HALOPERIDOL AND ATTENTIONAL LEARNING IN AUTISTIC CHILDRE

本申请的目的有两个：（1）批判性地评估 纳洛酮治疗自闭症的有效性和安全性： 它对行为症状和学习的影响。 40个孩子， 2至7岁，DSM-III-R诊断为自闭症， 婴儿期发作将以平行组设计、双- 持续6周的纳洛酮盲法安慰剂对照研究。 在2周安慰剂基线后，儿童将随机 被分配到纳洛酮或安慰剂组3周， 最后一周服用安慰剂 剂量范围为0.5至1.0 mg/kg/天;纳洛酮的稳态血浆浓度将 与临床应答相关，受试者将通过多项 各种主观和客观量表的评分员， 参与操作性条件反射，学习辨别 在自动化实验室中的任务。 这项研究对于评估 每天服用纳洛酮的效果， 在自闭症儿童的开放式急性药物试验中有效。 氟哌啶醇的替代治疗， 需要药物治疗的自闭症儿童的药物治疗， 是因为高发病率的抗精神病药物相关的 运动障碍 (2)我们也希望继续我们的长期 氟哌啶醇治疗孤独症儿童的前瞻性研究 对行为症状，智力功能，生长， 刻板印象和与毒品有关的运动障碍 30个新的孩子 并添加到样本中。 设计需要一个初始的 基线评估，随后使用氟哌啶醇6个月，然后 安慰剂治疗1个月。 需要进一步治疗的儿童 然后药物治疗开始另一个7个月的周期。 自闭症儿童 属于基线发生率较高的患者人群， 与精神抑制剂无关的异常运动（刻板） 局 特别是在口腔和舌头的区域， 很难有时甚至不可能区分 无基线的抗精神病药（戒断）运动障碍 考核 一个研究问题，这也是一个伟大的临床 重要的是要区分这两种类型的 动作 在我们的前瞻性研究中，每个受试者都有稳定的 由多名评定者对刻板印象进行基线评估，3次评定 在固定的时间内重复测量和录像。 我们的研究是 在评估长期治疗的效果方面是独一无二的。 氟哌啶醇，并阐明发生，地形，和因素 影响神经安定剂相关运动障碍的发作， 公共卫生问题。 我们现在有足够多的样本 仔细研究儿童，以便对儿童的 随着时间的推移收集了许多措施。

The aims of this application are two-fold: (1) To critically assess the efficacy and safety of naltrexone in the treatment of autism: its effects on behavioral symptoms and on learning. 40 children, ages 2 to 7 years, with DSM-III-R diagnoses of Autistic Disorder, Infantile Onset will be entered in a parallel groups design, double- blind placebo-controlled study of naltrexone lasting 6 weeks. Following a 2-week placebo baseline children will be randomly assigned to either naltrexone or placebo for 3 weeks followed by a final week on placebo. Dosage will range from 0.5 to 1.0 mg/kg/day; steady state plasma concentration of naltrexone will be related to clinical response, subjects will be rated by multiple raters on a variety of subjective and objective scales and will participate in an operant conditioning, learning discrimination task in an automated laboratory. This study is necessary to assess the effects of daily administration of naltrexone, a drug which has been effective in open, acute drug trails with autistic children. Alternative treatments to haloperidol, the most commonly used medication with autistic children who require pharmacotherapy, are sought because of the high incidence of neuroleptic-related dyskinesias. (2) We also wish to continue our long-term prospective study of haloperidol in autistic children: to assess its effects on behavioral symptoms, intellectual functioning, growth, stereotypes and drug-related dyskinesias. 30 new children will be enrolled and added to the sample. The design calls for an initial baseline assessment followed by 6 months on haloperidol and then 1 month on placebo. Children requiring further treatment with medication then begin another 7-month cycle. Autistic children belong to a population of patients who have high baseline rate of abnormal movements (stereotypies) unrelated to neuroleptic administration. Particularly in the area of mouth and tongue, it is difficult and at times impossible to differentiate stereotypies from neuroleptic (withdrawal) dyskinesias without a baseline assessment. A research question which is also of great clinical importance is to differentiate between these two types of movements. In our prospective study, each subject has a stable baseline assessment of stereotypies by multiple raters, on 3 rating scales and videotaping repeated at fixed times. Our study is unique in assessing the effects of long-term treatment of haloperidol and to clarify the occurrence, topography, and factors affecting the onset of neuroleptic-related dyskinesias, a major public health concern. We now have a large enough sample of carefully studied children to permit statistical analyses of the many measures collected over time.