Brain Phospholipid Composition in Schizophrenia

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DESCRIPTION (provided by applicant): Studies of erythrocytes and platelets have suggested that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) metabolism and composition in the brain. A hypothesis of schizophrenia based on cell membrane abnormalities can potentially explain a range of findings, and is consistent with abnormalities in multiple neurotransmitter systems and neurodevelopment. Examination of PL precursors and degradation products by in vivo 31P nuclear magnetic resonance (NMR) suggests alterations in brain PL metabolism in schizophrenia. A limitation of these in vivo NMR studies is that PLs are not observed directly because they are solid-like. For the 31 P in vivo NMR results to support strongly the membrane hypothesis of schizophrenia, changes in PL precursors and degradation products must be linked with actual changes in PL composition in the brain. In preliminary studies in our lab using 31P in vitro NMR, elevated phosphatidylinositol, elevated phosphatidylcholine with one saturated and one unsaturated side chain, and a trend toward increased total PLs, were found in extracts of postmortem schizophrenic brain (frontal cortex) relative to control. These results support the notion that PL abnormalities occur in the brain in schizophrenia. It is hypothesized that the PL compositions in frontal and temporal cortices (but not occipital cortex), regions implicated in schizophrenia, are different in schizophrenics than in controls. It is also hypothesized that, in the cases where in vivo 31 P NMR detects changes in PL precursors and/or degradation products, changes in PL composition are also occurring. It is proposed to measure both the PL composition (organic solvent extract and bile-salt solubilization) and PL precursors and degradation products (perchloric acid extract) in left frontal, temporal and occipital cortices of the same individuals (20 schizophrenics, 20 controls, and 10 psychiatric controls) using 31 P in vitro NMR. This study will shed light on the sometimes conflicting results of previous PL studies both on peripheral tissue and in vivo. It will also potentially provide support and clarification for several aspects of the membrane hypothesis of schizophrenia.