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: 7656685
• 负责人: JOHN Horace GILMORE
• 金额: $ 193.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7656685
• 关键词: Prospective; Studies; Pathogenesis; Schizophrenia

DESCRIPTION (as provided by applicant): 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.

描述（由申请人提供）：精神分裂症与MRI上脑结构的细微异常有关，包括侧脑室增大、皮质灰质体积减少、海马体积减少以及白质扩散特性异常。虽然人们假设这些大脑异常是在大脑发育早期出现的，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，我们开发了磁共振图像（MRI）采集和图像分析工具，用于研究精神分裂症高危儿童的早期大脑发育。其中包括遗传高风险组——患有精神分裂症的妇女的后代，以及“结构性”高风险组——产前患有孤立的轻度脑室肥大的儿童。我们的结果数据表明，与正常对照相比，新生儿MRI显示，精神分裂症母亲的后代皮质灰质体积减少。这是第一个具体的证据，证明早期皮质发育受到遗传易感性的损害。围产期和产后早期是皮层连通性发育的关键时期之一，是突触快速生长的时期，也是本中心研究的重点。此外，我们还建立了一大批正常对照。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，应用我们新的图像分析方法在一个扩大的队列中研究灰质和白质的发育，并研究纵向的大脑发育变化，因为我们跟踪我们的队列到儿童中期。具体来说，我们将通过3T MRI（包括弥散张量成像）研究精神分裂症高危儿童的纵向脑发育，并在0岁、1岁、2岁、4岁和6岁时进行神经发育评估。我们还将研究双相情感障碍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，我们已经获得了一大批正常新生儿的DNA和核磁共振成像，并将确定风险基因的多态性是否会影响生命早期的皮质发育。