Increased phospholipid breakdown in schizophrenia. Evidence for the involvement of a calcium-independent phospholipase A2.

BACKGROUND 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. DESIGN 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. RESULTS 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. CONCLUSIONS 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.