Inflammatory Biomarkers in First Episode Psychosis: A Mexico/US Collaboration

首发精神病中的炎症生物标志物：墨西哥/美国合作

基本信息

批准号：
8842718
负责人：
KRISTIN S. CADENHEAD
金额：
$ 10.41万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2017-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8842718
关键词：
Acute Affect Animal Model Anti-Inflammatory Agents Anti-inflammatory Antipsychotic Agents Apoptosis Attenuated Basic Science Biological Markers Brain Brain Diseases California Chronic Schizophrenia Cities Collaborations Data Development Diagnostic Diffusion Magnetic Resonance Imaging Disease Disease Outcome Early Intervention Exposure to Fostering Grant Health Human Image Image Analysis Infection Inflammation Inflammatory Inflammatory Response Institutes Interferons Interleukin-1 Interleukin-12 Interleukin-6 Intervention Knowledge Lead Longevity Longitudinal Studies Magnetic Resonance Imaging Measures Mexican Mexican Americans Mexico Microglia Morbidity - disease rate Neurobehavioral Manifestations Neurobiology Neurons Oligodendroglia Pathogenesis Patients Pharmaceutical Preparations Phase Population Preparation Process Production Psychotic Disorders Publications Relapse Reporting Research Research Infrastructure Research Personnel Resources Sampling Schizophrenia Serum Site Staging Stimulus Study Subject Surface Symptoms System Techniques Thick Training Travel Tumor Necrosis Factor-alpha United States Universities Water axonal degeneration cytokine early life exposure extracellular first episode psychosis gray matter insight morphometry mortality neurodevelopment neurogenesis neuroimaging neuroinflammation neuropsychological prenatal programs response synaptogenesis translational study white matter

项目摘要

DESCRIPTION (provided by applicant): The current proposal in response to PAR 11-031, Brain Disorders in the Developing World: Research Across the Lifespan (R21) will build on an existing collaboration between University of California San Diego (UCSD) and the Instituto Nacional de Neurolog¿a y Neurocirug¿a (INNN), Mexico City. Further collaboration, with an emphasis on understanding and treating the neuropathological changes in early psychosis could have a significant impact on early psychosis research in Mexico since INNN is a central training site in this city of over 20 million people. The proposed R21 will 1) provide resources to develop the recruitment infrastructure for potentially very large numbers of antipsychotic na¿ve first episode psychosis patients in Mexico City. In addition, the Mexican site will enhance their neuroimaging program at the INNN by obtain training from UCSD in Magnetic resonance imaging (MRI) analysis techniques including segmentation analysis of cortical thickness and free water analysis of Diffusion Tensor Imaging (DTI) data. To assure between site reliability of neuroimaging biomarkers, we will perform a traveling subjects study during the first three months of the project. Finally, 2) we will also obtain pilot neuroimaging and inflammatory biomarker data in antipsychotic naive first episode patients and normal controls at both sites in preparation for a longitudinal study that investigates neuroinflammation and anti-inflammatory treatment in the same population. Ultimately we plan to submit a translational R01 that will investigate neuroinflammatory mechanisms in human and animal models of early psychosis. It has been postulated that early-life exposure to infection and/or inflammation has the potential to induce latent neuroinflammatory abnormalities that can be unmasked by exposure to stressful stimuli, activating microglia and enhancing the production of pro-inflammatory cytokines in the CNS. Animal models have demonstrated that the neurodevelopment effects of prenatal infection/inflammation can be attenuated by interventions targeting activated inflammatory response systems or associated physiologically processes. Consistent with the basic science research, recent studies in early psychosis patients suggest that anti-inflammatory interventions may attenuate negative and cognitive symptoms. In contrast, anti-inflammatory strategies are not effective in chronic schizophrenia, suggesting that neuroinflammatory processes are active during the early phase of disease and an important target for intervention. The use of multimodal neurobiological techniques as proposed in this application can provide further insight into the mechanism by which psychosis emerges. With increasing knowledge of the aberrant neurodevelopmental processes at the onset of psychosis, it may become possible to develop better treatment interventions to modify the disease outcome, morbidity and mortality.

描述（由应用程序提供）：当前的提案响应于第11-031套第11-031套，发展中国家的脑部疾病：整个生命周期（R21）的研究将基于加州圣地亚哥大学（UCSD）（UCSD）与研究所Neurolog研究的现有合作。进一步的合作，重点是理解和治疗早期精神病的神经病理学变化，可能会对墨西哥的早期精神病研究产生重大影响，因为Innn是这个超过2000万人的中央培训地点。拟议的R21将1）提供资源开发墨西哥城的招聘基础设施，以实现大量的抗精神病药na¿此外，墨西哥站点将通过在磁共振成像中获得UCSD训练（MRI）分析技术，从而增强其在INNN的神经影像学计划，包括对皮质厚度的分割分析和扩散张量成像（DTI）数据的游离水分析。为了确保神经成像生物标志物的站点可靠性之间，我们将在项目的前三个月内进行旅行主题研究。最后，2）我们还将在两个部位的抗精神病药天真幼稚的第一事件患者和正常对照中获得试验性神经影像学和炎症生物标志物数据，以准备一项纵向研究，该研究研究了同一人群中神经神经炎症和抗炎治疗的纵向研究。最终，我们计划提交一种翻译R01，该R01将研究早期精神病的人和动物模型中的神经炎症机制。我们已经假设，早期感染和/或感染的潜力有可能诱导潜在的神经炎症异常，可以通过暴露于压力的刺激，激活小胶质细胞并增强CNS中促炎细胞因子的产生。动物模型表明，靶向激活的炎症反应系统或相关生理过程的干预措施可以减弱产前感染/炎症的神经发育作用。与基础科学研究一致，对早期精神病患者的最新研究表明，抗炎干预措施可能会减轻阴性和认知症状。相反，抗炎策略在慢性精神分裂症中无效，表明神经炎症过程在疾病的早期阶段是活跃的，并且是干预的重要目标。本应用程序中提出的多模式神经生物学技术的使用可以进一步了解精神病出现的机制。随着对精神病开始时对异常神经发育过程的了解，可能有可能开发出更好的治疗干预措施以改变疾病结果，发病率和死亡率。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Striatal glutamate, subcortical structure and clinical response to first-line treatment in first-episode psychosis patients.

DOI：
10.1016/j.pnpbp.2021.110473
发表时间：
2022-03-08
期刊：
Progress in neuro-psychopharmacology & biological psychiatry
影响因子：
5.6
作者：
Reyes-Madrigal F;Guma E;León-Ortiz P;Gómez-Cruz G;Mora-Durán R;Graff-Guerrero A;Kegeles LS;Chakravarty MM;de la Fuente-Sandoval C
通讯作者：
de la Fuente-Sandoval C

Impairment of novelty-related theta oscillations and P3a in never medicated first-episode psychosis patients.