究还 建立在我们正在进行的工作，使用急性和慢性压力模式，以了解压力是如何与 精神分裂症谱系障碍的脑结构和功能连接体这个新的命题在美国。 中国心理健康研究领域有初步的数据支持。能够应用 尖端的连接体协议使用先进的研究指定扫描仪在北京也将 增强我们使用多模态成像工具的能力，以帮助减少生物学上的异质性。在一起， 这项研究将产生可行的策略来治疗和预防大脑连接体退化， 精神病发作后临床恢复。

项目成果

TGF-β1 is associated with deficits in cognition and cerebral cortical thickness in first-episode schizophrenia.

• DOI: 10.1503/jpn.210121
• 发表时间: 2022-03
• 期刊: JOURNAL OF PSYCHIATRY & NEUROSCIENCE
• 影响因子: 4.3
• 作者: Pan, Shujuan;Zhou, Yanfang;Yan, Ling;Xuan, Fangling;Tong, Jinghui;Li, Yanli;Huang, Junchao;Feng, Wei;Chen, Song;Cui, Yimin;Yang, Fude;Tan, Shuping;Wang, Zhiren;Tian, Baopeng;Hong, L. Elliot;Tan, Yun-Long;Tian, Li
• 通讯作者: Tian, Li

Glial receptor PLXNB2 regulates schizophrenia-related stress perception via the amygdala.

• DOI: 10.3389/fimmu.2022.1005067
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3

The age of onset and cognitive impairment at the early stage of schizophrenia.

精神分裂症的发病年龄和早期认知障碍。

• DOI: 10.1007/s11571-022-09814-1
• 发表时间: 2023
• 期刊: Cognitive neurodynamics
• 影响因子: 3.7
• 作者: Yin,Yi;Li,Shuangshuang;Tong,Jinghui;Huang,Junchao;Tian,Baopeng;Chen,Song;Cui,Yimin;Tan,Shuping;Wang,Zhiren;Yang,Fude;Tong,Yongsheng;Hong,LElliot;Tan,Yunlong
• 通讯作者: Tan,Yunlong

Computerized cognitive remediation therapy effects on resting state brain activity and cognition in schizophrenia.

计算机认知矫正疗法对精神分裂症静息态大脑活动和认知的影响

• DOI: 10.1038/s41598-017-04829-9
• 发表时间: 2017-07-06
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Fan F;Zou Y;Tan Y;Hong LE;Tan S
• 通讯作者: Tan S

CSF1R regulates schizophrenia-related stress response and vascular association of microglia/macrophages.

• DOI: 10.1186/s12916-023-02959-8
• 发表时间: 2023-08-04
• 期刊: BMC MEDICINE
• 影响因子: 9.3
• 作者: Yan, Ling;Li, Yanli;Fan, Fengmei;Gou, Mengzhuang;Xuan, Fangling;Feng, Wei;Chithanathan, Keerthana;Li, Wei;Huang, Junchao;Li, Hongna;Chen, Wenjin;Tian, Baopeng;Wang, Zhiren;Tan, Shuping;Zharkovsky, Alexander;Hong, L. Elliot;Tan, Yunlong;Tian, Li
• 通讯作者: Tian, Li