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，因为在情感障碍的表现中对5-羟色胺能机制感兴趣。尽管它们被广泛使用，但没有任何5-羟色胺再摄取抑制剂（SRI）在自闭症儿童中的对照临床试验来支持这种做法。西酞普兰是在美国上市的最新的SRI，并提供了一些潜在的药代动力学优势。我们建议通过三个具体目标的实验来研究自闭症儿童情感障碍的治疗：目标I。确定5-羟色胺再摄取抑制剂西酞普兰是否能有效治疗自闭症儿童的行为障碍。 目的II：确定是否生理或遗传标记，家庭功能的措施，或特定的治疗前症状是预测西酞普兰治疗的敏感性和反应。 瞄准三号。通过识别影响父母和临床医生对变化的评价的因素，更好地了解自闭症儿童临床试验中的反应，并制定新的策略来捕获对治疗干预的反应。 除了临床试验之外，该项目还将研究如何最好地捕捉有意义的治疗反应， 自闭症儿童最近在这一人群中进行的临床试验经验表明，目前的评估策略可以改进。目前的措施可能容易受到非特异性影响，表现为安慰剂效应。同样，重要的临床改善可能无法捕获或被目前采用的评估工具稀释。该提案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，不仅通过重要的研究促进自闭症的知识，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，制定新的评估策略，提高自闭症儿童评估和治疗的区域可及性，该中心将与网络中的其他中心进行有效合作，并将成为UDDer New Enaland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.