Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD
Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD
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DOI：
10.1038/npp.2013.349
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发表时间：
2014-05-01
影响因子：
7.6
通讯作者：
Benkelfat, Chawki
中科院分区：
文献类型：
--
作者：
Cherkasova, Mariya V.;Faridi, Nazlie;Benkelfat, Chawki
来自临床、临床前、神经影像学和遗传学研究的证据表明，多巴胺神经传递与注意缺陷多动障碍（ADHD）的病理生理有关。体内神经受体成像证据也表明ADHD患者多巴胺系统发生改变；然而，它们的性质和行为意义尚未确定。在这里，我们使用[C-II]raclopride PET与d-安非他明刺激研究ADHD的纹状体多巴胺能功能。我们还研究了纹状体多巴胺对ADHD症状和神经认知功能的反应。共有15名无治疗，无合并症的ADHD成年男性（年龄：29.87 +/- 8.65）和18名健康男性对照（年龄：25.44 +/- 6.77）接受了两次PET扫描：一组使用乳糖安慰剂，另一组使用d-安非他明（0.3 mg/kg, p.o），双盲和随机顺序进行各组平衡。在没有药物的单独会议中，参与者进行了一系列神经认知测试。与健康对照组相比，ADHD患者作为一个群体，表现出更大的d-安非他明诱导的纹状体[C-II]氯氯pride结合减少，并且在反应抑制方面表现更差。在各组中，d-安非他明诱导的[I - I - graclopride结合电位的较大程度变化与反应抑制和ADHD症状的较差表现相关。我们的研究结果表明纹状体多巴胺能反应在治疗初期ADHD中增强。虽然与之前的研究结果相反，但这一发现似乎与多动症患者阶段性多巴胺释放过度的模型一致。对增加的阶段性多巴胺反应的易感性可能有助于ADHD的特征，如抑制能力差和冲动。
Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [C-II]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 +/- 8.65) and 18 healthy male controls (age: 25.44 +/- 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [C-II]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [I I graclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.