Bellgrove Mark A, Barry Edwina, Johnson Katherine A, Cox Marie, Dáibhis Aoife, Daly Michael, Hawi Ziarih, Lambert David, Fitzgerald Michael, McNicholas Fiona, Robertson Ian H, Gill Michael, Kirley Aiveen
Cognitive Neuroscience Laboratory, School of Psychology and Queensland Brain Institute, University of Queensland, Brisbane, Qld., Australia.
Neuropsychopharmacology. 2008 Sep;33(10):2536-45. doi: 10.1038/sj.npp.1301637. Epub 2007 Nov 28.
Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (3' untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 3'-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD.
注意力缺陷多动障碍（ADHD）是一种遗传性的儿童期起病的疾病，其特征在于多个层面的变异性，包括临床表现、认知概况以及对兴奋剂药物的反应。有人认为，这种变异性可能反映了病因学上的差异，特别是在潜在遗传学层面。本研究考察了一种注意力表型——空间注意力偏差是否可作为ADHD症状严重程度、遗传风险和兴奋剂反应的标志物。共有96名患有ADHD的儿童和青少年接受了地标任务评估，该任务是对空间注意力偏差的一种敏感测量方法。所有儿童都对多巴胺转运体基因（DAT1）的多态性（3'非翻译区（UTR）和内含子8可变串联重复序列（VNTRs））进行了基因分型。空间注意力偏差与ADHD症状水平相关，并根据DAT1基因型而有所不同。DAT1 3'-UTR VNTR的10重复等位基因纯合的儿童表现出向右的注意力偏差，与低风险基因型的儿童相比，其症状水平更高。其中共有26名未服用过药物的儿童在基线时进行了地标任务，然后在服用兴奋剂药物6周后再次进行该任务。基线时左侧注意力不集中（向右偏差）与6周时对兴奋剂的反应增强有关。此外，兴奋剂药物引起的空间偏差变化因DAT1基因型而异。本研究表明了一种与ADHD症状严重程度和遗传风险相关的注意力表型，并且可能在预测ADHD的兴奋剂反应方面具有实用价值。
