1/3 Understanding PTSD through Postmortem Targeted Brain Multi-omics
1/3 通过死后靶向脑多组学了解 PTSD
基本信息
- 批准号:9815771
- 负责人:
- 金额:$ 60.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-07-25 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:Amygdaloid structureAnteriorAreaArousalAutopsyBioinformaticsBiologicalBiological MarkersBrainBrain DiseasesBrain regionCell NucleusCellsChronicChronic Post Traumatic Stress DisorderClinicalCollaborationsComplexCoupledCritical PathwaysDNADNA MethylationDataData SetDevelopmentDiseaseDisease modelEpigenetic ProcessExonsFollow-Up StudiesFrightGene ExpressionGene ProteinsGenesGeneticGenetic ModelsGenetic TranscriptionGenomicsGenotypeHealthcare SystemsHippocampus (Brain)HospitalsHumanHuman BiologyIndividualInstitutesLinkLiquid ChromatographyMajor Depressive DisorderMeasurementMedialMedicalMental disordersMethylationMilitary PersonnelModelingMolecularMolecular BiologyMolecular ProfilingMood DisordersMorbidity - disease rateMultiomic DataNatural DisastersNegative ValenceNeurobiologyOutcomePathologicPathway interactionsPatientsPatternPhenotypePilot ProjectsPost-Traumatic Stress DisordersPrefrontal CortexPrevalenceProspective StudiesProteinsProteomeProteomicsPublicationsPublishingQuantitative Trait LociRNARegulationResearch Domain CriteriaResearch Project GrantsResolutionRiskSamplingSiteSmall RNAStatistical ModelsSurvivorsSymptomsSyndromeTerrorismTissuesTranscriptTranslatingTraumaUniversitiesUntranslated RNAValidationVehicle crashWarbasebrain tissuecase controlclinically significantcohortdentate gyrusdiagnostic biomarkerdifferential expressiondisorder riskepigenomeepigenomicsexperiencegenetic variantgenome wide association studygenome-widemethylation patternmind controlmortalitymultiple omicsneural circuitnew therapeutic targetnovelnovel therapeuticspredictive modelingprotein expressionpsychobiologicpsychologicrelating to nervous systemtandem mass spectrometrytherapeutic targettranscriptometranscriptome sequencingtranscriptomicstrauma exposureviolent crimewhole genome
项目摘要
Summary
Post-traumatic Stress Disorder (PTSD) is among the most prevalent of psychiatric disorders.
Trauma exposure is common, including natural disasters, terrorism, wars, automobile crashes, and violent
crime. Although the majority of trauma victims experience the symptoms of re-experiencing, avoidance
and hyperarousal, for the large majority of such individuals, these symptoms do not become chronic nor
do they develop syndromal PTSD. It is critical to identify the underlying neurobiology of PTSD because of
the very significant medical and psychiatric morbidity and mortality, and the promise of new therapeutics
based on its biological underpinnings. Despite its clinical importance, there have yet to be human biology-
focused postmortem studies of well-matched cases and controls to leverage the fact that this is arguably
among the best understood Psychiatric Disorder in terms of neural circuit regulation.
This proposal utilizes a Linked R01 mechanism across 3-sites (University of Miami (1), Lieber
Institute for Brain Development (2), and McLean Hospital with Emory University (3)), to perform a
postmortem, multi-omic study of brains from 300 total subjects: PTSD (civilian + military trauma, n=100),
mood disorder non-PTSD psychiatric controls (n=100), and normal controls (n=100). We will focus on
targeted brain regions with known differential association with PTSD risk as a function of identified
intermediate phenotypes, including amygdala, prefrontal cortex and hippocampal dentate gyrus. We will
determine differential DNA genotyping / methylation, RNA expression, and Proteomic patterns across
brain areas. We hypothesize 1) that known pathways we have previously identified in the periphery and in
PTSD models will be differentially identified in the brain regions of PTSD subjects, and 2) that genome-
wide exploratory approaches will identify novel epigenetically gene pathways. Our main outcome will be a
predictive model of genetic, epigenetic, transcriptomic, and proteomic profiles of brain regions from cases
vs. controls. These data will allow an understanding of the region-specific genotype-dependent
transcriptional and translational profiles, and findings will be integrated with detailed multi-omic data from
other studies.
We will use state-of-the-art statistical modeling, combined with rich biological and psychological
phenotype measurements to determine a predictive model across conserved brain regions and molecular
pathways. This novel, integrated, and impactful linked R01 proposal will lead to the identification of so far
unknown trauma-associated genes and proteins, noncoding RNAs, and epigenetic marks in trauma
related disorders and will allow the identification of novel therapeutic targets on the level of regulatory
RNAs and proteins. Such a strategy has the potential to help redefine psychobiological subtypes of PTSD
as well as to reduce the burden of chronic PTSD on our healthcare system.
总结
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)
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CHARLES B NEMEROFF其他文献
CHARLES B NEMEROFF的其他文献
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{{ truncateString('CHARLES B NEMEROFF', 18)}}的其他基金
Prediction of Alcohol Use Disorder and PTSD After Trauma in Adolescents
青少年创伤后酒精使用障碍和创伤后应激障碍 (PTSD) 的预测
- 批准号:
10367692 - 财政年份:2022
- 资助金额:
$ 60.38万 - 项目类别:
Prediction of Alcohol Use Disorder and PTSD After Trauma in Adolescents
青少年创伤后酒精使用障碍和创伤后应激障碍 (PTSD) 的预测
- 批准号:
10693806 - 财政年份:2022
- 资助金额:
$ 60.38万 - 项目类别:
1/3 Understanding PTSD through Postmortem Targeted Brain Multi-omics
1/3 通过死后靶向脑多组学了解 PTSD
- 批准号:
9924647 - 财政年份:2018
- 资助金额:
$ 60.38万 - 项目类别:
1/3 Understanding PTSD through Postmortem Targeted Brain Multi-omics
1/3 通过死后靶向脑多组学了解 PTSD
- 批准号:
10159964 - 财政年份:2018
- 资助金额:
$ 60.38万 - 项目类别:
1/3 Understanding PTSD through Postmortem Targeted Brain Multi-omics
1/3 通过死后靶向脑多组学了解 PTSD
- 批准号:
10405109 - 财政年份:2018
- 资助金额:
$ 60.38万 - 项目类别:
Stem Cell Therapy, Inflammation and Treatment Response inAlcoholism-Depression Comorbidity
干细胞疗法、酒精中毒抑郁症合并症的炎症和治疗反应
- 批准号:
9380069 - 财政年份:2017
- 资助金额:
$ 60.38万 - 项目类别:
1 of 2 - Prospective Determination of Psychobiological Risk Factors for PTSD
1 of 2 - PTSD 心理生物学风险因素的前瞻性确定
- 批准号:
8290799 - 财政年份:2012
- 资助金额:
$ 60.38万 - 项目类别:
1 of 2 - Prospective Determination of Psychobiological Risk Factors for PTSD
1 of 2 - PTSD 心理生物学风险因素的前瞻性确定
- 批准号:
8659508 - 财政年份:2012
- 资助金额:
$ 60.38万 - 项目类别:
1 of 2 - Prospective Determination of Psychobiological Risk Factors for PTSD
1 of 2 - PTSD 心理生物学风险因素的前瞻性确定
- 批准号:
8470246 - 财政年份:2012
- 资助金额:
$ 60.38万 - 项目类别:
EARLY LIFE STRESS IN NON HUMAN PRIMATES AND HUMANS
非人类灵长类动物和人类的早期生活压力
- 批准号:
7958154 - 财政年份:2009
- 资助金额:
$ 60.38万 - 项目类别:
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