THE PHARMACOGENETICS OF TREATMENT FOR INSISTENCE SAMENESS IN AUTISM

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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.