ON-OFF MOOD CHANGE IN PARKINSONS DISEASE

帕金森病的情绪时断时续的变化

• 批准号: 2460468
• 负责人: KEVIN J BLACK
• 金额: $ 8.68万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-09 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2460468
• 关键词: Macaca nemestrina; Parkinson's disease; antiparkinson drugs; autoradiography; baboons; blood flow measurement; clinical research; dihydroxyphenylalanine; dopamine agonists; dosage; drug adverse effect; drug metabolism; human subject; magnetic resonance imaging; memory; mood disorders; neuroanatomy; neurons; neuropharmacology; positron emission tomography; psychomotor function; sensory depression; visual stimulus

The proposed career development plan will form a bridge from the applicant's past clinical and research experience to a productive research career focused on the functional neuroanatomy of movement disorders. This is seen as a natural extension of the applicant's prior research experience, and his longstanding clinical interests in movement disorders and neuropsychiatry. Short-term career goals include (1) continued development of an in vivo test of dopamine-mediated pathway function, and application of this test to a suitable clinical population. (2) This will provide important new research skills leading to independent research with positron emission tomography (PET). (3) Further clinical expertise with movement disorders is another short-term goal. Long-term goals include the application of this PET technique or similar methods to other neuropsychiatric illnesses with abnormal dopaminergic function; the proposed research provides a natural stepping stone to these goals. Additional elements of the career development plan include limited, focused clinical work, and regular seminars in PET methods, movement disorders, and neuropharmacology. The environment in which this will occur is unparalleled. This laboratory is internationally recognized as a leader in PET methodology and applications, and is fully equipped. Also literally under the same roof are major research and clinical MRI facilities. The mentor has extensive experience both in clinical aspects of movement disorders and in the application of PET to their study. He has also contributed substantially to the development and application of basic PET methods. In addition, significant opportunities for informal and formal collaboration exist with other independent investigators in this laboratory and elsewhere on campus, especially within the departments of neurology, neurobiology, psychiatry and radiology. The goal of the proposed animal research is to further develop an in vivo test of the sensitivity of specific dopamine-mediated pathways. The localized effects of specific dopamine agonists on cerebral blood flow (rCBF) measured with PET will be used to indicate changes in neuronal activity. Although a fairly novel application of PET, this is analogous to the well-known "activation " of rCBF by visual stimuli or memory tasks, and autoradiographic animal studies of metabolic changes due to dopamine agonists support its validity and utility. Preliminary data, both in patients with Parkinson's disease (PD) and baboons, demonstrate athe feasibility of this approach. The proposed clinical PET study will examine the effects of L-DOPA and specific dopamine agonists on rCBF in a group of PD patients with marked dopamine-related changes in mood (off-period depression), as compared to a carefully matched group of PD patients without off-period depression. Localized, pharmacologically specific group differences are hypothesized. This research potentially has wide applicability, not only to the many PD patients with off-period depression, but also to other clinically-defined subgroups of patients with PD, as well as patients affected by idiopathic major depression, dystonia, schizophrenia, and Tourette syndrome.

拟议的职业发展计划将成为 申请人过去从事生产性研究的临床和研究经验 Career专注于运动障碍的功能神经解剖学。这 被视为申请人先前研究的自然延伸 经验，以及他在运动障碍方面的长期临床兴趣 和神经精神病学。短期职业目标包括(1)继续 开发多巴胺介导的途径功能的体内测试，以及 这项测试在合适的临床人群中的应用。(2)这将 提供重要的新研究技能，从而实现独立研究 正电子发射断层扫描(PET)。(3)进一步的临床专业知识 运动障碍是另一个短期目标。长期目标包括 这种PET技术或类似方法在其他方面的应用 多巴胺能功能异常的神经精神疾病； 拟议中的研究为实现这些目标提供了天然的垫脚石。 职业发展计划的其他内容包括有限的、重点突出的 临床工作，以及PET方法、运动障碍和定期研讨会 神经药理学。发生这种情况的环境是 无与伦比的。这个实验室是国际公认的领先实验室 PET方法和应用，并配备齐全。也是字面上的 同一屋檐下是主要的研究和临床核磁共振设施。这个 曼托在运动的临床方面都有丰富的经验 以及正电子发射计算机断层扫描在他们的研究中的应用。他还 为基础聚酯的开发和应用做出了重大贡献 方法：研究方法。此外，非正式和正式的重要机会 与该实验室中的其他独立调查人员存在合作 在校园的其他地方，特别是在神经科， 神经生物学、精神病学和放射学。提议的动物的目标是 研究是为了进一步开发一种体内试验的敏感性 特定的多巴胺介导的通路。特定的局部化效果 多巴胺激动剂对脑血流量(RCBF)的PET测量将是 用来表示神经元活动的变化。虽然这是一部相当新奇的小说 PET的应用，这类似于众所周知的“激活” 视觉刺激或记忆任务的rCBF，以及放射自显影动物研究 多巴胺激动剂引起的代谢变化支持其有效性 实用程序。帕金森氏病(PD)患者的初步数据 和狒狒，证明了这种方法的可行性。建议数 临床正电子发射体层摄影研究将考察L-多巴和特异性多巴胺的作用 激动剂对多巴胺相关PD患者局部脑血流的影响 情绪变化(非经期抑郁)，与仔细比较 对照组为无间期抑郁的帕金森病患者。本地化， 药理上特定的组别差异是假设的。这 研究可能具有广泛的适用性，不仅适用于许多PD 间歇期抑郁症患者，也要以其他临床定义 帕金森病患者亚组以及受特发性疾病影响的患者 严重的抑郁症、肌张力障碍、精神分裂症和多发性抽动症。