Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Plot: I-24, Sector-J, E.M. Bypass, Kolkata, 700107, India.
Umea University, Umeå, Sweden.
Mol Biol Rep. 2022 Aug;49(8):7315-7325. doi: 10.1007/s11033-022-07521-y. Epub 2022 May 13.
Impulsivity (Imp), being one of the cardinal symptoms of Attention Deficit Hyperactivity Disorder (ADHD), often leads to inappropriate responses to stimuli. Since the dopaminergic system is the primary target for pharmaceutical intervention in ADHD, we investigated the association between ADHD-related Imp and functional gene variants of the dopamine transporter (SLC6A3) and catechol-O-methyltransferase involved in dopamine clearance.
Indo-Caucasoid families with ADHD probands (N = 217) were recruited based on the Diagnostic and Statistical Manual of Mental Disorders (DSM). Imp of the probands was assessed using the Domain Specific Imp Scale for Children and DSM. Peripheral blood was collected after obtaining informed written consent for participation, genomic DNA was isolated, and target sites were genotyped by DNA sequencing. The association of genetic variants with Imp was examined by the Quantitative trait analysis (QTA) and Analysis of variance (ANOVA). Post-Hoc analysis following QTA and ANOVA showed significant associations of rs2254408, rs2981359, and rs2239393 with different domains of Imp (P < 0.05). Various haplotypic combinations also showed statistically significant associations with Imp (P < 0.05). Multifactor dimensionality reduction models revealed strong effects of the variants on Imp. ADHD probands harboring the risk alleles exhibited a deficit in performance during cognitive assessment. Longitudinal follow-up revealed a significant association of rs2254408 with trait persistence.
The present study indicates the influence of the studied genetic variants on ADHD-associated imp, executive deficit, and disease persistence. Thus, these variants may be helpful as predictors for the success of individual therapeutic sessions during cognitive training.
冲动性（Imp）是注意力缺陷多动障碍（ADHD）的主要症状之一，常导致对刺激的不当反应。由于多巴胺能系统是 ADHD 药物干预的主要靶点，我们研究了与 ADHD 相关的 Imp 与多巴胺清除相关的多巴胺转运体（SLC6A3）和儿茶酚-O-甲基转移酶的功能性基因变异之间的关联。
根据《精神障碍诊断与统计手册》（DSM），我们基于 ADHD 先证者（N=217）招募了印度-高加索家族。使用儿童特定冲动量表和 DSM 评估先证者的冲动性。在获得参与的书面知情同意后收集外周血，分离基因组 DNA，并通过 DNA 测序对目标位点进行基因分型。通过定量性状分析（QTA）和方差分析（ANOVA）检查遗传变异与 Imp 的关联。QTA 和 ANOVA 后的事后分析显示，rs2254408、rs2981359 和 rs2239393 与 Imp 的不同域显著相关（P<0.05）。各种单倍型组合也与 Imp 显示出统计学上的显著关联（P<0.05）。多因素维度缩减模型显示，这些变异对 Imp 有强烈影响。携带风险等位基因的 ADHD 先证者在认知评估中表现出表现缺陷。纵向随访显示 rs2254408 与特质持续存在显著相关。
本研究表明，所研究的遗传变异对 ADHD 相关的冲动性、执行功能缺陷和疾病持续存在有影响。因此，这些变异可能有助于作为认知训练期间个别治疗疗程成功的预测因子。
