Tph2 gene variants modulate response control processes in adult ADHD patients and healthy individuals
Tph2 gene variants modulate response control processes in adult ADHD patients and healthy individuals
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DOI：
10.1038/mp.2008.39
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发表时间：
2009-11-01
影响因子：
11
通讯作者：
Fallgatter, A. J.
中科院分区：
文献类型：
--
作者：
Baehne, C. G.;Ehlis, A-C;Fallgatter, A. J.
虽然注意力缺陷多动障碍（ADHD）的治疗干预仍然集中在多巴胺能系统，最近的研究表明，多巴胺能功能障碍，以及这种疾病。在这方面，编码5-羟色胺（5-HT）生物合成限速酶的色氨酸羟化酶基因（TPH 2）的几种变体与ADHD有关。TPH 2基因的rs 4570625 G等位基因多态性已经与健康成年人在感知任务中对情绪刺激的大脑反应性改变有关。在这里，我们在成人ADHD患者（n = 124）和健康对照（n = 84）的大样本中研究了ADHD相关风险等位基因rs 4570625和rs 11178997在认知反应控制期间对前额叶脑功能的影响。在记录持续EEG期间，通过Go-NoGo任务（连续性能测试; CPT）引发反应控制。根据CPT的Go和NoGo条件下产生的事件相关电位，NoGo前化（NGA）已被计算为前额叶脑功能的有效神经生理参数。在目前的研究中，发现两种多态性的ADHD风险等位基因与健康对照和ADHD患者的NGA减少相关。这些发现与这样的观点一致，即与改变的多巴胺能神经传递相关的遗传变异也与反应抑制期间前额叶皮层的功能相关。这种机制也可能与ADHD的病理生理学有关。Molecular Psychiatry（2009）14，1032-1039; doi：10.1038/mp.2008.39; 2008年4月22日在线发表
Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), have been associated with ADHD. The rs4570625 G-allele polymorphisms of the TPH2 gene have already been related to altered reactivity of the brain during perception tasks with emotional stimuli in healthy adults. Here we investigated the influence of the ADHD related risk alleles for rs4570625 and for rs11178997 on prefrontal brain function during cognitive response control in large samples of adult ADHD patients (n = 124) and healthy controls (n = 84). Response control was elicited with a Go-NoGo task (continuous performance test; CPT) performed during recording of an ongoing EEG. From the resulting event-related potentials in the Go-and NoGo conditions of the CPT, the NoGo-anteriorization (NGA) has been calculated as a valid neurophysiological parameter for prefrontal brain function. In the current study, ADHD risk alleles of both polymorphisms were found to be associated with a reduction in the NGA in both healthy controls and ADHD patients. These findings are in line with the notion that genetic variations associated with altered serotonergic neurotransmission are also associated with the function of the prefrontal cortex during response inhibition. This mechanism might also be relevant in the pathophysiology of ADHD. Molecular Psychiatry (2009) 14, 1032-1039; doi:10.1038/mp.2008.39; published online 22 April 2008