Trauma and Genomics Modulate Brain Structure across Common Psychiatric Disorders

创伤和基因组学调节常见精神疾病的大脑结构

基本信息

  • 批准号:
    9974588
  • 负责人:
  • 金额:
    $ 45.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-06 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Exposure to trauma and abuse during childhood, a critical neurodevelopmental period, is a major risk factor for adult psychopathology. However, not all children exposed to childhood trauma will develop adult psychopathology. Variability in the risk for trauma-related pathology is expected to arise in part from genetic susceptibility. Several genes have recently been identified that interact with childhood trauma to increase rates of anxiety and mood disorders in adulthood. This risk can be more easily detected by examining endophenotypes such as brain measures obtained from MRI because of a simpler underlying genetic architecture with fewer individual genes or pathways than the multiple factors driving overall risk for psychopathology. Understanding the molecular-genetic contributors to brain structure that conspire with early-life environment (psychological trauma) and lead to adult psychopathology, will require large-scale collaborative efforts which harness big-data methodologies. Our goal is to conduct a GWAS of relevant structural brain measures in individuals exposed to childhood trauma, with the long-term goal of identifying genetic modulators of brain structure that are informative for early prediction and treatment for a range of psychiatric disorders where childhood trauma is a major risk factor. We hypothesize that (1) childhood trauma will interact with specific genetic markers to produce structural brain alterations and adult psychopathology, (2) that unique genetic variants, in the context of genetic vulnerability to childhood trauma, will influence the onset of specific disorders (e.g. depression vs PTSD), as well as (3) the presentation of specific symptom constructs (e.g. sustained threat) across disorders. Finding disease-associated genetic variation that point to molecular mechanisms of pathogenesis has proven challenging due to the polygenicity of clinical phenotypes. Leveraging neuroimaging phenotypes may offer a more direct path than clinical phenotypes in identifying these elusive genetic markers and relevant neurobiological pathways. Ultimately, the promise of finding genetic contributors of any psychiatric disorder is in identifying the presence of new biologic pathways for which targeted interventions may be devised and deployed.
摘要 在儿童时期,一个关键的神经发育时期,暴露于创伤和虐待是一个主要的风险因素 成人精神病理学然而,并不是所有遭受童年创伤的儿童都会成长为成年人。 精神病理学创伤相关病理风险的变异性预计部分来自遗传因素。 易感性最近发现了几个与儿童创伤相互作用的基因, 焦虑和情绪障碍的风险。这种风险可以通过检查 内表型,如从MRI获得的脑测量,因为更简单的潜在遗传 与驱动总体风险的多个因素相比,单个基因或途径较少的结构 精神病理学了解大脑结构的分子遗传贡献者, 早期生活环境(心理创伤)并导致成人精神病理学,将需要大规模的 利用大数据方法的协作努力。我们的目标是进行一次GWAS, 在暴露于童年创伤的个体中进行脑结构测量,其长期目标是识别 大脑结构的遗传调节剂,为早期预测和治疗一系列疾病提供信息。 童年创伤是主要风险因素的精神疾病。我们假设(1)童年创伤 将与特定的遗传标记相互作用,产生大脑结构改变和成人精神病理学, (2)独特的遗传变异,在遗传脆弱性的背景下,儿童创伤,将影响 特定疾病的发作(例如抑郁症vs PTSD),以及(3)特定症状的表现 构建(例如持续威胁)跨疾病。发现与疾病相关的遗传变异, 由于临床表型的多基因性,发病的分子机制已被证明是具有挑战性的。 利用神经影像表型可能比临床表型提供更直接的识别途径 这些难以捉摸的遗传标记和相关的神经生物学通路。最终,找到遗传基因的希望 任何精神疾病的贡献者是在确定新的生物途径, 可以设计和部署有针对性的干预措施。

项目成果

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NEGAR FANI其他文献

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{{ truncateString('NEGAR FANI', 18)}}的其他基金

Neural Mechanisms of Vibroacoustically Augmented Breath Focused Mindfulness for Dissociative Traumatized People
振动声学增强呼吸聚焦正念对于解离性创伤患者的神经机制
  • 批准号:
    10600443
  • 财政年份:
    2021
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neural Mechanisms of Vibroacoustically Augmented Breath Focused Mindfulness for Dissociative Traumatized People
振动声学增强呼吸聚焦正念对于解离性创伤患者的神经机制
  • 批准号:
    10554379
  • 财政年份:
    2021
  • 资助金额:
    $ 45.93万
  • 项目类别:
Inflammation Changes Associated with Interoception Changes following Vibroacoustically Augmented Breath Focused Mindfulness for Dissociation
振动声学增强呼吸集中正念解离后与内感受变化相关的炎症变化
  • 批准号:
    10632723
  • 财政年份:
    2021
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neural Mechanisms of Vibroacoustically Augmented Breath Focused Mindfulness for Dissociative Traumatized People
振动声学增强呼吸聚焦正念对于解离性创伤患者的神经机制
  • 批准号:
    10782111
  • 财政年份:
    2021
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neural Mechanisms of Vibroacoustically Augmented Breath Focused Mindfulness for Dissociative Traumatized People
振动声学增强呼吸聚焦正念对于解离性创伤患者的神经机制
  • 批准号:
    10330586
  • 财政年份:
    2021
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neural Mechanisms of Cognitive Control in Posttraumatic Stress Disorder
创伤后应激障碍认知控制的神经机制
  • 批准号:
    9031160
  • 财政年份:
    2014
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neural Mechanisms of Cognitive Control in Posttraumatic Stress Disorder
创伤后应激障碍认知控制的神经机制
  • 批准号:
    8841831
  • 财政年份:
    2014
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neural Mechanisms of Cognitive Control in Posttraumatic Stress Disorder
创伤后应激障碍认知控制的神经机制
  • 批准号:
    9246595
  • 财政年份:
    2014
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neural Mechanisms of Cognitive Control in Posttraumatic Stress Disorder
创伤后应激障碍认知控制的神经机制
  • 批准号:
    8700677
  • 财政年份:
    2014
  • 资助金额:
    $ 45.93万
  • 项目类别:
Neuroendophenotypes and Risk for Posttraumatic Stress Disorder
神经内表型和创伤后应激障碍的风险
  • 批准号:
    8203312
  • 财政年份:
    2011
  • 资助金额:
    $ 45.93万
  • 项目类别:
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