This Mentored Research Scientist Development Award (K01) will provide the candidate with advanced training in developmental affective neuroscience and psychopathology. The proposed research will test a novel neurodevelopmental model of depression in which stressful life events and insufficient sleep increase risk for depression in adolescents by disrupting the development of reward-related neural circuitry. Two studies are proposed to test this model of depression. The first study will evaluate whether neural and behavioral response to rewards and depressive symptoms are associated with daily stressful life events and sleep duration from the previous week. Participants for this study will be recruited from an ongoing longitudinal fMRI study of neural reward circuitry and risk for depression in adolescent girls. The second study will evaluate whether increasing sleep duration can increase neural and behavioral response to rewards and decrease depressive symptoms in 18- to 20-year-old girls with insufficient sleep and depressive symptoms. Participants for this study will be recruited from university and college health clinics and the surrounding community. In combination, these studies will help characterize reward processing as a putative mechanism of depression onset and provide data on the efficacy of sleep extension as an intervention for depressive symptoms in late adolescent girls. The candidate has expertise in several domains relevant to the proposed project, including affective bias in depression, the role of sleep in cognitive processing and psychopathology, and cognitive neuroscience research methods. She will build on this experience through her K01 by developing expertise in: 1) reward circuit neurodevelopment in late adolescence;2) stressful life events and physiological stress-reactivity;3) sleep and circadian rhythms;and 4) advanced skills for longitudinal data analysis. The University of Pittsburgh is an ideal environment to accomplish these research and training aims for two reasons. First, the applicant's selected mentors, Drs. Erika Forbes and Martica Hall, are both highly successful independent investigators with extensive mentorship experience and collective expertise in stress and sleep as risk factors for aberrant development of reward-related neural circuitry and depressive symptoms. Second, the University of Pittsburgh is one of the premier centers for affective developmental neuroscience and sleep research. The proposed research and training plan will contribute to a future R01 application that will examine neural and behavioral response to rewards and neural and physiological response to stress longitudinally as mechanisms of psychopathology in adolescents. This application is consistent with priorities outlined by the National Institute of Mental Health for research on the development and function of neural circuits, mechanisms and modifiers of aberrant developmental trajectories with a focus on periods of sensitivity to disruption, and Research Domain Criteria standards for research on basic dimensions of functioning (e.g., positive valence systems) that are relevant to psychopathology.
Depression often has its first onset during the transition from adolescence to early adulthood. Identifying the neurodevelopmental mechanisms of depression and their environmental modifiers is critical to preventing and treating this debilitating disorder
|Casement, Melynda D; Goldstein, Tina R; Gratzmiller, Sarah M et al. (2018) Social stress response in adolescents with bipolar disorder. Psychoneuroendocrinology 91:159-168|
|Hasler, Brant P; Casement, Melynda D; Sitnick, Stephanie L et al. (2017) Eveningness among late adolescent males predicts neural reactivity to reward and alcohol dependence 2 years later. Behav Brain Res 327:112-120|
|Casement, Melynda D; Keenan, Kate E; Hipwell, Alison E et al. (2016) Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence. Sleep 39:439-47|
|Hall, Martica H; Casement, Melynda D; Troxel, Wendy M et al. (2015) Chronic Stress is Prospectively Associated with Sleep in Midlife Women: The SWAN Sleep Study. Sleep 38:1645-54|