A pharmacogenetic study of escitalopram in autism spectrum disorders.
A pharmacogenetic study of escitalopram in autism spectrum disorders.
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DOI：
10.1002/aur.109
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发表时间：
2010-02
期刊：
影响因子：
4.7
通讯作者：
Cook, Edwin H.
中科院分区：
文献类型：
--
作者：
Owley, Thomas;Brune, Camille W.;Salt, Jeff;Walton, Laura;Guter, Steve;Ayuyao, Nelson;Gibbons, Robert D.;Leventhal, Bennett L.;Cook, Edwin H.
确定5-羟色胺转运蛋白多态性启动子区（5-HTTPLR）基因型变异（低、中和高表达组）对自闭症谱系障碍（ASD）儿童和青少年艾司西酞普兰治疗反应的影响。该研究采用强制滴定、开放标签设计，在研究完成前对基因型设盲。参与者是4至17岁的儿童和青少年，患有确诊的ASD（自闭症障碍，自闭症障碍或广泛性发育障碍，未另行说明）。在异常行为检查表易怒子量表（主要结局变量）上，基因型组与时间之间存在相互作用（线性MMLE =-4.84，Z =-2.89，SE = 1.67，p = 0.004）。检查基线至末次观察值的结转评分显示，基于先前血小板5-HT摄取研究的基因型分组显示，具有5-HTTLPR S/S基因型且内含子1中没有先前显示与血小板5-HT摄取增加相关的双倍型的基因型组的反应较低。这项基因型盲、前瞻性药物遗传学研究发现，既往研究中血小板5-HT摄取量最低的受试者组在接受艾司西酞普兰开放标签治疗后，ABC-应激评分降低最小。重复是必要的，以确认这些发现。许多患有自闭症谱系障碍的儿童都有焦虑，强迫，强迫和坚持事情保持不变的问题。当其他干预措施不能充分帮助儿童处理这些困难时，有时药物被认为是一种治疗选择。当血清素被一种叫做血清素转运蛋白的蛋白质带回神经细胞时，血清素就被灭活了。艾司西酞普兰阻断这种蛋白质。我们想知道产生艾司西酞普兰蛋白靶点的基因变异是否与这种治疗的反应有关。
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). The study used a forced titration, open label design, with genotype blind until study completion. Participants were children and adolescents aged 4 to 17 years of age with a confirmed ASD (Autistic Disorder, Asperger’s Disorder, or Pervasive Developmental Disorder, Not Otherwise Specified). There was an interaction between genotype group and time on the Aberrant Behavior Checklist Irritability Subscale (primary outcome variable) (linear MMLE = −4.84, Z = −2.89, SE = 1.67, p = 0.004). Examination of baseline to last-observation carried forward scores 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. 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. Many children with Autism Spectrum Disorders have problems with anxiety, obsessions, compulsions, and insisting that things stay the same. When other interventions are not adequately helping the child deal with these difficulties, sometimes medication is considered a treatment option. Serotonin is inactivated when it is taken back into nerve cells by a protein called the serotonin transporter. Escitalopram blocks this protein. We wanted to know if variation in the gene that produces the protein target for escitalopram would be related to response to this treatment.
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影响因子：
--
作者：
King, Bryan H.;Hollander, Eric;Sikich, Linmarie;McCracken, James T.;Scahill, Lawrence;Bregman, Joel D.;Donnelly, Craig L.;Anagnostou, Evdokia;Dukes, Kimberly;Sullivan, Lisa;Hirtz, Deborah;Wagner, Ann;Ritz, Louise
通讯作者：
Ritz, Louise
影响因子：
5.3
作者：
Benedetti, F;Colombo, C;Smeraldi, E
通讯作者：
Smeraldi, E
影响因子：
3.9
作者：
Lord, C;Risi, S;Rutter, M
通讯作者：
Rutter, M
影响因子：
7.6
作者：
Cross, Sarah;Kim, Soo-Jeong;Veenstra-VanderWeele, Jeremy
通讯作者：
Veenstra-VanderWeele, Jeremy
影响因子：
1.9
作者：
LAIRD, NM;WARE, JH
通讯作者：
WARE, JH