Examining Longitudinal Cognitive-Motivational Interactions in Adolescents with Depression

项目总结/摘要 抑郁症是一种使人衰弱的精神疾病，通常出现在青春期， 动态大脑和行为发展。认知和动机缺陷在抑郁症中很突出 并发生在经历特定发育变化的神经系统中。考虑到 在持续发展的背景下，这些缺陷，更好地理解认知和动机如何 青少年抑郁症的互动对于设计预防策略和治疗至关重要。 我建议进行补充研究，旨在检查认知动机的相互作用， 青少年抑郁症，并为我提供培训，我需要成为一个独立的调查员，专注于 发展性精神病理学中认知和情感的神经生物学。与我的主要导师，博士。 Anticevic，我设计了一个激励空间工作记忆范式，用于神经成像， 翻译自非人类灵长类动物的经典任务，并适用于衡量激励措施对 空间工作记忆准确性我们建议在患有抑郁症的青少年中使用这项任务， 为了检查空间工作记忆和激励空间工作的差异， 记忆表现，以及每一种表现背后的神经回路。将对所有参与者进行纵向随访， 比较抑郁症的影响和这些回路中的典型发展。他们将在9个月后返回 第一次就诊时记录症状和行为，18个月时记录症状、行为，并重复 激励空间工作记忆神经影像学范式。为了补充我们的横断面研究， 青少年抑郁症，我们提出的特点在认知和动机的变化，在一个大的群体， 通常是来自多地点青少年大脑认知发展（ABCD）研究的儿童。我们 将数据驱动的方法应用于ABCD研究收集的认知和激励措施， 量化共享的神经行为变异，可以区分认知动机表型。这 表征将作为未来研究的重要平台，以检查抑郁症的风险， 青春期 拟议的一系列研究提供了发育研究和神经成像方面的培训， 纵向研究设计和分析，以及应用于神经发育问题的数据驱动分析。我 导师是一个多学科的专家团队，主要在耶鲁，他们将指导和支持我， 实现这些培训目标。总的来说，这个K23应用程序提供了重要的额外培训， 我需要成功地过渡到一个独立的医生，科学家专注于神经生物学的经验 认知和情感的发展。

PROJECT SUMMARY / ABSTRACT 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.