Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders among children and is associated with myriad adverse long-term outcomes including incarceration, injury, substance abuse and lower employment rates. Despite advances in pharmacologic and behavioral interventions for ADHD, available treatments do not alter the course of the disorder for the majority of individuals. The proposed project aims to address a significant barrier to ADHD research and treatment, which is the etiological and neurobiological heterogeneity of the disorder. A common theory suggests that disruptions in neural circuitry supporting attention and inhibition may occur at the levels of perceptual orienting, action execution, and/or integration of those two processes. Alternately, recent literature indicates that atypical baseline cortical activation impedes attentive behavior during cognitive tasks. The proposed studies will utilize electrophysiology frequency (EEG) and event related potential (ERP) metrics to test competing latent profile models of homogenous, neurophysiologically-defined subtypes of ADHD in school age and young children. Study 1 (K99) will utilize confirmatory latent profile analysis to identify neurophysiological subtypes of ADHD in 100 affected, 7-11 year old children and 30 healthy controls, and to further characterize the cognitive and psychiatric profiles of the latent classes. Study 2 (R00) will extend the methods to 100 2.5-4 year olds at risk for ADHD, 30 2.5-4 year olds with no risk for ADHD, and an additional independent sample of 60 7-11 year old children with an ADHD diagnosis. The goals of Study 2 are to identify early developmental correlates of the latent classes identified in Study 1, and to replicate the results of Study 1 with an independent and pooled (i.e. Study 1 + Study 2) sample of affected children. The results of the proposed studies will directly inform future research on putative genetic and environmental factors associated with ADHD, and ultimately, development of precision medicine treatment for the disorder. Through the current proposal, the P.I. seeks intensive training in electrophysiology methods and latent class analysis, as well as continued training in developmental cognitive neuroscience. The proposed mechanism will support the P.I. in establishing her own laboratory in year 3, and will allow her to apply for future funding to support a prospective, longitudinal study of infants at-risk for ADHD. The P.I. will accomplish her training goals with the mentorship of a highly qualified team of senior investigators at the University of Washington, Seattle Children?s Hospital, Boston Children?s Hospital, and the University of Colorado. She plans to execute the K99 research at the Center on Human Development and Disability at the University of Washington Medical Center in Seattle, Washington.
Heterogeneity in the neurobiological etiology of attention deficit hyperactivity disorder (ADHD) significantly impedes efforts to identify pre-symptomatic markers that would facilitate development of preventative, individually tailored interventions for the disorder. The proposed studies will be the first to comprehensively characterize the neuropsychological and psychiatric profiles of homogenous, neurophysiologically-defined subtypes of ADHD in school-age and at-risk young children. Findings from this research will inform future work targeting putative genetic causes, risk biomarkers, and neuro-pharmacologic targets in ADHD.
