DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls.
DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls.
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DOI：
10.1038/npp.2010.124
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发表时间：
2010-11
期刊：
影响因子：
--
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选择冲动与多巴胺功能有关，并且在注意缺陷/多动障碍（ADHD）中一直被观察到，使用选择延迟范式，选择冲动倾向于小即时奖励而不是大延迟奖励。更复杂的延迟折扣范式产生了不一致的结果。环境和样本特征可能导致了这些变化。在这里，我们研究了类型（真实与假设）和奖励的大小以及多巴胺基因的变化对选择冲动的影响。选取36例adhd合并亚型（ADHD-CT）男性青少年和32例对照（平均年龄=15.42，SD=2.05），根据DAT110/6单倍型剂量（2拷贝，<2拷贝）组成4个大小大致相等的亚组。参与者也进行了COMTval158met和DRD448bp-VNTR多态性的基因分型，他们执行了一个假设的和一个实时的折扣任务，并提供了性格冲动的自我评定。ADHD-CT组只在假设任务中比对照组对奖励的折扣更大，影响选择的是延迟，而不是奖励的大小。与对照组相比，他们也认为自己更冲动。DAT110/6剂量和COMTVal158Met基因型预测了假设任务中的性状冲动性和折现率，但对实时任务没有预测作用。我们的研究结果直接将影响前额叶皮层（COMTVal158Met）和纹状体（DAT110/6）多巴胺信号的基因变异与假设任务（但不是实时任务）的折扣率和ADHD-CT和健康对照组的特质冲动性自我评定联系起来。假设任务中缺乏幅度效应表明，ADHD-CT中对该任务的贴现可能受到与健康对照组不同的过程的影响。
Choice impulsivity has been linked to dopamine function and is consistently observed in attention deficit/hyperactivity disorder (ADHD) as a preference for smaller-immediate over larger-delayed rewards using choice-delay paradigms. More sophisticated delay discounting paradigms have yielded inconsistent results. Context and sample characteristics may have contributed to these variations. Here we examine the effect of type (real versus hypothetical) and magnitude of reward as well as of variation in dopamine genes on choice impulsivity. We selected 36 male adolescents with ADHD-combined subtype (ADHD-CT) and 32 controls (mean age=15.42, SD=2.05) to form four roughly equally-sized subgroups on the basis of DAT110/6 haplotype dosage (2 copies, <2 copies). Participants, who were also genotyped for the COMTval158met and DRD448bp-VNTR polymorphisms, performed a hypothetical and a real-time discounting task and provided self-ratings of trait-impulsivity. The ADHD-CT group discounted rewards more steeply than controls only in the hypothetical task, with delay, but not reward magnitude, influencing choices. They also rated themselves as more impulsive compared to controls. DAT110/6 dosage and the COMTVal158Met genotype predicted trait-impulsivity and discounting rates in the hypothetical task, but not in the real-time task. Our results directly link variation in genes putatively influencing dopamine signaling in the prefrontal cortex (COMTVal158Met) and the striatum (DAT110/6) with discounting rates in a hypothetical task (but not a real-time task) and self-ratings of trait-impulsivity in ADHD-CT and healthy controls. The lack of magnitude effects in the hypothetical task suggests that discounting in this task may be influenced by different processes in ADHD-CT than in healthy controls.
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DOI：
10.1002/ajmg.b.30672
发表时间：
2008-12-05
影响因子：
2.8
作者：
Chen, Wai;Zhou, Kaixin;Asherson, Philip
通讯作者：
Asherson, Philip
影响因子：
17.7
作者：
Asherson, Philip;Brookes, Keeley;Faraone, Stephen V.
通讯作者：
Faraone, Stephen V.
影响因子：
3.5
作者：
Chapman, GB;Winquist, JR
通讯作者：
Winquist, JR
DOI：
10.1097/01.chi.0000246065.93200.a1
发表时间：
2007-02-01
影响因子：
13.3
作者：
Baldwin, Jennifer S.;Dadds, Mark R.
通讯作者：
Dadds, Mark R.
影响因子：
11
作者：
Brookes, K.;Xu, X.;Johansson, L.
通讯作者：
Johansson, L.