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，并且常常致残 影响伊拉克自由行动（OIF）、持久自由行动（OEF）和新行动的许多退伍军人的状况 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。 以及外周氧化应激（OXS）和炎症（INF）。对于这个提案，我们收集了一个独特的 具有分子遗传学和磁共振波谱 (MRS) 专业知识的研究人员团队 研究这些与慢性 PTSD 和 mTBI 相关的过程。该研究将借鉴大量 OIF/OEF/OND 退伍军人的精神状况存在异质性，现在平均部署后 10 年， 具有先前评估中提供的全基因组基因型数据。我们将获取新的 MRS 扫描 结合基因组数据进行分析，以检查 PTSD 和 mTBI 与神经和神经系统的关联 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，主要目标是 (a) 检查当前 PTSD、mTBI 病史、 OXS 和 INF 的 MRS 测量，(b) 询问 OXS 和 INF 途径中的基因以识别遗传 PTSD、mTBI 和 MRS 参数之间关联的调节因素，以及 (c) 检查关联 OXS 和 INF 的 MRS 测量值、神经完整性的其他 MRI 指标以及 OXS 的外周标志物之间 和INF。这项研究的最终目标是确定未来可用于 指导用于临床评估的血液检测和/或神经影像方案的开发，以及 患有慢性 PTSD 和 mTBI 的退伍军人药物干预的分子目标。

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