Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder: A Randomized Controlled Trial.
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.
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.|Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ayaka
A
Ishii-Takahashi
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ryu
R
Takizawa
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yukika
Y
Nishimura
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yuki
Y
Kawakubo
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Graduate School of Comprehensive Human Science, Graduate Course of Disability Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Kasumi
K
Hamada
Department of Electrical Engineering, Graduate School of Engineering, Kyoto University, Kyoto, Japan.|Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan.
Shiho
S
Okuhata
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Optical Topography Group, Application Development Office, Hitachi Medical Corporation, Chiba, Japan.
Shingo
S
Kawasaki
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Disability Services Office, Communication Support Room, Division for Counseling and Support, the University of Tokyo, Tokyo, Japan.
Hitoshi
H
Kuwabara
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takafumi
T
Shimada
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ayako
A
Todokoro
Department of Paediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|National Centre for Child Health and Development, Tokyo, Japan.
Takashi
T
Igarashi
Division for Counseling and support, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kei-Ichiro
K
Watanabe
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hidenori
H
Yamasue
Karasuyama Hospital Showa University School of Medicine, Tokyo, Japan.
Nobumasa
N
Kato
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kiyoto
K
Kasai
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yukiko
Y
Kano
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000473:pathology*; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D010108:Oxyhemoglobins / Q000378:metabolism; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D019265:Spectroscopy, Near-Infrared; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D010108:Oxyhemoglobins; D008774:Methylphenidate