Impact of Circadian Misalignment for Adolescents with ADHD: Observational and Mechanistic Data

About This Grant

PROJECT SUMMARY During adolescence, individuals with attention-deficit/hyperactivity disorder (ADHD) often show escalating academic and social impairments and comorbid psychopathology, a rapid decline in medication use and adherence, less engagement in psychosocial treatments, and limited data to guide those treatments. Sleep has emerged as a promising new intervention target to mitigate this confluence of undertreatment and risk. Even compared to their notoriously sleep-deprived typically-developing (TD) peers, adolescents with ADHD have worse sleep, irrespective of whether they are taking ADHD-targeting medications. Growing evidence links this poor sleep to functional impairment, and our team has shown these links to be causal. Experimentally shortened sleep causally degrades core inattentive symptoms and common comorbid symptoms for adolescents with ADHD. Conversely, the effects of lengthening sleep in these studies rivaled those of more intensive behavioral treatments. Sleep-targeted interventions show tremendous promise for adolescents with ADHD, but other observational data from our group also highlight a crucial puzzle to unlock this promise: how to best integrate sleep duration with sleep timing. Adolescents with later chronotypes (“owls,” who prefer later bedtimes and rise times) perform worse in school than those with earlier chronotypes (“larks”), even after controlling for sleep duration and quality. We assert that this reflects a “misalignment effect”: a timing mismatch between the early demands of school and the late circadian phase (internal body clock) of owls. Emerging data from our labs suggest that attention in TD adolescents is improved by lengthening sleep only if it is timed to align with the individual’s circadian phase. If this also holds true for adolescents with ADHD, it would light new paths towards individualized interventions that address misalignment. In addition, evidence suggests that adolescents with ADHD may have delayed circadian phase, which would make morning activities (e.g., school) misaligned. If so, it would point to circadian-informed interventions for adolescents with ADHD as a group. To guide and justify circadian-informed intervention development, we propose two concurrent studies that will yield complementary data. The first is an observational school-year study that will determine, for the first time, test whether adolescents ages 13-17 with ADHD (n=85) average a later circadian phase than sex- and age- matched TD peers (n=85), and whether misalignment is linked to real-world deficits in attention and functional outcomes. The second is a summer mechanistic clinical trial that will test, also for the first time, the causal impact of circadian misalignment on attention in adolescents with ADHD (N=50). Findings will provide unique insight into the role of circadian factors in adolescent ADHD, concurrently testing cause-effect relationships and real-world implications. If, as we predict, circadian misalignment is common amongst adolescents with ADHD, causally impacts attention, and is linked to real-world functional impairment, it would open important new avenues for intervention in a difficult-to-treat population at high risk for poor outcomes.