Investigation of Immune Markers in Adolescents with Clinical High Risk for Psychosis

 描述（由申请人提供）：这是James Yi，MD，PhD的K23奖申请，James Yi是一位具有分子生物学背景的儿童和青少年精神病学家，他正在将自己确立为精神分裂症前驱症状研究的年轻研究者。他专注于免疫功能障碍在精神病风险中的作用。这个职业发展奖将为他提供必要的支持，以获得免疫学方面的专业知识，使他能够发展独立的研究生涯，调查与精神分裂症相关的早期免疫机制。他提出了一个协调的培训计划的研究，导师和课程。沿着他的主要导师，宾夕法尼亚大学神经精神病学项目和精神分裂症中心主任Raquel Gur博士和共同导师，CHOP免疫遗传学实验室主任Steve道格拉斯博士，他组建了一个咨询委员会，由发育精神病理学、神经认知、高级生物统计学和研究职业发展方面的专家组成。 精神分裂症前驱症状是一个公认的早期干预治疗的机会窗口，越来越多的研究越来越多地集中在确定预测疾病进展的风险因素，这可能有助于早期干预。一些趋同的证据暗示免疫系统在精神分裂症的病理生理学，并可能提供新的治疗靶点。值得注意的是，在精神分裂症患者中观察到促炎细胞因子水平升高和单核细胞总数增加，这表明炎症过程可能导致疾病。然而，由于现有的研究主要是在成人患者中进行的，因此免疫系统功能障碍在前驱症状中的作用尚不清楚。利用一个独特的队列的青年与临床高风险的精神病建立通过费城神经发育队列，我们建议纵向检查促炎和抗炎细胞因子和单核细胞亚群，沿着全面评估阈下精神病的特点和神经认知表现牵连精神分裂症。通过研究免疫标记物与精神病特征的关系，我们相信拟议的研究将澄清免疫功能障碍的性质和免疫标记物在预测疾病进展中的效用。此外，这项研究将为跨多个分析单元检查免疫标记物提供基础，例如在未来的工作中检查的基因组和神经成像数据。

 DESCRIPTION (provided by applicant): This is an application for a K23 award for James Yi, MD, PhD, a child and adolescent psychiatrist with molecular biology background who is establishing himself as a young investigator in schizophrenia prodrome research. He is focusing on the role of immune dysfunction in psychosis risk. This Career Development Award will provide him with the necessary support to acquire expertise in immunology, enabling him to develop an independent research career, investigating early immune mechanisms associated with schizophrenia. He has proposed a coordinated training plan of research, mentorship and coursework. Along with his primary mentor, Dr. Raquel Gur, the Director of Neuropsychiatry program and Schizophrenia Center at University of Pennsylvania and co-mentor, Dr. Steve Douglas, the Director of Immunogenetics Laboratory at CHOP, he has assembled an Advisory Committee comprising experts in developmental psychopathology, neurocognition, advanced biostatics and research career development. Schizophrenia prodrome is a well-recognized window of opportunity for early intervention treatments and more studies have increasingly focused on identifying risk factors predictive of illness progression that could facilitate early interventions. Several convergent lines of evidence implicate the immune system in the pathophysiology of schizophrenia and may provide novel therapeutic targets. Notably, elevated levels of pro-inflammatory cytokines and increased total number of monocytes have been observed in patients with schizophrenia, implicating that inflammatory processes may contribute to the illness. However, because existing studies have been largely in adult patients, the role of immune system dysfunction during the prodrome is unclear. Capitalizing on a unique cohort of youths with clinical high-risk for psychosis established through the Philadelphia Neurodevelopmental Cohort, we propose to longitudinally examine both pro- and anti-inflammatory cytokines and monocyte subpopulations, along with a comprehensive assessment for subthreshold psychotic features and neurocognitive performances implicated in schizophrenia. By examining the trajectory of immune markers in relation to psychotic features, we believe the proposed study will clarify the nature of immune dysfunction and utility of immune markers in predicting the disease progression. Furthermore, this research will provide the basis for examining immune markers across multiple units of analysis such as genomic and neuroimaging data to be examined in future efforts.