Neurochemical and inflammatory biomarkers of the trajectory of depressive symptoms after acute illness

急性疾病后抑郁症状轨迹的神经化学和炎症生物标志物

• 批准号: 10453402
• 负责人: JOHN O BROOKS
• 金额: $ 23.4万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453402
• 关键词: Acute; Address; Anterior; Antioxidants; Anxiety; Biological Assay; Biological Markers; C-reactive protein; Cause of Death; Cerebrum; Dimensions; Early Diagnosis; Early treatment; Enrollment; Environment; Event; Evolution; Foundations; Functional disorder; Future; Genetic Transcription; Glutamates; Glutamine; Glutathione; Health Care Costs; IL8 gene; Incidence; Inflammation; Inflammatory; Interleukin-1; Interleukin-6; Intervention; Ischemic Stroke; Link; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measures; Medical; Mental Depression; Mental disorders; Neurotransmitters; Nuclear; Outcome; Participant; Patients; Peripheral; Phenotype; Prevention; Quality of life; Recovery; Research; Sampling; Scanning; Severities; Signal Transduction; Stroke; Symptoms; TNF gene; Work; acute stroke; comorbidity; comparative; cytokine; daily functioning; depressive symptoms; experience; gamma-Aminobutyric Acid; high risk; improved; indexing; inflammatory marker; insight; multimodality; neurochemistry; novel; novel strategies; post stroke; potential biomarker; predictive marker; prevent; relating to nervous system; single episode major depressive disorder; stroke victims; transcription factor

ABSTRACT Depressive symptoms frequently accompany acute illness and are associated with delayed recovery and return to premorbid function, as well as increased healthcare costs. In illnesses such as acute ischemic stroke, depressive symptoms and major depression occur in at least 30-50% of patients, yet little is known about the evolution or mechanism of the symptoms. Our overall hypothesis is that early neurotransmitter and inflammatory changes are biomarkers of subsequent depressive symptom trajectory. Understanding the biomarkers and pathophysiology of depressive symptoms after acute stroke is crucial because it can guide treatment to prevent symptoms from developing into an independent illness. In this project, we will identify multimodal biomarkers of depressive symptom trajectory after acute ischemic stroke. Our biomarkers will include levels of neurometabolites (glutamate and GABA) and a cerebral antioxidant (glutathione) as well as inflammation (both transcriptional and peripheral). Acute ischemic stroke is a `high signal' environment as there are known changes in both neurometabolites and inflammation and a high incidence of depressive symptoms. Our approach includes a novel advance over previous work through the simultaneous measures of multiple neurometabolites/antioxidant and indices of the inflammation cascade. While previous work has demonstrated relations between neurometabolites and inflammation in MDD, none of these factors have been examined simultaneously as biomarkers of depressive symptom trajectory following acute stroke. We will enroll 40 participants with a range of depressive symptoms who have been admitted for an acute initial ischemic stroke at the UCLA Comprehensive Stroke Center. At study entry, our carefully phenotyped sample will receive: a magnetic resonance spectroscopy (MRS) scan, assays of peripheral and transcriptional measures of inflammation; and measures of depressive symptoms. Inflammation measures will be repeated after one month to explore early inflammatory change as a potential biomarker. For four months we will obtain bimonthly ratings of depressive symptoms ratings and, for exploratory purposes, anxiety, quality of life, and level of daily function. We hypothesize that initial levels of neurometabolites/antioxidant and inflammation will be related to early depressive symptoms. Further, we hypothesize that neurometabolite and cerebral antioxidant levels, as well as early changes in inflammation, will predict the depressive symptom trajectory. This information will provide valuable insight into the pathobiology and course of depressive symptoms and create the foundation for future larger-scale studies and potential interventions.

摘要 抑郁症状经常伴随急性疾病，并与延迟恢复有关， 恢复到发病前的功能，以及增加医疗费用。在急性缺血性中风等疾病中， 至少30-50%的患者会出现抑郁症状和重度抑郁症，但人们对抑郁症的发病机制知之甚少。 症状的演变或机制。我们的总体假设是，早期神经递质和 炎症变化是随后抑郁症状轨迹的生物标志物。了解 急性卒中后抑郁症状的生物标志物和病理生理学是至关重要的，因为它可以指导 治疗，以防止症状发展成为一个独立的疾病。 在这个项目中，我们将确定急性缺血后抑郁症状轨迹的多模式生物标志物， 中风我们的生物标志物将包括神经代谢物（谷氨酸和GABA）和大脑代谢物的水平 抗氧化剂（谷胱甘肽）以及炎症（转录和外周）。急性缺血性卒中 “高信号”环境，因为神经代谢物和炎症都有已知的变化， 抑郁症状的发生率。 我们的方法包括一个新的进步，以前的工作，通过同时措施，多个 神经代谢物/抗氧化剂和炎症级联的指数。虽然之前的研究表明 MDD中神经代谢物和炎症之间的关系，这些因素中没有一个被检查过 同时作为急性卒中后抑郁症状轨迹的生物标志物。 我们将招募40名患有一系列抑郁症状的参与者，他们因急性抑郁症而入院， 在加州大学洛杉矶分校综合中风中心首次缺血性中风。在研究开始时，我们仔细的表型 样本将接受：磁共振波谱（MRS）扫描，外周和转录检测 炎症的测量;和抑郁症状的测量。将重复炎症措施 一个月后，探索早期炎症变化作为潜在的生物标志物。四个月内我们将获得 每两个月进行一次抑郁症状评分，出于探索性目的，还包括焦虑、生活质量，以及 日常功能水平。 我们假设，神经代谢物/抗氧化剂和炎症的初始水平将与早期 抑郁症状此外，我们假设神经代谢物和大脑抗氧化剂水平，以及 炎症的早期变化，将预测抑郁症状的轨迹。这些信息将提供 对抑郁症状的病理生物学和过程有价值的见解，并为未来的研究奠定基础。 更大规模的研究和潜在的干预措施。