Clinical studies of CRF-PACAP systems in human PTSD (Rosso)

CRF-PACAP 系统治疗人类 PTSD 的临床研究 (Rosso)

基本信息

  • 批准号:
    10580001
  • 负责人:
  • 金额:
    $ 74.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-04-01 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

PROJECT 4 (ROSSO LAB): SUMMARY Post-Traumatic Stress Disorder (PTSD) is a leading cause of global disease burden, and it is twice as common in women as in men. In addition to female sex, genetic factors are established risk factors for PTSD. Furthermore, the diagnosis requires exposure to at least one highly traumatizing stressor, which independently and synergistically with genetic vulnerability leads to long-lasting perturbations in biological arousal systems. A number of moderators of stress responsiveness may contribute to PTSD, including the differential risk seen in women. Altered function of corticotropin releasing factor (CRF) and pituitary adenylate cyclase-activating polypeptide (PACAP) systems represent candidate mechanisms of sex-dependent moderation of PTSD liability. Higher blood PACAP levels and allelic variation in the gene (ADCYAP1R1) encoding the PAC1R receptor predict greater anxious arousal symptoms and total symptoms in women with PTSD, and greater physiological arousal during anxiety-related paradigms. Variation in CRF and its Type-I receptor have also been associated with both PTSD and depression, and sex differences may produce persistent physiological arousal in women exposed to severe stress. Importantly, the neurobiological correlates of CRF/PACAP overlap with arousal-related brain circuitry that is implicated in PTSD, including extended amygdala (extAMG) and medial prefrontal cortex (mPFC). This project is designed to identify CRF-, PACAP-, CRF+PACAP-predominant intermediate phenotypes in women and men with PTSD. Two subregions of the extAMG, the amygdala (AMG) and bed nucleus of the stria terminalis (BNST), will be independently examined, due to evidence of their partially separable roles in fear versus anxiety, and their potentially differential contributions to PTSD. The mPFC will be a focus as a region that modulates arousal responses to threat via reciprocal connections with the AMG and BNST. Using blood samples from adults with DSM-5 PTSD, we will examine CRF and PACAP variation (genetic, epigenetic, mRNA) in relation to markers of hyperarousal across levels of analysis: (1) blood levels of PACAP and hypothalamic pituitary adrenal axis hormones (ACTH and cortisol) as indices of CRF function; (2) resting state functional magnetic resonance imaging of extAMG-mPFC; (4) diffusion tensor imaging of extAMG-mPFC; (5) magnetic resonance spectroscopy of mPFC glutamate metabolism and neuronal integrity (N-acetylaspartate); (6) physiological indices of arousal during fear conditioning and dark enhanced startle paradigms; and (7) clinical symptoms of hyperarousal: anxious arousal, dysphoric arousal, and sleep disruption (using self-report and actigraphy). Project 4 will enhance our understanding of biobehavioral mechanisms of CRF/PACAP in humans, with the potential to identify new PTSD biomarkers. Neuroimaging of BNST function and glutamate metabolism is particularly innovative and may facilitate development of improved diagnostics or therapeutics for individuals with PTSD. We focus on the same peptide systems and brain regions as the other SPARED Projects, and we will use new discoveries from across the Center to continuously refine and optimize our objectives.
项目4 (rosso实验室):总结

项目成果

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ISABELLE M ROSSO其他文献

ISABELLE M ROSSO的其他文献

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{{ truncateString('ISABELLE M ROSSO', 18)}}的其他基金

Progressive social withdrawal in trauma-exposed older adolescents and young adults: neurocircuitry predictors
遭受创伤的老年青少年和年轻人的渐进性社交退缩:神经回路预测因素
  • 批准号:
    10491228
  • 财政年份:
    2021
  • 资助金额:
    $ 74.6万
  • 项目类别:
Progressive social withdrawal in trauma-exposed older adolescents and young adults: neurocircuitry predictors
遭受创伤的老年青少年和年轻人的渐进性社交退缩:神经回路预测因素
  • 批准号:
    10672968
  • 财政年份:
    2021
  • 资助金额:
    $ 74.6万
  • 项目类别:
Multimodal imaging of hippocampal-cortical networks and mechanisms of trauma-related intrusions
海马皮质网络的多模态成像和创伤相关侵入的机制
  • 批准号:
    10159137
  • 财政年份:
    2019
  • 资助金额:
    $ 74.6万
  • 项目类别:
Multimodal imaging of hippocampal-cortical networks and mechanisms of trauma-related intrusions
海马皮质网络的多模态成像和创伤相关侵入的机制
  • 批准号:
    10393641
  • 财政年份:
    2019
  • 资助金额:
    $ 74.6万
  • 项目类别:
Clinical studies of CRF-PACAP systems in human PTSD (Rosso)
CRF-PACAP 系统治疗人类 PTSD 的临床研究 (Rosso)
  • 批准号:
    10356107
  • 财政年份:
    2019
  • 资助金额:
    $ 74.6万
  • 项目类别:
Clinical studies of CRF-PACAP systems in human PTSD (Rosso)
CRF-PACAP 系统治疗人类 PTSD 的临床研究 (Rosso)
  • 批准号:
    10116484
  • 财政年份:
    2019
  • 资助金额:
    $ 74.6万
  • 项目类别:
Multimodal imaging of hippocampal-cortical networks and mechanisms of trauma-related intrusions
海马皮质网络的多模态成像和创伤相关侵入的机制
  • 批准号:
    10597248
  • 财政年份:
    2019
  • 资助金额:
    $ 74.6万
  • 项目类别:
Cerebral GABA and Fear Conditioning in PTSD
创伤后应激障碍 (PTSD) 中的大脑 GABA 和恐惧调节
  • 批准号:
    9085462
  • 财政年份:
    2012
  • 资助金额:
    $ 74.6万
  • 项目类别:
Cerebral GABA and Fear Conditioning in PTSD
创伤后应激障碍 (PTSD) 中的大脑 GABA 和恐惧调节
  • 批准号:
    8688354
  • 财政年份:
    2012
  • 资助金额:
    $ 74.6万
  • 项目类别:
Cerebral GABA and Fear Conditioning in PTSD
创伤后应激障碍 (PTSD) 中的大脑 GABA 和恐惧调节
  • 批准号:
    8399764
  • 财政年份:
    2012
  • 资助金额:
    $ 74.6万
  • 项目类别:

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