Karlsson Per, Farde Lars, Halldin Christer, Sedvall Göran
Department of Clinical Neuroscience, Karlinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Am J Psychiatry. 2002 May;159(5):761-7. doi: 10.1176/appi.ajp.159.5.761.
Postmortem studies and a positron emission tomography (PET) study have suggested that there is a disturbance of central D(1) dopamine receptor function in schizophrenia. The objective of the present PET study was to compare D(1) receptor binding in first-admission, neuroleptic-naive patients with schizophrenia and in healthy subjects.
Ten healthy comparison subjects and 10 neuroleptic-naive patients with schizophrenia (diagnosed according to DSM-III-R) were examined twice by PET using (11)C-labeled SCH 23390 ([(11)C]SCH 23390) with high and low specific radioactivity, respectively. The binding potential, receptor density (B(max)), and affinity (K(d)) were determined for the caudate nucleus, the putamen, and several neocortical regions during both PET examinations. Scatchard plots from the two measurements were used to calculate regional D(1) B(max) and K(d). The regional binding values were tested for hemispheric asymmetry and for correlation to clinical symptoms measured by the Brief Psychiatric Rating Scale (BPRS).
[(11)C]SCH 23390 binding to D(1) receptors did not differ significantly between subjects with schizophrenia and healthy subjects in any of the brain regions or for any of the binding measures studied. Asymmetry of the regional binding values did not differ significantly between the two groups. Scores on the BPRS negative symptom subscale correlated significantly with the B(max) in the right frontal cortex.
These results do not replicate previous postmortem and PET findings of altered central dopamine D(1) receptor binding in schizophrenia. The finding of a positive correlation between frontal D(1) binding and scores on the negative symptom subscale of the BPRS is contrary to a previously reported finding of a negative correlation. These discrepancies motivate further studies using D(1) ligands with higher signals for cortical regions.
尸检研究和一项正电子发射断层扫描(PET)研究表明,精神分裂症患者存在中枢D(1)多巴胺受体功能紊乱。本PET研究的目的是比较首次入院、未服用抗精神病药物的精神分裂症患者与健康受试者的D(1)受体结合情况。
10名健康对照受试者和10名未服用抗精神病药物的精神分裂症患者(根据DSM-III-R诊断)分别使用高比活度和低比活度的(11)C标记的SCH 23390([(11)C]SCH 23390)进行两次PET检查。在两次PET检查期间,测定尾状核、壳核和几个新皮质区域的结合潜能、受体密度(B(max))和亲和力(K(d))。利用两次测量的Scatchard图计算区域D(1) B(max)和K(d)。对区域结合值进行半球不对称性测试,并与简明精神病评定量表(BPRS)测量的临床症状进行相关性分析。
在任何脑区或所研究的任何结合指标方面,精神分裂症患者与健康受试者之间[(11)C]SCH 23390与D(1)受体的结合均无显著差异。两组之间区域结合值的不对称性无显著差异。BPRS阴性症状分量表得分与右侧额叶皮质的B(max)显著相关。
这些结果并未重复先前尸检和PET研究中关于精神分裂症患者中枢多巴胺D(1)受体结合改变的发现。额叶D(1)结合与BPRS阴性症状分量表得分呈正相关的发现与先前报道的负相关发现相反。这些差异促使人们使用对皮质区域具有更高信号的D(1)配体进行进一步研究。