MARKERS OF GLUTAMATERGIC NEUROTRANSMISSION AND OXIDATIVE STRESS ASSOCIATED WITH TARDIVE-DYSKINESIA

Objective: Tardive dyskinesia is a movement disorder affecting 20%-40% of patients treated chronically with neuroleptic drugs. The dopamine supersensitivity hypothesis cannot account for the time course of tard ive dyskinesia or for the persistence of tardive dyskinesia and the as sociated structural changes after neuroleptics are discontinued. The a uthors hypothesized that neuroleptics enhance striatal glutamatergic n eurotransmission by blocking presynaptic dopamine receptors, which cau ses neuronal damage as a consequence of oxidative stress. Method: CSF was obtained from 20 patients with schizophrenia, 11 of whom had tardi ve dyskinesia. Markers for oxidative stress, including superoxide dism utase, lipid hydroperoxide, and protein carbonyl groups, and markers f or excitatory neurotransmission, including N-acetylaspartate, N-acetyl aspartylglutamate, aspartate, and glutamate, were measured in the CSF specimens. Patients were also rated for tardive dyskinesia symptoms wi th the Abnormal Involuntary Movement Scale. Results: Tardive dyskinesi a patients had significantly higher concentrations of N-acetylaspartat e, N-acetylaspartylglutamate, and aspartate in their CSF than patients without tardive dyskinesia when age and neuroleptic dose were control led for. The significance of the higher levels of protein-oxidized pro ducts associated with tardive dyskinesia did not pass Bonferroni corre ction, however. Tardive dyskinesia symptoms correlated positively with markers of excitatory neurotransmission and protein carbonyl group an d negatively with CSF superoxide dismutase activity. Conclusions: Thes e findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of whi ch may be relevant to the pathophysiology of tardive dyskinesia.