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

针对发育中大脑的生物状态的减少恐惧的新机制

基本信息

批准号：
9314714
负责人：
Dylan Grace Gee
金额：
$ 25.13万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-11 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9314714
关键词：
17 year old Adolescence Adolescent Adult Affect Age Amygdaloid structure Animals Anxiety Anxiety Disorders Behavior Biological Brain Child Childhood Classification Cognitive Therapy Conditioned Stimulus Cues Data Deltastab Development Diagnostic and Statistical Manual of Mental Disorders Disease Economic Burden Effectiveness Extinction (Psychology)Fright Functional Magnetic Resonance Imaging Galvanic Skin Response Goals Health Hippocampus (Brain)Human Image Individual Intervention Learning Literature Longevity Measures Mediating Mental disorders Methods Mus Neurobiology Onset of illness Outcome Pathway interactions Patients Play Process Psyche structure Research Research Domain Criteria Rest Rodent Role Safety Severities Signal Transduction Societies Testing Time Treatment Efficacy Youth adolescent brain development anxiety symptoms anxious base connectome efficacy testing emotion regulation experience flexibility insight learned behavior learning extinction neural circuit novel novel strategies preclinical study prevent psychologic response safety testing therapy development

项目摘要

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.

描述（由申请人提供）：青春期是精神疾病发病的高峰期，焦虑症是最常见的疾病，影响多达十分之一的青少年。焦虑症的一个核心特征是很难识别何时发生的情况。尽管在发育过程中支持情绪调节和恐惧消退的神经回路发生了巨大变化，但对青少年的干预措施主要基于成年期研究和实施的治疗原则。该应用的主要目标是进行调查。安全信号学习的有效性作为一种针对发育中大脑的生物状态的减少恐惧的新方法，研究表明，安全信号可以有效地减少焦虑，从而治疗和预防新恐惧的发展。然而，人类的安全信号学习在很大程度上尚未得到探索，特别是在焦虑达到顶峰的青春期，这项研究采用了动物研究中使用的范式来测试安全信号在健康儿童和青少年以及患有焦虑症的人的发育过程中的有效性。目标障碍。目标 1 将检查儿童和青少年时期安全信号学习和相关海马-额杏仁核回路的规范发展。目标 2 将测试安全信号学习是否可以减少儿童和青少年的恐惧焦虑，并检验海马-额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与安全信号学习和海马-额杏仁核发育的关系。它们在疾病发生和治疗效果方面所发挥的作用对于减轻精神疾病给个人和社会造成的沉重心理和经济负担至关重要。该项目预计将对疾病发生的时间和类型产生直接影响。对儿童和青少年焦虑的干预，填补了当前文献的巨大空白。