PROSPECTIVE STUDIES OF THE PATHOGENESIS OF SCHIZOPHRENIA

精神分裂症发病机制的前瞻性研究

• 批准号: 8171047
• 负责人: JOHN Horace GILMORE
• 金额: $ 0.91万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171047
• 关键词: 6 year old; Age; Brain; Child; Childhood; Chronic Disease; Computer Retrieval of Information on Scientific Projects Database; DNA; Data; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Funding; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Grant; Gray unit of radiation dose; Growth; Hippocampus (Brain); Image Analysis; Institution; Isolated mild ventriculomegaly; Life; Longitudinal Studies; Magnetic Resonance Imaging; Methodology; Mothers; Neonatal; Pathogenesis; Perinatal; Pharmaceutical Preparations; Property; Prospective Studies; Research; Research Personnel; Resources; Risk; Schizophrenia; Source; Staging; Structure; Synapses; Time; United States National Institutes of Health; Woman; cohort; comparison group; critical period; gray matter; high risk; lateral ventricle; neonate; novel; offspring; postnatal; prenatal; tool; white matter

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. Schizophrenia is associated with subtle abnormalities of brain structure on MRI, including enlarged lateral ventricles, reduced cortical gray matter volumes, reduced hippocampal volumes, as well as abnormal diffusion properties in white matter. While it has been hypothesized that these brain abnormalities arise during early brain development, there has been little direct evidence to support this idea. In the first funding period of this Conte Center project, we developed the magnetic resonance image (MRI) acquisition and image analysis tools to study very early brain development in children at high risk for schizophrenia. These included a genetic high risk group - the offspring of women with schizophrenia, and a "structural" high risk group - children with prenatal isolated mild ventriculomegaly. Our results to data indicate that compared to normal controls, the offspring of mothers with schizophrenia have reduced cortical gray matter volumes on neonatal MRI. This is the first concrete evidence that early cortical development is compromised by genetic vulnerability. The perinatal and early postnatal period is one of the critical periods in the development of cortical connectivity - a time of rapid synapse growth - one that is a focus of this Conte Center. In addition, we have developed a large cohort of normal controls. In the second funding period, we propose to continue our study of every early brain development in normal and high risk children, applying our novel image analysis methodologies to study gray and white matter development in an expanding cohort, and to study longitudinal brain developmental changes as we follow our cohort into mid childhood. Specifically we will study longitudinal brain development in children at high risk for schizophrenia with 3T MRI (including diffusion tensor imaging) and neurodevelopmental assessments at ages 0, 1, 2, 4, and 6 years of age. We will also study early brain development in the offspring of mothers with bipolar illness as a comparison group for non-specific effects of medication and chronic illness. Finally, we have obtained DNA and MRIs on a large group of normal neonates and will determine if polymorphisms of risk genes influence cortical development at this earliest stage of life.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 精神分裂症与 MRI 上大脑结构的细微异常有关，包括侧脑室扩大、皮质灰质体积减少、海马体积减少以及白质扩散特性异常。虽然有人假设这些大脑异常是在早期大脑发育过程中出现的，但几乎没有直接证据支持这一观点。在康特中心项目的第一个资助期间，我们开发了磁共振图像（MRI）采集和图像分析工具，以研究精神分裂症高危儿童的早期大脑发育。其中包括遗传性高风险群体——患有精神分裂症的妇女的后代，以及“结构性”高风险群体——产前孤立性轻度脑室扩张的儿童。我们的数据结果表明，与正常对照组相比，患有精神分裂症的母亲的后代在新生儿 MRI 上的皮质灰质体积减少。这是第一个具体证据表明早期皮质发育受到遗传脆弱性的影响。围产期和产后早期是皮质连接发展的关键时期之一，是突触快速生长的时期，也是该孔特中心的重点之一。此外，我们还开发了一大批正常对照。在第二个资助期，我们建议继续研究正常和高危儿童的每一个早期大脑发育，应用我们新颖的图像分析方法来研究不断扩大的队列中灰质和白质的发育，并研究随着我们的队列进入童年中期的纵向大脑发育变化。具体来说，我们将通过 3T MRI（包括扩散张量成像）研究精神分裂症高危儿童的纵向大脑发育，并在 0、1、2、4 和 6 岁时进行神经发育评估。我们还将研究患有躁郁症的母亲的后代的早期大脑发育，作为药物和慢性疾病的非特异性影响的对照组。最后，我们获得了一大群正常新生儿的 DNA 和 MRI，并将确定风险基因的多态性是否影响生命最早阶段的皮质发育。