Dolan R J, Fletcher P, Frith C D, Friston K J, Frackowiak R S, Grasby P M
Wellcome Department of Cognitive Neurology, Institute of Neurology, Queen Square, London, UK.
Nature. 1995 Nov 9;378(6553):180-2. doi: 10.1038/378180a0.
Dopaminergic dysregulation remains an empirical cornerstone for theories concerning the causation of schizophrenia. Evidence for a dopamine system dysfunction in schizophrenia includes the psychosis-inducing effects of dopaminergic agonists and the antipsychotic potency of dopaminergic antagonists. Here we use positron emission tomography (PET) to examine the regulatory role of dopamine on cortical function in normal subjects and unmedicated schizophrenic patients. Using a factorial experimental design, we compared the effect of dopaminergic manipulation with apomorphine on a neural response to a cognitive task. In the schizophrenic patients, relative to controls, an impaired cognitive activation of the anterior cingulate cortex was significantly modulated by a manipulation of dopaminergic neurotransmission. Thus, after apomorphine, the schizophrenic subjects displayed a significantly enhanced cognitive activation of the anterior cingulate cortex relative to the controls. These data provide in vivo evidence that an impaired cognitive-task-induced activation of the anterior cingulate cortex in schizophrenic patients can be significantly modulated by a dopaminergic manipulation.
多巴胺能调节异常仍然是有关精神分裂症病因理论的一个经验基石。精神分裂症中多巴胺系统功能障碍的证据包括多巴胺能激动剂的致精神病效应以及多巴胺能拮抗剂的抗精神病效力。在此，我们使用正电子发射断层扫描（PET）来研究多巴胺对正常受试者和未用药的精神分裂症患者皮质功能的调节作用。采用析因实验设计，我们比较了用阿扑吗啡进行多巴胺能操作对认知任务神经反应的影响。在精神分裂症患者中，相对于对照组，多巴胺能神经传递的操作显著调节了前扣带回皮质受损的认知激活。因此，在使用阿扑吗啡后，精神分裂症受试者相对于对照组在前扣带回皮质表现出显著增强的认知激活。这些数据提供了体内证据，表明精神分裂症患者认知任务诱导的前扣带回皮质激活受损可通过多巴胺能操作得到显著调节。
