Oxidative stress and tardive dyskinesia: pharmacogenetic evidence

Abstract

Tardive dyskinesia (TD) is a serious adverse effect of long-term antipsychotic use. Because of genetic susceptibility for developing TD and because it is difficult to predict and prevent its development prior to or during the early stages of medication, pharmacogenetic research of TD is important. Additionally, these studies enhance our knowledge of the genetic mechanisms underlying abnormal dyskinetic movements, such as Parkinson's disease. However, the pathophysiology of TD remains unclear. The oxidative stress hypothesis of TD is one of the possible pathophysiologic models for TD. Preclinical and clinical studies of the oxidative stress hypothesis of TD indicate that neurotoxic free radical production is likely a consequence of antipsychotic medication and is related to the occurrence of TD. Several studies on TD have focused on examining the genes involved in oxidative stress. Among them, manganese superoxide dismutase gene Ala-9Val polymorphisms show a relatively consistent association with TD susceptibility, although not all studies support this. Numerous pharmacogenetic studies have found a positive relationship between TD and oxidative stress based on genes involved in the antioxidant defense mechanism, dopamine turnover and metabolism, and other antioxidants such as estrogen and melatonin. However, many of the positive findings have not been replicated. We expect that more research will be needed to address these issues.

Keywords: AIMS; ATP; Abnormal Involuntary Movement Scale; CAT; CYP; FGAs; GABA; GSH-Px; GSTs; H(2)O(2); LID; MAO; MnSOD; NAD(P)H quinone oxidoreductase; NOS; NQO; O(2)(−); Oxidative stress; PD; Parkinson's disease; Pharmacogenetics; ROS; SGAs; SNP; SOD; TD; Tardive dyskinesia; UCP; adenosine triphosphate; catalase; cytochrome P450; first-generation antipsychotics; glutathione S-transferases; glutathione peroxidase; hydrogen peroxide; l-3,4-dihydroxyphenylalanine; l-DOPA; l-DOPA-induced dyskinesia; manganese superoxide dismutase; monoamine oxidase; nitric oxide synthase; reactive oxygen species; second-generation antipsychotics; single nucleotide polymorphism; superoxide anion; superoxide dismutase; tardive dyskinesia; uncoupling protein; γ-aminobutyric acid.