The increased activity of plasma manganese superoxide dismutase in tardive dyskinesia is unrelated to the Ala-9Val polymorphism.
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.
Department of Psychiatry, Nanjing Brain Hospital and Nanjing Medical University, PR China.
ZhiJun
Z
Zhang
XiaoBin
X
Zhang
Gang
G
Hou
WeiWei
W
Sha
Gavin P
GP
Reynolds
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects; D002648:Child; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D015698:Genomic Library; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011897:Random Allocation; D012559:Schizophrenia / Q000188:drug therapy; D013482:Superoxide Dismutase / Q000097:blood*
D014150:Antipsychotic Agents; D013482:Superoxide Dismutase