THE PHARMACOGNETICS OF TREATMENT FOR INSISTENCE SAMENESS IN AUTISM

自闭症坚持同一性治疗的药理学

• 批准号: 7718610
• 负责人: THOMAS B OWLEY
• 金额: $ 37.71万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718610
• 关键词: 5-HT6 receptor; Adolescent; Affect; Age-Years; Autistic Disorder; Behavior; Brain; Child; Classification; Clinical; Clinical Trials; Collaborations; Data; Disease; Escitalopram; Functional Magnetic Resonance Imaging; Genes; Genetic Variation; Genotype; HTR2A gene; Introns; Measurement; Measures; Mission; Neurodevelopmental Disorder; Patients; Pharmaceutical Preparations; Pharmacogenetics; Phase I Clinical Trials; Population; Positioning Attribute; Promoter Regions; Receptor Gene; Research; Rest; Rodent; Selective Serotonin Reuptake Inhibitor; Serotonin; Serotonin Receptor 5-HT2A; Severities; Single Nucleotide Polymorphism; Symptoms; System; Testing; Therapeutic; Translating; Variant; Week; base; design; human HTR2A protein; programs; response; serotonin transporter

The Autistic Spectrum Disorders (ASD) are a group of debilitating neurodevelopmental disorders. Insistence on sameness (IS) is a common and particularly troublesome feature of ASD, and IS has been hypothesized to be due to serotonergic dysmodulation in this population. Many patients with ASD and IS benefit from treatment with medications that affect serotonin, in particular the selective serotonin reuptake inhibitors (SSRIs); however, there is little information available about which particular IS symptoms respond to SSRIs, or which patients might be better candidates based on presenting symptoms or genetic variation. This pharmacogenetic study provides an opportunity to explore these questions through empirical measurement of clinical response of IS symptoms to an SSRI (escitalopram), and comparison of these differences in response to genetic variation in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) and in the second intron of the serotonin 2A receptor gene (HTR2A). Primary Analyses Specific Aim #1: Is there a significant difference in degree of therapeutic response on symptoms of IS to escitalopram in children and adolescents with autism 5 to 35 years of age as a function of allelic variation of 5-HTTPLR? Based on preliminary data, it is hypothesized that subjects with long/long genotype or long/short genotype (not-SS) will have a superior response to those with those with short/short genotype (SS group). Secondary Analyses Specific Aim #2: Is there a significant difference in degree of therapeutic response on symptoms of IS to escitalopram in children and adolescents with autism 5 to 35 years of age as a function of allelic variation of the HTR2A? It is hypothesized that subjects with single nucleotide polymorphism (SNP) rs7997012 in the second intron of the HTR2A will have a superior response to those with those without this SNP.

自闭症谱系障碍(ASD)是一组衰弱的神经发育障碍。坚持 关于同质性(IS)是ASD的一个常见且特别麻烦的特征，并且IS已被假设 可能是由于这一人群的5-羟色胺能失调。许多患有ASD的患者受益于 使用影响5-羟色胺的药物治疗，特别是选择性5-羟色胺再摄取抑制剂 (SSRIs)；然而，关于哪些特定的IS症状对SSRIs有反应的信息很少， 或者根据出现的症状或基因变异，哪些患者可能是更好的候选对象。这 药物遗传学研究提供了通过经验测量来探索这些问题的机会 IS症状对SSRI(艾司匹兰)的临床反应，并比较这些差异在 5-羟色胺转运体基因启动子区(5-HTTLPR)遗传变异的反应 5-羟色胺2A受体基因(HTR2A)的第二内含子。 初步分析 具体目标1：对IS-TO症状的治疗反应程度有显著差异吗？ 艾司匹林对5-35岁自闭症儿童和青少年的等位基因变异 5-HTTPLR？根据初步数据，假设具有Long/Long或Long/Short基因的受试者 基因型(非-SS)的反应优于短型/短型(SS组)。 二次分析 具体目标2：对IS-TO症状的治疗反应程度是否有显著差异 艾司匹林对5-35岁自闭症儿童和青少年的等位基因变异 HTR2A型？推测具有单核苷酸多态(SNP)rs7997012的受试者在 HTR2A的第二内含子将比那些没有该SNP的内含子有更好的反应。