Genotype and Phenotype of Response to Treatments of Autism

自闭症治疗反应的基因型和表型

• 批准号: 6802963
• 负责人: PATRICIA M RODIER
• 金额: $ 7.88万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-13 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802963
• 关键词: Genotype; Phenotype; Response; Treatments; Autism

DESCRIPTION (provided by applicant): Early intensive behavioral intervention is the only treatment for autism spectrum disorders for which a substantial number of studies have demonstrated efficacy. However, not all children respond to this treatment, and recent evidence suggests that success and failure are determined more by variations among patients than by variations among intensive intervention programs. To choose the best treatment for each child, it is important to determine which characteristics of children with ASDs predict their response to behavioral intervention. Further, since it is likely that responders and non-responders differ in etiology, successful categorization on this dimension could provide a way of stratifying children with ASDs into genetically meaningful subsets. Thus, successful prediction would serve both an important public health goal and an important basic science goal. Because many children in early intervention programs in our region receive very similar programs of ABA therapy at public expense, we have a population in which this question can be addressed at a reasonable cost. Over the first year of intervention, response to treatment will be measured by change in four domains: behaviors related to autism, language, cognition, and adaptive behavior. Measures of four possible predictor variables will be tested for their correlation with change. These are: aloof social style, obsessive self-stimulation of the senses, rudimentary receptive language, and imitation. The hypothesis is that the first two will predict low levels of response, and the last two will predict high levels of response to treatment. Each participant will be genotyped for alleles of six candidate genes (HOXA1, HOXB1, RELN, WNT2, HOXD1, GBX2), to determine whether either scores on the predictor variables or change scores are correlated with suspected genetic susceptibility factors for ASDs.

描述（由申请人提供）：早期强化行为干预是自闭症谱系障碍的唯一治疗方法，大量研究已证明其疗效。然而，并非所有儿童都对这种治疗有反应，最近的证据表明，成功和失败更多地取决于患者之间的差异，而不是强化干预计划之间的差异。为了为每个孩子选择最佳的治疗方法，重要的是要确定自闭症谱系障碍儿童的哪些特征可以预测他们对行为干预的反应。此外，由于有反应者和无反应者的病因可能不同，因此在这个维度上的成功分类可以提供一种将自闭症谱系障碍儿童分层为具有遗传意义的子集的方法。因此，成功的预测将服务于重要的公共卫生目标和重要的基础科学目标。由于我们地区许多参与早期干预计划的儿童都接受了非常相似的 ABA 治疗计划，这些计划是由公共费用承担的，因此我们的人口中这个问题可以以合理的成本得到解决。在干预的第一年，对治疗的反应将通过四个领域的变化来衡量：与自闭症相关的行为、语言、认知和适应性行为。将测试四个可能的预测变量的测量值与变化的相关性。它们是：冷漠的社交风格、强迫性的感官自我刺激、基本的接受性语言和模仿。假设是前两个将预测低水平的反应，后两个将预测对治疗的高水平反应。对每个参与者的六个候选基因（HOXA1、HOXB1、RELN、WNT2、HOXD1、GBX2）的等位基因进行基因分型，以确定预测变量分数或变化分数是否与疑似自闭症谱系障碍遗传易感性因素相关。