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

项目摘要 青春期后期（大约15至19岁）是一个发展时期，其特征是相互关联的 认知和神经生物学功能的变化，包括大规模功能网络的重组 提高了调节注意力和追求奖励的能力。青春期也是一个具有以下特征的时期 压力增加和情绪障碍（MD）症状增加，这反过来又与 在相同的大脑网络和认知领域中的神经认知异常， 青春期这些发展的趋同表明了一个模型，在这个模型中，关键的神经认知功能异常， 维度使青少年易患MD，可能是因为神经认知障碍阻碍了健康的压力应对 行为然而，共享的危险因素和各种MD早期诊断的相似性使得 确定神经认知异常导致MD的具体途径具有挑战性。的 拟议的研究将通过对风险“生物型”进行多模式、纵向评估来应对这些挑战 （由神经认知功能定义），应激反应和青春期MD症状的轨迹。我们 将招募n=130名15-19岁的青少年（n=96名具有MD高家族风险的青少年）参加一项24- 一项为期一个月的研究，包括神经影像学、认知测试和症状评估（基线和12 基于移动应用程序或电话随访评估（每6个月一次） 事件/反应和症状。我们将应用潜变量分析的认知和神经成像集 评估两个关键神经认知维度的个体差异的测量：（1）认知调节（CR）， 由认知控制任务表现和额岛网络功能定义，以及（2）奖励敏感性 (RS)根据对奖赏的行为反应和皮质纹状体网络功能来定义。多层次调解 模型将测试基线或CR和RS的变化对未来情绪症状的影响， 应激反应行为我们的第一个目标是研究神经认知功能之间的纵向联系， 维度和情绪症状，检验假设，即CR和RS维度的相互作用将 产生风险生物型，其中表现出较低CR和较低RS的青少年将报告快感缺乏增加 随着时间的推移，青少年表现出较低的CR与较高的RS一起将报告随着时间的推移躁狂症的增加。我们 第二个目的是研究将神经认知维度与情绪症状联系起来的介导机制， 检验较低CR/较低RS生物型将通过应激与未来快感缺乏相关的假设- 反应性行为戒断，较低的CR/较高的RS生物型将与未来的躁狂症相关， 应激反应行为冲动最终，这项工作可能是实现翻译目标的关键一步 使用神经认知生物型来鉴别诊断和预测MD。

Project Summary Late adolescence (approximately ages 15 to 19) 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 has 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” (defined by neurocognitive functioning), stress responses, and trajectories of MD symptoms in adolescence. We will recruit a sample of n=130 adolescents ages 15-19 (n=96 with 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-based or telephone follow-up evaluations (once per 6 months) of stress events/responses and symptoms. We will apply latent variable analysis to the set of cognitive and neuroimaging measures to evaluate individual differences in two key neurocognitive dimensions: (1) cognitive regulation (CR), defined by cognitive control task performance and frontoinsular network functioning, and (2) reward sensitivity (RS), defined by behavioral response to reward and corticostriatal network functioning. Multi-level mediation models will test the effects of baseline, or changes in, CR and RS on future mood symptoms as mediated by stress-reactive behaviors. Our first aim is to investigate longitudinal associations between neurocognitive dimensions and mood symptoms, testing the hypothesis that the interaction of CR and RS dimensions will produce risk biotypes in which teens showing lower CR together with lower RS will report increases in anhedonia over time, and teens showing lower CR together with higher RS will report increases in mania over time. Our second aim is to investigate mediating mechanisms linking neurocognitive dimensions to mood symptoms, testing the hypothesis that the lower CR/lower RS biotype will be associated with future anhedonia via stress- reactive behavioral withdrawal, and the lower CR/higher RS biotype will be associated with future mania via stress-reactive behavioral impulsivity. Ultimately, this work may be a crucial step towards the translational goal of using neurocognitive biotypes to differentially diagnose and predict MD.