Early neurodevelopment origins of anxiety

焦虑的早期神经发育起源

基本信息

  • 批准号:
    8475884
  • 负责人:
  • 金额:
    $ 213.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-09-01 至 2018-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Childhood anxious temperament (AT) is a key risk factor for developing anxiety and co- morbid depression. In primates, AT is evident early in life, stable, and associated with increased threat reactivity. Early adversity is known to increase the risk of developing extreme AT. While adversity is common, the neural mechanisms linking it to AT are not understood. This understanding would permit identification of novel therapeutic targets with the potential for developing neuroscientifically-informed interventions. This proposal builds on work validating the AT phenotype and identifying the neural circuit underlying AT. Recent microarray and RNA sequencing (RNA-seq) work suggests the hypothesis that extreme AT reflects neuroplasticity deficits in the lateral division of the central nucleus of the amygdala (CeL), a key regulator of amygdalar outflow to regions that give rise to signs of anxiety, and the region most predictive of AT in our imaging work. This proposal aims to understand how peer rearing (PR), a controlled early adversity manipulation, causes extreme AT in primates, something not possible in human studies. The use of primates increases the likelihood that discoveries will translate to at-risk children. PR and maternally- reared (MR) animals will be longitudinally assessed, testing adversity's impact on the development of AT. Repeated multimodal imaging will assess adversity's impact on the development of amygdala reactivity and prefrontal-amygdala anxiety regulation circuits. Importantly, the primate model affords an opportunity to test whether adversity's harmful effects on AT are mediated by alterations in CeL neuroplasticity pathways. Immunohistochemical and RNA-seq analyses will be performed on CeL microdissected neurons. This novel synthesis of tools promises new insights into how adversity-induced molecular alterations manifest in brain function, connectivity, and structure, and how these macroscopic changes contribute to extreme AT- insights not readily available from molecular-level rodent or systems-level human studies. Further, a stem cell model of CeL GABAergic neurons will be created and compared to neurons from CeL. A valid stem cell model would enhance understanding of AT's molecular bases and accelerate the screening of new therapeutics.
描述(由申请人提供):儿童焦虑气质(AT)是发展焦虑和共病抑郁症的关键危险因素。在灵长类动物中,AT在生命早期是明显的,稳定的,并且与增加的威胁反应性相关。众所周知,早期的逆境会增加患极端AT的风险。虽然逆境是常见的,但将其与AT联系起来的神经机制尚不清楚。这种理解将允许识别新的治疗靶点,具有开发神经科学干预的潜力。这项建议 建立在验证AT表型和识别AT背后的神经回路的基础上。最近的微阵列和RNA测序(RNA-seq)工作表明,极端AT反映杏仁核中央核外侧分裂的神经可塑性缺陷的假设 (CeL)这是杏仁核流出到引起焦虑症状的区域的关键调节器,也是我们成像工作中最能预测AT的区域。这项提案旨在了解同伴教养(PR),一种受控的早期逆境操纵,如何在灵长类动物中导致极端AT,这在人类研究中是不可能的。使用灵长类动物增加了将发现转化为风险儿童的可能性。将对PR和母系饲养的动物进行纵向评估,测试逆境对AT发展的影响。重复的多模态成像将评估逆境对杏仁核反应性和前额杏仁核焦虑调节回路发展的影响。重要的是,灵长类动物模型提供了一个机会来测试逆境对AT的有害影响是否是由细胞神经可塑性通路的改变介导的。将对CeL显微切割的神经元进行免疫组织化学和RNA-seq分析。这种新的工具合成有望对逆境诱导的分子改变如何在大脑功能,连接和结构中表现出新的见解,以及这些宏观变化如何促成极端AT-分子水平的啮齿动物或系统水平的人类研究中不容易获得的见解。此外,将创建CeL GABA能神经元的干细胞模型并与来自CeL的神经元进行比较。有效的干细胞模型将增强对AT分子基础的理解,并加速新疗法的筛选。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Richard J Davidson其他文献

Healthy Minds Index: A brief measure of the core dimensions of well-being
健康心态指数:幸福核心维度的简要衡量标准
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    T. Kral;Pelin Kesebir;Liz Redford;Cortland J. Dahl;C. Wilson;M. Hirshberg;Richard J Davidson;Raquel Tatar
  • 通讯作者:
    Raquel Tatar

Richard J Davidson的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Richard J Davidson', 18)}}的其他基金

The plasticity of well-being: A research network to define, measure and promote human flourishing
福祉的可塑性:定义、衡量和促进人类繁荣的研究网络
  • 批准号:
    10151850
  • 财政年份:
    2021
  • 资助金额:
    $ 213.43万
  • 项目类别:
The plasticity of well-being: A research network to define, measure and promote human flourishing
福祉的可塑性:定义、衡量和促进人类繁荣的研究网络
  • 批准号:
    10557178
  • 财政年份:
    2021
  • 资助金额:
    $ 213.43万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8727668
  • 财政年份:
    2014
  • 资助金额:
    $ 213.43万
  • 项目类别:
Summer Research Experience
暑期研究经历
  • 批准号:
    8727671
  • 财政年份:
    2014
  • 资助金额:
    $ 213.43万
  • 项目类别:
Early neurodevelopment origins of anxiety
焦虑的早期神经发育起源
  • 批准号:
    9132333
  • 财政年份:
    2013
  • 资助金额:
    $ 213.43万
  • 项目类别:
Early neurodevelopment origins of anxiety
焦虑的早期神经发育起源
  • 批准号:
    9323568
  • 财政年份:
    2013
  • 资助金额:
    $ 213.43万
  • 项目类别:
Early neurodevelopment origins of anxiety
焦虑的早期神经发育起源
  • 批准号:
    8913780
  • 财政年份:
    2013
  • 资助金额:
    $ 213.43万
  • 项目类别:
NEURAL BASES OF EMOTION REGULATION AND DYSREGULATION IN ADOLESCENCE
青春期情绪调节和失调的神经基础
  • 批准号:
    8076863
  • 财政年份:
    2010
  • 资助金额:
    $ 213.43万
  • 项目类别:
ADMINISTRATION CORE
管理核心
  • 批准号:
    8076865
  • 财政年份:
    2010
  • 资助金额:
    $ 213.43万
  • 项目类别:
BRAIN IMAGING CORE
脑成像核心
  • 批准号:
    7907926
  • 财政年份:
    2009
  • 资助金额:
    $ 213.43万
  • 项目类别:

相似海外基金

Identification of Prospective Predictors of Alcohol Initiation During Early Adolescence
青春期早期饮酒的前瞻性预测因素的鉴定
  • 批准号:
    10823917
  • 财政年份:
    2024
  • 资助金额:
    $ 213.43万
  • 项目类别:
Socio-Emotional Characteristics in Early Childhood and Offending Behaviour in Adolescence
幼儿期的社会情感特征和青春期的犯罪行为
  • 批准号:
    ES/Z502601/1
  • 财政年份:
    2024
  • 资助金额:
    $ 213.43万
  • 项目类别:
    Fellowship
Cognitive and non-cognitive abilities and career development during adolescence and adult development: from the perspective of genetic and environmental structure
青春期和成人发展期间的认知和非认知能力与职业发展:从遗传和环境结构的角度
  • 批准号:
    23K02900
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Reasoning about Spatial Relations and Distributions: Supporting STEM Learning in Early Adolescence
空间关系和分布的推理:支持青春期早期的 STEM 学习
  • 批准号:
    2300937
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
    Continuing Grant
Does social motivation in adolescence differentially predict the impact of childhood threat exposure on developing suicidal thoughts and behaviors
青春期的社会动机是否可以差异预测童年威胁暴露对自杀想法和行为的影响
  • 批准号:
    10785373
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
Mapping the Neurobiological Risks and Consequences of Alcohol Use in Adolescence and Across the Lifespan
绘制青春期和整个生命周期饮酒的神经生物学风险和后果
  • 批准号:
    10733406
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
The Role of Sleep in the Relationships Among Adverse Childhood Experiences, Mental Health Symptoms, and Persistent/Recurrent Pain during Adolescence
睡眠在不良童年经历、心理健康症状和青春期持续/复发性疼痛之间关系中的作用
  • 批准号:
    10676403
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
Thalamo-prefrontal circuit maturation during adolescence
丘脑-前额叶回路在青春期成熟
  • 批准号:
    10585031
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
Interdisciplinary Perspectives on the Politics of Adolescence and Democracy
青少年政治与民主的跨学科视角
  • 批准号:
    EP/X026825/1
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
    Research Grant
An Empirical Study on the Influence of Socioeconomic Status in Adolescence on Exercise Habits in Adulthood
青春期社会经济地位对成年期运动习惯影响的实证研究
  • 批准号:
    23K16734
  • 财政年份:
    2023
  • 资助金额:
    $ 213.43万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了