Towards Developing Biomarkers for Premature Aging in Schizophrenia

开发精神分裂症过早衰老的生物标志物

• 批准号: 10739528
• 负责人: Johanna Seitz-Holland
• 金额: $ 13.06万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-03 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739528
• 关键词: Affect; Age; Aging; Award; Biological; Biological Markers; Blood; Brain; Cell Aging; Cells; Clinical; Clinical Sciences; Cognition; Cognitive; Complement; Complex; Data; Data Set; Dementia; Deterioration; Development; Diagnosis; Diffusion; Disease; Elderly; Equation; Excess Mortality; Factor Analysis; Foundations; Functional disorder; Goals; Hospitals; Image; Impaired cognition; Individual; Knowledge; Life; Life Expectancy; Link; Longevity; Mediator; Medical; Medicine; Mental Depression; Mental Health; Mental disorders; Mentors; Mission; Modeling; Monitor; National Institute of Mental Health; Nerve Degeneration; Outcome; Phase; Phenotype; Physical Sufferings; Population; Premature aging syndrome; Process; Proteins; Psychiatry; Psychology; Psychotic Disorders; Public Health; Quality of life; Research; Research Personnel; Research Project Grants; Risk; Role; Schizophrenia; Science; Secretory Component; Solid; Structure; Tissues; Training; Translating; Translational Research; Woman; Work; aged; brain abnormalities; brain health; clinical practice; comorbidity; diagnostic tool; evidence base; experience; in vivo; indexing; instructor; medical schools; minimally invasive; multimodality; neuroimaging; neuroprotection; novel; novel strategies; physical conditioning; post-doctoral training; senescence; skills; statistics; treatment strategy; Affect; Age; Aging; Award; Biological; Biological Markers; Blood; Brain; Cell Aging; Cells; Clinical; Clinical Sciences; Cognition; Cognitive; Complement; Complex; Data; Data Set; Dementia; Deterioration; Development; Diagnosis; Diffusion; Disease; Elderly; Equation; Excess Mortality; Factor Analysis; Foundations; Functional disorder; Goals; Hospitals; Image; Impaired cognition; Individual; Knowledge; Life; Life Expectancy; Link; Longevity; Mediator; Medical; Medicine; Mental Depression; Mental Health; Mental disorders; Mentors; Mission; Modeling; Monitor; National Institute of Mental Health; Nerve Degeneration; Outcome; Phase; Phenotype; Physical Sufferings; Population; Premature aging syndrome; Process; Proteins; Psychiatry; Psychology; Psychotic Disorders; Public Health; Quality of life; Research; Research Personnel; Research Project Grants; Risk; Role; Schizophrenia; Science; Secretory Component; Solid; Structure; Tissues; Training; Translating; Translational Research; Woman; Work; aged; brain abnormalities; brain health; clinical practice; comorbidity; diagnostic tool; evidence base; experience; in vivo; indexing; instructor; medical schools; minimally invasive; multimodality; neuroimaging; neuroprotection; novel; novel strategies; physical conditioning; post-doctoral training; senescence; skills; statistics; treatment strategy

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.

项目摘要 /摘要 来自大型临床和神经影像学研究的累积证据表明， 精神分裂症涉及增加过早衰老的脆弱性。但是，这些知识不是 由于缺乏对早产的生物基础的了解，因此被转化为临床实践 精神分裂症的衰老。此外，目前仍缺乏用于检测和监视的诊断工具 在临床环境中经历过早衰老的个人。这种缺乏确定了发展的迫切需要 精神分裂症过早衰老的体内生物标志物，为诊断和 神经保护治疗。当前的提案提供了通过大型，大型， 精神分裂症的多模式研究。中心假设指出，精神分裂症患者更多 易受过早衰老的影响，如感应相关分泌的表达增加所表明 表型（SASP）蛋白质，SASP蛋白的表达增加说明了异常 精神分裂症的身体健康，认知和大脑结构。 申请人Johanna Seitz-Holland博士可以访问几个横截面数据集，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名早期精神分裂症和80个健康个体的数据来建立 SASP蛋白作为生物标志物的表达增加，以增加早期衰老的脆弱性 课程精神分裂症。在R00阶段，Seitz-Holland博士将包括来自700多个人的数据（18-85 年）并表征了SASP蛋白表达增加的作用作为介体 精神分裂症，身体健康，认知和结构性脑异常。成功的 这些目标的完成将产生一些有影响力的结果。这些发现将为发展的发展提供信息 临床上可行的，微创和低风险生物标志物，用于过早衰老。此外，调查结果将 允许开发一个简约的假设，该假设解释了大脑和身体健康的各个方面 缺陷。最后，它们将为开发新的神经保护疗法提供科学基础。 Seitz-Holland博士的长期目标是进行转化研究，以提高患有 精神病。该应用程序以她在多模式轨迹精神分裂症的博士后培训为基础 通过世界一流的专家在血液生物标志物使用和分析方面的培训和完成研究和完成 数据和老年科学。因此，该奖项将为她提供一个独特的机会，以发展成一个 可以有效地进行多模式精神研究并将发现转化为的独立研究人员 临床科学所需的基于证据的诊断和治疗策略。