Novel Mechanisms of Fear Reduction Targeting the Biological State of the Developing Brain

 描述（由申请人提供）：青春期是精神疾病发作的高峰期，焦虑是最常见的疾病，影响多达十分之一的青年。焦虑症的一个核心特征是难以识别过去经历过的威胁性情况目前是否安全。尽管在整个发展过程中，支持情绪调节和恐惧消退的神经回路发生了重大变化，但对青年的干预措施主要是基于在成年期研究和实施的治疗原则。本申请的主要目标是研究安全信号学习作为一种针对发育中大脑生物状态的恐惧减少新方法的功效。啮齿类动物的研究表明，安全信号可以有效地减少焦虑，以治疗和预防新的恐惧的发展。这种学习在很大程度上依赖于海马体，这是一个从童年到青春期显示出显著发展的区域。然而，人类的安全信号学习在很大程度上仍未被探索，特别是在焦虑高峰期的青春期。这项拟议的研究采用了动物研究中使用的范式，以测试健康儿童和青少年以及焦虑症患者在发育过程中安全信号的有效性。目的1将检查儿童和青少年时期安全信号学习和相关大脑半球-额杏仁核回路的规范性发展。目标2将测试安全信号学习，以减少焦虑的儿童和青少年的恐惧，并测试这一假设，即在这些人的大脑前额叶杏仁核电路偏离典型的发展。目的3将研究焦虑的类型和严重程度与安全信号学习和海马-额杏仁核发育的关系。了解这些神经发育变化及其在疾病发作和治疗效果中所起的作用，对于减轻精神疾病对个人和社会造成的沉重心理和经济负担至关重要。该项目预计将对儿童和青少年焦虑干预的时间和类型产生直接影响，填补目前文献中的巨大空白。

 DESCRIPTION (provided by applicant): Adolescence is a peak time for the onset of mental illnesses, with anxiety being the most common disorder and affecting as many as 1 in 10 youth. A core feature of anxiety disorders is difficulty identifying when situations that have been experienced as threatening in the past are currently safe. Despite substantial changes in the neural circuitry supporting emotion regulation and fear extinction across development, interventions for youth are largely based on treatment principles studied and implemented in adulthood. The primary goal of this application is to investigate the efficacy of safety signal learning as a novel method of fear reduction targeting the biological state of the developing brain. Rodent studies have shown that safety signals effectively reduce anxiety to treat and prevent the development of new fears. This learning relies largely on the hippocampus, a region that shows significant development from childhood to adolescence. Yet safety signal learning remains largely unexplored in humans, especially during adolescence when anxiety peaks. The proposed research adapts a paradigm used in animal studies to test the efficacy of safety signals across development in healthy children and adolescents and those with anxiety disorders. Aim 1 will examine the normative development of safety signal learning and related hippocampal-frontoamygdala circuitry across childhood and adolescence. Aim 2 will test safety signal learning for reducing fear among anxious children and adolescents and test the hypothesis that hippocampal-frontoamygdala circuitry deviates from typical development in these individuals. Aim 3 will examine how type and severity of anxiety relate to safety signal learning and hippocampal- frontoamygdala development. Understanding these neurodevelopmental changes and the roles that they play in both the emergence of illness onset and in treatment efficacy is critical to alleviating the high psychological and economic burden that psychiatric disorders have on the individual and on society. This project is expected to have direct implications for the timing and types of intervention for child and adolescent anxiety, fillng a large gap in the current literature.