An investigation of transdiagnostic mechanisms underlying ASD and ADHD traits among infants at risk

对高危婴儿 ASD 和 ADHD 特征的跨诊断机制的调查

• 批准号: 10617679
• 负责人: Meghan Rhys Miller
• 金额: $ 71.4万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617679
• 关键词: Address; Affect; Age Months; Attention; Attention deficit hyperactivity disorder; Award; Behavior; Behavioral; Child; Complex; Development; Diagnostic; Dimensions; Disease; Disease remission; Early Diagnosis; Early Intervention; Early identification; Exhibits; Genetic Risk; Goals; Heritability; Impairment; Individual; Infant; Informal Social Control; Intervention; Investigation; Link; Measures; Mediating; Mental disorders; Methods; National Institute of Mental Health; Nervous System Physiology; Nursery Schools; Outcome; Parasympathetic Nervous System; Pathway interactions; Pattern; Phenotype; Physiological; Prevention; Process; Psychophysiology; Regulation; Research; Research Domain Criteria; Risk; Sampling; Sinus Arrhythmia; Social Processes; Strategic Planning; Symptoms; Time; Toddler; Treatment Efficacy; United States National Institutes of Health; Visit; autism spectrum disorder; cognitive control; cognitive system; design; diagnostic biomarker; early childhood; emotion regulation; high risk; improved; indexing; informant; novel marker; respiratory; social communication; trait

PROJECT SUMMARY/ABSTRACT By the time they are typically detected, attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are already challenging to treat. ADHD is characterized, in part, by deficits in self-regulation, while social communication deficits are a hallmark of ASD. Although traditional diagnostic definitions imply distinct phenotypes, co-occurrence is common with evidence of shared heritability, but little is known about overlapping versus unique markers and mechanisms early in development. Putative shared processes include dysregulation of attention and affect. Based on links with these processes, respiratory sinus arrhythmia (RSA), an index of parasympathetic nervous system (PNS) functioning reflecting effort allocation and emotion regulation, has been suggested as a potential transdiagnostic biomarker. No prior studies have examined shared versus distinct contributions of atypical infant PNS functioning, attention regulation, and affect regulation to later self-regulation and social communication deficits in infants at genetic risk for such challenges. Moreover, few studies have characterized continuity of symptoms across early childhood in high-risk samples, nor have infant predictors of symptom continuity been examined. Addressing these points is imperative to enhancing early detection efforts, delineating mechanisms underlying symptom development, identifying targets and time points for prevention and intervention, and determining novel markers of treatment efficacy. This proposal seeks to better understand developmental pathways to the Research Domain Criteria (RDoC) domains of cognitive systems (cognitive control/self-regulation) and social processes (social communication) across early development in a sample enriched for such challenges: infants at familial risk for ASD (n = 60), familial risk for ADHD (n = 60), and low risk for both (n = 40). We aim to: (1) identify shared and distinct early behavioral and physiological markers of, and mechanisms underlying, self-regulation and social communication problems among infants at risk, and (2) evaluate continuity of self-regulation and social communication problems across early childhood, including delineation of infant predictors of such continuity. Leveraging previous NIH support (K99/R00 MH106642) and employing a multi-method, multi-informant, multi-dimensional design, infants will be evaluated at 6 or 9, 12, 18, 24, and 36 months of age with a focus on trajectories and mediational mechanisms. This R01 proposal responds to the NIMH Strategic Plan to “Define the Mechanisms of Complex Behaviors” and “Chart Mental Illness Trajectories to Determine When, Where, and How to Intervene.” Exploring shared versus distinct mechanisms underlying the development of self-regulation and social communication symptoms will improve early identification of disorders like ADHD and ASD and encourage the development of transdiagnostic, process-focused early interventions, consistent with RDoC goals.

项目摘要/摘要 当他们通常被检测到的时候，注意力缺陷/多动障碍(ADHD)和自闭症谱系 精神障碍(ASD)的治疗已经具有挑战性。ADHD的部分特征是缺乏自我调节， 而社交沟通障碍是自闭症的一个标志。尽管传统的诊断定义意味着 不同的表型，共同出现与共同遗传性的证据是常见的，但对此知之甚少 在发育早期，重叠与独特的标记和机制。假定的共享进程包括 注意力和情感的失调。基于与这些过程的联系，呼吸性窦性心律失常(RSA)， 反映努力分配和情绪的副交感神经系统(PNS)功能指标 调节，已被认为是一个潜在的跨诊断生物标志物。之前还没有研究过共享 与非典型婴儿三叉神经节功能、注意力调节和影响调节的不同贡献相比较 面临这种挑战的遗传风险婴儿的自我调节和社会沟通缺陷。此外，几乎没有人 在高危样本中，研究已经表征了儿童早期症状的连续性，婴儿也没有 对症状连续性的预测因素进行了检验。解决这些问题是加强早期教育的当务之急 检测工作，描述潜在症状发展的机制，确定目标和时间点 用于预防和干预，并确定治疗效果的新标记物。这项建议旨在 更好地理解认知的研究领域标准(RDoC)领域的发展路径 早期的系统(认知控制/自我调节)和社会过程(社会交流) 在样本中进行开发以应对这些挑战：有ASD家族风险的婴儿(n=60)， ADHD(n=60)，两者均为低风险(n=40)。我们的目标是：(1)识别共同和独特的早期行为和 自我调节和社会沟通问题的生理标志和潜在机制 在有风险的婴儿中，以及(2)评估自我调节和社会沟通问题的连续性 儿童早期，包括描述婴儿预测这种连续性的因素。利用之前的NIH支持 (K99/R00 MH106642)并采用多方法、多信息者、多维度设计，婴儿将 在6个月或9个月、12个月、18个月、24个月和36个月时进行评估，重点是轨迹和中介机制。 该R01提案响应了NIMH战略计划，以“定义复杂行为的机制”，并 绘制精神疾病轨迹图，以确定何时、何地以及如何进行干预。探索共享与 自我调节和社会沟通症状发展的不同机制将 改善对ADHD和ASD等疾病的早期识别，并鼓励发展跨诊断， 以流程为重点的早期干预，与RDoC目标一致。