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.

项目概要/摘要 以非侵入性连接为导向的神经影像方法的出现，为了解大脑的内部结构带来了新的曙光。 大脑的运作。大脑的功能和结构连接组在调节 从基因到神经系统再到精神疾病的途径。沿着这些路径，我们假设 先天应激免疫通路的异常活动对大脑连接组有重大贡献 精神分裂症谱系障碍早期阶段的破坏及其临床后果。项目 提议扩展精神疾病领域的连接组项目，以表征大脑回路及其与 中国精神分裂症谱系障碍早期应激-免疫轴功能障碍。我们提出一个 对大样本患者进行纵向研究，旨在克服关系中的异质性 精神疾病和压力-免疫-连接体轴之间的关系是推进研究的公认障碍 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压力和急性心理压力实验室范例进行评估 定义基线的压力生物标志物。这些患者将与250名年龄和性别匹配的患者进行比较 健康的控制。此次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 中国合作伙伴在精神分裂症方面的临床免疫学研究专业知识。拟议的研究还 建立在我们正在进行的工作的基础上，使用急性和慢性压力范式来了解压力如何与 精神分裂症谱系疾病中的大脑结构和功能连接组。美国的这一新颖提议 而中国的心理健康研究领域也得到了初步数据的有力支持。应用能力 使用北京先进研究指定扫描仪的尖端连接组协议也将 增强我们使用多模态成像工具来帮助减少基于生物学的异质性的能力。一起， 这项研究将产生可行的策略来治疗和预防大脑连接组恶化并促进 精神病发作后的临床恢复。

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