Complex versus Essential Autism: A Developmental Study of Risk

复杂自闭症与本质自闭症：风险的发展研究

• 批准号: 9897597
• 负责人: FREDERICK SHIC
• 金额: $ 68.83万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897597
• 关键词: Age-Months; Attention; Behavioral; Behavioral Assay; Biological Markers; Birth; Caregivers; Cerebrum; Characteristics; Child; Clinical; Cognitive; Complex; Control Groups; Data; Development; Diagnostic; Dimensions; Disease; Electroencephalography; Etiology; Exhibits; Eye; Face; Family; Female; Functional disorder; Gestational Age; Goals; Heritability; Heterogeneity; Impaired cognition; Incidence; Individual; Infant; Intervention; Label; Life; Longitudinal Studies; Low Birth Weight Infant; Macrocephaly; Magnetic Resonance Imaging; Measures; Medical; Microcephaly; Morphogenesis; Neurocognitive; Outcome; Parents; Pattern; Performance; Phenotype; Questionnaires; Reporting; Risk; Risk Factors; Sampling; Seizures; Sensitivity and Specificity; Shapes; Siblings; Signal Transduction; Social Functioning; Specificity; Symptoms; System; Testing; Time; Toddler; Very Low Birth Weight Infant; Work; autism spectrum disorder; autistic children; behavior test; biomarker discovery; cognitive ability; comorbidity; design; disorder risk; habituation; high risk; high risk infant; information processing; insight; male; neurobehavioral; neurophysiology; potential biomarker; prognostic; prospective; relating to nervous system; sex; social; social attention; trait; visual tracking

PROJECT SUMMARY/ABSTRACT In recognition of the developmental heterogeneity of ASD, Miles and colleagues divided ASD into two groups: "complex autism" and "essential autism". The label "complex autism" grouped together children with ASD who had overt evidence of abnormalities of early morphogenesis, e.g. as signaled by the presence of multiple dysmorphic features and/or microcephaly and associated with lower IQs, more seizures, and higher incidence of EEG and MRI abnormalities. Children with "essential autism", by comparison, had fewer dysmorphic features, had greater male to female ratios, and showed greater heritability of autism features within families. An implication of this work was that in complex autism, autism was expected to arise as the result of broad developmental insult that also impacted social function, whereas essential autism was viewed as the result of specific social neural systems dysfunction. In this study, we use this conceptualization of complex versus essential autism to longitudinally track from 6 to 36 months of age two groups of infants with distinct etiologies but common elevation of autism symptoms: very low birthweight (VLBW, n=100) infants, who, like children with complex autism, are expected to evidence a broad range of delays in multiple domains, and high-risk infant siblings of children with ASD (HR-Sibs, n=100), who, as in essential autism, show heightened heritability of ASD symptoms and greater risk for social and communicative challenges. These groups are compared against a control group of low-risk typically developing children (LR, n=100). We take promising eye tracking (ET) and EEG paradigms that have been associated with the emergence of ASD in HR-Sibs in the first year after life after birth, and which were primarily developed to capture social dimensions of function, and extend them in order to investigate analogous nonsocial information processing. We hypothesize that VLBW infants evidencing ASD symptoms will show decreased performance in both social and nonsocial tasks, highlighting generalized difficulty with information processing consistent with broader developmental risk, whereas we hypothesize that difficulties in HR-Sibs with similar ASD symptoms will show more specific social (c.f. nonsocial) atypicalities. By adapting and extending paradigms which have shown strong or unique signal for later ASD in HR-Sibs, we will further our understanding of mechanisms underlying ASD risk and inform potential biomarker discovery; by pairing this with different etiological risk groups, we will elucidate multilevel vulnerabilities that can shape developmental trajectories and the emergence of the disorder. In summary, this work will advance our understanding of developmental trajectories of risk associated with ASD, elucidate mechanisms underlying later emergence of core autism features, and help to test and refine the sensitivity and specificity of putative early neurobehavioral and neurocognitive biomarkers for ASD.

项目摘要/摘要 为了认识到ASD的发育异质性，Miles和他的同事将ASD分为两组： “复杂型自闭症”和“特发性自闭症”。标签“复杂的自闭症”将患有自闭症的儿童归类在一起 有早期形态发生异常的明显证据，例如，多发性硬化症 畸形特征和/或小头畸形，并与低智商、更多癫痫发作和更高的发病率相关 脑电和核磁共振的异常。相比之下，患有“特发性自闭症”的儿童变形障碍较少 男性与女性的比例更高，自闭症特征在家庭中的遗传性也更高。 这项工作的一个含义是，在复杂的自闭症中，自闭症预计会作为广泛的 发育性侮辱也影响了社会功能，而基础自闭症被认为是 特定的社会神经系统功能障碍。在这项研究中，我们使用了复杂与复杂的概念 两组病因不同的婴儿对6至36个月大的自闭症进行纵向追踪 但自闭症症状的普遍升高：极低出生体重(VLBW，n=100)婴儿，他们喜欢患有 复杂的自闭症，预计会在多个领域表现出广泛的延迟，并且是高危婴儿 自闭症儿童的兄弟姐妹(HR-Sibs，n=100)，他们在严重自闭症中表现出更高的遗传性 ASD症状和更大的社交和沟通挑战风险。将这些群体与 低风险典型发育儿童的对照组(LR，n=100)。我们采用前景看好的眼球跟踪(ET)和 与出生后第一年出现ASD的HR-Sibs相关的EEG范例 在出生后，主要是为了捕捉功能的社会维度，并将其扩展到 为了研究类似的非社会信息加工。我们假设极低出生体重儿 ASD症状的证据将显示在社交和非社交任务中表现下降，强调 普遍的信息处理困难与更广泛的发育风险一致，而我们 假设有类似ASD症状的HR-Sibs的困难将表现出更具体的社交(参见 非社会的)非典型的。通过调整和扩展已显示出强烈或独特的信号的范例 稍后在HR-SIB中，我们将进一步了解ASD风险的潜在机制并告知 潜在的生物标记物发现；通过将其与不同的病因风险组配对，我们将阐明多水平 可以塑造发育轨迹和出现这种疾病的脆弱性。总而言之，这是 这项工作将促进我们对与ASD相关的风险发展轨迹的理解，阐明 自闭症核心特征后来出现的潜在机制，并有助于测试和完善敏感性和 ASD早期神经行为和神经认知生物标记物的特异性。