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

项目摘要 青春期是一个以认知和神经生物学的相互关联的变化为标志的发展时期 功能，包括重组大规模功能网络和提高调节注意力的能力 追求回报。青春期也是一个时期的特点是高度紧张和症状增加 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 网络和认知领域在青春期是高度可塑的。这些发展趋同 提出了一个模型，在该模型中，关键神经认知维度的异常使青少年易患MD，可能 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的早期病理学的相似性使得确定特定的 神经认知异常导致MD的途径。拟议的研究将解决这些问题 挑战与风险的多模式，纵向评估“生物型”，压力反应，和MD症状， 青春期我们将招募144名14-19岁的青少年（96名有MD高家族风险）， 参加一项为期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），以及压力的移动应用程序/电话随访评估（每6个月一次） 事件/反应和症状。我们将把潜变量分析应用于行为和神经影像学 评估关键神经认知维度的个体差异的措施：（1）认知调节 (CR)（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 由应激反应行为介导的症状。我们的目标是首先使用由异常定义的生物型， 这些神经认知维度预测压力反应行为和情绪症状超过两年的随访- 上（目标1），第二，提供对神经认知子维度的更精确理解-聚焦 在RS子维度上-最好地雕刻情绪症状空间（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（探索目标1），并探索 生物型表达的调节因子，我们将测试生物性别和年龄的影响（探索性目的2）。 最终，这项工作可能是朝着使用神经认知生物型的转化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.