Behavior Therapy for Children with Chronic Tic Disorders

慢性抽动障碍（CTD），包括抽动秽语综合征（TS），是一种神经行为障碍，其特征是持续的运动和发声抽动模式。抽搐可以是短暂的，快速的，快速的动作，也可以是更复杂和有目的的动作。发声抽搐可以是简单的（例如，吸气，咕哝）或更复杂的声音（例如，单词和短语）。抽搐随着时间的推移而增加和减少，在青少年早期达到高峰。儿童抽动障碍可能与相当大的痛苦，歧视，社会和学术障碍，与损害， 在某些情况下观察到的成年期。CTD的确切原因尚不清楚，病因学涉及遗传和环境因素。大量证据表明，涉及丘脑、基底神经节和额叶皮质的皮质-皮质下通路功能障碍。行为/环境因素可能在抽动维持和泛化中发挥作用。抽搐抑制的标准治疗是药物治疗，特别是中枢作用的多巴胺阻断药物。然而，这些药物与一系列不良反应有关，可能导致依从性差和过早终止治疗。本申请中列出的研究人员的初步工作表明，习惯逆转训练（HRT）是一种有希望的抽搐干预措施。HRT是一种基于意识训练和竞争反应的多成分行为治疗。它可以与药物联合应用和/或作为单一疗法。虽然最初的HRT结果令人鼓舞，但迄今为止的研究都是病例研究或小型随机试验。需要大规模试验来证明HRT的疗效。 根据PA 00-094（儿童精神障碍的早期识别和治疗， 青少年），本申请描述了一项多地点调查，以评估手动HRT程序减少CTD青少年抽动的疗效。为了进行这项研究，图雷特综合征协会（TSA）组建了一个行为科学联盟（BSC），这是一个多学科的研究小组，代表了美国一些领先的TS研究项目，包括耶鲁大学、马萨诸塞州总医院（MGH）/哈佛大学、加州大学洛杉矶分校和约翰霍普金斯大学。另外两个中心，威尔福德霍尔医疗中心（WHMC）和威斯康星大学密尔沃基分校（UWM），有在HRT的具体专业知识的调查。BSC的使命是为CTD患者开发、测试和传播行为干预。在这项研究中，120名患有CTD的青少年将被随机分配到8个疗程（10周）的HRT或比较心理社会治疗，然后是3个月的强化疗程。主要结局将是由盲法临床评估者评估的抽搐严重程度的变化。还将探讨对整体功能、生活质量和治疗结果的可能预测因素的影响。TSA、JHU、UCLA和UWM将作为招募地点，而MGH、WHMC和耶鲁大学的研究人员将提供特定的质量 通过单独的分包合同提供保证和评估服务，并将组建DSMB以进行数据和安全性监测。耶鲁信息组将提供数据管理服务。

Chronic tic disorders (CTD), including Tourette Syndrome (TS), are neurobehavioral disorders characterized by a persistent pattern of motor and vocal tics. Tics can be brief, rapid and darting movements or more complex and purposeful in appearance. Vocal tics can be simple (e.g., sniffing, grunting) or more complex sounds (e.g., words and phrases). Tics wax and wane over time with peak severity in early teens. Childhood tic disorders can be associated with considerable distress, discrimination, and social and academic impairment, with impairment into adulthood observed in some cases. The exact causes of CTD are unknown with both genetic and environmental factors implicated in etiology. Substantial evidence implicates dysfunction of cortical-subcortical pathways involving the thalamus, basal ganglia and the frontal cortex. Behavioral/environmental factors may play a role in tic maintenance and generalization. The standard treatment for tic suppression is medication, particularly centrally acting dopamine blocking drugs. However, these medications are associated with a range of adverse effects that can result in poor compliance and premature treatment termination. Preliminary work by investigators listed on this application suggests that habit reversal training (HRT) is a promising intervention for tics. HRT is a multicomponent behavioral treatment based on awareness training and competing response. It can be applied in combination with medication and/or as a monotherapy. While initial HRT results are encouraging, studies to date have all been case studies or small randomized trials. Large trials are needed to demonstrate HRT efficacy. In response to PA 00-094 (Early Identification and Treatment of Mental Disorders in Children and Adolescents), this application describes a multisite investigation to evaluate the efficacy of a manualized HRT program for tic reduction in youngsters with CTD. To conduct this study, the Tourette Syndrome Association (TSA) assembled a Behavioral Sciences Consortium (BSC), a multidisciplinary group of investigators representing some of the leading TS research programs in the country including Yale, Massachusetts General Hospital (MGH)/Harvard, UCLA, and Johns Hopkins. Two additional centers, Wilford Hall Medical Center (WHMC) and the University of Wisconsin-Milwaukee (UWM), have investigators with specific expertise in HRT. The mission of the BSC is to develop, test, and disseminate behavioral interventions for patients with CTD. In this study, 120 youngsters with CTD will be randomly assigned to 8 sessions (10 weeks) of HRT or comparison psychosocial treatment followed by 3 monthly booster sessions for responders. The primary outcome will be change in tic severity assessed by blind clinician raters. The effects on overall functioning, quality of life, and possible predictors of treatment outcome will also be explored. Working under subcontract to TSA, JHU, UCLA, and UWM will serve as recruitment sites while investigators from MGH, WHMC, and Yale will provide specific quality assurance and assessment services via separate subcontracts, and a DSMB will be assembled for data and safety monitoring purposes. The Yale Infomatics group will provide data management services.