Ross B M, Hudson C, Erlich J, Warsh J J, Kish S J
Clarke Institute of Psychiatry, University of Toronto, Toronto, Ontario.
Arch Gen Psychiatry. 1997 May;54(5):487-94. doi: 10.1001/archpsyc.1997.01830170113015.
Magnetic resonance spectroscopy studies have suggested above-normal turnover of membrane phospholipids in brains of patients with schizophrenia. One possible explanation for these findings is increased activity of the phospholipid-catabolizing enzyme phospholipase A2 (PLA2). However, attempts to demonstrate higher PLA2 activity in the serum of subjects with schizophrenia have led to conflicting results. We hypothesized that this was due to serum PLA2 activity consisting of a family of different enzymes, with each group of investigators measuring activity of different PLA2 forms.
Activity of PLA2 in serum samples obtained from 24 individuals with schizophrenia was compared with serum obtained from 33 age- and sex-matched control subjects, using both fluorometric and radiometric assays with different substrates. Each method had previously yielded conflicting results concerning the status of the enzyme in schizophrenia.
With the fluorometric assay, serum PLA2 activity in individuals with schizophrenia was markedly increased by 49% compared with control subjects (P < .001). In contrast, radiometric assay of the same serum samples resulted in PLA2 activity not significantly different between patients and control subjects. Further investigations demonstrated that, whereas the radiometric assay measured activity of a calcium-dependent enzyme, the fluorometric assay detected a calcium-insensitive enzyme possessing an acid-neutral pH optimum.
Increased calcium-independent PLA2 activity was seen in the serum of patients with schizophrenia. This change, if present also in the brain, may well explain the increased levels of phosphodiesters observed using magnetic resonance spectroscopy and therefore may contribute to the pathophysiological features of the disorder.
磁共振波谱研究表明，精神分裂症患者大脑中膜磷脂的周转率高于正常水平。这些发现的一种可能解释是磷脂分解酶磷脂酶A2（PLA2）的活性增加。然而，试图证明精神分裂症患者血清中PLA2活性更高的研究结果相互矛盾。我们推测这是由于血清PLA2活性由一系列不同的酶组成，每组研究人员测量的是不同PLA2形式的活性。
使用针对不同底物的荧光测定法和放射性测定法，将24名精神分裂症患者的血清样本中的PLA2活性与33名年龄和性别匹配的对照受试者的血清进行比较。此前，每种方法关于精神分裂症中该酶的状态都得出了相互矛盾的结果。
采用荧光测定法时，精神分裂症患者的血清PLA2活性与对照受试者相比显著增加了49%（P <.001）。相比之下，对相同血清样本进行放射性测定时，患者和对照受试者之间的PLA2活性没有显著差异。进一步研究表明，放射性测定法测量的是一种钙依赖性酶的活性，而荧光测定法检测到的是一种对钙不敏感、最适pH为酸中性的酶。
在精神分裂症患者的血清中观察到钙非依赖性PLA2活性增加。这种变化如果也存在于大脑中，很可能解释了使用磁共振波谱观察到的磷酸二酯水平升高的现象，因此可能导致该疾病的病理生理特征。
