Integrative Epigenomic Mapping of Co-Morbid OUD and PTSD

OUD 和 PTSD 共病的综合表观基因组图谱

• 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
• 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

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）通常与创伤后应激障碍（PTSD）共同发生，特别是在 老百姓。患有OUD和PTSD（OUD+PTSD）的人表现出更差的健康和身体状况。 结果和不良的治疗反应。以往的研究发现，多巴胺能信号（DA能） 前额叶皮层（PFC）在调节认知和情感效应中起着关键作用。 应力暴露（即，PTSD）在阿片类药物滥用的脆弱性。药物滥用与PFC神经元的调节 应激反应可能是由表观遗传机制介导的。PAS-18-625呼吁研究， 研究心理社会压力对阿片类药物使用模式的机制。在这项研究中，我们假设， PFC对OUD+PTSD共病患者认知和情感效应的调节作用可能是通过 表观遗传机制为此，我们将研究DA能系统内神经元特异性表观遗传特征 在全基因组水平上，在OUD+PTSD共病患者的死后PFC中。共有48 将对来自退伍军人事务国家创伤后应激障碍脑库（VA-NPBB）的死后脑样本进行检查。 我们将在共病的背景下研究甲基化组、羟甲基化组和转录组。 OUD+PTSD，并将整合产生的不同组学数据集，以确定相关的基因网络 这些疾病。这项研究将增加我们对生物学机制的理解， OUD+PTSD共病需要发现新的预防、预后和治疗目标。