Towards Developing Biomarkers for Premature Aging in Schizophrenia

项目总结/摘要 来自大型临床和神经影像学研究的累积证据表明， 精神分裂症会增加过早衰老的可能性。然而，这些知识并没有被 由于缺乏对早产儿的生物学基础的了解， 精神分裂症中的衰老此外，目前仍然缺乏用于检测和监测的诊断工具， 在临床环境中经历过早衰老的个体。这种缺乏表明迫切需要发展 精神分裂症中过早衰老的体内生物标志物，以提供一种新的诊断途径， 神经保护治疗目前的建议为通过一个大的、 精神分裂症的多模式研究核心假设指出，精神分裂症患者 易受过早衰老的影响，如衰老相关的分泌性蛋白表达增加所示。 表型（SASP）蛋白，并且SASP蛋白的表达增加解释了 精神分裂症患者的身体健康、认知和大脑结构。 申请人Johanna Seitz-Holland博士可以访问多个横截面数据集，包括临床， 认知，血液，结构和扩散数据，跨越精神分裂症的寿命。在K99阶段，她将 利用来自80名早期精神分裂症患者和80名匹配的健康个体的数据来建立 SASP蛋白表达增加作为早期衰老易感性增加的生物标志物 当然是精神分裂症。在R 00阶段，Seitz-Holland博士将包括来自700多名个体（18-85岁）的数据 年），并描述了SASP蛋白表达增加的作用， 精神分裂症，身体健康，认知和大脑结构异常。成功 实现这些目标将产生若干有影响的成果。研究结果将为制定一项 临床上可行的，微创的，低风险的生物标志物过早老化。此外，调查结果将 允许发展一个简约的假设，解释大脑和身体健康的各个方面， 赤字最后，它们将为开发新的神经保护治疗提供科学依据。 Seitz-Holland博士的长期目标是进行转化研究，以提高那些患有 精神障碍这个应用程序建立在她的博士后培训多模式轨迹精神分裂症 研究并通过世界一流的血液生物标志物使用和分析专家的培训来补充它 数据和老年科学。因此，该奖项将为她提供一个独特的机会，发展成为一个 独立研究人员，能够有效地进行多模式精神病学研究，并将研究结果转化为 临床科学所需的循证诊断和治疗策略。

Project Summary / Abstract Cumulative evidence from large-clinical and neuroimaging studies suggests that the pathophysiology of schizophrenia involves an increased vulnerability to premature aging. However, this knowledge has not been translated into clinical practice due to the lack of understanding of the biological underpinnings of premature aging in schizophrenia. Additionally, there remains a current lack of diagnostic tools for detecting and monitoring individuals who experience premature aging in a clinical setting. This lack establishes the critical need to develop in vivo biomarkers of premature aging in schizophrenia to provide a novel avenue toward diagnosis and neuroprotective treatment. The current proposal provides a step to tackling this challenge through a large, multimodal study of schizophrenia. The central hypotheses state that individuals with schizophrenia are more vulnerable to premature aging, as indicated by an increased expression of senescence-associated secretory phenotype (SASP) proteins, and that the increased expression of SASP proteins explains abnormalities in physical health, cognition, and brain structure in schizophrenia. The applicant, Dr. Johanna Seitz-Holland, has access to several cross-sectional datasets, including clinical, cognitive, blood, structural, and diffusion data, spanning the schizophrenia lifespan. In the K99 phase, she will utilize data from 80 individuals with early schizophrenia and 80 matched healthy individuals to establish the increased expression of SASP proteins as a biomarker for increased vulnerability to premature aging in early course schizophrenia. In the R00 phase, Dr. Seitz-Holland will include data from over 700 individuals (18-85 years) and characterize the role of the increased expression of SASP proteins as a mediator between schizophrenia, physical health, cognition, and structural brain abnormalities across the lifespan. Successful completion of these aims will yield several impactful outcomes. The findings will inform the development of a clinically feasible, minimally invasive, and low-risk biomarker for premature aging. In addition, the findings will allow the development of a parsimonious hypothesis that accounts for aspects of brain and physical health deficits. Lastly, they will provide a scientific basis for developing novel neuroprotective treatments. Dr. Seitz-Holland’s long-term goal is to conduct translational research to increase the life quality of those with psychotic disorders. This application builds on her postdoctoral training in multimodal trajectory schizophrenia studies and complements it with training from world-class experts in the use and analysis of blood biomarker data and geriatric science. This award will thus provide her with a unique opportunity to develop into an independent researcher who can effectively conduct multimodal psychiatric studies and translate findings into the evidence-based diagnosis and treatment strategies needed in clinical science.