A Longitudinal Brain and Behavior Study of Autism From Infancy Through Adolescence

从婴儿期到青春期自闭症的纵向大脑和行为研究

• 批准号: 10698069
• 负责人: Joseph Piven
• 金额: $ 230.48万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698069
• 关键词: 11 year old; 16 year old; Acceleration; Address; Adolescence; Adolescent; Adult; Age; Age Months; Amygdaloid structure; Anxiety; Anxiety Disorders; Area; Behavior; Behavior Disorders; Behavior assessment; Behavioral; Biological; Biology; Brain; Brain imaging; Categories; Characteristics; Child; Childhood; Clinical; Complex; Data; Data Reporting; Detection; Development; Diagnosis; Diagnostic; Dimensions; Early Diagnosis; Early Intervention; Early identification; Familial disease; Family Study; Female; Female Adolescents; Functional disorder; Funding; General Population; Genetic; Goals; Growth; Impairment; Individual; Infant; Intervention; Investments; Knowledge; Life; Link; Maps; Mental disorders; Nature; Outcome; Pattern; Phenotype; Predictive Value; Prospective cohort; Reporting; Research Design; Resources; Risk; Risk Marker; Sampling; School-Age Population; Siblings; Social Development; Specific qualifier value; Subgroup; Symptoms; Time; United States National Institutes of Health; Work; absorption; adolescent brain development; aging brain; autism spectrum disorder; behavior prediction; behavioral study; brain behavior; clinical predictors; clinically actionable; clinically relevant; clinically significant; design; disorder risk; early childhood; emerging adult; family genetics; follow-up; imaging study; improved; inclusion criteria; individuals with autism spectrum disorder; infancy; insight; interest; longitudinal, prospective study; male; novel strategies; outcome prediction; proband; prospective; psychiatric symptom; psychologic; skills; success; symptom cluster

Project Summary This application is a competing continuation of an Autism Centers of Excellence (ACE) Network entitled, “A Longitudinal Brain and Behavior Study of Autism from Infancy through Adolescence”. Prior funding supported a prospective, longitudinal study that has collected high quality brain imaging and behavior assessments in children at high- and low- familial risk (HR, LR) for autism spectrum disorder (ASD), starting in infancy, and at various points at 3-6-9-12-15-24-36 months to 7-11 years of age. Key findings from this network have revealed that: (1) early brain features of ASD are detectable by 6 months of age, well before diagnosis is possible; (2) ASD-specific brain and behavior features change substantially throughout early childhood, as ASD emerges; and (3) brain features in the first year of life are associated with later ASD behaviors and accurately predict ASD diagnosis in individuals at 24 months of age. The overarching goal of this ACE Network proposal is to extend into adolescence the follow-up of a prospective cohort of 400 subjects (300 HR; 100 LR) with detailed brain and behavior assessment between 13-16 years of age. Adolescence is a time of substantial challenges to autistic individuals. It is the time of peak onset of psychiatric disorders, rates of which are considerably higher in ASD than in the general population, with particular vulnerabilities in ASD females. Adolescence sets the stage for transition to early adulthood, a time when decline in daily living skills and worsening outcomes in ASD are commonly reported. In this application we therefore propose to: (Aim 1) characterize brain and brain-behavior trajectories in those with ASD, from infancy through adolescence, to gain insights into developmental mechanisms that inform the timing and targets of intervention; (Aim 2) identify infant-to-school-age brain and behavior features in those at elevated ASD familial risk, that predict clinically-relevant outcomes in adolescence and, (3) define the expression of familial ASD risk in adolescent females, identify early childhood markers of adolescent clinical impairment and, characterize patterns of infant-to-adolescent brain development, in adolescent females at high familial risk for ASD. This study would be the first prospective examination of brain and behavior features associated with ASD risk, in the same individuals, from infancy through adolescence. It has the potential to: (1) inform about the nature and timing of underlying mechanisms and targets of intervention; (2) elucidate childhood brain and behavior features that predict individual-level, adolescent dysfunction, related to familial ASD risk; and (3) to provide new insights regarding the expression of ASD risk in adolescent females, their identification earlier in childhood and associated patterns of brain development. This proposal addresses “areas of interest” specified in the ACE RFA, including: (1) a focus on under-studied subgroups e.g., individuals with ASD and co-occurring psychiatric conditions (Aim 1 and 2) and females with ASD (Aim 3); and (2) biological mechanisms related to family-genetic and environmental interactions (Aim 1 and 2).

项目摘要 该应用程序是自闭症卓越中心（ACE）网络的竞争延续，标题为“ 从婴儿期到青少年的自闭症的纵向大脑和行为研究”。先前的资金支持 预期的纵向研究已收集了高质量的大脑成像和行为评估 自闭症谱系障碍（ASD）的高家庭风险（HR，LR）的儿童，从婴儿期开始，在 以3-6-9-12-15-24-36月至7-11岁的年龄为3-6-9-9-12-15-24-36。该网络的主要发现揭示了 那是：（1）在可能的诊断之前，可以在6个月大时检测到ASD的早期大脑特征； （2） 正如ASD出现的那样，在整个幼儿期间，ASD特异性的大脑和行为特征在整个幼儿时期都有很大变化。 （3）生命第一年的大脑特征与以后的ASD行为有关，并准确预测ASD 24个月大的个体诊断。该ACE网络建议的总体目标是扩展 进入青少年，以详细的大脑和 13-16岁之间的行为评估。青少年是加速挑战的一个重大挑战时期 个人。这是精神疾病峰值发作的时代，ASD中的速度较高 比普通人群，在ASD女性中具有特殊的脆弱性。青少年为 过渡到成年早期，这是在日常生活技能下降和ASD令人担忧的结果的时期 通常报告。因此，在此应用中，我们建议：（ AIM 1）表征大脑和脑行为 从婴儿期到青少年，都有洞察力的轨迹，以洞悉发展 为干预的时机和目标提供的机制； （目标2）识别婴儿到学龄的大脑和 ASD家族风险升高的人的行为特征，预测青少年临床上与临床相关的结果 （3）定义青少年女性中ASD风险的表达，确定儿童早期标志 青少年临床障碍，表征婴儿到青春期大脑发育的模式， ASD家族风险高的青少年女性。这项研究将是对大脑的第一次前瞻性检查 从婴儿期到青少年，在同一个人中与ASD风险相关的行为特征。它 有潜力：（1）告知基本机制和干预目标的性质和时机； （2）阐明童年的大脑和行为特征，这些特征可以预测个人级别的青少年功能障碍，相关 农场ASD风险； （3）提供有关青少年女性ASD风险表达的新见解， 他们在童年和大脑发育的相关模式的早期认同。该提案解决了 ACE RFA中指定的“感兴趣领域”，包括：（1）专注于研究不足的子组，例如个人 与ASD和共同发生的精神病（AIM 1和2）以及ASD的女性（AIM 3）； （2）生物学 与家庭遗传和环境相互作用有关的机制（AIM 1和2）。