Abstract
BackgroundThe role of oxidative stress in schizophrenia has been demonstrated, particularly in subjects with treatment-resistant schizophrenia (TRS). In such patients, the decreased levels of antioxidants in conjunction with the increased generation of reactive oxygen species in the brain exposes the neurons to a higher risk of damage.Methods and findingsWe evaluated the association of deletion polymorphisms of two genes of the antioxidant Glutathione S-Transferase family, GSTT1 and GSTM1, with susceptibility to TRS. A total of 54 TRS patients (mean age 38.7 years) and 78 healthy control subjects (mean age 39.0 years) were enrolled in this study. The subjects were matched by sex, age, and smoking and alcohol consumption habits. In the case group, the frequencies of GSTT1-null and GSTM1-null genotypes were 24.1 and 51.9%, respectively, whereas for the control group, the frequencies were 12.8 and 46.2%, respectively. Analysis performed with respect to the risk of developing TRS associated with the GSTT1 and GSTM1 deletion polymorphisms, resulted in odds ratio (OR) values of 2.1 and 1.2, respectively. However, the association was not found to be significant (p = 0.1229 and p = 0.5916, respectively). The analysis performed with respect to the combined genotypes of GSTT1 and GSTM1 revealed that the double-null genotype confers a 4.6-fold increased risk of developing TRS (p = 0.0412).ConclusionThe results of the present study indicate that a combination of GST deficiencies may play a role in enhanced susceptibility to TRS, and the present genotype of one of these genes may buffer the deficiency caused by the lack (null genotype) of the other. The results suggest that combined deletion polymorphisms of GSTT1 and GSTM1 can have implications in the prediction of the clinical course of the disease.
Highlights
Schizophrenia is a severe disabling mental disorder that affects 0.4 to 0.7% of the general population [1] and is caused by the interaction of multiple genetic and environmental factors
There were no significant differences between the case and control groups in terms of proportion of smokers and drinkers, and there was no association observed with respect to these variables in all the analyses performed
Some studies have investigated the role of oxidative stress in schizophrenia, and most of these studies report that the impairment of the antioxidant system and significant changes
Summary
Schizophrenia is a severe disabling mental disorder that affects 0.4 to 0.7% of the general population [1] and is caused by the interaction of multiple genetic and environmental factors. As the consumption of oxygen by brain cells is very high (approximately 20% of the total body consumption), this can lead to generation of increased levels of reactive oxygen species in the brain, expositing the neurons to oxidative stress [4,5] This fact, along with the evidence that the antioxidant status is compromised in patients with schizophrenia [6,7,8,9], allows us to hypothesize that differences in the ability to deal with oxidative stress can be a risk factor for the development of mental disorders such as schizophrenia. The role of oxidative stress in schizophrenia has been demonstrated, in subjects with treatment-resistant schizophrenia (TRS) In such patients, the decreased levels of antioxidants in conjunction with the increased generation of reactive oxygen species in the brain exposes the neurons to a higher risk of damage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
