FREE-RADICAL PATHOLOGY AND ANTIOXIDANT DEFENSE IN SCHIZOPHRENIA - A REVIEW

There is increasing evidence that free radical-mediated CNS neuronal d ysfunction is involved in the pathophysiology of schizophrenia. Free r adicals (oxyradicals, such as superoxide, hydroxyl ions, and nitric ox ide) cause cell injury when they are generated in excess or the antiox idant defense is impaired. Both of these processes seem to be affected in schizophrenia. Evidence of excessive oxyradical generation is prem ised on the assumption that there is increased catecholamine turnover, though there is little direct evidence to support such a view, which is further accentuated by neuroleptic treatment. However, antioxidant enzymes (superoxide dismutase, SOD; glutathione peroxidase, GSHPx; and catalase, CAT) which are constitutively expressed in all tissues, are found to be altered in erythrocytes of schizophrenic patients. Also, possible oxyradical-mediated injury to CNS is suggested by increased l ipid peroxidation products in cerebrospinal fluid and plasma, and redu ced membrane polyunsaturated fatty acids (PUFAs) in the brain and RBC plasma membranes. The brain is more vulnerable to oxyradical-mediated injury, because its membranes are preferentially enriched in oxyradica l sensitive PUFAs, and damaged adult neurons cannot be replaced. In ad dition to their pathological role, oxyradicals have critical physiolog ical functions in neuronal development, differentiation, and signal tr ansduction, all of which may be altered in some cases of schizophrenia . It may be possible to define cellular injury processes, investigate underlying dynamic regulatory molecular processes, and find ways to pr event these injury processes using peripheral cell models, e.g., red b lood cells, lymphocytes and cultured skin fibroblasts. Information on the clinical implications of these processes are valuable for developi ng new and innovative therapeutic strategies for schizophrenia.