Molecular Mechanisms of Atypical Habituation in Autism Spectrum Disorders

自闭症谱系障碍非典型习惯的分子机制

基本信息

  • 批准号:
    8913271
  • 负责人:
  • 金额:
    $ 48.85万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-08-15 至 2019-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This project is designed to evaluate the efficacy of a novel imaging, biochemical, and behavioral approach for detecting autism spectrum disorder (ASD) and discovering mechanisms associated with ASD symptomology. Although considerable knowledge has been gained, the lack of reliable predictors during the first year of life remains a major impediment to implementing effective early interventions in children at-risk for ASD. The heterogeneity in ASD renders it unlikely that one specific biomarker will provide a pathognomonic sign of ASD. However, the combination of biomarkers and behavioral indicators being tested in this application has the potential to reveal a biosignature of ASD that can be identified in infancy. We are focusing on the amygdala and limbic system dysfunction in our application. Amygdala dysfunction has been proposed as a critical component of social impairment in ASD, the core symptom that differentiates ASD from other neurodevelopmental disorders. However, functional imaging biomarkers of amygdala dysfunction are yet to be discovered and validated. The current project combines two sensitive functional magnetic resonance imaging (fMRI) measures of amygdala dysfunction in ASD: rapid face detection and reduced amygdala habituation to faces into a new, robust, fMRI habituation paradigm. In addition, we developed a novel amygdala habituation measure using olfactory stimuli. First, we will confirm the sensitivity of our amygdala habituation measures (assayed using emotional faces and odors) for distinguishing children with ASD from typically developing controls. Second we address the mechanisms for atypical habituation, by testing whether reduced fMRI habituation in ASD is driven by alterations in levels of glutamate (excitatory) and/or gamma-amino butyric acid (GABA, inhibitory). Lastly, we are testing whether our battery of olfactory measures including odor detection, cyclic adenosine monophosphate (cAMP) levels (the primary signaling pathway used by olfactory sensory neurons), and fMRI alterations are sensitive and specific biomarkers of ASD. We propose that olfactory measures may be an effective proxy for socioemotional processing given the primacy of emotion in olfactory perception and its shared neuroanatomical substrates with limbic structures affected in ASD. To further investigate the specificity of olfactory measures, we will test the ability of our measures to discriminate between individuals with ASD, typically developing (TD) children and children with clinically significant sensory processing symptoms (SPD). The proposed research addresses Objective 1 of the NIMH Strategic Plan by integrating behavioral and biological markers and examining how neurobiological mechanisms - specifically GABA and glutamate levels - contribute to atypical brain habituation in ASD. Fifty children (8-12 years of age) with high functioning ASD (Full-scale IQ > 70), 50 children with clinically significant sensory processing symptoms (SPD) and 50 typically developing controls (TD) will participate in the study. The TD and SPD groups will be matched to the ASD group according to age, gender, and Full-scale IQ.
描述(由申请人提供):该项目旨在评估一种新的成像,生物化学和行为方法检测自闭症谱系障碍(ASD)和发现与ASD神经病学相关的机制的有效性。虽然已经获得了相当多的知识,但在生命的第一年缺乏可靠的预测因素仍然是对ASD风险儿童实施有效早期干预的主要障碍。ASD的异质性使得一种特异性生物标志物不太可能提供ASD的特异性体征。然而,在本申请中测试的生物标志物和行为指标的组合有可能揭示可以在婴儿期识别的ASD的生物特征。在我们的申请中,我们关注杏仁核和边缘系统功能障碍。杏仁核功能障碍已被认为是ASD中社交障碍的关键组成部分,ASD是区分ASD与其他神经发育障碍的核心症状。然而,杏仁核功能障碍的功能成像生物标志物尚未被发现和验证。目前的项目结合了两个敏感的功能磁共振成像(fMRI)措施杏仁核功能障碍的ASD:快速人脸检测和减少杏仁核习惯到一个新的,强大的,fMRI习惯化范式。此外,我们开发了一种新的杏仁核习惯性措施,使用嗅觉刺激。首先,我们将确认我们的杏仁核习惯化措施的敏感性(使用情绪化的面孔和气味进行分析),以区分自闭症儿童与典型的发展控制。第二,我们解决的机制,非典型的习惯,通过测试是否减少功能磁共振成像习惯在ASD是由谷氨酸(兴奋性)和/或γ-氨基丁酸(GABA,抑制性)水平的改变。最后,我们正在测试我们的嗅觉测量方法,包括气味检测,环磷酸腺苷(cAMP)水平(嗅觉感觉神经元使用的主要信号通路)和fMRI改变是否是ASD的敏感和特异性生物标志物。我们建议,嗅觉措施可能是一个有效的代理socioemotional处理的首要地位的情绪在嗅觉感知和其共享的神经解剖学基板与边缘系统结构的影响,在ASD。为了进一步研究嗅觉测量的特异性,我们将测试我们测量的能力 以区分患有ASD的个体,通常是发育中(TD)儿童和具有临床显著感觉处理症状(SPD)的儿童。拟议的研究通过整合行为和生物标志物并研究神经生物学机制-特别是GABA和谷氨酸水平-如何促进ASD的非典型大脑习惯化来解决NIMH战略计划的目标1。50名患有高功能ASD(全量表IQ > 70)的儿童(8-12岁)、50名具有临床显著感觉处理症状(SPD)的儿童和50名典型发育对照(TD)将参与该研究。TD和SPD组将根据年龄、性别和全面智商与ASD组进行匹配。

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 }}

Natalia M Kleinhans其他文献

Natalia M Kleinhans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('Natalia M Kleinhans', 18)}}的其他基金

4/5-The Autism Biomarkers Consortium for Clinical Trials
4/5-自闭症生物标志物临床试验联盟
  • 批准号:
    10675104
  • 财政年份:
    2015
  • 资助金额:
    $ 48.85万
  • 项目类别:
4/5-The Autism Biomarkers Consortium for Clinical Trials
4/5-自闭症生物标志物临床试验联盟
  • 批准号:
    10224938
  • 财政年份:
    2015
  • 资助金额:
    $ 48.85万
  • 项目类别:
4/5-The Autism Biomarkers Consortium for Clinical Trials
4/5-自闭症生物标志物临床试验联盟
  • 批准号:
    10439671
  • 财政年份:
    2015
  • 资助金额:
    $ 48.85万
  • 项目类别:
4/5-The Autism Biomarkers Consortium for Clinical Trials
4/5-自闭症生物标志物临床试验联盟
  • 批准号:
    10083891
  • 财政年份:
    2015
  • 资助金额:
    $ 48.85万
  • 项目类别:
Molecular Mechanisms of Atypical Habituation in Autism Spectrum Disorders
自闭症谱系障碍非典型习惯的分子机制
  • 批准号:
    9272444
  • 财政年份:
    2014
  • 资助金额:
    $ 48.85万
  • 项目类别:
Molecular Mechanisms of Atypical Habituation in Autism Spectrum Disorders
自闭症谱系障碍非典型习惯的分子机制
  • 批准号:
    8755424
  • 财政年份:
    2014
  • 资助金额:
    $ 48.85万
  • 项目类别:
Molecular Mechanisms of Atypical Habituation in Autism Spectrum Disorders
自闭症谱系障碍非典型习惯的分子机制
  • 批准号:
    9488535
  • 财政年份:
    2014
  • 资助金额:
    $ 48.85万
  • 项目类别:
Multimodal Brain Imaging in Autism Spectrum Disorders
自闭症谱系障碍的多模态脑成像
  • 批准号:
    7472617
  • 财政年份:
    2008
  • 资助金额:
    $ 48.85万
  • 项目类别:
Multimodal Brain Imaging in Autism Spectrum Disorders
自闭症谱系障碍的多模态脑成像
  • 批准号:
    7821266
  • 财政年份:
    2008
  • 资助金额:
    $ 48.85万
  • 项目类别:
Multimodal Brain Imaging in Autism Spectrum Disorders
自闭症谱系障碍的多模态脑成像
  • 批准号:
    7600595
  • 财政年份:
    2008
  • 资助金额:
    $ 48.85万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.85万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了