Gene expression in blood is associated with risperidone response in children with autism spectrum disorders
Gene expression in blood is associated with risperidone response in children with autism spectrum disorders
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DOI：
10.1038/tpj.2011.23
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发表时间：
2012-10-01
影响因子：
2.8
通讯作者：
Hendren, R. L.
中科院分区：
文献类型：
--
作者：
Lit, L.;Sharp, F. R.;Hendren, R. L.
患有自闭症谱系障碍 (ASD) 的儿童通常有严重的行为问题。并非所有患有这些问题的儿童都对非典型抗精神病药物有反应；因此，我们对 42 名 ASD 受试者（年龄 112.7 +/- 51.2 个月）进行利培酮（一种非典型抗精神病药）治疗前的外周血基因表达是否与利培酮治疗 8 周后严重行为障碍的改善相关。将利培酮治疗前血液中的外显子表达水平与利培酮治疗前异常行为检查表易激惹（ABC-I）评分的变化进行比较。五个基因内的外显子表达与所有利培酮治疗受试者的 ABC-I 评分变化相关：GBP6、RABL5、RNF213、NFKBID 和 RNF40 (alpha < 0.001)。 RNF40 位于 16p11.2，该区域与自闭症和精神分裂症有关。因此，治疗前表达的这些基因与随后的临床反应相关。未来的研究需要证实这些结果，并确定这种表达谱是否与其他疾病中的利培酮反应或自闭症谱系障碍中的替代抗精神病药反应相关。药物基因组学杂志 (2012) 12, 368-371; doi：10.1038/tpj.2011.23； 2011 年 6 月 7 日在线发布
Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whether peripheral blood gene expression before treatment with risperidone, an atypical antipsychotic, was associated with improvements in severe behavioral disturbances 8 weeks following risperidone treatment in 42 ASD subjects (age 112.7 +/- 51.2 months). Exon expression levels in blood before risperidone treatment were compared with pre-post risperidone change in Aberrant Behavior Checklist-Irritability (ABC-I) scores. Expression of exons within five genes was correlated with change in ABC-I scores across all risperidone-treated subjects: GBP6, RABL5, RNF213, NFKBID and RNF40 (alpha < 0.001). RNF40 is located at 16p11.2, a region implicated in autism and schizophrenia. Thus, these genes expressed before treatment were associated with subsequent clinical response. Future studies will be needed to confirm these results and determine whether this expression profile is associated with risperidone response in other disorders, or alternative antipsychotic response within ASD. The Pharmacogenomics Journal (2012) 12, 368-371; doi:10.1038/tpj.2011.23; published online 7 June 2011