RESPONSE VARIABILITY IN STIMULANT TREATMENT OF ADHD

拟议的以患者为导向的导师研究职业发展奖概述了临床儿科精神药理学的职业发展和研究计划。该计划的重点将是对160名患有注意力缺陷多动障碍(ADHD)的儿童和青少年进行哌醋甲酯的临床试验。尽管兴奋剂被认为是治疗ADHD的一线药物，但儿童个体对药物的反应存在巨大差异，而且没有方法事先确定可能提供最佳益处的特定兴奋剂或剂量。这项研究的具体目标将解决刺激治疗反应这种变异性的可能潜在机制。这一奖项的意义可能是加强对导致药物反应个体差异的因素的理解，并优化对ADHD和其他精神障碍的药理学反应。应聘者是一位有成就的临床医生和教育家。教育和研究计划旨在促进职业重点从临床医生和临床教师转变为临床调查员。拟议的研究特别旨在为将基础科学中的新兴概念应用于儿童心理健康的临床调查提供指导研究经验。这项为期五年的职业发展计划包括在加州大学洛杉矶分校神经精神病学研究所教授神经科学和临床研究，以及在加州大学洛杉矶分校医学院教授生物数学。拟议的教育计划包括临床研究方法学、药代动力学、神经生理学、统计分析、神经化学、神经药理学和人类遗传学等课程。额外的时间将用于分子精神病学、实验室方法、临床药理学和医学研究伦理学方面的指导个人课程。除了资助候选人过渡到独立研究之外，拟议的研究还将有助于我们了解精神障碍患者对药物治疗的个体反应基础。

The proposed Mentored Patient-Oriented Research Career Development Award outlines a program of career development and research in clinical pediatric psychopharmacology. A focus of this program will be a clinical trial with methylphenidate in 160 children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Although stimulant medications are regarded as first-line treatments for ADHD, individual children show tremendous differences in response to drug, and there is no method to determine a priori the particular stimulant or dose likely to provide optimal benefit. The Specific Aims of the study will address possible underlying mechanisms for this variability in response to stimulant treatment. Implications of this award may be enhanced understanding of factors contributing to individual differences in response to medication and optimization of pharmacological response to ADHD and other psychiatric disorders. The candidate is an accomplished clinician and educator. The educational and research plan is designed to facilitate a change in career emphasis from clinician and clinical teacher to clinical investigator. The proposed research is specifically intended to provide mentored research experience in the application of emerging concepts from basic sciences to clinical investigations in child mental health. The five-year career development plan includes didactic instruction in neurosciences and clinical research at the UCLA Neuropsychiatric Institute and biomathematics at the UCLA School of Medicine. The proposed educational plan includes courses in clinical research methodologies, pharmacokinetics, neurophysiology, statistical analysis, neurochemistry, neuropharmacology, and human genetics. Additional time will be devoted to supervised individual courses of study in molecular psychiatry, laboratory methods, clinical pharmacology, and medical research ethics. In addition to funding the candidate's transition to independent research the proposed study would also contribute to our knowledge of the basis of individual response to medication in psychiatric disorders.