Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity
Ayaka Ishii-Takahashi1,2,3, Ryu Takizawa3, Yukika Nishimura3
1Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Insights
Near-infrared spectroscopy (NIRS) can predict treatment response in children with attention-deficit hyperactivity disorder (ADHD) receiving methylphenidate hydrochloride (MPH). This neuroimaging biomarker shows potential for guiding MPH treatment decisions and monitoring effectiveness.
Area of Science:
- Neuroscience
- Pediatrics
- Biomarkers
Background:
- Methylphenidate hydrochloride (MPH) is a first-line ADHD treatment, but 30% of children do not respond.
- Predicting MPH response is crucial for effective ADHD management in children.
Purpose of the Study:
- To develop a neuroimaging biomarker using near-infrared spectroscopy (NIRS) to predict clinical response to MPH in children with ADHD.
- To assess the predictive value of baseline NIRS and single-dose MPH response (ΔNIRS) for long-term MPH treatment outcomes.
Main Methods:
- A double-blind, placebo-controlled, crossover trial involving single-dose MPH, followed by a 4-to-8-week open-label MPH trial and 1-year follow-up.
- NIRS measurements were taken at baseline, after single-dose MPH, and after continuous MPH administration in children with ADHD (drug-naïve and previously treated) and healthy controls.
- A leave-one-out classification algorithm was used to determine the accuracy of NIRS in predicting clinical outcomes (CGI-S scores).
Main Results:
- ΔNIRS significantly predicted Clinical Global Impressions-Severity (CGI-S) scores after 4-to-8-week and 1-year MPH administration.
- The NIRS-based classification algorithm achieved 81% accuracy in predicting treatment response.
- Drug-naïve children with ADHD showed lower baseline prefrontal activation, which normalized after MPH treatment, suggesting MPH's efficacy in modulating brain activity.
Conclusions:
- Supplementary NIRS measurements show promise as an objective biomarker for predicting and monitoring MPH treatment response in children with ADHD.
- NIRS could aid in personalized treatment strategies and improve clinical decision-making for MPH therapy.
- The findings support the use of NIRS to identify children likely to benefit from MPH and to track treatment effectiveness over time.
Abstract:
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.
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