The New Tics Study: A Novel Approach to Pathophysiology and Cause of Tic Disorders

新抽动研究：抽动障碍病理生理学和病因的新方法

• 批准号: 9503067
• 负责人: KEVIN J BLACK
• 金额: $ 63.61万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-09 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9503067
• 关键词: Advertisements; Age; Anniversary; Appearance; Attention; Attention deficit hyperactivity disorder; Biological Markers; Brain; Brain imaging; Budgets; Child; Childhood; Chronic; Clinical; Clinical Data; Data; Data Set; Development; Diagnosis; Disease; Disease remission; Enrollment; Epidemiology; Etiology; Evaluation; Family history of; Follow-Up Studies; Functional Magnetic Resonance Imaging; Functional disorder; Gilles de la Tourette syndrome; Image; Investigation; Laboratories; Life; Machine Learning; Magnetic Resonance Imaging; Measures; Methods; Motor; Movement; Neuropsychology; Noise; Outcome; Patients; Perfusion; Phase; Physiology; Population; Preparation; Prevention; Process; Prospective Studies; Psychiatric Diagnosis; Public Health; Publishing; Quality Control; Research; Research Design; Rest; Retrospective Studies; Sampling; Severities; Standardization; Structure; Symptoms; Testing; Tic disorder; Time; brain abnormalities; caudate nucleus; comparison group; critical period; dexterity; follow-up; habit learning; high risk; improved; inattention; interest; learning strategy; medical attention; novel; novel strategies; outcome forecast; outcome prediction; phenomenological models; prospective; public health relevance; recruit; research clinical testing; secondary analysis; vector

Project Abstract At least 20% of all children have tics at some time in their life, making tic disorders a subject of substantial public health interest. However, only about 3% of all children have tics that last for a year or more. Thus chronic tic disorders, including Tourette syndrome, can be conceptualized as a two- step process: tics start, and then they fail to remit. By the numbers, the second part of this process is the more unusual and perhaps more closely related to disease, yet surprisingly, almost no research has examined this critical period after a first tic appears but before it is clear whether the child will go on to have a chronic tic disorder. Therefore prior research that has identified abnormalities of brain structure and function in children with TS generally does not clarify whether these abnormalities are related to tic appearance or to the more important process of tic disappearance. Furthermore, tic disappearance can be observed prospectively, allowing powerful within-subject analyses to test whether features of brain structure or function shortly after tic onset predict remission of tics before TS is diagnosable, and whether such features are state-related or more durable markers of vulnerability to tics. Colleagues in the TS field have agreed that such studies would be valuable, but have suspected that recruitment would be extremely difficult. However, we have now demonstrated enrollment of subjects with New Tics (defined as beginning within the previous 6 months, median 3.6 months) at a rate of 16 subjects per year when recruitment efforts were at their peak—though still on a shoestring budget without full staffing or media advertisements. We have implemented subject preparation and quality control methods that have allowed us to acquire structural and functional MRI data of high quality in many subjects. We now propose to enroll an additional 70 subjects with New Tics and characterize them carefully at baseline and at the 1-year anniversary of tic onset (when TS can first be diagnosed). Both time points will include clinical data, structural and functional MRI, and neuropsychological measures including ability to suppress tics. We expect that complete data will be available for 55-70 subjects (including those already collected), since MRI is sensitive to movement and we are selecting for subjects with tics and additional difficulty holding still (about half of children with tics also have ADHD). We will compare baseline data from this sample to matched tic-free control subjects, and to matched subjects who already have TS or a chronic tic disorder (leveraging existing data in our laboratories to provide some of the clinical and MRI data for these groups). Analyses will include tests of specific a priori hypotheses as well as machine learning analyses of the complete dataset. These comparisons will allow us to discover whether imaging differences in children with TS are present long before TS can be diagnosed, whether they fade when tics improve, and whether they predict outcome in children with new tics. Investigation of this “pre-Tourette” population opens an entirely new window for etiologic discovery in tic disorders. It may also have important clinical consequences, if the results identify which newly- ticcing children are at highest risk for development of a chronic tic disorder.

项目摘要 至少 20% 的儿童在一生中的某个时期会出现抽动症，这使得抽动症成为治疗的一个主题 然而，只有约 3% 的儿童患有持续一年的抽动症。 因此，包括图雷特综合征在内的慢性抽动障碍可以被概念化为两种疾病。 步骤过程：抽动开始，然后他们无法汇出。根据数字，这个过程的第二部分是。 越不寻常，也许与疾病关系更密切，但令人惊讶的是，几乎没有研究 在第一次抽动出现后但在明确孩子是否会去之前检查了这个关键时期 因此，先前的研究已经确定了大脑的异常。 TS 儿童的结构和功能通常无法阐明这些异常是否是 与抽动的出现或更重要的抽动消失的过程有关。 可以前瞻性地观察消失，从而可以进行强大的受试者内分析来测试 抽动后不久的大脑结构或功能特征是否可以预测抽动之前的缓解 TS 是可诊断的，并且这些特征是否是状态相关的或更持久的标记 容易发生抽动。 TS 领域的同事一致认为此类研究很有价值，但他们怀疑 然而，我们现在已经展示了受试者的招募情况。 新抽动症（定义为在前 6 个月内开始，中位数 3.6 个月）的比率为 16 尽管预算仍然有限，但招募工作处于高峰期时每年都会有受试者 我们已经实施了科目准备和质量。 控制方法使我们能够获得高质量的结构和功能 MRI 数据 许多科目。 我们现在建议再招募 70 名 New Tics 受试者，并在以下网址仔细描述他们的特征： 基线和抽动发作一周年（可以首次诊断出 TS）。 将包括临床数据、结构和功能 MRI 以及神经心理学测量，包括 我们预计将获得 55-70 名受试者（包括受试者）的完整数据。 那些已经收集的），因为 MRI 对运动敏感，我们正在选择患有抽动的受试者 以及保持静止的额外困难（大约一半患有抽动症的儿童也患有多动症）。 将该样本的基线数据与匹配的无抽动对照受试者以及匹配受试者进行比较 已经患有 TS 或慢性抽动障碍的人（利用我们实验室的现有数据来提供 这些组的一些临床和 MRI 数据）分析将包括特定先验测试。 这些比较将进行假设以及对完整数据集的机器学习分析。 让我们能够发现 TS 儿童的影像学差异是否早在 TS 能够被诊断出来之前就已经存在了。 诊断，当抽动改善时它们是否会消失，以及它们是否可以预测患有抽动症的儿童的结果 新的抽动症。 对“抽动秽语前”人群的调查为病因发现打开了一个全新的窗口 如果结果确定了哪些新的抽动障碍，它也可能产生重要的临床后果。 抽动儿童患慢性抽动障碍的风险最高。