Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies
Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies
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DOI：
10.1177/026988119901300405
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发表时间：
1999-12-01
影响因子：
4.1
通讯作者：
Abi-Dargham, P
中科院分区：
文献类型：
--
作者：
Laruelle, M;Abi-Dargham, P
抗精神病药物的抗多巴胺能特性提示精神分裂症患者多巴胺功能的缺失。然而，直接证据表明，高多巴胺能状态的精神分裂症一直难以证明，考虑到难以测量多巴胺传输的生活中的人。个脑袋这种情况正在迅速改变。正电子发射断层扫描和单光子发射断层扫描技术的最新发展使测量突触多巴胺的急性波动。D-2受体附近。使用这种技术，我们和其他人测量了未经治疗的精神分裂症患者和匹配的健康受试者在急性安非他明激发后多巴胺传递的增加。在简要概述这些新的脑成像技术之后，描述了用这种方法在精神分裂症患者中获得的主要结果：（1）安非他明诱导的多巴胺释放在精神分裂症患者中升高，支持精神分裂症与多巴胺传递失调有关的观点;（2）安非他明后，多巴胺传递过度活跃与精神病性痴呆症的激活有关;（3）这种多巴胺释放的失调不是先前精神抑制剂治疗的长期后果，并且在经历疾病的第一次发作的从未用药的患者中检测到;和（4）相反，在疾病稳定期研究的患者中没有检测到多巴胺系统对安非他明暴露的这种夸大的反应，提示与精神分裂症相关的多巴胺能亢进状态随时间波动。总之，高多巴胺能状态可能存在于精神分裂症在首次发作和随后的复发，但不是在缓解期。这一发现对开发新的治疗方法和缓解期策略具有重要意义。
Abnormalities of dopamine function in schizophrenia are suggested by the common antidopaminergic properties of antipsychotic medications. However, direct evidence of a hyperdopaminergic state in schizophrenia has been difficult to demonstrate, given the difficulty of measuring dopamine transmission in the living human. brain. This situation is rapidly changing. Recent developments in positron emission tomography and single-photon emission tomographic techniques enabled measurement of acute fluctuation of synaptic dopamine in. the vicinity of D-2 receptors. Using this technique, we, and others, measured the increase in dopamine transmission following acute amphetamine challenge in untreated patients with schizophrenia and matched healthy subjects. Following a brief overview of these new brain imaging techniques, the main results derived with this method in patients with schizophrenia are described: (1) amphetamine-induced dopamine release is elevated in patients with schizophrenia, supporting the idea that schizophrenia is associated with dysregulation of dopamine transmission; (2) following amphetamine, hyperactivity of dopamine transmission is associated with activation of psychotic symptomatology; (3) this dysregulation of dopamine release is not a long-term consequence of previous neuroleptic treatment, and is detected in never-medicated patients experiencing a first episode of the illness; and (4) in contrast, this exaggerated response of the dopamine system to amphetamine exposure is not detected in patients studied during a period of illness stabilization, suggesting that the hyperdopaminergic state associated with schizophrenia fluctuates over time. In conclusion, a hyperdopaminergic state might be present in schizophrenia during the initial episode and subsequent relapses, but not during periods of remission. This finding has important consequences for the development of new treatment, strategies for the remission phase.