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（由适用提供）：青少年是精神疾病发作的高峰时段，焦虑症是最常见的疾病，影响十分之一的青年中有1个。焦虑症的一个核心特征很难确定何时过去遇到威胁的情况当前是安全的。尽管神经回路的实质性变化，支持情绪调节和恐惧范围内的发展，但对年轻人的干预措施主要基于成年后研究和实施的治疗原则。该应用的主要目的是研究安全信号学习的有效性，这是一种恐惧减少靶向发展大脑生物状态的新方法。啮齿动物研究表明，安全信号有效地减少了治疗和防止新恐惧的焦虑。这种学习在很大程度上取决于海马，该地区显示了从童年到青少年的重大发展。然而，在人类中，安全信号学习在很大程度上仍然是出乎意料的，尤其是在焦虑达到焦虑的青少年时期。拟议的研究适应了动物研究中用于测试健康儿童和青少年以及患有焦虑症患者的安全信号的有效性的范式。 AIM 1将检查整个儿童和青少年的安全信号学习和相关海马 - 弗朗特纳米甲状腺电路的正常发展。 AIM 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，并检验海马 - 弗朗顿亚乳糖电路的假设偏离了这些人的典型发展。 AIM 3将检查焦虑类型和严重性与安全信号学习和海马 - 富富纳米格达拉的发展如何相关。了解这些神经发育的变化以及它们在疾病发作和治疗效率中的作用，对于减轻精神疾病对个人和社会的高心理和经济燃烧至关重要。预计该项目对儿童和青少年焦虑的干预时间和类型有直接影响，在当前文献中填补了很大的空白。