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成人注意缺陷多动障碍中的多巴胺转运体单倍型与奖赏相关纹状体反应。

The dopamine transporter haplotype and reward-related striatal responses in adult ADHD.

机构信息

Department of Psychiatry, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.

出版信息

Eur Neuropsychopharmacol. 2013 Jun;23(6):469-78. doi: 10.1016/j.euroneuro.2012.05.011. Epub 2012 Jun 30.


DOI:10.1016/j.euroneuro.2012.05.011
PMID:22749356
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable disorder and several genes increasing disease risk have been identified. The dopamine transporter gene, SLC6A3/DAT1, has been studied most extensively in ADHD research. Interestingly, a different haplotype of this gene (formed by genetic variants in the 3' untranslated region and intron 8) is associated with childhood ADHD (haplotype 10-6) and adult ADHD (haplotype 9-6). The expression of DAT1 is highest in striatal regions in the brain. This part of the brain is of interest to ADHD because of its role in reward processing is altered in ADHD patients; ADHD patients display decreased striatal activation during reward processing. To better understand how the DAT1 gene exerts effects on ADHD, we studied the effect of this gene on reward-related brain functioning in the area of its highest expression in the brain, the striatum, using functional magnetic resonance imaging. In doing so, we tried to resolve inconsistencies observed in previous studies of healthy individuals and ADHD-affected children. In a sample of 87 adult ADHD patients and 77 healthy comparison subjects, we confirmed the association of the 9-6 haplotype with adult ADHD. Striatal hypoactivation during the reward anticipation phase of a monetary incentive delay task in ADHD patients was again shown, but no significant effects of DAT1 on striatal activity were found. Although the importance of the DAT1 haplotype as a risk factor for adult ADHD was again demonstrated in this study, the mechanism by which this gene increases disease risk remains largely unknown.

摘要

注意缺陷多动障碍(ADHD)是一种高度遗传性疾病,已经确定了几个增加疾病风险的基因。多巴胺转运蛋白基因 SLC6A3/DAT1 在 ADHD 研究中被研究得最多。有趣的是,这个基因的一个不同的单倍型(由 3'非翻译区和内含子 8 中的遗传变异形成)与儿童 ADHD(单倍型 10-6)和成人 ADHD(单倍型 9-6)有关。DAT1 的表达在大脑的纹状体区域最高。大脑的这一部分是 ADHD 感兴趣的,因为它在奖励处理中的作用在 ADHD 患者中发生了改变;ADHD 患者在奖励处理过程中显示出纹状体激活减少。为了更好地理解 DAT1 基因对 ADHD 的影响,我们使用功能磁共振成像研究了该基因对大脑中表达最高的纹状体区域与奖励相关的大脑功能的影响。在这样做的过程中,我们试图解决以前在健康个体和 ADHD 受影响儿童的研究中观察到的不一致性。在 87 名成年 ADHD 患者和 77 名健康对照组中,我们证实了 9-6 单倍型与成年 ADHD 的关联。在 ADHD 患者的金钱奖励延迟任务的奖励预期阶段再次显示出纹状体激活不足,但没有发现 DAT1 对纹状体活动的显著影响。尽管在这项研究中再次证明了 DAT1 单倍型作为成人 ADHD 的风险因素的重要性,但该基因增加疾病风险的机制在很大程度上仍不清楚。

相似文献

[1]
The dopamine transporter haplotype and reward-related striatal responses in adult ADHD.

Eur Neuropsychopharmacol. 2012-6-30

[2]
Enlarged striatal volume in adults with ADHD carrying the 9-6 haplotype of the dopamine transporter gene DAT1.

J Neural Transm (Vienna). 2016-8

[3]
Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine.

Behav Pharmacol. 2015-2

[4]
Association between the dopamine transporter gene and the inattentive subtype of attention deficit hyperactivity disorder in Taiwan.

Prog Neuropsychopharmacol Biol Psychiatry. 2010-8-26

[5]
Association of the dopamine transporter (SLC6A3/DAT1) gene 9-6 haplotype with adult ADHD.

Am J Med Genet B Neuropsychiatr Genet. 2008-12-5

[6]
Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity.

Biol Psychiatry. 2005-2-1

[7]
Dopamine transporter genotype conveys familial risk of attention-deficit/hyperactivity disorder through striatal activation.

J Am Acad Child Adolesc Psychiatry. 2008-1

[8]
A quantitative trait locus analysis of the dopamine transporter gene in adults with ADHD.

Neuropsychopharmacology. 2002-10

[9]
An association between a dopamine transporter gene (SLC6A3) haplotype and ADHD symptom measures in nonclinical adults.

Am J Med Genet B Neuropsychiatr Genet. 2015-3

[10]
A variable number of tandem repeats in the 3'-untranslated region of the dopamine transporter modulates striatal function during working memory updating across the adult age span.

Eur J Neurosci. 2015-8

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[3]
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