Depression is a debilitating psychiatric illness that commonly emerges during adolescence, a period of dynamic brain and behavioral development. Cognitive and motivational deficits are prominent in depression and occur in neural systems that undergo adolescent-specific developmental changes. Given the emergence of these deficits in the context of ongoing development, a better understanding of how cognition and motivation interact in adolescent depression is critical for designing prevention strategies and treatments. I am proposing complementary studies designed to examine cognitive-motivational interactions in adolescent depression, and provide me the training I need to become an independent investigator focused on the neurobiology of cognition and emotion in developmental psychopathology. With my primary mentor, Dr. Anticevic, I have designed an incentivized spatial working memory paradigm for neuroimaging that has been translated from classic tasks in non-human primates, and adapted to measure the effects of incentives on spatial working memory accuracy. We propose to use this task in adolescents with depression and neurotypical peers in order to examine differences in spatial working memory and incentivized spatial working memory performances, and the neural circuits underlying each. All participants will be followed longitudinally to compare the impact of depression and typical development in these circuits. They will return at 9 months after the first visit to chart symptoms and behavior, and at 18 months to chart symptoms, behavior, and repeat the incentivized spatial working memory neuroimaging paradigm. To complement our cross-sectional study of adolescent depression, we propose to characterize the variation in cognition and motivation in a large group of typically developing children from the multi-site Adolescent Brain Cognitive Development (ABCD) study. We will apply data-driven methods to cognitive and motivational measures collected by the ABCD study and quantify the shared neurobehavioral variation that may distinguish cognitive-motivational phenotypes. This characterization would serve as a vital platform for future studies to examine risk for depression in adolescence. The proposed set of studies provides training in developmental research and neuroimaging, longitudinal study design and analysis, and data-driven analytics applied to neurodevelopmental questions. My mentors are a multi-disciplinary team of experts based mostly at Yale who will guide and support me in achieving these training goals. Collectively, this K23 application provides the vital additional training and experiences I need to successfully transition to an independent physician-scientist focused on the neurobiology of cognition and emotion in developmental psychopathology.
Depression is one of the most debilitating psychiatric illnesses to emerge during adolescence, a period of critical brain development and transition towards adulthood. Cognitive and motivational deficits are prominent symptoms and the associated neural systems undergo adolescent-specific development, making understanding cognitive and motivational neurobehavioral interactions in adolescent depression crucial to designing future treatments and prevention strategies. This study proposes complementary approaches to examine cognitive-motivational neurobehavioral interactions, using: an incentivized spatial working memory neuroimaging paradigm in adolescents with depression, with longitudinal re-examination, and data-driven approaches applied to a large-scale dataset in typical children aimed at characterizing cognitive-motivational phenotypes as a platform for future studies to examine depression risk in adolescence.
