Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD

利用生物标志物对合并 PTSD 的酒精使用障碍进行个性化治疗

基本信息

项目摘要

Overall Summary The overarching goal of the proposed center is to leverage molecular and circuit biomarkers to advance the understanding of mechanisms and personalized treatment of topiramate treatment of Alcohol Use Disorder comorbid with PTSD. We propose an integrative translational focus on alterations in excitatory and inhibitory signaling, focusing on GABA and glutamate and related circuitry, to model the neurobiology of PTSD comorbid with PTSD and the mitigating effects of topiramate. We will characterize excitatory and inhibitory molecular markers in an animal model of AUD comorbid with PTSD, utilizing genomic markers in the brain and plasma markers in rodents. In clinical trial participants we will characterize excitatory and inhibitory neuronal signaling by ascertaining plasma markers, GRIK 1 genotype and neural circuit markers utilizing TMS evoked potentials in EEG, task-based functional MRI and MR spectroscopy. This goal will be achieved through the activities of three research projects supported by two research cores, the administrative core and the Scientific Advisory Board (Figure1). In Project 1 lead by Silvia Fossati Ph.D. and Jorge Manzanares Robles Ph.D. we will study the behavioral and molecular effects of two doses of topiramate vs. vehicle in animal models of AUD alone, PTSD alone and AUD+PTSD. In Project 2 lead by Michael Bogenschutz M.D. and Joshua Lee M.D. we will study the behavioral, genetic and plasma biomarker effects of topiramate vs. placebo in 150 participants with co-occurring AUD and PTSD. In project 3 lead by Amit Etkin M.D., Ph.D. and Charles R. Marmar M.D. we will ascertain multi-modal imaging markers including task based fMRI, TMS evoked potentials in EEG and MRS. Imaging markers will be used to characterize excitatory and inhibitory circuits in Project 2 clinical trial participants with AUD+PTSD to determine predictors and mechanisms of topiramate vs. placebo treatment outcomes. Plasma biomarkers in Project 2 will be related to the same or homologous plasma biomarkers in Project 1. Circuit markers from Project 3 will be related to genomic markers in the same or homologous brain regions in Project 1. The Biofluids Biomarker Core (BBC) lead by Dr. Fossati will support collection of plasma biomarkers (GABA, glutamate, HPA axis, neuropeptides, neuroinflammatory and oxidative stress) in animals in Project 1 and clinical trial participants in Project 2. The Analytics and Biostatistics Core (ABC) lead by Eugene Laska Ph.D. and Carole Segal Ph.D. will support experimental design, formulation of hypothesis, power calculations, and data integrity, management and analysis for Project 1, 2 and 3, implementing advanced statistical models for individualized prediction of response to topiramate in Project 1 and Project 2.
总体汇总 拟议中心的首要目标是利用分子和电路生物标志物来推进生物技术的发展。 了解托吡酯治疗酒精使用障碍的机制及个体化治疗 患有创伤后应激障碍我们提出了一个整合的翻译重点改变兴奋和抑制 信号传导,重点是GABA和谷氨酸和相关电路,以模拟PTSD共病的神经生物学 和托吡酯的缓解作用我们将描述兴奋性和抑制性分子 利用脑和血浆中的基因组标记物, 啮齿类动物的标记在临床试验参与者中,我们将描述兴奋性和抑制性神经元信号传导 利用TMS诱发电位确定血浆标记物、GRIK1基因型和神经回路标记物 在脑电图,基于任务的功能性磁共振成像和磁共振波谱。 这一目标将通过由两个研究核心支持的三个研究项目的活动来实现, 行政核心和科学咨询委员会(图1)。项目1由Silvia Fossati博士领导。 Jorge Manzanares Robles博士我们将研究两种剂量的 在单独的AUD、单独的PTSD和AUD+PTSD的动物模型中,托吡酯与赋形剂。在项目2中, Michael Bogenschutz医学博士和约书亚李医学博士我们将研究行为遗传和血浆生物标志物 托吡酯与安慰剂在150名患有AUD和PTSD的受试者中的作用。在项目3中, Amit Etkin医学博士,博士查尔斯·R。Marmar医学博士我们将确定多模态成像标记,包括 基于任务的fMRI,EEG和MRS中的TMS诱发电位。成像标记物将用于表征 在患有AUD+PTSD的项目2临床试验参与者中的兴奋和抑制回路,以确定预测因素 和托吡酯与安慰剂治疗结果的机制。项目2中的血浆生物标志物将是 与项目1中相同或同源的血浆生物标志物相关。项目3的电路标记将 与项目1中相同或同源脑区的基因组标记相关。生物流体生物标志物 由Fossati博士领导的核心(BBC)将支持收集血浆生物标志物(GABA、谷氨酸、HPA轴, 神经肽、神经炎症和氧化应激),以及 项目2.分析和生物统计学核心(ABC)由尤金拉斯卡博士领导。Carole Segal博士 将支持实验设计、假设制定、功效计算和数据完整性, 管理和分析项目1,2和3,实施先进的统计模型, 预测项目1和项目2中对托吡酯的反应。

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 }}

Charles R. Marmar其他文献

Examination of Patient and Provider Satisfaction, Benefits, and Challenges with Psychiatric Outpatient and Hospital-Based Telehealth Treatment during the COVID-19 Pandemic
  • DOI:
    10.1007/s11126-025-10150-w
  • 发表时间:
    2025-04-24
  • 期刊:
  • 影响因子:
    2.900
  • 作者:
    Christina Marini;Margot H. Steinberg;Carly D. Miron;Matthew Irwin;Bryana L. Schantz;David L. Ginsberg;Charles R. Marmar;Naomi M. Simon;Paraskevi Noulas;Kristin L. Szuhany
  • 通讯作者:
    Kristin L. Szuhany

Charles R. Marmar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('Charles R. Marmar', 18)}}的其他基金

Leveraging systems pharmacology to advance precision medicine for Gabapentin treatment of AUD
利用系统药理学推进加巴喷丁治疗 AUD 的精准医学
  • 批准号:
    10887866
  • 财政年份:
    2023
  • 资助金额:
    $ 120.49万
  • 项目类别:
Leveraging systems pharmacology to advance precision medicine for Gabapentin treatment of AUD
利用系统药理学推进加巴喷丁治疗 AUD 的精准医学
  • 批准号:
    10629306
  • 财政年份:
    2022
  • 资助金额:
    $ 120.49万
  • 项目类别:
Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD
利用生物标志物对合并 PTSD 的酒精使用障碍进行个性化治疗
  • 批准号:
    10237280
  • 财政年份:
    2018
  • 资助金额:
    $ 120.49万
  • 项目类别:
Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD
利用生物标志物对合并 PTSD 的酒精使用障碍进行个性化治疗
  • 批准号:
    10237281
  • 财政年份:
    2018
  • 资助金额:
    $ 120.49万
  • 项目类别:
Leveraging biomarkers for personalized treatment of alcohol use disorder comorbid with PTSD
利用生物标志物对合并 PTSD 的酒精使用障碍进行个性化治疗
  • 批准号:
    10473675
  • 财政年份:
    2018
  • 资助金额:
    $ 120.49万
  • 项目类别:
Cannabidiol as a treatment for alcohol use disorder comorbid with posttraumatic stress disorder
大麻二酚用于治疗伴有创伤后应激障碍的酒精使用障碍
  • 批准号:
    9436640
  • 财政年份:
    2017
  • 资助金额:
    $ 120.49万
  • 项目类别:
CBT for PTSD in Disaster Relief Workers
认知行为疗法治疗救灾人员的创伤后应激障碍
  • 批准号:
    6541484
  • 财政年份:
    2002
  • 资助金额:
    $ 120.49万
  • 项目类别:
POSTTRAUMATIC STRESS IN POLICE OFFICERS
警官的创伤后压力
  • 批准号:
    2407399
  • 财政年份:
    1997
  • 资助金额:
    $ 120.49万
  • 项目类别:
POSTTRAUMATIC STRESS IN POLICE OFFICERS
警官的创伤后压力
  • 批准号:
    6433890
  • 财政年份:
    1997
  • 资助金额:
    $ 120.49万
  • 项目类别:
Prospective Study of Traumatic Stress in Police Officers
警务人员创伤应激的前瞻性研究
  • 批准号:
    7755356
  • 财政年份:
    1997
  • 资助金额:
    $ 120.49万
  • 项目类别:

相似海外基金

Life outside institutions: histories of mental health aftercare 1900 - 1960
机构外的生活:1900 - 1960 年心理健康善后护理的历史
  • 批准号:
    DP240100640
  • 财政年份:
    2024
  • 资助金额:
    $ 120.49万
  • 项目类别:
    Discovery Projects
Development of a program to promote psychological independence support in the aftercare of children's homes
制定一项计划,促进儿童之家善后护理中的心理独立支持
  • 批准号:
    23K01889
  • 财政年份:
    2023
  • 资助金额:
    $ 120.49万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10452217
  • 财政年份:
    2022
  • 资助金额:
    $ 120.49万
  • 项目类别:
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10670838
  • 财政年份:
    2022
  • 资助金额:
    $ 120.49万
  • 项目类别:
Aftercare for young people: A sociological study of resource opportunities
年轻人的善后护理:资源机会的社会学研究
  • 批准号:
    DP200100492
  • 财政年份:
    2020
  • 资助金额:
    $ 120.49万
  • 项目类别:
    Discovery Projects
Creating a National Aftercare Strategy for Survivors of Pediatric Cancer
为小儿癌症幸存者制定国家善后护理策略
  • 批准号:
    407264
  • 财政年份:
    2019
  • 资助金额:
    $ 120.49万
  • 项目类别:
    Operating Grants
Aftercare of green infrastructure: creating algorithm for resolving human-bird conflicts
绿色基础设施的善后工作:创建解决人鸟冲突的算法
  • 批准号:
    18K18240
  • 财政年份:
    2018
  • 资助金额:
    $ 120.49万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Development of an aftercare model for children who have experienced invasive procedures
为经历过侵入性手术的儿童开发善后护理模型
  • 批准号:
    17K12379
  • 财政年份:
    2017
  • 资助金额:
    $ 120.49万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of a Comprehensive Aftercare Program for children's self-reliance support facility
为儿童自力更生支持设施制定综合善后护理计划
  • 批准号:
    17K13937
  • 财政年份:
    2017
  • 资助金额:
    $ 120.49万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Project#2 Extending Treatment Effects Through an Adaptive Aftercare Intervention
项目
  • 批准号:
    8742767
  • 财政年份:
    2014
  • 资助金额:
    $ 120.49万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了