Advancing Identification of Circadian Delay in ADHD Youth: Associations with Clinical Heterogeneity and Cognition

Duke University, Durham NC

Investigators

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is associated with substantial societal burden and personal impairment across the lifespan. Although empirically-based treatments exist, ADHD is highly heterogeneous with respect to treatment response as well as ADHD-related clinical profiles, including psychiatric comorbidity, cognitive performance, and sluggish cognitive tempo (SCT). Personalized treatments attuned to the biology and behavior of the child are critically needed to reduce the burden of ADHD. Sleep disturbances, particularly difficulties falling asleep and delayed/irregular sleep schedules, are implicated in ADHD and may represent key candidates for elucidating clinical heterogeneity and personalizing ADHD treatment. Two distinct mechanistic pathways (i.e., behavioral and biological) may contribute to sleep disturbance in ADHD. Both are characterized by difficulties falling asleep and delayed/irregular sleep schedules but are mechanistically distinct. In the behavioral pathway, sleep disturbances stem from ADHD symptoms (e.g., disorganization) and psychiatric comorbidity (e.g., oppositionality), while the biological pathway is characterized by an endogenous circadian rhythm delay. Although the behavioral pathway has received significant scientific attention to date, very little is known about the prevalence, impact, and optimal treatment of the biological (circadian) pathway in middle childhood—the peak period of ADHD diagnosis. Importantly, the development of identification and treatment strategies for children with circadian dysfunction has been limited by gold-standard circadian assessment (dim light melatonin onset [DLMO]), which is burdensome for families and difficult to implement in routine clinical settings. The overarching objective of this study is to characterize circadian function among 250 children with ADHD (ages 6-9) using gold-standard DLMO assessment and to establish the implications of circadian dysfunction for clinical and cognitive functioning. In addition, this study employs innovative wearable sensors (e.g., heat flux, rest/activity, mattress-based) to determine whether low-burden, in-home assessments have utility in identifying circadian dysfunction among children with ADHD. Aim 1 will characterize individual differences in circadian function, including behavioral and biological sleep profiles, in pediatric ADHD using lab- based DLMO, actigraphy, and parent report. Aim 2 will examine associations between circadian dysfunction, ADHD clinical presentation, and cognition. Aim 3 will investigate the utility of wearable sensors for indexing circadian dysfunction in children with ADHD. If successful, this study may transform clinical practice by facilitating holistic, objective sleep assessments in pediatric settings, which may spur the development of personalized treatments (e.g., behavioral sleep management therapy for behavioral pathway, chronotherapy for the biological pathway). Although we focus on ADHD, our methods have transdiagnostic applications. From a public health perspective, the improved measurement and treatment of sleep problems has the potential to improve educational, interpersonal, and occupational outcomes and result in broad economic savings.