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.

项目摘要/摘要 到通常检测到它们时，注意力缺陷/多动症（ADHD）和自闭症谱系 疾病（ASD）已经挑战治疗。 ADHD的特征是在自我调节中定义 尽管社会交流防御是ASD的标志。尽管传统诊断定义暗示 独特的表型，共同出现具有共同遗传力的证据很常见，但对 发展早期的重叠与独特的标记和机制。推定的共享过程包括 注意力和影响的失调。基于与这些过程的联系，呼吸窦性心律失常（RSA）， 副交感神经系统（PNS）的索引，反映了努力分配和情感 调节已被认为是潜在的转诊生物标志物。没有先前的研究检查共享 非典型婴儿PNS功能，注意调节和影响调节的不同贡献与不同的贡献 婴儿的自我调节和社会交流防御这种挑战的遗传风险。而且，很少 研究表征了高风险样本中幼儿期症状的连续性，婴儿也没有 检查了症状连续性的预测因子。解决这些观点对于早期增强至关重要 检测工作，描述症状发展的基础机制，确定目标和时间点 用于预防和干预，并确定治疗效率的新标记。该提议试图 更好地了解认知研究领域标准（RDOC）领域的发展途径 早期的系统（认知控制/自我调节）和社会过程（社会交流） 在富含此类挑战的样本中开发的开发：家庭有ASD风险的婴儿（n = 60），家庭风险 ADHD（n = 60），两者的风险较低（n = 40）。我们的目标是：（1）确定共享和独特的早期行为和 生理标志物以及基础，自我调节和社会交流问题的机制 在处于危险中的婴儿中，以及（2）评估自我调节和社会交流问题的连续性 幼儿期，包括对这种连续性的婴儿预测指标的描述。利用以前的NIH支持 （K99/R00 MH106642）并采用多方法，多维设计，婴儿将是 在6或9、12、18、24和36个月大时进行评估，重点是轨迹和中介机制。 R01提出对NIMH战略计划的响应，以“定义复杂行为的机制”和 “绘制精神疾病轨迹，以确定何时，何地和如何干预。”探索共享与 自我调节和社会交流症状发展的不同机制将 改善对ADHD和ASD等疾病的早期识别，并鼓励转诊的发展， 以过程为重点的早期干预措施与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.