Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia

1. Schizophrenia is a major mental disorder that has a lifetime risk of 1% and affects at young age (average age at the onset 24 +/- 4.6 years) in man y cultures around the world, The etiology is unknown, the pathophysiology i s complex, and most of the patients need treatment and care for the rest of their lives. 2. Cellular oxidative stress is inferred from higher tissue levels of react ive oxygen species (ROS, e.g., O-2(.-), OH., OH-, NO. and ONOO-) than its a ntioxidant defense that cause peroxidative cell injury, i.e., peroxidation of membrane phospholipids, particularly esterified essential polyunsaturate d fatty acids (EPUFAS), proteins and DNA. 3. Oxidative stress can lead to global cellular with predominantly neuronal peroxidation, since neurons are enriched in highly susceptible EPUFAs and proteins, and damages DNA is not repaired effectively. 4. Such neuronal peroxidation may affect its function (i.e., membrane trans port, loss of mitochondrial energy production, gene expression and therefor e receptor-mediated phospholipid-dependent signal transduction) that may ex plain the altered information processing in schizophrenia. 5. It is possible that the oxidative neuronal injury can be prevented by di etary supplementation of antioxidants (e.g,, vitamins E, C and A; beta -car otene; Q-enzyme, flavons, etc.) and that membrane phospholipids can be corr ected by dietary supplementation of EPUFAs. 6. It may be that the oxidative stress is lower in populations consuming a low caloric diet rich in antioxidants and EPUFAs, and minimizing smoking an d drinking. 7. Oxidative stress exists in schizophrenia based on altered antioxidant en zyme defense, increased lipid peroxidation and reduced levels of EPUFAs. Th e life style of schizophrenic patients is also prooxidative stress, i.e., h eavy smoking, drinking high caloric intake with no physical activity and tr eatment with pro-oxidant drugs. 8. The patients in developed countries show higher levels of lipid peroxida tion and lower levels of membrane phospholipids as compared to patients in the developing countries. 9. Initial observations on the improved outcome of schizophrenia in patient s supplemented with EPUFAs and antioxidants suggest the possible beneficial effects of dietary supplementation. 10. Since the oxidative stress exists at or before the onset of psychosis t he use of antioxidants from the very onset of psychosis may reduce the oxid ative injury and dramatically improve the outcome of illness.