Department of Psychiatry, NYU Langone Medical Center, New York, New York.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biol Psychiatry. 2022 Nov 15;92(10):791-799. doi: 10.1016/j.biopsych.2022.05.009. Epub 2022 May 14.
The dopamine (DA) hypothesis postulates hyperactivity of subcortical DA transmission and hypoactivity of cortical DA in schizophrenia (SCH). Positron emission tomography provides the ability to assess this hypothesis in humans. However, no studies have examined the relationship between cortical DA and striatal DA in this illness.
D receptor radiotracer [C]FLB457 BP (binding potential relative to nondisplaceable uptake) was measured in 14 off-medication subjects with SCH and 14 healthy control (HC) subjects at baseline and after the administration of 0.5 mg/kg oral d-amphetamine. The amphetamine-induced change in BP (ΔBP) was calculated as the difference between BP in the postamphetamine condition and BP in the baseline condition and expressed as a percentage of BP at baseline. DA release in the striatum using the radiotracer [C]NPA was also measured in these subjects.
[C]FLB457 ΔBP was greater in the HC group compared with the SCH group (F = 5.7; p = .02) with significant differences in [C]FLB457 ΔBP seen across cortical brain regions. Only in the SCH group was a significant negative correlation observed between [C]FLB457 ΔBP in the dorsolateral prefrontal cortex and [C]NPA ΔBP in the dorsal caudate (r = -0.71, p = .005).
Subjects with SCH demonstrated deficits of DA release in cortical brain regions relative to HC subjects. Examining both cortical and striatal DA release in the same subjects demonstrated an inverse relationship between cortical DA release and striatal DA release in SCH not present in HC subjects, providing support for the current DA hypothesis of SCH.
多巴胺（DA）假说提出精神分裂症（SCH）患者的皮质下 DA 传递过度活跃，皮质 DA 传递活动不足。正电子发射断层扫描（PET）提供了在人类中评估该假说的能力。然而，目前尚无研究检查该疾病中皮质 DA 与纹状体 DA 之间的关系。
在基线和 0.5mg/kg 口服 d-苯丙胺给药后，测量 14 名未服药的 SCH 患者和 14 名健康对照（HC）患者的 D 受体放射性示踪剂 [C]FLB457 BP（与不可置换摄取相比的结合潜能）。通过计算 [C]FLB457 BP 在苯丙胺后条件下的 BP 与基线条件下的 BP 之间的差异来计算 BP 的变化（ΔBP），并表示为基线 BP 的百分比。还在这些受试者中使用放射性示踪剂 [C]NPA 测量纹状体中的 DA 释放。
与 SCH 组相比，HC 组的 [C]FLB457 ΔBP 更大（F=5.7；p=0.02），皮质脑区之间存在显著差异。仅在 SCH 组中，背外侧前额叶皮质的 [C]FLB457 ΔBP 与背侧尾状核的 [C]FLB457 ΔBP 之间观察到显著的负相关（r=-0.71，p=0.005）。
与 HC 受试者相比，SCH 患者的皮质脑区 DA 释放存在缺陷。在相同受试者中同时检查皮质和纹状体 DA 释放，显示 SCH 患者中皮质 DA 释放与纹状体 DA 释放之间呈负相关，而 HC 患者中则不存在这种关系，这为 SCH 的当前 DA 假说提供了支持。
