Biotyping Mood Health in Late Adolescence: Neurocognitive Dimensions and Stress Pathways

项目摘要 青春期是以认知和神经生物学相互关联的变化为标志的发育期。 功能，包括重组大规模功能网络和提高调节注意力的能力 并追求回报。青春期也是压力增加和症状增加的时期 情绪障碍(MD)，这反过来又与同一大脑中的神经认知异常有关 青春期高度可塑性的网络和认知域。这些发展趋同 建议建立一个模型，在该模型中，关键神经认知维度的异常可能会使青少年容易患上MD 因为神经认知障碍阻碍了健康的压力应对行为。然而，共同的风险因素和 各种MD的早期症状相似，这使得确定其特异性具有挑战性 神经认知异常导致MD的途径。拟议的研究将解决这些问题 多模式、纵向评估风险“生物类型”、应激反应和MD症状的挑战 青春期。我们将招募144名14-19岁的青少年(其中96名为MD的高家族风险者)作为样本 参与一项为期24个月的研究，包括神经成像、认知测试和症状评估(在 基线和12个月)，以及移动应用程序/电话跟踪评估(每6个月一次) 事件/响应和症状。我们将把潜变量分析应用于行为和神经成像 评估关键神经认知维度的个体差异的措施涉及：(1)认知调节 (2)奖赏敏感性(RS)。多水平模型将测试CR和RS对未来情绪的影响 由应激反应行为引起的症状。我们的目标是首先使用由异常定义的生物型 这些神经认知维度可以预测两年后的应激反应行为和情绪症状 向上(目标1)，第二，提供对神经认知子维度的更精确的理解--聚焦 在RS子维度上--最好地划分情绪症状空间(目标2)。此外，为了探索 生物型的时间特征，我们将测试RS随时间的稳定性(探索性目标1)并探索 生物型表达的调节剂，我们将测试生物性别和年龄的影响(探索性目标2)。 最终，这项工作可能是朝着使用神经认知生物型来实现翻译目标迈出的关键一步 鉴别诊断和预测MD。

Project Summary Adolescence is a developmental period marked by interconnected changes in cognitive and neurobiological functioning, including reorganization of large-scale functional networks and improved ability to regulate attention and pursue rewards. Adolescence is also a period characterized by heightened stress and increased symptoms of mood disorders (MD), which are in turn associated with neurocognitive abnormalities in the same brain networks and cognitive domains that are highly plastic in adolescence. These developmental convergences suggest a model in which abnormalities in key neurocognitive dimensions predispose teens to MD, possibly because neurocognitive impairment impedes healthy stress coping behavior. However, shared risk factors and similarities in early-stage symptomatology of various MD have made it challenging to determine the specific pathways by which neurocognitive abnormalities contribute to MD. The proposed study will address these challenges with a multi-modal, longitudinal evaluation of risk “biotypes”, stress responses, and MD symptoms in adolescence. We will recruit a sample of n=144 adolescents ages 14-19 (n=96 at high familial risk of MD) to participate in a 24-month study consisting of neuroimaging, cognitive testing, and symptom assessment (at baseline and 12 months), and mobile-app/telephone follow-up evaluations (once per 6 months) of stress events/responses and symptoms. We will apply latent variable analysis to behavioral and neuroimaging measures to evaluate individual differences in key neurocognitive dimensions related to: (1) cognitive regulation (CR), and (2) reward sensitivity (RS). Multilevel models will test the effects of CR and RS on future mood symptoms as mediated by stress-reactive behaviors. We aim to first use biotypes defined by abnormalities in these neurocognitive dimensions to predict stress-reactive behavior and mood symptoms over a two-year follow- up (Aim 1), and to second, provide a more precise understanding of neurocognitive subdimensions – focusing on RS subdimensions - that best carve the mood symptom space (Aim 2). In addition, in order to explore temporal characteristics of biotypes, we will test the stability of RS over time (Exploratory Aim 1) and to explore moderators of biotype expression, we will test the effects of biological sex and age (Exploratory Aim 2). Ultimately, this work may be a crucial step towards the translational goal of using neurocognitive biotypes to differentially diagnose and predict MD.