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.

项目概要/摘要 认识到自闭症谱系障碍的发育异质性，迈尔斯和同事将自闭症谱系障碍分为两组： “复杂自闭症”和“本质自闭症”。 “复杂自闭症”这一标签将患有自闭症谱系障碍的儿童归为一类。 有早期形态发生异常的明显证据，例如正如多个存在所表明的 畸形特征和/或小头畸形，与较低的智商、更多的癫痫发作和更高的发病率相关 EEG 和 MRI 异常。相比之下，患有“原发性自闭症”的儿童畸形较少 特征，男性与女性的比例更大，并且显示出自闭症特征在家庭中的遗传性更大。 这项工作的一个含义是，在复杂的自闭症中，自闭症预计是由于广泛的自闭症而出现的。 发育损伤也影响了社会功能，而原发性自闭症被认为是由于 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化 本质自闭症纵向追踪 6 至 36 个月大的两组具有不同病因的婴儿 但自闭症症状的常见升高：出生体重极低（VLBW，n = 100）的婴儿，例如患有以下疾病的儿童 复杂的自闭症，预计会证明多个领域的广泛延迟，以及高危婴儿 患有 ASD 儿童的兄弟姐妹（HR-Sibs，n=100），与原发性自闭症一样，他们表现出较高的遗传性 自闭症谱系障碍症状以及社交和沟通挑战的更大风险。这些组与 对照组为低风险、正常发育的儿童（LR，n=100）。我们采用有前途的眼动追踪（ET）和 与HR-同胞在生后第一年出现自闭症谱系障碍相关的脑电图范式 出生后，其主要开发目的是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处理。我们假设 VLBW 婴儿 证据表明自闭症谱系障碍症状将表明社交和非社交任务的表现下降，强调 信息处理的普遍困难与更广泛的发展风险一致，而我们 假设具有类似 ASD 症状的 HR-Sibs 的困难将表现出更具体的社交（参见 非社会）非典型性。通过调整和扩展已经显示出强烈或独特信号的范式 稍后在 HR-Sibs 中进行 ASD，我们将进一步了解 ASD 风险的潜在机制并告知 潜在的生物标志物发现；通过将其与不同的病因学风险组配对，我们将阐明多层次的 可能影响发育轨迹和疾病出现的脆弱性。综上所述，这 这项工作将增进我们对 ASD 相关风险发展轨迹的理解，阐明 自闭症核心特征后来出现的机制，有助于测试和完善敏感性和 自闭症谱系障碍（ASD）推定的早期神经行为和神经认知生物标志物的特异性。