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

• 批准号: 8618758
• 负责人: KRISTIN S. CADENHEAD
• 金额: $ 14.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8618758
• 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; 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; public health relevance; response; synaptogenesis; translational study; white matter

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（由申请人提供）：当前针对 PAR 11-031“发展中国家的脑部疾病：整个生命周期的研究”(R21) 的提案将建立在加州大学圣地亚哥分校 (UCSD) 和研究所之间现有的合作基础上国家神经病学家y Neurocirug¿ a (INNN)，墨西哥城。进一步合作，重点是了解和治疗早期精神病的神经病理变化，可能会对墨西哥的早期精神病研究产生重大影响，因为 INNN 是这座拥有超过 2000 万人的城市的中心培训基地。拟议的 R21 将提供资源 为潜在大量抗精神病药物开发招募基础设施此外，墨西哥城的 5 名首发精神病患者将增强他们在 INNN 的神经影像项目，该项目是通过加州大学圣地亚哥分校 (UCSD) 的磁共振成像 (MRI) 分析技术培训获得的，包括皮质厚度的分割分析和扩散张量的自由水分析。为了确保神经影像生物标志物的站点可靠性，我们将在项目的前三个月进行流动受试者研究，最后，2) 我们还将获得试点神经影像和炎症生物标志物数据。在两个地点的首次接受抗精神病治疗的患者和正常对照中进行研究，为一项纵向研究做准备，该研究调查同一人群中的神经炎症和抗炎治疗，最终我们计划提交一份转化 R01，以研究人类和动物模型中的神经炎症机制。据推测，生命早期接触感染和/或炎症有可能诱发潜在的神经炎症异常，而这种异常可以通过暴露于压力刺激、激活小胶质细胞和增强促炎物质的产生而被发现。动物模型已经证明，针对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/炎症的神经发育影响，与基础科学研究一致，最近对早期精神病患者的研究表明，相比之下，抗炎策略对慢性精神分裂症无效，这表明神经炎症过程在疾病早期活跃，是干预的重要目标。本申请中提出的多模式神经生物学技术可以进一步深入了解精神病出现的机制，随着对精神病发作时异常神经发育过程的了解不断增加，有可能开发出更好的治疗干预措施来改变疾病结果。发病率和死亡率。