Methylphenidate-Elicited Distinct Neuropharmacological Activation Patterns Between Medication-Naive Attention Deficit Hyperactivity Disorder Children With and Without Comorbid Autism Spectrum Disorder: A Functional Near- Infrared Spectroscopy Study

Objective: We aimed to clarify the validity of fNIRS measurement for assessing the methylphenidate (MPH) induced neuropharmacological effect in medication-naïve children with attention deficit hyperactivity disorder (ADHD) with or without comorbid autism spectrum disorder (ASD), thereby providing the first evidence for differing neurofunctional pathology between the two groups. Methods: We monitored the effects of a single acute clinical dose of MPH on the cortical hemodynamics of 32 medication-naïve ADHD children (ADHD with ASD n=11 and ADHD without ASD n=21) performing a go/no-go task before and 1.5 h after MPH or placebo administration, using a randomized, double-blind, placebo-controlled, crossover design. In addition, all subjects’ symptoms were monitored using the Japanese version of the ADHD Rating Scale-IV (ADHDRS- IV-J) before and one month after MPH administration. Results: Medication-naïve ADHD children without ASD exhibited reduced right prefrontal activation. MPH medication elicited significant right prefrontal activation except in comparative conditions associated with the placebo effect. Medication-naïve ADHD children with ASD exhibited marginal activation before the first day of medication and reduced activation after MPH medication in the right prefrontal area. While the neuropharmacological effects of MPH were different, ADHD-RS-IV-J scores were significantly improved one month after MPH administration in ADHD groups both with and without ASD. Conclusion: Taken together, these results suggest that ADHD with ASD is characterized by a different underlying neurofunctional pathology for inhibition control than that without ASD. To our knowledge, this is the first comparative neuroimaging study between ADHD patients with and without comorbid ASD.