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，导致明显的社会损害。 这些人在成年后患情绪和焦虑症的风险也会增加，这使得这一点 关系到整个生命周期的公共卫生问题。迄今关于焦虑的病理生理学特征的工作 精神障碍集中在焦虑症状的一个领域--对潜在威胁的线索高度敏感，如 情绪面孔或负面图像(例如，阶段性反应)，而其他关键症状的生物标记 焦虑的影响，如持续的高度警觉和觉醒(例如，紧张性反应)，仍然相对未被研究。 这项研究的目标是：1)描绘大脑系统的典型发育 参与与威胁处理和警觉相对应的阶段性和主动性过程，2)提供初步 它们在代表全身性紧张性焦虑表型中的不同作用的证据 焦虑症；以及3)测试它们在家族病例中对风险的预测价值。拟议的工作将首先使用 功能神经成像和心理生理学，以表征大脑网络的功能特性 典型的发育中的横断面标本(K期)出现中等程度的紧张性和相性焦虑症状。 然后，将在患有儿科疾病的个体样本中识别出异常的神经和行为特征 广泛性焦虑障碍(GAD)是一种以慢性恐惧和警觉(K)为特征的临床综合征 阶段)。使用这些样本，我们将评估GAD的生物行为标记物是否在 基于家族史的焦虑症高危儿童样本(R期)。至 完成这些目标后，候选人将接受儿科和临床测试方面的广泛培训 通过发展和临床神经科学以及高级神经成像方面的教育支持的人群 包括静止态连通性、扩散张量连通性和网络建模在内的技术 方法论。这项工作和培训将为候选人建立独立实验室做好准备 具备发育、临床和高级神经影像研究能力。不管观察到的发现如何， 这项工作将作为未来R01资金申请的自然先驱，以跟踪高危个人 在临床研究中纵向和/或利用已识别的生物标记物来评估针对 补药系统及其相关的慢性焦虑症状。这项工作正在向终极迈进 确定焦虑症风险的预测性标志物的目标，这将有助于早期识别和 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.