Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan; Department of Psychiatry, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan; Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Radiology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Int J Neuropsychopharmacol. 2017 Nov 1;20(11):928-935. doi: 10.1093/ijnp/pyx063.
Dopamine D2 receptors are reported to have high-affinity (D2High) and low-affinity (D2Low) states. Although an increased proportion of D2High has been demonstrated in animal models of schizophrenia, few clinical studies have investigated this alteration of D2High in schizophrenia in vivo.
Eleven patients with schizophrenia, including 10 antipsychotic-naive and 1 antipsychotic-free individuals, and 17 healthy controls were investigated. Psychopathology was assessed by Positive and Negative Syndrome Scale, and a 5-factor model was used. Two radioligands, [11C]raclopride and [11C]MNPA, were employed to quantify total dopamine D2 receptor and D2High, respectively, in the striatum by measuring their binding potentials. Binding potential values of [11C]raclopride and [11C]MNPA and the binding potential ratio of [11C]MNPA to [11C]raclopride in the striatal subregions were statistically compared between the 2 diagnostic groups using multivariate analysis of covariance controlling for age, gender, and smoking. Correlations between binding potential and Positive and Negative Syndrome Scale scores were also examined.
Multivariate analysis of covariance demonstrated a significant effect of diagnosis (schizophrenia and control) on the binding potential ratio (P=.018), although the effects of diagnosis on binding potential values obtained with either [11C]raclopride or [11C]MNPA were nonsignificant. Posthoc test showed that the binding potential ratio was significantly higher in the putamen of patients (P=.017). The Positive and Negative Syndrome Scale "depressed" factor in patients was positively correlated with binding potential values of both ligands in the caudate.
The present study indicates the possibilities of: (1) a higher proportion of D2High in the putamen despite unaltered amounts of total dopamine D2 receptors; and (2) associations between depressive symptoms and amounts of caudate dopamine D2 receptors in patients with schizophrenia.
多巴胺 D2 受体被报道存在高亲和力（D2High）和低亲和力（D2Low）状态。尽管在精神分裂症的动物模型中已经证明了 D2High 的比例增加，但很少有临床研究调查过这种 D2High 在精神分裂症体内的改变。
研究了 11 名精神分裂症患者，包括 10 名未接受抗精神病药物治疗的患者和 1 名未接受抗精神病药物治疗的患者，以及 17 名健康对照者。采用阳性和阴性综合征量表（Positive and Negative Syndrome Scale）评估精神病理学，并采用 5 因素模型进行评估。采用[11C]raclopride 和[11C]MNPA 两种放射性配体，分别通过测量其结合潜能来定量纹状体中的总多巴胺 D2 受体和 D2High。使用多元协方差分析控制年龄、性别和吸烟因素，对两组诊断患者的纹状体亚区[11C]raclopride 和[11C]MNPA 的结合潜能值和[11C]MNPA 与[11C]raclopride 的结合潜能比值进行统计学比较。还检查了结合潜能与阳性和阴性综合征量表评分之间的相关性。
多元协方差分析显示，诊断（精神分裂症和对照组）对结合潜能比值有显著影响（P=.018），尽管诊断对[11C]raclopride 或[11C]MNPA 获得的结合潜能值的影响无统计学意义。事后检验显示，患者的纹状体中结合潜能比值显著升高（P=.017）。患者的阳性和阴性综合征量表“抑郁”因子与尾状核中两种配体的结合潜能值呈正相关。
本研究表明：（1）尽管总多巴胺 D2 受体数量不变，但壳核中 D2High 的比例可能更高；（2）精神分裂症患者的抑郁症状与尾状核多巴胺 D2 受体数量之间存在关联。
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