PET Studies of Amphetamine Treatment of ADHD

项目说明 注意力缺陷/多动障碍(ADHD)是一种非常普遍的神经精神障碍， 影响3-5%的儿童和1-5%的成人。近60%的被诊断为ADHD的成年人报告说 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安非他明。 安非他明最近被证明有可能破坏多巴胺(DA)轴突 非人灵长类动物(狒狒和松鼠猴)脑内终末的血浆浓度 类似于ADHD患者的症状。在这些研究中，安非他明是根据 模拟安非他明在ADHD治疗中的使用情况的给药时间表。这些 临床前观察，加上初步结果表明，成人ADHD患者以前 用苯丙胺治疗后，[11]Win 35,428标记的结合潜力(BP)不太可能降低 与苯丙胺对DAT的急性影响有关，提出关注苯丙胺对成人的治疗 ADHD可能与脑多巴胺神经毒性的风险有关。 这项拟议研究的目的是确定安非他明是否用于治疗 成人ADHD与脑多巴胺能神经毒性的风险有关。为此，正电子发射 体层摄影术(PET)将用于测量大脑DA轴突终末的两个结构元素，DAT和 曾接受药物治疗的成人ADHD患者的囊泡单胺转运体-2(VMAT-2) 安非他命。这一组的发现将与其他三组进行比较：1)患有ADHD的成年人 从未接受过ADHD药物治疗的人；2)接受过治疗的成人ADHD患者 使用哌醋甲酯，已知缺乏DA神经毒性潜力；以及3)年龄和性别匹配 健康的成年人从未使用过精神刺激剂。所有受试者均为18至40岁的成年人。 停用中枢神经系统活性药物(包括处方兴奋剂)至少两周 (大约30个苯丙胺的半衰期)在PET成像之前。 我们假设，以前接受过药物治疗的成年、无药物的ADHD患者 与所有三个对照组相比，苯丙胺的DAT和VMAT-2将持续下降。如果我们的 假设是正确的，研究结果将对ADHD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。

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.