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）：目前的提案是针对PAR 11-031，发展中国家的大脑疾病：整个生命周期的研究（R21），将建立在加州大学圣地亚哥分校（UCSD）和墨西哥城国家神经学和神经循环研究所（INNN）之间的现有合作基础上。进一步的合作，重点是了解和治疗早期精神病的神经病理变化，可能对墨西哥的早期精神病研究产生重大影响，因为INNN是这个拥有2000多万人口的城市的中心培训基地。拟议的R21将1)为以下方面提供资源