Do we still believe in the dopamine hypothesis? New data bring new evidence
Do we still believe in the dopamine hypothesis? New data bring new evidence
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DOI：
10.1017/s1461145704004110
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发表时间：
2004-03-01
影响因子：
4.8
通讯作者：
Abi-Dargham, A
中科院分区：
文献类型：
--
作者：
Abi-Dargham, A
精神分裂症的特征是阳性症状、阴性症状和认知障碍。精神分裂症的多巴胺假说假定皮质下多巴胺过量与阳性症状有关。与此同时，精神分裂症的消极和认知症状被认为是由于皮质中多巴胺的不足而引起的。在精神分裂症的大脑皮层下多巴胺过剩和皮层多巴胺赤字的共存的证据。神经受体成像技术，如SPECT和PET，已被用来提供证据。安非他明的挑战（刺激多巴胺释放）后，多巴胺传输显着增加精神分裂症患者的大脑与健康对照组相比。此外，安非他明挑战与精神分裂症阳性症状的增加有关。此外，急性多巴胺耗竭研究表明，与健康对照组相比，精神分裂症患者在基线时多巴胺对D1受体的占用增加。这与精神分裂症中D-2受体过度刺激的概念一致。在大脑皮层中，与对照组相比，精神分裂症患者的多巴胺1型（D-1）受体被发现上调;在背外侧前额叶皮层（一个参与工作记忆的大脑区域），这种增加与n-back任务的表现不佳有关。D-1受体的上调可能代表了皮层多巴胺缺乏的代偿作用。这些发现为精神分裂症患者大脑皮质/皮质下失衡提供了证据。
Schizophrenia is characterized by positive symptoms, negative symptoms and cognitive impairment. The dopamine hypothesis of schizophrenia postulates that an excess of dopamine subcortically is associated with the positive symptoms. At the same time, the negative and cognitive symptoms of schizophrenia are thought to arise from a deficit of dopamine in the cortex. Evidence for the co-existence of subcortical dopamine excess and cortical dopamine deficit in the schizophrenic brain is presented. Neuroreceptor-imaging techniques, such as SPECT and PET, have been used to provide that evidence. After amphetamine challenge (to stimulate dopamine release), dopamine transmission was substantially increased in the brains of schizophrenic subjects compared with healthy controls. In addition, amphetamine challenge was associated with an increase in positive symptoms of schizophrenia. Furthermore, acute dopamine depletion studies indicated that there was an increased occupancy of D, receptors by dopamine at baseline in schizophrenia in comparison with healthy controls. This is consistent with the notion of hyperstimulation of D-2 receptors in schizophrenia. In the cortex, dopamine type-1 (D-1) receptors were found to be upregulated in patients with schizophrenia compared to controls; in the dorsolateral prefrontal cortex, a brain region involved in working memory, this increase correlated with a poor performance on the n-back task. The up-regulation of D-1 receptors may represent a compensatory effect of the dopamine deficit in the cortex. These findings provide evidence for a cortical/subcortical imbalance in the schizophrenic brain.