PET Studies of Amphetamine Treatment of ADHD

安非他明治疗 ADHD 的 PET 研究

• 批准号: 8429516
• 负责人: GEORGE A RICAURTE
• 金额: $ 50.44万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8429516
• 关键词: Acute; Adult; Affect; Age; Amphetamines; Animals; Attention deficit hyperactivity disorder; Binding; Brain; Child; Control Groups; Corpus striatum structure; Coupled; Data; Diagnosis; Disease; Dopamine; Dose; Drug Administration Schedule; Elements; Functional disorder; Gender; Goals; Human; Image; Individual; Label; Life; Light; Measures; Methylphenidate; Narcolepsy; Papio; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Plasma; Positron-Emission Tomography; Presynaptic Terminals; Public Health; Reporting; Research; Risk; Role; Saimiri; Simulate; Symptoms; base; density; dopamine system; dopamine transporter; dopaminergic neuron; neuropsychiatry; neurotoxic; neurotoxicity; nonhuman primate; pre-clinical; psychostimulant; radioligand; vesicular monoamine transporter; vesicular monoamine transporter 2

Project Description Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neuropsychiatric disorder, affecting 3-5% of children and 1-5% of adults. Nearly 60% of adults who are diagnosed with ADHD report that they have been treated with medications, generally psychostimulants. One of the most common stimulants used to treat ADHD is amphetamine. Amphetamine has recently been shown to have the potential to destroy dopamine (DA) axon terminals in the brain of non-human primates (baboons and squirrel monkeys) at plasma concentrations similar to those that develop in ADHD patients. In these studies, amphetamine was given orally according to a schedule of drug administration that simulated the use of amphetamine in ADHD treatment. These preclinical observations, coupled with preliminary results indicating that adult ADHD patients previously treated with amphetamine have decrements [11] WIN 35,428-labeled binding potential (BP) that are unlikely to be related to acute effects of amphetamine on the DAT, raise concern that amphetamine treatment of adult ADHD may be associated with a risk of brain dopamine neurotoxicity. The purpose of the proposed research is to determine if the use of amphetamine for the treatment of adult ADHD is associated with a risk of brain dopaminergic neurotoxicity. To this end, positron emission tomography (PET) will be used to measure two structural elements of brain DA axon terminals, the DAT and the vesicular monoamine transporter-type 2 (VMAT-2), in adult ADHD patients previously treated with amphetamine. Findings in this group will be compared to those three other groups: 1) Adults with ADHD who have never received pharmacological treatment for ADHD; 2) Adults with ADHD who have been treated with methylphenidate, which is known to lack DA neurotoxic potential; and 3) Age- and gender- matched healthy adults never treated with psychostimulants. All subjects will be adults between the ages of 18 and 40 who have been free of CNS-active drugs (including prescribed stimulants) for at least two weeks (approximately 30 half-lives of amphetamine) prior to PET imaging. We hypothesize that adult, drug-free ADHD patients who have been previously treated with amphetamine will have lasting decreases in the DAT and VMAT-2 compared to all three control groups. If our hypothesis is correct, findings will have broad public health implications for the treatment of ADHD. Findings from this research should also shed additional light on the role of brain DA systems in the pathophysiology and symptoms of ADHD.

项目描述 注意力缺陷/多动障碍（ADHD）是一种非常普遍的神经精神疾病， 影响 3-5% 的儿童和 1-5% 的成人。近 60% 被诊断患有 ADHD 的成年人表示， 他们接受过药物治疗，通常是精神兴奋剂。最常见的兴奋剂之一 用于治疗多动症的是安非他明。 安非他明最近被证明具有破坏多巴胺 (DA) 轴突的潜力 非人类灵长类动物（狒狒和松鼠猴）血浆浓度下大脑中的末梢 与 ADHD 患者的症状相似。在这些研究中，根据以下方法口服安非他明： 模拟在多动症治疗中使用安非他明的给药时间表。这些 临床前观察，加上初步结果表明成年多动症患者以前 用安非他明治疗后会出现减少 [11] WIN 35,428 标记的结合电位 (BP) 不太可能 与安非他明对 DAT 的急性影响有关，引起人们对安非他明治疗成人的担忧 ADHD 可能与大脑多巴胺神经毒性的风险有关。 拟议研究的目的是确定是否使用安非他明来治疗 成人多动症与大脑多巴胺能神经毒性的风险有关。为此，正电子发射 断层扫描 (PET) 将用于测量大脑 DA 轴突末端的两个结构元件：DAT 和 囊泡单胺转运蛋白 2 型 (VMAT-2)，在既往接受过治疗的成人 ADHD 患者中 安非他明。该组的研究结果将与其他三个组进行比较：1) 患有多动症的成年人 从未接受过 ADHD 药物治疗的人； 2) 已接受治疗的多动症成人 与哌醋甲酯一起使用，已知哌醋甲酯缺乏 DA 神经毒性潜力； 3) 年龄和性别匹配 健康成年人从未接受过精神兴奋剂治疗。所有受试者均为 18 岁至 40 岁之间的成年人 至少两周未服用中枢神经系统活性药物（包括处方兴奋剂）的人 （大约 30 个安非他明的半衰期）在 PET 成像之前。 我们假设，以前接受过药物治疗的成人 ADHD 患者 与所有三个对照组相比，安非他明的 DAT 和 VMAT-2 会持续下降。如果我们的 假设是正确的，研究结果将对多动症的治疗产生广泛的公共卫生影响。发现 这项研究还应该进一步阐明大脑 DA 系统在病理生理学和 多动症的症状。