Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
PET Science Centre, Precision Medicine, R&D Oncology, AstraZeneca, Karolinska Institutet, Sweden.
Int J Neuropsychopharmacol. 2019 Jul 1;22(7):415-425. doi: 10.1093/ijnp/pyz017.
Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs.
Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390.
We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum.
This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.
使用正电子发射断层扫描研究检查健康对照者和精神分裂症患者之间 D1-多巴胺受体结合的差异,报告结果为额叶皮质中 D1-多巴胺受体结合更高、更低或没有差异。抗精神病药物的暴露被认为是这种异质性的一个可能来源,因此需要对未接触此类药物的疾病早期患者进行研究。
在这里,我们使用正电子发射断层扫描和 D1-多巴胺受体放射性配体 [11C]SCH23390 比较了 17 名健康对照者和 18 名首发未经神经阻滞剂治疗的精神分裂症或分裂情感性精神病患者。
我们观察到背外侧前额叶皮质存在统计学显著差异。与我们的预期相反,患者的 D1-多巴胺受体可用性减少,具有中等效应大小。在贝叶斯分析中,我们表明数据更有可能是在减少假设下发生的,而不是在增加假设下发生的。这种效应不是全球性的,因为我们的分析表明,在纹状体中,零假设比任何假设都更受青睐。
这项研究代表了使用 PET 检查未经神经阻滞剂治疗的患者的 D1-多巴胺受体可用性的最大单一样本研究,表明精神分裂症的病理生理学中存在前额叶 D1-多巴胺受体密度降低。然而,需要进一步的工作来达成共识。