Biomarkers of Autism at 12 months: From Brain Overgrowth to Genes

12 个月时自闭症的生物标志物：从大脑过度生长到基因

• 批准号: 8668524
• 负责人: ERIC COURCHESNE
• 金额: $ 46.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8668524
• 关键词: 2 year old; 3 year old; Address; Age; Autistic Disorder; Awareness; Behavioral; Behavioral Symptoms; Biological; Biological Markers; Brain; Child; Data; Defect; Development; Developmental Delay Disorders; Diagnosis; Early identification; Functional Magnetic Resonance Imaging; Genes; Genetic; Grant; Individual; Infant; Laboratories; Methods; Neurophysiology - biologic function; Paper; Pathway interactions; Physicians; Publishing; Research; Risk; Siblings; Sorting - Cell Movement; Time; Toddler; Variant; brain behavior; clinically relevant; cost; cost effective; developmental disease; effective therapy; flexibility; novel; novel diagnostics; outcome forecast; prospective; tool

Autism is a developmental disorder, but the least is known about what is most important: Development. What are the early brain abnormalities? What neural functions do they disrupt? What the first behavioral indicators of risk for autism? What is the prognosis for the toddler or child at first diagnosis? Which are likely to respond to known effective treatment and which not? Are their brain or other biological markers that could predict non-responders so that treatment research could be targeted towards discovery of treatments that could help them? What genes and gene pathways are responsible for early brain defects? The answer to each question comes to the same point: Early identification methods. These sorts of crucial questions cannot be addressed unless there is a way to identify infants at risk for autism. The most popular method is the infant sibling method. Now many groups are trying this method. The first two laboratories to use this method began their research five and seven years ago, and have published two original papers, one on 7 autism spectrum (ASD) infants and one on 27 ASD infants. They found no differences from typical development at 6 months, but did by 12 months. They provided no brain, neurofunctional, genetic or other biological data on the ASD infants. The infant sibling method has major cost, practicality and methodological limitations, which are detailed in our grant. Although popular and in progress for a long time, to date, studies using this method have provided no answer any of the major questions posed above. A simpler, quicker, more flexible, cost-effective and more clinically relevant and practical method is to study individuals referred by physicians because they display behavioral symptoms indicating risk for an ASD. In the 1990s, this method resulted in identification of mostly at-risk 3 year olds and up. By the early 2000s, the at-risk age for referral was age 2 years because of heightened awareness by physicians and new diagnostic tools. In each "era", others and we were able to vigorously investigate brain and behavior abnormalities and new treatment approaches at young ages in ASD. It was via this simple referral method that major discoveries about early brain overgrowth in ASD occurred in our laboratory. It was via this method that we have been able to perform the first fMRI activation studies on ASD at age 2-years. Now, via a novel variant of this proven effective prospective method (see Core B), in our ACE Center we will study 12-month old infants at-risk for ASD, infants at-risk for developmental delay and typical infants using advanced biological and behavioral methods. Each infant will be studied at intervals longitudinally and a final best estimate diagnosis made at 36 months providing a final step for group assignment for statistical

自闭症是一种发育障碍，但最重要的是最重要的：发展。早期的大脑异常是什么？它们会破坏什么神经功能？自闭症风险的第一个行为指标是什么？初次诊断时幼儿或孩子的预后是什么？哪些可能会响应已知的有效治疗，哪些不反应？他们的大脑或其他可以预测非反应者的生物标记物，以便可以针对发现可以帮助他们的治疗方法吗？哪些基因和基因途径导致早期大脑缺陷？ 每个问题的答案都达到了相同的观点：早期识别方法。除非有一种方法可以识别有自闭症风险的婴儿，否则这些关键问题无法解决。最流行的方法是婴儿兄弟姐妹方法。现在，许多小组正在尝试这种方法。使用该方法的前两个实验室五年前开始了他们的研究，并发表了两篇原始论文，一篇是7种自闭症谱系（ASD）婴儿，一个是27名ASD婴儿。他们发现6个月时与典型发展没有差异，但到12个月之前。他们没有提供有关ASD婴儿的大脑，神经功能，遗传或其他生物学数据。 婴儿同胞方法具有重大成本，实用性和方法论局限性，这在我们的赠款中详细介绍了。尽管很流行并在很长一段时间内正在进行中，但迄今为止，使用这种方法的研究尚未提供上述任何主要问题。 一种更简单，更快，更灵活，更具成本效益且在临床上相关和实用的方法是研究由医生转介的个体，因为它们表现出表明ASD风险的行为症状。在1990年代，这种方法导致了大多数3岁及以上的高风险。到2000年代初，由于医生和新的诊断工具的意识提高，转诊的高风险年龄为2岁。在每个“时代”中，其他人和我们能够在ASD年轻时大力研究大脑和行为异常和新的治疗方法。正是通过这种简单的推荐方法，关于ASD早期大脑过度生长的主要发现发生在我们的实验室中。正是通过这种方法，我们已经能够对2岁的ASD进行首次fMRI激活研究。 现在，通过这种有效的前瞻性方法的新型变体（请参阅Core B），在我们的ACE中心，我们将研究12个月大的ASD危险，适用于ASD的婴儿，婴儿在危险中，用于发育延迟，使用先进的生物学和行为方法。每个婴儿将纵向研究，并在36个月时进行最终的最佳估计诊断，为小组分配提供统计的最后一步

项目成果

Cognitive consilience: primate non-primary neuroanatomical circuits underlying cognition.

• DOI: 10.3389/fnana.2011.00065
• 发表时间: 2011
• 期刊: Frontiers in neuroanatomy
• 影响因子: 2.9
• 作者: Solari SV;Stoner R
• 通讯作者: Stoner R

The power and promise of identifying autism early: insights from the search for clinical and biological markers.

• 发表时间: 2009-07
• 期刊: Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists
• 作者: K. Pierce;S. Glatt;G. Liptak;L. L. McIntyre-L.

Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism.

• DOI: 10.1523/jneurosci.5714-09.2010
• 发表时间: 2010-03-24
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Schumann CM;Bloss CS;Barnes CC;Wideman GM;Carper RA;Akshoomoff N;Pierce K;Hagler D;Schork N;Lord C;Courchesne E
• 通讯作者: Courchesne E

Preference for geometric patterns early in life as a risk factor for autism.

• DOI: 10.1001/archgenpsychiatry.2010.113
• 发表时间: 2011-01
• 期刊: Archives of general psychiatry
• 作者: Pierce K;Conant D;Hazin R;Stoner R;Desmond J
• 通讯作者: Desmond J

Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism.

• DOI: 10.1038/s41380-021-01239-2
• 发表时间: 2021-12
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Lombardo MV;Busuoli EM;Schreibman L;Stahmer AC;Pramparo T;Landi I;Mandelli V;Bertelsen N;Barnes CC;Gazestani V;Lopez L;Bacon EC;Courchesne E;Pierce K
• 通讯作者: Pierce K