A Pharmacogenetic Study of Escitalopram in Autism

描述（由申请人提供）：对药物反应和遗传结构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，目前的大多数研究都强烈表明，这是一个涉及多个基因座的复杂遗传基础。也有大量的研究表明自闭症中有血清素能系统，这些患者被发现对控制该系统的药物有反应。阐明这些患者的基因和药物反应之间的确切关系仍然是一个相当大的挑战。候选人建议在遗传学和药理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。该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，并接受了自闭症患者评估和药物治疗方面的培训。该提案的具体目标是：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)验证自闭症患者血清素再摄取抑制剂的剂量反应与血清素转运体等位基因变异有关的假设。培训计划将包括在广泛性发育障碍、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，允许候选人实施在培训期间开发的技能。今年将招募110名患有自闭症的儿童和青少年作为样本，评估他们对血清素再摄取抑制剂的反应。通过完成拟议的发展和培训计划，获奖候选人将获得药理学研究领域的全面知识基础，并将进行独立的研究计划，旨在确定血清素在自闭症受试者对血清素能药物的反应中的作用。

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.