Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mov Disord. 2010 Jul 30;25(10):1470-6. doi: 10.1002/mds.23122.
In this study, we investigated the role of the dopamine receptor D4 (DRD4) 48-base pairs (bp) variable number of tandem repeats (VNTR) and perinatal adversities regarding severity of tics and comorbid symptoms in children with tic disorders. We genotyped 110 children with tics with regard to the 48-bp VNTR and assessed presence of prenatal smoking exposure, and pregnancy and delivery complications by parent questionnaires. We examined associations between 2, 3, 4, and 7 repeat (R) alleles and severity of tics and comorbid obsessive-compulsive, depressive, anxious, and autistic symptoms. Through linear regressions, we investigated whether perinatal adversities and the 2R, 3R, 4R, and 7R alleles would interact with severity ratings of tics or comorbid symptoms as outcome. Presence of a 2R allele was related to more severe obsessive-compulsive symptoms, and presence of a 3R allele to increased severity of autistic features. Pregnancy complications were associated with decreased obsessive-compulsive symptom severity, and prenatal smoking exposure to more severe depressive and autistic symptoms. In children without a 3R allele delivery complications were associated with more severe tics, but in children with a 3R variant an inverse relation between delivery complications and tic severity was found. Moreover, the relation between delivery complications and internalizing symptom severity appeared to be most pronounced in children with a 2R allele. In conclusion, this study provides evidence for a role of the 48-bp VNTR in the etiology of tic and associated disorders, and for interactions with delivery complications regarding severity of tics and co-occurring internalizing symptoms.
在这项研究中，我们调查了多巴胺受体 D4（DRD4）48 个碱基对（bp）串联重复数可变多态性（VNTR）和围产期逆境与抽动障碍儿童抽动严重程度和共患症状之间的关系。我们对 110 名抽动儿童进行了 48-bpVNTR 基因分型，并通过家长问卷评估了产前吸烟暴露以及妊娠和分娩并发症的情况。我们检查了 2、3、4 和 7 个重复（R）等位基因与抽动严重程度以及共患强迫症、抑郁、焦虑和自闭症症状之间的关联。通过线性回归，我们研究了围产期逆境和 2R、3R、4R 和 7R 等位基因是否会与抽动严重程度或共患症状的严重程度作为结果产生相互作用。存在 2R 等位基因与更严重的强迫症症状有关，存在 3R 等位基因与自闭症特征严重程度增加有关。妊娠并发症与强迫症症状严重程度降低有关，而产前吸烟暴露与更严重的抑郁和自闭症症状有关。在没有 3R 等位基因的儿童中，分娩并发症与更严重的抽动症有关，但在有 3R 变异的儿童中，分娩并发症与抽动症严重程度之间呈反比关系。此外，分娩并发症与内化症状严重程度之间的关系在携带 2R 等位基因的儿童中似乎最为明显。总之，这项研究为 48-bpVNTR 在抽动症和相关障碍的病因学中的作用以及与分娩并发症在抽动严重程度和共患内化症状方面的相互作用提供了证据。
