There is abundant evidence that free radicals play an important role in membrane pathology in the central nervous system (CNS) and, although they may not be the main contributory factor, free radicals may be involved in physiopathology of many diseases including schizophrenia [1–5].
Oxidative stress is characterised by an imbalance between oxidant molecules and antioxidant defence. Several studies suggest that the brain may be particularly vulnerable to oxidative stress [6–9]. The brain accounts for only 2% of the body weight but consumes 20% of the inspired oxygen, and its membranes are especially sensitive to oxidative damage because of their high content of polyunsaturated fatty acids.
It is difficult to determine the levels of free radicals in vivo because of their short half-life, but oxidative stress can be investigated indirectly by measuring the antioxidant defence system. The primary antioxidant cellular defence is enzymatic and includes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (cGPx). Glutathione (GSH) is the main non-enzymatic cellular antioxidant defence and protects cells from attack by reactive oxygen species. All of these chemical species are altered in patients with schizophrenia [10–12].
Results from animal models have shown that poorer environmental conditions are associated with more oxidative stress , and this is probably due to the need to transfer energy towards processes with a high energy cost, such as immune function, antioxidant defence and DNA repair processes . The relationship between environmental conditions and oxidative stress has not been examined in healthy humans. In a previous study, we have shown that antioxidant defence is decreased in children and adolescents with early onset first-episode psychosis . If environmental factors play a role in this, antioxidant defence may also be decreased in the unaffected relatives of such patients. Our hypothesis is that healthy control subjects with a family history of psychosis will have a lower antioxidant capacity than healthy subjects without this family history, and that the antioxidant capacity will be modulated by environmental family factors.
There is considerable evidence for the hereditary nature of schizophrenia, and the risk of developing the disease is increased in close relatives of people with schizophrenia [16, 17]. Oxidative stress levels are influenced by various factors, including genetics. It has been shown that antioxidant capacity could have a genetic basis [18–20], which would be modified throughout life by environmental factors , suggesting the possible presence of an early dysfunction in the antioxidant defence system in genetically predisposed individuals . Besides, high levels of expressed emotion are associated with a predominance of positive symptoms and with a worse outcome in patients with psychosis .
The objectives of this study are to determine antioxidant defence at the peripheral level in healthy subjects with a family history of psychosis and to compare it with that of healthy people without affected relatives. We also examine the association between oxidative stress and familiar environment.