Ishii-Takahashi Ayaka, Takizawa Ryu, Nishimura Yukika, Kawakubo Yuki, Hamada Kasumi, Okuhata Shiho, Kawasaki Shingo, Kuwabara Hitoshi, Shimada Takafumi, Todokoro Ayako, Igarashi Takashi, Watanabe Kei-Ichiro, Yamasue Hidenori, Kato Nobumasa, Kasai Kiyoto, Kano Yukiko
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Paediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Neuropsychopharmacology. 2015 Nov;40(12):2676-85. doi: 10.1038/npp.2015.128. Epub 2015 May 4.
Although methylphenidate hydrochloride (MPH) is a first-line treatment for children with attention-deficit hyperactivity disorder (ADHD), the non-response rate is 30%. Our aim was to develop a supplementary neuroimaging biomarker for predicting the clinical effect of continuous MPH administration by using near-infrared spectroscopy (NIRS). After baseline assessment, we performed a double-blind, placebo-controlled, crossover trial with a single dose of MPH, followed by a prospective 4-to-8-week open trial with continuous MPH administration, and an ancillary 1-year follow-up. Twenty-two drug-naïve and eight previously treated children with ADHD (NAÏVE and NON-NAÏVE) were compared with 20 healthy controls (HCs) who underwent multiple NIRS measurements without intervention. We tested whether NIRS signals at the baseline assessment or ΔNIRS (single dose of MPH minus baseline assessment) predict the Clinical Global Impressions-Severity (CGI-S) score after 4-to-8-week or 1-year MPH administration. The secondary outcomes were the effect of MPH on NIRS signals after single-dose, 4-to-8-week, and 1-year administration. ΔNIRS significantly predicted CGI-S after 4-to-8-week MPH administration. The leave-one-out classification algorithm had 81% accuracy using the NIRS signal. ΔNIRS also significantly predicted CGI-S scores after 1 year of MPH administration. For secondary analyses, NAÏVE exhibited significantly lower prefrontal activation than HCs at the baseline assessment, whereas NON-NAÏVE and HCs showed similar activation. A single dose of MPH significantly increased activation compared with the placebo in NAÏVE. After 4-to-8-week administration, and even after MPH washout following 1-year administration, NAÏVE demonstrated normalized prefrontal activation. Supplementary NIRS measurements may serve as an objective biomarker for clinical decisions and monitoring concerning continuous MPH treatment in children with ADHD.
尽管盐酸哌甲酯（MPH）是治疗儿童注意力缺陷多动障碍（ADHD）的一线药物，但其无反应率为30%。我们的目的是通过使用近红外光谱（NIRS）开发一种辅助神经影像生物标志物，以预测持续服用MPH的临床效果。在基线评估后，我们进行了一项双盲、安慰剂对照、单剂量MPH交叉试验，随后进行了为期4至8周的MPH持续给药前瞻性开放试验以及为期1年的辅助随访。将22名未接受过药物治疗和8名先前接受过治疗的ADHD儿童（未用药组和非未用药组）与20名健康对照者（HCs）进行比较，后者在未干预的情况下接受了多次NIRS测量。我们测试了基线评估时的NIRS信号或ΔNIRS（单剂量MPH减去基线评估）是否能预测4至8周或1年MPH给药后的临床总体印象-严重程度（CGI-S）评分。次要结果是单剂量、4至8周和1年给药后MPH对NIRS信号的影响。ΔNIRS显著预测了4至8周MPH给药后的CGI-S。使用NIRS信号的留一法分类算法准确率为81%。ΔNIRS也显著预测了1年MPH给药后的CGI-S评分。对于次要分析，在基线评估时，未用药组的前额叶激活显著低于HCs，而非未用药组和HCs表现出相似的激活。与安慰剂相比，单剂量MPH使未用药组的激活显著增加。在4至8周给药后，甚至在1年给药后MPH洗脱后，未用药组的前额叶激活显示正常化。补充NIRS测量可作为临床决策和监测ADHD儿童持续MPH治疗的客观生物标志物。
