Revealing Susceptibility Factors for Post Traumatic Stress Disorder

揭示创伤后应激障碍的易感因素

• 批准号: 10158417
• 负责人: Almira Vazdarjanova
• 金额: --
• 依托单位: CHARLIE NORWOOD VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158417
• 关键词: Accidents; Address; Animal Model; Antibodies; Anxiety; Anxiety Disorders; Award; Behavior; Behavioral; Blood; Brain; Brain region; Catfish; Cognitive; Data; Diagnosis; Diagnostic; Disease; Estrus; Etiology; Event; Exercise; Exposure to; Extinction (Psychology); Female; Financial Hardship; Freedom; Freezing; Fright; Gene Expression; Goals; Grant; Health; Hippocampus (Brain); Homer 1a; Human; Impairment; Incidence; Individual; Inflammation; Inflammatory; Injury; Interleukin-1; Interleukin-6; Knowledge; Link; Measures; Medial; Methods; Military Personnel; Minor; Modeling; Modification; Natural Disasters; Nature; Neurons; Outcome; Pathogenesis; Patient Care; Phase; Phenotype; Post-Traumatic Stress Disorders; Predisposition; Prefrontal Cortex; Prevalence; Probability; Procedures; Quality of life; Rattus; Recording of previous events; Recovery of Function; Research; Resistance; Resources; Role; Societies; Source; Startle Reaction; Synaptic plasticity; TNF gene; Techniques; Testing; Trauma; Trauma recovery; Treatment Cost; Treatment outcome; United States Department of Veterans Affairs; Veterans; Woman; anxiety-like behavior; assault; cellular imaging; conditioned fear; cost; design; disability; disability payment; effective intervention; emotional experience; emotional factor; emotional trauma; experience; experimental study; flexibility; generalized anxiety; heuristics; imaging modality; improved; male; men; military veteran; mindfulness; novel; operation; patient population; post-trauma; preservation; prevent; productivity loss; resilience; sexual dimorphism; stress related disorder; successful intervention; tool; traumatic event; wound

Experiencing an emotionally traumatic event, even without physical injury, results in developing a debilitating condition, termed Post-Traumatic Stress Disorder (PTSD) in an estimated 20-30% of people, including the over 2 million US military personnel deployed in guerilla-type warfare (Operations Enduring Freedom and Iraqi Freedom) which is characterized with high level of unpredictable and recurring exposure to traumatic events. Thus, it is not surprising that PTSD inflicts rising costs to the Veteran’s Administration and society, in general, due to loss of productivity and quality of life. The VA costs associated with paying PTSD-related disability have been steadily rising since 1999, reaching over $2 billion in treatment costs (2004-2009), plus nearly 5 billion in disability payments. Considering that 80% continue to require treatment past 3 years after diagnosis, it is clear that decreasing the number of veterans requiring treatment for PTSD would decrease VA costs associated with this disorder, and, importantly, increase the quality of life for many veterans. A previous history of PTSD or other anxiety disorders renders some people more susceptible to developing PTSD after subsequent traumatic events. Thus, veterans treated for PTSD, or with PTSD susceptibility, are more likely to develop PTSD when they experience non-combat trauma, such as auto accidents, assault, and natural disasters. Therefore, identifying susceptibility and ways to prevent it could decrease PTSD-associated VA costs. Understanding the susceptibility factors for developing PTSD can help reduce the probability of occurrence after experiencing emotional trauma. The goal of this grant is to build upon our recent discovery of susceptibility and sequelae factors of emotional trauma. We propose to investigate whether an elevated pro-inflammatory profile is a susceptibility factor and whether it contributes to the disrupted function of the medial prefrontal cortex (mPFC) and hippocampus before emotional trauma (Aim 1) that we have already identified. In Aim 2, we propose to investigate whether decreasing the pro- inflammatory state in susceptible rats will increase their resilience, measured by their post-trauma behavior and functional activation of the mPFC and hippocampus. For the proposed studies, we will combine two indispensable tools: 1) RISP: our behavioral rat model for revealing individual susceptibility to a PTSD-like phenotype before experiencing emotional trauma (fear conditioning). This phenotype includes: impaired fear extinction, lasting elevated startle response and generalized anxiety-like behavior. 2) Arc/Homer 1a catFISH method: the sensitive cellular imaging method, co- developed by the PI, which can assess both size and overlap of neuronal ensembles engaged in plasticity after two distinct behavioral events. The findings from this research have the potential to revolutionize the assessment of susceptibility to PTSD-like behaviors and suggest new ways to build resilience.

经历一次情感创伤的事件，即使没有身体伤害，也会导致 发生一种衰弱的情况，称为创伤后应激障碍(PTSD) 估计有20%到30%的人，包括部署的200多万美国军事人员 在游击型战争(持久自由行动和伊拉克自由行动)中， 具有高度不可预测和反复暴露于创伤性事件的特点。 因此，创伤后应激障碍给退伍军人管理局带来的成本上升也就不足为奇了 和社会，一般是由于生产力和生活质量的丧失。退伍军人管理局的成本 与支付创伤后应激障碍相关的费用自1999年以来一直在稳步上升， 超过20亿美元的治疗费用(2004-2009年)，加上近50亿的残疾 付款。考虑到80%的患者在三年后仍需接受治疗 诊断结果表明，减少需要治疗创伤后应激障碍的退伍军人人数 将降低与这种疾病相关的退伍军人管理局成本，更重要的是，增加 许多退伍军人的生活质量。既往有创伤后应激障碍或其他焦虑症病史 使一些人在随后的创伤后更容易患上创伤后应激障碍 事件。因此，接受创伤后应激障碍治疗的退伍军人或患有创伤后应激障碍易感性的退伍军人更有可能 当他们经历非战斗创伤时，如车祸、袭击、 和自然灾害。因此，识别易感性和预防方法可能会 降低与创伤后应激障碍相关的VA成本。 了解发生创伤后应激障碍的易感因素有助于减少 经历情感创伤后发生的可能性。这笔赠款的目标是 以我们最近发现的情感易感性和后遗症因素为基础 精神创伤。我们建议调查一个升高的促炎状态是否是一种 易感因素及其是否导致内侧动脉功能紊乱 情绪创伤前前额叶皮质(MPFC)和海马区(目标1) 已经确定了。在目标2中，我们建议调查是否降低PRO- 易感大鼠的炎症状态将增加它们的弹性，通过它们的 MPFC和海马区的创伤后行为和功能激活。 对于拟议的研究，我们将结合两个不可或缺的工具：1)RISP：我们的 揭示个体对创伤后应激障碍样表型易感性的行为大鼠模型 在经历情感创伤(恐惧条件反射)之前。这种表型包括： 受损的恐惧消退，持续的惊吓反应和广泛性焦虑症 行为。2)Arc/Hmer 1a法：灵敏细胞成像法 由PI开发，它可以评估神经元集合的大小和重叠 在经历了两次截然不同的行为事件后，他们开始变得可塑性。这项研究的发现 有可能彻底改变创伤后应激障碍类行为的易感性评估 并提出了建立韧性的新方法。

项目成果

Photobiomodulation prevents PTSD-like memory impairments in rats.

• DOI: 10.1038/s41380-021-01088-z
• 发表时间: 2021-11
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Li Y;Dong Y;Yang L;Tucker L;Zong X;Brann D;Hamblin MR;Vazdarjanova A;Zhang Q
• 通讯作者: Zhang Q

Nucleus basalis stimulation enhances working memory by stabilizing stimulus representations in primate prefrontal cortical activity.

• DOI: 10.1016/j.celrep.2021.109469
• 发表时间: 2021-08-03
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Qi XL;Liu R;Singh B;Bestue D;Compte A;Vazdarjanova AI;Blake DT;Constantinidis C
• 通讯作者: Constantinidis C

Sex Differences In Avoidance Extinction After Contextual Fear Conditioning: Anxioescapic Behavior In Female Rats.

• DOI: 10.1016/j.neuroscience.2022.06.031
• 发表时间: 2022-08-10
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Shanazz, Khadijah;Dixon-Melvin, Rachael;Nalloor, Rebecca;Thumar, Riya;Vazdarjanova, Almira I.
• 通讯作者: Vazdarjanova, Almira I.

Emotional state alters encoding of long-term spatial episodic memory.

• DOI: 10.1016/j.nlm.2021.107562
• 发表时间: 2022-01
• 期刊: NEUROBIOLOGY OF LEARNING AND MEMORY
• 影响因子: 2.7
• 作者: Dixon-Melvin, Rachael;Shanazz, Khadijah;Nalloor, Rebecca;Bunting, Kristopher M.;Vazdarjanova, Almira
• 通讯作者: Vazdarjanova, Almira

Light-Dark Open Field (LDOF): A novel task for sensitive assessment of anxiety.

• DOI: 10.1016/j.jneumeth.2021.109325
• 发表时间: 2021-11-01
• 期刊: Journal of neuroscience methods
• 影响因子: 3
• 作者: Shanazz K;Dixon-Melvin R;Bunting KM;Nalloor R;Vazdarjanova AI
• 通讯作者: Vazdarjanova AI