Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Korea.
Int J Neuropsychopharmacol. 2011 Nov;14(10):1399-410. doi: 10.1017/S146114571100099X. Epub 2011 Jun 28.
Research on psychostimulants, analysis of animal models and genetic association studies all suggest that the brain-derived neurotrophic factor gene (BDNF) may be a good candidate for pharmacogenetic studies of attention deficit hyperactivity disorder (ADHD). Yet to date there have been no pharmacogenetic studies of BDNF in ADHD. A total of 102 drug-naive ADHD children (8.7±2.1 yr) were treated with osmotic release oral system-methylphenidate (OROS-MPH) for 12 wk, and four kinds of response criteria were applied, based first, on a combined threshold of the ADHD Rating Scale - IV (ARS) and the Clinical Global Impression - Improvement scale (CGI-I); second, on scores of 1 or 2 vs. 3-7 on the CGI - Severity scale; third, on a >50% reduction in ARS scores; and fourth, on satisfaction of all of the aforementioned criteria. The Val⁶⁶Met polymorphism of BDNF and six single nucleotide polymorphisms from the SLC6A2, ADRA2A and NTF-3 genes were tested for association with each criterion. Relative to other genotypes, homozygosity for the Val allele of the BDNF Val⁶⁶Met polymorphism was associated with a greater relative frequency of good response under all four response criteria (after controlling for baseline ARS score, age, gender, final dose (mg/kg) of OROS-MPH at 12 wk, and level of academic functioning). This association was significant at the uncorrected level for the first and third response criteria (p=0.013 and p=0.018, respectively) and significant at a Bonferroni-corrected level for the second and fourth response criteria (p=0.0002, p=0.0003, respectively). Our findings support an association between homozygosity for the Val allele of BDNF and better response to OROS-MPH in Korean ADHD children as assessed by four different response criteria.
研究表明，包括兴奋剂研究、动物模型分析和遗传关联研究在内，脑源性神经营养因子（BDNF）基因都可能是注意缺陷多动障碍（ADHD）药物遗传学研究的一个很好的候选基因。然而，迄今为止，还没有关于 ADHD 中 BDNF 的药物遗传学研究。共有 102 名未经药物治疗的 ADHD 儿童（8.7±2.1 岁）接受了 12 周的奥昔布宁控释片（OROS-MPH）治疗，并应用了四种反应标准，首先是基于 ADHD 评定量表-IV（ARS）和临床总体印象-改善量表（CGI-I）的综合阈值；其次是 CGI-Severity 量表的 1 或 2 分与 3-7 分的评分；第三是 ARS 评分降低 50%以上；第四是满足所有上述标准。BDNF 的 Val⁶⁶Met 多态性和 SLC6A2、ADRA2A 和 NTF-3 基因的 6 个单核苷酸多态性与每个标准的相关性进行了测试。与其他基因型相比，BDNF Val⁶⁶Met 多态性的 Val 等位基因纯合与四种反应标准下的良好反应相对频率更高（在控制基线 ARS 评分、年龄、性别、12 周时 OROS-MPH 的最终剂量（mg/kg）和学业功能水平后）。这种相关性在未经校正的第一和第三反应标准下具有统计学意义（p=0.013 和 p=0.018），在第二和第四反应标准下具有统计学意义（p=0.0002，p=0.0003）。我们的研究结果支持 BDNF Val 等位基因纯合与韩国 ADHD 儿童对 OROS-MPH 反应更好之间的关联，这是通过四种不同的反应标准评估的。
