Shinkai Takahiro, Müller Daniel J, De Luca Vincenzo, Shaikh Sajid, Matsumoto Chima, Hwang Rudi, King Nicole, Trakalo Joseph, Potapova Natalia, Zai Gwyneth, Hori Hiroko, Ohmori Osamu, Meltzer Herbert Y, Nakamura Jun, Kennedy James L
Neurogenetics Section, Centre for Addiction and Mental Health, Clarke Division, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada, M5T 1R8.
Psychiatry Res. 2006 Feb 28;141(2):123-8. doi: 10.1016/j.psychres.2004.06.023. Epub 2006 Jan 18.
A possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in [Andreassen, O.A., Jorgensen, H.A., 2000. Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Progress in Neurobiology 61, 525-541.]). Long-term administration of neuroleptics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a possible functional polymorphism of the human glutathione peroxidase (GPX1) gene (an important antioxidant enzyme) was studied in 68 chronic treatment-refractory patients with schizophrenia. A proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) in the GPX1 gene was genotyped. No significant difference in total Abnormal Involuntary Movements Scale (AIMS) scores was observed among patients in the three genotype groups. Moreover, no significant differences in genotype or allele frequencies were observed between subjects with and without TD. Our results suggest that the GPX1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.
