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多巴胺能基因分析表明,注意力不集中而非智商对印度多动症先证者的执行功能障碍有影响。

Dopaminergic gene analysis indicates influence of inattention but not IQ in executive dysfunction of Indian ADHD probands.

作者信息

Maitra Subhamita, Chatterjee Mahasweta, Sinha Swagata, Mukhopadhyay Kanchan

机构信息

Manovikas Biomedical Research and Diagnostic Centre, Kolkata, India.

Mahidol University, Institute of Molecular Biosciences, Thailand.

出版信息

J Neurogenet. 2019 Dec;33(4):209-217. doi: 10.1080/01677063.2019.1672679. Epub 2019 Oct 30.

Abstract

Organizational inefficiency and inattention are speculated to be the reason for executive deficit (ED) of ADHD probands. Even with average IQ, probands often perform poorly due to higher inattention. Pharmacotherapy, cognitive behavioural therapy, and counselling provide only symptomatic relief. Several candidate genes showed involvement with ADHD; the most consistent are dopamine receptor 4 (DRD4) and solute carrier family 6 member 3 (SLC6A3). We analyzed association of rarely investigated DRD4 and SLC6A3 variants with ADHD core traits in Indo-Caucasoid probands. ED, inattention, organizational efficiency, and IQ were measured by Barkley Deficit in Executive Functioning-Child & Adolescent scale, DSM-IV-TR, Conners' Parent Rating Scale-revised, and WISC respectively. Target sites were analyzed by PCR, RFLP, and/or Sanger sequencing of genomic DNA. DRD4 variants mostly affected inattention while SLC6A3 variants showed association with IQ. Few DRD4 and SLC6A3 variants showed dichotomous association with IQ and inattention. DRD4 Exon3 VNTR >4R showed negative impact on all traits excepting IQ. Inattention showed correlation with attention span, organizational efficiency, and ED, while IQ failed to do so. We infer that IQ and attention could be differentially regulated by dopaminergic gene variants affecting functional efficiency in ADHD and the two traits should be considered together for providing better rehabilitation.

摘要

组织效率低下和注意力不集中被推测为多动症先证者执行功能缺陷(ED)的原因。即使智商平均,先证者也常因注意力不集中而表现不佳。药物治疗、认知行为疗法和咨询仅能缓解症状。几个候选基因显示与多动症有关;最一致的是多巴胺受体4(DRD4)和溶质载体家族6成员3(SLC6A3)。我们分析了在印度高加索先证者中很少研究的DRD4和SLC6A3变体与多动症核心特征的关联。分别通过执行功能缺陷儿童与青少年量表、《精神疾病诊断与统计手册》第四版修订版、康纳斯父母评定量表修订版和韦氏儿童智力量表来测量ED、注意力不集中、组织效率和智商。通过对基因组DNA进行PCR、RFLP和/或桑格测序来分析目标位点。DRD4变体大多影响注意力不集中,而SLC6A3变体显示与智商有关联。少数DRD4和SLC6A3变体与智商和注意力不集中呈二分关联。DRD4外显子3可变数目串联重复序列(VNTR)>4R对除智商外的所有特征均有负面影响。注意力不集中与注意力持续时间、组织效率和ED相关,而智商则不然。我们推断,智商和注意力可能受到影响多动症功能效率的多巴胺能基因变体的差异调节,在提供更好的康复治疗时应将这两个特征一起考虑。

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