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）迅速成为伊拉克自由行动（OIF）/持久自由行动（OEF）/新黎明行动（OEF）（OND）（OND）面临的最普遍的心理健康问题。 PTSD是一种毁灭性疾病，也增加了自杀，抑郁和药物使用障碍的风险。不幸的是，PTSD通常对当前的治疗干预措施有抵抗力，并且完全恢复并不常见。靶向疗法的发展是有效治疗PTSD的途径，但是要开发这些疗法，首先，我们必须更好地了解潜在的神经生物学机制。拟议项目的目的是确定具有PTSD的战斗退伍军人是否在质末端（BNST）介导的焦虑神经回路中发生了改变。在啮齿动物中，BNST介导了与PTSD症状相似的压力相似的动画，过度维护和行为影响。在具有PTSD的战斗退伍军人中，在威胁是不可预测的情况下，这些症状的增加。也就是说，威胁性事件可能发生也可能不会发生。我们建议比较有或没有PTSD的OEF/OIF/OND战斗暴露的退伍军人。我们开发了新的方法，可以使用功能磁共振成像（fMRI）检查BNST激活对不可预测的威胁。该研究将重点介绍三个特定目的：（1）与没有PTSD的战斗退伍军人相比，与PTSD的战斗退伍军人相比，BNST激活是否提高； （2）确定与PTSD的退伍军人中与焦虑回路其他区域的BNST连通性的变化； （3）确定应力反应（通过皮质醇和皮肤电导率测量）是否介导BNST功能（激活和连通性）和PTSD符号之间的关联。最终，我们旨在阐明PTSD基础的神经生物学机制，以鉴定新的大脑靶标。