注意缺陷多动障碍转换功能与NRXN1基因的关联研究

Association between set shifting in attention deficit/hyperactivity disorder(ADHD) and NRXN1 gene

目的:探讨注意缺陷多动障碍(ADHD)转换功能与NRXN1基因的关联。方法:顺序纳入符合美国精神障碍诊断与统计手册第4版(DSM-IV)ADHD诊断标准的ADHD儿童756例和年龄匹配的正常对照儿童133例。采用TMT连线测试(Trail Making Test)记录被试者转换功能各指标,包括数字连线时间、数字连线错误次数、数字字母连线时间和数字字母连线错误次数。选择NRXN1基因的两个单核苷酸多态性(rs1592728和rs4971652)位点,利用Sequenom基因分型平台进行基因型检测。在全部ADHD病例儿童和正常对照采用多重线性回归分析基因型对ADHD转换功能的影响因素,其次,分别在ADHD组和对照组中采用多重线性回归分层分析转换功能与基因型之间的关联。结果:多重线性回归显示转换功能与年龄(β=0.42,P<0.001)、智商(β=0.34,P<0.001)、罹患ADHD(β=0.08,P=0.004)和rs4971652GG基因型(β=0.06,P=0.039)负向关联;ADHD组转换功能与年龄(β=0.46,P<0.001)、智商(β=0.32,P<0.001)、rs4971652的GG基因型(β=0.07,P=0.018)负向关联,与ADHD亚型(β=0.06,P=0.033)正向关联,ADHD-I型比ADHD-C型患儿受损严重;对照组转换功能与年龄(β=0.25,P=0.002)、智商(β=0.40,P<0.001)负向关联。结论:ADHD患儿转换功能可能与NRXN1基因SNPs存在关联,GG基因型患者转换功能受损相对轻。

Objective： To study the association between set shifting in ADHD and NRXN1 gene. Methods： According to the diagnostic standard of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition （DSM-IV）. Totally 756 Hart Chinese ADHD children and 133 Han Chinese unaffected children were involved in the analysis. Set shifting, including number connection time （ NOTIM）, number connection error times （NOERR）, number and letter alternant connection time （LETIM）, number and letter alternant error times （LEERR）, and shifting time（each value was the difference between LETIM and NOTIM）, was recorded by trail making test （TMT）. Two SNPs （Single Nucleotide Polymorphisms） of NRXN1 gene, rs1592728 and rs4971652, were chose to detect genotype using Sequenom Mass ARRAY system by real time quantitative polymerase chain reaction. Linear regression analysis was applied to explore the influence of set shifting, then, stratified analysis was used to study the association between set shifting and rs1592728 as well as rs4971652 in ADHD cases and controls separately. Results： Linear regression analysis showed that there was a negative correlation between set shifting and month （β= 0. 42, P 〈 0. 001）, IQ （β = 0. 34, P 〈 0. 001）, group （β = 0. 08, P = 0. 004）, GG genotype of rs4971652 （β = 0. 06, P = 0. 039）. Among ADI-ID children, there was a negative relationship between set shifting and month （β = 0. 46, P 〈 0. 001）, IQ （β =0. 32, P 〈0. 001）, GG genotype of rs4971652 （/3 =0. 07, P =0. 018）, a positive association was found between set shifting and ADHDSUB （β = 0. 06, P = 0. 033）, set shifting damaged higher with ADHD-I children than ADHD-C children. While, in controls, set shifting was in inverse relation with month （β = 0. 25, P = 0. 002） and IQ （β = 0. 40, P 〈 0. 001）. Conclusion： It suggests that the association between shift in ADHD children and polymorphism of NRXN1 gene is existed, set shifting deficit less seriously in GG genotype.