Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:207-13. doi: 10.1016/j.pnpbp.2012.10.018. Epub 2012 Oct 31.
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.
迟发性运动障碍（TD）是长期使用抗精神病药物的严重不良反应。由于存在发生 TD 的遗传易感性，并且在药物治疗的早期阶段之前或期间难以预测和预防其发展，因此对 TD 的药物遗传学研究很重要。此外，这些研究增强了我们对异常运动障碍（如帕金森病）遗传机制的了解。然而，TD 的病理生理学仍然不清楚。TD 的氧化应激假说就是 TD 的可能病理生理模型之一。TD 的氧化应激假说的临床前和临床研究表明，神经毒性自由基的产生可能是抗精神病药物治疗的结果，并与 TD 的发生有关。几项关于 TD 的研究集中在检查涉及氧化应激的基因上。其中，锰超氧化物歧化酶基因 Ala-9Val 多态性与 TD 易感性有相对一致的关联，尽管并非所有研究都支持这一点。许多药物遗传学研究基于涉及抗氧化防御机制、多巴胺转化和代谢以及其他抗氧化剂（如雌激素和褪黑素）的基因，发现 TD 与氧化应激之间存在正相关关系。然而，许多阳性发现并未得到复制。我们预计需要进行更多的研究来解决这些问题。
