Neonatal Brain Activity and Risk for Anxiety Disorders in Early Childhood

焦虑症是最常见的儿科精神疾病，影响高达30%，严重 使20%的18岁以前的青少年受到损害。不幸的是，高达50%的儿童即使在 最好的治疗方法，使焦虑症成为一个主要的公共卫生问题。的主要障碍 为焦虑症设计新的治疗方法是，大脑病理生理学可能在出生或更早时就开始了， 但对大脑发育异常的最早阶段知之甚少。这项建议衡量大脑 焦虑症高危与低危新生儿的活动和大脑连接 导致焦虑症的神经发育途径的第一步;并提供了一个框架 用于早期识别、预防和开发新的治疗方法。成人焦虑症与 随着大脑网络对环境变化或“新奇事物”的反应而增加， 调节这种新奇反应的大脑网络活动减少。行为和脑电图数据表明， 这些过程可能始于婴儿期。具有持久增强的行为和神经功能的婴儿（如测量的 对新奇事物的反应被描述为具有“行为抑制（BI）”气质， 以后患上焦虑症的风险很高。母亲产前焦虑程度高与 对新奇事物的反应性增加，后代患焦虑症的风险增加。的 本申请的目的是识别新生儿的特定脑网络， 这种对新奇事物的持久增强的反应，代表了以后发展的风险增加， 焦虑症为了实现这一目标，我们将使用基于任务的功能磁共振成像来测量区域大脑活动， 是由睡眠中的新生儿突然的、意外的听觉刺激（"古怪"）引起的。由最初的 古怪的球代表最初的新奇反应，而由后来的古怪球引起的活动代表潜在的 监管回应。中心假设是，新生儿在高风险发展的焦虑症， (on高母亲焦虑或高BI的基础）表明大脑网络的活动增加， 对新奇事物的反应;再加上在反复介绍 刺激。我们还将使用静息状态功能磁共振成像来测量网络连接，我们预测焦虑的风险 疾病将与对新奇事物作出反应的网络中改变的连通性相关联。我们将测试这些 通过招募怀孕母亲并在出生2周内获得后代（n = 150）的MRI来进行假设。我们 然后在出生后的前2年内，在3次额外访视时评估新生儿和母亲。我们将评估 母亲在怀孕期间的焦虑与问卷调查和婴儿的气质，在前2年， 观察措施。结果可能为高危婴儿的预防措施开辟新的途径， 反复暴露于新的刺激;或刺激有问题的大脑网络。这些措施将 通过预防最普遍的儿童精神疾病，对公共卫生产生重大影响。

Anxiety disorders are the most common form of pediatric psychiatric illness, affecting up to 30% and severely impairing up to 20% of all youth prior to age 18. Unfortunately, up to 50% of children remain symptomatic even with the best available treatment, making anxiety disorders a major public health problem. A major barrier to devising new treatments for anxiety disorders is that the brain pathophysiology likely starts at birth or earlier, but little is known about the earliest stages of abnormal brain development. This proposal measures brain activity and brain connectivity in neonates at high versus low risk for developing an anxiety disorder; uncovers the first steps in the neurodevelopmental pathway that results in an anxiety disorder; and provides a framework for early identification, prevention, and new treatment development. Anxiety disorders in adults are associated with increased activity in brain networks that respond to changes in the environment or `novelty', coupled with decreased activity in brain networks that regulate this novelty response. Behavioral and EEG data suggest that these processes may start in infancy. Infants with an enduring enhanced behavioral and neural (as measured by EEG) reaction to novelty are described as having the `behavioral inhibition (BI)' temperament and are at high risk for later development of an anxiety disorder. High maternal prenatal anxiety is similarly associated with both increased reactivity to novelty and increased risk for developing an anxiety disorder in offspring. The objective of this application is to identify the specific brain networks in newborn infants that are associated with this enduring enhanced response to novelty and that represent increased risk for later development of an anxiety disorder. To achieve this objective, we will use task-based fMRI to measure regional brain activity that is elicited by sudden, unexpected auditory stimuli (`oddballs') in sleeping neonates. Activity evoked by the initial oddballs represents the initial novelty response, while activity evoked by later oddballs represents the potential regulatory response. The central hypotheses are that neonates at high risk for developing an anxiety disorder (on the basis of either high maternal anxiety or high BI) demonstrate increased activity in brain networks that respond to novelty; coupled with decreased activity in regulatory networks after repeated presentation of the stimuli. We will also use resting-state fMRI to measure network connectivity, and we predict that risk for anxiety disorders will be associated with altered connectivity in networks that respond to novelty. We will test these hypotheses by recruiting pregnant mothers and obtaining MRI in offspring (n=150) within 2 weeks of birth. We will then assess the neonates and mothers at 3 additional visits over the first 2 years of life. We will assess maternal anxiety during pregnancy with questionnaires and infant temperament in the first 2 years with observational measures. Results may open new avenues for preventative measures in high-risk infants, such as repeated exposure to new stimuli; or stimulation of problematic brain networks. Such measures would have major public health impact, by preventing the most prevalent childhood psychiatric disorder.