TREATMENT OF AFFECTIVE DISTURBANCE IN CHILDREN WITH AUTISM

5-羟色胺能异常长期以来一直与自闭症有关，人们对5-羟色胺能机制在情感障碍表现中的兴趣也是如此。尽管它们被广泛使用，但没有任何针对自闭症儿童的5-羟色胺再摄取抑制剂(SRI)的对照临床试验来支持这一做法。西酞普兰是在美国上市的最新SRIs，与同类药物相比具有一些潜在的药代动力学优势。我们建议通过实验研究自闭症儿童情感障碍的治疗，以解决三个具体目标：目的：1.确定5-羟色胺再摄取抑制剂西酞普兰是否有效治疗自闭症儿童的行为障碍。目的：确定生理或遗传标记、家庭功能测量或特殊的治疗前症状是否可以预测对西酞普兰治疗的敏感性和反应。瞄准伊利诺伊州通过确定影响父母和临床医生对变化的评级的因素，更好地了解自闭症儿童临床试验中的反应，并开发新的策略，通过这些策略来捕捉对治疗干预的反应。除了临床试验，这个项目还将研究如何最好地捕捉有意义的治疗反应 患有自闭症的儿童。最近在这一人群中进行临床试验的经验表明，目前的评估策略可以改进。目前的措施可能容易受到非特定影响，表现为安慰剂效应。同样，重要的临床改善可能没有被捕捉到，或者被当前使用的评估工具冲淡。这项建议整合了该中心其他项目的数据，并将为该中心的作用奠定基础，不仅通过重要研究增进对自闭症的认识，而且通过教育和治疗成为儿童和家庭的持续资源。通过正式研究目前的治疗方法，开发新的评估战略，改善评估和治疗自闭症儿童的区域可及性，该中心将能够与网络中的其他中心有效合作，并将成为了解新英格兰的关键资源。

Serotonergic abnormalities have long been associated with autism, as has interest in serotonergic mechanisms in the manifestation of affective disturbance. In spite of their widespread use, there are no controlled clinical trials of any serotonin reuptake inhibitors (SRIs) in children with autism to support this practice. Citalopram is the newest of the SRIs to become available in the U.S., and offers some potential pharmacokinetic advantages over the other drugs in its class. We propose to study the treatment of affective disturbance in children with autism through experiments addressing three specific aims: Aim I. To determine if the serotonin reuptake inhibitor, citalopram, is effective in the treatment of behavioral disturbance in children with autism. Aim II.To determine if physiological or genetic markers, measures of family function, or particular pretreatment symptoms are predictive of sensitivity and response to treatment with citalopram. Aim Ill. To better understand the response in clinical trials of children with autism by identifying factors influencing parent and clinician ratings of change and to develop new strategies by which to capture the response to therapeutic interventions. Beyond a clinical trial, then, this project will study how best to capture meaningful treatment response in children with autism. Recent experience with clinical trials in this population suggests that current assessment strategies can be improved. Current measures may be susceptible to nonspecific influences that show up as placebo effects. Likewise, important clinical improvement may go uncaptured or be diluted with assessment instruments currently employed. This proposal integrates data from the other projects in the Center, and will set the stage for the Center's role not only to advance knowledge of autism through important research, but to be an ongoing resource to children and families through education and treatment. By formally studying current treatment and by developing new assessment strategies and improving regional accessibility for evaluation and treatment of children with autism, the Center will be positioned to efficiently collaborate with other Centers in the network, and will be a pivotal resource to UDDer New Enaland.