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

摘要 抑郁症状经常伴随着急性疾病，并与康复延迟和 恢复发病前的功能，以及增加的医疗费用。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严重抑郁，但对这种情况知之甚少 症状的演变或机制。我们的总体假设是早期的神经递质和 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至关重要，因为它可以指导 防止症状发展为一种独立疾病的治疗。 在这个项目中，我们将确定急性脑缺血后抑郁症状轨迹的多模式生物标记物 卒中。我们的生物标记物将包括神经代谢物(谷氨酸和GABA)水平和大脑 抗氧化剂(谷胱甘肽)和炎症(转录和外周)。急性缺血性中风是 高信号环境，因为已知的神经代谢物和炎症的变化以及高信号 抑郁症状的发生率。 我们的方法包括通过同时测量多个 神经代谢物/抗氧化剂和炎症级联的指数。虽然之前的工作已经证明 神经代谢产物与MDD炎症的关系，这些因素都没有被研究过 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名有一系列抑郁症状的参与者，他们已经因急性 加州大学洛杉矶分校综合卒中中心的初始缺血性卒中。在研究进入时，我们仔细的表型 样本将接受：磁共振波谱(MRS)扫描，外周血细胞和转录水平分析 炎症指标和抑郁症状指标。将反复采取炎症措施 1个月后探讨早期炎性改变作为潜在的生物标志物。在四个月内我们将获得 每两个月进行一次抑郁症状评分，并对焦虑、生活质量和 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 早期炎症变化，将预示抑郁症状的发展轨迹。此信息将提供 对抑郁症状的病理生物学和病程有价值的洞察，并为未来奠定基础 更大规模的研究和潜在的干预措施。

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.