注意缺陷多动障碍男童SNAP-25基因MnlI多态性与静息态脑功能和工作记忆的相关性研究
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摘要
目的研究注意缺陷多动障碍男童SNAP-25基因MnlI多态性与静息态脑功能和工作记忆的相关性,探讨SNAP-25基因MnlI多态性对ADHD儿童脑功能的影响机制。方法采集36例TT纯合子基因型ADHD男童(简称TT组)和20例G等位基因型ADHD男童(简称TG组)静息态脑功能数据,采用局部一致性方法进行分析,比较两组之间静息态脑功能的差异。采用韦氏儿童智力量表第四版(WISC-Ⅳ)评估两组男童的工作记忆指数,独立样本t检验比较两组之间工作记忆能力的差异。当P<0.05认为差异有统计学意义。结果 1.静息态脑功能结果:与TG组比较,TT组:1)ReHo值高的脑区有:①默认模式网络(左后扣带回、双侧楔前叶、双侧额内侧回、左颞中下回、右颞中回);②语言功能区:左额上、中、下回,右额中回;③左中央前回等。2)ReHo值低的脑区有:①右中央后回;②左前扣带回,右前扣带回;③左顶上回等。2.工作记忆结果,TT组的工作记忆能力较TG组高,差异有统计学意义(P<0.05)。结论 SNAP-25基因MnlI多态性对ADHD男童脑功能具有不同的遗传效应,其不同基因型的工作记忆存在差异,fMRI可从神经网络角度解释其差异的脑功能基础。
Objective To investigate the association of SNAP-25 gene mnlI polymorphism with resting state brain eunction and working memory(WM) in boys with Attention-deficit/hyperactivity disorder(ADHD). Methods Resting stage functional magnetic resonance imaging was performed in 36 ADHD boys with TT homozygous genotype(TT group) and 20 ADHD boys with G allele(TG group). ReHo was used as a measure index. Two independent sample t-test was conducted to investigate the difference of ReHo values between the two groups. Wechsler Intelligence scale for Children(WISC-IV) was used to evaluate WM index of boys in the two groups. Two independent sample t-test was conducted to investigate different WM capacity between the two groups. The difference was statistically significant When P<0.05. Results 1. Compared with the TG group: 1)Increased ReHo values in TT group were found in: ① Default Mode Network: left posterior cingulate gyrus, left precuneus, right posterior cingulate, left medial superior frontal gyrus, right medial superior frontal gyrus, left middle temporal gyrus, right middle temporal gyrus; ② left superior frontal gyrus, left middle frontal gyrus, inferior frontal gyrus; ③ right middle frontal gyrus. 2)Decreased reHo values were found in: ① right postcentral gyrus, righ cerebellum posterior lobe; ② left Anterior cingulate, right Anterior cingulate; ③ left superior parietal gyrus. 2. WM in TT group was higher than that in TG group(P<0.05). Conclusion SNAP-25 gene MnlI polymorphism had different genetic impact on brain function in ADHD boys, and there were differences in WM between the two genotypes. f MRI can reveal possible basis from bran function network aspect.
Objective To investigate the association of SNAP-25 gene mnlI polymorphism with resting state brain eunction and working memory(WM) in boys with Attention-deficit/hyperactivity disorder(ADHD). Methods Resting stage functional magnetic resonance imaging was performed in 36 ADHD boys with TT homozygous genotype(TT group) and 20 ADHD boys with G allele(TG group). ReHo was used as a measure index. Two independent sample t-test was conducted to investigate the difference of ReHo values between the two groups. Wechsler Intelligence scale for Children(WISC-IV) was used to evaluate WM index of boys in the two groups. Two independent sample t-test was conducted to investigate different WM capacity between the two groups. The difference was statistically significant When P<0.05. Results 1. Compared with the TG group: 1)Increased ReHo values in TT group were found in: ① Default Mode Network: left posterior cingulate gyrus, left precuneus, right posterior cingulate, left medial superior frontal gyrus, right medial superior frontal gyrus, left middle temporal gyrus, right middle temporal gyrus; ② left superior frontal gyrus, left middle frontal gyrus, inferior frontal gyrus; ③ right middle frontal gyrus. 2)Decreased reHo values were found in: ① right postcentral gyrus, righ cerebellum posterior lobe; ② left Anterior cingulate, right Anterior cingulate; ③ left superior parietal gyrus. 2. WM in TT group was higher than that in TG group(P<0.05). Conclusion SNAP-25 gene MnlI polymorphism had different genetic impact on brain function in ADHD boys, and there were differences in WM between the two genotypes. f MRI can reveal possible basis from bran function network aspect.
引文
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[15] Fried R, Petty C, Faraone SV, et al. Is ADHD a risk factor for high school dropout a controlled study [J]. J Atten Disord, 2016, 20(5): 383-389.
[16] Mattfeld AT, Gabrieli JD, Biederman J, et al. Brain differences between persistent and remitted attention deficit hyperactivity disorder [J]. Brain, 2014, 137(Pt 9): 2423-2428.
[17] Barr CL, Feng Y, Wigg K, et al. Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder [J]. Mol Psychiatry, 2000, 5(4): 405-409.
[18] 单炎炎,贾艳滨,李雪果,等. 注意缺陷多动障碍的脑网络连接研究进展[J]. 中华精神科杂志, 2017, 50(3): 235-238.
[19] Wang C, Yang B, Fang D, et al. The impact of SNAP25 on brain functional connectivity density and working memory in ADHD [J]. Biol Psychol, 2018, 138(10): 35-40.
[20] de Melo BB V, Trigueiro MJ, Rodrigues PP. Systematic overview of neuroanatomical differences in ADHD: definitive evidence [J]. Dev Neuropsychol, 2018, 43(1): 52-68.
[2] Mohrmann R, de Wit H, Connell E, et al. Synaptotagmin interaction with SNAP-25 governs vesicle docking, priming, and fusion triggering [J]. J Neurosci, 2013, 33(36): 14417-14430.
[3] Caylak E. Biochemical and genetic analyses of childhood attention deficit/hyperactivity disorder [J]. Am J Med Genet B Neuropsychiatr Genet, 2012, 159B(6): 613-627.
[4] Gálvez JM, Forero DA, Fonseca DJ, et al. Evidence of association between SNAP25 gene and attention deficit hyperactivity disorder in a latin American sample [J]. Atten Defic Hyperact Disord, 2014, 6(1): 19-23.
[5] Zang Y, Jiang T, Lu Y, et al. Regional homogeneity approach to fMRI data analysis [J]. Neuroimage, 2004, 22(1): 394-400.
[6] Li G, Rossbach K, Jiang W, et al. Resting-state brain activity in Chinese boys with low functioning autism spectrum disorder [J]. Ann Gen Psychiatry, 2018, 17(1): 1-8.
[7] Hao H, Chen C, Mao W, et al. Aberrant brain regional homogeneity in first-episode drug-nave patients with major depressive disorder: a voxel-wise meta-analysis [J]. J Affect Disord, 2018, 245(2): 63-71.
[8] Zhou J, Gao Y, Bu X, et al. A multi-parameter resting-state functional magnetic resonance imaging study of brain intrinsic activity in attention deficit hyperactivity disorder children [J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2018, 35(3): 415-420.
[9] Chao-Gan Y, Yu-Feng Z, DPARSF: A MATLAB toolbox for "pipeline" data analysis of resting-state fMRI [J]. Front Syst Neurosci, 2010, 4(13): 1-8.
[10] Li W, Mai X, Liu C. The default mode network and social understanding of others: what do brain conectivity studies tell [J]. Front Hum Neurosci, 2014, 8(2): 1-15.
[11] Dennis EL, Thompson PM. Functional brain connectivity using fMRI in aging and Alzheimer's disease [J]. Neuropsychol Rev, 2014, 24(1): 49-62.
[12] Lee MH, Smyser CD, Shimony JS. Resting-state fMRI: a review of methods and clinical applications [J]. AJNR, 2013, 34(10): 1866-18672.
[13] Fried R, Abrams J, Hall A, Feinberg L, Pope A, Biederman J. Does Working Memory Impact Functional Outcomes in Individuals With ADHD: A Qualitative and Comprehensive Literature Review. J Atten Disord. 2017. 9 (1) : 1-8.
[14] Fried R, Chan J, Feinberg L, et al. Clinical correlates of working memory deficits in youth with and without ADHD: a controlled study [J]. J Clin Exp Neuropsychol, 2016, 38(5): 487-496.
[15] Fried R, Petty C, Faraone SV, et al. Is ADHD a risk factor for high school dropout a controlled study [J]. J Atten Disord, 2016, 20(5): 383-389.
[16] Mattfeld AT, Gabrieli JD, Biederman J, et al. Brain differences between persistent and remitted attention deficit hyperactivity disorder [J]. Brain, 2014, 137(Pt 9): 2423-2428.
[17] Barr CL, Feng Y, Wigg K, et al. Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder [J]. Mol Psychiatry, 2000, 5(4): 405-409.
[18] 单炎炎,贾艳滨,李雪果,等. 注意缺陷多动障碍的脑网络连接研究进展[J]. 中华精神科杂志, 2017, 50(3): 235-238.
[19] Wang C, Yang B, Fang D, et al. The impact of SNAP25 on brain functional connectivity density and working memory in ADHD [J]. Biol Psychol, 2018, 138(10): 35-40.
[20] de Melo BB V, Trigueiro MJ, Rodrigues PP. Systematic overview of neuroanatomical differences in ADHD: definitive evidence [J]. Dev Neuropsychol, 2018, 43(1): 52-68.