Integrative Epigenomic Mapping of Co-Morbid OUD and PTSD Supplement

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)并存，尤其是在 退伍军人。患有创伤后应激障碍和创伤后应激障碍的人表现出更差的健康和身体状况。 疗效差，治疗反应差。先前的研究发现，多巴胺能信号转导(DA能) 前额叶皮质(PFC)在认知和情感效应的调节中起着关键作用 阿片类药物滥用脆弱性中的压力暴露(即创伤后应激障碍)。PFC神经元调制与药物滥用 应激反应可能是由表观遗传机制介导的。PAS-18-625要求研究 研究心理社会压力对阿片类药物使用模式的影响机制。在这项研究中，我们假设 PFC对合并创伤后应激障碍的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DAR能系统内神经元特定的表观遗传学特征 在全基因组水平上，在患有创伤后应激障碍的人的死后PFC中。共有48个 来自退伍军人事务部国家创伤后应激障碍脑库(VA-Npbb)的尸检大脑样本将被检查。 我们将在共病的背景下研究甲基组、羟甲基组和转录组。 OUD PTSD，并将整合生成的不同组学数据集以识别相关的基因网络 患有这些疾病。这项研究将加深我们对生物机制的理解。 并发创伤后应激障碍需要发现预防、预测和治疗的新靶点。

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.