Structural and functional neural alterations in suicidality among Veterans with PTSD

患有创伤后应激障碍 (PTSD) 的退伍军人自杀倾向的结构和功能神经改变

• 批准号: 9854738
• 负责人: Lynnette Astrid Averill
• 金额: --
• 依托单位: VA CONNECTICUT HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9854738
• 关键词: Affect; Afghanistan; Age; Anatomy; Architecture; Area; Atrophic; Behavior; Behavior assessment; Biological Markers; Brain; Brain region; Cause of Death; Cessation of life; Characteristics; Clinical; Cognition; Data; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Environment; Feeling suicidal; Foundations; Frequencies; Functional disorder; Funding; Future; Goals; Graph; Healthcare; Individual; Infrastructure; Injury; Insula of Reil; Intervention; Investigation; Iraq; Lead; Limbic System; Literature; Location; Magnetic Resonance Imaging; Measures; Mental Depression; Mental Health; Mental disorders; Mentors; Mentorship; Military Personnel; Modeling; Moods; Neurobiology; Neurosciences; Parietal; Participant; Pathology; Pattern; Pharmacology; Post-Traumatic Stress Disorders; Prevalence; Prevention; Recording of previous events; Research; Rest; Risk; Severities; Stress; Structure; Suicide; Suicide attempt; Suicide prevention; Symptoms; Synapses; Technology; Thick; Time; Training; Trauma; Traumatic Brain Injury; Veterans; War; Work; base; biomarker identification; brain circuitry; career; cohort; comorbidity; cost; design; disorder prevention; drug development; experience; gray matter; ideation; improved; improved outcome; loved ones; mild traumatic brain injury; mood regulation; multimodality; neuroimaging; neuromechanism; novel; novel therapeutics; programs; relating to nervous system; resilience; sex; socioeconomics; statistics; stress related disorder; suicidal morbidity

PROJECT SUMMARY/ABSTRACT Research: Veterans of the U.S. military die by suicide at a rate of two to six times that of their civilian counterparts. Suicidal ideation (SI) and suicide attempts (SA), cardinal precursors to death by suicide, occur at significantly greater frequency than death and cause immense individual and societal burden, yet relatively little is known about their pathophysiology. This is especially so in posttraumatic stress disorder (PTSD), a signature injury of the wars in Iraq and Afghanistan. High rates of comorbidity and inflated prevalence of both suicidality and PTSD in Veterans, highlights the urgency of advancing understanding of the shared and distinguishing neural mechanisms between these. Evidence of trauma- and stress-related synaptic loss and large-scale alterations in intrinsic connectivity networks in brain regions implicated in mood, cognition, and behavior exists in both SI/SA and PTSD literature. However, a major obstacle in field is the scarcity of neurobiologically-based studies of SI/SA in PTSD cohorts. Preliminary data supports the notion that the location and pattern of synaptic alterations may interact with individual and environmental characteristics to affect clinical presentation and symptom severity. Specifically, Veterans with PTSD endorsing SI appear to have a neural signature of synaptic alterations distinct from PTSD symptom severity, depression, and age. Extending this work, state-of-the-art multimodal neuroimaging and behavioral assessment sessions will be conducted in 96 Veterans across 3 study groups (n=32/group): PTSD only; PTSD+SI; PTSD+SA. Robust, complimentary evidence of a unique pattern and location of synaptic alterations will be demonstrated using (a) whole-brain vertex-wise structural magnetic resonance imaging (MRI) to measure cortical thickness, (b) resting-state functional connectivity MRI (rs-fcMRI) to measure global brain connectivity (GBC), and (c) diffusion MRI to measure diffusion GBC (dGBC), a measure of microstructural architecture and connectivity. Veterans will be matched on age, sex, PTSD symptom severity, and history of traumatic brain injury. This study may identify biomarkers of treatment targets in two of the operational priority areas for the VA – suicide and PTSD, inform novel drug development of efficacious pharmacologic interventions, and ultimately advance the field making way to alleviate suffering of millions of individuals – Veteran and civilian alike - struggling with suicidality. Candidate: Dr. Averill has demonstrated an unwavering commitment to improving Veterans’ mental health care, with emphasis on PTSD and suicide prevention for well over a decade. Short-term goals include receipt of the CDA-2 to both advance her expertise through rigorous training objectives (focused on the neurobiology of SI/SA, multimodal neuroimaging, and statistics) and to provide data for future funding as she establishes a niche program of research in the National Center for PTSD-Clinical Neurosciences Division (NCPTSD-CND). Long-term goals include becoming a thought leader in the areas of suicide prevention and PTSD in Veterans through empirical investigations aimed at informing novel drug development and improved prevention, diagnostics, identification of biomarkers of risk and resilience in SI/SA, and treatment options. Environment: The infrastructure, quality of mentors, supplementary funding support, technology, and Veteran-focused research environment available at the National Center for PTSD-Clinical Neurosciences Division and Yale are unparalleled. This offers unique opportunity to support Dr. Averill in her transition to independence though exceptional targeted training/mentorship and to conduct a low cost/high yield study with great potential to advance the field, lead to improved outcomes for Veterans, and set a foundation for a successful VA-centric career.

项目摘要/摘要 研究：美国军方的退伍军人以自杀死亡的速度是平民的两到六倍 同行。自杀想法（SI）和自杀企图（SA），自杀死亡的主要前体，发生在 频率明显高于死亡，并引起巨大的个人和社会伯恩，但相对 关于他们的病理生理学知之甚少。在创伤后应激障碍（PTSD）中尤其如此 伊拉克和阿富汗战争的签名伤害。同时合并症的高率和两者的膨胀率 退伍军人的自杀和PTSD强调了对共享和共享的理解的紧迫性 区分这些神经机制。创伤和压力相关的合成损失和 在情绪，认知和认知和 行为存在于SI/SA和PTSD文献中。但是，现场的主要障碍是 基于神经生物学的SI/SA研究中的PTSD队列研究。初步数据支持 突触改变的位置和模式可能与个人和环境特征相互作用 影响临床表现和症状严重程度。具体而言，具有PTSD认可的退伍军人似乎 具有与PTSD符号严重程度，抑郁和年龄不同的突触改变的神经元信号。 扩展这项工作，最先进的多模式神经影像学和行为评估会议将是 在3个研究组（n = 32/组）的96名退伍军人中进行：仅PTSD； PTSD+SI; PTSD+SA。强壮的， 使用（a）将证明具有独特模式和突触改变的位置的免费证据 全脑顶点的结构磁共振成像（MRI）以测量皮质厚度，（b） 静止状态功能连通性MRI（RS-FCMRI）测量全球大脑连通性（GBC），并且（C） 扩散MRI测量扩散GBC（DGBC），这是微观结构和连通性的量度。 退伍军人将与年龄，性别，PTSD症状严重程度和创伤性脑损伤历史相匹配。这项研究 可以在VA和 PTSD，为有效的药物结肠干预措施的新型药物开发提供信息，并最终提高 在减轻数百万个人的痛苦（老兵和平民）中的领域，与之挣扎 自杀性。 候选人：Averill博士表现出对改善退伍军人心理健康的坚定承诺 十多年来，关注PTSD和自杀预防。短期目标包括收到 CDA-2既通过严格的培训目标来提高她的专业知识（重点是 SI/SA，多模式神经影像学和统计数据），并在她建立一个资金时提供数据 国家PTSD-Clinical神经科学部（NCPTSD-CND）研究中心研究计划。 长期目标包括成为预防自杀和PTSD领域的思想领袖 通过旨在告知新型药物开发并改善预防的实证研究， 诊断，SI/SA中风险和弹性的生物标志物的鉴定以及治疗选择。 环境：基础设施，导师质量，补充资金支持，技术和 国家PTSD-Clinical神经科学中心提供以资深的研究环境 分裂和耶鲁大学是无与伦比的。这为支持Averill博士的过渡提供了独特的机会 独立性虽然有针对性的培训/指导，并进行低成本/高收益研究 具有巨大的进步领域的潜力，可以改善退伍军人的成果，并为 成功以VA为中心的职业。