PET Centre, Centre for Addiction and Mental Health, Toronto, Ont.
J Psychiatry Neurosci. 2013 Mar;38(2):98-106. doi: 10.1503/jpn.110181.
The dopamine (DA) D2 receptors exist in 2 states: a high-affinity state (D2 high) that is linked to second messenger systems, responsible for functional effects, exhibits high affinity for agonists (e.g., DA), and a low-affinity state that is functionally inert exhibits lower affinity for agonists. The DA D3 receptor subtype exhibits high agonist affinity, whereas the existence of the multiple affinity states is controversial. Preclinical studies in animal models of psychosis have shown a selective increase of D2 high as the common factor in psychosis, and the D3 receptor has been suggested to be involved in the pathophysiology of schizophrenia.
We studied D2 high and D3 in people at clinical high risk (CHR) for schizophrenia and in antipsychotic-naive patients with schizophrenia using the novel positron emission tomography radiotracer, [11C]-(+)-PHNO. The binding potential nondisplaceable (BP(ND)) was examined in the regions of interest (ROI; caudate, putamen, ventral striatum, globus pallidus, substantia nigra and thalamus) using an ROI and a voxel-wise approach while participants performed a cognitive task.
We recruited 12 CHR individuals and 13 antipsychotic-naive patients with schizophrenia-spectrum disorder, whom we compared with 12 age- and sex-matched healthy controls. The BP(ND) between patients and controls did not differ in any of the ROIs, consistent with the voxel-wise analysis. Correlations between the BP(ND) in D3-rich regions and psychopathology warrant further investigation.
In the absence of resting-state (baseline) BP(ND) data, or following a depletion paradigm (i.e., α-methyl partyrosine), it is not possible to ascertain whether the lack of difference among the groups is owing to different levels of baseline DA or to release during the cognitive task.
To our knowledge, the present study represents the first effort to measure the D2 and D3 receptors under a cognitive challenge in individuals putative/prodromal for schizophrenia using [11C]-(+)-PHNO.
多巴胺（DA）D2 受体存在两种状态：一种是与第二信使系统相关的高亲和力状态（D2 高），负责功能效应，对激动剂（如 DA）具有高亲和力，另一种是无功能的低亲和力状态，对激动剂的亲和力较低。DA D3 受体亚型表现出高激动剂亲和力，而多种亲和力状态的存在存在争议。精神分裂症动物模型的临床前研究表明，D2 高选择性增加是精神分裂症的共同因素，D3 受体可能与精神分裂症的病理生理学有关。
我们使用新型正电子发射断层扫描示踪剂[11C] -（+）- PHNO 研究了处于精神分裂症临床高风险（CHR）的人群和未经抗精神病药物治疗的精神分裂症患者的 D2 高和 D3。使用 ROI 和体素方法，在参与者执行认知任务时，在 ROI（尾状核、壳核、腹侧纹状体、苍白球、黑质和丘脑）中检查不可置换结合势（BP（ND））。
我们招募了 12 名 CHR 个体和 13 名未经抗精神病药物治疗的精神分裂症谱系障碍患者，并将其与 12 名年龄和性别匹配的健康对照者进行比较。在任何 ROI 中，患者和对照组之间的 BP（ND）均无差异，与体素分析一致。D3 丰富区域的 BP（ND）与精神病理学之间的相关性需要进一步研究。
在没有静息状态（基线）BP（ND）数据或进行耗竭范式（即α-甲基苯丙氨酸）的情况下，无法确定各组之间的差异是由于基础 DA 水平不同还是由于认知任务期间的释放所致。
据我们所知，本研究首次使用[11C] -（+）- PHNO 在假定/前驱精神分裂症个体中，在认知挑战下测量 D2 和 D3 受体。
