Increased prefrontal cortical D1 receptors in drug naive patients with schizophrenia: a PET study with [11C]NNC112
Increased prefrontal cortical D1 receptors in drug naive patients with schizophrenia: a PET study with [11C]NNC112
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DOI：
10.1177/0269881111409265
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发表时间：
2012-06-01
影响因子：
4.1
通讯作者：
Slifstein, Mark
中科院分区：
文献类型：
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作者：
Abi-Dargham, Anissa;Xu, Xiaoyan;Slifstein, Mark
D-1受体是多巴胺在大脑皮层传递的主要媒介，并为精神分裂症患者的认知功能提供支持。先前的影像学研究表明，在精神分裂症中这些受体的表达异常，但尚未出现结论性的图像。差异的一个来源可能是先前的抗精神病药物暴露。我们使用正电子发射断层扫描（PET）和D-1示踪剂[C-11]NNC112对未接受药物治疗（DN, n = 12）和未接受药物治疗（DF, n = 13）的精神分裂症患者以及40名年龄、性别、种族、父母社会经济状况和吸烟情况相匹配的健康对照组（HC，总n = 40，每个对照组n = 24）进行检测。我们测量了结合电位BPP，修正了部分体积效应。结果测量是在皮质和纹状体亚区中获得的，这些亚区是在共同登记的个体mri上勾画出来的。部分体积效应校正的BPP测量结果在DN中明显高于皮质区对照组。在DF组与对照组的比较中没有发现这种增加。DF组DF间期与皮质BPP呈正相关。我们得出结论，精神分裂症中D-1受体的上调与疾病本身有关，并可能通过慢性抗精神病药物治疗得到纠正和正常化。
D-1 receptors are the main mediators of dopamine transmission in the cortex and subserve cognitive functions that are affected in patients with schizophrenia. Prior imaging studies have suggested abnormalities in the expression of these receptors in schizophrenia, but no conclusive picture has emerged yet. One source of discrepancy may have been prior antipsychotic exposure. We used positron emission tomography (PET) and a D-1 radiotracer, [C-11]NNC112, in drug naive (DN, n = 12) and drug free (DF, n = 13) patients with schizophrenia and 40 healthy control subjects (HC, n = 40 total, n = 24 per comparison group) matched for age, gender, ethnicity, parental socioeconomic status and cigarette smoking. We measured the binding potential BPP, corrected for partial volume effects. The outcome measure was obtained in cortical and striatal subregions outlined on coregistered individual MRIs. Partial volume effect corrected BPP measures were significantly higher in DN vs controls in cortical regions. No such increases were found in the DF versus controls comparison. Furthermore, in the DF group, DF interval correlated positively with cortical BPP. We conclude that upregulation of D-1 receptors in schizophrenia is related to the illness itself and may be corrected and normalized by chronic antipsychotic treatment.