The role of insufficient sleep and depression on hippocampal-dependent memory trajectories across the adolescent transition

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Project Summary This K08 proposal will address a critical gap in our fundamental knowledge of the effects of insufficient sleep and depression on longitudinal sleep-dependent memory development and will prepare this applicant, Katharine Simon, PhD, to become an independent translational investigator with expertise in sleep, memory, and psychopathology across development. Depression in adolescence is a growing public health concern, with symptoms beginning during the transition to adolescence (9 -12 years)1 and conferring heightened risk for long-term deleterious psychological and cognitive outcomes.20-21 In contrast to other clinical disorders, depression is associated with specific deficits in hippocampal-dependent (HcDep) memory (e.g., declarative memory).9-11 Although the brain mechanisms underlying depression-related memory deficits are not understood, one potential risk factor may be insufficient sleep (e.g., short sleep duration, variable timing, or poor quality) given the critical role of sleep in supporting new hippocampal-dependent memory formation (sleep dependent memory [Hc-SDM]).12 The transition to adolescence is a particularly vulnerable time that involves increasingly dramatic changes to sleep patterns.2,3 Although a few nights of insufficient sleep does not consistently affect HcDep memory performance in adolescents18,50-53; typical insufficient weekly sleep is associated with reduced hippocampal volume.19 At present, it is clear there is a fundamental gap in our knowledge of the individual trajectories of insufficient sleep, depression, and Hc-SDM across the adolescent transition and the longitudinal associations between these factors. To address this question, 27 pre-adolescents (9 to 12 years) will be assessed using a repeated measurement-burst design with sampling at quarterly intervals over a year using a personalized, mobile health (mHealth) platform. At each quarterly evaluation, for 7 consecutive days, participants will complete daily sleep diaries, ecological momentary assessments, and Hc-SDM tasks. The hypothesize is that insufficient sleep and depression symptoms across the adolescent transition will predict long-term Hc-SDM performance trajectory deficits. This Mentored Clinical Scientist Research Career Development Award will support Dr. Simon’s training goals to acquire skills and knowledge in 1) gaining expertise in naturalistic, longitudinal cognitive and clinical assessment using mHealth and wearable devices, 2) training in clinical pediatric research, and 3) intensive repeated-measure analyses. These training aims will build on Dr. Simon’s prior training in cognitive neuroscience and clinical psychology and expertise in short-term experimental sleep-dependent memory research. Furthermore, the training Dr. Simon will gain from this K08 is an essential step to become an independent developmental translational researcher and will directly lead to my future R01 application to further evaluate the longitudinal trajectories of insufficient sleep and depressive symptoms on older adolescents’ Hc-SDM memory and identify key windows in which sleep-based interventions can support cognitive trajectories in depressed adolescents.