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: 10813959
• 负责人: FREDERICK SHIC
• 金额: $ 18.04万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-29 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10813959
• 关键词: Age Months; Attention; Behavioral; Behavioral Assay; Biological Markers; Birth; Caregivers; Cerebral Palsy; Characteristics; Child; Clinical; Cognitive; Complex; Control Groups; Data; Development; Diagnostic; Dimensions; Disease; Dysmorphology; Electroencephalography; Equation; Etiology; Exhibits; Face; Family; Female; Functional disorder; Gestational Age; Goals; Heritability; Heterogeneity; Impaired cognition; Incidence; Individual; Infant; Intervention; Label; Life; Macrocephaly; 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; Social Interaction; 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; longitudinal, prospective study; magnetic resonance imaging/electroencephalography; male; neural; neurobehavioral; neurophysiology; potential biomarker; prognostic; 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 认识到ASD的发育异质性，Miles和同事将ASD分为两组： “复杂自闭症”和“本质自闭症”。“复杂自闭症”这个标签将患有ASD的儿童分组， 有明显的早期形态发生异常的证据，例如，通过存在多个 畸形特征和/或小头畸形，并与较低的智商，更多的癫痫发作和更高的发病率相关 脑电图和核磁共振成像异常相比之下，患有“原发性自闭症”的儿童 特征，有更大的男性对女性的比例，并显示出更大的遗传性自闭症功能的家庭内。 这项工作的一个含义是，在复杂的自闭症中，自闭症被认为是广泛的 发展侮辱，也影响了社会功能，而本质性自闭症被视为结果， 特定的社会神经系统功能障碍。在这项研究中，我们使用这种概念化的复杂与 从6到36个月纵向跟踪两组具有不同病因的婴儿 但常见的自闭症症状升高：极低出生体重（VLBW，n=100）婴儿， 复杂的自闭症，预计将证明在多个领域的广泛延迟，和高风险的婴儿， ASD儿童的兄弟姐妹（HR-Sibs，n=100），与原发性自闭症一样， ASD症状和社交和沟通挑战的更大风险。将这些群体与 低风险典型发育儿童对照组（LR，n=100）。我们采用有前景的眼动追踪（ET）， 与出生后第一年内HR-同胞ASD出现相关的EEG范式 出生后，主要是为了捕捉功能的社会层面，并将其扩展到 为了研究类似的非社会信息处理。我们假设极低出生体重儿 证明ASD症状将显示在社交和非社交任务中的表现下降， 信息处理的普遍困难与更广泛的发展风险一致，而我们 假设具有相似ASD症状的HR-Sib中的困难将显示出更具体的社会（参见 非社会性的）非社会性的。通过调整和扩展已显示出强烈或独特信号的范式， 以后ASD在HR同胞，我们将进一步了解ASD风险的机制，并告知 潜在的生物标志物发现;通过将其与不同的病因风险组配对，我们将阐明多水平 脆弱性，可以塑造发展轨迹和出现的障碍。总之，这 这项工作将促进我们对ASD相关风险发展轨迹的理解，阐明 核心自闭症特征出现的潜在机制，并有助于测试和完善敏感性， 推定的ASD早期神经行为和神经认知生物标志物的特异性。