FACTA UNIVERSITATIS Series: Medicine and Biology Vol.9, No 2, 2002, pp. 157 - 161 UC 616.895.8+616.89-008 OXIDATIVE STRESS AS MARKER OF POSITIVE SYMPTOMS IN SCHIZOPHRENIA Dušica Pavlović 1 , Vesna Tamburić 2 , Ivana Stojanović 1 , Gordana Kocić 1 , Tatjana Jevtović 1 , Vidosava orđević 1 1 Institute of Biochemistry, Faculty of Medicine, Niš, Yugoslavia 2 Clinic for Psychiatry, Faculty of Medicine, Niš, Yugoslavia Summary. Schizophrenia, a serious hereditary disease, is a biological disorder of the brain resulting from abnormalities that arise early in life and disrupt a normal development of the brain. The chemical nature of schizophrenic brain is still not completely understood. The brain and nervous system are particularly prone to free radical damage since the membrane lipids are very rich in polyunsaturated fatty acid chains, and areas of human brain are very rich in iron, which plays an essential role in generating free radical species. Following the hypothesis that chronic schizophrenics are under oxidative stress which has exhausted the ability of their antioxidative capacity to adapt the elevated levels of circulating peroxides, we decided to examine the erythrocyte levels of lipid peroxidation products and reduced glutathione and the activities of antioxidative defence enzymes - superoxide dismutase (EC 1.15.1.1), glutathione peroxidase (EC 1.11.1.9) and catalase (EC 1.11.1.6) - as well as erythrocyte susceptibility to H 2 O 2 -induced oxidative stress in schizophrenic patients. The obtained results suggest a misbalance in pro/antioxidant status of chronic schizophrenics, which is more expressed in patients with positive symptoms of the disease. Key words: Schizophrenia, oxidative stress, antioxidative defence Introduction A major mental disorder that affects young people, schizophrenia is characterised by unknown etiology, complex pathology and long-lasting and not completely successful treatment. A growing body of evidence sug- gests that peripheral activities of antioxidant enzymes and lipid peroxidation are abnormal in schizophrenic subjects (1,2). Mahadik found increased lipid peroxida- tion products and altered defence system in both chronic and drug-naive first episode schizophrenics (3). The accumulated results indicate that oxidative stress is in- tegral to this disease and not the result of neuroleptic treatment (4,5). Oxidative damage inflected by reactive oxygen spe- cies is also referred to as oxidative stress. Oxidative stress is a result of increased formation of free radicals and/or reduced antioxidative system capacity. Neurons are particularly vulnerable to radical-mediated damage. High oxygen consumption, lipid content and transition metals are particular risk factors (6,7). Free radicals contribute to neuronal loss in cerebral ischemia and haemorrhage, and may be involved in degeneration of neurons in normal aging (8), epilepsy (9), Parkinson's disease (10), Alzheimer's disease (11), and possibly in schizophrenia (12). In addition to their pathological role, free radicals have critical physiological functions in neuronal development, differentiation and signal transduction (13,14), all of which may be altered in some cases of schizophrenia. The effect of oxidative modification of neuronal phospholipids, DNA, and proteins on their function (i.e. membrane transport, loss of mitochondrial energy pro- duction, gene expression and, therefore, receptor-medi- ated phospholipid-dependent signal transduction (15,16)) may explain altered information processing in schizophrenia. Crow divided schizophrenia into two types (Crow's type I and II) according to clinical phe- nomenology, therapy response, and biochemical basis. Although it is obvious that these two syndromes fre- quently appear as two parts of a single process, it is pos- sible to distinguish them according to their structural, biochemical and endocrinological specificities. There- fore, we wanted to explore possible changes in pro/antioxidant status in schizophrenics with positive and negative symptoms. Recently, it was shown that red blood cells superoxide dismutase increase in positive schizophrenia (Crow's type I), but not in Crow's type II (17). Due to a lack of literature data about this problem, we set out to explore possible markers of distinguishing and, perhaps, predicting the symptoms of this serious disease. Since neuronal oxidative injury processes and un- derlying dynamic molecular regulatory mechanisms are reflected in peripheral blood cells, we could use red blood cells, platelets, lymphocytes and cultured skin fibroblasts in order to define these processes and find ways to prevent these kinds of injuries (18,19,20).