单胺氧化酶A基因单体型预测注意缺陷多动障碍哌甲酯治疗的反应  

Association of better methylphenidate response with a haplotype of monoamine oxidase A gene in the treatment of attention-deficit / hyperactivity disorder

作　　者：陈敏 陈芸[1] 汤宜朗[2] 张浩波[1] 李君[3] 汪冰 杨莉[1] 王玉凤[1] 

机构地区：[1]北京大学第六医院,北京大学精神卫生研究所,卫生部精神卫生学重点实验室(北京大学),北京100191 [2]埃默里大学医学院人类遗传学系,美国亚特兰大30322 [3]北京师范大学认知神经科学与学习国家重点实验室,北京100875

出　　处：《中国心理卫生杂志》2014年第10期748-753,共6页Chinese Mental Health Journal

基　　金：国家重点基础研究发展计划项目(973)(2014CB846100);国家自然科学基金(30800302)

摘　　要：目的：研究单胺氧化酶A基因（MAOA）变异对哌甲酯治疗注意缺陷多动障碍（ADHD）临床疗效的影响。方法：以90例符合美国精神障碍诊断统计手册第4版（DSM．Ⅳ）诊断标准的汉族ADHD男孩为研究对象，经2—4周的哌甲酯开放剂量滴定，至增加剂量没有进一步临床改善或出现不能耐受的不良作用时获得最佳治疗反应。平均终末剂量（17．5±7．7）mg／d。在基线和获得最佳剂量后使用ADHD评定量表（ADHD—RS）和Conners父母症状问卷评估行为变化，以ADHD—RS减分作为主要疗效评估指标，Conners多动指数（CIH）减分作为次要疗效评估指标。患者DNA经聚合酶链反应（PCR）扩增，使用聚丙烯酰胺凝胶电泳检测MAOA30bpVNTR，T941G和C1460T多态性。结果：本研究未能发现单个多态性与哌甲酯治疗反应的关联（P〉0．05）。但是单体型分析发现具有3TC单体型的患者ADHD—RS总分下降明显多于携带3GT和4TC单体型[（22．8．4-11．4）VS．（8．7±9．2）VS．（11．0±10．6），P〈0．05）]，携带3TC单体型患者对哌甲酯治疗反应优于未携带3TC单体型患者，ADHD—RS和CIH量表的得分差异均具有统计学意义（P〈0．05，效应值r=0．40—0．60）。两类单体型患者的差异在多变量方差分析中同样有统计学意义（P〈0．05）。结论：本研究提示MAOA基因多态性与哌甲酯治疗ADHD的临床反应存在关联，携带3TC单体型患者更有可能有较好治疗反应。Objective： To explore whether variants in monoamine oxidase A gene （MAOA） contribute to inter-individual variation of clinical response to methylphenidate in children with attention-deficit/hyperactivity disorder. Methods： Ninety Hart Chinese boys meeting criteria for ADHD in the Diagnostic and Statistical Manual ofMental Disorders, Fourth Edition, （DSM-Ⅳ） were recruited. Methylphenidate treatment was given in titrated doses in order to achieve optimal response. Behavior changes were measured with the ADHD Rating Scale （ADHD-RS） and the Conners Parent Rating Scales at baseline and after optimal doses were reached. The decrease of ADHD-RS scores were primary measures of the treatment effect, while the Conners Index of Hyperactivity （CIH） was the secondary measure. The MAOA 30bp variable number of tandem repeats （VNTR）, T941G and C1460T polymorphisms were genotyped by polymerase chain reaction （PCR） and polyacrylamide gelelectrophoresis （PAGE）. Resuits： There was no association between single polymorphisms and methylphenidate response after adjusting for baseline rating scores （P 〉 0. 05）. In contrast, haplotype analysis revealed that some patients with the rare 3TC haplotype showed more decrease of the ADHD-RS total score than those with 3GT and 4TC haplotypes [（22. 8 ±11.4） vs. （8.7±9. 2） vs. （ 11.0 ± 10. 6）, P = 0. 012]. Patients carrying 3TC haplotype showed better response to methylphenidate than those not carrying 3TC, with statistical significance in score changes of both ADHD-RS and CIH （P 〈 0. 05, effect size： r = 0.40 ～ 0. 60, Multi-variant Analysis of Variance（MANOVA） also had statistical sig- nificance （P 〈 0. 05）. Conclusion： These results suggest association between MAOA polymorphisms and ADHD response with methylphenidate （MPH） treatment, and patients carrying 3TC haplotype are more likely to show better response to methylphenidate.

关 键 词：注意缺陷多动障碍 单胺氧化酶 基因 哌甲酯 遗传相关性研究 

分 类 号：R749.94[医药卫生—神经病学与精神病学]