Mental Health Organization GGZ Centraal, Amersfoort, the Netherlands.
Psychopharmacology (Berl). 2012 Feb;219(3):727-36. doi: 10.1007/s00213-011-2394-1. Epub 2011 Jul 13.
Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system.
This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample.
In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways).
Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the -141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD.
Two associations were found between genetic variation TaqI_D and the -141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way.
迄今为止，抗精神病药引起的精神分裂症运动障碍（MD）的药物遗传学研究主要集中在迟发性运动障碍上。只有少数研究检查了更急性的抗精神病药引起的 MD，如帕金森病和静坐不能。值得注意的是，所有 MD 都与多巴胺系统的失调有关。
本研究旨在在一个年轻的白种人群体中复制先前报道的候选基因与急性和迟发性抗精神病药引起的 MD 之间的关联。
在 402 名患者（中位年龄 26 岁）中，总共对从文献中预先选择的八个与多巴胺相关的候选基因中的 13 个多态性进行了基因分型（涉及多巴胺和 5-羟色胺受体、多巴胺降解和自由基清除酶途径）。
与无 MD 的患者相比，有 MD 的患者平均使用的氟哌啶醇剂量当量更高。MD 的患病率很高，并且在第一代和第二代抗精神病药之间没有差异。发现以下显著关联：（a）TaqI_D 多态性与静坐不能（每个额外的 C-等位基因的 OR=2.3，p=0.001）和（b）-141C 多态性与迟发性运动障碍（每个额外的 Del 等位基因的 OR=0.20，p=0.001）之间存在显著关联。其他多态性与 MD 没有显著关联。
DRD2 基因中的 TaqI_D 和-141C 多态性与抗精神病药引起的 MD 之间存在两种关联；一种与急性静坐不能有关，另一种与迟发性运动障碍有关。这两种多态性先前分别与迟发性运动障碍和急性帕金森病有关。这些结果表明，这些 DRD2 基因变异在抗精神病药引起的 MD 的易感性中的作用是以更普遍或多效性的方式发生的。
