注意缺陷多动障碍儿童5-HTTLPR长等位基因A-G单核苷酸多态性与静息态脑功能及行为学的相关性

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1424 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：分析注意缺陷多动障碍（ADHD）患儿SLA基因型与SLG基因型间脑低频振荡振幅（ALFF）的差异以及静息态ALFF与行为学的相关性，探讨A-G单核苷酸多态性对5-HTTLPR长等位基因（L）转录活动的影响。方法：22例ADHD患儿通过PCR基因检测技术筛查出SLA基因型（SLA基因组）12例、SLG基因型（SLG基因组）10例，用磁共振扫描仪对患儿进行功能磁共振静息状态扫描，采用ALFF评估静息态脑功能，Conners儿童行为问卷评估行为现状，有意义脑区的ALFF平均信号与Conners儿童行为问卷的各项指标做两两相关分析。结果：SLA基因组在右额上回、左额中回、左脑岛、右边缘扣带回ALFF值高于SLG基因组，其中左额中回的ALFF值与Conners儿童行为问卷的冲动多动评分呈显著负相关（r=-0.359，P=0.020），右边缘扣带回的ALFF值与冲动多动评分、品行问题评分均呈显著负相关（r=-0.479，P=0.024；r=-0.542，P=0.009）。SLA基因组低于SLG基因组的脑区ALFF值差异均无统计学意义。结论：与SLG基因型相比，SLA基因型在大脑的多个区域均表现出更为活跃的功能活动，且倾向于更严重的冲动多动症状和品行问题。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	张晓燕
	梁艳
	杜松妹
	林海西
	王维千
	陈宏
	刘惠茹
	王美豪
	赵永忠
	杨闯

关键词 ：注意缺陷多动障碍, 5-羟色胺转运体, 多态性, 单核苷酸, 磁共振成像

Abstract：Objective: To study the differences of amplitude of low frequency fluctuation (ALFF) between genotypes of SLA and SLG with attention deficit hyeractivity disorder (ADHD) children using functional magnetic resonance imaging (fMRI) and the relationship between ALFF and behavioristic. Methods: Screened out the genotypes of SLA and SLG of ADHD children by PCR gene detection technology. And all of the ADHD children were scanned with fMRI scanner in the resting state, using ALFF to assess the resting state cerebral function. And the Conners children behavior questionnaire was used to assess the behavior status quo. Results: Compared with the SLG genotype, SLA genotype showed ALFF were increased in right superior frontal gyrus, left middle frontal gyrus, left insula, right limbic cingulate gyrus, and no brain region with decreased ALFF. The ALFF of left middle frontal gyrus was significantly negative correlative with impulse-hyperactivity ratings of conners children behavior questionnaire, and ALFF of right limbic cingulate gyrus was significantly negative correlative with impulse-hyperactivity ratings and conduct problem score. Conclusion: Compared with the SLG genotype, the SLA genotype shows more yauld cerebral functional activities, and tend to be more serious impulse-hyperactivity and conduct problem.

Key words： attention deficit hyperactivity disorder serotonin transporter polymorphism, single nucleotide magnetic resonance imaging

收稿日期: 2017-03-04

基金资助:浙江省自然科学基金资助项目（LY14H090012）；温州市科技计划项目（Y20140399，Y20130163）。

通讯作者: 杨闯，副主任医师，Email：dryangchuang@163.com

作者简介: 张晓燕（1983-），女，浙江温岭人，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I11/781

[1] KUNTSI J, RIJSDIJK F, RONALD A, et al. Genetic influences on the stability of attention-deficit/hyperactivity disorder symptoms from early to middle childhood[J]. Biol Psychiatry, 2005, 57(6): 647-654.
[2] RIETVELD M J, HUDZIAK J J, BARTELS M, et al. Heritability of attention problems in children: longitudinal results from a study of twins, age 3 to 12[J]. J Child Psychol Psychiatry, 2004, 45(3): 577-588.
[3] HU X, OROSZI G, CHUN J, et al. An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk[J]. Alcohol Clin Exp Res, 2005, 29(1): 8-16.
[4] LIPSKY R H, HU X Z, GOLDMAN D. Additional functional variation at the SLC6 A4 gene[J]. Am J Med Genet B Neuropsychiatr Genet, 2009, 150B(1): 153.
[5] 刘豫鑫, 刘津, 王玉凤. 简明儿童少年国际神经精神访谈儿童版的信效度[J]. 中国心理卫生杂志, 2011, 25(1): 8-13.
[6] CHAO G Y, YU F Z. DPARSF: A matlab toolbox for “pipeline” data analysis of resting-state fMRI[J]. Front Syst Neurosci, 2010, 4(13): 13.
[7] HSU A L, CHOU K H, CHO Y P, et al. Physiological contribution in spontaneous oscillations: An approximate quality-assurance index for resting-state fMRI signals[J]. PLoS One, 2016, 11(2): e0148393.
[8] ZANG Y F, HE Y, ZHU C Z, et al. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI[J]. Brain Dev, 2007, 29(2): 83-91.
[9] SCHALL J D. On the role of frontal eye field in guiding attention and saccades[J]. Vision Res, 2004, 44(12): 1453-1467.
[10] SUSKAUER S J, SIMMONDS D J, CAFFO B S, et al. fMRI of intrasubject variability in ADHD: anomalous premotor activity with prefrontal compensation[J]. J Am Acad Child Adolesc Psychiatry, 2008, 47(10): 1141-1150.
[11] PARK B Y, PARK H. Connectivity differences between adult male and female patients with attention deficit hyperactivity disorder according to resting-state functional MRI [J]. Neural Regen Res, 2016, 11(1): 119-25.
[12] MOSTERT J C, SHUMSKAYA E, MENNES M, et al. Characterising resting-state functional connectivity in a large sample of adults with ADHD[J]. Prog Neuropsychopharmacol
Biol Psychiatry, 2016, 67: 82-91.
[13] KONARAD K, NEUFANG S, HANISCH C, et al. Dysfunctional attentional networks in children with attention deficit/hyperactivity disorder: evidence from an event-related functional magnetic resonance imaging study[J]. Biol Psychiatry, 2006, 59(7): 643-651.
[14] CAO X, CAO Q, LONG X, et al. Abnormal resting-state functional connectivity patterns of the putamen in medication-naive children with attention deficit hyperactivity disor-der[J]. Brain Res, 2009, 1303: 195-206.
[15] HALPERIN J M, NEWCORN J H, SCHWARTZ S T, et al. Age-related changes in the association between serotonergic function and aggression in boys with ADHD[J]. Biol Psychiatry, 1997, 41(6): 682-689.
[16] OADES R D. Dopamine-serotonin interactions in attention-deﬁcit hyperactivity disorder (ADHD)[J]. Prog Brain Res, 2008, 172(1): 105.
[17] THAKUR G A, GRIZENKO N, SENGUPTA S M, et al. The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD[J]. BMC Psychiatry, 2010, 10: 50.
[18] KENNETH D G, CARLA J D, VICTORIA I S, et al. Allele-specific associations of 5-HTTLPR/rs25531 with ADHD and autism spectrum disorder[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2013, 40(2): 292-297.
[19] JILLIAN L W, JIRAIR K B, SCOTT J P, et al. The impact of serotonin transporter (5-httlpr) genotype on the development of resting-state functional connectivity in children and adolescents: A preliminary report[J]. Neuroimage, 2012, 59(3): 2760-2770.
[20] NATALIA J, FRANK P M, JANE F, et al. The influence of 5-HTTLPR and Val66Met polymorphisms on cortical thickness and volume in limbic and paralimbic regions in depression: a preliminary study[J]. BMC Psychiatry, 2016, 16(1): 1-10.
[21] WILLEIT M, PRASCHAK R N. Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry[J]. Neuro Image, 2010, 53(3): 878-892.
[22] BORG J, HENNINGSSON S, SAIJO T, et al. Serotonintransporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in humans [J]. Int J Neuropsychopharmacol, 2009, 12(6): 783-792.