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.

项目摘要 /摘要 非侵入性连通性的神经影像学方法的出现使内在的新光线散发出来 大脑的起作用。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。沿着这些途径，我们假设 先天应力免疫途径的异常活性对大脑连接组有很大的贡献 精神分裂症谱系障碍及其临床后果的早期阶段破坏。项目 提议将精神疾病中的连接组项目扩展到表征脑电路及其与之的关系 中国精神分裂症谱系障碍早期的应力免疫轴功能障碍。我们提出了一个 大量患者的纵向研究旨在克服关系中的异质性 在精神疾病和压力免疫连接体轴之间，这是一个公认的障碍 和治疗。我们将在五年内招募500名精神分裂症谱系障碍患者 发作。将使用现代慢性压力和急性心理压力实验室范例评估它们 在基线时定义应力生物标志物。将患者与250岁和性别匹配的比较 健康控制。该协作利用了美国合作伙伴和 中国伴侣在精神分裂症方面的临床免疫学研究专业知识。拟议的研究也 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了解压力如何与 精神分裂症谱系中的大脑结构和功能连接组。这个在美国的小说命题 和中国心理健康研究领域的初步数据得到了强有力的支持。应用的能力 使用北京的高级研究指定扫描仪的尖端连接组协议也将 增强我们使用多模式成像工具来帮助基于生物学的异质性降低的能力。一起， 这项研究将产生可行的策略，以治疗和防止大脑连接症的恶化并促进 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