Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807, USA.
Synapse. 2012 Apr;66(4):352-68. doi: 10.1002/syn.21520. Epub 2011 Dec 29.
Utilizing postmortem data (Breese et al. [2000] Neuropsychopharmacology 23:351-364), we hypothesized that the densities of high-affinity neuronal α4β2 nicotinic acetylcholine receptors (nAChRs) in the brain exist in a continuum from highest to lowest as follows: smokers without schizophrenia > smokers with schizophrenia > nonsmokers without schizophrenia > nonsmokers with schizophrenia. Application of the Kruskal-Wallis Test (Statacorp, 2003) to the postmortem data (Breese et al. [2000] Neuropsychopharmacology 23:351-364) confirmed the hypothesized order in the cortex and the hippocampus and attained significance in the caudate and the thalamus. Positron emission tomography (PET) was performed for 60 min at 6 h after the intravenous administration of 444 megabequerels [MBq] (12 mCi) 2-[¹⁸F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[¹⁸F]FA), a radiotracer for high-affinity neuronal α4β2 nAChRs, as a bolus plus continuous infusion to 10 adults (seven men and three women) (six smokers including five with paranoid schizophrenia and four nonsmokers) ranging in age from 22 to 56 years (mean 40.1, standard deviation 13.6). The thalamic nondisplaceable binding potential (BP(ND) ) was 1.32 ± 0.19 (mean ± standard deviation) for healthy control nonsmokers; 0.50 ± 0.19 for smokers with paranoid schizophrenia; and 0.51 for the single smoker without paranoid schizophrenia. The thalamic BP(ND) s of nonsmokers were significantly higher than those of smokers who smoked cigarettes a few hours before the scans (P = 0.0105) (StataCorp, 2003), which was likely due to occupancy of nAChRs by inhaled nicotine in smokers. Further research is needed to rule out the effects of confounding variables.
利用尸检数据（Breese 等人，[2000]Neuropsychopharmacology 23:351-364），我们假设大脑中高亲和力神经元α4β2 烟碱型乙酰胆碱受体（nAChR）的密度从最高到最低呈连续分布，具体如下：无精神分裂症的吸烟者>有精神分裂症的吸烟者>无精神分裂症的不吸烟者>有精神分裂症的不吸烟者。Kruskal-Wallis 检验（Statacorp，2003）应用于尸检数据（Breese 等人，[2000]Neuropsychopharmacology 23:351-364）证实了皮质和海马中假设的顺序，并在尾状核和丘脑达到了显著水平。在静脉注射 444 兆贝克勒尔（MBq）（12 毫居里）2-[¹⁸F]氟-3-（2(S)-氮杂环丁烷甲氧基）吡啶（2-[¹⁸F]FA）6 小时后，对 10 名成年人（7 名男性和 3 名女性）（包括 5 名偏执型精神分裂症患者的 6 名吸烟者和 4 名不吸烟者）进行了 60 分钟的正电子发射断层扫描（PET），这是一种用于高亲和力神经元α4β2 nAChR 的放射性示踪剂，以推注加连续输注的方式进行。年龄从 22 岁到 56 岁不等（平均 40.1，标准差 13.6）。健康对照不吸烟者的丘脑不可置换结合潜能（BP(ND)）为 1.32±0.19（平均值±标准差）；偏执型精神分裂症患者的吸烟者为 0.50±0.19；而唯一一位没有偏执型精神分裂症的吸烟者为 0.51。不吸烟者的丘脑 BP(ND)明显高于扫描前几小时吸烟的吸烟者（P=0.0105）（StataCorp，2003），这可能是由于吸烟者吸入的尼古丁占据了 nAChR。需要进一步的研究来排除混杂变量的影响。
