The antioxidant defense system at the onset of psychosis

Abstract

Findings from in vivo NMR spectroscopic studies and studies of peripheral tissues from schizophrenic patients implicate altered cell membrane lipid metabolism. Aside from structural functions, cell membrane fatty acids are integrally involved in second messenger systems and prostaglandin synthesis. We examined the fatty acid composition of cell membranes of cultured skin fibroblasts from 12 schizophrenic patients (8 were drug-naive), 8 normal controls, and 6 chug-free bipolar patients. The most salient findings ,sere a significantly lower content of 22 carbon fatty acids, especially 22:6n-3 (docosahexanoic acid, DHA) and a higher ¢06:¢o-3 fatty acid ratio in fibroblasts from schizophrenic patients, but not in those from bipolar patients. Given that DHA precursor levels were not low, this suggests that schizophrenia may be associated with impaired activity of **4-desaturase, which converts 22:5n-3 to 22:6n-3 (DHA) and 22:4n-6 to 22:5n-6. DHA is highly concentrated in the brain, especially in synaptic membranes, and DHA deficiency results in impaired learning in animal models. Two studies found RBC DHA levels to be lower in schizophrenic patients with prominent negative symptoms and, in the steady state, RBC DHA reliably reflects brain DHA levels. The hypothesis will be presented that deficiency of omega-3 fatty acids, especially DHA, contributes to the deficit syndrome of schizophrenia, and may explain crossnational differences in outcome observed in the WHO studies and the effects of in utero exposure to influenza vires or severe famine on its incidence.