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 注意缺陷/多动症（ADHD）是一种高度普遍的神经精神疾病， 影响3-5％的儿童和1-5％的成年人。被诊断为多动症报告的成年人中，近60％ 他们已经接受了药物治疗，通常是精神刺激剂。最常见的兴奋剂之一 用于治疗多动症的是苯丙胺。 苯丙胺最近被证明具有破坏多巴胺（DA）轴突的潜力 血浆浓度的非人类灵长类动物（狒狒和松鼠猴）大脑中的末端 类似于ADHD患者发展的患者。在这些研究中，苯丙胺是根据口服的 药物管理时间表，模拟了在ADHD治疗中使用苯丙胺的时间表。这些 临床前观察结果，再加上初步结果，表明先前成年ADHD患者 用苯丙胺处理的降低[11] Win 35,428标记的结合电位（BP）不太可能 要与苯丙胺对DAT的急性作用有关，请担心苯丙胺对成人的治疗 多动症可能与脑多巴胺神经毒性的风险有关。 拟议研究的目的是确定使用苯丙胺是否用于治疗 成人多动症与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）将用于测量脑DA轴突终端的两个结构元素，DAT和 囊泡单胺转运蛋白型2（VMAT-2），在先前接受治疗的成年ADHD患者中 苯丙胺。该组中的发现将与其他三个组进行比较：1）ADHD的成年人 从未接受过多动症药理治疗的人； 2）接受治疗的成年人 与甲化酯相关，已知缺乏DA神经毒性潜力； 3）年龄和性别匹配 健康的成年人从未接受过精神刺激剂的治疗。所有受试者将是18至40岁之间的成年人 他们没有CNS活性药物（包括规定的兴奋剂）至少两个星期 （大约30个半衰期的苯丙胺）在宠物成像之前。 我们假设以前曾接受过接受治疗的成年，无药物ADHD患者 与所有三个对照组相比，苯丙胺在DAT和VMAT-2的持续下降。如果我们 假设是正确的，发现将对多动症的治疗产生广泛的公共卫生影响。发现 通过这项研究，还应阐明大脑DA系统在病理生理学和 多动症的症状。