The role of sleep in neurodevelopmental plasticity and emotion dysregulation in youth

PROJECT SUMMARY Emotion dysregulation, defined as the inability to regulate the intensity and quality of emotions, is a common transdiagnostic symptom of mood disorders in early adolescence and a major risk factor for youth suicide. Evidence indicates that sleep disruption may be a driver of emotion dysregulation, and that sleep indices such

as poor sleep efficiency – a greater time spent awake during attempted sleep – both precede and predict the onset of mood disorders. It is therefore critical to understand the neurodevelopmental mechanisms through which sleep disruption relates to emotion dysregulation during adolescence. Prior studies have linked alterations in the

Default Mode Network (DMN) to both sleep disruption and emotion dysregulation. In parallel, findings indicate that sleep significantly impacts synaptic plasticity mechanisms crucial for brain maturation. Importantly, the protracted maturational program of the DMN may render this network particularly vulnerable to sleep disruption

during adolescence; however, this has not been directly tested. Recent methodological advances provide a strong premise for the relevance of low frequency fMRI fluctuation amplitude as a non-invasive marker of developmental plasticity. Using this measure, our lab recently demonstrated a period of increased plasticity in

the DMN during early to mid-adolescence, indicating that the DMN is highly malleable during this period. However, no work has comprehensively characterized the impact of sleep disruption on DMN developmental plasticity and emotion dysregulation in humans. In response to this gap, the current proposal will test the

overarching hypothesis that poor sleep efficiency in early to mid-adolescence blunts developmental plasticity in the DMN and is associated with emotion dysregulation. To test this, the current proposal will apply advanced neuroimaging approaches to two complementary datasets. In Aim 1, cross-sectional relationships between sleep

efficiency, emotion dysregulation, and DMN plasticity will be defined in a prospectively collected sample (ages 11-16) of 100 individuals with mood disorders and 50 typically developing comparators. This sample will include high-precision phenotyping not available in large-scale data, including digital phenotyping of emotion regulation

and next generation multi-echo fMRI sequences that enhance sensitivity. Aim 2 will delineate how sleep efficiency impacts longitudinal development of plasticity in the DMN and emotion dysregulation by leveraging the large-scale longitudinal Adolescent Brain Cognitive Development (ABCD) Study (ages 11-16). Both datasets will

include wristwatch-recorded sleep, providing objective measures of sleep efficiency. Taken together, findings will provide critical new insights into the neurodevelopmental underpinnings of sleep disruption and emotion dysregulation. Supported by a strong mentorship team with complementary expertise (Drs. Satterthwaite,

Mackey, Gehrman, Shou, and Barch) and the world-class resources of the University of Pennsylvania, this proposal aligns with a cohesive training plan that will form the ideal foundation for an independent career at the intersection of neurodevelopment, sleep, and computational psychiatry. 1