Schizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of "endogenous" sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and positron emission tomography. Healthy volunteers (n = 28, 14 female) underwent a baseline and then a post-amphetamine scan before and after a mildly sensitizing regimen of repeated oral amphetamine. Unmedicated patients with first-episode psychosis (n = 21; 6 female) underwent a single pair of baseline and then post-amphetamine scans. Furthermore, T1 weighted magnetic resonance imaging of the prefrontal cortex was performed. Patients with first-episode psychosis showed larger release of dopamine compared to healthy volunteers. After sensitization of healthy volunteers their dopamine release was significantly amplified and no longer different from that seen in patients. Healthy volunteers showed a negative correlation between prefrontal cortical volume and dopamine release. There was no such relationship after sensitization or in patients. Our data in patients with untreated first-episode psychosis confirm the "endogenous sensitization" hypothesis and support the notion of impaired prefrontal control of the dopamine system in schizophrenia.

中文翻译：

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关于首发精神病与苯丙胺致敏状态的关系：多巴胺D2 / 3受体激动剂放射性配体研究。

精神分裂症的特征在于对多巴胺释放药物的行为和神经化学反应增加。尽管多巴胺能紊乱的确切基础和前额叶皮质调节的可能作用仍不确定，但这提示了精神病是多巴胺系统“内源性”致敏状态的假说。为了证明患有精神病的首发患者在苯丙胺刺激下比健康志愿者释放出更多的多巴胺，并首次揭示了反复暴露于苯丙胺引起的前瞻性致敏作用使未接受兴奋剂的健康志愿者的多巴胺释放增加到患者所观察到的水平。 ，我们使用多巴胺D2 / 3受体激动剂放射性配体[11C]-（+）-PHNO和正电子发射断层摄影术收集了苯丙胺诱导的多巴胺释放的数据。健康的志愿者（n = 28，14位女性）接受了基线治疗，然后在反复口服安非他明的轻度致敏方案前后进行了安非他命后扫描。未经药物治疗的首发精神病患者（n = 21； 6名女性）接受了单对基线，然后进行了安非他明后扫描。此外，对前额叶皮层进行了T1加权磁共振成像。与健康志愿者相比，首发精神病患者的多巴胺释放量更大。对健康志愿者进行敏化后，他们的多巴胺释放显着增强，与患者所见不再相同。健康的志愿者显示前额叶皮层体积与多巴胺释放之间呈负相关。致敏后或患者中没有这种关系。