Neural Oscillatory Biomarkers for Genetics and Animal Models of Schizophrenia

精神分裂症遗传学和动物模型的神经振荡生物标志物

基本信息

批准号：
8460095
负责人：
L Elliot Elliot Hong
金额：
$ 52.57万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8460095
关键词：
Acute Address Agonist Anatomy Animal Model Animals Antipsychotic Agents Auditory Auditory Evoked Potentials Behavioral Sciences Biological Markers Brain Candidate Disease Gene Cells Chronic Clinical Clinical Research Cognitive Complex Computer Simulation Data Data Analyses Dimensions Disease Dose Drug Formulations Electroencephalography Event Evoked Potentials Excitatory Postsynaptic Potentials Exhibits Family member First Degree Relative Frequencies Functional disorder GABA Agents GABA Agonists Genes Genetic Genetic Markers Genotype Glossary Glutamate Decarboxylase Glutamatergic Agents Glutamates High Frequency Oscillation Hippocampus (Brain)Human Impaired cognition Investigation Ketamine Laboratory Animals Lead Location Measurable Measures Methodology Methods Microdialysis Modeling Molecular Molecular Target Mutation N-Methyl-D-Aspartate Receptors N-Methylaspartate Neurons Neurosciences Nucleus Accumbens Pathology Patients Pattern Performance Personality Pharmaceutical Preparations Phenotype Population Prefrontal Cortex Process Psychotic Disorders Quantitative Trait Loci Rattus Relative (related person)Research Research Project Grants Rest Retrieval Risk Rodent Rodent Model Role Sampling Scalp structure Schizophrenia Sensory Sensory Process Series Severities Short-Term Memory Signal Transduction Staging System Testing Time Translational Research Translations auditory stimulus awake base brain electrical activity clinical phenotype cognitive function density design disability disease phenotype drug development endophenotype executive function follow-up functional disability gamma-Aminobutyric Acid neurogenesis novel postsynaptic pre-clinical public health relevance receptor relating to nervous system research study response sensory gating severe mental illness simulation sound tool visual stimulus

项目摘要

DESCRIPTION (provided by applicant): Neural Oscillatory Biomarkers for Genetics and Animal Models of Schizophrenia Project Summary: Neural oscillations are electrical activities of the brain measurable at different frequencies. They can be obtained at many levels, ranging from single cell to local field potentials in animals, to large-scale synchronized activities in human scalp. Patients with schizophrenia exhibit impaired neural oscillatory activities during sensory and cognitive tasks such as sensory gating, working memory, executive functions, and even at rest and during processing of monotonous visual and auditory stimuli. New evidence suggests that there may be common underlying abnormalities in oscillatory activities that are associated with schizophrenia-related cognitive and functional impairments. We have modified and developed experimental paradigms that will elicit oscillatory responses from basic sensory to more complex cognitive performance. We plan to isolate the common oscillatory abnormality in schizophrenia across tasks. In addition, since neural oscillations can be measured in animals and in humans in a similar fashion, it is possible to carry out parallel animal and human research using similar neural oscillatory measures as disease biomarkers. Towards this aim, these electrophysiological paradigms are constructed in a way that they are potentially feasible both in clinical population phenotyping and in small animal implementation, so that neural oscillatory biomarkers validated by this study in schizophrenia patients, and subsequent genetic findings from these neural oscillation phenotypes, can be applied to translational research in animals. Using the Building Translational Research in Integrative Behavioral Science mechanism, we propose to initiate similar paradigms in rodents. The basic neuroscience component of this application is to establish analogous rodent models using experimental paradigm closely matched with that of the human experiments, and then to conduct initial mechanistic studies on the pathophysiological origins of the abnormal neural oscillations found in patients with schizophrenia. This effort should lay the necessary groundwork for interpreting clinical findings and ultimately using neural oscillations as a translational tool in studying the molecular path from genes to pathophysiology and their treatment in schizophrenia. The neurogenesis of neural oscillations is under intense study. However, systematic investigations of their roles as disease phenotypes in schizophrenia populations are needed. The potentially novel biomarkers thus described and validated should significantly shorten the research cycle from biomarker discovery to gene identification and novel drug development in animal models.

描述（由申请人提供）：精神分裂症项目概述的遗传学和动物模型的神经振荡生物标志物：神经振荡是可在不同频率下可测量的大脑的电活动。它们可以在许多层面上获得，从单个细胞到动物的局部场电位，再到人类头皮中的大规模同步活动。精神分裂症患者在感觉门控，工作记忆，执行功能，静止和处理过程中以及单调视觉和听觉刺激期间的感觉和认知任务期间表现出受损的神经振荡活动。新的证据表明，与精神分裂症相关的认知和功能障碍相关的振荡活动中可能存在共同的基本异常。我们已经修改并开发了实验范式，这些范式将引起从基本感觉到更复杂的认知性能的振荡反应。我们计划跨任务隔离精神分裂症的常见振荡异常。此外，由于可以以类似的方式在动物和人类中测量神经振荡，因此可以使用类似的神经振荡措施与疾病生物标志物进行平行的动物和人类研究。为了实现这一目标，这些电生理范例的构建方式是，它们在临床人群表型和小动物实施中可能是可行的，因此该研究在精神分裂症患者中通过这项研究验证的神经振荡生物标志物，以及这些神经振荡现象的随后的遗传发现，可用于翻译动物。使用综合行为科学机制中的建筑转化研究，我们建议在啮齿动物中启动类似的范式。该应用的基本神经科学组成部分是使用与人类实验的实验范式建立类似的啮齿动物模型，然后对异常神经振荡的病理生理起源进行初步机械研究，该研究在精神分裂症患者中发现。这项工作应该为解释临床发现并最终使用神经振荡作为研究从基因到病理生理学及其在精神分裂症中治疗的分子路径的必要基础。神经振荡的神经发生正在进行中。但是，需要系统地研究它们作为精神分裂症种群中疾病表型的作用。如此描述和验证的潜在新型生物标志物应大大缩短研究周期，从生物标志物发现到基因鉴定和动物模型中的新药物发育。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lack of association between COMT gene and deficit/nondeficit schizophrenia.

COMT 基因与缺陷/非缺陷型精神分裂症之间缺乏关联。

DOI：
10.1186/1744-9081-2-42
发表时间：
2006
期刊：
Behavioral and brain functions : BBF
影响因子：
0
作者：
Wonodi,Ikwunga;Mitchell,BraxtonD;Stine,OColin;Hong,LElliot;Elliott,Amie;Kirkpatrick,Brian;CarpenterJr,WilliamT;Thaker,GunvantK;Buchanan,RobertW
通讯作者：
Buchanan,RobertW

Antigliadin Antibodies (AGA IgG) Are Related to Neurochemistry in Schizophrenia.

DOI：
10.3389/fpsyt.2017.00104
发表时间：
2017
期刊：
Frontiers in psychiatry
影响因子：
4.7
作者：
Rowland LM;Demyanovich HK;Wijtenburg SA;Eaton WW;Rodriguez K;Gaston F;Cihakova D;Talor MV;Liu F;McMahon RR;Hong LE;Kelly DL
通讯作者：
Kelly DL