Mechanisms for Behavior Change and Maintenance of Treatment for CKD Comorbid Depression

项目摘要/摘要 本申请的目的是了解为什么对重度抑郁症的干预治疗 在慢性肾脏疾病(CKD)患者中，随着时间的推移，疾病(MDD)最初起作用或不起作用。这 该项目将在我正在进行的NIH R01资助的研究(R01DK124379-05)中添加评估，结合了 CKD并发抑郁的治疗方法，以帮助阐明介导反应的作用机制 治疗；采用治疗的促进者和障碍；以及维持治疗反应。我们会 收集免费数据，这些数据将使用已完成 父母研究，以调查抑郁症治疗效果的机制，或缺乏机制，并确定 在积极干预期后维持治疗效果的初步缓解者 治疗8周后抑郁。在亲代R01研究中，我们目前正在比较两种药物的疗效 MDD的16周治疗策略与对照：(1)行为激活疗法(BAT)或(2) 安非他酮药物治疗，在8周后，在未缓解的患者中，每种药物都增加到两者的组合。我们会 让已完成父母试验的参与者子集参与：目标1.确定机制 通过确定候选炎症性因素，确定干预效果的作用与缺乏 慢性肾脏病患者MDD治疗反应的中介/调节因子。我们将使用(A)RNA测序 来自冷冻样本的血液基因表达和(B)血浆炎症生物标记物 在基线和第8周收集自母研究(N)至少完成8周的患者 =76)。我们将评估候选先天免疫是否在基线基础上有所改变 靶向全基因组转录图谱和血浆中的激活/炎症途径 (A)抑郁缓解者中的生物标志物(定义为抑郁症状评分快速清单- QDS-SR≤5)与不缓解的患者相比；以及(B)对治疗有反应的患者(定义为QDS-SR得分的下降 从基线开始≥3分)与治疗无应答者相比。目标2.评估或 行为采用障碍，在这种情况下，坚持MDD治疗干预措施(逐药计数 和BAT远程治疗)，在CKD患者中。我们将在50名参与者中进行焦点小组，这些参与者 完成了为期16周的试验，以收集参与者的经验、干预障碍和促进者的数据 参与度和坚持性，以及干预的预期好处。目标3.评估MDD的维护情况 随时间推移的治疗反应，超过16周积极干预期(N=50)，汇款与 8周时未缓解的患者，通过评估以患者为中心的抑郁结局的改善情况 症状；(B)疲劳；(C)睡眠；(D)整体功能。这个应用程序对应于我的父母R01‘S 行为和社会科学办公室的范围和时间表以及目的和要求 研究。AIMS不会干扰父R01的原始范围，也不会与其重叠。

Project Summary/Abstract The purpose of this application is to understand why interventions for the treatment of Major Depressive Disorder (MDD) work or do not work initially and over time in patients with Chronic Kidney Disease (CKD). This project will add assessments to my ongoing NIH R01-funded study (R01DK124379-05), Combination of Novel Therapies for CKD Comorbid Depression, to help illuminate mechanisms of action mediating response to treatment; facilitators and barriers to adoption of treatment; and maintenance of treatment response. We will collect complimentary data that will use information from the subset of participants who have completed the parent study to investigate mechanisms for depression treatment effect, or lack thereof, and also identify the maintenance of treatment effect beyond the active intervention period in those who initially have remission in depression after 8 weeks of treatment. In the parent R01 study, we are currently comparing the efficacy of two 16-week strategies vs. control for treatment of MDD starting with (1) Behavioral Activation Therapy (BAT) or (2) bupropion drug therapy, each augmented to a combination of both in non-remitters after 8 weeks. We will engage the subset of participants that have completed the parent trial to: Aim 1. Identify mechanisms of action of intervention effect, vs. lack thereof, by identifying candidate inflammatory mediators/moderators of MDD treatment response in CKD patients. We will use (a) RNA-Sequencing of whole blood gene expression and (b) plasma inflammatory biomarkers from frozen samples that have already been collected at baseline and at week 8 from patients who completed at least 8 weeks from the parent study (N =76). We will evaluate whether there is a modification from baseline in candidate innate immune activation/inflammatory pathways through targeted whole genomic transcriptional profiling and plasma biomarkers in (a) depression remitters (defined as Quick Inventory of Depressive Symptomatology score - QIDS-SR ≤5) vs. non-remitters; and (b) responders to treatment (defined as a decrease in the QIDS-SR score by ≥3 points from baseline) vs. non-responders to treatment. Aim 2. Assess underlying facilitators of or barriers to behavior adoption, in this case adherence to MDD treatment interventions (drug by pill count and BAT teletherapy sessions), in patients with CKD. We will conduct focus groups in 50 participants who have finished the 16-week trial to gather data on participants’ experiences, barriers to and facilitators of intervention engagement and adherence, and perceived benefits of the intervention. Aim 3. Assess maintenance of MDD treatment response over time, beyond the 16-week active intervention period (N =50), in remitters vs. non-remitters at 8 weeks, by assessing improvement in patient-centered outcomes of (a) depressive symptoms; (b) fatigue; (c) sleep; (d) overall functioning. This application corresponds with my parent R01’s scope and timeline and the purpose and requirements of the Office of Behavioral and Social Sciences Research. The aims will not interfere and do not overlap with the original scope of the parent R01.