Neonatal Brain Activity and Risk for Anxiety Disorders in Early Childhood

焦虑症是儿科精神疾病最常见的形式，影响高达30%且严重 高达20%的青少年在18岁之前受损。不幸的是，高达50%的儿童即使在18岁之前仍有症状 使用最好的治疗方法，使焦虑症成为一个主要的公共卫生问题。一个主要障碍是 设计新的治疗焦虑症的方法是大脑的病理生理很可能在出生或更早的时候就开始了， 但人们对大脑发育异常的早期阶段知之甚少。这项建议测量大脑 高风险与低风险患焦虑症的新生儿的活动和大脑连接；发现 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、预防和新的治疗方法的开发。成年人的焦虑症与 大脑网络中对环境或新鲜感的变化做出反应的活动增加，加上 调节这种新奇反应的大脑网络活动减少。行为和脑电数据表明 这些过程可能在婴儿期就开始了。行为和神经(测量)持续增强的婴儿 通过脑电)对新奇事物的反应被描述为具有行为抑制(BI)气质，并且 患焦虑症的风险很高。母亲的高度产前焦虑也与此类似 这既增加了对新奇事物的反应性，也增加了后代患焦虑症的风险。这个 这项应用的目的是确定新生儿中特定的大脑网络，这些网络与 这种对新颖性的持久增强反应，意味着以后开发的风险增加 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来测量区域大脑活动， 是由睡眠中的新生儿突然的、意想不到的听觉刺激(“奇怪的球”)引起的。由声母引起的活动 古怪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。中心假设是新生儿患焦虑症的风险很高。 (基于母亲高度焦虑或高BI)表明大脑网络活动增加， 对新颖性作出反应；再加上在反复介绍 刺激物。我们还将使用静息状态功能磁共振来测量网络连接，并预测焦虑的风险 障碍将与网络中对新奇事物做出反应的连接性改变有关。我们将测试这些 通过招募怀孕母亲并在出生后2周内对后代(n=150)进行核磁共振检查来进行假设。我们 然后在新生儿和母亲出生后头两年的3次额外探视中进行评估。我们将评估 孕妇孕期焦虑与婴儿出生后2年气质的关系 观察性测量。结果可能为高危婴儿的预防措施开辟新的途径，如 如反复接触新的刺激；或刺激有问题的大脑网络。这样的措施本可以 通过预防最普遍的儿童精神障碍，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.