Neurobiological mechanisms underlying PTSD

PTSD 背后的神经生物学机制

• 批准号: 9223570
• 负责人: JENNIFER URBANO BLACKFORD
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223570
• 关键词: Address; Adult; Afghanistan; Amygdaloid structure; Anxiety; Behavioral; Brain; Brain imaging; Brain region; Country; Data; Development; Disease; Event; Exhibits; Freedom; Fright; Functional Magnetic Resonance Imaging; Galvanic Skin Response; General Population; Goals; Health; Hippocampus (Brain); Human; Hydrocortisone; Hypothalamic structure; Individual; Intervention; Iraq; Knowledge; Light; Literature; Maps; Measures; Mediating; Mental Depression; Mental Health; Methods; Neurobiology; Nucleic Acid Regulatory Sequences; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Public Health; Publishing; Recovery; Resistance; Rodent; Role; Soldier; Stress; Structure of terminal stria nuclei of preoptic region; Substance Use Disorder; Symptoms; Testing; Therapeutic Intervention; Time; Trauma; Veterans; base; biological adaptation to stress; cohort; combat; common symptom; effective therapy; in vivo; neural circuit; neurobiological mechanism; neuroimaging; novel; operation; prevent; public health relevance; relating to nervous system; response; suicidal risk; targeted treatment

 DESCRIPTION (provided by applicant): Post-traumatic stress disorder (PTSD) is rapidly becoming the most prevalent mental health problem facing Veterans of Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF)/Operation New Dawn (OND). PTSD is a devastating disorder that also increases risk for suicide, depression, and substance use disorders. Unfortunately, PTSD is often resistant to current therapeutic interventions and a full recovery is uncommon. The development of targeted therapies is a promising avenue for the effective treatment of PTSD, but to develop these treatments, first we must better understand the underlying neurobiological mechanisms. The goal of the proposed project is to determine whether combat Veterans with PTSD have alterations in an anxiety neural circuit mediated by the bed nucleus of the stria terminalis (BNST). In rodents, the BNST mediates anxiety, hypervigilance, and behavioral effects of stress-similar to symptoms of PTSD. In combat Veterans with PTSD, these symptoms are increased in situations where a threat is unpredictable; that is, a threatening event may or may not occur. We propose to compare OEF/OIF/OND combat-exposed Veterans with and without PTSD. We have developed novel methods to examine BNST activation to unpredictable threats using functional magnetic resonance imaging (fMRI). The study will focus on three specific aims: (1) determine whether combat Veterans with PTSD have heightened BNST activation compared to combat Veterans without PTSD; (2) identify alterations in BNST connectivity with other regions of the anxiety circuit in Veterans with PTSD; (3) determine whether stress response (measured by cortisol and skin conductance) mediates the association between BNST function (activation and connectivity) and PTSD symptoms. Ultimately we aim to elucidate the neurobiological mechanisms underlying PTSD to identify novel brain targets for treatment.

 描述（由申请人提供）： 创伤后应激障碍 (PTSD) 正在迅速成为伊拉克自由行动 (OIF)/持久自由行动 (OEF)/新黎明行动 (OND) 退伍军人面临的最普遍的心理健康问题 PTSD 是一种毁灭性的疾病，也会增加风险。不幸的是，创伤后应激障碍 (PTSD) 通常对当前的治疗干预有抵抗力，并且完全康复的情况并不常见。 靶向治疗的开发是有效治疗创伤后应激障碍 (PTSD) 的一个有希望的途径，但首先要开发这些治疗方法。我们必须更好地理解该项目的目标是确定患有 PTSD 的退伍军人是否存在由终纹床核（BNST）介导的焦虑神经回路的改变，在啮齿类动物中，BNST 介导焦虑、过度警觉和焦虑。压力的行为影响——与创伤后应激障碍（PTSD）的症状类似，在威胁不可预测的情况下，这些症状会增加；也就是说，我们建议进行比较。 OEF/OIF/OND 患有或不患有 PTSD 的经历过战斗的退伍军人我们开发了新方法，使用功能磁共振成像 (fMRI) 检查 BNST 的激活情况。与没有 PTSD 的退伍军人相比，患有 PTSD 的退伍军人有肉质的 BNST 激活；(2) 确定患有 PTSD 的退伍军人中 BNST 与焦虑回路其他区域的连接发生变化；(3) 确定是否有压力反应（通过皮质醇测量）。和皮肤电导）介导 BNST 功能（激活和连接）与 PTSD 症状之间的关联，最终我们的目标是阐明 PTSD 背后的神经生物学机制，以确定新的大脑治疗靶点。