Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine.
Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine.
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DOI：
10.1097/fbp.0000000000000116
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发表时间：
2015-02
影响因子：
1.6
通讯作者：
Cools R
中科院分区：
文献类型：
--
作者：
Aarts E;van Holstein M;Hoogman M;Onnink M;Kan C;Franke B;Buitelaar J;Cools R
注意力缺陷/多动障碍 (ADHD) 伴有认知控制障碍，例如任务切换缺陷。我们研究了这些问题及其药物治疗是否反映了 ADHD 中异常的奖励动机和相关的纹状体多巴胺传递。我们使用功能遗传神经影像学来评估多巴胺能药物和奖励动机对 23 名患有 ADHD 的成人、服用哌甲酯和停用哌醋甲酯以及 26 名健康对照者的任务转换和纹状体 BOLD 信号的影响。至关重要的是，我们通过利用编码多巴胺转运蛋白的 DAT1 基因中的常见遗传多态性 (3'-UTR VNTR) 考虑了纹状体多巴胺的个体间变异。结果显示，纹状体中基因型相互作用存在高度显着的群体。这是因为 ADHD 患者的一个亚组在停止使用多巴胺能药物时，在任务切换过程中奖励对纹状体 BOLD 信号的影响明显夸大。具体来说，携带 9R 等位基因的患者比携带该等位基因的健康对照显示出更强的纹状体信号，而在 10R 纯合子中没有观察到诊断效果。当携带 9R 的 ADHD 患者接受药物治疗时，异常纹状体反应正常化。这些试验数据表明，异常奖励动机、纹状体多巴胺和个体间遗传差异在成人多动症认知过程中发挥着重要作用。
Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3′-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD.