Shared and Distinct Developmental Pathways to ADHD and Autism Spectrum Disorder

 描述(由申请人提供)：拟议项目的首要目标是确定自闭症谱系障碍(ASD)和注意力缺陷/多动障碍(ADHD)症状的共同和独特的早期行为指标，并更好地了解每种综合征风险儿童的ASD和ADHD的早期发展途径。ASD和ADHD是两种在儿童早期出现的流行疾病，每一种都会导致显著的长期损害。共病很常见，有证据表明有共同的遗传性和家族遗传，以及重叠的神经和神经认知异常，但我对诊断前发育早期的独特和共同特征知之甚少。很明显，确定与ASD或ADHD发展唯一相关的早期迹象对于加强准确的早期发现工作和确定理想的干预靶点和时间点至关重要。不太被认识到的是，预防和早期干预努力的影响也将通过确定跨诊断因素或跨障碍共享的过程来加强，这些因素是症状发展的基础。这是一种适用于ASD和ADHD研究的理想方法，因为，鉴于有共同的生物和行为异常的证据，一些早期行为指标可能也会重叠，作为非典型发育的一般指标，可用于跨诊断治疗的开发和预防工作。建议进行两项纵向研究，以考察三组儿童的早期行为指标和发展轨迹：ASD儿童的婴儿兄弟姐妹(高危ASD)、ADHD儿童的婴儿兄弟姐妹(高危ADHD)和典型发育儿童的婴儿兄弟姐妹(低风险)。K99的这项研究旨在确定在24个月龄时，在12个月和18个月龄时，在关键的认知、语言、社交和行为领域中，对ASD和ADHD症状的发展进行维度测量的早期共享和独特的预测因素。R00研究将以K99研究为基础，跟踪36个月的独立婴儿样本，纳入其他测量策略和明确的诊断结果，允许检查ASD儿童与ADHD儿童共同和独特的早期发育轨迹诊断结果。在每项研究中，多方法、多信息者、多维度的评估将包括直接行为评估、眼球跟踪、父母完成的评分表和审查员完成的评分。这些研究对于：(A)阐明共同的与不同的发育途径；(B)准确的早期筛查、评估和鉴别诊断；(C)确定制定有针对性的、以过程为重点的干预和预防计划的关键领域和时间点，这些计划可以在生命早期应用于许多患有各种诊断或面临各种诊断风险的人群，符合NIH研究领域标准(RDoC)的目标。

 DESCRIPTION (provided by applicant): The overarching goals of the proposed project are to identify shared and distinct early behavioral indicators for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) symptoms, and to better understand early developmental pathways to ASD and ADHD in children at risk for each syndrome. ASD and ADHD are two prevalent disorders emerging early in childhood, each conferring significant long-term impairment. Co-occurrence is common, and there is evidence of shared heritability and familial transmission, as well as overlapping neural and neurocognitive abnormalities, but little i known about unique and shared features very early in development, prior to diagnosis. It is clear that determining early signs uniquely associated with the development of ASD or ADHD is critical to enhancing accurate early detection efforts and identifying ideal targets and time point for intervention. What has been less well appreciated is that the impact of prevention and early intervention efforts will also be heightened by identifying transdiagnostic factors, or processes shared across disorders, that underlie symptom development. This is an ideal approach to apply to the study of ASD and ADHD because, given evidence of shared biological and behavioral abnormalities, it is likely that some early behavioral indicators also overlap, serving as general indices of atypical development that could be leveraged for transdiagnostic treatment development and prevention efforts. Two longitudinal studies are proposed to examine early behavioral indicators and developmental trajectories in three groups of children: infant siblings of children with ASD (high-risk ASD), infant siblings of children with ADHD (high-risk ADHD), and infant siblings of typically developing children (low-risk). The K99 study aims to identify early shared and distinct predictors of the development of dimensionally-measured ASD versus ADHD symptoms at 24 months of age across key cognitive, language, social, and behavioral domains at 12 and 18 months of age. The R00 study will build upon the K99 study, following an independent sample of infants through 36 months and incorporating additional measurement strategies and categorical diagnostic outcomes, allowing for the examination of shared and distinct early developmental trajectories of children with ASD versus ADHD diagnostic outcomes. Within each study, multi-method, multi-informant, multidimensional evaluations will include direct behavioral assessments, eye tracking, parent-completed rating scales, and examiner- completed ratings. These studies will be critical for (a) elucidating shared versus distinct developmental pathways; (b) accurate early screening, assessment, and differential diagnosis; and (c) determining key domains and time points for the development of targeted, process-focused intervention and prevention programs that can be applied early in life across many groups of individuals with, or at risk for, various diagnoses, consistent with the NIH Research Domain Criteria (RDoC) goals.