Development of Tonic and Phasic Neural Systems Mediating Affect and Anxiety

儿童焦虑症影响大约十分之一的儿童，导致明显的社会障碍。 这些人在成年后患情绪和焦虑症的风险也很高， 这是一个关乎整个生命周期的公共卫生问题。迄今为止描述焦虑症病理生理学特征的工作 焦虑症集中在焦虑症状的一个领域-对潜在威胁的线索过敏， 情绪化的面孔或负面图像（例如，阶段性反应），而其他关键症状的生物标志物 焦虑，如持续的过度警觉和觉醒（例如，紧张性反应），仍然相对未被探索。 本研究计划的目标是：1）描绘大脑系统的典型发育 参与映射到威胁处理和警惕的阶段性和紧张性过程，2）提供初步的 证据表明，它们在代表紧张性焦虑表型特征的广义 焦虑症;和3）测试他们的预测价值的风险，在家族病例。该项目将首先使用 功能性神经影像学和心理生理学来表征大脑网络的功能特性， 介导焦虑的紧张性和阶段性症状，典型的发展中样本（K期）。 然后，异常神经和行为特征将被确定在一个样本的个人与儿科 广泛性焦虑症（GAD）是一种以慢性恐惧和警觉为特征的临床综合征（K 阶段）。使用这些样本，我们将评估广泛性焦虑症的生物行为标志物是否也明显存在于 基于家族史（R期）的焦虑症高危儿童样本。到 完成这些目标，候选人将接受广泛的培训，在测试儿科和临床 受发育和临床神经科学教育以及高级神经影像学支持的人群 技术包括静止状态连接、扩散张量连接和网络建模 方法论。这项工作和培训将为候选人启动独立实验室做好准备 能够进行发育、临床和高级神经影像学研究。不管观察到的结果如何， 这项工作将作为未来R 01基金应用于跟踪高风险个体的自然先导 纵向和/或在临床研究中利用鉴定的生物标志物来评价靶向肿瘤的新疗法。 紧张系统及其相关的慢性焦虑症。这项工作正朝着最终 目标是确定焦虑症风险的预测标志物，以促进早期识别， 预防

Childhood anxiety disorders affect approximately one in ten children resulting in marked social impairment. These individuals also carry a heightened risk for mood and anxiety disorders in adulthood, rendering this a public health issue relevant to the entire lifespan. Work to date characterizing the pathophysiology of anxiety disorders has focused on one sphere of anxious symptoms- hypersensitivity to cues of potential threat such as emotional faces or negative images (e.g., phasic responses), while biological markers for other key symptoms of anxiety, such as sustained hypervigilance and arousal (e.g., tonic responses), remain relatively unexplored. The objectives of this program of research are: 1) to delineate the typical development of brain systems involved in phasic and tonic processes that map onto threat processing and vigilance, 2) to provide preliminary evidence for their differential roles in representing tonic anxious phenotypes characteristic of generalized anxiety disorder; and 3) to test their predictive merit for risk in familial cases. The proposed work will first use functional neuroimaging and psychophysiology to characterize the functional properties of brain networks that mediate tonic and phasic symptoms of anxiety in a cross-sectional, typically developing sample (K phase). Then, deviant neural and behavioral signatures will be identified in a sample of individuals with pediatric Generalized Anxiety Disorder (GAD), a clinical syndrome marked by chronic apprehension and vigilance (K phase). Using these samples, we will assess whether biobehavioral markers of GAD are also evident in a sample of children at heightened risk for developing anxiety disorders based on family history (R phase). To accomplish these objectives, the candidate will receive extensive training in testing pediatric and clinical populations bolstered by education in developmental and clinical neuroscience, and advanced neuroimaging techniques including resting-state connectivity, diffusion tensor connectivity and network modeling methodologies. This work and training will prepare the candidate for initiating an independent laboratory capable of developmental, clinical and advanced neuroimaging research. Irrespective of the observed findings, this work will serve as a natural precursor to future R01 funding applications to track high-risk individuals longitudinally and/or utilize identified biomarkers in clinical research evaluating new therapies targeting the tonic system and its associated chronic anxious symptomatology. This work is progressing toward the ultimate goal of identifying predictive markers of risk for anxiety disorders that will facilitate early identification and prevention.