Characterizing the role of sleep brain dynamics in the emergence of depression in adolescents

PROJECT SUMMARY Adolescent onset of major depressive disorder (MDD) is a major public health concern causing greater risk for a chronic and recurrent depression course, and an increased risk for suicide. Offspring of parents with a history of MDD are at particularly high risk for developing depression. As depression rates among adolescents have been steadily rising in the past decade, research on the discovery of biological markers of youth depression onset, particularly among highly vulnerable populations, is crucially needed to develop early interventions targeting malleable factors. Sleep changes are a hallmark of depression emergence, with sleep disturbances and changes in sleep architecture serving as a precursor to depression onset in youth. Adolescents show high rates of poor sleep and strong vulnerability to emotional dysregulation driven by poor sleep. This is paired to youth cortical neurodevelopment being crucial to emotional regulation, and signatures of sleep brain dynamics changing in parallel with neurodevelopment. While current research shows associations between depression and subjective sleep complaints, these studies rely on subjective measures and are mostly cross-sectional investigations, which limits information on causal mechanisms of MDD emergence in youth. One promising objective marker of sleep disturbances linked to adolescent depression is altered sleep brain oscillations. Specifically, youth with MDD show increased frontal slow wave activity (SWA) and reduced frontal sleep spindles. Furthermore, high risk (HR) youth of depressed mothers show changes similar to those found in MDD, albeit less pronounced, suggesting that these sleep profiles may represent the substrate of a biological vulnerability that precedes the development of depression. This imbalance in sleep oscillations is functionally relevant, as cortical Slow Oscillations (SOs, dynamic contributors to SWA), spindles, and their coordination are associated with health, restorative properties of sleep, cognitive processing, average intelligence, and brain homeostasis. However, there is currently no data on the predictive potential of quantifiers of sleep oscillations in depression emergence in youth. Furthermore, recent work from PI Malerba introduced novel space-time analyses of SOs and spindles enabling enhanced understanding of their biophysics and coordination. Since these properties are crucial to SO and spindle functional roles, structural changes in SOs and spindles related to MDD risk in youth could inform on mechanisms of depression emergence and novel targets for intervention. The proposed study will: (Aim 1) identify the space-time profiles of SO and spindles, and contrast-compare the resulting properties across 92 youth at high and low risk for depression; then (Aim 2) establish the predictive role of these space-time profiles in relation to increases in depression symptoms at 3 and 6 months, and finally (Aim 3) explore the potential mediating role of emotional regulation in the relation between sleep profiles and depression trajectories in youth. These findings will inform future research on early detection of MDD in youth and the development of interventions that can manipulate these oscillations in youth with MDD.