Functional neuroanatomy of social and perceived internal threat in anxious youth at high-risk for bipolar disorder

项目总结/摘要 这个K23应用程序的目的是支持我的短期职业目标，获得多式联运 神经影像学，神经计算，生物统计学和理论社会认知知识的研究 双相情感障碍（BD）高危青年的焦虑和情绪调节。纵向证据表明 患有任何情绪障碍高风险BD的年轻人在早期经历焦虑症， 先行词因此，焦虑是BD发展轨迹中的一个重要症状。之一 青少年焦虑的最大来源是社会关系的质量，这极大地影响了青少年的生活质量。 感知生活质量。然而，对于青少年社会认知的神经基础知之甚少， BD的高风险或日常社会交往如何影响焦虑和情绪调节，这是一个标志， BD的特点。在之前的一项试点研究中（P.I.罗伊巴尔，美国儿童和青少年学会 精神病学/礼来试点研究奖），我显示了大脑激活和功能连接的差异 当两组都经历了功能性磁刺激时， 共振成像（fMRI）社交拒绝任务。我将这个功能磁共振成像的社会排斥任务应用于高风险的青少年， BD（P.I.罗伊巴尔，霍格心理健康基金会）。这里提出的研究将增加样本量 因为它建议使用相同的功能磁共振成像社交拒绝任务，并添加功能磁共振成像任务， 评估社会排斥后的内部威胁感。行为评估和功能磁共振成像将 用于评估HR组的功能神经解剖学相关性。我们的假设预测HR 在涉及显著区域的社会拒绝任务中， 社会排斥，特别是膝下前扣带皮层和前扣带皮层，但也将涉及 边缘系统区域在社会排斥中并不常见，特别是杏仁核和海马体。我们假设 在HR组中，在社交拒绝任务期间观察到过度激活和异常连接 会与经历社会排斥后的焦虑感有关。我们还将研究 对影响情绪的内部威胁线索的社会排斥。我们假设HR组会表现出更大的 杏仁核激活和杏仁核与前额叶皮层之间较弱的功能连接， 理论上是调节杏仁核相对于HC在HR组中，异常激活和连接 将与情绪自我调节的能力相关。治疗患有BD和BD高危的青少年 和基本的神经影像学经验为我实现培训目标奠定了坚实的基础 并完成这项研究。拟议的综合研究、指导和教学培训方案， 结合德克萨斯大学健康科学中心的优秀研究环境， 安东尼奥，将促进我的长期职业目标，成为一个领先的专家，在多模态社会认知神经 模型，因为它们与BD高危儿童的焦虑和情绪调节有关。

Project Summary/Abstract The purpose of this K23 application is to support my short-term career objectives of acquiring multimodal neuroimaging, neurocomputational, biostatistical, and theoretical social cognitive knowledge in the study of anxiety and emotion regulation in youth at high-risk for bipolar disorder (BD). Longitudinal evidence suggests that youth at high-risk for BD that develop any mood disorder experience an anxiety disorder as an early antecedent. Anxiety is therefore an important symptom in the developmental trajectory of BD. One of the largest sources of anxiety in youth is the quality of social relationships, which greatly influence youth's perceived quality of life. However, little is known about the neural underpinnings of social cognition in youth at high-risk for BD or how everyday social interactions affect anxiety and emotion regulation, which is a hallmark characteristic of BD. In a previous pilot study (P.I. Roybal, American Academy of Child and Adolescent Psychiatry/Lilly Pilot Research Award), I showed differences in brain activation and functional connectivity between youth with BD relative to healthy controls (HC) when both groups experienced a functional magnetic resonance imaging (fMRI) social rejection task. I applied this fMRI social rejection task to youth at high-risk for BD (P.I. Roybal, Hogg Foundation for Mental Health). The research proposed here will add to the sample size of this high-risk group (HR) as it proposes to use the same fMRI social rejection task and add on an fMRI task evaluating perceived internal threat subsequent to social rejection. Behavioral assessments and fMRI will be used to assess functional neuroanatomical correlates in the HR group. Our hypotheses predict that the HR group will have functional neural deficits relative to HC during a social rejection task that involve regions salient to social rejection, specifically subgenual anterior cingulate cortex and anterior insula, but also will involve limbic areas not typically seen in social rejection, specifically the amygdala and hippocampus. We hypothesize that within the HR group, hyperactivation and abnormal connectivity observed during the social rejection task will correlate with subsequent anxiety felt after experiencing social rejection. We will also examine the effects of social rejection on internal threat cues that affect mood. We hypothesize the HR group will exhibit greater amygdala activation and weaker functional connectivity between amygdala and prefrontal cortex, a structure theorized to regulate the amygdala, relative to HC. Within the HR group, abnormal activation and connectivity will be correlated with the ability to emotionally self-regulate. Both treating youth with and at high-risk for BD and having basic neuroimaging experience have laid a solid foundation for me to achieve my training goals and complete this study. The proposed integrated research, mentorship, and didactic training programs, combined with the outstanding research environment at the University of Texas Health Science Center at San Antonio, will foster my long-term career objective of being a leading expert in multimodal social cognitive neural models as they relate to anxiety and emotion regulation in children at high-risk for BD.