Differential alteration of phospholipase A(2) activities in brain of patients with schizophrenia

We recently reported that the activity of a calcium-independent subtype of phospholipase A(2) is increased in blood of patients with schizophrenia. Th e present investigation examined whether similar changes take place in brai n of patients with this disorder, and for comparison, in patients with bipo lar disorder. The activity of two classes of PLA(2), calcium-stimulated and independent, were assayed in autopsied temporal, prefrontal and occipital cortices, putamen, hippocampus and thalamus of 10 patients with schizophren ia, 8 patients with bipolar disorder and 12 matched control subjects. Calci um-independent PLA(2) activity was increased by 45% in the temporal cortex of patients with schizophrenia as compared with the controls but was not si gnificantly altered in other brain areas. In contrast, calcium-stimulated P LA(2) activity was decreased by 27-42% in the temporal and prefrontal corti ces and putamen, with no significant alterations in other brain regions. Br ain PLA(2) activity was normal in patients with bipolar disorder. Calcium-s timulated PLA(2) activity was normal in cortex, cerebellum and striatum of rats treated acutely or chronically with haloperidol, whereas calcium-indep endent PLA(2) activity was decreased in striatum of chronically treated ani mals, indicating that altered PLA(2) activity in patients with schizophreni a is unlikely to be a direct effect of medication. Studies of the cellular role played by PLA(2) suggest that decreased calcium-stimulated PLA(2) acti vity, as also occurs in striatum of chronic human cocaine users, may be due , in part, to increased dopaminergic activity in the disorder, whereas incr eased calcium-independent PLA(2) activity may be related to abnormal fatty acid metabolism and oxidative stress in schizophrenia. (C) 1999 Elsevier Sc ience B.V. All rights reserved.