Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis, but this has not been tested directly in vivo. Here, we investigated synaptic vesicle glycoprotein 2A (SV2A) levels and their relationship to symptoms and structural brain measures using [11C]UCB-J positron emission tomography in 18 patients with schizophrenia and 18 controls. We found significant group and group-by-region interaction effects on volume of distribution (VT). [11C]UCB-J VT was significantly lower in the frontal and anterior cingulate cortices in schizophrenia with large effect sizes (Cohen's d = 0.8-0.9), but there was no significant difference in the hippocampus. We also investigated the effects of antipsychotic drug administration on SV2A levels in Sprague-Dawley rats using western blotting, [3H]UCB-J autoradiography and immunostaining with confocal microscopy, finding no significant effects on any measure. These findings indicate that there are lower synaptic terminal protein levels in schizophrenia in vivo and that antipsychotic drug exposure is unlikely to account for them.

中文翻译：

---

精神分裂症患者的突触密度标记 SV2A 降低，但大鼠中不受抗精神病药物的影响。

假设突触功能障碍在精神分裂症发病机制中发挥关键作用，但这尚未在体内进行直接测试。在这里，我们使用 [11C]UCB-J 正电子发射断层扫描技术，研究了 18 名精神分裂症患者和 18 名对照者的突触小泡糖蛋白 2A (SV2A) 水平及其与症状和大脑结构测量的关系。我们发现群体和群体与区域之间的相互作用对分布容积（VT）有显着的影响。[11C]UCB-J VT 在精神分裂症患者的额叶和前扣带皮层中显着降低，效应大小较大（Cohen's d = 0.8-0.9），但在海马中没有显着差异。我们还使用蛋白质印迹、[3H]UCB-J 放射自显影和共聚焦显微镜免疫染色研究了抗精神病药物给药对 Sprague-Dawley 大鼠 SV2A 水平的影响，发现对任何测量都没有显着影响。这些发现表明，精神分裂症患者体内的突触末端蛋白水平较低，而抗精神病药物暴露不太可能是其原因。