Xu Chengai, Sellgren Carl M, Fatouros-Bergman Helena, Piehl Fredrik, Blennow Kaj, Zetterberg Henrik, Brinkmalm Ann, Santillo Alexander Frizell, Lundgren Sofia, Cervenka Simon, Engberg Göran, Erhardt Sophie
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm & Stockholm Health Care Services, Stockholm County Council, Sweden.
IBRO Rep. 2020 Apr 13;8:136-142. doi: 10.1016/j.ibror.2020.04.001. eCollection 2020 Jun.
Post-mortem studies consistently show evidence of reduced synaptic protein levels in patients with schizophrenia. Clinically high-risk subjects show a steeper decrease in grey matter thickness and modeling using patient-derived cells implicate excessive synaptic pruning during neurodevelopment as a part of the schizophrenia pathophysiology. However, it is unclear to what extent synapse elimination is present during various stages of the disease, which is of clinical importance as in a real-world setting most subjects received their first-episode psychosis (FEP) diagnosis not until their mid-twenties. In the present study, we measured cerebrospinal fluid (CSF) concentrations of the two pre-synaptic proteins synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT-1), both of which are increased in conditions of ongoing synaptic degeneration, in 44 FEP subjects (mean age 29.9 years) and 21 healthy controls (25.9 years) using immunoprecipitation mass spectrometry. Neither protein was found to differ between healthy controls and patients, and they showed no correlation with symptom ratings, cognitive performance or antipsychotic medication. Additional studies in high-risk subjects in the early prodromal phase will be needed to address if excessive synapse destruction occurs before the development of overt psychotic symptoms.
尸检研究一致表明，精神分裂症患者存在突触蛋白水平降低的证据。临床高危受试者的灰质厚度下降更为明显，使用患者来源细胞进行的建模表明，神经发育过程中过度的突触修剪是精神分裂症病理生理学的一部分。然而，目前尚不清楚在疾病的各个阶段，突触消除的程度如何，这具有临床重要性，因为在现实世界中，大多数患者直到二十多岁才被诊断为首次发作精神病（FEP）。在本研究中，我们使用免疫沉淀质谱法测量了44名FEP受试者（平均年龄29.9岁）和21名健康对照者（25.9岁）脑脊液（CSF）中两种突触前蛋白——突触体相关蛋白25（SNAP-25）和突触结合蛋白-1（SYT-1）的浓度，这两种蛋白在持续的突触退化情况下都会增加。结果发现，健康对照者和患者之间这两种蛋白均无差异，且它们与症状评分、认知表现或抗精神病药物治疗均无相关性。需要对前驱期早期的高危受试者进行更多研究，以确定在明显精神病症状出现之前是否发生了过度的突触破坏。
