RESPONSE VARIABILITY IN STIMULANT TREATMENT OF ADHD

拟议的指导以病人为导向的研究职业发展奖概述了职业发展和临床儿科精神药理学研究的计划。 该计划的重点将是在160名患有注意缺陷多动障碍（ADHD）的儿童和青少年中进行哌甲酯的临床试验。 虽然兴奋剂药物被认为是ADHD的一线治疗方法，但个别儿童对药物的反应存在巨大差异，并且没有方法可以先验地确定可能提供最佳益处的特定兴奋剂或剂量。 本研究的具体目的将阐述兴奋剂治疗反应中这种变异性的可能潜在机制。 该奖项的意义可能是提高对药物反应个体差异的因素的理解，并优化对ADHD和其他精神疾病的药理反应。候选人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到临床研究者的转变。 拟议的研究是专门为提供指导的研究经验，从基础科学的新兴概念，在儿童心理健康的临床调查的应用。 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研究所和生物数学在加州大学洛杉矶分校医学院的神经科学和临床研究的教学指导。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。 额外的时间将致力于分子精神病学，实验室方法，临床药理学和医学研究伦理学的监督个人课程的研究。 除了资助候选人向独立研究的过渡外，拟议的研究还将有助于我们了解精神疾病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.