TREATMENT OF AFFECTIVE DISTURBANCE IN CHILDREN WITH AUTISM

长期以来，5 -羟色胺能异常与自闭症有关，对5 -羟色胺能在情感障碍表现中的机制也很感兴趣。尽管5 -羟色胺再摄取抑制剂（SRIs）被广泛使用，但在自闭症儿童中没有任何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SRIs，与同类其他药物相比，它具有一些潜在的药代动力学优势。我们提出通过实验来研究自闭症儿童情感障碍的治疗，主要有三个目的：目的1 .确定血清素再摄取抑制剂西酞普兰对自闭症儿童行为障碍的治疗是否有效。目的二世。确定生理或遗传标记、家庭功能测量或特定的预处理症状是否可预测对西酞普兰治疗的敏感性和反应。目的生病。通过确定影响父母和临床医生对变化评分的因素，更好地了解自闭症儿童在临床试验中的反应，并制定新的策略来捕捉对治疗干预的反应。在临床试验之外，该项目将研究如何最好地捕获有意义的治疗反应

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.