Le stress oxydant est la résultante d’un déséquilibre entre la production de radicaux libres et les systèmes de défenses antioxydants. Le système nerveux central, de par sa consommation importante en oxygène, sa surface étendue d’échange membranaire et un taux relativement bas d’enzymes antioxydantes, représente un lieu privilégié pour le stress oxydant. Ce dernier serait d’ailleurs impliqué dans plusieurs pathologies du système nerveux central, telles que la maladie d’Alzheimer, la maladie de Parkinson ou la chorée de Hungtington. Dans ce travail, nous proposons d’étudier, à travers une revue de la littérature, les différentes perturbations des systèmes antioxydants observées dans la schizophrénie, leurs corrélations avec les caractéristiques cliniques et thérapeutiques, et de discuter l’implication de ces observations dans la physiopathologie de la schizophrénie. Une baisse de l’activité des enzymes antioxydantes (super­oxyde dismutase, glutathion peroxydase, catalase), des concentrations plasmatiques des différents constituants du système de défense non enzymatique (albumine, bilirubine, acide urique, oligoéléments…) ainsi qu’une augmentation de la peroxydation des lipides ont été constatées chez les patients schizophrènes. Ces perturbations sont corrélées à la sévérité des signes négatifs de la maladie et peuvent être influencées par le traitement neuroleptique. Ces résultats font suggérer la place de ces perturbations, comme base biochimique des anomalies du système nerveux central, observées dans la schizophrénie, et évoquer le rôle potentiel des antioxydants dans la stratégie thérapeutique.

Background. Schizophrenia is a devastating psychiatric disorder with a broad range of behavioural and biologic manifestations. There are several clinical characteristics of the illness that have been consistently associated with poor premorbid adjustment, long duration of psychosis prior to treatment and prominent negative symptoms. The etiopathogenic mechanisms of lack of insight in patients with schizophrenia are to date unknown, although several hypotheses have been suggested. A point of convergence for the theoretical models occurs with regard to the neuronal membrane. Neuronal membrane contains a high proportion of polyunsaturated fatty acid and is the site for oxidative stress. Oxidative stress is a state when there is unbalance between the generation of reactive oxygen species and antioxidant defence capacity of the body. It is closely associated with a number of diseases including Parkinson’s disease, Alzheimer-type dementia and Huntington’s chorea. Accumulating evidence points to many interrelated mechanisms that increase production of reactive oxygen or decrease antioxidant protection in schizophrenic patients. Objectives. This review aims to summarize the perturbations in antioxidant protection systems during schizophrenia, their interrelationships with the characteristic clinics and therapeutics and the implications of these observations in the pathophysiology of schizophrenia are discussed. Literature findings. In schizophrenia there is evidence for deregulation of free radical metabolism, as detected by abnormal activity of critical antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase). Many studies conclude in the decrease in the activity of key antioxidant enzymes in schizophrenia. A few studies have examined levels of non enzymatic antioxidants such as plasma antioxidant proteins (albumin, bilirubine, uric acid) and trace elements. How showed decreased levels in schizophrenic patients. Others studies have provided evidence of oxidative membrane damage by examining levels of lipid peroxidation products. Such abnormalities have been associated with certain clinical symptoms and therapeutic features. Negative symptoms have been associated with low levels of GSH-Px. Positive symptoms have been positively correlated with SOD activity. Plasma TAS was significantly lower in drug-free and haloperidol treated patients with schizophrenia. A low erythrocyte SOD activity has been found in never-treated patients, but with haloperidol treatment, SOD activity increased. Discussion. These results demonstrate altered membrane dynamics and antioxidant enzyme activity in schizophrenia. Membrane dysfunction can be secondary to free a radical-mediated pathology, and may contribute to specific aspects of the schizophrenia symptomatology. Membrane defects can significantly alter a broad range of membrane functions and presumably modify behavior through multiple downstream biological effects. Phospholipid metabolism in the brain may be perturbed in schizophrenia, with reduced amounts of phosphatidylcholins and phosphatidylethanolamine in post-mortem brain tissue from schizophrenic patients, and large amounts of lipofuscin-like materiel in the oligodendrocytes. The existence of these products within cell membranes results in an unstable membrane structure, altered membrane fluidity and permeability and impaired signal transduction. Recent findings suggest that multiple neurotransmitter systems may be faulty. CNS cells are more vulnerable to the toxic effects of free radicals because they have a high rate of catecholamine oxidative metabolic activity. Neurotransmitters, like glutamate, can induce the same metabolic processes that increase free radical production and can lead to impaired dopamine-glutamate balance. These results question the role of this imbalance in the biochemical basis evoked in the etipathogenic mechanisms of schizophrenia, as well as the role of antioxidants in the therapeutic strategy and their implication in preventive and early intervention approaches in populations at risk for schizophrenia.