Meyer-Lindenberg Andreas, Miletich Robert S, Kohn Philip D, Esposito Giuseppe, Carson Richard E, Quarantelli Mario, Weinberger Daniel R, Berman Karen Faith
Unit on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, 10-4C101, 9000 Rockville Pike, Bethesda, Maryland 20892-1365, USA.
Nat Neurosci. 2002 Mar;5(3):267-71. doi: 10.1038/nn804.
Both dopaminergic neurotransmission and prefrontal cortex (PFC) function are known to be abnormal in schizophrenia. To test the hypothesis that these phenomena are related, we measured presynaptic dopaminergic function simultaneously with regional cerebral blood flow during the Wisconsin Card Sorting Test (WCST) and a control task in unmedicated schizophrenic subjects and matched controls. We show that the dopaminergic uptake constant Ki in the striatum was significantly higher for patients than for controls. Patients had significantly less WCST-related activation in PFC. The two parameters were strongly linked in patients, but not controls. The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.
已知多巴胺能神经传递和前额叶皮质(PFC)功能在精神分裂症中均存在异常。为了验证这些现象相关的假说,我们在威斯康星卡片分类测试(WCST)及一项对照任务期间,对未用药的精神分裂症患者及匹配的对照者,同时测量了突触前多巴胺能功能及局部脑血流量。我们发现,患者纹状体中的多巴胺能摄取常数Ki显著高于对照者。患者PFC中与WCST相关的激活明显较少。在患者中这两个参数紧密相关,而在对照者中则不然。这些值在患者体内紧密相关,PFC激活减少预示着纹状体6-氟多巴摄取增加,这支持了前额叶皮质功能障碍可能导致多巴胺能传递异常的假说。