Autistic Traits: Life Course & Genetic Structure

自闭症特征：生命历程

• 批准号: 8303302
• 负责人: JOHN N. CONSTANTINO
• 金额: $ 53.11万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8303302
• 关键词: 11p; Accounting; Adolescence; Adolescent; Adult; Affect; African American; Age; Architecture; Asperger Syndrome; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Behavioral; Biocompatible Materials; Biological Psychiatry; Brothers; Candidate Disease Gene; Caucasians; Caucasoid Race; Characteristics; Child; Childhood; Clinical; Clinical Research; Collection; Complex; DNA; DSM-IV; Data; Data Linkages; Data Reporting; Data Set; Databases; Development; Developmental Process; Diagnosis; Diagnostic; Disadvantaged; Disease; Dysmorphology; Enrollment; Ethnic Origin; Ethnic group; Event-Related Potentials; Factor Analysis; Family; Family Study; Female; Funding; Gender; Gene Frequency; General Population; Generations; Genes; Genetic; Genetic Load; Genetic Structures; Genotype; Health; Hispanics; Impaired cognition; Impairment; Incidence; Individual; Infant; Intervention; Interview; Life; Life Cycle Stages; Longevity; Longitudinal Studies; Manuals; Manuscripts; Measurement; Measures; Methods; Minority; Missouri; Modeling; Motor; Neurobiology; North Carolina; Nursery Schools; Outcome; Parents; Partner in relationship; Pattern; Phenotype; Population; Predisposition; Psychiatry; Public Health; Publishing; Questionnaires; Recruitment Activity; Registries; Reporting; Research; Research Personnel; Rest; Role; Sampling; Schedule; Schizoid Personality Disorder; Secure; Sensory; Severities; Siblings; Signal Transduction; Sister; Site; Social Development; Spouses; Stimulus; Structure; Study Subject; Susceptibility Gene; Symptoms; Testing; Time; Underrepresented Minority; Universities; Validation; Variant; Washington; autism spectrum disorder; base; design; endophenotype; family genetics; follow-up; functional disability; genetic linkage analysis; genetic pedigree; genetic resource; grandparent; indexing; infancy; intergenerational; intervention effect; longitudinal course; member; novel; phenome; primary outcome; proband; programs; relating to nervous system; response; segregation; social; social communication; somatosensory; teacher; trait; transmission process; treatment effect; volunteer

DESCRIPTION (provided by applicant): This is an application for a 5-year competing continuation of an ongoing longitudinal (R01) study of autistic social impairment in sibling pairs. Given recent findings regarding the genetic and neurobiologic architecture of autism, it has become clear that a more precise characterization of heritable quantitative components of the autism phenome might accelerate the discovery of specific genetic and neurobiologic causes of autism. This study will involve quantitative phenotyping of 5576 subjects (from 1295 clinically ascertained families of children with and without autism spectrum disorders (ASD). It will include: assessment of parents and affected individuals in extended pedigrees; examination of whether patterns of distribution of quantitative autistic traits in families vary as a function of gender, ethnicity, simplex versus multiplex versus "complex" autism, or other phenotypic covariates; longer-term follow-up of existing longitudinal study subjects to better elucidate the developmental course of autistic social impairment over time; and examination among sib-pairs of novel quantitative endophenotypes (motor, somatosensory, and electrophysiologic) that may relate both to severity of autistic social impairment and to core genetic and neurobiologic determinants of autism. In this application, we have attempted to be responsive to the problem that previous family-genetic studies of autism have often under-represented minority and disadvantaged populations, for whom specific liabilities to autism (if present) would be overlooked in existing studies and data sets. In addition to enhanced phenotypic characterization of this large clinically-ascertained sibling sample, 475 of the families will be genotyped (parents and sibling sets) by either of two ongoing national linkage studies of autism (the Autism Genetic Resource Exchange and the Simons Simplex Collection). In addition to implications for the genetics and neurobiology of autism, the findings from the study will enhance methods for measuring subtle effects of treatment, will identify intervals in the lifespan when interventions might have particular influence on social development, and will elucidate the manner in which functional disability incurred by a wide range of non-ASD child psychiatric conditions, including ADHD can be exacerbated when superimposed (as is common) by the co-occurrence of sub clinical autistic traits. PUBLIC HEALTH RELEVANCE: Autism and related disorders affect 1 out of every 150 children in the US and result in profound social impairment throughout life. This study examines how autistic social impairments change over the course of childhood, how they are transmitted across generations, and which normal developmental processes they disrupt. The results of the study will aid in the search for the genes and neural abnormalities that cause autism, will enhance methods for measuring subtle but important effects of intervention, and will identify intervals in the lifespan when interventions might have their greatest impact on social development in affected children.

描述（由申请人提供）：这是一项为期 5 年的竞争性延续申请，旨在对兄弟姐妹中的自闭症社交障碍进行一项正在进行的纵向 (R01) 研究。鉴于最近关于自闭症遗传和神经生物学结构的发现，很明显，对自闭症现象的遗传定量成分进行更精确的表征可能会加速自闭症特定遗传和神经生物学原因的发现。这项研究将涉及 5576 名受试者（来自 1295 个临床确定的患有和不患有自闭症谱系障碍 (ASD) 的儿童家庭）的定量表型分析。它将包括：对大谱系中的父母和受影响个体进行评估；检查家庭中数量自闭症特征的分布模式是否随性别、种族、单一自闭症与多重自闭症与“复杂”自闭症或其他因素而变化。 表型协变量；对现有纵向研究对象进行长期随访，以更好地阐明自闭症社交障碍随时间的发展过程；和检查之间 新型定量内表型（运动、体感和电生理）的同胞对可能与自闭症社交障碍的严重程度以及自闭症的核心遗传和神经生物学决定因素有关。在本申请中，我们试图解决这样的问题：以前的自闭症家族遗传学研究往往代表性不足的少数群体和弱势群体，对他们来说，现有的研究和数据集中会忽视自闭症的特定责任（如果存在）。除了增强这一临床确定的大型兄弟姐妹样本的表型特征外，还将通过两项正在进行的自闭症国家连锁研究（自闭症遗传资源交换和西蒙斯单纯收集）中的任何一个对 475 个家庭进行基因分型（父母和兄弟姐妹组）。除了对自闭症遗传学和神经生物学的影响外，该研究的结果还将增强测量治疗微妙效果的方法，将确定干预措施可能对社会发展产生特殊影响的生命周期间隔，并将阐明包括多动症在内的各种非自闭症儿童精神疾病（包括多动症）引起的功能障碍在叠加（这是常见的） 亚临床自闭症特征的同时出现。公共卫生相关性：美国每 150 名儿童中就有 1 人患有自闭症和相关疾病，并导致终生严重的社交障碍。这项研究探讨了自闭症社交障碍在整个过程中如何变化。 童年时期，它们如何代代相传，以及它们破坏了哪些正常的发育过程。该研究的结果将有助于寻找导致自闭症的基因和神经异常，将增强测量干预的微妙但重要影响的方法，并将确定干预可能对受影响儿童的社会发展产生最大影响的生命周期间隔。

项目成果

On the Continuity Between Autistic and Schizoid Personality Disorder Trait Burden: A Prospective Study in Adolescence.

关于自闭症和分裂样人格障碍特质负担之间的连续性：青春期的前瞻性研究。

• DOI: 10.1097/nmd.0000000000001105
• 发表时间: 2020
• 期刊: The Journal of nervous and mental disease
• 作者: Cook,MichalLauren;Zhang,Yi;Constantino,JohnN
• 通讯作者: Constantino,JohnN

Sibling recurrence and the genetic epidemiology of autism.

• DOI: 10.1176/appi.ajp.2010.09101470
• 发表时间: 2010-11
• 期刊: The American journal of psychiatry
• 作者: Constantino JN;Zhang Y;Frazier T;Abbacchi AM;Law P
• 通讯作者: Law P

Evidence for shared genetic influences on self-reported ADHD and autistic symptoms in young adult Australian twins.

• DOI: 10.1375/twin.11.6.579
• 发表时间: 2008-12
• 期刊: Twin research and human genetics : the official journal of the International Society for Twin Studies
• 作者: Reiersen AM;Constantino JN;Grimmer M;Martin NG;Todd RD
• 通讯作者: Todd RD

Multi-informant ratings of psychiatric symptom severity in children with autism spectrum disorders: the importance of environmental context.

• DOI: 10.1007/s10803-009-0694-7
• 发表时间: 2009-06
• 期刊: JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
• 影响因子: 3.9
• 作者: Kanne, Stephen M.;Abbacchi, Anna M.;Constantino, John N.
• 通讯作者: Constantino, John N.

Developmental course of autistic social impairment in males.

• DOI: 10.1017/s095457940900008x
• 发表时间: 2009
• 期刊: DEVELOPMENT AND PSYCHOPATHOLOGY
• 影响因子: 3.3
• 作者: Constantino, John N.;Abbacchi, Anna M.;Lavesser, Patricia D.;Reed, Hannah;Givens, Leah;Chiang, Lily;Gray, Teddi;Gross, Maggie;Zhang, Yi;Todd, Richard D.
• 通讯作者: Todd, Richard D.