<摘要Text标签=\"背景\">已经提出,大脑中特定蛋白质的聚集可能是精神分裂症和其他慢性疾病的病理因素。现在已经通过验尸调查发现了多种这样的聚集蛋白,包括NPAS3(神经元PAS结构域蛋白3),dysbindin-1(由DTNBP1,Dystrobrevin结合蛋白1,基因编码)和TRIOBP(三结合蛋白,多个同工型)。虽然大脑中蛋白质聚集体的存在在理解病理学方面很有趣,作为生物标志物是不切实际的。因此,最近在精神分裂症患者和对照组的血清中研究了这些蛋白质,显示患者通常血清中NPAS3水平较高。TRIOBP-1和异常结合蛋白-1也处于不可溶状态,暗示聚集,但没有明确对应于疾病状态。
主题和方法:我们重新审视了最初招募的50名精神分裂症患者中的47名,他们都是克罗地亚人,年龄在18至72岁之间。我们使用PANSS(阳性和阴性症状量表)评估其症状特异性和严重程度,将血清中具有NPAS3,不溶性抗结合蛋白-1和/或不溶性TRIOBP-1的那些与缺乏任何此类蛋白质失调的那些进行比较。这些患者中每个个体潜在蛋白质病理的频率太低,无法进行有意义的统计分析,然而,与36例未显示这些病变的患者相比,11例表现出一种或多种病变(NPAS3,dysbindin-1,TRIOBP-1和/或TRIOBP-5/6)的PANSS总分略有但显着增加(p=0.031),似乎主要是由一般精神病理学量表得分增加所驱动。虽然目前所涉及的患者人数不允许得出确切的结论,这提供了第一个迹象,即血清中的蛋白质紊乱,聚集在精神分裂症患者大脑中的蛋白质,可能与精神分裂症症状的严重程度有关。。
It has been proposed that aggregation of specific proteins in the brain may be a pathological element in schizophrenia and other chronic disorders. Multiple such aggregating proteins have now been implicated through post mortem investigation, including NPAS3 (Neuronal PAS domain protein 3), dysbindin-1 (encoded by the DTNBP1, Dystrobrevin Binding Protein 1, gene) and TRIOBP (Trio-Binding Protein, multiple isoforms). While the presence of protein aggregates in the brain is interesting in terms of understanding pathology, it is impractical as a biomarker. These proteins were therefore investigated recently in blood serum of schizophrenia patients and controls, showing patients to have higher levels of NPAS3 in their serum generally. TRIOBP-1 and dysbindin-1 were also found in an insoluble state, implying aggregation, but did not clearly corresponding to disease state.
We revisit 47 of the originally recruited 50 patients with schizophrenia, all of whom are Croatian and aged between 18 and 72. We assessed their symptom specificity and severity using PANSS (the Positive and Negative Symptoms Scale), comparing those with NPAS3, insoluble dysbindin-1 and/or insoluble TRIOBP-1 in their blood serum to those lacking any such protein dysregulation.
The frequency of each individual potential protein pathology among these patients was too low for meaningful statistical analysis, however the 11 patients that displayed one or more of these pathologies (NPAS3, dysbindin-1, TRIOBP-1 and/or TRIOBP-5/6) showed a subtle but significant increase in total PANSS scores compared to the 36 patients displaying none of the pathologies (p = 0.031), seemingly driven principally by increased scores on the general psychopathology scale.
While the numbers of patients involved do not allow firm conclusions to be drawn at this time, this provides the first indication that disturbed proteostasis in blood serum, of proteins that aggregate in the brains of schizophrenia patients, may correlate with the severity of schizophrenia symptoms.