Glantz L A, Lewis D A
Department of Neuroscience, University of Pittsburgh, Pa., USA.
Arch Gen Psychiatry. 1997 Oct;54(10):943-52. doi: 10.1001/archpsyc.1997.01830220065010.
Multiple lines of evidence indicate that the prefrontal cortex is a site of dysfunction in schizophrenia. However, the apparent absence of gross structural abnormalities in this area suggests that the pathophysiological characteristics of schizophrenia may involve more subtle disturbances in prefrontal cortical circuitry, such as alterations in synaptic connectivity and transmission. In this study, immunoreactivity for synaptophysin, an integral membrane protein of small synaptic vesicles, was used to assess the integrity of cortical synaptic circuitry in schizophrenia.
Using immunocytochemical techniques and adjusted optical density measurements, we examined synaptophysin immunoreactivity in prefrontal cortical areas 9 and 46 and in area 17 (the primary visual cortex) from 10 pairs of case subjects with schizophrenia and control subjects matched on a pairwise basis for age, sex, race, and postmortem interval, and in 5 matched pairs of nonschizophrenic psychiatric case subjects and normal control subjects.
Compared with levels found in matched control subjects, synaptophysin immunoreactivity in areas 46 and 9 was significantly decreased (P < .001 and P < .008, respectively) across all cortical layers in the case subjects with schizophrenia. In contrast, no differences were observed in area 17. In addition, levels of synaptophysin immunoreactivity in areas 46, 9, and 17 did not differ between 5 nonschizophrenic psychiatric case subjects and their matched controls, suggesting that decreased synaptophysin levels in the prefrontal cortex of patients with schizophrenia may be specific to that disorder.
Additional studies are required to determine if the decrease in levels of synaptophysin immunoreactivity is caused by a decrease in the number or size of presynaptic terminals, a decrease in the number of synaptic vesicles per terminal, or a decrease in the expression of synaptophysin. However, all of these potential explanations are consistent with a disturbance in synaptic transmission in the prefrontal cortex of patients with schizophrenia.
多项证据表明，前额叶皮质是精神分裂症功能障碍的一个部位。然而，该区域明显没有明显的结构异常，这表明精神分裂症的病理生理特征可能涉及前额叶皮质回路中更细微的紊乱，如突触连接和传递的改变。在本研究中，使用小突触囊泡的整合膜蛋白突触素的免疫反应性来评估精神分裂症患者皮质突触回路的完整性。
采用免疫细胞化学技术和调整后的光密度测量方法，我们检查了10对精神分裂症病例受试者和按年龄、性别、种族和死后间隔进行配对的对照受试者的前额叶皮质9区和46区以及17区（初级视觉皮质）中的突触素免疫反应性，以及5对匹配的非精神分裂症精神病例受试者和正常对照受试者。
与匹配的对照受试者相比，精神分裂症病例受试者所有皮质层中46区和9区的突触素免疫反应性显著降低（分别为P <.001和P <.008）。相比之下，17区未观察到差异。此外，5名非精神分裂症精神病例受试者及其匹配对照之间46区、9区和17区的突触素免疫反应性水平没有差异，这表明精神分裂症患者前额叶皮质中突触素水平的降低可能是该疾病所特有的。
需要进一步的研究来确定突触素免疫反应性水平的降低是由突触前终末数量或大小的减少、每个终末突触囊泡数量的减少还是突触素表达的减少引起的。然而，所有这些潜在的解释都与精神分裂症患者前额叶皮质中突触传递的紊乱一致。
