Effects of Early Life Stress and Sleep Disturbance on Frontolimbic Development and Risk for Depression Across Adolescence

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Project Summary/Abstract Major depressive disorder (MDD) is among the most prevalent, recurrent, and functionally debilitating of all psychiatric disorders. The incidence of MDD rises sharply during adolescence, and individuals who have an onset of MDD in adolescence tend to have a more chronic and severe course of depression than do those with a later onset. Thus, there is an urgent need to develop effective approaches for early identification, prevention, and intervention for MDD. Experiences of early life adversity (ELA), which affect over 40% of children, are a strong predictor of MDD. Research suggests that one pathway by which ELA increases risk for MDD is through alterations in the structural and functional development of frontolimbic regions implicated in stress reactivity and regulation; however, the direction of these effects and how they unfold over time are not known. Moreover, the biobehavioral mechanisms by which ELA influences neurodevelopment and risk for MDD are not well understood. In this context, sleep disturbances is a significant risk factor for MDD across the lifespan and is an underexplored pathway by which ELA might increase risk for MDD during adolescence. Sleep disturbances tend to increase during adolescence due to a combination of normative biological and psychosocial changes; indeed, over 70% of high-school students report getting insufficient sleep. Emerging research suggests that adolescents with greater sleep disturbances have both attenuated white matter development in tracts that connect frontolimbic regions and heightened frontolimbic reactivity to stress. The overlapping neurobiological and health effects of ELA and sleep disturbances suggest that sleep disturbance is a critical pathway that links ELA to frontolimbic alterations and increased risk for MDD. The proposed research addresses critical gaps in the literature by examining the multivariate and longitudinal effects of ELA, sleep disturbances, and frontolimbic connectivity during adolescence and how these factors predict risk for depression in young adulthood. Leveraging data from a multimethod longitudinal study, the proposed project investigates sleep disturbances as a pathway linking ELA with alterations in frontolimbic development and risk for MDD across adolescence and young adulthood (9-20 years of age). The results of this project will not only increase our understanding of the neurobiological mechanisms by which ELA relates to increased risk for MDD, but will also provide insight into sleep disturbances as a potential target of intervention during adolescence to ameliorate the effects of ELA. Moreover, the proposed training plan will enable the applicant to gain theoretical and methodological expertise in studying the relations among ELA, sleep quality, frontolimbic development, and psychopathology during adolescence, and to develop professional skills necessary to transition to an independent research career. Stanford University, the institution at which the applicant will be training, has experts and resources relevant to all domains of the proposal, making it an ideal training environment for the applicant.