背景:迟发性运动障碍是一种以不自主性肌肉运动为特征的疾病,是抗精神病药物长期治疗的并发症。已提出与皮质-纹状体-丘脑-皮质回路的运动部分的间接途径的功能障碍有关,这可能是由氧化应激引起的神经毒性。
方法:我们的研究目的是调查来自3个不同精神病研究所的491名白种人精神分裂症患者中磷脂酰肌醇-4-磷酸-5-激酶IIa型(PIP5K2A)功能与迟发性运动障碍之间的可能关联。西伯利亚。异常非自愿运动量表用于评估迟发性运动障碍。对个体进行了PIP5K2A基因中的3个单核苷酸多态性的基因分型:rs10828317、rs746203和rs8341。
结果:在PIP5K2A基因(rs10828317)的功能突变N251S多态性与迟发性运动障碍之间建立了显着关联,而其他2个检查的非功能性单核苷酸多态性则不相关。
结论:我们从这一关联得出结论,PIP5K2A可能参与了防止迟发性运动障碍诱导的神经毒性的机制。这对应于我们的假设,即迟发性运动障碍与纹状体间接途径中型棘状神经元的神经毒性有关。
BACKGROUND: Tardive dyskinesia is a disorder characterized by involuntary muscle movements that occur as a complication of long-term treatment with antipsychotic drugs. It has been suggested to be related to a malfunctioning of the indirect pathway of the motor part of the cortical-striatal-thalamic-cortical circuit, which may be caused by oxidative stress-induced neurotoxicity.
METHODS: The purpose of our
study was to investigate the possible association between phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) function and tardive dyskinesia in 491 Caucasian patients with schizophrenia from 3 different psychiatric institutes in West Siberia. The Abnormal Involuntary Movement Scale was used to assess tardive dyskinesia. Individuals were genotyped for 3 single nucleotide polymorphisms in PIP5K2A gene: rs10828317, rs746203, and rs8341.
RESULTS: A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene (rs10828317) and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related.
CONCLUSIONS: We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.