Biomarkers of ADHD Treatment Response

Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder associated with psychiatric, social, academic, occupational, and health impairments across the lifetime. Although pharmacological interventions for pediatric ADHD are safe and effective, there is considerable variability in treatment response at the individual level. As a result, identification of optimal medication class and dose is often not attained in community clinical settings. The current application constitutes a translational biomarkers study aimed at identifying electroencephalography (EEG) and event related potential (ERP) biomarkers of preferential response to two commonly prescribed psychostimulants among children with ADHD. The results of this investigation will improve understanding of individual differences in neurobiological mechanisms of ADHD and provide preliminary data for a large-scale clinical trial aimed at developing a precision medicine care model for pharmacological treatment of ADHD. With the support of the Translational Neuroscience Center Clinical Research Operations services and in collaboration with the Boston Children's Hospital Primary Care Center (CHPCC), the investigators will execute a sequential crossover design study examining pre-treatment EEG and ERP biomarkers of response to methylphenidate (MPH; Concerta) among all children and to mixed amphetamine salts (MAS; Adderall-XR) among children with suboptimal response to MPH. Additional pre- and post-treatment assessments will be integrated with standard clinical care provided by Dr. Chan (co-PI) in the Division of Developmental Medicine. The study will recruit 30 stimulant-treatment-naïve children with ADHD, ages 7-11, from the CHPCC. Additionally, analyses will capitalize on Dr. Arnett's (co-PI) existing EEG/ERP data on 40 typically developing (TD) children in the same age range to maximize power for statistical comparisons. The investigators hypothesize that, consistent with Dr. Arnett's prior work, the EEG and ERP profiles will differentiate children with positive response to MPH versus preferential response to MAS. Specifically, the investigators hypothesize that MPH responders will have reduced P3 ERP amplitude and normal aperiodic spectral slope, while MAS preferential responders will have normal P3 amplitude and flatter aperiodic spectral slope. The investigators expect that slow individual alpha peak will be associated with reduced response to both MPH and MAS, as suggested by prior literature. Additionally, the investigators hypothesize that at optimal dosing, treatment-related change in EEG/ERP biomarkers will be associated with ADHD symptom improvement; this will indicate that individual differences in psychostimulant response reflect individual differences in the neurobiological etiology of ADHD symptoms. The results of this pilot study will support application for federal funding for a large-scale clinical trial. The long-term outcomes of this line of research stand to benefit children and families with ADHD, as well as children with other primary diagnoses commonly associated with ADHD (e.g., autism spectrum disorder; genetic syndromes). Moreover, differences in neurophysiological correlates of differential stimulant response have potential to increase our knowledge of neural mechanisms underlying psychostimulant medication effects.