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.
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Grant Number: 5F31MH136685-02
NIH Institute/Center: NIH
Principal Investigator: Joelle Bagautdinova