Krause Johanna
Expert Rev Neurother. 2008 Apr;8(4):611-25. doi: 10.1586/14737175.8.4.611.
Abnormalities of frontostriatal circuits, which are modulated by dopamine, have been found by brain imaging studies in patients with attention-deficit/hyperactivity disorder (ADHD). With special radiolabeled ligands selective imaging of the dopamine transporter (DAT), which has a key function in dopamine metabolism, can be performed by SPECT and PET. Most of the studies showed a higher DAT availability in untreated patients with ADHD compared with controls. The relationship between DAT availability and a polymorphism of DAT1 gene in patients with ADHD is not clear and the results are controversial. It has been shown that methylphenidate lowers DAT availability very effectively in normal people and in patients with ADHD. First results seem to indicate that nonresponders to methylphenidate among ADHD patients have a low primary DAT availability, whereas patients with a good response to the drug have high DAT. Nicotine seems to lower DAT availability such as stimulant medication; this may explain the high percentage of smokers among patients with ADHD. Zinc is a DAT inhibitor and seems to have a positive therapeutic effect on ADHD symptoms. This article reviews the function and structure of the DAT, the results of DAT imaging with SPECT and PET, the relations between DAT availability and the DAT1 gene polymorphism, the influence of stimulants on DAT and the significance of DAT for therapeutic response, nicotine, zinc and psychotic symptoms in patients with ADHD.
脑成像研究发现,注意缺陷多动障碍(ADHD)患者存在受多巴胺调节的额纹状体回路异常。利用特殊的放射性标记配体,可通过单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET)对在多巴胺代谢中起关键作用的多巴胺转运体(DAT)进行选择性成像。大多数研究表明,未经治疗的ADHD患者的DAT可用性高于对照组。ADHD患者中DAT可用性与DAT1基因多态性之间的关系尚不清楚,结果存在争议。已表明哌甲酯能非常有效地降低正常人及ADHD患者的DAT可用性。初步结果似乎表明,ADHD患者中对哌甲酯无反应者的初始DAT可用性较低,而对该药反应良好的患者DAT可用性较高。尼古丁似乎能像刺激性药物一样降低DAT可用性;这可能解释了ADHD患者中吸烟者的高比例。锌是一种DAT抑制剂,似乎对ADHD症状有积极的治疗作用。本文综述了DAT的功能和结构、SPECT和PET对DAT成像的结果、DAT可用性与DAT1基因多态性的关系、兴奋剂对DAT的影响以及DAT对ADHD患者治疗反应、尼古丁、锌和精神症状的意义。