Olfactory Function in Schizophrenia: A Lifespan Analysis

精神分裂症的嗅觉功能：寿命分析

• 批准号: 7822568
• 负责人: PAUL J MOBERG
• 金额: $ 33.8万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7822568
• 关键词: Acoustic Rhinometry; Adolescent; Adult; Affect; Anterior; Anterior nares; Area; Arts; Award; Basal Cell; Behavioral; Biological; Biopsy; Brain; Brain region; Cerebrum; Characteristics; Classification; Collection; Complex; Cultured Cells; Data; Detection; Development; Discrimination; Disease; Dose; Dysmorphology; Economics; Electroencephalography; Electrophysiology (science); Epithelial; Event-Related Potentials; Evoked Potentials; Exhibits; Face; Family member; First Degree Relative; Future; Gene Expression Profiling; Goals; Hereditary Disease; Histologic; Human; Image; Impairment; In Vitro; Individual; Life; Location; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Medicine; Methodology; Methods; Modeling; Molecular; Morphogenesis; Morphology; Mucous Membrane; Nasal Epithelium; Nasal cavity; Natural regeneration; Nerve Degeneration; Neurobiology; Neurons; Nose; Occupations; Odors; Olfactory Cortex; Olfactory Epithelium; Olfactory Receptor Neurons; Oral; Oral cavity; Palate; Parents; Patients; Performance; Peripheral; Pharmaceutical Preparations; Photography; Physiological; Positioning Attribute; Process; Psychophysics; Psychophysiology; Psychotic Disorders; Recovery; Relative (related person); Research; Resolution; Risk; Role; Sampling; Scalp structure; Schizophrenia; Sensory Process; Smell Perception; Source; Structure; Symptoms; System; Temporal Lobe; Three-dimensional analysis; Tissues; Training; Work; base; behavior test; cell type; craniofacial; cranium; density; digital imaging; endophenotype; fetal; follow-up; functional disability; healthy volunteer; hedonic; high risk; in vivo; insight; intimate behavior; molecular marker; nerve stem cell; neurodevelopment; neurogenesis; neuron apoptosis; neuron development; novel; olfactory bulb; olfactory stimulus; proband; public health relevance; response; sensory stimulus; stimulus processing; synaptogenesis; tissue culture

DESCRIPTION (provided by applicant): This Revision Application proposal seeks to break new ground in regard to the scope and aims of the parent RO1, which was awarded for 5 years beginning 03/01/08. Consistent with the goals of the Recovery Act and notice NOT-OD-09- 058, we plan to systematically collect and analyze olfactory epithelial biopsy tissue as well as perform detailed peripheral and central electrophysiological studies of the olfactory system in schizophrenia patients and healthy controls. Olfactory epithelium is unique in that it constitutes the sole source of regenerating neural cells that can be obtained from a living human. That is, the location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. Primary cultures derived from human olfactory epithelial biopsies can subsequently be utilized to study neurobiological characteristics of individuals under different conditions and disease states. The collection of olfactory biopsy tissue will allow for further characterization of basal cells in OE in terms of their ultrastructural features as well as gene expression profiling to better define the role of each cell type in neurogenesis. New methodologies will be employed to examine peripheral components of olfactory sensory processing, i.e., olfactory event-related potentials (OERPs), as well as more traditional scalp recordings of the olfactory- evoked potential. We will study 30 schizophrenia patients and 30 unrelated healthy controls. Results from the in vivo electrophysiological studies will be integrated with the results of the cellular and molecular studies that use ORN tissue biopsies obtained from the same subjects. Our working model is that olfactory deficits reflect genetically-mediated abnormalities in neuron-to-neuron connectivity, arising from neurodevelopmentally disturbed processes of neurogenesis and synapse formation. Penn Medicine contributes substantially to the local economy. In 2008, Penn Medicine created 37,000 jobs and $5.4 billion in regional economic activity, with the area's highly trained workforce producing more than 24,600 applications for just 840 open Penn staff research positions. The current proposal will create or retain 2.5 jobs. PUBLIC HEALTH RELEVANCE: Schizophrenia is currently thought to be a complex genetic disorder, with altered neuronal development, perhaps very early in life, important in determining vulnerability. Neurogenesis and neurodevelopment occur in the adult olfactory epithelium (OE), and the collection and study of olfactory biopsy tissue may provide insights into the neuro- biological basis of altered neurodevelopment in this disorder. We plan to collect and analyze OE biopsy tissue as well as perform detailed peripheral and central electrophysiological studies of the olfactory system in schizophrenia patients and healthy controls. Penn Medicine contributes substantially to the local economy. In 2008, Penn Medicine created 37,000 jobs and $5.4 billion in regional economic activity, with the area's highly trained workforce producing more than 24,600 applications for just 840 open Penn staff research positions. The current proposal will create or retain 2.5 jobs.

描述(由申请人提供)：本修订申请方案寻求在父RO1的范围和目标方面取得新的突破，该申请从2008年3月1日开始，为期5年。根据恢复法和通知NOT-OD-09-058的目标，我们计划系统地收集和分析嗅觉上皮活检组织，并对精神分裂症患者和健康对照组的嗅觉系统进行详细的外周和中枢电生理学研究。嗅觉上皮的独特之处在于，它是再生神经细胞的唯一来源，可以从活人身上获得。也就是说，嗅觉感受器神经元在鼻上皮中的位置允许对活体受试者的这些神经元进行非侵入性接触。这为直接评估患者体内神经元的完整性提供了一个独特的机会。取自人类嗅觉上皮活组织的原代培养物可用于研究不同条件和疾病状态下个体的神经生物学特征。嗅觉活检组织的收集将允许进一步表征OE中的基底细胞的超微结构特征以及基因表达谱，以更好地确定每种细胞类型在神经发生中的作用。新的方法将被用来检测嗅觉感觉处理的外围组件，即嗅觉事件相关电位(OERPs)，以及更传统的嗅觉诱发电位的头皮记录。我们将研究30名精神分裂症患者和30名无亲属关系的健康对照。体内电生理研究的结果将与使用从相同受试者获得的ORN组织活检的细胞和分子研究的结果整合在一起。我们的工作模型是，嗅觉缺陷反映了遗传介导的神经元到神经元连接的异常，源于神经发生和突触形成的神经发育障碍过程。宾夕法尼亚医科大学为当地经济做出了巨大贡献。2008年，宾夕法尼亚医科大学创造了3.7万个就业机会和54亿美元的区域经济活动，该地区训练有素的劳动力仅为840个宾夕法尼亚大学员工研究职位空缺就产生了超过24600份申请。目前的提案将创造或保留2.5个就业岗位。 与公共卫生相关：精神分裂症目前被认为是一种复杂的遗传性疾病，神经元发育改变，可能在生命的早期，对确定脆弱性很重要。神经发生和神经发育发生在成人嗅觉上皮(OE)，收集和研究嗅觉活检组织可以提供对这种疾病神经发育改变的神经生物学基础的见解。我们计划收集和分析OE活检组织，并对精神分裂症患者和健康对照组的嗅觉系统进行详细的外周和中枢电生理研究。宾夕法尼亚医科大学为当地经济做出了巨大贡献。2008年，宾夕法尼亚医科大学创造了3.7万个就业机会和54亿美元的区域经济活动，该地区训练有素的劳动力仅为840个宾夕法尼亚大学员工研究职位空缺就产生了超过24600份申请。目前的提案将创造或保留2.5个就业岗位。