THE PHARMACOGNETICS OF TREATMENT FOR INSISTENCE SAMENESS IN AUTISM

自闭症谱系障碍（ASD）是一组使人衰弱的神经发育障碍。坚持 相似性（IS）是ASD的常见且特别麻烦的特征，并且IS已被假设为 是由于这一人群中的多巴胺能调节障碍。许多ASD和IS患者受益于 用影响血清素的药物治疗，特别是选择性血清素再摄取抑制剂 （SSRIs）;然而，关于哪些特定的IS症状对SSRIs有反应的信息很少， 或者根据症状或遗传变异，哪些患者可能是更好的候选人。这 药物遗传学研究提供了一个机会，探索这些问题，通过实证测量 IS症状对SSRI（艾司西酞普兰）的临床反应，并比较这些差异， 对5-羟色胺转运蛋白基因（SLC 6A 4）启动子区（5-HTTLPR）遗传变异的反应 和5-羟色胺2A受体基因（HTR 2A）的第二内含子中。 主要分析 具体目标#1：对IS症状的治疗反应程度是否存在显著差异， 依他普仑在5 - 35岁自闭症儿童和青少年中作为等位基因变异的函数 5-HTTPLR？基于初步数据，假设具有长/长基因型或长/短基因型的受试者 基因型（非SS）的患者将比那些具有短/短基因型（SS组）的患者具有上级的反应。 次要分析 具体目标#2：对IS症状的治疗反应程度是否存在显著差异， 依他普仑在5 - 35岁自闭症儿童和青少年中作为等位基因变异的函数 HTR2A？假设具有单核苷酸多态性（SNP）rs7997012的受试者在基因组中的多态性与基因型无关。 HTR 2A的第二内含子将具有比那些没有该SNP的人上级的应答。

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.