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: 10832333
• 负责人: Meghan Rhys Miller
• 金额: $ 14万
• 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/10832333
• 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.

项目总结/摘要 当他们被发现时，注意力缺陷/多动障碍（ADHD）和自闭症谱系 ADHD的特征部分在于自我调节的缺陷， 而社交沟通障碍是自闭症的标志虽然传统的诊断定义意味着 不同的表型，共同出现是常见的共享遗传力的证据，但鲜为人知的是， 重叠与独特的标志物和机制的早期发展。假定的共享过程包括 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）， 副交感神经系统（PNS）功能的指数，反映了努力分配和情绪 调节，已被建议作为潜在的转诊断生物标志物。以前没有研究检查共享 与非典型婴儿PNS功能、注意力调节和对以后的情感调节的不同贡献相比 自我调节和社会沟通缺陷的婴儿在遗传风险的这种挑战。此外，少数 研究表明，在高风险样本中，儿童早期症状的连续性， 检查了症状连续性的预测因素。解决这些问题对于尽早加强 检测工作，描述症状发展的潜在机制，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志物。这项建议旨在 更好地理解认知领域研究领域标准（RDoC）领域的发展途径 系统（认知控制/自我调节）和社会过程（社会沟通） 在富含此类挑战的样本中的发育：有ASD家族风险的婴儿（n = 60）， ADHD（n = 60）和两者的低风险（n = 40）。我们的目标是：（1）确定共同的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机制 在高危婴儿中，（2）评估自我调节和社会沟通问题的连续性， 幼儿期，包括描绘这种连续性的婴儿预测因素。利用以前的NIH支持 (K99/R 00 MH 106642），采用多方法、多受试者、多维设计， 在6或9、12、18、24和36个月大时进行评估，重点关注轨迹和中介机制。 该R 01提案响应了NIMH战略计划“定义复杂行为的机制”， “绘制精神疾病轨迹以确定何时，何地以及如何干预。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ADHD和ASD等疾病的早期识别，并鼓励跨诊断的发展， 以过程为中心的早期干预，与RDoC目标一致。

项目成果

Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit/hyperactivity disorder: A rich club-organization study.

• DOI: 10.1002/hbm.22603
• 发表时间: 2014-12
• 期刊: HUMAN BRAIN MAPPING
• 影响因子: 4.8
• 作者: Ray, Siddharth;Miller, Meghan;Karalunas, Sarah;Robertson, Charles;Grayson, David S.;Cary, Robert P.;Hawkey, Elizabeth;Painter, Julia G.;Kriz, Daniel;Fombonne, Eric;Nigg, Joel T.;Fair, Damien A.
• 通讯作者: Fair, Damien A.

Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder?

• DOI: 10.1007/s13311-012-0124-y
• 发表时间: 2012-07-01
• 期刊: NEUROTHERAPEUTICS
• 影响因子: 5.7
• 作者: Green, Chloe T.;Long, Debra L.;Schweitzer, Julie B.
• 通讯作者: Schweitzer, Julie B.

Does childhood executive function predict adolescent functional outcomes in girls with ADHD?

• DOI: 10.1007/s10802-009-9369-2
• 发表时间: 2010-04
• 期刊: JOURNAL OF ABNORMAL CHILD PSYCHOLOGY
• 影响因子: 3.6
• 作者: Miller, Meghan;Hinshaw, Stephen P.
• 通讯作者: Hinshaw, Stephen P.

A video-based measure to identify autism risk in infancy.

一种基于视频的方法，用于识别婴儿期自闭症风险。

• DOI: 10.1111/jcpp.13105
• 发表时间: 2020
• 期刊: Journal of child psychology and psychiatry, and allied disciplines
• 作者: Young,GregoryS;Constantino,JohnN;Dvorak,Simon;Belding,Ashleigh;Gangi,Devon;Hill,Alesha;Hill,Monique;Miller,Meghan;Parikh,Chandni;Schwichtenberg,AJ;Solis,Erika;Ozonoff,Sally
• 通讯作者: Ozonoff,Sally

Autism symptoms and internalizing psychopathology in girls and boys with autism spectrum disorders.

• DOI: 10.1007/s10803-011-1215-z
• 发表时间: 2012-01
• 期刊: JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
• 影响因子: 3.9
• 作者: Solomon, Marjorie;Miller, Meghan;Taylor, Sandra L.;Hinshaw, Stephen P.;Carter, Cameron S.
• 通讯作者: Carter, Cameron S.