Separation of Cognitive Impairments in Attention-Deficit/Hyperactivity Disorder Into 2 Familial Factors
Separation of Cognitive Impairments in Attention-Deficit/Hyperactivity Disorder Into 2 Familial Factors
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DOI：
10.1001/archgenpsychiatry.2010.139
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发表时间：
2010-11-01
影响因子：
--
通讯作者：
Asherson, Philip
中科院分区：
文献类型：
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作者：
Kuntsi, Jonna;Wood, Alexis C.;Asherson, Philip
背景：注意力缺陷/多动障碍(ADHD)与广泛的认知障碍有关，但尚不清楚这种明显的多重障碍是共同的病因还是存在单独的病因途径。目的：利用多变量家系因素分析方法，确定是否有一个或多个家族性因素与ADHD相关的缓慢和可变的反应时、反应抑制受损和选择冲动。设计：ADHD和对照同胞配对设计。地点：比利时、德国、爱尔兰、以色列、西班牙、瑞士和英国。参与者：总共1265名参与者：464名ADHD先证者和456名他们的兄弟姐妹(524名ADHD合并亚型)结果：最终模型由2个家族性因素组成。较大的因子反映了ADHD家族变异的85%，捕捉了98%到100%对平均反应时和反应时变异性的家族影响。第二个较小的因素反映了ADHD的13%的家庭变异，反映了62%到82%的家庭对开始/不进行任务中的委托和遗漏错误的影响。由于模型拟合度较差，最终模型中排除了选择冲动。结论：研究结果提示ADHD患者存在两条认知障碍的家族通路，为未来的分子遗传学研究提供了有前景的认知靶点。这两种认知障碍之间的家族差异与最近关于ADHD两个可分离的潜在过程的理论模型--发展模型和唤醒-注意模型--是一致的。未来在发育框架内测试家庭模型的研究可能会为发展敏感的干预措施提供信息。
Context: Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations.Objectives: To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD.Design: An ADHD and control sibling-pair design.Setting: Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom.Participants: A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants.Main Outcome Measures: Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task.Results: The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit.Conclusions: The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models-a developmental model and an arousal-attention model-of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions.