Neurodegenerative Changes in Post-Stroke Depression

中风后抑郁症的神经退行性变化

• 批准号: 10744198
• 负责人: Rodrigo Machado Vieira
• 金额: $ 19.74万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10744198
• 关键词: Affect; Anatomy; Antidepressive Agents; Area; Atrophic; Autopsy; Binding; Biological; Brain; Brain Injuries; Brain imaging; Brain region; Clinical; Complication; Data; Diagnosis; Early Diagnosis; Family; Fiber; Funding; Genes; Glycoproteins; Hippocampus; Human; Infarction; Injury; Ischemic Stroke; Lesion; Limbic System; Magnetic Resonance Imaging; Measures; Mental Depression; Moods; Nerve Degeneration; Neurologic Deficit; Pathologic; Patients; Persons; Pilot Projects; Positron-Emission Tomography; Pre-Clinical Model; Prefrontal Cortex; Proteins; Proxy; Quality of life; Recovery of Function; Rehabilitation therapy; Reporting; Research; Role; Severities; Site; Stress; Stroke; Structure; Synapses; Synaptic Vesicles; Testing; Therapeutic; Thick; Time; Tissues; United States; Wallerian Degeneration; axon injury; density; depressive symptoms; disability; disability burden; frontal lobe; high reward; high risk; imaging biomarker; imaging study; in vivo; indexing; middle cerebral artery; mortality; neuroimaging; neuron loss; neuropsychiatric symptom; neuropsychiatry; personalized medicine; physically handicapped; post stroke; post stroke depression; radioligand; recruit; research clinical testing; serial imaging; stroke patient; stroke recovery; stroke survivor; stroke victims; synaptic function; tool; white matter

PROJECT SUMMARY Stroke is one of the leading causes of long-term mortality and disability, affecting nearly 800,000 people in the United States each year. Nearly one-third of stroke victims report post-stroke depression (PSD) after a stroke that significantly affects stroke recovery and is associated with an enormous disability burden and poor quality of life. Post-stroke depression (PSD) is a common and severe complication of cerebrovascular stroke, affecting about one-third of stroke survivors. PSD is associated with poor functional recovery from stroke-related disability, mortality, and poor life quality. The diagnosis and treatment decisions are currently based on clinical evaluation; treatments are not tailored to the brain injury. We hypothesize that identifying specific pathological changes in PSD is the first step towards developing personalized treatments for PSD. Evidence suggests brain anatomical changes (i.e, neurodegeneration - volume loss, microstructures, and disconnections) in prefrontal-limbic circuitry remote from primary stroke lesion and may be causally related to PSD. The primary objectives of this pilot project are to investigate the role of prefrontal-limbic anatomy using MRI and will evaluate synaptic density using a state- of-the-art Positron Emission Tomography (PET) imaging-based synaptic marker. We propose anatomical structural changes and synaptic density losses in prefrontal-limbic circuitry as a biological mechanism underlying PSD. The findings from this study will provide preliminary evidence; (1) if neurodegeneration in the mood-related prefrontal-limbic circuitry underlies depression symptoms, and (2) to develop brain circuit-based neurodegeneration markers underlying neuropsychiatric symptoms in stroke.

项目概要 中风是导致长期死亡和残疾的主要原因之一，影响着美国近 80 万人。 美国每年。近三分之一的中风患者报告中风后出现中风后抑郁症（PSD） 严重影响中风康复，并与巨大的残疾负担和低质量相关 的生活。卒中后抑郁（PSD）是脑血管卒中常见且严重的并发症，影响 大约三分之一的中风幸存者。 PSD 与中风相关残疾的功能恢复不良有关， 死亡率高，生活质量差。目前的诊断和治疗决定基于临床评估； 治疗方法并不适合脑损伤。我们假设识别特定的病理变化 PSD 是开发 PSD 个性化治疗的第一步。有证据表明大脑解剖学 前额叶边缘回路的变化（即神经退行性变——体积损失、微观结构和断开） 远离原发性中风病变，可能与 PSD 存在因果关系。该试点项目的主要目标 将使用 MRI 研究前额叶边缘解剖学的作用，并将使用状态评估突触密度 最先进的基于正电子发射断层扫描 (PET) 成像的突触标记。我们建议解剖学 前额叶边缘回路的结构变化和突触密度损失作为潜在的生物机制 PSD。这项研究的结果将提供初步证据； (1)神经退行性疾病是否与情绪有关 前额叶边缘回路是抑郁症状的基础，(2) 开发基于脑回路的 中风神经精神症状背后的神经退行性标志物。