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

患有 PTSD 和 TBI 的 OEF/OIF 退伍军人氧化应激的磁共振波谱分析和遗传分析

• 批准号: 10546424
• 负责人: MARK W MILLER
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546424
• 关键词: Address; Affect; Biological Markers; Blood; Brain region; C-reactive protein; Chronic Post Traumatic Stress Disorder; Clinical Protocols; Clinical assessments; Data; Development; Diagnosis; Freedom; Future; Gamma-glutamyl transferase; Genes; Genetic; Genetic Variation; Genomics; Genotype; Glutathione; Goals; Human; Individual Differences; Inflammation; Inositol; Intervention; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Medial; Methods; Molecular Genetics; Molecular Target; Motor Cortex; N-acetylaspartate; Neurobiology; Oxidative Stress; Pathway interactions; Peripheral; Pharmacology; Phenotype; Plasma; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Recording of previous events; Research Personnel; Scanning; Serum; Source; Technology; Thick; Veterans; cohort; genetic analysis; genome-wide; genomic data; in vivo; indexing; interest; mild traumatic brain injury; neuroimaging; operation; polygenic risk score; relating to nervous system; risk variant; virtual

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.

创伤后应激障碍（PTSD）和轻度创伤性脑损伤（MTBI）很常见，并且经常残疾 影响许多行动退伍军人伊拉克自由（OIF），持久自由（OEF）和新的条件 黎明（OND）。新兴的证据表明，这两种情况都与中央的水平升高有关 和外周氧化应激（OX）和炎症（INF）。对于此建议，我们组装了一个独特的 具有分子遗传学和磁共振光谱（MRS）专业知识的研究人员团队 研究了与慢性PTSD和MTBI有关的这些过程。该研究将从大型和 OIF/OEF/OND退伍军人的精神上有异质的队列，现在平均10年后， 借助以前的评估可获得全基因组基因型数据。我们将获得新的扫描夫人 分析与基因组数据相结合，以检查PTSD和MTBI与神经和MTBI的关联 牛和inf的外围指数，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）检查当前PTSD的关联，MTBI的历史， 和MRS的牛和INF的测量 PTSD，MTBI和MRS参数之间关联的主持人，以及（c）检查关联 在MRS的牛和INF测量之间，神经完整性的其他MRI指数和OX的外围标记 和inf。这项研究的最终目的是确定将来可以使用的神经生物学途径 指导临床评估的血液板和/或神经影像学方案的开发以及/或 用于患有慢性PTSD和MTBI的退伍军人的药理学干预的分子靶标。

项目成果

The association between blast exposure and transdiagnostic health symptoms on systemic inflammation.

爆炸暴露与全身炎症的跨诊断健康症状之间的关联。

• DOI: 10.1038/s41386-021-01138-8
• 发表时间: 2022
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Hayes,JasmeetP;Pierce,MeghanE;Valerio,KateE;Miller,MarkW;Huber,BertrandRussell;Fortier,CatherineB;Fonda,JenniferR;Milberg,William;McGlinchey,Regina
• 通讯作者: McGlinchey,Regina

Oxidative Stress, Inflammation, and Neuroprogression in Chronic PTSD.

• DOI: 10.1097/hrp.0000000000000167
• 发表时间: 2018
• 期刊: Harvard review of psychiatry
• 影响因子: 3.8
• 作者: Miller MW;Lin AP;Wolf EJ;Miller DR
• 通讯作者: Miller DR

The PPM1F gene moderates the association between PTSD and cortical thickness.

• DOI: 10.1016/j.jad.2019.08.055
• 发表时间: 2019-12
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Danielle R. Sullivan;Filomene G. Morrison;E. Wolf;M. Logue;C. Fortier;D. Salat;J. Fonda;Annjanette Stone;S. Schichman;W. Milberg;R. McGlinchey;Mark W. Miller

Methylation of the AIM2 gene: An epigenetic mediator of PTSD-related inflammation and neuropathology plasma biomarkers.

• DOI: 10.1002/da.23247
• 发表时间: 2022-04
• 期刊: Depression and anxiety
• 影响因子: 7.4
• 作者: Hawn SE;Neale Z;Wolf EJ;Zhao X;Pierce M;Fein-Schaffer D;Milberg W;McGlinchey R;Logue M;Miller MW
• 通讯作者: Miller MW