A Pharmacogenetic Study of Escitalopram in Autism

艾司西酞普兰治疗自闭症的药物遗传学研究

• 批准号: 6650746
• 负责人: THOMAS B OWLEY
• 金额: $ 17.12万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-23 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650746
• 关键词: adolescence (12-20); autism; behavioral /social science research tag; clinical research; dosage; human subject; human therapy evaluation; interview; mental disorder chemotherapy; middle childhood (6-11); paroxetine; pharmacogenetics; polysomnography; psychopharmacology; questionnaires; serotonin transporter

DESCRIPTION (provided by applicant): The study of the interaction between pharmacological response and genetic constitution is increasingly being recognized as making significant contributions to the clinical management of psychiatric illness. Such information is likely to be especially useful for a disease process like autistic disorder where the majority of current research strongly suggests a complex genetic basis involving multiple loci. There is also an enormous amount of research that implicates the serotonergic system in autistic disorder, and these patients have been found to be responsive to medications that manipulate this system. Elucidating the exact relationship(s) between genes and drug response in these patients remains a considerable challenge. The candidate proposes training and development in the investigation of the interplay between genetics and pharmacological response that will provide a foundation for addressing these problems. The candidate, an Assistant Professor in the Department of Psychiatry at the University of Chicago, completed a child psychiatry fellowship at the University of Chicago, and has been trained in the assessment and pharmacological treatment of autistic patients. The specific aims of this proposal are: 1) to develop expertise in genetics and psychopharmacology that will foster the ability to undertake independent research; 2) to test the hypothesis that dose response to serotonin reuptake inhibitors is a function of the allelic variation of the serotonin transporter in autistic subjects. The training program will include supervision under the direction of experts in the fields of the Pervasive Developmental Disorders, genetics, statistics, psychopharmacology, and epidemiology. The program includes beginning the collection of data during the second year, allowing the candidate to implement the skills developed during the training period. A sample of 110 children and adolescents with autistic disorder will be recruited during this year, and their response to a serotonin reuptake inhibitor assessed. By completing the proposed development and training program, the award candidate will attain a comprehensive knowledge base in the area of pharmacogenetic research, and will pursue an independent program of research aimed at identifying the role of serotonin in the response of autistic subjects to serotonergic agents.

描述(由申请人提供)：对药物反应和遗传构成之间相互作用的研究越来越被认为对精神疾病的临床管理做出了重大贡献。这些信息可能对自闭症这样的疾病过程特别有用，目前的大多数研究强烈表明，涉及多个基因座的复杂遗传基础。还有大量的研究表明，5-羟色胺能系统与自闭症有关，这些患者被发现对操纵这一系统的药物有反应。阐明这些患者的基因和药物反应之间的确切关系(S)仍然是一个相当大的挑战。候选人建议在遗传学和药理学反应之间相互作用的研究方面进行培训和发展，这将为解决这些问题提供基础。这位候选人是芝加哥大学精神病学系的助理教授，在芝加哥大学完成了儿童精神病学奖学金，并接受过自闭症患者的评估和药物治疗方面的培训。这项建议的具体目标是：1)发展遗传学和精神药理学方面的专业知识，以培养进行独立研究的能力；2)检验对5-羟色胺再摄取抑制剂的剂量反应是自闭症患者5-羟色胺转运体等位基因变异的函数的假设。培训计划将包括在普遍发育障碍、遗传学、统计学、精神药理学和流行病学领域专家的指导下进行监督。该计划包括在第二年开始收集数据，使应聘者能够实施在培训期间培养的技能。今年将招募110名自闭症儿童和青少年的样本，并评估他们对5-羟色胺再摄取抑制剂的反应。通过完成拟议的开发和培训计划，获奖候选人将获得药物遗传学研究领域的全面知识基础，并将继续开展一项旨在确定5-羟色胺在自闭症患者对5-羟色胺能药物反应中的作用的独立研究计划。