AUTISM--A MODEL OF ANOMALOUS NEURAL SYSTEMS DEVELOPMENT

自闭症——神经系统发育异常的模型

• 批准号: 6393849
• 负责人: Pauline A. Filipek
• 金额: $ 29.86万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393849
• 关键词: adolescence (12-20); autism; behavioral /social science research tag; clinical research; developmental neurobiology; human puberty; human subject; longitudinal human study; magnetic resonance imaging; middle childhood (6-11); neuroanatomy

DESCRIPTION: By school age, the rate of normal human brain growth declines sharply, but these final phases are especially critical to the maturation of motor, linguistic, cognitive and social aptitudes in the acquisition of adaptive behaviors. These growth rates reflect a delicate balance of normal progressive and regressive histogenic mechanisms. The developmental disorders can be a model for study of anomalous brain development, in particular autistic disorder (AD), which is characterized by deficits in socialization, attention, concept formation, verbal and non-verbal communication, and ritualistic, perseverative behaviors. The investigator's prior MRI-based morphometric analysis in children with AD, developmental language disorders (DLD), non-autistic low IQ (NILIQ), and normal children have shown that both AD and DLD brains are unexpectantly larger in volume and controls which is due to excessive white matter disproportionately localized to the temporal and posterior parietal region, including the angular gyrus, superior parietal lobule, and visual/association regions. These results point to maldevelopment of neocortical systems and are consistent with some of the classic neocortical localization theories. The investigators propose: 1) To recruit three new cohorts of children in early adolescence, aged 10.0 through 15.11, N=30 in each: a) autistic disorder, divided into high IQ (nonverbal IQ70) and low (nonverbal IQ<70) AD cohort; b) nonautistic low IQ (nonverbal IQ<70); c) normal control volunteers are children with headaches, with normal birth, development, and medical histories, and normal, cognitive, linguistic and behavioral function (nonverbal IQ<70); 2) To replicate the investigator's previous morphometric findings of localized anomalous white matter volumes in the AD cohorts by performing the first of two sequential high-resolution three dimensional (3D) gradient echo T(1) - weighted MRI scans. Complete morphometric analysis will include computation of volume for whole brain, individual substructures, and hemisphere gradients. A new method of cortical localization and parcellation will then be applied to these MRI scans, reference to the Brodnann architectonic map and compatible with the Mesulem scheme of neurosystems hierarchy; 3) To test the hypothesis that the anomalous dysfunctional neurosystems are related to linguistic and neurobehavioral deficits in AD, independent of nonverbal IQ; and 4) To further investigate the effects of puberty on brain development in AD by performing a second of two sequential MRI scans three years later with repeated morphometric and cortical parcellation analysis on these AD and control cohorts.

描述：到了学龄期，正常人类大脑的生长速度会下降 急剧，但这些最后阶段对于成熟尤其关键 习得的运动、语言、认知和社交能力 适应性行为。 这些增长率反映了正常的微妙平衡 进行性和回归性组织发生机制。 发展性的 疾病可以成为研究大脑异常发育的模型 特殊的自闭症（AD），其特征是缺乏 社交、注意力、概念形成、言语和非言语 沟通、仪式性、持久的行为。 调查员的 先前对患有 AD、发育障碍的儿童进行基于 MRI 的形态测量分析 语言障碍 (DLD)、非自闭症低智商 (NILIQ) 和正常儿童 研究表明，AD 和 DLD 的大脑体积都出乎意料地大 并控制由于白质过多而引起的不成比例的 定位于颞叶和后顶叶区域，包括 角回、顶上小叶和视觉/关联区域。 这些结果表明新皮质系统发育不良，并且 与一些经典的新皮质定位理论一致。 研究人员建议：1）招募三组新的儿童 青春期早期，10.0 岁至 15.11 岁，每组 N=30：a) 自闭症 障碍，分为高智商（非语言智商70）和低智商（非语言智商<70）AD 队列； b) 非自闭性低智商（非语言智商<70）； c) 正常对照 志愿者是患有头痛、出生、发育和发育正常的儿童。 病史以及正常、认知、语言和行为功能 （非语言智商<70）； 2) 复制研究者之前的形态测量 AD 队列中局部白质体积异常的发现 执行两个连续高分辨率三维扫描中的第一个 (3D) 梯度回波 T(1) - 加权 MRI 扫描。 完整的形态测量 分析将包括计算整个大脑、个体的体积 子结构和半球梯度。 皮质的新方法 然后定位和分割将应用于这些 MRI 扫描， 参考 Brodnann 建筑地图并与 Mesulem 兼容 神经系统层次结构图； 3）检验假设 异常功能失调的神经系统与语言和 AD 中的神经行为缺陷，与非语言智商无关； 4) 至 进一步研究青春期对 AD 大脑发育的影响 三年后进行两次连续 MRI 扫描中的第二次 对这些 AD 和皮质分区进行重复的形态测量和皮质分区分析 控制队列。

项目成果

Mitochondrial dysfunction in autistic patients with 15q inverted duplication.

15q 倒置重复自闭症患者的线粒体功能障碍。

• 发表时间: 2003-06
• 影响因子: 11.2
• 作者: Filipek, Pauline A;Juranek, Jenifer;Smith, Moyra;Mays, Lee Z;Ramos, Erica R;Bocian, Maureen;Masser;Laulhere, Tracy M;Modahl, Charlotte;Spence, M Anne;Gargus, J Jay
• 通讯作者: Gargus, J Jay