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Evidence for the Involvement of a Calcium-Independent Phospholipase A2

Brian M. Ross, PhD; Craig Hudson, MD; Jeffrey Erlieft; Jerry J. Warsh, MD, PhD; Stephen J. Kish, PhD

Arch Gen Psychiatry. 1997;54(5):487-494.

Abstract
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 radiometrie 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, radiometrie assay of the same serum samples resulted in PLA₂ activity not significantly different between patients and control subjects. Further investigations demonstrated that, whereas the radiometrie 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.

Author Affiliations
From the Clarke Institute of Psychiatry (Drs Ross, Hudson, Warsh, and Kish and Mr Erlich), the Departments of Psychiatry (Drs Ross, Warsh, and Kish) and Pharmacology (Drs Warsh and Kish), and the Institute of Medical Science (Drs Hudson, Warsh, and Kish), University of Toronto, Toronto, Ontario.

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