NEUROIMAGING STUDIES OF NEUROPHYSIOLOGICAL PHENOTYPES IN SCHIZOPHRENIA

精神分裂症神经生理表型的神经影像学研究

• 批准号: 7951158
• 负责人: ELIZABETH HONG-GELLER
• 金额: $ 1.26万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951158
• 关键词: Affect; Antipsychotic Agents; Auditory; Biological; Biological Markers; Blood; Brain; Candidate Disease Gene; Clinical Research; Cognitive; Computer Retrieval of Information on Scientific Projects Database; DNA; Data; Disease; Enrollment; Epidemiology; Etiology; Event-Related Potentials; Evoked Potentials; Eye Movements; Family history of; First Degree Relative; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genomics; Genotype; Grant; Image; Imaging Techniques; Imaging technology; Individual; Institution; Investigation; Knowledge; Measures; Output; Patients; Pharmaceutical Preparations; Phenotype; Procedures; Process; Protocols documentation; Psychophysiology; Psychotic Disorders; Reporting; Research; Research Personnel; Research Subjects; Resources; Sampling; Schizophrenia; Siblings; Smooth Pursuit; Source; Symptoms; Testing; Translating; United States National Institutes of Health; Visual Motion; base; behavior measurement; design; insight; minimal risk; neural circuit; neuroimaging; neurophysiology; relating to nervous system; research study; response; sound

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The etiopathophysiology of schizophrenia is not completely understood. Genetic epidemiological data indicate a strong genetic component in the etiology of the illness. Several neurophysiological measures, including smooth pursuit eye movement (SPEM), evoked potentials (ERP), and functional imaging abnormalities, are shown to be related to the genetic liability of schizophrenia. For example, SPEM abnormalities are some of the most reproducible biological findings associated with the illness. Interestingly, these eyetracking abnormalities are not only observed in patients with schizophrenia, but are also found in first degree relatives of patients who do not have psychotic symptoms, suggesting that SPEM abnormalities mark a genetic liability of the illness. It has been suggested that SPEM abnormalities can serve as a phenotypic marker of schizophrenia. However, the neural basis of reported abnormalities in SPEM is not well understood, and even less is known about how genetic effects are translated into aberrant neural circuit controlling SPEM. Another example is evoked potential brain wave abnormalities, which also have been identified as potential biological markers for the genetic liability of the illness. Knowledge of the psychophysical and biological mechanisms underlying these neurophysiological phenotypes and their relationship to the schizophrenia phenotype may provide critical insight into the etiology of this disease. For this investigation we designed fMRI and event-related potential (ERP) experiments to examine the perceptual and cognitive contributions to cortical mechanisms controlling eye movement outputs. Three groups of subjects will be tested: schizophrenic patients (~ n=60), full siblings of patients (~60), and healthy controls without family history of psychosis (~60), for a total target enrollment of about 180 subjects. We expect that fMRI and ERP will provide a safe, non-invasive approach to carefully examine the neurophysiological process leading to pursuit eye movement and evoked potential dysfunction in schizophrenia in this multi-year project. We have included full siblings to examine the familial aggregation of these neurophysiological abnormalities. Since most of the siblings are not on antipsychotic medications, their inclusion allows an examination of some of the dysfunctions associated with schizophrenia in individuals not affected by antipsychotic medications. Blood DNA sample will be collected and stored in GCRC Genomic Core. We will examine candidate genes and their effects on neural imaging phenotypes. In summary, using fMRI and ERP imaging technology, we propose in this project to gain direct evidence of the abnormal circuitry controlling the candidate neurophysiological phenotypes in schizophrenia. This approach could potentially have a higher yield than behavioral measures in identifying the genetic etiology of schizophrenia because imaging techniques should be a better measure of the core biological deficits controlled by the putative disease-related genes. We should expect more robust genotype-phenotype association using imaging based phenotypes. The procedures included in this protocol, e.g., ERP recording, fMRI, or response to auditory sounds or visual motion presentations are not invasive and should pose minimal risk to research subjects.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 精神分裂症的病因病理生理学尚未完全了解。遗传流行病学数据表明，在疾病的病因学中有很强的遗传成分。一些神经生理学指标，包括平稳追踪眼球运动（SPEM），诱发电位（ERP），和功能成像异常，被证明与精神分裂症的遗传易感性。例如，SPEM异常是与疾病相关的一些最可重复的生物学发现。有趣的是，这些眼动异常不仅在精神分裂症患者中观察到，而且在没有精神病症状的患者的一级亲属中也发现了，这表明SPEM异常标志着疾病的遗传易感性。有人认为，SPEM异常可以作为精神分裂症的表型标志物。然而，报告的SPEM异常的神经基础还没有很好地理解，甚至更少有人知道遗传效应是如何转化为异常的神经回路控制SPEM。另一个例子是诱发电位脑电波异常，这也被确定为疾病遗传易感性的潜在生物标志物。了解这些神经生理表型背后的心理物理和生物学机制及其与精神分裂症表型的关系可能会为了解这种疾病的病因提供重要见解。在这项研究中，我们设计了功能磁共振成像和事件相关电位（ERP）的实验，以检查知觉和认知的贡献，控制眼动输出的皮层机制。将对三组受试者进行测试：精神分裂症患者（~ n=60）、患者的同胞兄弟姐妹（~60）和无精神病家族史的健康对照（~60），总目标入组约180例受试者。我们希望，功能磁共振成像和ERP将提供一个安全的，非侵入性的方法，仔细检查神经生理过程中导致追求眼球运动和诱发电位功能障碍的精神分裂症在这个多年的项目。我们已经包括了全同胞，以检查这些神经生理异常的家族聚集性。由于大多数兄弟姐妹没有服用抗精神病药物，因此将其纳入研究可以检查未受抗精神病药物影响的个体中与精神分裂症相关的一些功能障碍。将采集血液DNA样本并储存在GCRC基因组核心中。我们将研究候选基因及其对神经成像表型的影响。综上所述，本研究拟利用功能磁共振成像和事件相关电位成像技术，获得精神分裂症患者神经生理学表型异常控制回路的直接证据。这种方法可能有一个更高的产量比行为措施在确定精神分裂症的遗传病因，因为成像技术应该是一个更好的措施的核心生物缺陷控制的推定疾病相关基因。我们应该期待更强大的基因型-表型关联使用成像为基础的表型。本方案中包括的程序，例如，ERP记录，功能磁共振成像，或对听觉声音或视觉运动呈现的反应都不是侵入性的，应该对研究对象造成最小的风险。