Targeted Pharmacologic Interventions for Autism

描述(由申请人提供)：项目摘要：自闭症(自闭症)和其他普及性发育障碍是神经精神发育障碍，越来越多地被诊断出来。尽管它们的频率和相关的损害可能是严重的和终身的，但到目前为止，受控药物研究有限。我们研究的长期目标是推进自闭症和相关疾病药物治疗背后的科学。这一点尤其重要，因为很少有治疗方法被证明对这种毁灭性的疾病有效。此外，对药物的反应往往非常不同，对指导治疗的反应的预测因素尚未确定。一个重大的治疗挑战是当患有自闭症时如何管理严重的多动症。在这个项目中，我们将评估托莫西汀治疗显著多动的疗效和耐受性，并确定反应的药物遗传学预测因素。我们将通过完成四个具体目标来实现这一目标：1.患有自闭症的儿童和青少年(n=86)将被随机接受为期8周的托莫西汀或安慰剂治疗，以在为期8周的双盲研究过程中确定其短期疗效。2.对托莫西汀有反应的人将再接受10个月的治疗，以确定是否保持反应。3.将在短期和长期研究中监测一些重要的不良事件(例如，应激性)和健康参数。4.分析细胞色素P450 2D6基因的遗传多态性，以确定它们与对托莫西汀的反应和耐受性的关系。当这项研究完成后，它将第一次分析托莫西汀对儿童和青少年自闭症的疗效以及药物遗传学数据。相关性：在这个项目中，我们将检验托莫西汀对与自闭症相关的多动症的疗效。这项研究解决了当今心理健康领域最大的公共卫生需求之一，即找到更安全、更有效的自闭症医疗方法。这项研究在确定自闭症药物治疗反应的遗传预测因素方面也是独一无二的。

DESCRIPTION (provided by applicant): Project Summary: Autistic disorder (autism) and other pervasive developmental disorders are neuropsychiatric developmental disorders which are increasingly being diagnosed. Despite their frequency and associated impairments which can be severe and lifelong, there have been limited controlled drug studies to date. The long-term goal of our research is to advance the science behind the pharmacologic treatment of autism and related disorders. This is especially important since there are very few treatments that have been shown to be effective for this devastating disorder. Furthermore, the response to medications is frequently quite variable and predictors of response to guide treatment have not been identified. A significant treatment challenge has been the management of severe hyperactivity when comorbid with autism. In this project, we will evaluate the efficacy and tolerability of atomoxetine for significant hyperactivity and determine pharmacogenetic predictors of response. We will accomplish this goal by completing four specific aims: 1. Children and young adolescents with autism (n=86) will be randomized to atomoxetine or placebo for 8 weeks to determine its short-term efficacy over the course of an 8-week double-blind study. 2. Responders to atomoxetine will be followed for an additional 10 months of treatment to determine whether response is maintained. 3. A number of important adverse events (e.g., irritability) and health parameters will be monitored over the short- and longer-term studies. 4. Genetic polymorphisms of the cytochrome P450 2D6 gene will be analyzed to determine their relationship to response and tolerability to atomoxetine. When this study is complete, it will be the first to analyze both the efficacy of atomoxetine along with pharmacogenetic data in children and adolescents with autism. Relevance: In this project, we will examine the efficacy of atomoxetine for hyperactivity associated with autism. This research addresses one of the greatest public health needs in mental health today which is finding safer and more effective medical treatments for autism. This research is also unique in its plan to identify genetic predictors of response to drug treatment in autism.