As the principle degradative enzyme for amine neurotransmitters in the central nervous system, mitochondrial monoamine oxidase (MAO) has been the sujbect of numerous investigations of biochemical determinants of mental illness. Schizophrenia has been the subject of the great majority of these studies, which have for the most part focused on activity of the enzyme in the clinically accessible blood platelets of patients as a marker for effects in the brain. The majority opinion is that there are significantly lower levels of platelet MAO associated with schizophrenia and that the effect perhaps most pronounced in a chronic paranoid subgroup, however the interpretation of these findings and their relation to etiology of the disease remain controversial. We have recently found the phospholipid, phosphatidylserine (PS), to be a potent and highly specific inhibitor of B-type MAO, the form found in platelets. As a natural minor constitutent of most cell membranes with numerous demonstrated effects on CNS components in vitro and in vivo, we have proposed that PS may be a natural regulator of MAO activity. An altered PS-MOA interaction might thus offer a molecular mechanism for the lower platelet MAO of schizophrenics, as well as providing a link to other biochemical parameters of the disorder. To test this hypothesis we plan to undertake a comparative study of the relation of PS to platelet MAO activity in two subgroups of schizophrenics (paranoid and residual) with both normals and personality disorder patients serving as controls. Parameters to be measured will include sensitivity of MAO to exogenous PS and correlation of basal MAO activity with endogenous PS levels and metabolism. The study will include 120 age matched, male subjects for the 3 years of the project. A portion of these will be followed longitudinally to correlate any biochemical effects observed with changes in symptomatology. Schizophrenic and personality disorder subjects will all be inpatients at the Psychiatry Service wards, Sepulveda, California, V.A.M.C. The clinical studies will be supported by an ongoing effort to eludicate the molecular mechanism of the interaction of PS with platelet MAO as an aid in interpretation of effects in clinical blood samples. We also wish to examine the effect of PS in vivo on brain MAO via CNS injections of PS liposomes or stimulated biosynthesis using rats as an animal model.
| Buckman, T D; Kling, A; Sutphin, M S et al. (1990) Platelet glutathione peroxidase and monoamine oxidase activity in schizophrenics with CT scan abnormalities: relation to psychosocial variables. Psychiatry Res 31:1-14 |
| Buckman, T D; Chang, R; Sutphin, M S et al. (1988) Interaction of 1-methyl-4-phenylpyridinium ion with human platelets. Biochem Biophys Res Commun 151:897-904 |
| Buckman, T D; Kling, A S; Eiduson, S et al. (1987) Glutathione peroxidase and CT scan abnormalities in schizophrenia. Biol Psychiatry 22:1349-56 |
| Orologas, A G; Buckman, T D; Eiduson, S (1986) A comparison of platelet monoamine oxidase activity and phosphatidylserine content between chronic paranoid schizophrenics and normal controls. Neurosci Lett 68:293-8 |
| Buckman, T D; Eiduson, S (1985) Photoinactivation of B-type monoamine oxidase by a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolite. J Biol Chem 260:11899-902 |
