A Pharmacogenetic Study of Escitalopram in Autism Spectrum Disorders

作者：Owley Thomas; Brune Camille W^*; Salt Jeff; Walton Laura; Guter Steve; Ayuyao Nelson; Gibbons Robert D; Leventhal Bennett L; Cook Edwin H

来源：Autism Research, 2010, 3(1): 1-7.

DOI：10.1002/aur.109

• autistic disorder
• escitalopram
• pharmacogenetics
• open label
• drug treatment

To determine the effect of serotonin transporter polymorphism promoter region (5-HTTPLR) genotypic variation (low, intermediate, and high expression groups) on response to escitalopram treatment of children and adolescents with autism spectrum disorders (ASDs). Method: The study used a forced titration, open label design, with genotype blind until study completion. Participants were children and adolescents aged 4-17 years of age with a confirmed ASD (autistic disorder, Asperger's disorder, or pervasive developmental disorder, not otherwise specified). Results: There was an interaction between genotype group and time on the Aberrant Behavior Checklist (ABC) Irritability Subscale (primary outcome variable) (linear maximum marginal likelihood estimation = -4.84, Z = -2.89, SE = 1.67, P = 0.004). Examination of baseline to last visit revealed that a genotype grouping based on a previous study of platelet 5-HT uptake revealed less response in the genotype group that had S/S genotype for 5-HTTLPR and did not have a diplotype in intron 1 previously shown to be associated with increased platelet 5-HT uptake. Conclusion: This genotype-blind, prospective pharmacogenetic study found the group of subjects with associated with the lowest platelet 5-HT uptake from previous study had the smallest reduction in ABC-Irritability scores after open label treatment with escitalopram. Replication is necessary to confirm these findings.

• 出版日期2010-2