Magnetic Resonance Spectroscopy and Genetic Analysis of Oxidative Stress in OEF/OIF Veterans with PTSD and TBI

创伤后应激障碍(PTSD)和轻度创伤性脑损伤(MTBI)是常见的，通常是致残的 影响许多退伍军人的条件伊拉克自由(OIF)、持久自由(OEF)和新 黎明(OND)。新出现的证据表明，这两种情况都与中枢神经系统水平升高有关。 外周氧化应激(OXS)和炎症(INF)。对于这项提案，我们汇集了一个独特的 具有分子遗传学和磁共振波谱(MRS)专业知识的研究团队 研究这些过程与慢性创伤后应激障碍和mTBI的关系。这项研究将从一项大型和 OIF/OEF/OND退伍军人的精神状态不同的队列，现在平均在部署后10年， 从先前的评估中获得全基因组的基因数据。我们将获得新的MRS扫描 结合基因组数据进行分析，以检验创伤后应激障碍和mTBI与神经和 OXS和INF的外周指数，并确定这些关联中个体差异的基因组来源。 更具体地说，主要目的是(A)审查当前创伤后应激障碍、mTBI病史、 和MRS测量OXS和INF，(B)询问OXS和INF途径中的基因以确定遗传 创伤后应激障碍、mTBI和MRS参数之间关联的主持人，以及(C)审查关联 OXS和INF的MRS测量、神经完整性的其他MRI指标与OXS的外周标志物之间的关系 和INF。这项研究的最终目标是确定未来可以用于 指导制定用于临床评估的血液面板和/或神经成像方案，以及 退伍军人慢性创伤后应激障碍和脊髓损伤药物干预的分子靶点。

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common and often disabling conditions affecting many veterans of Operations Iraqi Freedom (OIF), Enduring Freedom (OEF), and New Dawn (OND). Emerging evidence suggests that both conditions are associated with elevated levels of central and peripheral oxidative stress (OXS) and inflammation (INF). For this proposal, we have assembled a unique team of investigators with expertise in molecular genetics and magnetic resonance spectroscopy (MRS) to study these processes in relation to chronic PTSD and mTBI. The study will draw from a large and psychiatrically heterogeneous cohort of veterans of OIF/OEF/OND, now on average 10 years post-deployment, with genome-wide genotype data available from a previous assessment. We will acquire new MRS scans for analysis in combination with the genomic data to examine associations of PTSD and mTBI with neural and peripheral indices of OXS and INF and identify genomic sources of individual differences in these associations. More specifically, the primary aims are to (a) examine associations between current PTSD, history of mTBI, and MRS measures of OXS and INF, (b) interrogate genes in the OXS and INF pathways to identify genetic moderators of the associations between PTSD, mTBI and MRS parameters, and (c) examine associations between MRS measures of OXS and INF, other MRI indices of neural integrity, and peripheral markers of OXS and INF. The ultimate goal of this study is to identify neurobiological pathways that can be used in the future to guide the development of blood panels and/or neuroimaging protocols for clinical assessment, as well as molecular targets for pharmacologic intervention for veterans suffering from chronic PTSD and mTBI.