Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia.
Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia.
复制标题
与迟发性运动障碍相关的谷氨酸能神经传递和氧化应激的标志物。
DOI：
10.1176/ajp.155.9.1207
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Coyle,JT
中科院分区：
文献类型：
--
作者：
Tsai,G;Goff,DC;Chang,RW;Flood,J;Baer,L;Coyle,JT
迟发性运动障碍是一种运动障碍，影响20%-40%的长期接受精神抑制药物治疗的患者。多巴胺超敏假说无法解释迟发性运动障碍的时间过程，也无法解释迟发性运动障碍的持续存在以及停药后相关的结构变化。作者假设，抗精神病药物通过阻断突触前多巴胺受体，从而导致神经元损伤的氧化stress.MethodCSF的后果，提高纹状体amatergic神经传递，从20例精神分裂症，其中11人迟发性运动障碍。在CSF标本中测量氧化应激标志物（包括超氧化物歧化酶、脂质过氧化氢和蛋白质羰基）和兴奋性神经传递标志物（包括N-乙酰天冬氨酸、N-乙酰乙酰谷氨酸、天冬氨酸和谷氨酸）。患者也被评为迟发性运动障碍的症状与异常不自主运动Scale.ResultsTardive运动障碍患者有显着较高的浓度N-乙酰天冬氨酸，N-乙酰乙酰基谷氨酸，天冬氨酸在他们的CSF比患者没有迟发性运动障碍时，年龄和抗精神病药物剂量控制。然而，与迟发性运动障碍相关的较高水平的蛋白质氧化产物的意义没有通过Bonferroni校正。迟发性运动障碍症状与兴奋性神经传递和蛋白质羰基组标记物呈正相关，与CSF超氧化物歧化酶活性呈负相关。结论这些发现表明，迟发性运动障碍中氧化应激和多巴胺能神经传递水平升高，这两者可能与迟发性运动障碍的病理生理学相关。美国精神病学杂志1998; 155：1207-1213
ObjectiveTardive 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 tardive dyskinesia or for the persistence of tardive dyskinesia and the associated structural changes after neuroleptics are discontinued. The authors hypothesized that neuroleptics enhance striatal glutamatergic neurotransmission by blocking presynaptic dopamine receptors, which causes neuronal damage as a consequence of oxidative stress.MethodCSF was obtained from 20 patients with schizophrenia, 11 of whom had tardive dyskinesia. Markers for oxidative stress, including superoxide dismutase, lipid hydroperoxide, and protein carbonyl groups, and markers for excitatory neurotransmission, including N-acetylaspartate, N-acetylaspartylglutamate, aspartate, and glutamate, were measured in the CSF specimens. Patients were also rated for tardive dyskinesia symptoms with the Abnormal Involuntary Movement Scale.ResultsTardive dyskinesia patients had significantly higher concentrations of N-acetylaspartate, N-acetylaspartylglutamate, and aspartate in their CSF than patients without tardive dyskinesia when age and neuroleptic dose were controlled for. The significance of the higher levels of protein-oxidized products associated with tardive dyskinesia did not pass Bonferroni correction, however. Tardive dyskinesia symptoms correlated positively with markers of excitatory neurotransmission and protein carbonyl group and negatively with CSF superoxide dismutase activity.ConclusionsThese findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of which may be relevant to the pathophysiology of tardive dyskinesia.Am J Psychiatry 1998; 155: 1207-1213