The increased activity of plasma manganese superoxide dismutase in tardive dyskinesia is unrelated to the Ala-9Val polymorphism

• Published in: Journal of psychiatric research Vol. 36; no. 5; pp. 317 - 324
• Main Authors: Zhang, ZhiJun, Zhang, XiaoBin, Hou, Gang, Sha, WeiWei, Reynolds, Gavin P
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2002; Elsevier
• Subjects: Adolescent; Adult; Antipsychotic Agents - adverse effects; Association study; Biological and medical sciences; Child; Drug toxicity and drugs side effects treatment; Dyskinesia, Drug-Induced - enzymology; Dyskinesia, Drug-Induced - etiology; Dyskinesia, Drug-Induced - genetics; Gene Expression - genetics; Genomic Library; Genotype; Humans; Male; Manganese superoxide dismutase (MnSOD); Medical sciences; Middle Aged; Pharmacogenetics; Pharmacology. Drug treatments; Polymerase Chain Reaction; Polymorphism; Polymorphism, Genetic - genetics; Random Allocation; Schizophrenia; Schizophrenia - drug therapy; Superoxide Dismutase - blood; Tardive dyskinesia; Toxicity: nervous system and muscle; Schizophrenia; Association study; Pharmacogenetics; Manganese superoxide dismutase (MnSOD); Tardive dyskinesia; Polymorphism; Psychotropic; Neuroleptic; Toxicity; Male; Superoxide dismutase; Free radical; Involuntary movement; Psychosis; Gene; Genetics; Neurological disorder; Dyskinesia; Human; Nervous system diseases; Late; Enzyme; Prediction; Chemotherapy; Chronic; Treatment; Oxidoreductases; Comparative study; Extrapyramidal syndrome; Manganese
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/S0022-3956(02)00007-9

That tardive dyskinesia (TD) may have its origins in free-radical toxicity has stimulated investigations into one enzyme important in the control of oxidative free radicals: superoxide dismutase (SOD). The manganese-containing form of this enzyme (MnSOD) is the major superoxide scavenger in mitochondria; a weak association between a functional genetic polymorphism (Ala-9Val) in the mitochondrial targeting sequence (MTS) of this enzyme and TD has been reported in a Japanese population. We have undertaken to determine both the plasma activity of MnSOD and the association of the Ala-9Val polymorphism in a well-matched series of male Chinese schizophrenic patients with ( n=42) and without ( n=59) TD, and normal male controls ( n=50). MnSOD activity was elevated in the TD subjects over those without TD ( P<0.05) and normal controls ( P<0.05), an effect that was independent of age, age at first antipsychotic treatment, drug dosage and duration of illness. A significant positive correlation between total AIMS score and MnSOD activity was also observed ( P<0.0001). No significant reduction in the frequency of the Ala allele was observed in the TD group (0.14) below non-TD (0.18) or control subjects (0.17); nor was there any relationship between MnSOD activity and the polymorphism. There was no difference between the mean AIMS scores for the two genotypes (V/V and A/V) in the TD group. We conclude that while we have further evidence of a disturbance in the mechanisms regulating oxidative free radicals in TD, this effect is not under the control of the genetic polymorphism investigated here.