Clinical subtyping reveals significant differences in calcium-dependent phospholipase A2 activity in schizophrenia

Background: Inconsistent results in the study of phospholipid metabolism in schizophrenia may reflect the heterogeneous nature of the illness(es). Differences in patients’ responses to niacin, a compound causing vasodilation via stimulation of phospholipid dependent signaling cascades, defines more homogeneous patient subgroups in which the rate limiting enzyme of this signaling pathway, phospholipase A2 (PLA2), can be studied. Methods: Subjects were categorized as niacin-insensitive (10 schizophrenic patients and 1 control) or niacin-sensitive (13 schizophrenic patients and 29 controls). Comparisons of serum calcium-dependent PLA2 were undertaken with and without consideration of niacin sensitivity. Results: Significantly more schizophrenic patients were niacin-insensitive than controls (χ2(1) = 12.8, p< .001). Comparison of mean serum calcium-dependent PLA2 level of all schizophrenic subjects with all healthy controls revealed no statistical difference (t(51) = .79, NS). Subtyping the schizophrenia group by niacin sensitivity/insensitivity, however, allowed significant differences to emerge (F(2,49) = 4.40, p = .018). Post-hoc tests showed the mean PLA2 activity level of niacin-sensitive subjects was lower than that of healthy subjects. Conclusions: Treatment strategies which increase calcium-dependent PLA2 activity may aid in reducing states of excess dopaminergic activity by activating second messenger systems rather than receptor blockade. Biol Psychiatry 1999;46:401–405© 1999 Society of Biological Psychiatry