TESTING THE PHASIC DOPAMINE RELEASE HYPOTHESIS IN TOURETTE SYNDROME: PILOT

测试抽动秽语综合症中的阶段性多巴胺释放假说：试点

基本信息

批准号：
8514731
负责人：
KEVIN J BLACK
金额：
$ 10.94万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8514731
关键词：
Address Adult Affect Amphetamines Appearance Back Brain Brain imaging Carbidopa Cerebrovascular Circulation Child Childhood Chronic Cognitive Comorbidity Core-Binding Factor Corpus striatum structure Data Disadvantaged Dopamine Dopamine D2 Receptor Euphoria Experimental Designs Functional Magnetic Resonance Imaging Functional disorder Funding Genes Gilles de la Tourette syndrome Image Intravenous infusion procedures Learning Levodopa Life Link Magnetic Resonance Imaging Measures Methods Motor Movement Nature Noise Performance Persons Pilot Projects Placebos Positron-Emission Tomography Protocols documentation Public Health Quality of life Raclopride Radiation Randomized Controlled Trials Research Rest Role Sample Size Scanning Sensory Severities Short-Term Memory Signal Transduction Spin Labels Stereotyping Study Subject Technology Testing Thalamic structure Tic disorder Time Work base behavior change experience follow-up in vivo indexing interest monoamine novel strategies postsynaptic presynaptic psychosocial putamen rapid technique receptor research study response sequence learning success theories uptake

项目摘要

DESCRIPTION (provided by applicant): Up to 20% of all children have tics at some time in their life, and about 3% of all children have a chronic tic disorder such as Tourette syndrome (TS), making tic disorders a subject of substantial public health interest. Despite steadily increasing research, no treatment for TS works for more than half those treated, and the cause and pathophysiology of TS are poorly understood. Based on the observation that dopamine D2 receptor antagonists significantly reduce tic severity, one longstanding hypothesis has been that tics may involve abnormalities in transient (phasic) dopamine release in the striatum, while baseline (tonic) dopamine release may be normal. Several experiments in the past 15 years attempted to address this hypothesis by measuring striatal dopamine release in TS in response to amphetamine. One could argue, however, that this assessed only maximal possible dopamine release under nonphysiological conditions. The present proposal represents the first step in a plan to directly test phasic dopamine release in TS by measuring striatal dopamine release in response to a cognitive task with and without exogenous levodopa. The proposal will exploit the newly developed Siemens PET-MRI scanner to acquire rCBF simultaneously with the receptor imaging. The applicants have preliminary data on most aspects of this approach, considered individually, but none for the combined approach. This application proposes to test the full protocol on a small group of TS and matched control subjects, in order to demonstrate feasibility and estimate variance for a planned R01 application. The planned R01-funded follow-up study would include sample sizes adequate to test the effects of psychiatric comorbidity, past treatment, and demographic variables.

描述（由申请人提供）：高达 20% 的儿童在一生中的某个时间会出现抽动症，大约 3% 的儿童患有慢性抽动症，例如抽动秽语综合征 (TS)，这使得抽动症成为重要的主题。公共卫生利益。尽管研究不断增加，但 TS 的治疗方法对一半以上的治疗者无效，而且 TS 的病因和病理生理学知之甚少。基于多巴胺 D2 受体拮抗剂显着降低抽动严重程度的观察，一种长期存在的假设是抽动可能涉及纹状体短暂（阶段性）多巴胺释放异常，而基线（强直性）多巴胺释放可能正常。过去 15 年的几项实验试图通过测量 TS 中对安非他明的反应而释放的纹状体多巴胺来解决这一假设。然而，有人可能会争辩说，这仅评估了非生理条件下最大可能的多巴胺释放。本提案代表了通过测量纹状体多巴胺释放来直接测试 TS 中阶段性多巴胺释放的计划的第一步，该释放响应于有或没有外源性左旋多巴的认知任务。该提案将利用新开发的西门子 PET-MRI 扫描仪在受体成像的同时采集 rCBF。申请人拥有该方法大多数方面的初步数据（单独考虑），但没有组合方法的初步数据。该应用程序建议在一小组 TS 和匹配的对照受试者上测试完整协议，以证明计划的 R01 应用程序的可行性并估计方差。计划中的 R01 资助的后续研究将包括足够的样本量，以测试精神共病、既往治疗和人口变量的影响。