Olfactory Neuroimaging Markers of Heightened Developmental Risk for Schizophrenia

精神分裂症发育风险升高的嗅觉神经影像标志物

基本信息

批准号：
8788658
负责人：
BRUCE I TURETSKY
金额：
$ 56.14万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8788658
关键词：
Acoustic Rhinometry Adult Affect Attenuated Behavioral Brain Brain region Clinical Data Detection Development Diffusion Discrimination Disease Distress Early Intervention Early identification Embryonic Development Exhibits Family member Fetal Development First Degree Relative Future Genetic Genetic Risk Glutamates Glutamine Health Health Care Costs Impairment Individual Investigation Link Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measurement Measures Medial Methods Molecular Nasal cavity Neurobiology Neurons Odors Olfactory Cortex Olfactory Pathways Onset of illness Pathology Patients Performance Phenotype Prosencephalon Psychotic Disorders Public Health Research Residual state Risk Risk Marker Sampling Sampling Studies Schizophrenia Second Pregnancy Trimester Sensitivity and Specificity Spectrum Analysis Staging Structure Symptoms Youth base behavior measurement behavior test behavioral impairment clinical risk critical period disability endophenotype fetal functional disability high risk insight neuroimaging olfactory bulb olfactory sulcus psychotic symptoms sensory system success trait

项目摘要

DESCRIPTION (provided by applicant): Interventions early in the course of the illness could have an enormous impact on the public health costs and functional disability associated with schizophrenia. Early intervention requires a reliable method to identify young people who are at risk for developing psychosis. Youths with sub-psychotic or "prodromal" symptoms severe enough to prompt a clinical referral have a relatively high rate of conversion to psychosis. They often also exhibit subtle neurobiological and behavioral abnormalities, so-called endophenotypes, that are similar to those found in schizophrenia. These are thought to reflect the abnormal brain development that predisposes towards the illness. A judicious assessment of endophenotypes could, potentially, enhance the identification of individuals who are truly at risk for developing psychosis. To the extent that these developmental markers are evident before the impairment associated with sub-psychotic symptoms becomes obvious, they may also facilitate identification of at-risk youths at an earlier stage in the course of the prodrome. Research focusing on unaffected first-degree relatives of schizophrenia patients has identified many robust endophenotypes that are heritable, trait-like, and independent of overt illness. But these are also extremely poor predictors of future illness. This project will examine a set of neurobiological and behavioral markers that are likely to have more specific utility in predicting schizophrenia risk status. The rationale for this is based on two principles: 1)useful predictive measures should distinguish individuals with sub-psychotic clinical symptoms from unaffected first degree relatives without prodromal symptoms, who are unlikely to develop the illness~ 2) measures that can be mechanistically linked to a dysregulation of embryonic development during the critical late first - early second trimester risk period of fetal development should be more informative than relatively nonspecific indicators of compromised brain structure or function. It is proposed that measures of the neuronal integrity of the olfactory system represent just such specific risk markers. The olfactory system develops during this critical fetal risk perid in close coordination with development of the medial forebrain. It is intimately associated with the limbic brain regions commonly implicated in schizophrenia and is, itself, markedly impaired in schizophrenia. It can therefore illuminate early developmental contributions to heightened disease vulnerability. 35 patients with recent onset schizophrenia, 35 youths with a schizophrenia family member (genetic risk), 35 youths with prodromal symptoms (clinical risk), and 35 healthy comparison youths (low risk) will be studied. Behavioral tests will assess the integrity of olfactory capacity. 3T MR imaging and acoustic rhinometry will assess the structural integrity of the primary olfactory system. 7T 1HMR spectroscopy will assess the neuronal integrity of the primary olfactory system on a molecular level, through measurement of NAA and glutamate. The principal hypothesis is that schizophrenia patients and clinical-risk youths will both exhibit compromised olfactory neuronal integrity that distinguishes them from youths with isolated genetic risk or no risk for the illness.

描述（由申请人提供）：疾病早期的干预措施可能会对与精神分裂症相关的公共卫生成本和功能障碍产生巨大影响。早期干预需要一种可靠的方法来识别有患精神病风险的年轻人。具有亚精神病或“前驱”症状的年轻人严重到足以提示临床转诊的症状相对较高的转化率。它们通常还表现出微妙的神经生物学和行为异常，即所谓的内表型，与精神分裂症中发现的类似。这些被认为反映了易于疾病的脑发育异常。明智地评估内向型型，可能会增强对真正患有精神病风险的人的识别。在某种程度上，在与亚精神病症状相关的障碍之前，这些发育标记是显而易见的，它们也可能促进在前期的早期阶段对处于危险的年轻人的识别。精神分裂症患者不受影响的一级亲戚的研究确定了许多可遗传，特质且独立于明显疾病的强大内型型。但是，这些也是对未来疾病的预测指标。该项目将检查一组神经生物学和行为标记，这些神经生物学和行为标记可能在预测精神分裂症风险状态方面具有更具体的效用。这样的理由是基于两个原则：1）有用的预测措施应将其亚精神临床症状的个体与没有前途症状的未受影响的一级亲戚区分开比相对非特异性的大脑结构或功能的指标更具信息性。有人提出，嗅觉系统的神经元完整性的度量代表只是这种特定的风险标记。嗅觉系统在这种关键的胎儿风险中发展，与内侧前脑的发展密切协调。它与通常与精神分裂症有关的边缘大脑区域密切相关，并且本身在精神分裂症中显着受损。因此，它可以阐明对疾病脆弱性增强的早期发育贡献。将研究35名精神分裂症患者，35名精神分裂症家庭成员（遗传风险），35名患有前天症状的年轻人（临床风险）和35名健康比较年轻人（低风险）。行为测试将评估嗅觉能力的完整性。 3T MR成像和声性隆突计评估将评估原发性嗅觉系统的结构完整性。 7T 1HMR光谱法将通过测量NAA和谷氨酸在分子水平上评估一级嗅觉系统的神经元完整性。主要假设是，精神分裂症患者和临床风险青年都会表现出受损的嗅觉神经元完整性，使他们与遗传风险或没有疾病风险的年轻人区分开。