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

 描述(申请人提供)：青春期是精神疾病发作的高峰期，焦虑是最常见的障碍，影响多达十分之一的年轻人。焦虑症的一个核心特征是很难识别过去被认为具有威胁性的情况现在是安全的。尽管支持情绪调节和恐惧消退的神经回路在整个发育过程中发生了实质性变化，但对青少年的干预主要基于成年后研究和实施的治疗原则。这项应用的主要目标是研究安全信号学习作为一种新的减少恐惧的方法的有效性，目标是针对发育中的大脑的生物状态。啮齿类动物的研究表明，安全信号有效地减少焦虑，治疗和防止新的恐惧的发展。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都有显著发展的区域。然而，安全信号的学习在很大程度上仍未在人类身上得到探索，特别是在焦虑达到顶峰的青春期。这项拟议的研究采用了动物研究中使用的范式，以测试安全信号在健康儿童和青少年以及患有焦虑症的儿童和青少年中的发育效果。目标1将研究儿童和青春期安全信号学习和相关的海马额杏仁核回路的标准化发展。目标2将测试在焦虑的儿童和青少年中减少恐惧的安全信号学习，并测试这些人的海马-额叶-杏仁核回路偏离典型发育的假设。目标3将研究焦虑的类型和严重程度如何与安全信号学习和海马额杏仁核发育相关。了解这些神经发育变化及其在疾病发病和治疗效果的出现中所起的作用，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的干预时机和类型产生直接影响，填补当前文献中的一个很大空白。

 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.