Association between redox imbalance, pterin metabolism markers, and early extrapyramidal side effects of antipsychotics in schizophrenia: pilot study

Abstract

Antipsychotics (AP) administration in schizophrenia patients is associated with several side effects (SE), in particular, with extrapyramidal (EP). Data suggests that oxidative damage to dopaminergic neurons in the EP system may be related to tardive dyskinesia and Parkinson's disease (PD) development, although data on the role of oxidative stress in the development of early EPSE of AP is lacking. Another poorly studied hypothesis of the EP-symptoms pathogenesis considers disorders of folate (pterin) metabolism.Objective: to evaluate the relationship between redox imbalance and pterin metabolism with the severity of early EPSE caused by AP used in the schizophrenia treatment.Patients and methods. The study included 50 patients with the first episode of schizophrenia. EP symptoms were evaluated using the UKU Side-Effect Rating Scale (“UKU-SERS-Clin” version). The levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), aldehyde-2,4-dinitrophenylhydrazone, ketone-2,4-dinitrophenylhydrazone were assessed in blood plasma; levels of BH4, folate, cobalamin (vitamin B12), and homocysteine – in blood serum; superoxide dismutase (SOD) and catalase activity – in erythrocytes.Results and discussion. EPSE severity was inversely proportional inversely proportional to the GSH level and directly proportional to the SOD activity. EPSE severity was also associated with AP selectivity, but not with their dosages. However, AP selectivity was not associated with studied biochemical parameters. MDA level in patients prescribed with amantadine was lower than in other participants.Conclusion. Early AP-induced EPSE were associated with redox imbalance, which indicates the necessity for further research aiming at prevention of secondary neurodegenerative diseases in patients with schizophrenia receiving AP.

Keywords

• antipsychotics
• extrapyramidal side effects
• oxidative stress
• pterin metabolism