Integrative Epigenomic Mapping of Co-Morbid OUD and PTSD

OUD 和 PTSD 共病的综合表观基因组图谱

基本信息

批准号：
10265996
负责人：
Janitza Liz Montalvo-Ortiz
金额：
$ 16.36万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10265996
关键词：
Address Affective Algorithms Autopsy Biological Brain Brain Diseases Cell Nucleus Cognitive DNA DNA Methylation Data Data Set Disease Drug abuse Environmental Risk Factor Epigenetic Process Exhibits Flow Cytometry Fluorescence Gene Activation Gene Expression Genes Genetic Goals Health Human Individual Letters Link Mediating Mental disorders Neurons Outcome Pathway Analysis Pathway interactions Pattern Peripheral Play Post-Traumatic Stress Disorders Prefrontal Cortex Prevention strategy Preventive Prognosis Psychosocial Stress Research Role Sampling Severities Signal Transduction Sorting - Cell Movement Specimen Stress Symptoms System Therapeutic Translating United States Department of Veterans Affairs Veterans Work base biological adaptation to stress bisulfite sequencing brain tissue cohort comorbidity demethylation epigenomics experience experimental study gene repression genome-wide genome-wide analysis glutamatergic signaling methylome military veteran novel opioid abuse opioid use opioid use disorder prognostic trait transcriptome transcriptome sequencing treatment response treatment strategy whole genome

项目摘要

Project Summary Opioid use disorder (OUD) often co-occurs with post-traumatic stress disorder (PTSD), particularly in the veteran population. People with comorbid OUD and PTSD (OUD+PTSD) exhibit worse health and physical outcomes and poor treatment response. Previous studies have found that dopaminergic signaling (DAergic) within the prefrontal cortex (PFC) plays a key role in the modulation of the cognitive and affective effects of stress exposure (i.e., PTSD) in opioid abuse vulnerability. PFC neuronal modulation involved in drug abuse and stress response may be mediated by epigenetic mechanisms. PAS-18-625 calls for research to investigate the mechanisms of psychosocial stress on opioid use patterns. In this study, we hypothesize that the PFC’s modulatory role on cognitive and affective effects of comorbid OUD+PTSD may be mediated by epigenetic mechanisms. For this, we will examine neuron-specific epigenetic profiles within the DAergic system and at a genome-wide level, in postmortem PFC of people with comorbid OUD+PTSD. A total of 48 postmortem brain samples from the Veteran Affair’s National PTSD Brain Bank (VA-NPBB) will be examined. We will investigate the methylome, hydroxymethylome, and transcriptome in the context of comorbid OUD+PTSD and will integrate the different –omics datasets generated to identify gene networks associated with these disorders. This study will increase our understanding on the biological mechanisms that underlie comorbid OUD+PTSD needed to uncover novel targets for preventative, prognostic, and treatment efforts.

项目摘要阿片类药物使用障碍（OUD）经常与创伤后应激障碍（PTSD）共同出现，特别是在资深人口。 Comorbid Oud和PTSD（OUD+PTSD）的人暴露了健康和身体状况的情况下结果和治疗反应不佳。先前的研究发现多巴胺能信号（DAERGIC）在前额叶皮层（PFC）中，在调制认知和情感效应中起关键作用在卵毒素滥用脆弱性中，压力暴露（即PTSD）。涉及药物滥用的PFC神经元调节和应力反应可以通过表观遗传机制介导。 PAS-18-625呼吁进行研究研究对阿片类药物使用模式的社会心理压力的机制。在这项研究中，我们假设 PFC在合并OUD+PTSD的认知和情感效果上的调节作用可能是由表观遗传机制。为此，我们将检查DAERGIC系统中的神经元特异性表观遗传谱在整个基因组水平上，在Comorbid Oud+PTSD的人的验尸PFC中。总共48 将检查来自资深事务国家PTSD脑库（VA-NPBB）的验尸大脑样本。我们将在合并症的背景下研究甲基甲基，羟基甲基和转录组 OUD+PTSD，并将集成生成的不同–omics数据集，以识别关联的基因网络这些疾病。这项研究将提高我们对基于生物学机制的理解合并的OUD+PTSD需要揭示用于预防，预后和治疗工作的新目标。